LIST OF REFERENCES Part 2: Other Substances

LIST OF REFERENCES Part 2: Other Substances 

Brussels, 20 July 2007 

ALPHA-LIPOIC ACID and Antioxidant properties .................................................................... 6 

ALPHA-LIPOIC ACID and Metabolism of carbohydrates ........................................................ 7 

ANTIOXIDANT FROM PROCESSED FRUITS AND VEGETABLES AND JUICES and 

Antioxidant properties................................................................................................................ 8 

ARABINOGALACTAN and Intestinal health ............................................................................. 9 

ARGININE and Vascular health................................................................................................ 10 

BACTERIAL LYSATE and Immune health .............................................................................. 11 

BETA-ALANINE and Physical performance ........................................................................... 13 

BETA-CAROTENE and Antioxidant properties / Protection of DNA .................................... 14 

BETA-CAROTENE and Skin aging / Skin health .................................................................... 14 

BETA-CAROTENE and Immune health ................................................................................... 17 

BETA-CAROTENE and Immune health in relation to UV-radiation ...................................... 18 

BETA-CAROTENE and Antioxidative properties / Protection against UV-induced erythema 

.................................................................................................................................................... 19 

BETA-CAROTENE IN COMBINATION WITH VITAMIN E AND VITAMIN C - Eye health and 

vision.......................................................................................................................................... 20 

BETA-SITOSTEROL and Cholesterol ...................................................................................... 22 

BETA-SITOSTEROL and Kidney and prostate health............................................................ 23 

BETAINE and Hearth health and vascular system................................................................. 23 

BETALAINS and Antioxidant properties................................................................................. 24 

BIOFLAVONOIDS and Vein health........................................................................................... 26 

BIOFLAVONOIDS FROM CITRUS and Vascular health ......................................................... 26 

BOVINE COLOSTRUM and Immune health/source of immunoglobulins ........................... 26 

BOVINE LACTOFERRIN and Antimicrobial / Antiviral / Innate host defense ...................... 27 

BRANCHED CHAIN AMINO ACIDS (LEUCINE, ISOLEUCINE, VALINE) and Muscle 

metabolism ................................................................................................................................ 28 

BROMELAIN and Immune health............................................................................................. 30 

BROMELAIN and Vascular health ........................................................................................... 33

C12-PEPTION and Vascular health.......................................................................................... 36 

CAFFEINE (FROM TEA/COFFEE/CHOCOLATE OR ADDED IN PURE FORM) and Fat 

metabolism / Energy Expenditure ........................................................................................... 39 

CAFFEINE (FROM TEA/COFFEE/CHOCOLATE OR ADDED IN PURE FORM) and Cognitive 

and mental performance ..........................................................................................................40 

CAFFEINE (FROM TEA, COFFEE, COCOA OR ADDED IN PURE FORM) and Physical 

Performance (short term and endurance activities) .............................................................. 42 

CARNITINE and Fat metabolism............................................................................................. 45 

CARNITINE and Muscle metabolism / Recovery after exercise........................................... 46 

CARNITINE and Heart health ................................................................................................... 47 

CARNITINE and Vegetarism..................................................................................................... 48 

CARNITINE and Pregnancy...................................................................................................... 49 

CAROTENOIDS FROM FRUITS AND VEGETABLES JUICES and Antioxidant properties . 49 

CASEIN PROTEIN HYDROLYSATE and Physical performance............................................ 50 

CHITOSAN and Weight Management ...................................................................................... 52 

CHLORELLA and Immune health ........................................................................................... 54 

CHOLINE and Development..................................................................................................... 54 

CHONDROITIN and Joint Health.............................................................................................. 55 

COCOA FLAVANOLS and Antioxidative properties .............................................................. 56 

COCOA FLAVANOLS and Vascular health............................................................................. 57 

COENZYME Q10 (UBIQUINONE) and Energy metabolism .................................................... 60 

COENZYME Q10 (UBIQUINONE) and Hearth health .............................................................. 60 

COENZYME Q10 (UBIQUINONE) and Antioxidant properties............................................... 62 

COLLAGEN HYDROLYSATE and Joint health ....................................................................... 63 

CONJUGATED LINOLEIC ACID (CLA) and Weight management ......................................... 65 

CONJUGATED LINOLEIC ACID (CLA) and Insulin sensitivity .............................................. 66 

CONJUGATED LINOLEIC ACID (CLA) and Immune health................................................... 66 

CONJUGATED LINOLEIC ACID (CLA) ((CIS-9, TRANS-1CONJUGATED LINOLEIC ACID, 

AND TRANS-10, CIS-12 CONJUGATED LINOLEIC ACID (50:50) TRIGLYCERIDES) and 

Body Weight management....................................................................................................... 67 

CREATINE and Energy metabolism ........................................................................................ 68 

CYSTEIN RICH PROTEIN HYDROLYSATES and Glutathione metabolism.......................... 70 

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DOCOSAHEXAENOIC ACID (DHA) and Human neurodevelopment .................................... 72 

DOCOSAHEXAENOIC ACID (DHA) and Optimization of brain maturation .......................... 74 

DOCOHEXAENOIC ACID (DHA) and Cognitive function in the elderly................................ 76 

DOCOHEXAENOIC ACID (DHA) and Eye health..................................................................... 77 

EPIGALLO-CATECHIN-3-GALLATE (EGCG) / GREEN TEA EXTRACT, RICH IN EGCG - 

Weight management................................................................................................................. 77 

EPIGALLO-CATECHI-3-GALLATE (EGCG) / GREEN TEA EXTRACT, RICH IN EGCG and 

Blood glucose levels ................................................................................................................ 79 

EPIGALLO-CATECHIN-3-GALLATE (EGCG) / GREEN TEA EXTRACT, RICH IN EGCG and 

Cardio-vascular health ............................................................................................................. 81 

ESTER-C and Antioxidant properties/immune health ........................................................... 84 

EVENING PRIMROSE OIL and Skin Health............................................................................. 84 

EVENING PRIMROSE OIL and Menstrual health.................................................................... 84 

EVENING PRIMROSE OIL AND FISH OIL and Bone health................................................... 85 

FORMULATED PALM AND OAT OIL EMULSION and Weight management........................ 85 

GLUCOMANAN and Weight management .............................................................................. 86 

GLUCOSAMINE and Joint health............................................................................................. 86 

GLUCOSINOLATES and Immune health................................................................................. 88 

GLUTAMINE AND GLUTAMIN PEPTIDE and Metabolic stress / Protein synthesis / Gut 

permeability / Carbohydrate metabolism................................................................................ 91 

GLUTAMINE and Immune health ............................................................................................. 92 

GLUTAMINE and Muscle function ........................................................................................... 95 

GLUTAMINE and Mental health ............................................................................................... 97 

HYDROLYSATE WITH PEPTIDE and Stress ........................................................................... 97 

LACTOTRIPEPTIDES and Blood pressure ............................................................................. 98 

LIGNANS and Phyto-estrogenic properties.......................................................................... 100 

LUTEIN and Eye health...........................................................................................................101 

LUTEIN and Skin health..........................................................................................................106 

LYCOPENE and Skin health................................................................................................... 107 

LYCOPENE and Prostate health ............................................................................................ 108 

LYCOPENE and Antioxidant properties................................................................................ 111 

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LYCOPENE and Antioxidant properties / protection of DNA.............................................. 112 

LYCOPENE and Heart health ................................................................................................. 113 

LYCOPENES FROM TOMATO JUICES and Antioxidant properties ................................... 115 

LYSINE and Body tissues ...................................................................................................... 116 

MEDIUM CHAIN TRIGLYCERIDES (MCT) and Weight management .................................. 117 

METHIONINE and Lipid metabolism...................................................................................... 118 

NUCLEOTIDES and Immune health....................................................................................... 118 

PAPAIN and Immune health................................................................................................... 119 

PHENYLALANINE and Mental health .................................................................................... 122 

PHOSPHATIDYL CHOLINE / LECITHIN and Cholesterol / Heart health ............................. 123 

PHOSPHATIDYL CHOLINE / LECITHIN and Cognitive function ......................................... 124 

PHOSPHATIDYL SERINE and Mental health / Cognitive function...................................... 128 

PHOSPHOLIDIPS (PHOSPHATIDYL CHOLINE, PHOSPHATIDYL ETHANOLAMINE, 

PHOSPHATIDYL INOSITOL, LYSOPHOSPHATIDYL CHOLIN) and Liver health ............... 131 

PHYTOSTEROLS (MIXTURE OF BETA-SITOSTEROL, CAMPESTEROL, STIGMASTEROL, 

BRASSICASTEROL, STIGMASTANOL, ERGOSTANOL, CAMPESTANOL) and Cholesterol 

metabolism .............................................................................................................................. 132 


BRASSICASTEROL, STIGMASTANOL, ERGOSTANOL, CAMPESTANOL) and Prostate 

health........................................................................................................................................ 133 

POLYPHENOLS FROM PROCESSED FRUITS AND VEGETABLES AND JUICES and 

Antioxidant properties............................................................................................................ 133 

POLYPHENOLS (GENERAL AND FROM GRAPE, OLIVE AND CACAO IN PARTICULAR) 

and Antioxidant properties .................................................................................................... 135 

POLYPHENOLS FROM OLIVE (OLIVE FRUIT, OLIVE MILD WASTE WATERS OR OLIVE 

OIL) and Antioxidant properties / Lipid metabolism............................................................ 140 

POLYPHENOLS FROM OLIVE (OLIVE FRUIT, OLIVE MILD WASTE WATERS OR OLIVE 

OIL) and Lipid metabolism ..................................................................................................... 140 

POLYPHENOLS DERIVED FROM RED WINE and Antioxidant properties......................... 141 

POLYPHENOLS DERIVED FROM RED WINE and Lipid metabolism ................................. 142 

POLYPHENOLS FROM RED WINE and Vascular functions................................................ 143 

POLYPHENOLS FROM TEA and Antioxidant properties .................................................... 144 

PROTEIN HYDROLYSATE and Insulin secretion and blood sugar levels ......................... 148 

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QUERCETIN and Antioxidative properties ........................................................................... 149 

RED YEAST RICE and Cholesterol........................................................................................ 152 

RYE GRASS POLLEN EXTRACT and Prostate health ......................................................... 153 

SILICA / SILICIOUS EARTH and Essential part of the connective tissues, skin and hair 154 

SOY ISOFLAVONES and Menopause.................................................................................... 156 

SOY ISOFLAVONES and Bone health................................................................................... 158 

STANDARDISED POTATO EXTRACT and Satiety / Weight management / Promotion of 

CCK release............................................................................................................................. 160 

STEARIC ACID and Lipid metabolism................................................................................... 162 

STEROLS / STANOLS AND THEIR ESTERS and Heart health and artery health because of 

LDL cholesterol loweringh ..................................................................................................... 162 

TROXERUTIN and Vascular health........................................................................................ 163 

ZEAXANTHIN and Eye health and vision.............................................................................. 164 

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ALPHA-LIPOIC ACID and Antioxidant properties 

Reviews 

- Biewenga GP, Haenen GR, Bast A: The pharmacology of the antioxidant lupoic acid. Gen 

Pharmacol 1997; 29 (3): 315-331 

- Packer L, Tritschler H J, Wessel K. Neuroprotection by the metabolic antioxidant α-lipoic acid. 

Free Radical Biology & Medicine 1997; 22: 359-378 

- Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes 

complications. Nutrition 2001; 17: 888-895 

- Packer L, Witt E H, Tritschler H J. Alpha-lipoic acid as a biological antioxidant. Free Radical 

Biology & Medicine 1995; 19: 227-250 

- Roy S, Packer L: Redox regulation of cell functions by alpha-lipoate: biochemical and 

molecular aspects. Biofactors 1998; 7(3): 263-267 

- Smith A R, Shenvi S V, Widlansky M, Suh J H, Hagen T M. Lipoic acid as a potential therapy 

for chronic diseases associated with oxidative stress: The roller coaster of antioxidant therapy. 

Current medicinal chemistry 2004; 11: 1135-1146 

Individual Clinical Studies 

- Borcea V, Nourooz-Zadeh J, Wolff SP, Klevesath M, Hofmann M, Urich H, Wahl P, Ziegel R, 

Tritschler H, Halliwell B, Nawroth PP: Alpha-Lipolic acid decreases oxidative stress even in 

diabetic patients with poor glycemic control and albuminuria. Free Radic Biol Med 1999; 26: 

1495-1500 

- Park K G, Kim M J, Kim H S, Lee S J, Song D K, Lee I K. Prevention and treatment of 

macroangiopathy: focusing on oxidative stress. Diabetes Res Clin Pract 2004; 66: 57-62 

- Marangon K, Kevaraj S, Tirosh O, Packer L, Jialal I. Comparison of the effect of α-lipoic acid 

and α-tocopherol supplementation on measures of oxidative stress. Free Radical 

Animal Studies 

- Biewenga GP, Haenen GR, Bast A: The pharmacology of the antioxidant lipolic acid. Gen 

Pharmacol 1997; 29:315-331 

- Busse E, Zimmer G, Schopohl B, Kornhuber B: Influence of alpha-lipolic acid on intracellular 

glutathionate in vitro and in vivo. Arzneimittelforschung 1992; 42:829-831 

- Cakatay U, Telci A, Kayali R, Sivas A, Akcay T: Effect of alpha-lipoic acid supplementation on 

oxidative protein damage in the streptozotocin-diabetic rat. Res Exp Med 2000; 199:243-251 

- Kagan VE, Shvedova A, Serbinova E, Khan S, Swanson C, Powell R, Packer L: Dihydrolipoic 

acid- a universal antioxidant both in the membrane and in the aqueous phase. Reduction of 

peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol 1992; 44: 1637-1649 

- Kowluru RA: Diabetic retinopathy: mitochondrial dysfunction and retinal capillary cell death. 

Antioxid Redox Signal 2005; 7 (11-12): 1581-1587 

- Kowluru RA, Odenbach S: Role of interleukin-1 beta in the development of retinopathy in 

rats:effect of antioxidants. Ivest Ophthalmol Vis Sci 2004; 45 (11):4161-4166 

- Kowluru RA, Odenbach S: Effect of long-term administration of alpha-lipoic acid on retinal 

capillary cell death and the development of retinopathy in diabetic rats. Diabetes 2004; 53: 

3233-3238 

- Lin J, Bierhaus A, Bugert P, Dietrich N, Feng Y, Vom Hagen F, Nawroth P, Brownlee M, 

Hammes HP: Effect of lipoic acid on experimental diabetic retinophathy. Diabetologia 2006; 49: 

1089-1096 

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- Midaoui AE, Elimadi A, Wu L, Haddad PS, de Champlain J: Lipoic acid prevents hypertension, 

hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J Hypertens 

2003; 16:173-179 

- Obrosova IG, Fathallah L, Liu E, Nourooz-Zadeh J: Early oxidative stress in the diabetic 

kidney: effect of alpha-lipoic acid. Free Radic Biol Med 2003; 34: 186-195 

- Obrosova IG, Minchenko AG, Marinescu V, Fathallah L, Kennedy A, Stockert CM, Frank RN, 

Stevens MJ: Antioxidants attenuate early up regulation of retinal vascular endothelian growth 

factor in streptozotocin-diabetic rats. Diabetologia 2001; 44: 1102-1110 

- Obrosova I G, Fathallah L, Greene D A. Early changes in lipid peroxidation and antioxidative 

defense in diabetic rat retina: effect of DL-alpha- lipoic acid. Eur J Pharmacol 2000; 398: 139- 

146 

- Stevens M J, Obrosova I, Cao X, Huysen C V, Greene D A. Effects of DL-α-Lipoic Acid on 

peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in 

experimental diabetic neuropathy. Diabetes 2000; 49: 1006-1015 

- Stitt A, Gardiner T A, Anderson N L, Canning P, Frizzell N, Duffy N, Boyle C, Januszewski A S, 

Chachich M, Baynes J W, Thorpe S R. The AGE inhibitor Pyridoxamine inhibits development of 

retinopathy in experimental diabetes. Diabetes 2002; 51: 2826-2832 

- Voloboueva L A, Lui J, Suh J H, Ames B N, Miller S S. (R)-α-lipoic acid protects retinal pigment 

epithelial cells from oxidative damage. Invest Ophthalmol Vis Sci 2005; 46: 4302-4310 

ALPHA-LIPOIC ACID and Metabolism of carbohydrates 

Review 

- Bilska A, Wlodek L. Lipoic acid - the drug of the future? Pharmacol Rep. 2005 Sep- 

Oct;57(5):570-7. 

- Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for 

chronic diseases associated with oxidative stress. Curr Med Chem. 2004 May;11(9):1135-46. 

- Henriksen EJ. Exercise training and the antioxidant alpha-lipoic acid in the treatment of insulin 

resistance and type 2 diabetes. Free Radic Biol Med. 2006 Jan 1;40(1):3-12. 

- Evans J L, Goldfine I D.Alpha-lipoic acid: a multifunctional antioxidant that improves insulin 

sensitivity in patients with type 2 diabetes. Diabetes Technol Ther 2000; 2: 401-413 

Human studies 

- Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett 

K: Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with 

type 2 diabetes mellitus: a placebo- controlled pilot trial. Free Radic Biol Med 1999; 27: 309- 

314 

- Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung WI, Augustin 

HJ, Dietze GJ: Enhancement of glucose disposal in patients with type 2 diabetes by alphalipoic 

acid. Arzneimittelforschung 1995; 45: 872-874 

- Kamenova P: Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after 

oral administration of alpha-lipolic acid. Hormones (Athens) 2006; 5:251-258 

- Konrad T, Vicini P, Kusterer K, Hoflich A, Assadkhani A, Bohles HJ, Sewell A, Tritschler HJ, 

Cobelli C, Usaden KH: Alpha-lipoic acid treatment decreases serum lactate and pyruvate 

concentrations and improves glucose effectiveness in lean and obese patients with type 2 

diabetes. Diabetes Care 1999; 22:280-287 

- Negrisanu G, rosu M, Bolte B, Lefter D, Dabelea D. Effects of 3-month treatment with the 

antioxidant alpha-lipoic acid in diabetic peripheral neuropathy. Rom J Intern Med 1999; 37: 

297-306 

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- Rekhabivic M, Reichel G, Rett K, Lobisch M, Schuette K, Möller W, Tritschler H J, Mehnert H. 

Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic-acid): a two 

year multicenter randomized double-blind placebo-controlled trial (ALADIN 2). Alpha Lipoic 

Acid in Diabetic Neuropathy. Free Radic Res 1999; 31: 171-179 

- Tankova t, Koev D, Dakovska L. Alpha-lipoic acid in the treatment of autonomic diabetic 

neuropathy (controlled, randomized, open-lavel study). Rom J Intern Med 2004; 42: 457- 464 

- Ziegler D, Hanefeld M, Ruhnau K J, Hasche H, Lobisch M, Schütte K, Kerum G, Malessa R. 

Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7month 

multicenter randomized controlled trial (ALADIN 3 Study). ALADIN 3 Study Group. 

Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care 1999; 22: 1296-1301 

Animal studies 

- Yi X, Maeda N. alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes 

in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Diabetes. 2006 

- 

Aug;55(8):2238-44. 

Thirunavukkarasu V, Anitha Nandhini AT, Anuradha CV. Lipoic acid improves glucose 

utilisation and prevents protein glycation and AGE formation. Pharmazie. 2005 Oct;60(10):772- 

5. 

- Song KH, Lee WJ, Koh JM, Kim HS, Youn JY, Park HS, Koh EH, Kim MS, Youn JH, Lee KU, 

Park JY. alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem 

Biophys Res Commun. 2005 Jan 7;326(1):197-202. 

In vitro study 

- Targonsky ED, Dai F, Koshkin V, Karaman GT, Gyulkhandanyan AV, Zhang Y, Chan CB, 

Wheeler MB. alpha-lipoic acid regulates AMP-activated protein kinase and inhibits insulin 

secretion from beta cells. Diabetologia. 2006 Jul;49(7):1587-98. Epub 2006 May 13. 

ANTIOXIDANT FROM PROCESSED FRUITS AND VEGETABLES AND JUICES and 

Antioxidant properties 

Authoritative body 

- Martin A, coordonnateur (2001) AFSSA, CNERNA-CNRS Apports nutritionnels conseillés pour 

la population française, 3è édition. pp 226-227. Editions Tec & Doc, Paris 

Monographs 

- Lecerf JM (1999) Pasteur Institute – Lille Les antioxidants et les autres éléments protecteurs 

dans les jus de fruits et légumes - Publication : 

- 

www.unijus.org/juice/site/fo/unijus/publications.html 

Lecerf JM (2006) Pasteur Institute – Lille Functional claims of article 13 : Polyphenols in juices. 

References and scientific evidences. 

- Ruxton H. S. Carrie, Gardner J. Elaine2, & Walker Drew3, Can pure fruit and vegetable juices 

protect against cancer and cardiovascular disease too? A review of the evidence, International 

Journal of Food Sciences and Nutrition 2006, 1_24, PrEview article 

Critical Reviews 

- Lecerf JM (1999) Pasteur Institute – Lille Les antioxidants et les autres éléments protecteurs 

dans les jus de fruits et légumes. 

- Lecerf JM (1997) Pasteur Institute – Lille Nutrition, antioxydants et athéroclérose. Rev Fr 

Endocrinol Clin 38 :119-141. 

Individual studies – clinical trials 

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- Brouwer IA, van Dusseldorp M, West CE and al (1999) Dietary folate from vegetables and 

citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled 

trial. J Nutr 129:1135-1139. 

- Harats D, Chevion S, Nahir M and al (1998) Citrus fruit supplementation reduces lipoprotein 

oxidation young men ingesting a diet high in saturated fat : presumptive evidence for an 

interaction between vitamins C and E in vivo. Am J Clin Nutr 67:240-5. 

- Harats D, Chevion S, Nahir M and al (1998) Citrus fruit supplementation reduces lipoprotein 

oxidation young men ingesting a diet diet high in saturated fatty acids to determine the effects 

of vitamin C on cardiovascular risk factors 

- Tucker KL, Selhub J, Wilson PWF and al (1996) Dietary intake pattern relates to plasma folate 

and homocysteine concentrations in the Framingham Heart Study. J Nutr 126:3025-3031. 

Individual studies – epidemiological studies 

- Kushi LH, Folsom AR, Prineas RJ and al (1996) Dietary antioxidant vitamins and death from 

coronary heart disease in postmenopausal women. N Engl J Med 334:1156-1162. 

Individual studies – technological studies 

- Dewanto V, Wu X, Liu RH (2002) Processed sweet corn has higher antioxidant capaacity. J 

Agric Food Chem 50:4959-4964. 

- Jiratanan T, Liu RH (2004) Antioxidant activity of processed table beets and green beans. J 

Agric Food Chem 52 : 2659-2670. 

- Kalt W (2005) Effects of production and processing factors on major fruit and vegetable 

antioxidants. J Food Sci 70(1), R11-R19. 

- Ninfali P, Bacchiocca M (2003) Polyphenols and antioxidant capacity of vegetables under fresh 

and frozen 

- Conditions. J Agric Food Chem 51:2222-2226. 

- Ayala-Zavala JF, Wang SY, Wang CY and Gonzalez-Aguilar GA (2004) Effect of storage 

temperatures on antioxidant capacity and aroma compounds in strawberry fruit. Lebensmittel 

Wissenschaft und Technologie 37(7):687-695. 

- Chaovanalikit A, Wrolstad RE (2004b) Total anthocyanins and total phenolics of fresh and 

processed cherries and their antioxidant properties. J Food Sci 69(1), C67-72. 

ARABINOGALACTAN and Intestinal health 

Authoritative/Scientific Bodies 

- FDA GRAS Notification 

- Affsa opinion (Affsa-Saisine no 2005-SA0098, 14.10.05) 

- FCC Monograph 

Reviews 

- Cummings J H, Macfarlane G T, Englyst H N: Prebiotic digestion and fermentation. Am J Clin 

Nutr 2001; 73(suppl):415S–420S 

- Jeraci J L, Lewis B A, van Soest PJ: Interaction between human Gut bacteria and fibrous 

substrates. CRC Handbook of Dietary Fiber in Human Nutrition 2nd ed 1993: 371-376 

- Robinson R R, Causey J, and Slavin J L: Nutritional benefits of Larch Arabinogalactan. In: 

Advanced Dietary Fiber Technology. Chapter 38, 443-451 

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- Tungland B C, Meyer D: Nondigestible oligo- and polysaccharides (dietary fiber): Their 

physiology and role in human health and food. Comp Rev Food Science and Food Safety 

2002; 1:73-92 

- D’Adamo P (1996). Larch arabinogalactan. J Naturopath Med, 6:33-37 

- Kelly GS (1999). Larch arabinogalactan: clinical relevance of a novel immune-enhancing 

polysaccharide. Altern Med Rev, 4(2):96-103 

Individual studies 

- Bayliss C E, Houston A P: Characterization of plant polysaccharide- and mucin-fermenting 

anaerobic bacteria from human feces. Appl Environ Microbiol 1984; 48(3):626-632 

- Thesis by Causey-O’Brien J L: Biological impacts of Arabino- galactans in humans: 

Ethnopharmacology and modern pharmacognosy., Sept. 2002, University of Minnesota 

- Englyst H N, Hay S, Macfarlane R T: Polysaccharide breakdown by mixed populations of 

human faecal bacteria. FEMS Microbiology Ecology 1987;95:163-171 

- Mazur A W, Mohlenkamp M J, Hiler G: Digestibility of selected carbohydrates by anaerobic 

bacteria. J Agric. Food Chem. 1993;41:1925-1930 

- Robinson R R, Feirtag J, and Slavin J L: Effects of dietary Arabinogalactan on gastrointestinal 

and blood parameters in healthy human subjects. J Am Coll Nutr 2001; 20(4): 279-285 

- Vince A J, McNeil N I, Wagner J D, Wrong O M: The effect of lactulose, pectin, arabinogalactan 

and cellulose on the production of organic acids and metabolism of ammonia by intestinal 

bacteria in a faecal incubation system. Br J Nutr. 1990;63(1):17-26 

- Derbyshire E (2007). The importance of adequate fluid and fibre intake during pregnancy. Nurs 

Stand, 21-27;21(24):40-43 

- Meier R & Gassull MA (2004). Consensus recommendations on the effects and benefits of fibre 

in clinical practice. Clin Nutr Supp 1, 73-80 

ARGININE and Vascular health 


- Encyclopedia of Human Nutrition (1st Edition) p 203, 1397, 1666, 1856 Editors: M. J. Sadler, J. 

J. Strain, B. Caballero 

Reviews 

- Boger SH, Ron SE, L-Arginine improves vascular function by overcoming deleterious effects of 

ADMA, a novel cardiovascular risk factor. Altern,Med. Rev 2005;10:14-23 

- Boger SH, Zoccali C, ADMA: a novel risk factor that explains excess cardiovascular event rate 

in patients with end-stage renal disease. Atheroscler. Suppl. 2003; 4: 23 – 28 

- Curran JN, Winter DC, Bouchier-Hayes D, Biological fate and clinical implications of arginine 

metabolism in tissue healing. Wound Repair Regen. 2006; 14: 376 – 386 

- Gornik HL, Creager MA, Arginine and endothelial and vascular health. J. Nutr. 2004; 134: 

2880S-2887S 

Individual human studies 

- Adams MR, Jessup W, Celermajer, Cigarette smoking is associated with increased human 

monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C. J. 

Am. Coll. Cardiol. 1997; 29: 491-497 

- Barbul A, Lazarou SA, Efron DT, et al., Arginine enhances wound healing and lymphocyte 

immune responses in humans. Surgery 1990; 108: 331 – 336 

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- Bednarz B, Jaxa-Chamiec T, Maciejewski P, et al., Efficacy and safety of orally given Larginine 

in acute myocardial infarction: results of the multicenter, randomized, double-blind, 

placebo-controlled “ARAMI” pilot trial. Kardiol. Pol. 2005; 62: 421-426 

- Blum, L. Hathaway, R. Mincemoyer, WH, et al., Effects of oral L-arginine on endotheliumdependent 

vasodilation and markers of inflammation in healthy postmenopausal women. J Am 

Coll Cardiol. 2000; 35: 271 – 276 

- Bode-Boger SM, Boger SH, Galland A, et al., L-arginine-induced vasodilation in healthy 

humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998; 46: 489 - 

497 

- Clarkson P, Adams MR, Powe AJ, et al., Oral L-arginine improves endothelium-dependent 

dilation in hypercholesterolemic young adults. J. Clin. Invest. 1996; 97: 1989-1994 

- Creager MA, Gallagher SJ, Girerd XJ, et al., L-arginine improves endothelium-dependent 

vasodilation in hypercholesterolemic humans. J. Clin. Invest. 1992 ; 90: 1248 – 1253 

- Evans RW, Fernstrom JD, Thompson J, et al., Oral arginine reduces systemic blood pressure 

in type 2 diabetes: its potential role in nitric oxide generation. Nutr. Biochem. 2004; 15: 534-539 

- Hambrecht R Hilbrich L, Erbs S, et al., Correction of endothelial dysfunction in chronic heart 

failure: additional effects of exercise training and oral L-arginine supplementation. American 

College of Cardiology. 2000; 35:706-713 

- Huynh NT, Tayek JA, Oral arginine reduces systemic blood pressure in type 2 diabetes: its 

potential role in nitric oxide generation. J. Am. Coll. Nutr. 2002; 21: 422 – 427 

- Lekakis JP, Papathanassiou S, Papaioannou TG, et al., Oral L-arginine improves endothelial 

dysfunction in patients with essential hypertension. Int. J. Cardiol. 2002; 86: 317-323 

- Lerman A, Burnett JC, Higano ST,et al., Long-term L-arginine supplementation improves smallvessel 

coronary endothelial function in humans. Circulation. 1998; 97: 2123-2128 

- Rytlewski K, Olszanecki R, Korbut R, et al., Effects of prolonged oral supplementation with larginine 

on blood pressure and nitric oxide synthesis in preeclampsia. Eur. J. Clin Invest. 2005; 

35: 32-37 

- Schulman SP, Becker LC, Kass DA, et al., L-arginine therapy in acute myocardial infarction: 

the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical 

trial. JAMA. 2006; 295, 58-64. (see: Editorial Commentary. Ignaro LJ, Bland J, JAMA, 2006, 9 

No.2:1-3) 

- Siani A, Pagano E, Iacone R, et al., Blood pressure and metabolic changes during dietary Larginine 

supplementation in humans. Am. J. Hypertens. 2000; 13: 547-551 

- WascherTC, Graier WF, Dittrich P, et al., Effects of low dose L-arginine on insulin-mediated 

vasodilation and insulin sensitivity. Eur. J. Clin. Invest. 1997; 27: 690-695 

- Wolf A, Zalpour C, Theilmeier G, et al., Dietary L-Arginine Supplementation Normalizes Platelet 

Aggregation in Hypercholesterolemic Humans. J. Am. Cardiol. 1997; 29: 479-485 

BACTERIAL LYSATE and Immune health 

Textbook - Review 

- Handbook of Probiotics. Lee Y, Nomoto K, Salminen S, Gorbach S. 1999. 

Individual Studies 

- Bach JF. Strategies in immunotherapy of insulin-dependent diabetes mellitus. Ann NY Acad 

Sci 1993; 696: 364 – 376 

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- Boulloche J, Mouterde O, Mallet E. Management of acute diearrhea in infants and toddlers. 

Controlled study of the antidiarrheal efficacy of killed Lacto-bacillus acidophilus (LB strain) 

versus a placebo and a reference agent (loperamide). Ann Pediatr 1994; 41: 57 – 463 

- Chauvière G, Coconnier MH, Kernéis S, Darfeuille-Michaud A, Joly B, Servin AL. Competitive 

exclusion of diarrheagenic Escherichia coli (ETEC) from enterocyte-like Caco-2 cells in culture. 

FEMS Microbiol Lett 1992; 91: 213 – 218 

- Brandtzaeg P. History of oral tolerance and mucosal immunity. Ann NY Acad Sci 1996; 778: – 

27 

- De Simone C, Ciardi A, Grassi A, Lambert-Gardini S, Tzantzoglou S, Trinchieri V, Moretti S, 

Jirillo E. Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and 

peripheral blood B lymphocytes. Immunopharmacol Immunotoxicol 1992; 14: 33– 340 

- Furuse M, Tsuneoka K, Uchida K, Nomoto K. Acceleration of granulocytic cell recovery in 

irradiated mice by a single subcutaneous injection of a heat-killed Lactobacillus casei 

preparation. J Radiat Res Tokyo 1997; 38: 11– 120 

- Hatcher GE, Lambrecht RS. Augmentation of macrophage phagocytic activity by cell-free 

extracts of selected lactic acid-producing bacteria. J Dairy Sci 1993; 76: 2485 – 2492 

- Kato I, Yokokura T, Mutai M. Augmentation of natural killer cell activity by Lactobacillus casei 

and its surface antigen. Microbiol Immunol 1984; 28: 209 – 212 

- Kato I, Yokokura T, Mutai M. Effects of oral administration of Lactobacillus casei on anti-tumor 

response induced by tumor resection in mice. Int J Immunopharmacol 1994; 16: 29 – 35 

- Link-Amster H, Rochat F, Saudan KY, Mignot O, Aeschlimann JM. Modulation of a specific 

humoral immune response and changes in intestinal flora mediated through fermented milk 

intake. FEMS Immunol Med Microbiol 1994; 10: 55 – 63 

- Matsuzaki T, Nagata Y, Kado S, Uchida K, Kato I, Hashimoto S, Yokokura T. Prevention of 

onset in an insulin-dependent diabetes mellitus model, NOD mice, by oral feeding of Lactobacillus 

casei. APMIS 1997; 105: 643 – 649 

- Matsuzaki T, Ymazaki R, Hashimoto S, Yokokura T. The effect of oral feeding of Lactobacillus 

casei strain Shirota on immunoglobulin E production in mice. J Dairy sci 1998; 81: 48 – 53 

- Matsuzaki T, Yamazaki R, Hashimoto S, Yokokura T. Antidiabetic effects of an oral 

administration of Lacto-bacillus casei in non-insulin-dependent diabetes mellitus model using 

KK-Ay mice. Endocr J 1997; 44; 357 – 365 

- Nanno M, Shimizu T, Mike A, Ohwaki M, Mutai M. Role of macrophages in serum colonystimulationg 

factor induction by Lactobacillus casei in mice. Infect Immun 1988; 56: 357 – 362 

- Okawa T, Niibe H, Arai T, Sekiba K, Noda K, Takeuchi S, Hashimoto S, Ogawa N. Effect of 

LC9018 combined with radiation therapy on carcinoma of the uterine cervix. A phase III, 

multicenter, randomized, controlled study. Cancer 1993; 72: 1949 – 54 

- Perdigon G, de Macias MEN, Alvarez S, Oliver G, de Ruiz Holgado AP. Systemic augmentation 

of the immune response in mice by feeding fermented milks with Lactobacillus casei and 

Lactobacillus acidophilus. Immunology 1988; 63: 17 – 23 

- Perdigon G, Nader de Macias ME, Alvarez S, Oliver G, Pesce de Ruiz Holgado AA. Effect of 

perorally administered lactobacilli on macrophage activation in mice. Infect Immun 1986; 53: 

404 – 410 

- Perdigon G, Valdez JC, Rachid M. Antitumour activity of yoghurt: study of possible immune 

mechanisms. J Dairy Res 1998; 65: 129 – 138 

- Sadelain MWJ, Qin HY, Lavzon J, Singh B. Prevention of type I diabetes in NOD mice by 

adjuvant immunotherapy. Diabetes 1990; 39: 583 – 589 

- Shida K, Makino K, Morishita A, Takamizawa K, Hachimura S, Ametani A, Sato T, Kumagai Y, 

Habu S, Kaminogawa S. Lactobacillus casei inhibits antigen-induced IgE secretion through 

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egulation of cytokine production in murine splenocyte cultures. Int Arch Allergy Immunol 1998; 

115: 278 – 287 

- Takahashi T, Oka T, Iwana H, Kuwata T, Yamamoto Y. Immune response of mice to orally 

administered lactic acid bacteria. Biosci Biotechnol Biochem 1993; 57: 1559 – 1560 

- Watanabe T. Supressive effects of Lacto-bacillus casei cells, a bacterial immuno-stimulant, on 

the incidence of spontaneous thymic lymphoma in AKR mice. Cancer immunol Immunother 

1996; 42: 285 – 290 

- Watanabe T, Saito H. Protection of mice against herpes simplex virus infection by LC 9018 in 

combination with inactivated viral antigen. Microbiol Immunol 1986; 30: 11– 122 

- Watanabe T, Horikawa Y, Saito H. Effects of Lactobacillus casei on Pseudomonas aeruginose 

infection in normal and dexamethasone–treated mice. Microbiol Immunol 1986; 30: 249 – 254 

BETA-ALANINE and Physical performance 

Human studies 

- Kim HJ, Cho J, Kim CK, Harris RC, Harris DB, Sale C, Wise JA. Effect On Muscle Fibre 

Morphology And Carnosine Content After 12 Days Training Of Korean Speed Skaters. Med Sci 

Sport Ex. 2005; 37 (5): 988. 

- Suzuki Y, Ito O, Mukai N, Takahashi H, Takamatsu K. High levels of skeletal muscle carnosine 

contributes to the later half of exercise performance during maximal cycle ergometer sprinting. 

Jap J Physiol. 2002; 52: 199 - 205. 

In vitro (animal) Studies 

- Cameron JN. Intracellular buffering by dipeptides at. high and low temperature in the blue 

crab. Callinectes sapidus. J Exp Biol. 1989; 143: 543 – 548 

- Dunnet and Harris 1999 Influence of oral beta-alanine and L-histidine supplementation on the 

carnosine content of the gluteus medius. Equine Vet J Suppl. 1999 Jul;30:499-504 

- Horinishi H, Grillo M, Margolis FL. Purification and characterization of carnosine synthetase 

from mouse olfactory bulbs. J Neurochem. 1978; 31: 909 - 19. 

- Plowman JE, Close EA. An evaluation of a method to differentiate the species of origin of 

meats on the basis of the contents of anserine, beta-alanine and carnosine in skeletal muscle. 

J Sci Fd Agric. 1988; 45: 69 - 78. 

- Suyama M, Suzuki T, Maruyama M, Saito K. Determination of carnosine, anserine and 

balenine in the muscle of animals. Bull Jpn Soc Sci Fish. 1970; 36: 1048 - 1053. 

- Tamaki N, Tsunemori F, Wakabayashi M, Hama T . Effect of histidine-free and -excess diets on 

anserine and carnosine contents in rat gastrocnemius muscle. J Nutr Sci Vitaminol (Tokyo). 

1977; 23 (4): 331 - 40. 

In vitro (human) studies 

- Bakardjiev A, Bauer WJ. Transport of b-alanine and biosynthesis of carnosine by skeletal 

muscle cells in primary culture. Eur J Biochem. 1994; 225: 617 - 623. 

- Harris RC, Dunnett M, Greenhaff PL. Carnosine and Taurine contents in individual fibres of 

human vastus lateralis muscle. J Sport Sci. 1998; 16: 639 - 643. 

- Lenney JF, Peppers SC, Kucera-Orallo CM, George RP. Characterization of human tissue 

carnosinase. Biochem J. 1985; 228: 653 -660. 

- Mannion AF, Jakeman PM, Dunnett M, Harris RC, Willan PL. Carnosine and anserine 

concentrations in the quadriceps femoris muscle of healthy humans. Eur J Appl Physiol Occup 

Physiol. 1992; 64 (1): 47 - 50. 

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- Tallon MJ, Harris RC, Boobis LH. Carnosine contents in the vastus lateralis of extremely 

hypertrophied skeletal muscle. J Strength Cond Sci. 2005; 19 (4): 725 - 729. 

BETA-CAROTENE and Antioxidant properties / Protection of DNA 

Individual human intervention studies: 

- Torbergsen, A.C., Collins, A.R. 2004. Recovery of human lymphocytes from oxidative DNA 

damage; the apparent enhancement of DNA repair by carotenoids is probably simply an 

antioxidant effect. European Journal of Nutrition 39: 80-85. 

- Zhao, X., Aldini, G., Johnson, E.J., Rasmussen, H., Kraemer, K., Woolf, H., Musaeus, N., 

Krinsky, N.I., Russell, R.M., Yeum, K.J. 2006. Modification of lymphocyte DNA damage by 

carotenoid supplementation in postmenopausal women. American Journal of Clinical Nutrition 

83: 163-169. 

Evidence from Review articles: 

- Moller, P., Loft, S. 2006. Dietary antioxidants and beneficial effect on oxidatively damaged 

DNA. Free Radical Biology & Medicine 4(3): 388-415. 

- Stahl, W., Sies, H. 2005. Bioactivity and protective effects of natural carotenoids. Biochimica 

Biophysica Acta 1740 (2): 101-107. 

Evidence from experimental studies: 

- Astley, SB, Elliott, R.M, Archer, D.B., Southon, S. 2002. Increased cellular carotenoid levels 

reduce the persistence of DNA single strand breaks after oxidative challenge. Nutrition and 

Cancer, 43: 202-213. 

- Matos, H.R., Marques, S.A., Gomes, O.F., Silva, A.A., Heimann, J.C., Di Mascio, P., Medeiros, 

M.H. 2006. Lycopene and beta-carotene protect in vivo iron-induced oxidative stress damage 

in rat prostate. Brazilian Journal of Medical and Biological Research 39(2): 203-210. 

BETA-CAROTENE and Skin aging / Skin health 

References as to sunburn (erythema) development 

Individual human intervention studies 

- Garmyn M, Ribaya-Mercado JD, Russel RM, Bhawan J, Gilchrest BA. 1995. Effect of betacarotene 

supplementation on the human sunburn reaction. Exp Dermatol 4(2):104-11. 

- Gollnick H, Hopfenmuller W, Hemmes C, Chun S, Schmid C, Sundermeier K, Biesalski HK. 

1996. Systemic beta carotene plus topical UV-sunscreen are an optimal protection against 

harmful effects of natural UV-sunlight: results of the Berli-Eilath study. Eur J Dermatol 6(3):200- 

205. 

- Stahl W, Heinrich U, Jungmann H, Sies H, Tronnier H. 2000. Carotenoids and carotenoids plus 

vitamin E protect against ultraviolet light-induced erythema in humans. Am J Clin Nutr 

71(3):795-8. 

- Lee J, Jiang S, Levine N, Watson RR. 2000. Carotenoid supplementation reduces erythema in 

human skin after simulated solar radiation exposure. Proc Soc Exp Biol Med 223(2):170-4. 

- Greul AK, Grundmann JU, Heinrich F, Pfitzner I, Bernhardt J, Ambach A, Biesalski HK, 

Gollnick H. 2002. Photoprotection of UV-irradiated human skin: an antioxidative combination of 

vitamins E and C, carotenoids, selenium and proanthocyanidins. Skin Pharmacol Appl Skin 

Physiol 15(5):307-15. 

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- Heinrich U, Gartner C, Wiebusch M, Eichler O, Sies H, Tronnier H, Stahl W. 2003. 

Supplementation with beta-carotene or a similar amount of mixed carotenoids protects humans 

from UV-induced erythema. J Nutr 133(1):98-101. 

- Cesarini JP, Michel L, Maurette JM, Adhoute H, Bejot M. 2003. Immediate effects of UV 

radiation on the skin: modification by an antioxidant complex containing carotenoids. 

Photodermatol Photoimmunol Photomed 19(4):182-9. 

- Mathews-Roth MM, Pathak MA, Parrish J, Fitzpatrick TB, Kass EH, Toda K, Clemens W. 1972. 

A clinical trial of the effects of oral beta-carotene on the responses of human skin to solar 

radiation. J Invest Dermatol 59(4):349-53. 

- McArdle F, Rhodes LE, Parslew RA, Close GL, Jack CI, Friedmann PS, Jackson MJ. 2004. 

Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced 

oxidative stress in human skin. Am J Clin Nutr 80(5):1270-5. 

- Wolf C, Steiner A, Honigsmann H. 1988. Do oral carotenoids protect human skin against 

ultraviolet erythema, psoralen phototoxicity, and ultraviolet-induced DNA damage? J Invest 

Dermatol 90(1):55-7. 

Evidence from Meta-Analysis: 

- [Koepcke 2007] Koepcke et al., 2007. Protection from sunburn with ß-carotene – A meta 

Analysis. In preparation for publication. 

References as to photoaging markers: 

Evidence from intervention studies 

- Battistutta D, Williams DL, Green A. 2000. Effectiveness of daily sunscreen application and bcarotene 

intake for prevention of photaging: A community-based randomised trial. 13th Int. 

Congress on Photobiology, July 1-6, 2000 Abstr. 58. 





Gollnick H. 2002. Photoprotection of UV-irradiated human skin: an antioxidative combination of 


Physiol 15(5):307-15. 

- Heinrich U, Tronnier H, Stahl W, Bejot M, Maurette JM. 2006. Antioxidant supplements improve 

parameters related to skin structure in humans. Skin Pharmacol Physiol 19(4):224-31. 

References as to photoimmune modulation: 


- Fuller CJ, Faulkner H, Bendich A, Parker RS, Roe DA. 1992. Effect of beta-carotene 

supplementation on photosuppression of delayed-type hypersensitivity in normal young men. 

Am J Clin Nutr 56(4):684-90. 

- Gollnick H, Hopfenmuller W, Hemmes C, Chun S, Schmid C, Sundermeier K, Biesalski HK. 

1996. Systemic beta carotene plus topical UV-sunscreen are an optimal protection against 

harmful effects of natural UV-sunlight: results of the Berli-Eilath study. Eur J Dermatol 6(3):200- 

205. 

- Herraiz LA, Hsieh WC, Parker RS, Swanson JE, Bendich A, Roe DA. 1998. Effect of UV 

exposure and beta-carotene supplementation on delayed-type hypersensitivity response in 

healthy older men. J Am Coll Nutr 17(6):617-24. 

Evidence from reviews 

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- Boelsma E, Hendriks HF, Roza L. 2001. Nutritional skin care: health effects of micronutrients 

and fatty acids. Am J Clin Nutr 73(5):853-64. 

- Chew BP, Park JS. 2004. Carotenoid action on the immune response. J Nutr 134(1):257S- 

261S. 

- Hughes DA. 1999. Effects of carotenoids on human immune function. Proc Nutr Soc 58(3):713- 

718. 

- Hughes DA. 2001. Dietary carotenoids and human immune function. Nutrition 17(10):823-827. 

References as to skin color and tanning: 


- Alaluf S, Heinrich U, Stahl W, Tronnier H, Wiseman S. 2002. Dietary carotenoids contribute to 

normal human skin color and UV photosensitivity. J Nutr 132(3):399-403. 




- Postaire E, Jungmann H, Bejot M, Heinrich U, Tronnier H. 1997. Evidence for antioxidant 

nutrients-induced pigmentation in skin: results of a clinical trial. Biochem Mol Biol Int 

42(5):1023-33. 

Mechanistic studies in vivo and in vitro 

- Goralczyk R, Wertz K. accepted, to be published in 2007. Skin photoprotection by carotenoids. 

In: Britton G, Liaaen-Jensen S, Pfander H, ditors. Carotenoids: Part C Carotenoids against 

disease: Birkhäuser. p Chapter 4. 

- Wertz K, Seifert N, Hunziker PB, Riss G, Wyss A, Lankin C, Goralczyk R. 2004. beta-carotene 

inhibits UVA-induced matrix metalloprotease 1 and 10 expression in keratinocytes by a singlet 

oxygen-dependent mechanism. Free Radic Biol Med 37(5):654-70. 

- Wertz K, Hunziker PB, Seifert N, Riss G, Neeb M, Steiner G, Hunziker W, Goralczyk R. 2005. 

beta-Carotene Interferes with Ultraviolet Light A-Induced Gene Expression by Multiple 

Pathways. J Invest Dermatol 124(2):428-34. 

- Wertz K, Seifert N, Hunziker PB, Riss G, Wyss A, Hunziker W, Goralczyk R. 2006. Betacarotene 

interference with UVA-induced gene expression by multiple pathways. Pure and 

Applied Chemistry 78(8):1539-1550. 

- Bando N, Hayashi H, Wakamatsu S, Inakuma T, Miyoshi M, Nagao A, Yamauchi R, Terao J. 

2004. Participation of singlet oxygen in ultraviolet-a-induced lipid peroxidation in mouse skin 

and its inhibition by dietary beta-carotene: an ex vivo study. Free Radic Biol Med 37(11):1854- 

63. 




- McArdle F, Rhodes LE, Parslew RA, Close GL, Jack CI, Friedmann PS, Jackson MJ. 2004. 

Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced 

oxidative stress in human skin. Am J Clin Nutr 80(5):1270-5. 

- O'Connor I, O'Brien N. 1998. Modulation of UVA light-induced oxidative stress by betacarotene, 

lutein and astaxanthin in cultured fibroblasts. J Dermatol Sci 16(3):226-30. 

- Skoog ML, Ollinger K, Skogh M. 1997. Microfluorometry using fluorescein diacetate reflects the 

integrity of the plasma membrane in UVA-irradiated cultured skin fibroblasts. Photodermatol 

Photoimmunol Photomed 13(1-2):37-42. 

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- Someya K, Totsuka Y, Murakoshi M, Kitano H, Miyazawa T. 1994. The effect of natural 

carotenoid (palm fruit carotene) intake on skin lipid peroxidation in hairless mice. J Nutr Sci 

Vitaminol (Tokyo) 40(4):303-14. 

- Obermuller-Jevic UC, Francz PI, Frank J, Flaccus A, Biesalski HK. 1999. Enhancement of the 

UVA induction of haem oxygenase-1 expression by beta-carotene in human skin fibroblasts. 

FEBS Lett 460(2):212-6. 

- Offord EA, Gautier JC, Avanti O, Scaletta C, Runge F, Kramer K, Applegate LA. 2002. 

Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in 

UVA-irradiated human skin fibroblasts. Free Radic Biol Med 32(12):1293-303. 

- Trekli MC, Riss G, Goralczyk R, Tyrrell RM. 2003. Beta-carotene suppresses UVA-induced 

HO-1 gene expression in cultured FEK4. Free Radic Biol Med 34(4):456-64. 

- Eicker J, Kurten V, Wild S, Riss G, Goralczyk R, Krutmann J, Berneburg M. 2003. 

Betacarotene supplementation protects from photoaging-associated mitochondrial DNA 

mutation. Photochem Photobiol Sci 2(6):655-9. 

- Offord EA, Gautier JC, Avanti O, Scaletta C, Runge F, Kramer K, Applegate LA. 2002. 

Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in 

UVA-irradiated human skin fibroblasts. Free Radic Biol Med 32(12):1293-303. 

- Antille C, Tran C, Sorg O, Saurat JH. 2004. Topical beta-carotene is converted to retinyl esters 

in human skin ex vivo and mouse skin in vivo. Exp Dermatol 13(9):558-61. 

- Wei RR, Wamer WG, Lambert LA, Kornhauser A. 1998. beta-Carotene uptake and effects on 

intracellular levels of retinol in vitro. Nutr Cancer 30(1):53-8. 

BETA-CAROTENE and Immune health 

Evidence from human studies [intervention and epidemiology] 

- Prabhala RH, Garewal HS,, Hicks M, Sampliner R, Watson R; The Effects of 13-cis-Retinoic 

Acid and Beta-Carotene on Cellular Immunity in Humans. Cancer 1991; 67:1556-1560 

- Moriguchi S, Okishima N, Sumida S, Okamura K, Doi T, Kishino Y. Beta-carotene 

supplementation enhances the lymphocyte proliferation with mitogens in human peripheral 

blood lymphocytes. Nutr Res 1996;16:211-218 

- Santos MS, Meydani SN, Leka L, Wu D, Fotouhi N, Meydani M, Hennekens CH, Gaziano JM. 

Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation.Am J 

Clin Nutr. 1996;64:772-777 

- Santos MS, Gaziano JM, Leka LS, Beharka AA, Hennekens CH, Meydani SN. Beta-caroteneinduced 

enhancement of natural killer cell activity in elderly men: an investigation of the role of 

cytokines. Am J Clin Nutr. 1998;68:164-170. 

- Wood SM, Beckham1 C, Yosioka2 A, Darban3 H, Watson RR. beta-Carotene and selenium 

supplementation enhances immune response in aged humans. 

- 

Integr. Med.. 2000;2:85-92. 

Inserra PF, Jiang S, Solkoff D, Lee J, Zhang Z, Xu M, Hesslink R, Wise J, Watson RR. Immune 

Function In Elderly Smokers And Nonsmokers Improves During Supplementation With Fruit 

and Vegetable Extracts. Integr Med 1999;2:3-10 

- Watzl B, Bub A, Briviba K, Rechkemmer G. Supplementation of a low-carotenoid diet with 

tomato or carrot juice modulates immune functions in healthy men. Ann Nutr Metab. 

2003;47:255-261. 

- van der Horst-Graat JM, Kok FJ, Schouten EG. Plasma carotenoid concentrations in relation 

to acute respiratory infections in elderly people. Br J Nutr. 2004;92:113-118 

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- Watzl B, Kulling SE, Moseneder J, Barth SW, Bub A.. A 4-wk intervention with high intake of 

carotenoid-rich vegetables and fruit reduces plasma C-reactive protein in healthy, nonsmoking 

men. Am J Clin Nutr. 2005;82:1052-1058 

Recognised text books, monographs and further supporting information 

- Hughes DA: Carotenoids and Immune Responses. In: Carotenoids in Health and Disease 

(Krinsky NI, Mayne ST, Sies H, eds.) Marcel Dekker, New York 2004, pp 503-517. 

- Chew BP, Park JS. Carotenoid action on the immune response. J Nutr. 2004;134:257S-261S 

- Hughes DA. Effects of carotenoids on human immune function. Proc Nutr Soc. 1999;58:713- 

718 

- Meydani SN, Wu D, Santos MS, Hayek MG. Antioxidants and immune response in aged 

persons: overview of present evidence. Am J Clin Nutr. 1995;62:1462S-1476S. 

- Roe DA, Fuller CJ: Carotenoids and Immune Function. In: Nutrition and Immunology (Klurfeld 

DM, ed,) Plenum Press, New York 1993, pp 229-238. 

- Bendich A. Beta-carotene and the immune response. Proc Nutr Soc. 1991;50:263-274. 

- Bendich A. Carotenoids and the immune response. J Nutr. 1989;119:112-115 

- Clausen SW. Carotenenemia and respiratory infections. Trans Am Pediatr Soc 1931;43:27-30 

- Palozza P, Serini S, Torsello A, Di Nicuolo F, Piccioni E, Ubaldi V, Pioli C, Wolf FI, Calviello G. 

Beta-carotene regulates NF-kappaB DNA-binding activity by a redox mechanism in human 

leukemia and colon adenocarcinoma cells. J Nutr. 2003;133):381-388. 

- Bai SK, Lee SJ, Na HJ, Ha KS, Han JA, Lee H, Kwon YG, Chung CK, Kim YM. beta-Carotene 

inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by 

suppressing redox-based NF-kappaB activation. Exp Mol Med. 2005;37):323-334. 

- Albers R, Antoine JM, Bourdet-Sicard R, Calder PC, Gleeson M, Lesourd B, Samartin S, 

Sanderson IR, Van Loo J, Vas Dias FW, Watzl B. Markers to measure immunomodulation in 

human nutrition intervention studies. Br J Nutr. 2005;94:452-481 

- Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheralblood 

lymphocytes and cancer incidence: an 11-year follow-up study of a general population. 

Lancet 2000; 356: 1795-99. 

- Ogata K, An E, Shioi Y, Nakamura K, Luo S, Yokose N, Minami S, Dan K. Association between 

natural killer cell activity and infection in immunologically normal elderly people. Clin Exp 

Immunol. 2001;124:392-397 

BETA-CAROTENE and Immune health in relation to UV-radiation 

Evidence from human intervention studies 

- Fuller CJ, Faulkner H, Bendich A, Parker RS, Roe DA. Effect of beta-carotene supplementation 

on photosuppression of delayed-type hypersensitivity in normal young men. Am J Clin Nutr. 

1992;56:684-690. 

- Gollnick, H, Hopfenmüller, W, Hemmes, C, Chun, SC, Schmid, C, Sundermeier, K, Biesalski, 

HK. Systemic beta-carotene plus topical UV sunscreen are an optimal protection against 

harmful effects of natural UV-sunlight: results of the Berlin-Eilath study. Eur J Dermatol. 

1996;6:200-205 

- Herraiz LA, Hsieh WC, Parker RS, Swanson JE, Bendich A, Roe DA. Effect of UV exposure 

and beta-carotene supplementation on delayed-type hypersensitivity response in healthy older 

men. J Am Coll Nutr. 1998;17:617-624. 


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- Clydesdale GJ, Dandie GW, Muller HK. Ultraviolet light induced injury: immunological and 

inflammatory effects. Immunol Cell Biol. 2001;79:547-568 

- Granstein RD, Matsui MS. UV radiation-induced immunosuppression and skin cancer. Cutis. 

2004;74(Suppl):4-9 

- Stahl W, Sies H: Carotenoids in systemic protection against sun-burn. In: Carotenoids in Health 

and Disease (Krinsky NI, Mayne ST, Sies H, eds.) Marcel Dekker, New York 2004, pp 491-502. 

- White WS, Kim CI, Kalkwarf HJ, Bustos P, Roe DA. Ultraviolet light-induced reductions in 

plasma carotenoid levels. Am J Clin Nutr. 1988;47:879-883. 

- Biesalski HK, Hemmes C, Hopfenmuller W, Schmid C, Gollnick HP. Effects of controlled 

exposure of sunlight on plasma and skin levels of beta-carotene. Free Radic Res. 

1996;24:215-224 

- Albers et al, Markers to measure immunomodulation in human nutrition intervention studies. Br 

J Nutr. 2005;94:452-481 

BETA-CAROTENE and Antioxidative properties / Protection against UV-induced erythema 

Evidence from human studies [intervention and cross-sectional (No 7)] 

- Mathews-Roth MM, Pathak MA, Parrish J, Fitzpatrick TB, Kass EH, Toda K, Clemens W. A 

clinical trial of the effects of oral beta-carotene on the responses of human skin to solar 

radiation. J Invest Dermatol. 1972;59:349-353. 

- Wolf C, Steiner A, Honigsmann H. Do oral carotenoids protect human skin against ultraviolet 

erythema, psoralen phototoxicity, and ultraviolet-induced DNA damage?. J Invest Dermatol. 

1988 90:55-57 

- Garmyn M, Ribaya-Mercado JD, Russel RM, Bhawan J, Gilchrest BA. Effect of beta-carotene 

supplementation on the human sunburn reaction. Exp Dermatol. 1995;4:104-111 

- Gollnick, H, Hopfenmüller, W, Hemmes, C, Chun, SC, Schmid, C, Sundermeier, K, Biesalski, 

HK. Systemic beta-carotene plus topical UV sunscreen are an optimal protection against 

harmful effects of natural UV-sunlight: results of the Berlin-Eilath study. Eur J Dermatol. 

1996;6:200-205 

- Lee J, Jiang S, Levine N, Watson RR. Carotenoid supplementation reduces erythema in 

human skin after simulated solar radiation exposure. Proc Soc Exp Biol Med. 2000;223:170- 

174. 

- Stahl W, Heinrich U, Jungmann H, Sies H, Tronnier H. Carotenoids and carotenoids plus 

vitamin E protect against ultraviolet light-induced erythema in humans. Am J Clin Nutr. 

2000;71:795-798. 

- Alaluf S, Heinrich U, Stahl W, Tronnier H, Wiseman S. Dietary carotenoids contribute to normal 

human skin color and UV photosensitivity. J Nutr. 2002;132:399-403. 


Gollnick H. Photoprotection of UV-irradiated human skin: an antioxidative combination of 


Physiol. 2002;15:307-315. 

- Cesarini JP, Michel L, Maurette JM, Adhoute H, Bejot M. Immediate effects of UV radiation on 

the skin: modification by an antioxidant complex containing carotenoids. Photodermatol 

Photoimmunol Photomed. 2003;19:182-189. 

- Heinrich U, Gartner C, Wiebusch M, Eichler O, Sies H, Tronnier H, Stahl W. Supplementation 

with beta-carotene or a similar amount of mixed carotenoids protects humans from UV-induced 

erythema. J Nutr. 2003;133:98-101. 

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- McArdle F, Rhodes LE, Parslew RA, Close GL, Jack CI, Friedmann PS, Jackson MJ. Effects of 

oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced oxidative 

stress in human skin. Am J Clin Nutr. 2004;80:1270-1275. 


- Steenvoorden DP, van Henegouwen GM. The use of endogenous antioxidants to improve 

photoprotection. J Photochem Photobiol B. 1997;4:1-10. 

- Fuchs J. Potentials and limitations of the natural antioxidants RRR-alpha-tocopherol, Lascorbic 

acid and beta-carotene in cutaneous photoprotection. Free Radic Biol Med. 

1998;25:848-873. 

- Biesalski HK, Obermueller-Jevic UC. UV light, beta-carotene and human skin-beneficial and 

potentially harmful effects. Arch Biochem Biophys. 2001;389:1-6. 

- Boelsma E, Hendriks HF, Roza L Nutritional skin care: health effects of micronutrients and fatty 

acids. Am J Clin Nutr. 2001;73:853-856 

- Anstey AV. Systemic photoprotection with alpha-tocopherol (vitamin E) and beta-carotene. Clin 

Exp Dermatol. 2002;27:170-176. 

- Stahl W, Sies H. Carotenoids and protection against solar UV radiation. Skin Pharmacol Appl 

Skin Physiol. 2002;15:291-296. 

- Sies H, Stahl W. Nutritional protection against skin damage from sunlight. Annu Rev Nutr. 

2004;24:173-200. 

- Darvin M, Zastrow L, Sterry W, Lademann J Effect of supplemented and topically applied 

antioxidant substances on human tissue. Skin Pharmacol Physiol. 2006;19:238-247 

- Pelz R, Schmidt-Faber B, Heseker H. Carotenoid intake in the German National Food 

Consumption Survey. Z Ernahrungswiss 1998;37:319-327 

- Darr D, Fridovich I. Free radicals in cutaneous biology. J Invest Dermatol. 1994;102:671-675 

- Badminton MN, Elder GH. Management of acute and cutaneous porphyrias. Int J Clin Pract. 

2002;56:272-278. 

- Stahl W, Heinrich U, Jungmann H, von Laar J, Schietzel M, Sies H, Tronnier H. Increased 

dermal carotenoid levels assessed by noninvasive reflection spectrophotometry correlate with 

serum levels in women ingesting Betatene. J Nutr. 1998;128:903-907. 

- Stahl W, Sies H: Carotenoids in systemic protection against sun-burn. In: Carotenoids in Health 

and Disease (Krinsky NI, Mayne ST, Sies H, eds.) Marcel Dekker, New York 2004, pp 491-502 

BETA-CAROTENE IN COMBINATION WITH VITAMIN E AND VITAMIN C - Eye health and 

vision 

Human intervention studies 

ARC and AMC related 

- AREDS Research Group, "The Age-related Eye Disease Study (AREDS): design implications - 

AREDS report No. 1", Contr. Clin. Trials, 20 573-600 (1999). 

- AREDS Research Group, "A randomized, placebo-controlled, clinical trial of high-dose 

supplementation with vitamins C and E and beta carotene for age-related cataract and vision 

loss - AREDS report no. 9", Arch. Ophthalmol., 119 (10), 1439-1452 (2001). 

- AREDS Research Group, "A randomized, placebo-controlled, clinical trial of high-dose 

supplementation with vitamins C and E, b-carotene, and zinc for age-related macular 

degeneration and vision loss: AREDS report no. 8", Arch. Ophthalmol., 119 (10), 1417-1436 

(2001). 

20 

20

- ATBC Study Group, "The effect of vitamin E and beta-carotene on the incidence of lung cancer 

and other cancers in male smokers." N Engl J Med, 330 1029-1035 (1994). 

- Christen, W., Glynn R., Sperduto R., et al., "Age-related cataract in a randomized trial of betacarotene 

in women." Ophthalmic Epidemiol., 11 (5), 401-412 (2004). 

- Christen, W.G., Manson J.E., Glynn R.J., et al., "A randomized trial of beta carotene and agerelated 

cataract in US physicians." Arch Ophthalmol., 121 (3), 372-378 (2003). 

- Christen, W.G., Gaziano J.M.and Hennekens C.H., "Design of Physicians' Health Study II--a 

randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, 

cardiovascular disease, and eye disease, and review of results of completed trials", Annals of 

Epidemiology, 10 (2), 125-134 (2000). 

- Christen, W.G., "beta-carotene and age-related cataract in a randomized trial of U.S. 

Physicians." Invest. Ophthalmol. Vis. Sci., 42 S518, Abstract 2790 (2001). 

- Chylack, L.T., Jr., Wolfe J.K., Friend J., et al., "Validation of methods for the assessment of 

cataract progression in the Roche European-American Anticataract Trial (REACT)", 

Ophthalmic Epidemiology, 2 (2), 59-75 (1995). 

- Chylack, L.T., Jr., Brown N.P., Bron A., et al., "The Roche European American Cataract Trial 

(REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant 

micronutrient mixture to slow progression of age-related cataract", Ophthalmic Epidemiology, 9 

(1), 49-80 (2002). 

- Gritz, D.C., Srinivasan M., Smith S.D., et al., "The Antioxidants in Prevention of Cataracts 

Study: effects of antioxidant supplements on cataract progression in South India." Br J 

Ophthalmol., 90 (7), 847-851 (2006). 

- PHS-Group, "Final report on the aspirin component of the ongoing Physicians' Health Study. 

Steering Committee of the Physicians' Health Study Research Group." New Engl J Med., 321 

(3), 129-135 (1989). 

- Sperduto, R.D., Hu T.S., Milton R.C., et al., "The Linxian cataract studies. Two nutrition 

intervention trials", Arch. Ophthalmol., 111 (9), 1246-1253 (1993). 

- Teikari, J.M., Virtamo J., Rautalahti M., et al., "Long-term supplementation with alphatocopherol 

and beta-carotene and age-related cataract", Acta Ophthalmol Scand, 75 (6), 634- 

640 (1997) . 

- Teikari, J.M., Laatikainen L., J. V., et al., "Six-year supplementation with alpha-tocopherol and 

beta-carotene and age-related maculopathy", Acta-Ophthalmol-Scand, 76 (2), 224-229 (1998). 

Epidemiological Studies 

- Knekt, P., Heliovaara M., Rissanen A., et al., "Serum antioxidant vitamins and risk of cataract", 

British Medical Journal, 305 (6866), 1392-1394 (1992). 

- Mares-Perlman, J.A., Millen A.E., Ficek T.L., et al., "The body of evidence to support a 

protective role for lutein and zeaxanthin in delaying chronic disease. Overview." J Nutr., 132 

(3), 518S-524S (2002). 

- Jacques, P.F.and Chylack L.T., "Epidemiologic evidence of a role for the antioxidant vitamins 

and carotenoids in cataract prevention." Am J Clin Nutr., 53 (1 (Suppl.)), 352S-355S (1991). 

- Jacques, P.F., Taylor A., Moeller S., et al., "Long-term nutrient intake and 5-year change in 

nuclear lens opacities." Arch Ophthalmol, 123 (4), 517-526 (2005). 

- Taylor, A.and Hobbs M., "2001 assessment of nutritional influences on risk for cataract." 

Nutrition, 17 (10), 845-857 (2001). 

Reviews 

21 

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- Schalch, W.and Chylack L.T.j., "Antioxidative Mikronährstoffe und Katarakt - Ein Überblick und 

ein Vergleich der Kataraktstudien "AREDS" und "REACT" (German, "Antioxidant micronutrients 

and cataract - review and comparison of the AREDS and REACT cataract studies")", 

Ophthalmologe, 100 (3), 181-189 (2003). 

Beta carotene, vitamin C and vitamin E presence and antioxidant action in lens and 

aqueous 

- Augustin, A.J., Dick H.B., Winkgen A., et al., "[Cause and prevention of oxidative damage to 

the eye. Current knowledge]", Ophthalmologe., 98 (8), 776-796; quiz 796-777 (2001). 

- Bates, C.J.and Cowen T.D., "Effects of age and dietary vitamin C on the contents of ascorbic 

acid and acid-soluble thiol in lens and aqueous humour of guinea-pigs." Exp. Eye Res., 46 (6), 

937-945 (1988). 

- Bates, C.J., Chen S.J., Macdonald A., et al., "Quantitation of vitamin E and a carotenoid 

pigment in cataractous human lenses, and the effect of a dietary supplement", Int J Vitam Nutr 

Res, 66 (4), 316-321 (1996). 

- Handelman, G.J., Snodderly D.M., Adler A.J., et al., "Measurement of carotenoids in human 

and monkey retinas", Methods in Enzymology, 213 220-230 (1992). 

- Burton, G.W.and Ingold K.U., "beta-carotene: an unusual type of lipid antioxidant", Science, 

224 (4649), 569-573 (1984). 

- Jacques, P.F., Taylor A., Moeller S., et al., "Long-term nutrient intake and 5-year change in 

nuclear lens opacities." Arch Ophthalmol, 123 (4), 517-526 (2005). 

- Kwan, M., Niinikoski J.and Hunt T.K., "In Vivo Measurements of Oxygen Tension in the 

Cornea, Aqueous Humor, and Anterior Lens of the Open Eye." Invest. Ophthalmol. Vis. Sci., 11 

108-114 (1972). 

- Reiss, G.R., Werness P.G., Zollman P.E., et al., "Ascorbic acid levels in the aqueous humor of 

nocturnal and diurnal mammals", Arch Ophthalmol., 104 (5), 753-755 (1986). 

- Taylor, A., Jacques P.F., Nowell T., et al., "Vitamin C in human and guinea pig aqueous, lens 

and plasma in relation to intake", Curr. Eye Res., 16 (9), 857-864 (1997). 

- Tessier, F., Moreaux V., Birlouez-Aragon I., et al., "Decrease in vitamin C concentration in 

human lenses during cataract progression." Int J Vitam Nutr Res., 68 (5), 309-315 (1998). 

- Wu, S.Y.and Leske M.C., "Antioxidants and cataract formation: a summary review", Int 

Ophthalmol Clin., 40 (4), 71-81 (2000). 

- Yeum, K.J., Taylor A., Tang G., et al., "Measurement of carotenoids, retinoids, and tocopherols 

in human lenses", Invest. Ophthalmol. Vis. Sci., 36 (13), 2756-2761 (1995). 

- Yeum, K.J., Shang F.M., Schalch W., et al., "Fat-soluble nutrient concentrations in different 

layers of human cataractous lens", Curr. Eye Res., 19 (6), 502-505 (1999) 

BETA-SITOSTEROL and Cholesterol 

Monographs: 

- Phytosterol and Phytosterol Esters. Healthful Lipids. Edited by Casimir C. Akoh, Oi-Ming Lai. 

Champaign, Illinois. AOCS Press, 2005. ISBN: 1-893997-51-0 

Peer-reviewed publications: 

- Fassbender K, Lütjohann D, Dik MG, Bremmer M, König J, Walter S, Liu Y, Letièmbre M, von 

Bergmann K, Jonker C. Moderately elevated plant sterol levels are associated with reduced 

cardiovascular risk – The LASA study. Atherosclerosis, Article in press (2006) 

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- Rozner S, Garti N. The activity and absorption relationship of cholesterol and phytosterols. 

Colloids and SurfacesA: Physicochem. Eng. Aspects 282-283: 435-456 (2006) 

- Wolfs M, de Jong N, Ocké M.C, Verhagen H,Verschuren WMM. Effectiveness of customary 

use of phytosterol/-stanol enriched margarines on blood cholesterol lowering. Food and 

Chemical Toxicology 44, (1): 1682-1688 (2006). 

BETA-SITOSTEROL and Kidney and prostate health 

Review 

- Gerber GS. Phytotherapy for benign prostatic hyperplasia. Curr Urol Rep. 2002 Aug;3(4):285- 

91. 

- Wilt TJ, MacDonald R, Ishani A. Beta-sitosterol for the treatment of benign prostatic 

hyperplasia: a systematic review. BJU Int. 1999 Jun;83(9):976-83. 

- Wilt T, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J. Beta-sitosterols for benign prostatic 

hyperplasia. Cochrane Database Syst Rev. 2000;(2):CD001043. 

Human studies 

- Berges RR, Kassen A, Senge T. Treatment of symptomatic benign prostatic hyperplasia with 

beta-sitosterol: an 18-month follow-up. BJU Int. 2000 May;85(7):842-6. 

- Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of 

beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH- 

Phyto Study group. Br J Urol. 1997 Sep;80(3):427-32. 

- Preuss HG, Marcusen C, Regan J, Klimberg IW, Welebir TA, Jones WA. Randomized trial of a 

combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of 

benign prostatic hyperplasia (BPH). Int Urol Nephrol. 2001;33(2):217-25. 

- Berges RR, Windeler J, Trampisch HJ, Senge T. Randomised, placebo-controlled, double-blind 

clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study 

Group. Lancet. 1995 Jun 17;345(8964):1529-32. 

- Kobayashi Y, Sugaya Y, Tokue A. Clinical effects of beta-sitosterol (phytosterol) on benign 

prostatic hyperplasia: preliminary study. Hinyokika Kiyo. 1998 Dec;44(12):865-8. 

Animal study 

- Ryokkynen A, Nieminen P, Mustonen AM, Pyykonen T, Asikainen J, Hanninen S, Mononen J, 

Kukkonen JV. Phytoestrogens alter the reproductive organ development in the mink (Mustela 

vison). Toxicol Appl Pharmacol. 2005 Jan 15;202(2):132-9. 

In vitro studies 

- Kassen A, Berges R, Senge T. Effect of beta-sitosterol on transforming growth factor-beta-1 

expression and translocation protein kinase C alpha in human prostate stromal cells in vitro. 

Eur Urol. 2000 Jun;37(6):735-41. 

- Awad AB, Gan Y, Fink CS. Effect of beta-sitosterol, a plant sterol, on growth, protein 

phosphatase 2A, and phospholipase D in LNCaP cells. Nutr Cancer. 2000;36(1):74-8. 

- Chuu CP, Kokontis JM, Hiipakka RA, Liao S. Modulation of liver X receptor signaling as novel 

therapy for prostate cancer. J Biomed Sci. 2007 Mar 20; [Epub ahead of print] 

BETAINE and Hearth health and vascular system 

Peer-reviewed articles 

- Barak AJ, Tuma DJ. Betaine, metabolic by-product or vital methylating agent? Life Sci 

1983;32:771-4. 

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- Boushey CJ, et al. A quantitative assessment of plasma homocysteine as a risk factor for 

vascular disease. Probable benefits of increasing folic acid intakes. JAMA. Oct 4, 1995; 

274(13): 1049-1057. 

- Brower IA, Verhoef P, Urgert R. Betaine supplementation and plasma homocysteine in healthy 

volunteers. Arch Inter Med. 2000; 160:2546-2547. 

- Eikelboom JW, Lonn E, Genest J, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular 

disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999;131:363-375. 

- Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular disease. A 

statement for healthcare professionals from the nutrition committee, American Heart 

Association. Circulation. 1999;99:178-182. 

- Mar MH, Zeisel SH. Betaine in wine: answer to the French paradox? Med Hypotheses. 

1999;53(5):383-385. 

- Sarkar PK, Lambert LA. Aetiology and treatment of hyperhomocysteinaemia causing ischaemic 

stroke. Int J Clin Pract. 2001;55(4):262-268. 

- van Guldener C, Stehouwer CD. Homocysteine-lowering treatment: an overview. Expert Opin 

Pharmacother. 2001;2(9):1449-1460. 

- Schwab et al.(2006): Orally administered Betaine has an acute and dose-dependent effect on 

serum betaine and plasma homocysteine concentrations in healthy humans. J.Nutr. 136: 34-38 

Textbooks 

- Pizzorno JE, Murray MT, eds. Textbook of Natural Medicine. Vol 1. 2nd ed. Churchill 

Livingstone; 1999:462-466. 

- Shils M, Olson J, Shike M, eds. Modern Nutrition in Health and Disease Vol 1. 9th ed. Media: 

Williams & Wilkins; 1999: 452. 

BETALAINS and Antioxidant properties 


- British Nutrition Foundation – Plants: Diet and Health – The Report of the British Nutrition 

Foundation Task Force – Edited by Dr Gail Goldberg 

Reviews 

- Cai Y, Sun M, Corke H. Antioxidant activity of betalains from plants of the amaranthaceae. J 

Agric Food Chem. 2003 Apr 9;51(8):2288-94. 

- Gandia-Herrero F, Escribano J, Garcia-Carmona F. Characterization of the activity of 

tyrosinase on betanidin. J Agric Food Chem. 2007 Feb 21;55(4):1546-51. Epub 2007 Jan 27. 

- Kanner J, Harel S, Granit R. Betalains--a new class of dietary cationized antioxidants. J Agric 

Food Chem. 2001 Nov;49(11):5178-85. 

- Sembries S, Dongowski G, Mehrlander K, Will F, Dietrich H. Physiological effects of extraction 

juices from apple, grape, and red beet pomaces in rats. J Agric Food Chem. 2006 Dec 

27;54(26):10269-80. 

- Stintzing FC, Herbach KM, Mosshammer MR, Carle R, Yi W, Sellappan S, Akoh CC, Bunch R, 

Felker P. Color, betalain pattern, and antioxidant properties of cactus pear (Opuntia spp.) 

clones. J Agric Food Chem. 2005 Jan 26;53(2):442-51. 

- Strack D, Vogt T, Schliemann W. Recent advances in betalain research. Phytochemistry. 

2003 Feb;62(3):247-69. Review. 

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- Tesoriere L, Allegra M, Butera D, Gentile C, Livrea MA. Cytoprotective effects of the 

antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. Free Radic Res. 

2006 Jul;40(7):753-61. 

- Tesoriere L, Allegra M, Butera D, Livrea MA. Absorption, excretion, and distribution of dietary 

antioxidant betalains in LDLs: potential health effects of betalains in humans. Am J Clin Nutr. 

2004 Oct;80(4):941-5. 

- Tesoriere L, Butera D, Allegra M, Fazzari M, Livrea MA. Distribution of betalain pigments in 

red blood cells after consumption of cactus pear fruits and increased resistance of the cells to 

ex vivo induced oxidative hemolysis in humans. J Agric Food Chem. 2005 Feb 23;53(4):1266- 

70. 

- Tesoriere L, Butera D, D'Arpa D, Di Gaudio F, Allegra M, Gentile C, Livrea MA. Increased 

resistance to oxidation of betalain-enriched human low density lipoproteins. Free Radic Res. 

2003 Jun;37(6):689- 96. 


- Allegra M, Furtmuller PG, Jantschko W, Zederbauer M, Tesoriere L, Livrea MA, Obinger C. 

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and 

hypochlorous acid. Biochem Biophys Res Commun. 2005 Jul 8;332(3):837-44. 

- Butera D, Tesoriere L, Di Gaudio F, Bongiorno A, Allegra M, Pintaudi AM, Kohen R, Livrea MA. 

Antioxidant activities of sicilian prickly pear (Opuntia ficus indica) fruit extracts and reducing 

properties of its betalains: betanin and indicaxanthin. J Agric Food Chem. 2002 Nov 

6;50(23):6895-901. 

- Frank T, Stintzing FC, Carle R, Bitsch I, Quaas D, Strass G, Bitsch R, Netzel M. Urinary 

pharmacokinetics of betalains following consumption of red beet juice in healthy humans. 

Pharmacol Res. 2005 Oct;52(4):290-7. 

- Kapadia GJ, Azuine MA, Sridhar R, Okuda Y, Tsuruta A, Ichiishi E, Mukainake T, Takasaki M, 

Konoshima T, Nishino H, Tokuda H. Chemoprevention of DMBA-induced UV-B promoted, 

NOR-1- induced TPA promoted skin carcinogenesis, and DEN-induced phenobarbital 

promoted liver tumors in mice by extract of beetroot. Pharmacol Res. 2003 Feb;47(2):141-8. 

- Kugler F, Stintzing FC, Carle R. Identification of betalains from petioles of differently colored 

Swiss chard (Beta vulgaris L. ssp. cicla [L.] Alef. Cv. Bright Lights) by high-performance liquid 

chromatography-electrospray ionization mass spectrometry. J Agric Food Chem. 2004 May 

19;52(10):2975-81. 

- Lee CH, Wettasinghe M, Bolling BW, Ji LL, Parkin KL. Betalains, phase II enzyme-inducing 

components from red beetroot (Beta vulgaris L.) extracts. Nutr Cancer. 2005;53(1):91-103. 

- Pavlov A, Kovatcheva P, Georgiev V, Koleva I, Ilieva M. Biosynthesis and radical scavenging 

activity of betalains during the cultivation of red beet (Beta vulgaris) hairy root cultures. Z 

Naturforsch [C]. 2002 Jul-Aug;57(7-8):640-4. 

- Pavlov A, Kovatcheva P, Tuneva D, Ilieva M, Bley T. Radical scavenging activity and stability 

of betalains from Beta vulgaris hairy root culture in simulated conditions of human 

gastrointestinal tract. lant Foods Hum Nutr. 2005 Jun;60(2):43-7. 

- Reddy MK, Alexander-Lindo RL, Nair MG. Relative inhibition of lipid peroxidation, 

cyclooxygenase enzymes, and human tumor cell proliferation by natural food colors. J Agric 

Food Chem. 2005 Nov 6;53(23):9268-73. 

- Rudrappa T, Neelwarne B, Aswathanarayana RG. In situ and Ex situ adsorption and recovery 

of betalains from hairy root cultures of Beta vulgaris. Biotechnol Prog. 2004 May- 

Jun;20(3):777-85. 

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BIOFLAVONOIDS and Vein health 

- Martinez MJ et al. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 20: 

CD003229, 2005 

- Katsenis K. Micrinized purified flavonoid fraction (MPFF): a review of itspharmacological 

effects, therapeutic efficacy and benefits in the management of chronic venous insufficicency. 

Curr Vasc Pharmacol. 3: 1-9, 2005 

BIOFLAVONOIDS FROM CITRUS and Vascular health 

Expert reviews and opinions 

- Diehm, C., 1996. The role of oedema protective drugs in the treatment of chronic venous 

insufficiency: A review of evidence based on placebo-controlled clinical trials with regard to 

efficacy and tolerance. Phlebology 1(1), 23-29. 

- Lyseng-Williamson, K. A.; Perry, C. M., 2003. Micronised purified flavonoid fraction - A review 

of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs 63 (1), 71- 

100. 

- Struckmann, J. R.; Nicolaides, A. N., 1994. Flavonoids - A Review of the Pharmacology and 

Therapeutic Efficacy of Daflon 500 Mg in Patients with Chronic Venous Insufficiency and 

Related Disorders. Angiology 45 (6), 419-428. 


- Cospite, M., 1994. Double-Blind, Placebo-Controlled Evaluation of Clinical Activity and Safety 

of Daflon 500Mg in the Treatment of Acute Hemorrhoids. Angiology 45 (6), 566-573. 

- Guilhou, J. J.; Dereure, O.; Marzin, L.; Ouvry, P.; Zuccarelli, F.; Debure, C.; VanLanduyt, H.; 

GilletTerver, M. N.; Guillot, B.; Levesque, H.; Mignot, J.; PIllion, G.; Fevrier, B.; Dubeaux, D., 

1997. Efficacy of Daflon 500 mg in venous leg ulcer healing: A double-blind, randomized, 

controlled versus placebo trial in 107 patients. Angiology 48 (1), 77-85. 

- Misra, M. C.; Parshad, R., 2000. Randomized clinical trial of micronized flavonoids in the early 

control of bleeding from acute internal haemorrhoids. British Journal of Surgery 87 (7), 868- 

872. 

- Thanapongsathorn, W.; Vajrabukka, T., 1992. Clinical-Trial of Oral Diosmin (Daflon(R)) in the 

Treatment of Hemorrhoids. Diseases of the Colon & Rectum 35 (11), 1085-1088. 

In vitro experiments 

- Villa, P.; Cova, D.; Defrancesco, L.; Guaitani, A.; Palladini, G.; Perego, R., 1992. Protective 

Effect of Diosmetin on Invitro-Cell Membrane Damage and Oxidative Stress in Cultured Rat 

Hepatocytes. Toxicology 73 (2), 179-189. 

BOVINE COLOSTRUM and Immune health/source of immunoglobulins 

Generally accepted role(s) 

- Bostwick et al (2000), Lactoglobulins. In: Natural Food Antimicrobial Systems (ed. A.S.Naidu), 

CRC Press, Boca Raton 

- Kelly GS (2003), Bovine colostrums : a review of clinical uses. Alternative Medicine Review 8 

(no.4), 378-394 

- Korhonen et al (2000), Milk immunoglubulins and complement factors. British Journal of 

Nutrition 84, Suppl.1, S75-S80 

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- Playford et al (2000), Colostrum and milk-derived peptide growth factors for the treatment of 

gastrointestinal disorders. American Journal Clinical Nutrition 72, 5–14 

Meta-analyses and Critical Expert Reviews 

- Mehra et al (2006), Milk immunoglobulins for health promotion. International Dairy Journal 

16(11), 1262-1271 

- Valenti & Antonini (2005), Lactoferrin: an important host defence against microbial and viral 

attack. Cellular and Molecular Life Sciences 62(22), 2576-2587 


- Plettenberg et al (1993) A preparation from bovine colostrum in the treatment of HIV-postive 

patients with chronic diarrhea. Clinical Investigations 71, 42-45. 

- Rump et al (1992) Treatment of diarrhoea in human immunodeficiency virus-infected patients 

with immunoglobulins from bovine colostrum. Clinical Investigations 70, 588-594 

- Stephan et al (1990), Antibodies from colostrums in oral immunotherapy. Journal Clinical 

Chemistry Clinical Biochemistry 28,19-23. 

BOVINE LACTOFERRIN and Antimicrobial / Antiviral / Innate host defense 

Textbooks 

- Faber et al (1997) ; Altered domain closure and iron binding in lactoferrin mutants, In: 

Hutchens, T.W. & Lönnerdal, B. (editors), Lactoferrin: interactions and biological functions, 

Humana Press, New Jersey, 25-38 

- Naidu (2000); Lactoferrin. In: Natural Food Antimicrobial Systems (ed. A.S.Naidu), CRC press, 

Boca Raton, 17-102. 

- Reiter (1985); The biological significance of the non-immunoglobulin protective proteins in milk 

: lysozyme, lactoferrin and lactoperoxidase. In: Developments in Dairy Chemistry-3 (ed. 

P.F.Fox), 281-336, Elsevier Applied Science Publishers, London. 

Reviews 

- Baker HM, Baker EN. Lactoferrin and iron: structural and dynamic aspects of binding and 

release. Biometals. 2004 Jun;17(3):209-16. 

- Legrand D, Elass E, Carpentier M, Mazurier J. Lactoferrin: a modulator of immune and 

inflammatory responses. Cell Mol Life Sci. 2005 Nov;62(22):2549-59. 

- Lonnerdal B, Iyer S. Lactoferrin: molecular structure and biological function. Annu Rev Nutr. 

1995;15:93-110. 

- Seganti L, Di Biase AM, Marchetti M, Pietrantoni A, Tinari A, Superti F. Antiviral activity of 

lactoferrin towards naked viruses. Biometals. 2004 Jun;17(3):295-9. 

- Steijns JM, van Hooijdonk AC. Occurrence, structure, biochemical properties and technological 

characteristics of lactoferrin. Br J Nutr. 2000 Nov;84 Suppl 1:S11-7. 

- van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK. Antiviral activities of 

lactoferrin. Antiviral Res. 2001 Dec;52(3):225-39. 

- Valenti P, Antonini G. Lactoferrin: an important host defence against microbial and viral attack. 

Cell Mol Life Sci. 2005 Nov;62(22):2576-87. 

- Yamauchi K, Wakabayashi H, Shin K, Takase M. Bovine lactoferrin: benefits and mechanism 

of action against infections. Biochem Cell Biol. 2006 Jun;84(3):291-6 


27 

27

- Ajello M.; Greco R.; Giansanti F.; Massucci M.T.; Antonini G.; Valenti P. Anti-invasive activity of 

bovine lactoferrin towards group A streptococci. 2002) Biochemistry and Cell Biology 80(1), 

119-124. 

- Di Mario F, Aragona G, Dal Bo N, Cavestro GM, Cavallaro L, Iori V, Comparato G, Leandro G, 

Pilotto A, Franze A. Use of bovine lactoferrin for Helicobacter pylori eradication. Dig Liver Dis. 

2003 Oct;35(10):706-10. 

- Groot F, Geijtenbeek TB, Sanders RW, Baldwin CE, Sanchez-Hernandez M, Floris R, van 

Kooyk Y, de Jong EC, Berkhout B. Lactoferrin prevents dendritic cell-mediated human 

immunodeficiency virus type 1 transmission by blocking the DC-SIGN--gp120 interaction. J 

Virol. 2005 Mar;79(5):3009-15. 

- Ishii K, Takamura N, Shinohara M, Wakui N, Shin H, Sumino Y, Ohmoto Y, Teraguchi S, 

Yamauchi K. Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 

12 months. Hepatol Res. 2003 Mar;25(3):226-233. 

- Okuda M, Nakazawa T, Yamauchi K, Miyashiro E, Koizumi R, Booka M, Teraguchi S, Tamura 

Y, Yoshikawa N, Adachi Y, Imoto I. Bovine lactoferrin is effective to suppress Helicobacter 

pylori colonization in the human stomach: a randomized, double-blind, placebo-controlled 

study. J Infect Chemother. 2005 Dec;11(6):265-9. 

- Yamauchi K, Hiruma M, Yamazaki N, Wakabayashi H, Kuwata H, Teraguchi S, Hayasawa H, 

Suegara N, Yamaguchi H. Oral administration of bovine lactoferrin for treatment of tinea pedis. 

A placebo-controlled, double-blind study. Mycoses. 2000;43(5):197-202. 

- Zimecki M, Wlaszczyk A, Wojciechowski R, Dawiskiba J, Kruzel M. Lactoferrin regulates the 

immune responses in post-surgical patients. Arch Immunol Ther Exp (Warsz). 2001;49(4):325- 

33. 

General References 

- Baker EN, Anderson BF, Baker HM, Day CL, Haridas M, Norris GE, Rumball SV, Smith CA, 

Thomas DH. Three-dimensional structure of lactoferrin in various functional states. Adv Exp 

Med Biol. 1994;357:1-12. 

- Spik G, Coddeville B, Mazurier J, Bourne Y, Cambillaut C, Montreuil J. Primary and threedimensional 

structure of lactotransferrin (lactoferrin) glycans. Adv Exp Med Biol. 1994;357:21- 

32. 

- Pierce A, Colavizza D, Benaissa M, Maes P, Tartar A, Montreuil J, Spik G. Molecular cloning 

and sequence analysis of bovine lactotransferrin. Eur J Biochem. 1991 Feb 26;196(1):177-84. 

- Moore SA, Anderson BF, Groom CR, Haridas M, Baker EN. Three-dimensional structure of 

diferric bovine lactoferrin at 2.8 A resolution. J Mol Biol. 1997 Nov 28;274(2):222-36. 

- Haridas M, Anderson BF, Baker EN. Structure of human diferric lactoferrin refined at 2.2 A 

resolution. Acta Crystallogr D Biol Crystallogr. 1995 Sep 1;51(Pt 5):629-46. 

- Brodie AM, Ainscough EW, Baker EN, Baker HM, Shongwe MS, Smith CA. Synergism and 

substitution in the lactoferrins. Adv Exp Med Biol. 1994;357:33-44. 

- GRAS Notice GRN000077 (http://www.cfsan.fda.gov/~rdb/opa-gras.html) 

BRANCHED CHAIN AMINO ACIDS (LEUCINE, ISOLEUCINE, VALINE) and Muscle 

metabolism 


- Encyclopedia of Human Nutrition (1st edition), p 1842, 1856 

- Editors: M. J. Sadler, J. J. Strain, B. Caballero 

28 

28

Reviews 

- Blomstrand E, Newsholme EA, The plasma level of some amino acids and physical and mental 

fatigue. Experientia 1996; 15: 413-415 

- Ohtani M, Sugita M, Maruyama K, Amino acid mixture improves training efficiency in athletes J. 

Nutr. 2006; 136, 538S-543S 


- Blomstrand E, Saltin B, BCAA intake affects protein metabolism in muscle after but not during 

exercise in humans. Am. J. Physiol. Endocrinol. Metab. 2001, 281: E365-E374 

- Blomstrand, Hassmen P, Ek E, et al., Effects of branched-chain amino acid supplementation 

on serum creatine kinase and lactate. Acta Physiol. Scand. 1997; 159: 41-49 

- Blomstrand E, Newsholme EA, Effect of branched-chain amino acid supplementation on the 

exercise-induced change in aromatic amino acid concentration in human muscle. Acta Physiol. 

Scand. 1992; 146: 293-298 

- Børsheim E, Tipton KD, Wolf SE, Wolfe RR, Effects of branched-chain amino acid 

supplementation on serum creatine kinase and lactate. Am. J. Physiol. Endocrinol. Metab. 

2002; 283: E648– E657 

- Coombes JS, McNaughton LR, Effects of branched-chain amino acid supplementation on 

serum creatine kinase and lactate. The Journal of Sports Medicine and Physical Fitness 2000; 

40: 240-246 

- Crowe MJ, Jarrad N, Weatherson JN, et al., Effects of dietary leucine supplementation on 

exercise performance. Eur. J. Appl. Physiol. August 2005 

- Karlsson HKR, Nilsson PA, Nilsson J, et al., Branched-chain amino acids increase p70S6k 

phosphorylation in human skeletal muscle after resistance exercise. Am. J. Physiol. Endocrinol. 

Metab. 2004 ; 287: E1-E7 

- Mittleman KD, Ricci MR, Bailey SP, Branched-chain amino acids prolong exercise during heat 

stress in men and women. J. Sports Med. Phys. Fitness 2000; 40: 240-246 

- Nosaka K, Sacco P, Mawatari K, Effects of Amino Acid Supplementation on Muscle Soreness 

and Damage. Int. J. Sport. Nutr. Exerc. Metab. 2006; 16: 620-635 

- Parry-Billings P, Budgett R, Koutedakis Y, et al., Plasma amino acid concentrations in the 

overtraining syndrome: possible effects on the immune system. Med. Sci. Sports Exerc. 1992; 

24: 1353-1358 

- Rasmussen BB, Tipton KD, Miller SL, et al., An oral essential amino acid-carbohydrate 

supplement enhances muscle protein anabolism after resistance exercise. J. Appl. Physiol. 

2000 ; 88: 386-392 

- Schena F, Guerrini F, Tregnaghi P, et al., Branched-chain amino acid supplementation during 

trekking at high altitude. The effects on loss of body mass, body composition, and muscle 

power. Eur. J. Appl. Physiol. 1992; 65: 394-398 

- Shimomura Y, Yamamoto Y, Bajotto G, et al., Nutraceutical effects of branched-chain amino 

acids on skeletal muscle. J. Nutr. 2006 ; 136 : 1S-4S 

- Van Hall G, Saltin B, Wagenmakers AJ, Muscle protein degradation and amino acid 

metabolism during prolonged knee-extensor exercise in humans. Clin Sci (Lond). 1999; 97: 

557-567 

- Watson P, Shirreffs SM, Maughan RJ, The effect of acute branched-chain amino acid 

supplementation on prolonged exercise capacity in a warm environment. Eur. J. Appl. Physiol. 

2004; 93: 306-314 

29 

29

BROMELAIN and Immune health 

Expert organization opinion: 

- Guideliness for ATC classification and DDD assignment. WHO Collaborating Centre for Drug 

Statistics Methodology. Oslo 1998 (bromelain belongs to the group: enzymes with fibrinolytic 

properties) 

- Blumenthal M. (Senior Editor). The Complete German Commission E Monographs - 

Therapeutic Guide to Herbal Medicine. Austin TX: American Botanical Council, 1998 

- Reynolds JEF (Hrsg.) (1996) Martindale: The Extrapharmacopoeia. 31. Aufl. The 

Pharmaceutical Press, London (bromelain: page 1681) 

Textbooks, monographs: 

- Vanhoof G. & Cooreman W. (1997) Bromelain. Pharmaceutical Enzymes (eds A. Lauwers & S. 

Scharpé), pp. 131-153. Marcel Dekker, New York. 

- Netti C., Bandi GL., & Pecile A. (1972) Anti-inflammatory action of proteolytic enzymes of 

animal vegetable or bacterial origin administered orally compared with that of known antiphlogistic 

compounds. Il Farmaco - Edizione Pratica 27, 453-466. 

- Lincova D. et Farghali H. et al., Zakladni a aplikovana farmakologie (2001). Galen a Karolinum, 

532-537. 

- Fragakis A. Z., (2003) The Health Professional’s Guide to Popular Dietary Supplements, 

American Dietetic Association, Chicago. 

- Leung, A. (1980) Encyclopedeia of Common Natural Ingredients Used in Foods, Drugs, and 

Cosmetics. New York, NY: John Wiley & Sons;74-76. 

- Morton JF. Major Medicinal Plants. Springfield, IL: Thomas; 1977. 

- Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press; 1985. 

Meta-analysis and critical reviews: 

- Van Eimeren W., Biehl GGG., Tuluweit K (1994) Therapie traumatisch verursachter 

Schwellungen. Adjuvante sytemische Therapie mit proteolytischen Enzymen. G. Thieme 

Verlag, StuttgartNew York (includes metaanalises of clinical trials) 

- Leipner J, Iten F, Saller R (2001) Therapy with proteolytic enzymes in rheumatic disorders. 

Biodrugs 15, 779 – 789 

Review articles, monographs: 

- Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 

2001;58:1234-1245 

- Moss J. N. et al., (1963) Bromelains. The Pharmacology of Enzymes. Arch. Int. Pharmacodyn. 

147, No 1-2 

- Ito C., Yamaguchi K., Shibutani Y., Suzuki K., Yamazaki Y., Komachi H., Ohnishi H. & Fujimura 

H. (1979) Anti-inflammatory actions of proteases, bromelain, trypsin and their mixed 

preparation. Nippon Yakurigaku Zasshi 75, 227-237. 

- Taussig J. et Batkin S., (1998) Bromelain, The Enzyme complex of Pineapple (Ananas 

Comosus) and ist clinical application. An Update. Journal of Ethnopharmacology, 22, 191 – 

203. 

- Lehmann P. V., (1996) Immunomodulation by proteolytic enzymes. Nephrol Dial Transplant 11 

No. 6, 953-955 

- Wood G. R. et al. (1997) Sequential effects of and oral enzyme combination with rutosid in vitro 

and in vivo models of inflammation. Int J Immunotherapry XIII (3/4), 139 – 145 

30 

30

- Kelly G.S., (1996). Bromelain: A literature Review and Discussion of its Therapeutic 

Application. Alt Med Rev, 1(4), 243-257) 

- MacKay D, Miller AL. Nutritional support for wound healing. Altern Med Rev. 2003;8:359-377. 

- Snowden HM, Renfrew MJ, Woolridge MW. Treatments for breast engorgement during 

lactation. Cochrane Database Syst Rev. 2001;(2):CD000046. 

Clinical trials: 

- Walker A. et al, (2002) Bromelain reduces mild acute knee pain and improves well-being in a 

dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine, 9, 681- 

686. 

- Ernst E (1994) Orale Therapie mit proteolytischen Enzymen: Effekte auf hämorrheologische 

Parameter. Perfusion 7, 440 – 441 

- Kleine M. W., (1998) Evidence of the efficacy of an enzyme combination preparation using the 

method of artificial hematomas in combination with a pressure maker: A placebo conrolled 

randomized, prospective double blind study. Journal of Clinical Research, 1, 87 – 102. 

- Baumüller M. (1992) Enzyme zur Wiederherstellung nach Sprunggelenksdistorsionen. 

Zeitschrift für Allgemeinmedizin 68, 61-65. 

- Koshkin VM et Kirienko A.I., Systemic Enzyme Tharapy in The Treatment of Acute Thrombosis 

of Superficial Veins in The Lower Extremities and Posthrombophlebitic Disease (2001) Int. J. 

Immunotherapy XVII (2/3/4) 121-124 

- Vinzenz K. (1991) Ödembehandlung bei zahnchirurgischen Eingriffen mit hydrolytischen 

Enzymen. Die Quitessenz. Chirurgische zahnheilkunde.(Randomisierte Doppelblindstudie 

gegen Placebo) 

- Wörschhauser S., Zuschlag J. M. (1991) Prophylaxe der Weichteilverletzungen bei 

Kontaktsporten. Enzympräparate zur Reduzierung von Ansfallzeiten bei Verletzungen. Der 

Allgemeinarzt 16, 1285-1287. 

- Akhtar NM. et al., (2004) Oral enzyme combination versus diclofenac in the treatment of 

osteoarthritis of the knee- a double-blind prospective randomized study. Clin Rheumatol. 

23(5):410-5 

- Lackovic V, Rovensky J, Horvathová M, Malis F (1997) Interferon production in whole blood 

cultures from volunteers and rheumatoid arthritis patients afer medication with oral enzymes. 

International Journal of Immunotherapy 13: 159-166. 

Metaanalysis of following trials is published in: 



Verlag, StuttgartNew York (163-167). 

Double blind placebo controlled trials: 

- Howat,R.C.L., Lewis, G.D.: The effect of bromelain therapy on episioto-my wounds. - A double 

blind controlled clinical trial. J. Obstet. Gynaec. 79 (1972)951-953 

- Mäder,H.: Vergleichende Untersuchung zwischen Bromelin und Oxy phenbutazon auf ihre 

Wirkung bei Episiotomie-Schmerzen. Schweiz. Rdsch. Med. Prax.62 (1973) 1064-1067 

- Zatuchni, G. J., Colombi, D.: Bromelains therapy for the prevention of epi-siotomy pain. Obst. 

Gynecol.29 (1967)275-278 

- Tassman,G.C., Zafran,J.N., Zayon, G. M.: A double-blind crossover study of a plant proteolytic 

enzyme in oral surgery. J. dent. Med. 20 (1965) 51-54 

31 

31

- Spaeth, G.L.: The effect of bromelains on the inflammatory response caused by cataract 

extraction: A double-blind study Eye, Ear, Nose Thr. Monthyl 47 (1968) 634-639 

- Seltzer, A.P.: A double-blind study of bromelain in the treatment of edema and ecchymoses 

following surgical and non-surgical trauma to the face. Eye, Ear, Nose Thr. Monthly 43 (1964) 

54-57 

- Nitzschke,E., Leonhardt,R.: Therapie der postoperativen Vorfußschwellun-gen mit Bromelain: 

eine randomisier-te, placebo-kontrollierte Doppelblindstudie. Orthop. Prax.2 (1989) 111-115 

- Woolf. R. M., Snow, J. W., Walker, J.H., Broadbent,T.R.: Resolution of an artifically induced 

hemato-ma and the influence of a proteolytic enzyme. J. Trauma 5 (1965) 491-494 

- Blonstein,J.L.: Control of swelling in boxing injuries. Practioner203 (1969) 206 

Controlled trials: 

- Cirelli, M. G.: Five years of clinical experience with bromelains in therapy of edema and 

inflammation in postoperative tissue reaction, skin infections and trauma. Clin. Med. 74 (1967) 

55-59 

- DunantJ.H., Waibel,P.P.: Zur Hä-matomprophylaxe in der Varizenchi-rurgie. Schweiz. Rdsch. 

Med. (Prax.) 61 (1972) 950-951 

- Trillig, J.: Behandlung posttraumatischer Entzündungs- und Schwellungs-zustände. 

Therapiewoche 33 (1983) 4281-4284 

„Open“ trials: 

- Baumgartner,P.: Erfahrungen mit Traumanase bei postoperativen Hämato-men. Praxis59 

(1970) 217-219 

- Bünnagel,W.: Erfahrungen mit einem proteolytischen Enzym in der Landpraxis. Therapiewoche 

35 (1966) 1163-1164 

- Graber,G.: Klinische Erfahrungen mit dem pflanzlichen proteolytischen Enzymkomplex 

„Traumanase" in der zahnärztlichen präprothetischen Chirurgie. Schweiz. Zahnheilk. 80 (1970) 

1206-1212 

- Lorber,C. G.: Möglichkeiten zur medikamentösen Therapie der postoperativen Schwellung in 

der Stomatologie. Dtsch. zahnärztl. Z. 22 (1967) 734-741 

- Mascetti,P., Molteni,A.: Enzimi pro-teolitici e mucopiolitici in associazione nella medicina 

sportiva. Med. Sport 34 (1981) 399-402 

- Morrison, A. W., Morrison, M. C. T.: Bromelain - a clinical assessment in the post-operative 

treatment of ar-throtomies of the knee and facial injuries. Brit. J. Clin. Pract.19 (1965) 207-210 

- Pasha,N.I.: The use of an anti-inflammatory drug in plastic surgery. Clin. Med. 84 (1974) 17-19 

- Rühl,F., Otto,H.: Über die perorale Therapie posttraumatischer Schwellungen und Hämatome 

mit dem pflanzlichen, proteolytischen Ferment Bromelin. Therapiewoche 11 (1965) 555-559 

- Vogt-Suter,T.: Die Beeinflussung von postoperativen Oedemen und Häma-tomen in der 

kosmetischen Chirurgie durch Behandlung mit Traumanase. Praxis 19 (1970) 712-713 

- Weisskirchen, H., El-Salamouny, A. R.: Zur Behandlung posttraumatischer sowie postoperativ 

auftretender Schwellungen mit proteolytischen Enzymen. Med. Welt 52 (1967) 3211-3212 

Experiments: 

- Engwerda CR, Andrew E, Ladhams A, Mynott TL. Bromelain modulates T cell and B cell 

immune responses in vitro and in vivo. Cell Immunol. 2001;210:66-75. 

32 

32

- Mynott TL, Ladhams A, Scarmato P, Engwerda CR. Bromelain, from pineapple stems, 

proteolytically blocks activation of extracellular regulated kinase-2 in T cells. J Immunol. 

1999;163:2568-2575. 

- Engwerda CR, Andrew D, Murphey M, Mynott TL. Bromelain activates murine macrophages 

and natural killer cells in vitro. Cell Immunol. 2001;210:5-10. 

- Mynott TL, Guandalini S, Raimondi F, Fasano A. Bromelain prevents secretions caused by 

Vibrio cholerae and Escheria coli enterotoxins in rabbit ileum in vitro. Gastroenterology. 

1997;113:175-184. 

- Chandler DS, Mynott TL. Bromelain protects piglets from diarrhoea caused by oral challenge 

with K88 positive enterotoxigenic Escherichia coli. Gut. 1998;43:196-202. 

- Edenharder R, John K, Ivo-Boor H. Antimutagenic activity of vegetable and fruit extracts 

against in vitro benzo(a)-pyrene [in German]. Z Gesamte Hyg. 1990;36:144-147. 

- Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J 

Agric Food Chem. 2002;50:7449-7454. 

- Helser MA, Hotchkiss JH, Roe DA. Influence of fruit and vegetable juices on the endogenous 

formation of N-nitrosoproline and N-nitrosthiozolidine-4-carboxylic acid in humans on controlled 

diets. Carcinogenesis. 1992;13:227-2280. 

- Desser L., et al., Cytokine synthesis in human peripheral blood mononuclear cells after oral 

administration of polyenzyme preparations. Oncology 1993, 50, pp. 403-407 

- Heidland A. et al., (1997) Renal fibrosis: Role of impaired proteolysis and potential therapeutic 

strategies. Kidney International, Vol. 52 Suppl 62, S32-S35. 

BROMELAIN and Vascular health 


- Guideliness for ATC classification and DDD assignment. WHO Collaborating Centre for Drug 

Statistics Methodology. Oslo 1998 (bromelain belongs to the group: enzymes with fibrinolytic 

properties) 

- Blumenthal M. (Senior Editor). The Complete German Commission E Monographs - 

Therapeutic Guide to Herbal Medicine. Austin TX: American Botanical Council, 1998 


Pharmaceutical Press, London (bromelain: page 1681) 


- Vanhoof G. & Cooreman W. (1997) Bromelain. Pharmaceutical Enzymes (eds A. Lauwers & S. 

Scharpé), pp. 131-153. Marcel Dekker, New York. 

- Netti C., Bandi GL., & Pecile A. (1972) Anti-inflammatory action of proteolytic enzymes of 

animal vegetable or bacterial origin administered orally compared with that of known antiphlogistic 

compounds. Il Farmaco - Edizione Pratica 27, 453-466. 


532-537. 

- Fragakis A. Z., (2003) The Health Professional’s Guide to Popular Dietary Supplements, 

American Dietetic Association, Chicago. 



- Morton JF. Major Medicinal Plants. Springfield, IL: Thomas; 1977. 


33 

33






Biodrugs 15, 779 – 789 

Review articles, monographs: 

- Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 

2001;58:1234-1245 

- Moss J. N. et al., (1963) Bromelains. The Pharmacology of Enzymes. Arch. Int. Pharmacodyn. 

147, No 1-2 

- Ito C., Yamaguchi K., Shibutani Y., Suzuki K., Yamazaki Y., Komachi H., Ohnishi H. & Fujimura 

H. (1979) Anti-inflammatory actions of proteases, bromelain, trypsin and their mixed 

preparation. Nippon Yakurigaku Zasshi 75, 227-237. 

- Taussig J. et Batkin S., (1998) Bromelain, The Enzyme complex of Pineapple (Ananas 

Comosus) and ist clinical application. An Update. Journal of Ethnopharmacology, 22, 191 – 

203. 


No. 6, 953-955 



- Kelly G.S., (1996). Bromelain: A literature Review and Discussion of its Therapeutic 

Application. Alt Med Rev, 1(4), 243-257) 

- MacKay D, Miller AL. Nutritional support for wound healing. Altern Med Rev. 2003;8:359-377. 

- Snowden HM, Renfrew MJ, Woolridge MW. Treatments for breast engorgement during 

lactation. Cochrane Database Syst Rev. 2001;(2):CD000046. 


- Walker A. et al, (2002) Bromelain reduces mild acute knee pain and improves well-being in a 

dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine, 9, 681- 

686. 

- Ernst E (1994) Orale Therapie mit proteolytischen Enzymen: Effekte auf hämorrheologische 

Parameter. Perfusion 7, 440 – 441 

- Kleine M. W., (1998) Evidence of the efficacy of an enzyme combination preparation using the 

method of artificial hematomas in combination with a pressure maker: A placebo conrolled 

randomized, prospective double blind study. Journal of Clinical Research, 1, 87 – 102. 

- Baumüller M. (1992) Enzyme zur Wiederherstellung nach Sprunggelenksdistorsionen. 

Zeitschrift für Allgemeinmedizin 68, 61-65. 

- Koshkin VM et Kirienko A.I., Systemic Enzyme Tharapy in The Treatment of Acute Thrombosis 

of Superficial Veins in The Lower Extremities and Posthrombophlebitic Disease (2001) Int. J. 

Immunotherapy XVII (2/3/4) 121-124 

- Vinzenz K. (1991) Ödembehandlung bei zahnchirurgischen Eingriffen mit hydrolytischen 

Enzymen. Die Quitessenz. Chirurgische zahnheilkunde.(Randomisierte Doppelblindstudie 

gegen Placebo) 

- Wörschhauser S., Zuschlag J. M. (1991) Prophylaxe der Weichteilverletzungen bei 

Kontaktsporten. Enzympräparate zur Reduzierung von Ansfallzeiten bei Verletzungen. Der 

Allgemeinarzt 16, 1285-1287. 

34 

34

- Akhtar NM. et al., (2004) Oral enzyme combination versus diclofenac in the treatment of 

osteoarthritis of the knee- a double-blind prospective randomized study. Clin Rheumatol. 

23(5):410-5 

- Lackovic V, Rovensky J, Horvathová M, Malis F (1997) Interferon production in whole blood 

cultures from volunteers and rheumatoid arthritis patients afer medication with oral enzymes. 

International Journal of Immunotherapy 13: 159-166. 






- Howat,R.C.L., Lewis, G.D.: The effect of bromelain therapy on episioto-my wounds. - A double 

blind controlled clinical trial. J. Obstet. Gynaec. 79 (1972)951-953 

- Mäder,H.: Vergleichende Untersuchung zwischen Bromelin und Oxy phenbutazon auf ihre 

Wirkung bei Episiotomie-Schmerzen. Schweiz. Rdsch. Med. Prax.62 (1973) 1064-1067 

- Zatuchni, G. J., Colombi, D.: Bromelains therapy for the prevention of epi-siotomy pain. Obst. 

Gynecol.29 (1967)275-278 

- Tassman,G.C., Zafran,J.N., Zayon, G. M.: A double-blind crossover study of a plant proteolytic 

enzyme in oral surgery. J. dent. Med. 20 (1965) 51-54 

- Spaeth, G.L.: The effect of bromelains on the inflammatory response caused by cataract 

extraction: A double-blind study Eye, Ear, Nose Thr. Monthyl 47 (1968) 634-639 

- Seltzer, A.P.: A double-blind study of bromelain in the treatment of edema and ecchymoses 

following surgical and non-surgical trauma to the face. Eye, Ear, Nose Thr. Monthly 43 (1964) 

54-57 

- Nitzschke,E., Leonhardt,R.: Therapie der postoperativen Vorfußschwellun-gen mit Bromelain: 

eine randomisier-te, placebo-kontrollierte Doppelblindstudie. Orthop. Prax.2 (1989) 111-115 

- Woolf. R. M., Snow, J. W., Walker, J.H., Broadbent,T.R.: Resolution of an artifically induced 

hemato-ma and the influence of a proteolytic enzyme. J. Trauma 5 (1965) 491-494 

- Blonstein,J.L.: Control of swelling in boxing injuries. Practioner203 (1969) 206 

Controlled trials: 

- Cirelli, M. G.: Five years of clinical experience with bromelains in therapy of edema and 

inflammation in postoperative tissue reaction, skin infections and trauma. Clin. Med. 74 (1967) 

55-59 

- DunantJ.H., Waibel,P.P.: Zur Hä-matomprophylaxe in der Varizenchi-rurgie. Schweiz. Rdsch. 

Med. (Prax.) 61 (1972) 950-951 

- Trillig, J.: Behandlung posttraumatischer Entzündungs- und Schwellungs-zustände. 

Therapiewoche 33 (1983) 4281-4284 

„Open“ trials: 

- Baumgartner,P.: Erfahrungen mit Traumanase bei postoperativen Hämato-men. Praxis59 

(1970) 217-219 

- Bünnagel,W.: Erfahrungen mit einem proteolytischen Enzym in der Landpraxis. Therapiewoche 

35 (1966) 1163-1164 

35 

35

- Graber,G.: Klinische Erfahrungen mit dem pflanzlichen proteolytischen Enzymkomplex 

„Traumanase" in der zahnärztlichen präprothetischen Chirurgie. Schweiz. Zahnheilk. 80 (1970) 

1206-1212 

- Lorber,C. G.: Möglichkeiten zur medikamentösen Therapie der postoperativen Schwellung in 

der Stomatologie. Dtsch. zahnärztl. Z. 22 (1967) 734-741 

- Mascetti,P., Molteni,A.: Enzimi pro-teolitici e mucopiolitici in associazione nella medicina 

sportiva. Med. Sport 34 (1981) 399-402 

- Morrison, A. W., Morrison, M. C. T.: Bromelain - a clinical assessment in the post-operative 

treatment of ar-throtomies of the knee and facial injuries. Brit. J. Clin. Pract.19 (1965) 207-210 

- Pasha,N.I.: The use of an anti-inflammatory drug in plastic surgery. Clin. Med. 84 (1974) 17-19 

- Rühl,F., Otto,H.: Über die perorale Therapie posttraumatischer Schwellungen und Hämatome 

mit dem pflanzlichen, proteolytischen Ferment Bromelin. Therapiewoche 11 (1965) 555-559 

- Vogt-Suter,T.: Die Beeinflussung von postoperativen Oedemen und Häma-tomen in der 

kosmetischen Chirurgie durch Behandlung mit Traumanase. Praxis 19 (1970) 712-713 

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- Smith AP, Brockman P, Flynn R, Maben A, Thomas M. “Investigation of the effects of coffee on 

alertness and performance during the day and night”. Neuropsychobiology 1993;27(4):217-23 

- Van Dongen HP, Price NJ, Mullington JM, Szuba MP, Kapoor SC, Dinges DF. “Caffeine 

eliminates psychomotor vigilance deficits from sleep inertia”. Sleep 2001;24(7):813-9 

- Warburton DM. “Effects of caffeine on cognition and mood without caffeine abstinence”. 

Psychopharmacology (Berl) 1995;119(1):66-70 

Authoritative Body 

- SCF: Report of the Scientific Committee on Food on composition and specification of food 

intended to meet the expenditure of intense muscular effort, especially for sportsmen. 

SCF/CS/NUT/SPORT/5 Final, 28 February 2001. 

Textbook 

- Encyclopedia of Human Nutrition (Second Edition), Editor in Chief: Benjamin Caballero, 

Elsevier Academic Press, 2005, Volume 1, pp. 249-250 

Reviews 

- Dodd SL, Herb RA, Powers SK. Caffeine and exercise performance. An update. Sports Med 

1993; 25(1): 14-23. 

- French C, McNaughton L, Davies P, Tristram S. Caffeine ingestion during exercise to 

exhaustion in elite distance runners. Revision. J Sports Med Phys Fitness 1991; 31(3): 425- 

432. 

- Graham TE, Spriet LL. Caffeine and exercise performance. Sports Science Exchange 1996; 

9(1): 60. 

- Nehlig A and Debry G. Caffeine and sports activity: a review. International Journal of Sports 

Medicine 1994; 15: 215-223 

- Paluska S A. Caffeine and exercise. Current Sports Medicine Reports 2003; 2: 213-219 

- Individual Studies 

- Acheson, J. et al. Caffeine and coffee: their influence on metabolic rate and substrate utilization 

in normal weight and obese individuals. Am J Clin Nutr 1980; 33: 

- 

989-97 

Anderson ME, Bruce CR, Fraser SF, Stepto NK, Klein R, Hopkins WG, Hawley JA. Improved 

2000-meter rowing performance in competitive oarswomen after caffeine ingestion. Int J Sport 

Nutr Exerc Metab 2000; 10(4): 464-75 

- Astrup A, Toubro S, Cannon S, Hein P, Breum L, Madsen J. Caffeine: a double-blind, placebocontrolled 

study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. 

Am J Clin Nutr 1990; 51: 759-67 

44 

44

- Berglund B & Hemmingsson P. Effects of caffeine ingestion on exercise performance at low 

and 

234-6 

high altitudes in cross country skiers. Int J Sports Med 1982; 3: 

- Bruce CR, Anderson ME, Fraser SF, Stepto NK, Klein R, Hopkins WG, Hawley JA. 

Enhancement of 2000-m rowing performance after caffeine ingestion. Med Sci Sports Exerc 

2000; 32(11): 1958-63 

- Costill DL, Dalsky GP, Fink WJ. Effects of caffeine ingestion on metabolism and exercise 

performance. Med Sci Sports 1978; 10: 155-8 

- Cadarette et al. Effects of varied doses of caffeine on endurance exercise to fatigue. Biochem 

Exercise, 1983; 13: 871 

- Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS. Normal caffeine consumption: influence 

on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am 

J Clin Nutr 1989; 49(1): 44-50 

- Ferrauti A, Weber K, Struder HK. Metabolic and ergogenic effects of carbohydrate and caffeine 

beverages 

258-66 

in tennis. J Sports Med Phys Fitness, 1997; 37(4): 

- Flinn S, Gregory J, McNaughton LR, Tristram S, Davies P. Caffeine ingestion prior to 

incremental cycling to exhaustion in recreational cyclists. Int J Sports Med 1990; 11(3): 188-93. 

- Fulco C.S, Rock PB, Trad LA, Rose MS, Forte VA, Young PM, Cymerman A. Effect of caffeine 

on submaximal exercise performance at altitude. Aviat Space Environ Med 1994; 65(6): 539- 

45. 

- Graham TE, Spriet LL. Performance and metabolic responses to a high caffeine dose during 

prolonged exercise. J Appl Physiol 1991; 71(6): 2292-2298 

- Graham TE, Spriet LL. Metabolic, catecholamine, and exercise performance responses to 

various doses of caffeine. J Appl Physiol. 1995 Mar;78(3):867-74. 

- Hollands, M.A. et al., A simple apparatus for comparative measurements of energy expenditure 

in human subjects: the thermic effect of caffeine. Am J Clin Nutr 1981;34:2291-4 

- Pasman WJ, van Baak MA, Jeukendrup AE, de Haan A. The effect of different dosages of 

caffeine on endurance performance time. Int J Sports Med 1995 May; 16(4): 225-30. 

- Spriet LL, MacLean DA, Dyck DJ, Hultman E, Cederblad G, Graham TE. Caffeine ingestion 

and muscle metabolism during prolonged exercise in humans. Am J Physiol 1992; 262(6 Pt 1): 

E891-898 

- Ryu S, Choi SK, Joung SS, Suh H, Cha YS, Lee S, Lim K. “Caffeine as a lipolytic food 

component increases endurance performance in rats and athletes”. J Nutr Sci Vitaminol 

(Tokyo) 2001; 47(2): 139-46 

- Wemple R D et al. Caffeine vs caffeine-free sports drinks: effects on urine production at rest 

and during prolonged exercise. International Journal of Sports Medicine 1997; 18: 40-46 

CARNITINE and Fat metabolism 

Reviews 

- Barlett K, Eaton S: Mitochondrial β-oxidation. Eur J Biochem 2004;271:462-469 

- Borum PR: Carnitine. Ann Rev Nutr 1983;3:233 

- Kerner J & Hoppel CL: Carnitine Palmitoyltransferase 1 and Regulation of mitochondrial fatty 

acid oxidation. Chem Month 2005;136:1311-1323 

- Kerner J & Hoppel CL: Fatty acid import into mitochondria. Biochim Biophys Acta 

2000;1486(1):1-17 

45 

45

- Wutzke KD, Lorenz H: The effect of L-Carnitine on fat oxidation, protein turnover, and body 

composition in slightly overweight subjects. Metabolism 2004;53(8):1002-1006 


- Hoppel C: The role of Carnitine in normal and altered fatty acid metabolism. Am J Kidney Dis 

2003;41(S4),S4-S12 

- Jensen MD: Fatty acid oxidation in human skeletal muscles. J Clin Invest 2002;110:1607-1609 

- Johnston CS, Corte C et al.: Marginal vitamin C status is associated with reduced fat oxidation 

during submaximal exercise in young adults. Nutr & Metabolism 2006;3:35-40 

- Müller DM, Seim H et al.: Effects of oral L-Carnitine supplementation on in vivo long-chain fatty 

acid oxidation in healthy adults. Metabolism 2002;51(11):1389-1391 

- Reda E et al: The carnitine system and body composition. Acta Diabetol 2003;40:S106-113 

- Vaz FM & Wanders RJA: Carnitine biosynthesis in mammals. Biochem J 2002;361, 417-429 

- Wutzke KD, Lorenz H: The effect of L-Carnitine on fat oxidation, protein turnover, and body 

composition in slightly overweight subjects. Metabolism 2004;53(8):1002-1006 

- Müller DM. Et al. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid 

oxidation in healthy adults. Metabolism. 2002, 51:1389-1391 

- Pauly DF, Pepine CJ. The role of carnitine in myocardial dysfunction. Am J Kidney Dis. 2003 

Apr;41(4 Suppl 4):S35-43. 

CARNITINE and Muscle metabolism / Recovery after exercise 

Text books 

- Robert Murray, Darryl Granner, Peter Mayes and Victor Rodwell (1990) Harpers Biochemistry, 

22nd Edition, Prentice Hall, London p210 

- Stryer (1981) Biochemistry 2nd Edition, Freeman, New York, p388 

Reviews 

- Karlic H et al (2004). Supplementation with L-Carnitine in athletes: Does it make sense? 

Nutrition 20:709 


- Giamberardino MA et al (1996). Effects of prolonged L-Carnitine administration on delayed 

muscle pain and CK release after eccentric effort. Int J Sports Med 17:320 

- Karlic H et al (2004). Supplementation with L-Carnitine in athletes: Does it make sense? 

Nutrition 20:709 

- Kraemer WJ et al (2005). L-Carnitine supplementation: A new paradigm for its role in exercise. 

Chem Month 136:1383 

- Maggini S et al (2000). L-Carnitine supplementation results in improved recovery after 

strenuous exercise: A preliminary study. Ann Nutr Metab 44(2):86 

- Spiering BA, Kraemer WJ et al (2007). Responses of criterion variables to different 

supplemental doses of L-Carnitine L-Tartrate. J Strength Cond Res 21(1):259-264 

- Swart I et al (1997). The effect of carnitine supplementation on plasma carnitine levels on 

various performance parameters of male marathon athletes. Nutr Res 17:405 

- Volek JS et al (2002). L-Carnitine L-tartrate supplementation favourably affects markers of 

recovery from exercise stress. Am J Physiol Endocrinol Metab 282:E474 

46 

46

CARNITINE and Heart health 

Reviews 

- Löster H (2003). Carnitine and cardiovascular diseases. Ponte Press Verlags GmbH, Bochum 

- Scholte HR & DeJong PC (1987). Metabolism, function and transport of carnitine in health and 

disease. In: Gitzelamm R, Baerlocher K, Steinmann B (Eds), Carnitin in der Medizin. 

Schattauer, Stuttgart, New York, 21-59 

- Veselá E et al. (2001). Effect of L-Carnitine supplementation in hemodialysis patients. Nephron 

88, 218-223 

- Kendler BS (2006). Supplemental conditionally essential nutrients in cardiovascular disease 

therapy. J Cardiovasc Nurs 21(1):9-16 

- Löster H (2003). Carnitine and cardiovascular diseases. Ponte Press Verlags GmbH, Bochum 

- Pauly DF & Pepine CJ (2003). The role of carnitine in myocardial dysfunction. Am J Kidney Dis 

41(4):S35-43 

- Pepine CJ (1991). The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther 

13(1):2-21 

- Retter AS (1999). Carnitine and its role in cardiovascular disease. Heart Disease 1(2):108-113 


- Diaz M et al. (2000). L-Carnitine effects on chemical composition of plasma lipoproteins of 

rabbits fed with normal and high cholesterol diets. Lipids 35 (6); 627-632 

- Digiesi V et al. (1994). L-carnitine adjuvant therapy in essential hypertension. Clin Ter 144:391- 

395 

- Fernandez C & Proto C (1992). L-carnitine in the treatment of chronic myocardial ischemia. An 

analysis of 3 multicenter studies and a bibliographic review. Clin Ter 140:353-377 

- Lurz R & Fischer R (1998). Carnitine as supporting agent in weight loss in adiposity. 

Ärztezeitschr Naturheilverf 39 (1); 12-15 

- Mondola P et al. (1988). The effect of L-Carnitine on the apolipoprotein pattern of rats fed a 

cholesterol-rich diet. Comp Biochem Physiol 89B (1); 69-73 

- Pistone G et al. (2003). Levocarnitine administration in elderly subjects with rapid muscle 

fatigue. Drugs Aging 20 (10); 761-767 

- Sayed-Ahmed MM et al. (2001). L-Carnitine prevents the progression of atherosclerotic lesions 

in hypercholesterolaemic rabbits. Pharm Res 44 (3); 235-242Sirtori CR et al. (2000). Lcarnitine 

reduces plasma lipoprotein(a) levels in patients with hyper Lp(a). Nutr Metab 

Cardiovasc Dis 10(5):247-251 

- Stefanutti C et al. (1998). Effect of L-carnitine on plasma lipoprotein fatty acids pattern in 

patients with primary hyperlipoproteinemia. Clin Ter149:115-119 

- Cacciatore L et al. (1991). The therapeutic effect of L-carnitine in patients with exerciseinduced 

stable angina: a controlled study. Drugs Exp Clin Res 17:225-235 

- Calvani M et al. (2000). Regulation by carnitine of myocardial fatty acid and carbohydrate 

metabolism under normal and pathological conditions. Basic Res Cardiol 95(2): 75-83 

- Davini P et al. (1992). Controlled study on L-carnitine therapeutic efficacy in post-infarction. 

Drugs Exp Clin Res 18:355-365 

- Kumaran S et al. (2005). Supplementation of L-Carnitine improves mitochondrial enzymes in 

heart and skeletal muscle of aged rats. Exp Aging Res 31(1):55-67 

47 

47

- Pepine CJ (1991). The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther 

13(1):2-21 

- Singh RB et al. (1996). A randomised, double-blind, placebo-controlled trial of L-carnitine in 

suspected acute 

- Lango R et al. (2001). Influence of L-carnitine and its derivatives on myocardial metabolism 

and function in ischemic heart disease and during cardiopulmonary bypass. Cardiovasc Res 

51(1):21-9 

- Canale C et al. (1988). Bicycle ergometer and echocardiographic study in healthy subjects and 

patients with angina pectoris after administration of L-carnitine: semiautomatic computerized 

analysis of M-mode tracing. Int J Clin Pharmacol Ther Toxicol 26:221-224 

- Cherchi A et al. (1895). Effects of L-carnitine on exercise tolerance in chronic stable angina: a 

multicenter, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharmacol 

Ther Toxicol 23:569-572 

- Iyer RN et al. (2000). L-carnitine moderately improves the exercise tolerance in chronic stable 

angina. J Assoc Physicians India 48:1050-1052 

- Kamikawa T et al. (1984). Effects of L-carnitine on exercise tolerance in patients with stable 

angina pectoris. Jpn Heart J 25:587-597 

- Löster H et al. (1999). Prolonged oral L-carnitine substitution increases bicycle ergometer 

performance in patients with severe, ischemically induced cardiac insufficiency. Cardiovasc 

Drugs Ther 13:537-546. 

CARNITINE and Vegetarism 

Reviews 

- Krajcovicova-Kudlackova M et al. (2000). Correlation of carnitine levels to methionine and 

lysine intake. Physiol Res 49(3), 399-402 

- Krähenbühl, S (2000). L-Carnitine and Vegetarianism. Ann Nutr Metab 44, 81-82 

- Rebouche C et al. (1989). Utilization of dietary precursors for carnitine synthesis in human 

adults. J Nutr 119, 1907-1913 


- Barth CA et al. (1985). L-Carnitine concentrations in milk from mothers on different diets. 

Compos Physiol Prop Hum Milk. 229-238 

- Chen W et al. (1998). Urinary, plasma and erythrocyte carnitine concentrations during 

transition to a lactoovovegetarian diet with vitamin B-6 depletion and repletion in young adult 

women. Am J Clin Nutr 67, 221-230 

- Delanghe J et al. (1989). Normal reference values for Creatine, Creatinine and Carnitine are 

lower in vegetarians. Clin Chem 35 (8); 1802-1803 

- Etzioni A et al. (1984). Systemic Carnitine deficiency exacerbated by a strict vegetarian diet. 

Arch Dis Childhood S9 (2); 177-179 

- Föhrenbach R et al. (1993). Der Einfluss von L-Carnitin auf den Lipidstoffwechsel von 

Hochleistungssportlern. Dtsch Z Sport Med 8, 349-352 

- Richter V et al. (1999). Lipoproteins and other clinical-chemistry parameters under the 

conditions of lacto-ovo-vegetarian nutrition. Nutr Res 19 (4), 545-554 

- Sachan DS et al. (1997). Vegetarian elderly women may risk compromised Carnitine status. 

Veg Nutr 1, 64-69 

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48

- Lombard KA et al. (1989). Carnitine status of lactoovovegetarians and strict vegetarian adults 

and children. Am J Clin Nutr 50, 301-306 

CARNITINE and Pregnancy 

Reviews 

- Lohninger A (2000). The role of L-Carnitine in pregnancy and disorders of lipid metabolism. 

Ann Nutr Metab 44, 75-96 

- Lohninger A, Karlic H et al. (2005). Carnitine in Pregnancy. Chem Month 136, 1523-1533 


- Bargen-Lockner C, Hahn P et al. (1981). Plasma carnitine in pregnancy. Am J Obstet Gynecol 

140, 412-414 

- Cederblad G, Fahraeus L et al. (1986). Plasma Carnitine and renal-carnitine clearance during 

pregnancy. Am J Clin Nutr 44, 379-383 

- Cederblad G, Niklasson A et al. (1985). Carnitine in maternal and neonatal plasma. Acta 

Paediatr Scand 74, 500-504 

- Genger H, Sevelda P et al. (1988). Carnitinspiegel während der Schwangerschaft. Z Geburtsh 

u Perinat 192, 134-136 

- Gynecol Endocrinol 8, 115-120 

- Lohninger A, Salzer H et al. (2001). Pregnancy-associated carnitine deficiency causes 

downregulation of carnitine acyltransferase genes: reversal by carnitine supplementation is 

dose-dependent. FASEB abstract 36 

- Marzo A, Cardace G et al. (1994). Plasma concentration, urinary excretion and renal clearance 

of L-Carnitine during pregnancy: a reversible secondary L-Carnitine deficiency. 

- Schmidt-Sommerfeld E, Penn D et al. (1981). The influence of maternal fat metabolism on fetal 

carnitine levels. Early Human Development 5, 233-242 

- Schoderbeck M, Auer B et al. (1995). Pregnancy-related changes of carntine and acylcarnitine 

concentrations of plasma and erythrocytes. J Perinat Med 23, 477-485 

- Winter SC, Linn LS et al. (1995). Plasma carnitine concentrations in pregnancy, cord blood, 

and neonates and children. Clin Chim Acta 243, 87-93 

CAROTENOIDS FROM FRUITS AND VEGETABLES JUICES and Antioxidant properties 




Textbook 

- Lecerf JM (2005) Les pigments xanthophylles. pp 34-38 Micronutrition et oeil en pratique : les 

bases (tome 1). Ouvrage coordonné par le Groupe d’Experts en Micronutrition Oculaire. Baush 

& Lomb, laboratoires Chauvin. 

Monographs 

- Lecerf JM (1999) Pasteur Institute – Lille Les antioxydants et les autres éléments protecteurs 

dans les jus de fruits et légumes. 


49 

49

- Van Den Berg H (1999) Carotenoid interactions. Nutr Rev 57(1):1-10. 

- Krinsky NI, Johnson EJ (2005) Carotenoid actions and their relation to health and disease. Mol 

Aspects Med 26(6):459-516. 

- Sommerburg O, Keunen JEE, Bird AC, Van Kuij F (1998) Fruits and vegetables that are 

sources for lutein and zeaxanthin : the macular pigment in human eye. Br J Ophtalmol 82:907- 

910. 

Individual studies – clinical trials/intervention studies 

- Torronen R, Lehmusaho M, Hakkinen S and al ; (1996) Serum b-carotene response to 

supplementation with raw carrots, carrot juice or purified b-carotene in healthy non-smocking 

women. Nutr Res 16(4):565-71. 

- Fuhrman B, Ben Yaish L, Attias J (1997) Tomato lycopene and b-carotene inhibit low density 

lipoprotein oxidation and this effect depends on the lipoprotein vitamin E content. Nutr Metab 

Cardiovasc Dis 7:433-43. 

- Pool-Zobel BL, Bub A, Muller H and al. (1997) Consumption of vegetables reduces genetic 

damage in humans : first results of a human intervention trial with carotenoids-rich foods. 

Carcinogenesis 18(9):1847-50. 

- Berson ER, Hankinson SE and al. (2001) A population-based case-control study of carotenoid 

and vitamin A intake and ovarian cancer (United States). Cancer Causes Control 12(1):83-90. 

- Knekt P, Heliovaara M, Rissanen A and al. (1992) Serum antioxidant vitamins and risk of 

cataract. BMJ 305:1392-4. 

- Hammond BR, Johnson EJ, Russell RM and al. (1997) Dietary modification of human macular 

pigment density. Invest Ophtalmol Vis Sci 38:1795-1801. 

- Seddon JM, ajani UA, Sperduto RD and al. (1994) Dietary carotenoids, vitamins A, C and E, 

and advanced age-related macular degeneration. JAMA 272:1413-1429. 

Individual studies – in vivo studies 

- Khachik F, Bernstein PS, Garland DL (1997) Identification of lutein and zeaxanthin oxidation 

products in human and monkey retinas. Invest Ophtalmol Vis Sci 38:1802-1811. 

CASEIN PROTEIN HYDROLYSATE and Physical performance 

Recovery after exercise 

Evidence from authorative / scientific bodies 

- SCIENTIFIC COMMITTEE ON FOOD (SCF), 2001. Report of the Scientific Committee on 

Food on composition and specification of food intended to meet the expenditure of intense 

muscular effort, especially for sportsmen. European Commission; Health & Consumer 

Protection Directorate-General. Directorate C - Scientific Opinions. C2 - Management of 

scientific committees; scientific co-operation and networks. SCF/CS/NUT/SPORT/5 Final 

(corrected), 28 February 2001 

Evidence from reviews / textbooks 

- McArdle, W.D., F.I. Katch, and V.L. Katch, 2001. Exercise Physiology. 5th ed., Lippincot, 

Williams and Wilkins, Philadelphia, USA. 

Evidence from individual human studies 

- Alf, D. and J. Broja. Comparison of a commercial intact whey protein sports drink with a peptide 

sports drink (PeptoPro®) in well trained athletes. Submitted for publication. 

50 

50

- Alf, D., J. Broja, A. Butt, and D. Kocak. A peptide recovery drink (PeptoPro®) improves 

subsequent performance in top athletes. Submitted for publication. 

- [0]Ivy, J.L., H.W. Goforth, B.W. Damon, T.R. McCauley, E.C. Parsons, and T.B. Price, 2002. 

Early post exercise muscle glycogen recovery is enhanced with a carbohydrate-protein 

supplement. J.Appl.Physiol. 93:1337-1344. 

- Kaastra, B., R.J.F. Manders, E. van Breda, A. Kies, A.E. Jeukendrup, H.A. Keizer, H. Kuipers, 

and L.J.C. van Loon, 2006. Effects of increasing insulin secretion on acute postexercise blood 

glucose disposal. Med.Sci.Sports Exerc., 2006, 38(2):268-275. 

- Saris W.H.M. and L.J.C. van Loon, 2004. [Nutrition and health - nutrition and performance in 

sports] Ned Tijdschr Geneeskd. 148(15):708-12. 

- Van Hall G., W.H.M. Saris, P.A. van de Schoor, and A.J.M. Wagenmakers, 2000. The effect of 

free glutamine and peptide ingestion on the rate of muscle glycogen resynthesis in man. 

Int.J.Sports Med. 21(1):25-30. 

- Van Loon L.J.C., M. Kruijshoop, H. Verhagen, W.H.M. Saris, and A.J.M. Wagenmakers, 2000a. 

Ingestion of protein hydrolysate and amino acid-carbohydrate mixtures increases postexercise 

plasma insulin responses in men. J Nutr. 130(10):2508-13. 

- Van Loon L.J.C., W.H.M. Saris, H. Verhagen, and A.J.M. Wagenmakers, 2000b. Plasma 

insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. 

Am..J.Clin.Nutr. 72(1):96-105. 

- Van Loon L.J.C., W.H.M. Saris, M. Kruijshoop, and A.J.M. Wagenmakers, 2000c. Maximizing 

postexercise muscle glycogen synthesis: carbohydrate supplementation and the application of 

amino acid or protein hydrolysate mixtures. Am.J.Clin.Nutr. 72(1):106-11. 

- Williams, M.B., P.B. Raven, D.L. Fogt, and J.L. Ivy, 2003. Effects of recovery beverages on 

glycogen restoration und endurance exercise performance. J.Strenght Cond.Res. 17:12-19. 

Endurance and time to fatigue 


- [0]Ivy, J.L., H.W. Goforth, B.W. Damon, T.R. McCauley, E.C. Parsons, and T.B. Price, 2002. 

Early post exercise muscle glycogen recovery is enhanced with a carbohydrate-protein 

supplement. J.Appl.Physiol. 93:1337-1344. 

- Ivy, J.L., P.T. Res, R.C. Sprague, and M.O. Widzer, 2003. Effect of a carbohydrate-protein 

supplement on endurance performance during exercise of varying intensity. Int.J.Sport 

Nutr.Exerc.Metab. 13(3):382-395. 

- Moore, R.W., M.J. Saunders, C.A. Pratt, M.C. Hammer, K.L. Lehman, K. Todd, J.A. Flohr, and 

A.K. Kies. Improved time to exhaustion with carbohydrate-protein hydrolysate beverage. 

Submitted for publication. 

- Saunders M.J., M.D. Kane, and M.K. Todd, 2004. Effects of a carbohydrate-protein beverage 

on cycling endurance and muscle damage. Med.Sci.Sports Exerc. 36(7):1233-1238. 



Physical performance of athletes 


- [0]Alf, D., J. Broja, A. Butt, and D. Kocak. A peptide recovery drink (PeptoPro®) improves 


51 

51

- Ivy, J.L., P.T. Res, R.C. Sprague, and M.O. Widzer, 2003. Effect of a carbohydrate-protein 

supplement on endurance performance during exercise of varying intensity. Int.J.Sport 

Nutr.Exerc.Metab. 13(3):382-395. 

- Romano-Ely, B.C., M.K. Todd, M.J. Saunders, and T.G. St. Laurent, 2006. Effect of an 

isocaloric carbohydrate-protein-antioxidant drink on cycling performance. Med.Sci.Sports 

Exerc. 38(9):1608-1616. 



- Saunders M.J., N.D. Luden, C.A. Pratt, and R.W. Moore, 2006. Carbohydrate and protein 

hydrolysate beverage improves late-race cycling performance and prevents post-exercise 

muscle damage. Journal of the International Society of Sports Nutrition 3(1):S20. 

- Kurosawa Y., R. Kirne, N. Murase, T. Osada, K. Shiroishi, K. Shimomura, M. Mori-Matsumura, 

M. Anjo, S. Ichimura, and T. Katsumura, 2006. Milk Peptide PeptoPro® Intake Enhances 

Bicycle Exercise Performance after Exhaustive Exercise. Medicine & Science in Sports & 

Exercise, 38(Suppl 5):S125. 



Exercise induced muscle damage and muscle pain 


- Alf, D., J. Broja, A. Butt, and D. Kocak. A peptide recovery drink (PeptoPro®) improves 


- Alf, D. And K. Flechsenhar, 2005. [Ergebnisse einer Anwendungsbeobachtung zur Kollagen 

hydrolysate] CH-alpha Othopädische Praxis 41 Heft 9, 486-494. 

- Ready, S.L., J.G. Seifert, and E. Burke, 1999. The effect of two sports drink formulations on 

muscle stress and performance. Med.Sci.Sports Exerc. 31:S119. 

- Romano-Ely, B.C., M.K. Todd, M.J. Saunders, and T.G. St. Laurent, 2006. Effect of an 

isocaloric carbohydrate-protein-antioxidant drink on cycling performance. Med.Sci.Sports 

Exerc. 38(9):1608-1616. 



- Saunders M.J., N.D. Luden, C.A. Pratt, and R.W. Moore, 2006. Carbohydrate and protein 

hydrolysate beverage improves late-race cycling performance and prevents post-exercise 

muscle damage. Journal of the International Society of Sports Nutrition 3(1):S20. 

CHITOSAN and Weight Management 

Peer-reviews (with metaanalysis) 

- Ernst E., Pittler MH. Chitosan as a treatment for body weight reduction. A meta-analysis. In 

Chitosan per os: from dietary supplement to drug carrier. RAA Muzzareilli, ed. Atec, 

Grottammare, 2000. – ISBN 88-86889-03-8 

Studies 

- Kanauchi O, Deuchi K, Imasato Y, et al. Mechanism for the inhibition of fat digestion by 

Chitosan and for the synergistic effect of ascorbate. Biosci Biotechnol Biochem 59:786-90, 

1995. 

- Sugano M, Fujikawa T, Hiratsuji Y, et al. A novel use of Chitosan as a hypocholesterolemic 

agent in rats. Amer J Clin Nutr 33:787-93, 1980. 

52 

52

- Furda I. Aminopolysaccharides - their potential as dietary fiber. In: Unconventional Sources of 

Dietary Fiber. ACS Symposium Series 214, 1983. 

- Vahouny GV, Satchithanandam S, Cassidy MM, et al. Comparative effect of Chitosan and 

cholestyramine on lymphatic absorption of lipids in the rat. Am J Clin Nutr 38:278-84, 1983. 

- Furda I. Nonabsorbable Lipid Binder. U.S. Patent 4,223,023, 1983. 

- Sciutto AM, Colombo P. Lipid-lowering effect of Chitosan dietary integrator and hypocaloric diet 

in obese subjects. Acta Toxicol Ther 16;4:215-229, 1995. 

- Colombo P, Sciutto AM. Nutritional aspects of Chitosan employment in hypocaloric diet. Acta 

Toxicol Ther 17;4:287-302, 1996. 

- Giustina A, Ventura P. Weight-reducing regimens in obese subjects: Effects of a new dietary 

fiber integrator. Acta Toxicol Ther 16;4:199-214, 1995. 

- Veneroni G, Veneroni F, Contos S, et al. Effect of a new Chitosan on hyperlipidemia and 

overweight in obese patients. Chitin Enzymology 2;1:55-62, 1996. 

- Acchi G. A new approach to the treatment of obesity: Chitosan's effects on body weight 

reduction and plasma cholesterol levels. Acta Toxicol Ther 17;4:303-320, 1996. 

- Colombo P, Sciutto AM. Nutritional aspects of Chitosan employment in hypocaloric diet. Acta 

Toxicol Therap 17:287-302, 1996. 

- Ventura P. Lipid lowering activity of Chitosan, a new dietary integrator. Chitin Enzymol 2;1:55- 

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cholesteol-fed rats. Nutr Rep Intl 18;5:531-7, 1978. 

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viscosity in rats. Lipids 23:187-91, 1988. 

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Elsevier Applied Science, London, UK, 472-78, 1992. 

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CHLORELLA and Immune health 


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of Nutrition 125 (10), 2511-2515. 

In vitro/ veterinary experiments 

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Phytochemistry 40 (5), 1433-1437. 

CHOLINE and Development 

Textbook/References 

- Garrow, T. (2001) Choline and carnitine; in Bowman BA, Russel RM (eds): Present knowledge 

in Nutrition, 8th edition. Washington, DC, ILSI Press, chapter 25, pp 261-270 

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- Institute of medicine (1998) Choline in Dietary Reference Intakes for thiamine, riboflavine, 

niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin and choline, pp 390-422, 

Washington DC: National Academy Press 

- Zeisel, S.H. (1999) Choline and phosphatidylcholine in Modern Nutrition in Health and Disease, 

pp. 513-523, 9th edition, Shils et al., Williams and Wilkins eds. Baltimore 

- Zeisel, S.H. and Holmes-McNary, M. (2001) Handbook of vitamins; 3rd ed, revised and 

expanded. Marcel Dekker Inc, New York, chapter 14, pp 513-528 

Human Clinical Studies: 

- Ladd, S.L.; Sommer, S.A.; LaBerge, S. and Toscano, W. (1993) Effect of phosphatidylcholine 

on explicit memory. Clin Neuropharmacol, 16(6), 540-549 

- Sitaram, N.; Weingartner, H.; Caine, E.D. and Gillin, J.C. (1978) Choline: Selective 

enhancement of serial learning and encoding of low imagery words in man. Life Sci. 22(17), 

1555-1560 

Reviews: 

- Zeisel, S.H.; da Costa, K.A.; Franklin, P.D.; Alexander, E.A.; Lamont, J.T.; Sheard, N.F. and 

Beiser, A. (1991) Choline, an essential nutrient for humans. FASEB J: 5, 2093-2098 

- Zeisel, S.H. (1997) Choline: essential for brain development and function. Adv. Pediatr. 44, 

263-295 

- Zeisel, S.H. (2000a) Choline: an essential nutrient for humans. Nutrition 16 (7/8), 669-67 

- Zeisel, S.H. (2000b) Choline: needed for normal development of memory. J. Am. Coll. Nutr. 19 

(5 Suppl) 528S-531S 

- Zeisel, S.H. (2006) Choline: Critical Role During Fetal Development and Dietary Requirements 

in Adults. Annu Rev Nutr.26, 229-250 

CHONDROITIN and Joint Health 

Human intervention trials (RCT): 

- Hungerford DS, Jones LC: Glucosamine and chondroitin sulfate are effective in the 

management of osteoarthritis. J Arthroplasty. 2003 Apr;18(3 Suppl 1):5-9. 

- Mazieres B, Combe B, Phan Van A, Tondut J, Gryfeltt M: Chondroitin sulfate in osteoarthritis of 

the knee: a prospective, double blind, placebo controlled multicenter clinical study. J 

Rheumatol. 200Jan;28(1):173-81 

- Michel BA: Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled 

trial. Arthritis Rheum. 2005 Mar;52(3):779-86. 

- Uebelhart D, Thonar EJ, Delmas PD, Chantraine A, Vignon E.: Effects of oral chondroitin 

sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthritis Cartilage. 1998 

May;6 Suppl A:39-46. 

- Uebelhart D, Malaise M, Marcolongo R, De Vathaire F, Piperno M, Mailleux E, Fioravanti A, 

Matoso L, Vignon E.: Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a 

one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis 

Cartilage.2004 Apr;12(4):269-76. 

- Verbruggen G., Goemaere S, Veys EM: Effects of oral chondroitin sulfate on the progression of 

knee osteoarthritis: a pilot study. Osteoarthritis Cartilage. 1998 May;6 Suppl A:39-46. 

Meta-analysis of human intervention trials: 

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- McAlindon TE, LaValley MP, Gulin JP, Felson DT :Glucosamine and chondroitin for treatment 

of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000 Mar 

15;283(11):1469-75. Review. 

- Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Structural and 

symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis. Arch Intern Med 

2003; 163: 1514-2 

COCOA FLAVANOLS and Antioxidative properties 


- Food and Agriculture Organization / World Health Organization. Diet, Nutrition and the 

Prevention of Chronic Diseases. 2003. 

- USDA, Agricultural Research Service: Phytonutrients PL FAQs, available at: 

http://www.ars.usda.gov 

Reviews 

- Arts IC, Hollmann PC. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr. 

2005;81:317S-325S. 

- Bravo L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr 

Rev. 1998 Nov;56(11):317-33. Review. 

- Del Rio D, Stewart AJ, Pellegrini N. A. Review of recent studies on malondialdehyde as toxic 

molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis. 2005 

Aug;15(4):316-28. Review. 

- Keen CL, Holt RR, Oteiza PI, Fraga CG, Schmitz HH. Cocoa antioxidants and cardiovascular 

health. Am J Clin Nutr. 2005 Jan;81(1 Suppl):298S-303S. 

- Mensink RP et al. PASSCLAIM-diet related cardiovascular disease. Eur J Nutr. 

2003;42(S1):1/6-1/27. 

- Scalbert A, Williamson G. Dietary intake and bioavailablility of polyphenols. J Nutr. 

2000;130:2073S-2085S. Review 


- Buijsse B, Feskens EJ, Kok FJ, Kromhout D. Cocoa intake, blood pressure, and cardiovascular 

mortality: the Zutphen Elderly Study. Arch Intern Med. 2006 Feb 27;166(4):411-7. 

- Engler MB, Engler MM. The vasculoprotective effects of flavonoid-rich cocoa and chocolate. 

Nutrition Research 24 (2004):695-706 

- Fraga CG, Actis-Goretta L, Ottaviani JI, Carrasquedo F, Lotito SB, Lazarus S, Schmitz HH, 

Keen CL. Regular consumption of a flavanol-rich chocolate can improve oxidant stress in 

young soccer players. Clin Dev Immunol. 2005 Mar;12(1):11-7. 

- Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Desideri G, Blumberg JB, 

Ferri C. Cocoa reduces blood pressure and insulin resistance and improves endotheliumdependent 

vasodilation in hypertensives. Hypertension. 2005a Aug;46(2):398-405. Epub 2005 

Jul 18. 

- Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark 

chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood 

pressure in healthy persons. Am J Clin Nutr. 2005b Mar;81(3):611-614. 

- Hirano R, Osakabe N, Iwamoto A, Matsumoto A, Natsume M, Takizawa T, Igarashi O, Itakura 

H, Kondo K. Antioxidant effects of polyphenols in chocolate on low-density lipoprotein both in 

vitro and ex vivo. J Nutr Sci Vitaminol (Tokyo). 2000 Aug;46(4):199-204. 

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- Hollenberg NK, Schmitz H, MacDonald I, Poulter N. Cocoa, flavanols and cardiovascular risk. 

Br J Cardiol.2004; 11:379-86. 

- Mathur S, Devaraj S, Grundy SM, Jialal I. Cocoa products decrease low density lipoprotein 

oxidative susceptibility but do not affect biomarkers of inflammation in humans. J Nutr. 2002 

Dec;132(12):3663-7. 

- Osakabe N, Baba S, Yasuda A, Iwamoto T, Kamiyama M, Takizawa T, Itakura H, Kondo K. 

Daily cocoa intake reduces the susceptibility of low-density lipoprotein to oxidation as 

demonstrated in healthy human volunteers. Free Radic Res. 2001 Jan;34(1):93-9. 

- Rein D, Lotito S, Holt RR, Keen CL, Schmitz HH, Fraga CG. Epicatechin in human plasma: in 

vivo determination and effect of chocolate consumption on plasma oxidation status. J Nutr. 

2000 Aug;130(8S Suppl):2109S-14S. 

- Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A. Plasma antioxidants 

from chocolate. Nature. 2003 Aug 28;424(6952):1013. 

- Steinberg FM, Holt RR, Schmitz HH, Keen CL. Cocoa procyanidin chain length does not 

determine ability to protect LDL from oxidation when monomer units are controlled. J Nutr 

Biochem. 2002 Nov;13(11):645-652. 

- Stoclet JC, Chataigneau T, Ndiaye M, et al. Vascular protection by dietary polyphenols. Eur J 

Pharmacol 2004;500:299-313. 

- Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and blood pressure in elderly individuals 

with isolated systolic hypertension. JAMA. 2003 Aug 27;290(8):1029-30. 

- Wan Y, Vinson JA, Etherton TD, Proch J, Lazarus SA, Kris-Etherton PM. Effects of cocoa 

powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in 

humans. Am J Clin Nutr. 2001 Nov;74(5):596-602. 

- Wiswedel I, Hirsch D, Kropf S, Gruening M, Pfister E, Schewe T, Sies H. Flavanol-rich cocoa 

drink lowers plasma F(2)-isoprostane concentrations in humans. Free Radic Biol Med. 2004 

Aug 1;37(3):411-21. 

COCOA FLAVANOLS and Vascular health 

Reviews 

- Balzer J, Heiss C, Schroeter H, Brouzos P, Kleinbongard P, Matern S, Lauer T, Rassaf T, Kelm 

M. Flavanols and cardiovascular health: effects on the circulating NO pool in humans. J 

Cardiovasc Pharmacol. 2006;47 Suppl 2:S122-7; discussion S172-6. 

- Ding EL, Hutfless SM, Ding X, Girotra S. Chocolate and prevention of cardiovascular disease: 

a systematic review. Nutr Metab (Lond). 2006;3:2. 

- Heiss C, Schroeter H, Balzer J, Kleinbongard P, Matern S, Sies H, Kelm M. Endothelial 

function, nitric oxide, and cocoa flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S128-35; 

discussion S172-6. 

- Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L. Cocoa flavanols and platelet and leukocyte 

function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol. 2006;47 

Suppl 2:S197-205; discussion S206-9. 

- Holt RR, Actis-Goretta L, Momma TY, Keen CL. Dietary flavanols and platelet reactivity. J 

Cardiovasc Pharmacol. 2006;47 Suppl 2:S187-96; discussion S206-9. 

- McCullough ML, Chevaux K, Jackson L, Preston M, Martinez G, Schmitz HH, Coletti C, 

Campos H, Hollenberg NK. Hypertension, the Kuna, and the Epidemiology of Flavanols. J 

Cardiovasc Pharmacol. 2006; 47 Suppl 2:S103-S109. 

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- Sudano I, Spieker LE, Hermann F, Flammer A, Corti R, Noll G, Luscher TF. Protection of 

endothelial function: targets for nutritional and pharmacological interventions. J Cardiovasc 

Pharmacol. 2006;47 Suppl 2:S136-50; discussion S172-6. 

- Watzl B, Rechkemmer G. Flavonoide. Ernährungs-Umschau 2001, 48(12):498-502. 

- Sies H, Stahl W, Sevanian A. Nutritional, dietary and postprandial oxidative stress. J Nutr. 

2005;135(5):969-72. 

Meta-Analyses 

- Taubert D, Roesen R, Schomig E. Effect of cocoa and tea intake on blood pressure: a metaanalysis. 

Arch Intern Med. 2007;167(7):626-34. 

Epidemiological studies 

- Arts IC, Hollman PC, Feskens EJ, Bueno de Mesquita HB, Kromhout D. Catechin intake might 

explain the inverse relation between tea consumption and ischemic heart disease: the Zutphen 

Elderly Study. Am J Clin Nutr. 2001;74(2):227-32. 

- Buijsse B, Feskens EJM, Kok FJ, Kromhout D. Cocoa intake, blood pressure, and 

cardiovascular mortality. Arch Intern Med 2006;166:411-7. 

- Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids 

and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993;342:1007-11. 

- Hollenberg N, Martinez G, McCullough M, Meinking T, Passan D, Preston M, Rivera A, Taplin 

D, Vicaria-Clement M. Aging, acculturation, salt intake, and hypertension in the Kuna of 

Panama. Hypertension 1997;29:171-6. 


- Engler MB, Engler MM, Chen CY, Malloy MJ, Browne A, Chiu EY, Kwak HK, Milbury P, Paul 

SM, Blumber J, Mietus- Snyder ML. Flavonoid-rich dark chocolate improves endothelial 

function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Cardio 

2004;23:197-204. 

- Fisher NDL, Hughes M, Gerhard-Herman M, Hollenberg NK. Flavanol-rich cooca induces nitricoxide-dependent 

vasodilation in healthy humans. J Hypertens 2003;21:2281-6. 

- Fraga CG, Actis-Goretta L, Ottaviani JI, Carrasquedo F, Lotito SB, Lazarus S, Schmitz HH, 

Keen CL. Regular consumption of a flavanol-rich chocolate can improve oxidant stress in 

young soccer players. Clin Dev Immunol 2005 Mar;12(1):11-7. 

- Freedman JE, Parker C 3rd, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Lafrati MD, Folts JD. 

Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric 

oxide release. Circulation 2001;103(23):2792-8. 

- Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark 

chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood 

pressure in healthy persons. Am J Clin Nutr 2005a;81:611-4. 

- Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Desideri G, Blumberg JB, 

Ferri C. Cocoa reduces blood pressure and insulin resistance and improves endotheliumdependent 

vasodilation in hypertensives. Hypertension 2005;46(2):398-405. 

- Heiss C, Finis D, Kleinbongard P, Hoffmann A, Rassaf T, Kelm M, Sies H. Sustained increase 

in flow-mediated dilation after daily intake of high-flavanol cocoa drink over week. J Cardiovasc 

Pharmacol. 2007;49(2):74-80. 

- Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H, Kelm M. Vascular effects of cocoa rich 

in flavan-3-ols. JAMA 2003;290:1030-1. 

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- Hermann F, Spieker LE, Ruschitzka F, Sudano I, Hermann M, Binggeli C, Luscher TF, Riesen 

W, Noll G, Corti R. Dark chocolate improves endothelial and platelet function. Heart. 2006; 

92(1):119-20. 

- Holt RR, Lazarus SA, Sullards MC, Zhu QY, Schramm DD, Hammerstone JF, Fraga CG, 

Schmitz HH, Keen CL. Procyanidin dimmer B2 (epicatechin- [4beta-8]-epicatechin) in human 

plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 2002;76:798-804. 

- Holt RR, Schramm DD, Keen CL, Lazarus SA, Schmitz H. Flavonoid rich chocolate and platelet 

function. JAMA 2002;287:2212-3. 

- Innes AJ, Kennedy G, McLaren M, Bancroft AJ, Belch JJ. Dark chocolate inhibits platelet 

aggregation in healthy volunteers. Platelets. 2003 Aug;14(5):325-7. 

- Keevil JG, Osman HE, Reed JD, Folts, JD. Grape juice, but not orange juice or grapefruit juice, 

inhibits human platelet aggregation. J Nutr 2000;130:53-6. 

- Murphy KJ, Chronopoulos AK, Singh I, Francis MA, Moriaty H, Pike MJ, Turner AH, Mann NJ, 

Sinclair AJ. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit 

platelet function. Am J Clin Nutr 2003;77:1466-73. 

- Neukam K, Stahl W, Tronnier H, Sies H, Heinrich U.Consumption of flavanol-rich cocoa acutely 

increases microcirculation in human skin. Eur J Nutr. 2007;46(1):53-6. 

- Pearson D, Paglieroni T, Rein D, Wun T, Schramm DD, Wang JF, Holt RR, Gosselin R, 

Schmitz HH, Keen CL. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet 

function. Thromb Res 2002;106:191-7. 

- Rein D, Paglieroni TG, Wun T, Pearson DA, Schmitz HH, Gosselin R, Keen CL. Cocoa inhibits 

platelet activation and function. Am J Clin Nutr 2000;72:30-5. 

- Rein R, Lotito S, Holt RR, Keen CL, Schmitz HH, Fraga CG. Epicatechin in human plasma: In 

vivo determination and effect of chocolate consumption on plasma antioxidant capacity. J Nutr 

2000a;130(8S):2109S-14S. 

- Richelle M, Tavazzi I, Enslen M, Offord EA. Plasma kinetics in man of epicatechin from black 

chocolate. Eur J Clin Nutr., 1999;53(1):22-6. 

- Schramm DD, Karim M, Schrader HR, Holt RR, Kirkpatrick NJ, Polagruto JA, Ensunsa JL, 

Schmitz HH, Keen CL. Food effects on the absorption and pharmacokinetics of cocoa 

flavanols. Life Sciences 2003;73:857-69. 

- Schramm DD, Wang JF, Holt RR, Ensunsa JL, Gonsalves JL, Lazarus SA, Schmitz HH, 

German JB, Keen CL. Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in 

humans and human aortic endothelial cells. Am J Clin Nutr 2001;73:36-40. 

- Schroeter H, Holt RR, Orozco TJ, Schmitz HH, Keen CL. Nutrition: milk and absorption of 

dietary flavanols. Nature 2003;426:787-8. 

- Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A. Plasma antioxidants 

from chocolate. Nature 2003, 28;424(6952):1013. 

- Sies H, Schewe T, Heiss C, Kelm M. Cocoa polyphenols and inflammatory mediators. Am J 

Clin Nutr 2005;81(Suppl):304S-12S. 

- Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and blood pressure in elderly individuals 

with isolated systolic hypertension. JAMA 2003;290:1029-30. 

- Vlachopoulos C, Aznaouridis K, Alexopoulos N, Economou E, Andreadou I, Stefanadis C. 

Effect of dark chocolate on arterial function in healthy individuals. Am J Hypertens 

2005;18(6):785-91. 

- Wang JF, Schramm DD, Holt RR, Ensunsa JL, Fraga CG, Schmitz HH, Keen CL. A dose 

response effect from chocolate consumption on plasma epicatechin and oxidative damage. J 

Nutr 2000;130:2115S-9S. 

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- Wang-Polagruto JF, Villablanca AC, Polagruto JA, Lee L, Holt RR, Schrader HR, Ensunsa JL, 

Steinberg FM, Schmitz HH, Keen CL. Chronic Consumption of Flavanol-rich Cocoa Improves 

Endothelial Function and Decreases Vascular Cell Adhesion Molecule in Hypercholesterolemic 

Postmenopausal Women. J Cardiovasc Pharmacol. 2006; 47 Suppl 2:S177-S186. 

In vitro and animal studies 

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inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost. 

2005;3(2):369-76. 

- Karim M, McCormick K, Kappagoda TC. Effects of cocoa extracts on endothelium dependent 

relaxation. Am J Clin Nutr. 2000;130(8S):2105S-8S. 

Studies investigating the polyphenol and flavanol content of foods 

- Hammerstone JF, Lazarus SA, Schmitz HH. Procyanidin content and variation in some 

commonly consumed foods. J Nutr. 2000;130(8S Suppl):2086S-92S. 

- Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food sources and 

bioavailability. Am J Clin Nutr. 2004;79(5):727-47. 

- Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of 

polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 

2005;81(Suppl):230S-242S. 

- USDA Database for the Flavonoid Content of Selected Foods. Beltsville: U.S. Department of 

Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, 

Nutrient Data Laboratory, 2003:1-79. 

COENZYME Q10 (UBIQUINONE) and Energy metabolism 

Monograph 

- Dutton PL, Ohnishi T, Darrouzet E, Leonard, MA, Sharp RE, Cibney BR, Daldal F and Moser 

CC. 4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport (pp 65-82) 

in Coenzyme Q: Molecular mechanisms in health and disease edited by Kagan VE and Quinn 

PJ, CRC Press (2000), Boca Raton 

Textbook 

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edited by Coates PM et al, Marcel Dekker Press, New York (2005). 

Review 

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- Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. 

Biochim Biophys Acta 1271: 195-204, 1995 

COENZYME Q10 (UBIQUINONE) and Hearth health 

Textbook 

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Dietary Supplements edited by Cupp MJ and Tracy TS Humana press, Totowa, New Jersey 

(2003) 

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treatment of hypertension: a meta-analysisi of the clinical trials. J Human Hypertension 21: 

297-306, 2007 

- Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme CoQ10 

illuminated by meta-analyses of clinical trials. Mol Aspects Med. 1997; 18 Suppl:S159-68 

Individual Human Trials 

- Yamagami T, Takagi M, Akagami H, et al. Effect of coenzyme Q10 on essential hypertension, 

a double blind controlled study. Biomed and Clin Aspects of Coenzyme Q. vol. 5: 337-343, 

1986 

- Digiesi V, Cantini F and Brodbeck B. Effect of coenzyme Q10 on essential arterial 

hypertension. Curr Ther Res. 47:841-844, 1990 

- Digiesi V, Cantini F, Oradei A, Bisi G Guarino C Brocchi A. Bellandi F, Mancini M and Littarru 

GP. Coenzyme Q10 in essential hypertension. Molec Aspects Med vol.15 (Supplement): s257- 

263, 1994 

- Burke BE, Neuenschwander R, Olson RD: Randomized, double-blind, placebo-controlled trial 

of coenzyme Q10 in isolated systolic hypertension. South Med J. 94: 1112-1117, 2001 

- Hodgson JM, Watts GF, Playford DA Burke V and Croft KD. Coenzyme Q10 improves blood 

pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J of Clin 

Nutr, 56:1137-1142, 2002 

Other Individual Studies 

- Berman M, Erman A, Ben-Gal T, et al. Coenzyme Q10 in patients with end stage heart failure 

awaiting cardiac transplantation: a randomised, placeb ocontrolled study. Clin Cardiol 2004; 

27:295–299. 

- Damian MS, Ellenberg D, Gildemeister R, et al. Coenzyme Q10 combined with mild 

hypothermia after cardiac arrest. Circulation 2004; 110:3011–3016. 

- Folkers, K.; Vadahanavikit, S.; Mortensen, S.A. Biochemical rationale and myocardial tissue 

data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc. Natl. Acad. Sci. 

U.S.A. 1985, 82, 901–904. 

- Littarru GP, Lippa S., Oradei A., Fiorini R.M., and Mazzanti L. (1991) Metabolic and diagnostic 

implication of human blood CoQ10 levels. Biomedical and Clinical Aspects of Coenzyme Q. Vol 

VI, 167-178 

- Littarru GP, Ho L, Folkers K. Deficiency of coenzyme Q10 in human heart disease: part I þ II. 

Int J Vit Nutr Res 1972; 42:291–305. 

- Mortensen SA. Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. 

BioFactors 2003; 18:79–89. 

- Mortensen SA. Symptomatic effects of coenzyme Q10 in heart failure: Q-SYMBIO study status. 

Presented at the 4th conference of the International CoQ10 Association, Los Angeles, 

California, 14–17 April 2005. InternationalCoQ10 Association; 2005. pp. 57–58. 

- Rosenfeldt F, Marasco S, Lyon W, et al. Coenzyme Q10 therapy before cardiac surgery 

improves mitochondrial function and in vitro contractility of myocardial tissue. J Thorac 

Cardiovasc Surg 2005; 129:25–32. 

- Sacher, H.L.; Sacher, M.L.; Landau, S.W.; Kersten, R.; Dooley, F.; Sacher, A.; Sacher, 

M.;Dietrick, K.; Ichkhan, K. The clinical and hemodynamic effects of coenzyme Q10 in 

congestive cardiomyopathy. Am. J. Ther. 1997, 4, 66–72. 

- Tran MT, Mitchell TM, Kennedy DT, Giles JT. Role of coenzyme Q10 in chronic heart failure, 

angina, and hypertension. Pharmacotherapy 2001; 21:797-806 

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61

- Turunen, M.; Olsson, J.; Dallner, G. Metabolism and function of coenzyme Q. Biochim. 

Biophys. Acta. 2004, 1660, 171–199. 

COENZYME Q10 (UBIQUINONE) and Antioxidant properties 

Monograph 

- Thomas S R and Stocker R. 9 Mechanisms of antioxidant action of ubiquinol-10 for low density 

lipoprotein. pp131-150 in Coenzyme Q: Molecular mechanisms in health and disease edited 

by Kagan VE and Quinn PJ, CRC Press (2000), Boca Raton 

Textbook 

- Dallner G and Stocker R. Coenzyme Q10, pp 121-13in Encyclopedia of Dietary Supplements 

edited by Coates PM et al, Marcel Dekker Press, New York (2005). 

Reviews 

- Crane FL: Biochemical functions of coenzyme Q10. J Am Coll Nutr. 20: 591-598, 2001 

- Quinn PJ, Fabisiak JP, Kagan VE.: Expansion of antioxidant function of vitamin E by coenzyme 

Q. BioFactors 9: 149-154, 1999 

- Beal MF. Mitochondrial dysfunction and oxidative damage in Alzheimer’s and Parkinson’s 

diseases and coenzyme Q10 as a potential treatment. J Bioenerg Biomembr 2004; 36:381– 

386. A comprehensive review. 

Individual Human Trials 

- Weber C, Sejersgard Jakobsen T, Mortensen SA, Paulsen G and Holmer G. Antioxidative 

effect of dietary coenzyme Q10in human blood plasma. Internat. Vit Nutr Res 64:311-315, 

1994 

- Alleva R, Tomasetti M, Battino M, Curatola G, Littarru GP, Folkers K: The roles of coenzyme 

Q10 and vitamin E on peroxidation of human low density subfractions. Proc Nat Acad Sci. 

USA, 92: 9388-9391, 1995 

Other Individual Studies 

- Arroyo A, Kagan VE, Tyurin VA, Burgess JR, de Cabo R, Navas P, Villalba JM: NADH and 

NADPH-dependent reduction of coenzyme Q at the plasma membrane. Antioxid Redox Signal. 

2: 251-262, 2000 

- Arsenio L., Frega N., Littarru G.P. Livelli sierici di CoQ10 e vitamina E Progress in Nutrition 

vol.7, n. 3, 183-191, 2005 

- Chapidze G, Kapanadze S, Dolidze N, et al. Prevention of coronary atherosclerosis by the use 

of combination therapy with antioxidant coenzyme Q10 and statins. Georgian Med News 2005; 

1:20–25. 

- Chew GT, Watts GF, Coenzyme. Q10 and diabetic endotheliopathy: oxidative stress and the 

‘recoupling hypothesis’. QJM 2004; 97:537– 548. 2 years. 

- Gille G, Hung ST, Reichmann H, Rausch WD. Oxidative stress to dopaminergic neurons as 

models of Parkinson’s disease. Ann N Y Acad Sci 2004; 1018:533–540. 

- Kontush A, Hubner, C., Finckh, B., Kohlschutter, A., and Beisiegel, U. (1994) Low density 

lipoprotein oxidizability by copper correlates to its initial ubiquinol-10 and polyunsaturated fatty 

acid content. FEBS Lett. 341,69-73. 

- Kwong LK, Kamzalov S, Rebrin I, Bayne A-C V, Jana CK, Morris P, Forster MJ, Sohal RS: 

Effects of coenzyme Q10 administration on its tissue concentrations, mitochondrial oxidant 

generation, and oxidative stress in the rat. Free Radic Biol Med. 33: 627-638, 2002 

62 

62

- Mohr, D.; Bowry, V.W.; Stocker, R. Dietary supplementation with coenzyme Q10 results in 

increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of 

human low-density lipoprotein to the initiation of lipid peroxidation. Biochim. Biophys. Acta. 

1992, 1126, 247–254. 

- Quiles JL, Ochoa JJ, Huertas JR, Mataix J: Coenzyme Q supplementation protects from agerelated 

DNA double-strand breaks and increases lifespan in rats fed on PUFA-rich diet. 

Experimental Gerontology, 39:189-194, 2004 

- Quiles JL, Ochoa JJ, Battino M, Gutierrez-Rios P, Nepomuceno EA, Lopez Frias M, Huertas 

JR, Mataix J: Life-long supplementation with a low dosage of coenzyme Q10 in the rat: Effects 

on antioxidant status and DNA damage. Biofactors, 25: 73-86, 2005 

- Somayajulu M, McCarthy S, Hung M, et al. Role of mitochondria in neuronal cell death induced 

by oxidative stress: neuroprotection by coenzyme Q10. Neurobiol Dis 2005; 18:618–627. 

- Sohmiya M, Tanaka M, Tak NW, et al. Redox status of plasma coenzyme Q10 indicates 

elevated systemic oxidative stress in Parkinson’s disease. J Neurol Sci 2004; 223:161–166. 

- Stocker R, Bowry, V. W., and Frei, B. (1991) Ubiquinol-10 protects human low density 

lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. 

- 

Proc.Natl.Acad.Sci.U.S.A. 88,1646-1650. 

Thomas SR, Witting, P. K., and Stocker, R. (1999) A role for reduced coenzyme Q in 

atherosclerosis? Biofactors. 9,207-224. 

- Tomasetti, M.; Littarru, G.P.; Stocker, R.; Alleva, R. Coenzyme Q10 enrichment decreases 

oxidative DNA damage in human lymphocytes. Free Radic. Biol. Med. 1999, 27, 1027–1032. 

- Winkler-Stuck K,Widemann FR, Wallesch CW, Kunz WS. Effect of coenzyme Q10 on the 

mitochondrial function of skin fibroblasts from Parkinson patients. J Neurol Sci 2004; 220:41– 

48. 

- Witting, K.; Pettersson, K.; Letters, J.; Stocker, R. Anti-atherogenic effect of coenzyme Q10 in 

apolipoprotein E gene knockout mice. Free Radic. Biol. Med. 2000, 29, 295–305. 

COLLAGEN HYDROLYSATE and Joint health 

Review 

- Bello AE, Oesser S : Collagen hydrolysate for the treatment of osteoarthritis and other joint 

disorders : a review of the literature. Current Medical Research and Oprinion, Vol 22, no 11, 

2006, 2221 – 2232 


- Adam M : Gelatine – möglicher medizinischer Einsatz. Apothekerjournal, 9 / 1995, 18 - 22 

- Adam M : Welche Wirkung haben Gelatinepräparate ? Therapiewoche 41 (1991) 2456 - 2461 

- Adam M, Špaček P, Helejová H, Galianová A, Blahoš J : May collagen hydrolysate rich diet 

(CHRD) extend the effect of calcitonin in postmenopausal osteoporosis ? Connective Tissue 

Diseases (1998), XVII : 25 – 36 

- Beeinflussung des Gelenkknorpels durch Kollagenhydrolysat – ein wissenschaft-liches 

Kompendium (ISBN 3 – 936033 – 13 -7) 

- Beuker F, Eck T, Rosenfeld J : Biochemical and clinical examinations of the effects of regular 

applications of gelatine on dgenerative damages of the motoric system. International Journal of 

Sports Medicine 17 (1996) 

- Clark K : Collagen hydrolysate in joint health. Natural Pharmacy, Vol 9, no 6, December 2005 

13 – 16 

63 

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- Clark K : Nutritional considerations in joint health. Submitted for publication in the journal 

“Clinics in Sports Medicine” 

- Deal LD, Moskowitz RW : Neutraceuticals as therapeutic agents in osteoarthritis. Rheumatic 

Disease Clinics of North America, May 1999, 379 - 395 

- Döll : Arthrose – endlich schmerzfrei durch Biostoffe (ISBN 3 – 7766 – 2338 – 1) 

- Eid K, Thornhill TS, Glowacki J : Disparate effects of gelatine hydrolysates on human 

chondrocytes. Submitted for publication 

- Flechsenhar K, Alf D : Ergebnisse einer Anwendungsbeobachtung zu Kollagen-Hydrolysat CH- 

Alpha. Orthopädische Praxis , 9 / 2005, 486 – 494 

- Götz B : Gut genährter Knorpel knirscht nicht mehr. Ärztliche Praxis, 92 (1982) 3130 – 3134 

- Hesse K : Anwendungsbeobachtung über die Supplementierung von Gelatinehydro-lysat bei 

arthrotischen Hunden. Kleintiermedizin Nr. 1, 2 / 2006, 17 – 22 

- Kasper : Ernährungsmedizin und Diätetik (ISBN 3 – 437 – 42011 – 9) 

- Kasper H : Die chondroprotektive Wirkung von Gelatine. Die Medizinische Welt, 3 / 2000, 54, 

47 - 49 

- Krug E : Zur unterstützenden Therapie bei Osteo- und Chondropathien. Zeitschrift für 

Erfahrungsheilkunde. 11 (1979), 930 – 938 

- Moskowitz RW : Role of collagen hydrolysate in bone and joint disease. Seminars in Arthritis 

and Rheumatism, October 2000, 87 - 99 

- Ng KW, Saliman JD, Kelly T-AN, Statman LY, Ateshian GA, Hung CT : Collagen hydrolysate 

increases the mechanical properties and type II collagen synthesis of tissue engeneered 

articular cartilage. Paper no 0259. 51st Annual Meeting of the Orthopaedic Research Society in 

Washington (USA) in February 2005. 

- Oberschelp U : Indivudelle Arthrosetherapie ist möglich. Therapiewoche 44 (1985) 5094 – 

5097 

- Oesser S, Adam M, Babel W, Seifert J : Oral administration of 14C labelled gelatin hydrolysate 

leads to an accumulation of radioactivity in cartilage of mice (C57/BL). Journal of Nutrition, 129 

(1999), 1891 – 1895 

- Oesser S, Seifert J : Stimulation of type II collagen biosynthesis and secretion in bovine 

chondrocytes cultured with degraded collagen. Cell Tissue Res 311 (2003), 393 – 399 

- Oesser S, Seifert J : Einfluss von Kollagenfragmenten auf Neusynthese und Degra-dation der 

extrazellulären Knorpelmatrix. Orthopädische Praxis, 10 / 2005, 565 – 568 

- Ribas Fernández J Ll, Molinero Pérez O : Effecto de los hidrolizados de gelatina en la 

prevención de las lesiones en deportistas (Effects of gelatine hydrolysates in the prevention of 

sportsmen and women injuries). Archivos de Medicina del Deporte, Vol XV, no 66 (1998), 277 

– 282 

- Rippe : The Joint Health Prescription 

- Seeligmüller K, Happel KH : Kann eine Gelatine/L-Cystin-Mischung die Kollagen- und 

Proteoglykansynthese stimulieren ? Therapiewoche 39, 3153 – 3157 (1989) 

- Seeligmüller K, Happel KH : Dem Knorpel auf die Sprünge helfen. Therapiewoche 43, 36, 1810 

– 1813 (1993) 

- Weh L : Was ist dran an der Gelatine ? Extracta Orthopaedica, 5 / 1999, 15 - 17 

- Weh L, Petau C : Änderungen des Gewebeeigenschaften durch Gelatineeinnahme – eine 

biomecahnische in-vivo-Pilotstudie. Extracta Orthopaedica, 4 / 2001, 12 – 16 

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CONJUGATED LINOLEIC ACID (CLA) and Weight management 

Reviews/Meta Analyses 

- Atkinson R. International meeting: LIPID FORUM, Denmark june 1999. Abstract: Clinical 

implications for conjugated linoleic acid (CLA) in the treatment of obesity 

- Berven G, Bye A, Hals O, Blankson H, Fagertun H, Thom E, Wadstein J, Gudmundsen O. 

Safety of conjugated linoleic acid (CLA) in overweight or obese human volunteers. European J. 

Lipid Sci. Technol. 2000; 102: 455–462. 

- Kreider RB, Ferreira MP, Greenwood M, Wilson M, Almada AL. Effects of conjugated linoleic 

acid supplementation during resistance-training on body composition. Bone density, strength, 

and selected hematological markers. J Strength Cond Res 2002; 3: 325-34. 

- Smedman A, Vessby, B. Conjugated linoleic acid supplementation in humans - Metabolic 

effects. Lipids 2001;36:773–781. 

- Wang et al. (2004): Conjugated linoleic acid and obesity control: efficacy and mechanism. 

Int.J.Obes.Relat.Metab.Disord. 28(8): 941-55 

- Watras AC, Buchholz AC, Close RN, Zhang Z, Schoeller DA (2006) The role of conjugated 

linoleic acid in reducing body fat and preventing holiday weight gain. Int J Obes (Lond) 

- Whigham LD, Watras AC, Schoeller DA (2007) Efficacy of conjugated linoleic acid for reducing 

fat mass: a meta-analysis in humans. Am J Clin Nutr. 2007 May;85(5):1203-11. 

Human Intervention Studies 

- Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Conjugated 

Linoleic Acid reduces body fat mass in overweight and obese humans. Journal of Nutrition 

2000;130:2943-48 

- Gaullier JM, Halse J, Høivik HO, Høye K, Syvertsen C, Nurminiemi M, Hassfeld C, Einerhand 

A, O'Shea M, Gudmundsen O (2007) Six months supplementation with conjugated linoleic acid 

(CLA) induces regional-specific fat mass decreases in overweight and obese. Br J Nutr, 

Volume 97, No. 3, on pages 550 to 560. 

- Gaullier JM, Hasle J, Hoye K, Kristiansen K, Halse, J, Fagertun H, Vik H, and Gudmundsen O. 

Conjugated linoleic acid supplementation for 1 year reduces body fat mass in healthy 

overweight humans. Am J Clin Nutr 2004; 79: 1118-25 


Supplementation with Conjugated Linoleic Acid for 24 Months Is Well Tolerated by and 

Reduces Body Fat Mass in Healthy, Overweight Humans, J. Nutr 2005; 135, 778-784. 

- Gaullier JM, Berven G, Blankson H, Gudmonson O. Clinical trial results support a preference 

for using CLA preparations enriched with two isomers rather than four isomers in human 

studies. Lipids. 2002; 37: 1019-25. 

- Jean-Michel G et al Conjugated linoleic acid supplementation for 1 y reduces body fat mass in 

healthy overweight humans; Am J Clin Nutr 2004;79:1118 –25. 

- Kamphuis MMJW, Lejeune MPGM, Saris WHM, Westerterp-Plantinga MS. The effect of 

conjugated linoleic acid supplementation after weight loss on body weight regain, body 

composition, and resting metabolic rate in overweight subjects. Int J Obesity 2003; 27: 840- 

847. 

- Kamphuis MMJW, Lejeune MPGM, Saris WHM, Westerterp-Plantinga MS. Effect of 

conjugated linoleic acid supplementation after weight loss on appetite and food intake in 

overweight subjects, Eur J Clin Nutr 2003; 57; 1268-74 

- Larsen TM, Toubro S, Gudmundsen O, Astrup A. Conjugated linoleic acid supplementation for 

1 y does not prevent weight or body fat regain. Am J Clin Nutr 2006;83:606-12. 

65 

65

- Mougios V, Matsakas A, Petridou A, Ring S, Sagredos A, Melissopoulou A, Tsigilis N, 

Nikolaidis M. Effect of supplementation with conjugated inoleic acid on human serum lipids 

and body fat. J Nutr Biochem 2001; 12: 585-94. 

- Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB, Facci M, Farthing JP, Zello 

GA. The effects of conjugated linoleic acid supplementation during resistance training.GA. Med 

Sci Sports Exerc. 2006;38:339-48. 

- Riserus U, Berglund L, Vessby B. Conjugated linoleic acid (CLA) reduced abdominal adipose 

tissue in obese middle-aged men with signs of metabolic syndrome: a randomised controlled 

trial. International Journal of Obesity 2001: 25; 1129-1135. 

- Rockway SW. Dietary conjugated acid alters body composition and lowers cholesterol and 

triglycerides in healthy men. Lake Bluff, Illinois: PharmaNutrients, Inc; 2000. 

- Thom E. Wadstein J. Gudmundsen O. Conjugated linoleic acid reduces body fat in healthy 

exercising humans.[erratum appears in J Int Med Res 2001 Mar-Apr;30(2):210 Note: 

Correction of dosage error in abstract.]. [Clinical Trial. Journal Article. Randomized Controlled 

Trial] Journal of International Medical Research. 29(5):392-6, 2001 Sep-Oct. 

- Whigham LD, O'Shea M, Mohede IC, Walaski HP, Atkinson R L, Safety profile of conjugated 

linoleic acid in a 12-month trial in obese humans, Food Chem Toxicol. 2004; 42: 1701-9. 

- Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley DS, Nelson GJ. Conjugated 

linoleic acid supplementation in humans: Effects on body composition and energy expenditure. 

Lipids 2000; 35: 777–82 

- Zambell KL. Horn WF. Keim NL. Conjugated linoleic acid supplementation in humans: effects 

on fatty acid and glycerol kinetics. Lipids. 2001: 36(8):767-72, 

CONJUGATED LINOLEIC ACID (CLA) and Insulin sensitivity 


- Belury MA, Mahon A, Banni S. The conjugated linoleic acid (CLA) isomer, t10c12-CLA, is 

inversely associated with changes in body weight and serum leptin in subjects with type 2 

diabetes mellitus. Journal of Nutrition 2003;133:257-260 

- Eyjolfson V, Spriet LL, Dyck DJ. Conjugated linoleic acid improves insulin sensitivity in young, 

sedentary humans. Medicine & science in sports & exercise 2004;Vol. 36,No. 5:814-820 

- Risérus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans10 cis12 conjugated 

linoleic acid causes isomer specific insulin resistance in obese men with the metabolic 

syndrome. Diabetes Care 2002;25:1516-1521 

- Schrezenmeir et al. Randomized, placebo-controlled, double-blind clinical study on effect of 

CLA on endothelial function und traits of the metabolic syndrome. 2006 (7) 

CONJUGATED LINOLEIC ACID (CLA) and Immune health 


- Albers R, van der Wielen RPJ, Brink EJ, Hendriks HFJ, Dorovska-Taran VN, Mohede ICM. 

Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on 

immune function in healthy man. European Journal of Clinical Nutrition 2003; 57: 595-603 

- Hayden FG, O’Shea M. Effect of Conjugated Linoleic Acid on Experimental Rhinovirus Illness. 

US CLA Network meeting 2005 

- Kelley DS, Tayler PC, Rudolph IL, Benito P, Nelson GJ, Mackey BE, Erickson KL. Dietary 

Conjugated Linoleic Acid Did Not Alter Immune Status in Young Health Women. Lipids 2000; 

35: 1065-1071 

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66

- Song H-J, Grant I, Rotondo D, Mohede I, Sattar N, Heys SD and Wahle KWJ. Effect of CLA 

supplementation on immune function in young healthy volunteers. European Journal of Clinical 

Nutrition 2005:1-10 

- Fava C, Attridge S, Singhera GK, Bahzad M, Dorscheid DR. Use of conjugated linoleic acid 

(CLA) improves markers of inflammation in asthma. Abstract held at the 2004 annual 

conference of the American Thoracic Society (ATS) 

- Turpeinen A, Aro A. Effects of cis-9, trans-11 CLA on immunological parameters in subjects 

with birch pollen allergy. EFL Madrid 2006 

In vivo studies 

- Bassaganya-Riera J, Pogranichniy RM, Jobgen SC, Halbur PG, Yoon K-J, O’Shea M, Mohede 

I, Hontecillas R. Conjugated linoleic acid ameliorates viral infectivity in a pig model of virally 

induced immunosuppression. Journal of Nutritional 2003; 133:3204-3214 

- Bassaganya-Riera J, Hontecillas-Magarzo R, Bregendahl K, Wannemuehler MJ, Zimmerman 

DR. Effects of dietary conjugated linoleic acid in nursery pigs of dirty and clean environments 

on growth, empty body composition, and immune competence. American society of animal 

science 2001;79:714-721 

- Bassaganya-Riera J, Reynolds K, Martino-Catt S, Cui Y, Hennighausen L, Gonzalez F, Rohrer 

J, Benninghoff AU, Hontecillas R. Activation of PPAR γ and δ by Conjugated Linoleic Acid 

Mediates Protection From Experimental Inflammatory Bowel Disease. Gastroenterology 2004; 

127: 777-791 

CONJUGATED LINOLEIC ACID (CLA) ((CIS-9, TRANS-1CONJUGATED LINOLEIC ACID, AND 

TRANS-10, CIS-12 CONJUGATED LINOLEIC ACID (50:50) TRIGLYCERIDES) and Body 

Weight management 

Meta-analysis 

- Whigham LD, Watras AC, Schoeller DA (2007) Efficacy of conjugated linoleic acid for reducing 

fat mass: a meta-analysis in humans. 

Am J Clin Nutr. 2007 May;85(5):1203-11. 


- Atkinson R. International meeting: LIPID FORUM, Denmark june 1999. Abstract: Clinical 

implications for conjugated linoleic acid (CLA) in the treatment of obesity 

- Berven G, Bye A, Hals O, Blankson H, Fagertun H, Thom E, Wadstein J, Gudmundsen O. 

Safety of conjugated linoleic acid (CLA) in overweight or obese human volunteers. European J. 

Lipid Sci. Technol. 2000; 102: 455–462. 

- Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Conjugated 

linoleic acid (CLA) reduces body fat mass in overweight and obese humans. J Nutr 2000; 130: 

2943-8. 

- Gaullier JM, Berven G, Blankson H, Gudmonson O. Clinical trial results support a preference 

for using CLA preparations enriched with two isomers rather than four isomers in human 

studies. Lipids. 2002; 37: 1019-25. 

- Gaullier JM, Halse J, Høivik HO, Høye K, Syvertsen C, Nurminiemi M, Hassfeld C, Einerhand 

A, O'Shea M, Gudmundsen O (2007) Six months supplementation with conjugated linoleic acid 

(CLA) induces regional-specific fat mass decreases in overweight and obese. Br J Nutr, 

Volume 97, No. 3, on pages 550 to 560. 


Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight 

humans. Am J Clin Nutr 2004; 79: 1118-25 

67 

67


Supplementation with Conjugated Linoleic Acid for 24 Months Is Well Tolerated by and 

Reduces Body Fat Mass in Healthy, Overweight Humans, J. Nutr 2005; 135, 778-784. 

- Kamphuis MMJW, Lejeune MPGM, Saris WHM, Westerterp-Plantinga MS. The effect of 

conjugated linoleic acid supplementation after weight loss on body weight regain, body 

composition, and resting metabolic rate in overweight subjects. Int J Obesity 2003; 27: 840- 

847. 

- Kamphuis MMJW, Lejeune MPGM, Saris WHM, Westerterp-Plantinga MS. Effect of 

conjugated linoleic acid supplementation after weight loss on appetite and food intake in 

overweight subjects, Eur J Clin Nutr 2003; 57; 1268-74 

- Kreider RB, Ferreira MP, Greenwood M, Wilson M, Almada AL. Effects of conjugated linoleic 

acid supplementation during resistance-training on body composition. Bone density, strength, 

and selected hematological markers. J Strength Cond Res 2002; 3: 325-34. 

- Larsen TM, Toubro S, Gudmundsen O, Astrup A. Conjugated linoleic acid supplementation for 

1 y does not prevent weight or body fat regain. Am J Clin Nutr 2006;83:606-12. 

- Mougios V, Matsakas A, Petridou A, Ring S, Sagredos A, Melissopoulou A, Tsigilis N, 

Nikolaidis M. Effect of supplementation with conjugated inoleic acid on human serum lipids 

and body fat. J Nutr Biochem 2001; 12: 585-94. 

- Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB, Facci M, Farthing JP, Zello 

GA. The effects of conjugated linoleic acid supplementation during resistance training.GA. Med 

Sci Sports Exerc. 2006;38:339-48. 

- Riserus U, Berglund L, Vessby B. Conjugated linoleic acid (CLA) reduced abdominal adipose 

tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised 

controlled trial. Int J Obes Relat. Metab Disord 2001; 25: 1129-35 

- Smedman A, Vessby, B. Conjugated linoleic acid supplementation in humans - Metabolic 

effects. Lipids 2001;36:773–8. 

- Taylor JS, Williams SR, Rhys R, James P, Frenneaux MP. Conjugated Linoleic Acid Impairs 

Endothelial Function. Arterioscler Thromb Vasc Biol 2006;26:307-12. 

- Thom E, Wadstein J, Gudmundson O. Conjugated linoleic acid reduces body fat in healthy 

exercising humans. J Int Med Res 2001; 29: 392-6. 

- Watras AC, Buchholz AC, Close RN, Zhang Z, Schoeller DA (2006) The role of conjugated 

linoleic acid in reducing body fat and preventing holiday weight gain. Int J Obes (Lond) 

- Whigham LD, O'Shea M, Mohede IC, Walaski HP, Atkinson R L, Safety profile of conjugated 

linoleic acid in a 12-month trial in obese humans, Food Chem Toxicol. 2004; 42: 1701-9. 

- Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley DS, Nelson GJ. Conjugated 

linoleic acid supplementation in humans: Effects on body composition and energy expenditure. 

Lipids 2000; 35: 777–82 

CREATINE and Energy metabolism 

Text books 

- Komi (1994) Strength and power in sport. Blackwell Science, London. 


- Child (2007) Scientific justification for creatine maintenance and creatine loading doses 

proposed by the european specialist sports nutrition alliance (ESSNA), Version 12, pages 1-29. 

- Balsom PD, Söderlund K, Ekblom B (1994) Creatine in humans with special reference to 

creatine supplementation. Sports Med. 18; 268-280. 

68 

68

- Mesa JL, Ruiz JR, González-Gross MM, Gutiérrez Sáinz A, Castillo Garzón MJ. (2002) Oral 

creatine supplementation and skeletal muscle metabolism in physical exercise. Sports Med. 

32; 903-944. 

- SCF (2000) Opinion of the Scientific Committee on Food on safety aspects of creatine 

supplementation. SCF/CS/NUT/SPORT/9 Final 12/9/2000. European Commission, Health and 

Consumer Protection Directorate General. Pages 1-6. 

Meta-analysis 

- Niessen SL et al. Effect of dietary supplements on lean mass and strenght gains with 

resistence exercize: a meta-analysis. J Appl Physiol. 94: 651-659, 2003 

- Branch JD. Effect of creatine supplementation on body composition and performance: a metaanalysis. 

Int J Sport Nutr Exerc Metab. 13: 198-226, 2003 

Review 

- Rawson ES et al. Effects of creatine supplementation and resistance training on muscle 

strength and weightlifting performance. J Strength Cond Res. 17: 822-831, 2003 

- Bemben MG et al. Creatine supplementation and exercise performance: recent findings. Sports 

Med. 35: 107-125, 2005 

- Volek JS et al. Scientific basis and practical aspects of creatine supplementation for athletes. 

Nutrition. 20: 609-614, 2004 

- Bizzarini E et al. Is the use of oral creatine supplementation safe? J Sports Med Phys Fitness. 

44: 411-416, 2004 

- Mesa JL et al. Oral creatine supplementation and skeletal muscle metabolism in physical 

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895 

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acids. Importance for the early development of the nervous system. Ann NY Acad Sci 967 : 

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and biochemical profiles in obese patients with polycystic ovary syndrome-a randomized 

placebo-controlled trial." J Soc Gynecol Investig 13(1): 63-8. 

- Westerterp-Plantenga, M. S., M. P. Lejeune, et al. (2005). "Body weight loss and weight 

maintenance in relation to habitual caffeine intake and green tea supplementation." Obes Res 

13(7): 1195-204. 

Human intervention studies as to energy expenditure and fat oxidation: 

- Berube-Parent, S., C. Pelletier, et al. (2005). "Effects of encapsulated green tea and Guarana 

extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy 

expenditure and fat oxidation in men." Br J Nutr 94(3): 432-6 

- Dulloo, A.G.; Duret, C.; Rohrer, D.; Girardier, L.; Mensi, N.; Fathi, M.; Chantre, P. and 

Vandermander, J. (1999) Efficacy of a green tea extract rich in catechin polyphenols and 

caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am. J. Clin. Nutr. 

70, 1040-1045. 

- Komatsu, T. (2003). "Oloong tea increases energy metabolism in Japanese females." J. Med. 

Invest. 50: 170-175. 

- Ota, N., S. Soga, et al. (2005). "Effects of combination of regular exercise and tea catechins 

intake on energy expenditure in humans." J Health Scil 51(2): 233-236. 

- Rudelle, S., M. G. Ferruzzi, et al. (2007). "Effect of a thermogenic beverage on 24-hour energy 

metabolism in humans." Obesity (Silver Spring) 15(2): 349-55. 

- Rumpler, W.; Seale, J.; Clevidence, B.; Judd, J.; Wiley, E.; Yamamoto, S.; Komatsu, T.; 

Sawaki, T.; Ishikura, Y. and Hosoda, K. (2001) Oolong tea increases metabolic rate and fat 

oxidation in men. J Nutr. 131(11), 2848-2852 

- Thielecke et al. (2007) (submitted for publication) Nutritional intervention study to investigate 

the effects of the green tea extract TEAVIGO, high in EGCG, on the fat oxidation in 

overweight/obese volunteers, Charité Berlin, 2004-2005. 

Evidence from epidemiological studies: 

- Wu, C. H., F. H. Lu, et al. (2003). "Relationship among habitual tea consumption, percent body 

fat, and body fat distribution." Obes Res 11(9): 1088-95. 

Animal studies and mechanistic plausibility: 

- Crespy, V. and G. Williamson (2004). "A review of the health effects of green tea catechins in 

in vivo animal models." J Nutr 134(12 Suppl): 3431S-3440S. 

- Dulloo, A.G.; Seydoux, J.; Girardier, L.; Chantre, P. and Vandermander, J. (2000) Green tea 

and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic 

activity. Internat. J. Obes. 24, 252-258 

- Kao, Y. H., H. H. Chang, et al. (2006). "Tea, obesity, and diabetes." Mol Nutr Food Res 50(2): 

188-210. 

- Wolfram, S., Y. Wang, et al. (2006). "Anti-obesity effects of green tea: from bedside to bench." 

Mol Nutr Food Res 50(2): 176-87 

Reviews: 

- St.-Onge, M.P. (2005) Dietary fats, teas, dairy and nuts:potential functional foods for weight 

control. Am. J. Clin. Nutr. 81, 7-15 

78 

78

EPIGALLO-CATECHI-3-GALLATE (EGCG) / GREEN TEA EXTRACT, RICH IN EGCG and 

Blood glucose levels 


- Fukino, Y.; Shimbo, M.; Aoki, N.; Okubo, T.; Iso, H. (2005).” Randomized controlled trial for an 

effect of green tea consumption on insulin resistance and inflammation markers.” J Nutr Sci 

Vitaminol (Tokyo) (51) 335-42. 


50(7): 599-605 

- Hosoda, K., M. F. Wang, et al. (2003). "Antihyperglycemic effect of oolong tea in type 2 

diabetes." Diabetes Care 26(6): 1714-8. 

- Rizvi, S. I., M. A. Zaid, et al. (2005). "Protective role of tea catechins against oxidation-induced 

damage of type 2 diabetic erythrocytes." Clin Exp Pharmacol Physiol 32(1-2): 70-5. 

- Ryu, O. H., J. Lee, et al. (2006). "Effects of green tea consumption on inflammation, Insulin 

resistance and pulse wave velocity in type 2 diabetes patients." Diabetes Res Clin Pract 71(3): 

356-8. 

- Tsuneki, H., M. Ishizuka, et al. (2004). "Effect of green tea on blood glucose levels and serum 

proteomic patterns in diabetic (db/db) mice and on glucose metabolism in healthy humans." 

BMC Pharmacol 4(1): 18. 

- Zhong, L., J. K. Furne, et al. (2006). "An extract of black, green, and mulberry teas causes 

malabsorption of carbohydrate but not of triacylglycerol in healthy volunteers." Am J Clin Nutr 

84(3): 551-5. 




- Dufresne, C. J. and E. R. Farnworth (2001). "A review of latest research findings on the health 

promotion properties of tea." J Nutr Biochem 12(7): 404-421. 

- Higdon, J. V. and B. Frei (2003). "Tea catechins and polyphenols: health effects, metabolism, 

and antioxidant functions." Crit Rev Food Sci Nutr 43(1): 89-143. 

- Diabetes Kao, Y. H., H. H. Chang, et al. (2006). "Tea, obesity, and diabetes." Mol Nutr Food 

Res 50(2): 188-210. 


Mol Nutr Food Res 50(2): 176-87. 

Others 

- Bravo, L. (1998). "Polyphenols: chemistry, dietary sources, metabolism, and nutritional 

significance." Nutr Rev 56(11): 317-33. 

- Bronner, W. E. and G. R. Beecher (1998). "Method for determining the content of catechins in 

tea infusions by high-performance liquid chromatography." J Chromatogr A 805(1-2): 137-42. 

- Chen, L., M. J. Lee, et al. (1997). "Absorption, distribution, elimination of tea polyphenols in 

rats." Drug Metab Dispos 25(9): 1045-50. 



- Dufresne, C. J. and E. R. Farnworth (2001). "A review of latest research findings on the health 

promotion properties of tea." J Nutr Biochem 12(7): 404-421. 

- Fujiki, H., M. Suganuma, et al. (1998). "Cancer inhibition by green tea." Mutat Res 402(1-2): 

307-10. 

79 

79

- Fukino, Y.; Shimbo, M.; Aoki, N.; Okubo, T.; Iso, H. (2005).” Randomized controlled trial for an 

effect of green tea consumption on insulin resistance and inflammation markers.” J Nutr Sci 

Vitaminol (Tokyo) (51) 335-42. 


50(7): 599-605. 



- Hosoda, K., M. F. Wang, et al. (2003). "Antihyperglycemic effect of oolong tea in type 2 

diabetes." Diabetes Care 26(6): 1714-8. 

- Imai, K. and K. Nakachi (1995). "Cross sectional study of effects of drinking green tea on 

cardiovascular and liver diseases." Bmj 310(6981): 693-6. 

- Iso, H., C. Date, et al. (2006). "The relationship between green tea and total caffeine intake and 

risk for self-reported type 2 diabetes among Japanese adults." Ann Intern Med 144(8): 554-62. 

- Kao, Y. H., H. H. Chang, et al. (2006). "Tea, obesity, and diabetes." Mol Nutr Food Res 50(2): 

188-210. 

- Lee, M. J., P. Maliakal, et al. (2002). "Pharmacokinetics of tea catechins after ingestion of 

green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and 

individual variability." Cancer Epidemiol Biomarkers Prev 11(10 Pt 1): 1025-32. 

- Lee, M. J., Z. Y. Wang, et al. (1995). "Analysis of plasma and urinary tea polyphenols in human 

subjects." Cancer Epidemiol Biomarkers Prev 4(4): 393-9. 

- Meng, X., S. Sang, et al. (2002). "Identification and characterization of methylated and ringfission 

metabolites of tea catechins formed in humans, mice, and rats." Chem Res Toxicol 

15(8): 1042-50. 

- Nakagawa, K. and T. Miyazawa (1997). "Absorption and distribution of tea catechin, (-)epigallocatechin-3-gallate, 

in the rat." J Nutr Sci Vitaminol (Tokyo) 43(6): 679-84. 

- Pietta, P., P. Simonetti, et al. (1998). "Relationship between rate and extent of catechin 

absorption and plasma antioxidant status." Biochem Mol Biol Int 46(5): 895-903. 

- Record, I. R., Lane, J. M. (2001). "Simulated intestinal digestion of green and black teas." Food 

Chemistry 73: 481-486. 

- Rizvi, S. I., M. A. Zaid, et al. (2005). "Protective role of tea catechins against oxidation-induced 

damage of type 2 diabetic erythrocytes." Clin Exp Pharmacol Physiol 32(1-2): 70-5. 

- Ryu, O. H., J. Lee, et al. (2006). "Effects of green tea consumption on inflammation, insulin 


356-8. 

- Sasazuki, S., H. Kodama, et al. (2000). "Relation between green tea consumption and the 

severity of coronary atherosclerosis among Japanese men and women." Ann Epidemiol 10(6): 

401-8. 

- Schlesier, K., V. Böhm, et al. (2001). "Unterschiede im protektiven Potential von Grün- und 

Schwarztee aus gleichen Teeblättern." Proceedings of the german nutrition society 3: 22. 

- Scholz E, B. B., Kuntze O (1995). "Camellia sinensis - Der Teestrauch, Inhaltsstoffe und 

Wirkungen von Grünem und Schwarzem Tee, Portrait einer Arzneipflanze,." Zeitschrift für 

Phytotherapie 4: 231-246. 

- Teeverband (2003). Deutsche Teewirtschaft mit Geschäftsjahr zufrieden. 2004. 

- Tsubono, Y., T. Takahashi, et al. (1997). "Dietary differences with green tea intake among 

middle-aged Japanese men and women." Prev Med 26(5 Pt 1): 704-10. 

80 

80

- Tsuneki, H., M. Ishizuka, et al. (2004). "Effect of green tea on blood glucose levels and serum 

proteomic patterns in diabetic (db/db) mice and on glucose metabolism in healthy humans." 

BMC Pharmacol 4(1): 18. 

- Ullmann, U., J. Haller, et al. (2004). "Plasma-kinetic characteristics of purified and isolated 

green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy 

volunteers." Int J Vitam Nutr Res 74(4): 269-78. 

- Ullmann, U., J. Haller, et al. (2003). "A single ascending dose study of epigallocatechin gallate 

in healthy volunteers." Journal of International Medical Research. 

- Van Amelsvoort, J. M., K. H. Van Hof, et al. (2001). "Plasma concentrations of individual tea 

catechins after a single oral dose in humans." Xenobiotica 31(12): 891-901. 


Mol Nutr Food Res 50(2): 176-87. 

- Yamaji, T., T. Mizoue, et al. (2004). "Coffee consumption and glucose tolerance status in 

middle-aged Japanese men." Diabetologia 47(12): 2145-51. 

- Yang, C. S., J. Y. Chung, et al. (2000). "Mechanisms of inhibition of carcinogenesis by tea." 

Biofactors 13(1-4): 73-9. 

- Yang, C. S., S. Kim, et al. (1999). "Inhibition of carcinogenesis by tea: bioavailability of tea 

polyphenols and mechanisms of actions." Proc Soc Exp Biol Med 220(4): 213-7. 

- Yang, C. S. and J. M. Landau (2000). "Effects of tea consumption on nutrition and health." J 

Nutr 130(10): 2409-12. 

- Zhong, L., J. K. Furne, et al. (2006). "An extract of black, green, and mulberry teas causes 

malabsorption of carbohydrate but not of triacylglycerol in healthy volunteers." Am J Clin Nutr 

84(3): 551-5. 

EPIGALLO-CATECHIN-3-GALLATE (EGCG) / GREEN TEA EXTRACT, RICH IN EGCG and 

Cardio-vascular health 

Evidence from human studies 

- Kim, W., M. H. Jeong, et al. (2006). "Effect of green tea consumption on endothelial function 

and circulating endothelial progenitor cells in chronic smokers." Circ J 70(8): 1052-7. 

- Murakami, T. and K. Ohsato (2003). "Dietary green tea intake preserves and improves arterial 

compliance and endothelial function." Journal of the American College of Cardiology. 41(6 

Supplement A): 271A. 

- Nagaya, N., H. Yamamoto, et al. (2004). "Green tea reverses endothelial dysfunction in healthy 

smokers." Heart 90(12): 1485-6. 



356-8. 

- Vlachopoulos, C., N. Alexopoulos, et al. (2006). "Acute effect of black and green tea on aortic 

stiffness and wave reflections." J Am Coll Nutr 25(3): 216-23. 

- Yang, Y. C., F. H. Lu, et al. (2004). "The protective effect of habitual tea consumption on 

hypertension." Arch Intern Med 164(14): 1534-40. 



- Nakachi, K., S. Matsuyama, et al. (2000). "Preventive effects of drinking green tea on cancer 

and cardiovascular disease: epidemiological evidence for multiple targeting prevention." 

Biofactors 13(1-4): 49-54. 

81 

81

- Pearson, D. A., E. N. Frankel, et al. (1998). "Inhibition of endothelial cell mediated low-density 

lipoprotein oxidation by green tea extracts." J Agric Food Chem 46: 1445-1449. 

- Princen, H. M., D. van, et al. (1998). "No effect of consumption of green and black tea on 

plasma lipid and antioxidant levels and on LDL oxidation in smokers." Arteriosclerosis, 

Thrombosis & Vascular Biology. 18(5): 833-841. 

- Sano, J., S. Inami, et al. (2004). "Effects of green tea intake on the development of coronary 

artery disease." Circ J 68(7): 665-70. 

- Serafini, M., J. A. Laranjinha, et al. (2000). "Inhibition of human LDL lipid peroxidation by 

phenol-rich beverages and their impact on plasma total antioxidant capacity in humans." J Nutr 

Biochem 11(11-12): 585-590. 



401-8. 

- Sung, H., W. K. Min, et al. (2005). "The effects of green tea ingestion over four weeks on 

atherosclerotic markers." Ann Clin Biochem 42(Pt 4): 292-7. 

Others 

- Bronner, W. E. and G. R. Beecher (1998). "Method for determining the content of catechins in 

tea infusions by high-performance liquid chromatography." J Chromatogr A 805(1-2): 137-42. 

- Chen, Z. Y., W. I. Law, et al. (2000). "Inhibitory effects of purified green tea epicatechins on 

contraction and proliferation of arterial smooth muscle cells." Acta Pharmacol Sin 21(9): 835- 

40. 

- Cheng, T. O. (2006). "All teas are not created equal: the Chinese green tea and cardiovascular 

health." Int J Cardiol 108(3): 301-8. 



- Ikeda, M., C. Suzuki, et al. (2007). "Preventive effects of green tea catechins on spontaneous 

stroke in rats." Med Sci Monit 13(2): BR40-45. 



- Kim, W., M. H. Jeong, et al. (2006). "Effect of green tea consumption on endothelial function 

and circulating endothelial progenitor cells in chronic smokers." Circ J 70(8): 1052-7. 

- Kuriyama, S., T. Shimazu, et al. (2006). "Green tea consumption and mortality due to 

cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study." Jama 296(10): 

1255-65. 

- Lee, M. J., Z. Y. Wang, et al. (1995). "Analysis of plasma and urinary tea polyphenols in human 

subjects." Cancer Epidemiol Biomarkers Prev 4(4): 393-9. 

- Locher, R., L. Emmanuele, et al. (2002). "Green tea polyphenols inhibit human vascular 

smooth muscle cell proliferation stimulated by native low-density lipoprotein." Eur J Pharmacol 

434(1-2): 1-7. 

- Murakami, T. and K. Ohsato (2003). "Dietary green tea intake preserves and improves arterial 

compliance and endothelial function." Journal of the American College of Cardiology. 41(6 

Supplement A): 271A. 

- Nagaya, N., H. Yamamoto, et al. (2004). "Green tea reverses endothelial dysfunction in healthy 

smokers." Heart 90(12): 1485-6. 

- Nakachi, K., S. Matsuyama, et al. (2000). "Preventive effects of drinking green tea on cancer 

and cardiovascular disease: epidemiological evidence for multiple targeting prevention." 

Biofactors 13(1-4): 49-54. 

82 

82

- Pearson, D. A., E. N. Frankel, et al. (1998). "Inhibition of endothelial cell mediated low-density 

lipoprotein oxidation by green tea extracts." J Agric Food Chem 46: 1445-1449. 

- Potenza, M. A., F. L. Marasciulo, et al. (2007). "Epigallocatechin Gallate, a Green Tea 

Polyphenol, improves endothelial function and insulin sensivity, reduces blood pressure and 

protects against myocardial ischemia/reperfusion injury in Spontaneously Hypertensive Rats 

(SHR)." Am J Physiol Endocrinol Metab. 

- Princen, H. M., D. van, et al. (1998). "No effect of consumption of green and black tea on 

plasma lipid and antioxidant levels and on LDL oxidation in smokers." Arteriosclerosis, 

Thrombosis & Vascular Biology. 18(5): 833-841. 



356-8. 

- Sano, J., S. Inami, et al. (2004). "Effects of green tea intake on the development of coronary 

artery disease." Circ J 68(7): 665-70. 

- Sasazuki, S. and e. al. (2000). "Relation between green tea consumption and the severity of 

coronary atherosclerosis among japanese men and woman." Ann Epidemiol 10: 401-408. 



401-8. 

- Sato, Y., H. Nakatsuka, et al. (1989). "Possible contribution of green tea drinking habits to the 

prevention of stroke." Tohoku J Exp Med 157(4): 337-43. 

- Schlesier K, B. V., Bitsch R. (Sypmposium 22. und 23 September). Assessment of the 

protective potential of green tea. In: Vitamine und Zusatzstoffe in der Ernährung von Mensch 

und Tier, 7. 

- Scholz E, B. B., Kuntze O (1995). "Camellia sinensis - Der Teestrauch, Inhaltsstoffe und 

Wirkungen von Grünem und Schwarzem Tee, Portrait einer Arzneipflanze,." Zeitschrift für 

Phytotherapie 4: 231-246. 

- Serafini, M., J. A. Laranjinha, et al. (2000). "Inhibition of human LDL lipid peroxidation by 

phenol-rich beverages and their impact on plasma total antioxidant capacity in humans." J Nutr 

Biochem 11(11-12): 585-590. 

- Stangl, V., M. Lorenz, et al. (2006). "The role of tea and tea flavonoids in cardiovascular 

health." Mol Nutr Food Res 50(2): 218-28. 

- Sung, H., W. K. Min, et al. (2005). "The effects of green tea ingestion over four weeks on 

atherosclerotic markers." Ann Clin Biochem 42(Pt 4): 292-7. 

- Tijburg, L. B., T. Mattern, et al. (1997). "Tea flavonoids and cardiovascular disease: a review." 

Crit Rev Food Sci Nutr 37(8): 771-85. 

- Tsubono, Y., T. Takahashi, et al. (1997). "Dietary differences with green tea intake among 

middle-aged Japanese men and women." Prev Med 26(5 Pt 1): 704-10. 

- Vita, J. A. (2003). "Tea consumption and cardiovascular disease: effects on endothelial 

function." J Nutr 133(10): 3293S-3297S. 

- Vlachopoulos, C., N. Alexopoulos, et al. (2006). "Acute effect of black and green tea on aortic 

stiffness and wave reflections." J Am Coll Nutr 25(3): 216-23. 

- Yang, F., W. J. de Villiers, et al. (1998). "Green tea polyphenols block endotoxin-induced tumor 

necrosis factor-production and lethality in a murine model." J Nutr 128(12): 2334-40. 

- Yang, Y. C., F. H. Lu, et al. (2004). "The protective effect of habitual tea consumption on 

hypertension." Arch Intern Med 164(14): 1534-40. 

83 

83

- Yusuf, S., S. Hawken, et al. (2005). "Obesity and the risk of myocardial infarction in 27,000 

participants from 52 countries: a case-control study." Lancet 366(9497): 1640-9. 

ESTER-C and Antioxidant properties/immune health 

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Better tolerated than regular vitamin C. Zila Nutraceuticals Inc. 2006 

- Ester-C is a plus for cold sufferers. Chemist and druggist. 2002 Nov: 10 

EVENING PRIMROSE OIL and Skin Health 

Meta-Analysis 

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Efamol evening primrose oil in atopic eczema. Where do we go from here in light of more 

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EVENING PRIMROSE OIL and Menstrual health 


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Premenstrual Syndrome (PMS). Obstet Gynecol 1993;81:93-8. Puolakka J, Mäkäräinen L, 

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EVENING PRIMROSE OIL AND FISH OIL and Bone health 


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essential fatty acids on bone mineral density in healthy pre-and postmenopausal women: 

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FORMULATED PALM AND OAT OIL EMULSION and Weight management 

Individual human studies: 

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yoghurt containing a novel fat emulsion on energy and macronutrient intakes in nonoverweight, 

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novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption. 

Eur J Clin Nutr 2002; 56: 368-77. 

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the medium-term effects of Olibra fat emulsion on food intake in non-obese subjects. Eur J Clin 

Nutr 2006; 60: 1081-91. 

- Effects of addition of Olibra to a shake on satiety and energy intake. Principal Investigators: 

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GLUCOMANAN and Weight management 

Critical reviews 

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2005 Nov-Dec;11(6):30-4. (see abstract below) 

Studies 

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1988;44:22–27. 

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postinfarcted patients after cardiac rehabilitation. Curr Res Ther. 1990;47:753–758. 

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3):190–197. 

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study. Int J Obes. 1984;8:289–293. 

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1996;48:577–582. 

- Vido L, Facchin P, Antonello I, Gobber D, Rigon F. Childhood obesity treatment: double blinded 

trial on dietary fibres (glucomannan) versus placebo. Padiatr Padol. 1993;28:133–136. 

- Vuksan V, Jenkins DJ, Spadafora P, Sievenpiper JL, Owen R, Vidgen E, Brighenti F, Josse R, 

Leiter LA, Bruce-Thompson CKonjac-mannan (glucomannan) improves glycemia and other 

associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled 

metabolic trial. Diabetes Care. 1999;22:913–919. 

- Birketvedt GS, Shimshi M, Erling T, Florholmen , Experiences with three different fiber 

supplements in weight reduction. J. Med Sci Monit. 2005 Jan;11(1):PI5-8 (see abstract below) 

GLUCOSAMINE and Joint health 

Systematic Reviews/Meta-analysis 

- Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, 

Wells G. Glucosamine therapy for treating osteoarthritis. Glucosamine therapy for treating 

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86

osteoarthritis. The Cochrane Database of Systematic Reviews: Reviews 2005 Issue 2 John 

Wiley & Sons, Ltd Chichester, UK DOI: 10.1002/14651858.CD002946.pub2 

- McAlindon T E, LaValley M P, Gulin J P, Felson D T Glucosamine and chondroitin for 

treatment of osteoarthritis: a systematic quality assessment and meta-analysis JAMA 2000, 

283: 1469-1475 

- Poolsup N, Suthisisang C, Channark P, Kittikulsuth W Glucosamine long-term treatment and 

the progression of knee osteoarthritis: systematic review of randomized controlled trials Annals 

of Pharmacotherapy 2005, 39, 1080-1087 

- Richy F, Bruyere O, Ethgen O, Cucherat M, Honrotin Y, Reginster J Structural and 

symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis Archives of Internal 

Medicine 2003, 163: 1514-1522 

Reviews & Opinions 

- Bandolier Glucosamine and arthritis Bandolier, 1997: 

http://www.jr2.ox.ac.uk/bandolier/band46/b46-2.html 

- Bandolier Glucosamine and arthritis update Bandolier, 2001 

- 

http://www.jr2.ox.ac.uk/bandolier/band85/b85-2.html 

Setnikar I. Palumbo R. Canali S. Zanolo G. Pharmacokinetics of Glucosamine in Man. 

Arzneimittel-Forschung. 43(10):1109-13, 1993 Oct. 

- Monograph: Glucosamine Sulfate. Alternative Medicine Review 1999, 4 (3): 193-195 

- Kelly GS. The role of glucosamine sulfate and chondroitin sulfates in the treatment of 

degenerative joint disease Alternative Medicine Review 1998, 3 (1): 27-39. 

Review 

- Owens S et al. Recent advances in glucosamine and chndroitin supplementation. J Knee Surg. 

17: 185-193, 2004 

- Matheson AJ et al. Glucosamine: a review of its use in the menagement of osteoarthritis. Drugs 

Aging. 20: 1041-1060, 2003 

List of Human intervention trials (RCT): 

- Bruyere O, Honore A, Ethgen O, Rovati LC, Giacovelli G, Henrotin YE, Seidel L, Reginster 

JY:Correlation between radiographic severity of knee osteoarthritis and future disease 

progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect 

of glucosamine sulfate. Osteoarthritis Cartilage. 2003 Jan;11(1):1-5 

- Herrero-Beaumont 1, JA Román 2, MC Trabado 3, FJ Blanco 4 , P. Benito 5, E. Martin-Mola 6, 

J. Paulino 7, JL Marenco 8, A. Porto 9, A. Laffon 10, D. Araùjo 11, M. Figueroa 12, J. Branco 

13. Fund. J. Diaz, Madrid, Spain; 2 H Peset, Valencia, Spain; 3 H Clinic, Barcelona, Spain; 4 

CH Juan Canalejo, A Coruña, Spain; 5 H del Mar, Barcelona, Spain; 6 H U La Paz, Madrid, 

Spain; 7 C H C R, Ciudad Real, Spain; 8 H N.S. de Valme, Sevilla, Spain; 9 H U, Coimbra, 

Portugal; 10 H Princesa, Madrid, Spain; 1H C. Bertiandos, Ponte de Lima, Portugal; 12 H 

Donostia, San Sebastian, Spain; 13 H E. Moniz, Lisboa, Portugal: Effects of Glucosamine 

Sulfate on 6-Month Control of Knee Osteoarthritis Symptoms vs Placebo and Acetaminophen: 

Results from the Glucosamine Unum in Die Efficacy (GUIDE) TrialAbstract, American College 

of Rheumatology, 2005 

- Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC.: Glucosamine 

sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebocontrolled, 

double-blind study. Arch Intern Med. 2002 Oct 14;162(18):2113-23. 

- Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, 

Dacre JE, Gossett C: Long-term effects of glucosamine sulphate on osteoarthritis progression: 

a randomised, placebo-controlled clinical trial. Lancet. 200Jan 27;357(9252):251-6. 

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87

Meta-analysis of human intervention trials: 

- McAlindon TE, LaValley MP, Gulin JP, Felson DT :Glucosamine and chondroitin for treatment 

of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000 Mar 

15;283(11):1469-75. Review. 

- Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Structural and 

symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis. Arch Intern Med 

2003; 163: 1514-2 

- Reiter S. Evidence-based evaluation of study results of symptomatic glucosamine therapy. Z 

Rheumatol. 64: 456-466, 2005 

- Towheed TE et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst 

Rev. 18: CD002946, 2005 

GLUCOSINOLATES and Immune health 




Text Book 

- Encyclopedia of Human Nutrition – Potential Importance of Glucosinolate Derivates and 

Related Compounds to Human Health. Vol 3:505-507 

Meta-analysis 

- Benito E, Obrador A, Stiggelbout A, et al. A population-based case-control study of colorectal 

cancer in Majorca. I. Dietary factors. Int J Cancer. 1990;45(1):69-76. 

- Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl 

Cancer Inst. 2000;92(1):61-68. 

- Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous 

vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003;12(12):1403-1409. 

- Graham S, Dayal H, Swanson M, Mittelman A, Wilkinson G. Diet in the epidemiology of cancer 

of the colon and rectum. J Natl Cancer Inst. 1978;61(3):709-714. 

- Hsing AW, McLaughlin JK, Schuman LM, et al. Diet, tobacco use, and fatal prostate cancer: 

results from the Lutheran Brotherhood Cohort Study. Cancer Res. 1990;50(21):6836-6840. 

- J, Allen N, Appleby P, et al. Fruits and vegetables and prostate cancer: no association among 

1104 cases in a prospective study of 130544 men in the European Prospective Investigation 

into Cancer and Nutrition (EPIC). Int J Cancer. 2004;109(1):119-124. 

- Jain MG, Hislop GT, Howe GR, Ghadirian P. Plant foods, antioxidants, and prostate cancer 

risk: findings from case-control studies in Canada. Nutr Cancer. 1999;34(2):173-184. 

- Kojima M, Wakai K, Tamakoshi K, et al. Diet and colorectal cancer mortality: results from the 

Japan Collaborative Cohort Study. Nutr Cancer. 2004;50(1):23-32. 

- Kolonel LN, Hankin JH, Whittemore AS, et al. Vegetables, fruits, legumes and prostate cancer: 

a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev. 2000;9(8):795-804. 

- Miller AB, Altenburg HP, Bueno-de-Mesquita B, et al. Fruits and vegetables and lung cancer: 

Findings from the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 

2004;108(2):269-276. 

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88

- Schuurman AG, Goldbohm RA, Dorant E, van den Brandt PA. Vegetable and fruit consumption 

and prostate cancer risk: a cohort study in The Netherlands. Cancer Epidemiol Biomarkers 

Prev. 1998;7(8):673-680. 

Reviews 

- Cauley JA, Zmuda JM, Danielson ME, et al. Estrogen metabolites and the risk of breast cancer 

in older women. Epidemiology. 2003;14(6):740-744. 

- Fenwick GR, Heaney RK, Mullin WJ. Glucosinolates and their breakdown products in food and 

food plants. Crit Rev Food Sci Nutr. 1983;18(2):123-201. 

- Feskanich D, Ziegler RG, Michaud DS, et al. Prospective study of fruit and vegetable 

consumption and risk of lung cancer among men and women. J Natl Cancer Inst. 

2000;92(22):1812-1823. 

- Halkier BA, Gershenzon J. Biology and biochemistry of glucosinolates. Annu Rev Plant Biol. 

2006;57:303-33. 

- Keum YS, Jeong WS, Kong AN. Chemopreventive functions of isothiocyanates. Drug News 

Perspect. 2005 Sep;18(7):445-51.. 

- Kristal AR, Lampe JW. Brassica vegetables and prostate cancer risk: a review of the 

epidemiological evidence. Nutr Cancer. 2002;42(1):1-9. 

- Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: genetic polymorphisms 

alter the preventive effects of cruciferous vegetables. J Nutr. 2002;132(10):2991-2994. 

- Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr. 

2004;134(12 Suppl):3479S-3485S. 

- Lugasi A, Varga T. [Non-nutritive biologically active plant components: glucosinolates, their 

sources and their nutritional significance] Orv Hetil. 2006 Jul 23;147(29):1361-8. Review. 

Hungarian. 

- Michels KB, Edward G, Joshipura KJ, et al. Prospective study of fruit and vegetable 

consumption and incidence of colon and rectal cancers. J Natl Cancer Inst. 2000;92(21):1740- 

1752. 

- Ray A. Cancer preventive role of selected dietary factors. Indian J Cancer. 2005 Jan- 

Mar;42(1):15-24. 

- Sarkar FH, Li Y. Indole-3-carbinol and prostate cancer. J Nutr. 2004;134(12 Suppl):3493S- 

3498S. 

- Schneider J, Kinne D, Fracchia A, et al. Abnormal oxidative metabolism of estradiol in women 

with breast cancer. Proc Natl Acad Sci U S A. 1982;79(9):3047-3051. 


- Ambrosone CB, McCann SE, Freudenheim JL, Marshall JR, Zhang Y, Shields PG. Breast 

cancer risk in premenopausal women is inversely associated with consumption of broccoli, a 

source of isothiocyanates, but is not modified by GST genotype. J Nutr. 2004;134(5):1134- 

1138. 

- Auborn KJ, Fan S, Rosen EM, et al. Indole-3-carbinol is a negative regulator of estrogen. J 

Nutr. 2003;133(7 Suppl):2470S-2475S. 

- Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-hydroxyestrone: the 'good' estrogen. J 

Endocrinol. 1996;150 Suppl:S259-265. 

- Coles BF, Kadlubar FF. Detoxification of electrophilic compounds by glutathione S-transferase 

catalysis: determinants of individual response to chemical carcinogens and chemotherapeutic 

drugs? Biofactors. 2003;17(1-4):115-130. 

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89

- Fowke JH, Chung FL, Jin F, et al. Urinary isothiocyanate levels, brassica, and human breast 

cancer. Cancer Res. 2003;63(14):3980-3986. 

- Ho GH, Luo XW, Ji CY, Foo SC, Ng EH. Urinary 2/16 alpha-hydroxyestrone ratio: correlation 

with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast 

cancer risk. Ann Acad Med Singapore. 1998;27(2):294-299. 

- Holst B, Williamson G. A critical review of the bioavailability of glucosinolates and related 

compounds. Nat Prod Rep. 2004;21(3):425-447. 

- Joseph MA, Moysich KB, Freudenheim JL, et al. Cruciferous vegetables, genetic 

polymorphisms in glutathione s-transferases m1 and t1, and prostate cancer risk. Nutr Cancer. 

2004;50(2):206-213. 

- Kabat GC, Chang CJ, Sparano JA, et al. Urinary estrogen metabolites and breast cancer: a 

case-control study. Cancer Epidemiol Biomarkers Prev. 1997;6(7):505-509. 

- Kensler TW, Chen JG, Egner PA, Fahey JW, Jacobson LP, Stephenson KK, Ye L, Coady JL, 

Wang JB, Wu Y, Sun Y, Zhang QN, Zhang BC, Zhu YR, Qian GS, Carmella SG, Hecht SS, 

Benning L, Gange SJ, Groopman JD, Talalay P. Effects of glucosinolate-rich broccoli sprouts 

on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical 

trial in He Zuo township, Qidong, People's Republic of China. Cancer Epidemiol Biomarkers 

Prev. 2005 Nov;14(11 Pt 1):2605-13. 

- Lewis S, Brennan P, Nyberg F, et al. Re: Spitz, M. R., Duphorne, C. M., Detry, M. A., Pillow, P. 

C., Amos, C. I., Lei, L., de Andrade, M., Gu, X., Hong, W. K., and Wu, X. Dietary intake of 

isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung 

cancer risk. Cancer Epidemiol. Biomark. Prev., 9: 1017-1020, 2000. Cancer Epidemiol 

Biomarkers Prev. 2001;10(10):1105-1106. 

- Lin HJ, Probst-Hensch NM, Louie AD, et al. Glutathione transferase null genotype, broccoli, 

and lower prevalence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 

1998;7(8):647-652. 

- London SJ, Yuan JM, Chung FL, et al. Isothiocyanates, glutathione S-transferase M1 and T1 

polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China. Lancet. 

2000;356(9231):724-729. 

- McCullough ML, Robertson AS, Chao A, et al. A prospective study of whole grains, fruits, 

vegetables and colon cancer risk. Cancer Causes Control. 2003;14(10):959-970. 

- McMillan M, Spinks EA, Fenwick GR. Preliminary observations on the effect of dietary brussels 

sprouts on thyroid function. Hum Toxicol. 1986;5(1):15-19. 

- McNaughton SA, Marks GC. Development of a food composition database for the estimation of 

dietary intakes of glucosinolates, the biologically active constituents of cruciferous vegetables. 

Br J Nutr. 2003;90(3):687-697. 

- Meilahn EN, De Stavola B, Allen DS, et al. Do urinary oestrogen metabolites predict breast 

cancer? Guernsey III cohort follow-up. Br J Cancer. 1998;78(9):1250-1255. 

- Neuhouser ML, Patterson RE, Thornquist MD, Omenn GS, King IB, Goodman GE. Fruits and 

vegetables are associated with lower lung cancer risk only in the placebo arm of the betacarotene 

and retinol efficacy trial (CARET). Cancer Epidemiol Biomarkers Prev. 

2003;12(4):350-358. 

- Seow A, Shi CY, Chung FL, et al. Urinary total isothiocyanate (ITC) in a population-based 

sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and 

glutathione S-transferase M1/T1/P1 genotypes. Cancer Epidemiol Biomarkers Prev. 

1998;7(9):775-781. 

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GLUTAMINE AND GLUTAMIN PEPTIDE and Metabolic stress / Protein synthesis / Gut 

permeability / Carbohydrate metabolism 


- Encyclopedia of Human Nutrition (1st Edition): p70, 80, 203, 204, 1402, 1651,1819, 1824, 1856 

Editors: M. J. Sadler, J. J. Strain, B. Caballero 

Generally accepted role(s) 

- Battezzati et al (2004), Am J Physiol Endocrinol Metab 286, E129-E135, Nonhepatic glucose 

production in humans. 

- C. Duffan, J. Gannon, and W.A. Walker (2002) Am.J.Clin.Nutr. 75(5):789-808. Protective 

nutrients and functional foods for the gastrointestinal tract. 

- Lacey JM & Wilmore DW (1990) Nutrition Reviews; 48; 297-309. Is glutamine a conditionally 

essential amino acid? 

- Newsholme et al (2003) Cell Biochem Funct 21, 1-9. Glutamine and glutamate – their central 

role in cell metabolism and function 

- Stumvoll M et al (1999) Kidney International 55, 778-92. Role of glutamine in human 

carbohydrate metabolism in kidney and other tissues. 

- Souba, WW (1991) Ann Rev Nutr 11, 283-308. Glutamine: a key substrate for the splachnic 

bed. 

- Ziegler TR et al (2003) Annu Rev Nutr 23, 229-61. Trophic and cytoprotective nutrition for 

intestinal adaptation, mucosal repair, and barrier function. 

Meta-analyses and Critical Expert Reviews 

- Kreymann KG et al, Clinical Nutrition (2006) 25, 210–223. ESPEN Guidelines on Enteral 

Nutrition:Intensive care (“Glutamine should be supplemented in patients suffering from burns or 

trauma”) 

- Rowbottom DG et al (1996) Sports Medicine 21(2), 80-97. The emerging role of glutamine as 

an indicator of exercise stress and overtraining. 

- Newsholme EA et al (1991) In : Medicine and Sport Science 32 - Advances in Nutrition and 

Top Sport (ed. Brouns F) , 79-93, Karger, Basel. A biochemical mechanism to explain some 

characteristics of overtraining. 

Reviews 

- Castell LM, Poortmans JR, and Newsholme EA,. Does glutamine have a role in reducing 

infections in athletes. Eur. J. Appl. Physiol. & Occup. Physiol. 1996; 73: 488-490 

- Castell LM, and Newsholme EA, The relation between glutamine and the immuno-depression 

observed in exercise. Amino Acids 2001; 20: 49-61 

- Castell LM and Newsholme EA, Glutamine and the effects of exhaustive exercise upon the 

immune response. Can. J. Physiol. Pharmacol. 1998; 76: 524-532 

- Garcia-de-Lorenzo A, Zarazaga A, Garcia-Luna PP, et al., Clinical evidence for enteral 

nutritional support with glutamine. Nutrition 2003; 19: 805-811 

- Neu J, DeMarco V, Li N., Glutamine: clinical applications and mechanisms of action. Curr. 

Opin. Clin. Nutr. Metab. Care 2002; 5: 69-75 

- Newsholme P. Why is L-glutamine metabolism important to cells of the immune system in 

health, post-injury, surgery or infection? J. Nutr. 2001; 131: 2515S-2522S 

- Reeds PJ , Burrin DG, Glutamine and the bowel. J. Nutr. 2001; 131: 2505S-2508S 

91 

91

- Tubman TRJ, Thompson SW, McGuire W, Cochrane database of systematic reviews(Online) 

2005, No1 CD001457 

- Walsh NP, Blannin AK, Robson PJ, et al., Glutamine, exercise and immune function. Links and 

possible mechanisms. Sports Med. 1998; 26: 177-191 


- Bowtell JL et al (1999) J Appl Physiol 86(6), 1770-1777, Effect of oral glutamine on whole body 

carbohydrate storage during recovery from exhaustive exercise 

- Coëffier M et al (2003), Am J Physiol Gastrointest Liver Physiol 285, 266-273. Enteral 

glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut 

mucosa 

- Hammarqvist et al (2005), Clinical Nutrition 24, 236–243, Free amino acid and glutathione 

concentrations in muscle during short-term starvation and refeeding. 

- Krzywkowski K, Petersen EW, Ostrowski K, et al., Effect of glutamine and protein 

supplementation on exercise-induced decreases in salivary IgA. Am. J. Physiol. Cell Physiol. 

2001; 281: 50-54 

- Perriello et al (1997) Am J Physiol 272, E437-E445, Regulation of gluconeogenesis by 

glutamine in normal postabsorptive humans 

- Rohde T, MacLean DA. Hartkopp A, et al., The immune system and serum glutamine during a 

triathlon. Eur. J. Appl. Physiol. 1997; 74: 428-434 

- Varnier M et al (1995) Am J of Physiol 269, E309-E315. Stimulatory effect of glutamine on 

glycogen accumulation in human skeletal muscle. 

- Yoshida S, Matsui M, Shirouzu Y, Fujita H, Yamana H, Shirouzu K. Effects of glutamine 

supplements and radiochemotherapy on systemic immune and gut barrier function in patients 

with advanced esophageal cancer. Annals of Surgery. 1998; 227: 485-91 

- Ziegler TR, Young LS, Benfell K, et al., Clinical and Metabolic Efficacy of Glutamine 

supplemented Parenteral Nutrition after Bone Marrow Transplantation. Ann. Internal Med. 

1992; 116: 821-828 

GLUTAMINE and Immune health 

Reviews 

- Child (1999) Running and tissue damage. In 'Improving performance in middle and long 

distance running: A scientific approach to race preparation.' Advisory panel Bangsbo J., 

Clarkson P.M., Hargreaves M., Williams C. Eds. J.L. Fallowfield and D.M. Wilkinson, John 

Wiley & Sons, Chichester, pages 122-139. 

- Furst and Stehle 2004 What Are the Essential Elements Needed for the Determination of 

Amino Acid Requirements in Humans? J. Nutr. 134: 1558S–1565S, 2004. 

- Hood and Turjung (1990) Amino acid metabolism during exercise and following endurance 

training. Sports Med. 9; 23-35. 

- Millward (1999) Inherent difficulties in defining amino acid requirements. In Protein and Amino 

Acids, pages 169-216. 

- Wagenmakers (1998) Muscle amino acid at rest and during exercise: Role in human 

physiology and metabolism. Exercise and Sports Science Reviews 26; 287-314. 

Text book 

- Newsholme, EA, Leech, AR: Biochemistry for the Medical Sciences. John Wiley & Sons, 

Chichester/New York, 1995 

92 

92

- Souba, W. W. Glutamine Physiology, Biochemistry, and Nutrition in. Critical Illness. Austin: 

R.G. Landes Co., 1992. 

Peer reviewed papers 

- Kerksick CM, Rasmussen CJ, Lancaster SL, Magu B, Smith P, Melton C, Greenwood M, 

Almada AL, Earnest CP, Kreider RB. The effects of protein and amino acid supplementation on 

performance and training adaptations during ten weeks of resistance training. J Strength Cond 

Res. 2006 Aug;20(3):643-53. 

- Tang FC. Influence of branched-chain amino acid supplementation on urinary protein 

metabolite concentrations after swimming. J Am Coll Nutr. 2006 Jun;25(3):188-94. 

- Malandain H. Transglutaminases: a meeting point for wheat allergy, celiac disease, and food 

safety. Allerg Immunol (Paris). 2005 Dec;37(10):397-403. Review. 

- Ohtani M, Sugita M, Maruyama K. Amino acid mixture improves training efficiency in athletes. J 

Nutr. 2006 Feb;136(2):538S-543S. 

- Kargotich S, Rowbottom DG, Keast D, Goodman C, Dawson B, Morton AR. Plasma glutamine 

changes after high-intensity exercise in elite male swimmers. Res Sports Med. 2005 Jan- 

Mar;13(1):7-21. 

- Blomstrand E, Moller K, Secher NH, Nybo L. Effect of carbohydrate ingestion on brain 

exchange of amino acids during sustained exercise in human subjects. Acta Physiol Scand. 

2005 Nov;185(3):203-9. 

- Durham WJ, Miller SL, Yeckel CW, Chinkes DL, Tipton KD, Rasmussen BB, Wolfe RR. Leg 

glucose and protein metabolism during an acute bout of resistance exercise in humans. J Appl 

Physiol. 2004 Oct;97(4):1379-86. . 

- Krieger JW, Crowe M, Blank SE.Chronic glutamine supplementation increases nasal but not 

salivary IgA during 9 days of interval training. J Appl Physiol. 2004 Aug;97(2):585-91. 

- Bailey DM, Davies B, Castell LM, Collier DJ, Milledge JS, Hullin DA, Seddon PS, Young IS. 

Symptoms of infection and acute mountain sickness; associated metabolic sequelae and 

problems in differential diagnosis. High Alt Med Biol. 2003 Fall;4(3):319-31. 

- Hiscock N, Petersen EW, Krzywkowski K, Boza J, Halkjaer-Kristensen J, Pedersen BK. 

Glutamine supplementation further enhances exercise-induced plasma IL-6.J Appl Physiol. 

2003 Jul;95(1):145-8. 

- Bacurau RF, Bassit RA, Sawada L, Navarro F, Martins E Jr, Costa Rosa LF. Carbohydrate 

supplementation during intense exercise and the immune response of cyclists. Clin Nutr. 2002 

Oct;21(5):423-9. 

- Mourtzakis M, Graham TE. Glutamate ingestion and its effects at rest and during exercise in 

humans. J Appl Physiol. 2002 Oct;93(4):1251-9. 

- Bassit RA, Sawada LA, Bacurau RF, Navarro F, Martins E Jr, Santos RV, Caperuto EC, Rogeri 

P, Costa Rosa LF. Branched-chain amino acid supplementation and the immune response of 

long-distance athletes. Nutrition. 2002 May;18(5):376-9. 

- Dalsgaard MK, Ide K, Cai Y, Quistorff B, Secher NH. The intent to exercise influences the 

cerebral O(2)/carbohydrate uptake ratio in humans. J Physiol. 2002 Apr 15;540(Pt 2):681-9. 

- Khogali SE, Pringle SD, Weryk BV, Rennie MJ. Is glutamine beneficial in ischemic heart 

disease? Nutrition. 2002 Feb;18(2):123-6. 

- Antonio J, Sanders MS, Kalman D, Woodgate D, Street C. The effects of high-dose glutamine 

ingestion on weightlifting performance. J Strength Cond Res. 2002 Feb;16(1):157-60. 

- Krzywkowski K, Petersen EW, Ostrowski K, Kristensen JH, Boza J, Pedersen BK. Effect of 

glutamine supplementation on exercise-induced changes in lymphocyte function. Am J Physiol 

Cell Physiol. 2001 Oct;281(4):C1259-65. 

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93

- Blomstrand E, Saltin B. BCAA intake affects protein metabolism in muscle after but not during 

exercise in humans. Am J Physiol Endocrinol Metab. 2001 Aug;281(2):E365-74. 

- Lambert GP, Broussard LJ, Mason BL, Mauermann WJ, Gisolfi CV. Gastrointestinal 

permeability during exercise: effects of aspirin and energy-containing beverages. J Appl 

Physiol. 2001 Jun;90(6):2075-80. 

- Engelen MP, Wouters EF, Deutz NE, Does JD, Schols AM. Effects of exercise on amino 

- 

acid metabolism in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care 

Med. 2001 Mar;163(4):859-64. 

Blanchard MA, Jordan G, Desbrow B, MacKinnon LT, Jenkins DG. The influence of diet and 

exercise on muscle and plasma glutamine concentrations. Med Sci Sports Exerc. 2001 

Jan;33(1):69-74. 

- Bassit RA, Sawada LA, Bacurau RF, Navarro F, Costa Rosa LF. The effect of BCAA 

supplementation upon the immune response of triathletes. Med Sci Sports Exerc. 2000 

Jul;32(7):1214-9. 

- Nieman DC. Exercise immunology: future directions for research related to athletes, nutrition, 

and the elderly.Int J Sports Med. 2000 May;21 Suppl 1:S61-8. Review. 

- Walsh NP, Blannin AK, Bishop NC, Robson PJ, Gleeson M. Effect of oral glutamine 

supplementation on human neutrophil lipopolysaccharide-stimulated degranulation following 

prolonged exercise. Int J Sport Nutr Exerc Metab. 2000 Mar;10(1):39-50. 

- van Hall G, Saris WH, van de Schoor PA, Wagenmakers AJ. The effect of free glutamine and 

peptide ingestion on the rate of muscle glycogen resynthesis in man. Int J Sports Med. 2000 

Jan;21(1):25-30. 

- Bailey SP, Zacher CM, Mittleman KD. Effect of menstrual cycle phase on carbohydrate 

supplementation during prolonged exercise to fatigue. J Appl Physiol. 2000 Feb;88(2):690-7. 

- Bowtell JL, Gelly K, Jackman ML, Patel A, Simeoni M, Rennie MJ.Effect of oral glutamine on 

whole body carbohydrate storage during recovery from exhaustive exercise. J Appl Physiol. 

1999 Jun;86(6):1770-7. 

- Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M. Effects of exercise intensity, 

duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med. 1999 

Feb;20(2):128-35. 

- Nieman DC, Pedersen BK. Exercise and immune function. Recent developments. Sports Med. 

1999 Feb;27(2):73-80. Review. 

- Haub MD, Potteiger JA, Nau KL, Webster MJ, Zebas CJ. Acute L-glutamine ingestion does not 

improve maximal effort exercise. J Sports Med Phys Fitness. 1998 Sep;38(3):240-4. 

- MacLean D, Vissing J, Vissing SF, Haller RG. Oral branched-chain amino acids do not improve 

exercise capacity in McArdle disease. Neurology. 1998 Nov;51(5):1456-9. 

- Rohde T, Asp S, MacLean DA, Pedersen BK. Competitive sustained exercise in humans, 

lymphokine activated killer cell activity, and glutamine--an intervention study. Eur J Appl 

Physiol Occup Physiol. 1998 Oct;78(5):448-53. 

- Rohde T, MacLean DA, Pedersen BK. Effect of glutamine supplementation on changes in the 

immune system induced by repeated exercise. Med Sci Sports Exerc. 1998 Jun;30(6):856-62. 

- Mitchell JB, Pizza FX, Paquet A, Davis BJ, Forrest MB, Braun WA. Influence of carbohydrate 

status on immune responses before and after endurance exercise. J Appl Physiol. 1998 

Jun;84(6):1917-25. 

- Gleeson M, Blannin AK, Walsh NP, Bishop NC, Clark AM. Effect of low- and high-carbohydrate 

diets on the plasma glutamine and circulating leukocyte responses to exercise.Int J Sport Nutr. 

1998 Mar;8(1):49-59. 

94 

94

- Vukovich MD, Sharp RL, Kesl LD, Schaulis DL, King DS. Effects of a low-dose amino acid 

supplement on adaptations to cycling training in untrained individuals. Int J Sport Nutr. 1997 

Dec;7(4):298-309. 

- Corley RA, Markham DA, Banks C, Delorme P, Masterman A, Houle JM. Physiologically based 

pharmacokinetics and the dermal absorption of 2-butoxyethanol vapor by humans. Fundam 

Appl Toxicol. 1997 Oct;39(2):120-30. 

- Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after 

prolonged, exhaustive exercise. Nutrition. 1997 Jul-Aug;13(7-8):738-42. 

- Hack V, Weiss C, Friedmann B, Suttner S, Schykowski M, Erbe N, Benner A, Bartsch P, Droge 

W. Decreased plasma glutamine level and CD4+ T cell number in response to 8 wk of 

anaerobic training.Am J Physiol. 1997 May;272(5 Pt 1):E788-95. 

- Castell LM, Poortmans JR, Leclercq R, Brasseur M, Duchateau J, Newsholme EA. Some 

aspects of the acute phase response after a marathon race, and the effects of glutamine 

supplementation. Eur J Appl Physiol Occup Physiol. 1997;75(1):47-53. 

- Kinscherf R, Hack V, Fischbach T, Friedmann B, Weiss C, Edler L, Bartsch P, Droge W. Low 

plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell 

mass in healthy individuals: the effect of N-acetyl-cysteine. J Mol Med. 1996 Jul;74(7):393-400. 

- MacLean DA, Graham TE, Saltin B. Stimulation of muscle ammonia production during exercise 

following branched-chain amino acid supplementation in humans. J Physiol. 1996 Jun 15;493 ( 

Pt 3):909-22. 

- Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections 

in athletes? Eur J Appl Physiol Occup Physiol. 1996;73(5):488-90. 

- Blomstrand E, Andersson S, Hassmen P, Ekblom B, Newsholme EA. Effect of branched-chain 

amino acid and carbohydrate supplementation on the exercise-induced change in plasma and 

muscle concentration of amino acids in human subjects. Acta Physiol Scand. 1995 

Feb;153(2):87-96. 

- Sewell DA, Gleeson M, Blannin AK. Hyperammonaemia in relation to high-intensity exercise 

duration in man.Eur J Appl Physiol Occup Physiol. 1994;69(4):350-4. 

- MacLean DA, Graham TE. Branched-chain amino acid supplementation augments plasma 

ammonia responses during exercise in humans. J Appl Physiol. 1993 Jun;74(6):2711-7. 

- Hanet C, Pouleur H, Harlow BJ, Rousseau MF. Effects of long-term combined dosing with 

nicardipine and propranolol on coronary hemodynamics, myocardial metabolism, and exercise 

tolerance in patients with angina pectoris: comparison with monotherapy. Am Heart J. 1988 

Aug;116(2 Pt 1):431-9. 

- Greenhaff PL, Gleeson M, Maughan RJ. The effects of diet on muscle pH and metabolism 

during high intensity exercise. Eur J Appl Physiol Occup Physiol. 1988;57(5):531-9. 

GLUTAMINE and Muscle function 

Reviews 

- Child (1999) Running and tissue damage. In 'Improving performance in middle and long 

distance running: A scientific approach to race preparation.' Advisory panel Bangsbo J., 

Clarkson P.M., Hargreaves M., Williams C. Eds. J.L. Fallowfield and D.M. Wilkinson, John 

Wiley & Sons, Chichester, pages 122-139. 

- Furst and Stehle 2004 What Are the Essential Elements Needed for the Determination of 

Amino Acid Requirements in Humans? J. Nutr. 134: 1558S–1565S, 2004. 

- Hood and Turjung (1990) Amino acid metabolism during exercise and following endurance 

training. Sports Med. 9; 23-35. 

95 

95

- Millward (1999) Inherent difficulties in defining amino acid requirements. In Protein and Amino 

Acids, pages 169-216. 

- Wagenmakers (1998) Muscle amino acid at rest and during exercise: Role in human 

physiology and metabolism. Exercise and Sports Science Reviews 26; 287-314. 

Text book 

- Newsholme, EA, Leech, AR: Biochemistry for the Medical Sciences. John Wiley & Sons, 

Chichester/New York, 1995 

- Souba, W. W. Glutamine Physiology, Biochemistry, and Nutrition in. Critical Illness. Austin: 

R.G. Landes Co., 1992. 

Peer reviewed papers 

- Kargotich S, Rowbottom DG, Keast D, Goodman C, Dawson B, Morton AR. Plasma glutamine 

changes after high-intensity exercise in elite male swimmers. Res Sports Med. 2005 Jan- 

Mar;13(1):7-21. 

- Krieger JW, Crowe M, Blank SE.Chronic glutamine supplementation increases nasal but not 

salivary IgA during 9 days of interval training. J Appl Physiol. 2004 Aug;97(2):585-91. 

- Hiscock N, Petersen EW, Krzywkowski K, Boza J, Halkjaer-Kristensen J, Pedersen BK. 

Glutamine supplementation further enhances exercise-induced plasma IL-6.J Appl Physiol. 

2003 Jul;95(1):145-8. 

- Bacurau RF, Bassit RA, Sawada L, Navarro F, Martins E Jr, Costa Rosa LF. Carbohydrate 

supplementation during intense exercise and the immune response of cyclists. Clin Nutr. 2002 

Oct;21(5):423-9. 

- Krzywkowski K, Petersen EW, Ostrowski K, Kristensen JH, Boza J, Pedersen BK. Effect of 

glutamine supplementation on exercise-induced changes in lymphocyte function. Am J Physiol 

Cell Physiol. 2001 Oct;281(4):C1259-65. 

- Walsh NP, Blannin AK, Bishop NC, Robson PJ, Gleeson M. Effect of oral glutamine 

supplementation on human neutrophil lipopolysaccharide-stimulated degranulation following 

prolonged exercise. Int J Sport Nutr Exerc Metab. 2000 Mar;10(1):39-50. 

- van Hall G, Saris WH, van de Schoor PA, Wagenmakers AJ. The effect of free glutamine and 

peptide ingestion on the rate of muscle glycogen resynthesis in man. Int J Sports Med. 2000 

Jan;21(1):25-30. 

- Bowtell JL, Gelly K, Jackman ML, Patel A, Simeoni M, Rennie MJ.Effect of oral glutamine on 

whole body carbohydrate storage during recovery from exhaustive exercise. J Appl Physiol. 

1999 Jun;86(6):1770-7. 

- Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M. Effects of exercise intensity, 

duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med. 1999 

Feb;20(2):128-35. 

- Rohde T, Asp S, MacLean DA, Pedersen BK. Competitive sustained exercise in humans, 

lymphokine activated killer cell activity, and glutamine--an intervention study. Eur J Appl 

Physiol Occup Physiol. 1998 Oct;78(5):448-53. 

- Rohde T, MacLean DA, Pedersen BK. Effect of glutamine supplementation on changes in the 

immune system induced by repeated exercise. Med Sci Sports Exerc. 1998 Jun;30(6):856-62. 

- Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after 

prolonged, exhaustive exercise. Nutrition. 1997 Jul-Aug;13(7-8):738-42. 

- Kinscherf R, Hack V, Fischbach T, Friedmann B, Weiss C, Edler L, Bartsch P, Droge W. Low 

plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell 

mass in healthy individuals: the effect of N-acetyl-cysteine. J Mol Med. 1996 Jul;74(7):393-400. 

96 

96

GLUTAMINE and Mental health 

Monographs 

- HAGER-ROM 2004, Springer Verlag, Heidelberg; Ebel, S.; Schlager, H.; Rommelspacher, H.; 

L-Glutamin 

- Martindale: The Extra Pharmacopoeia; Thirty-fifth edition published 2007; Pharmaceutical 

Press 2007; Glutamine; pp. 1785-86 

Textbooks 

- Lexikon der Ernährung; [Red.: Udo Maid-Kohnert]; Heidelberg, Berlin: Spektrum, Akad. Verl., 

Bd. 2 Fettl bis M. - 2002, 104-106 

- Burgersteins Handbuch Nährstoffe; Karl F. Haug Verlag, Heidelberg; 2000; 9. Auflage; 

Glutamin; 214-215 

Peer reviewed publications 

- Arwert, L.I.; Deijen, J.B.; Drent, M.L.; Effects of an oral mixture containing glycine, glutamine 

and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects, Nutritional 

neuroscience, 6, 5, 2003, pp. 269 - 275 

- Blonde-Cynober, F. et al.; Use of ornithine α-ketoglutarate in clinical nutrition of elderly 

patients; Nutrition 2003; 19: 73-5 

- Falcao De Arruda, I.S.; De Aguilar-Nascimento, J.E.; Benefits of early enteral nutrition with 

glutamine and probiotics in brain injury patients, Clinical science, 106, 3, 2004, pp. 287 - 292 

- Field, C.J.; Johnson, I.; Pratt, V.C.; 2000, Glutamine and arginine: imunonutrients for improved 

health; Med. Sci. Sports Exercise 32 (Suppl 7), 377-388 

- Hertz, L. et al (Eds.): Glutamine, glutamate and GABA in the central nervous system; Alan Liss, 

New York 1983 

- Mcentee, W.J.; CROOK, T.H.: Glutamate: its role in learning, memory, and the aging brain. 

Psychopharmacology Berl 111 (1993) 391 

- Novak, F. et al.; Glutamine supplementation in serious illness: a systematic review of the 

evidence; Crit Care Med 2002; 30:2022-9 

- Stehle, P. et al.: Glutamin - ein unentbehrlicher Nährstoff bei metabolischem Stress. Ernähr.- 

Umschau 43 (1996) 318. 

- Vrba, R.; Studies on metabolic function of the brain and on its relation to physical stress. V. 

Role of glutamin in restorative processes of the brain, Physiologia Bohemoslovaca, 5, 3, 1956, 

pp. 257 – 268 

HYDROLYSATE WITH PEPTIDE and Stress 

Authoritative bodies 

- DGCCRF, dated January 16th 2006 

- AFSSA (French Food Safety Agency) – 2004 –SA -0277 DATED April 1st 2005 

http://www.afssa.fr/Ftp/Afssa/29412-29413.pdf 

- Food and Drug Administration – 75-Day Premarket notifications for New dietary Ingredients – 

RPT 242 : lactium®, milk protein hydrolysate – 08/04/2004 

http://www.fda.gov/ohrms/dockets/dockets/95s0316/16.htm 

97 

97

Peer-reviewed articles : 

- Miclo L., Perrin E., Driou A., Papadopoulos V., Boujrad N., Vanderesse R., Boudier J.F., Desor 

D., Linden G. and Gaillard J.-L. (2001). Characterization of α-casozepine, a tryptic peptide from 

bovine α-s1-casein with benzodiazepine-like activity. The FASEB Journal, 15 : 1780-2 

Human studies with Peer-reviewed articles : 

- Messaoudi M., Lefranc-Millot C., Desor D., Demagny B., Bourdon L. (2005) Effects of a tryptic 

hydrolysate from bovine milk alpha(S1)-casein on hemodynamic responses in healthy human 

volunteers facing successive mental and physical stress situations. European Journal of 

Nutrition , 44(2), 128-32 

- Kim J.H., Desor D., Kim Y.T., Yoon W.J., Kim K.S., Jun J.S., Pyun K.H., and Shim I. (2006). 

Efficacy of as1-casein hydrolysate on stress-related symptoms in women. European Journal of 

Clinical Nutrition, 1-6. 

Animals studies with Peer-reviewed articles: 

- Authors : Guesdon B., Messaoudi M., Lefranc C., Fromentin G., Tomé D., Even P. (2006). A 

tryptic hydrolysate from bovine milk α-s1-casein improves sleep in rats subjected to chronic 

mild stress. Peptides, 27, 1476-82 

- Violle N., Messaoudi M., Lefranc-Millot C., Desor D., Nejdi A., Demagny B. and Schroeder H. 

(2006). Ethological comparison of the effects of a bovine as1-casein tryptic hydrolysate and 

diazepam on the behaviour of rats in two models of anxiety. Pharmacology, Biochemistry and 

Behavior, 84(3), 517-523. 

Other Individual studies without per-reviewed articles 

- Messaoudi M., Bresson J.-L., Desor D., Lefranc C., Boudier J.F. and Paquin P. (2002). 

Anxiolytic-like effects of the milk protein hydrolysate Prodiet F200 in healthy human volunteers. 

Stress, 5 (suppl.), 124. 

- Lanoir D., Canini F., Messaoudi M., Lefranc C., Demagny B., Martin S. and Bourdon L. (2002). 

Long term effects of a bovine milk alpha-s1 casein hydrolysate on healthy low and high stress 

responders. Stress, 5 (suppl.), 124. 

- Schroeder H., Violle N., Messaoudi M., Lefranc-Millot C., Nejdi A., Demagny B., Desor D., 

(2003). Effects of ING-911, a tryptic hydrolysate from bovine milk aS1-casein on anxiety of 

Wistar male rats measured in the conditioned defensive burying paradigm and the elevated 

plus maze test. Behavioural Pharmacology, 14 (S1), S38, P31 

- Miclo L., (1994). Caractérisation et activité de type benzodiazépine d’un décapeptide trypsique 

de la caséine αs1 bovine. PhD Thesis. Henri Poincaré Nancy I University. 

- Miclo L., Perrin E., Driou A., Boudier J.F., Iung C. and Linden G. (Nov.30, 1995). Use of a 

decapeptide with benzodiazepine-type activity for preparing medicines and food supplements. 

EP 0 714 910 B1 Patent. 

LACTOTRIPEPTIDES and Blood pressure 

Reviews. 

- Fitzgerald RJ, Murray BA, Walsh DJ. Hypotensive peptides from milk proteins. J Nutr 2004. 

134:980S-988S. 

- Huth P.J., DiRienzo D.B. and Miller G.D.. Major Scientific Advances with Dairy Food in 

Nutrition and Health. Journal of Dairy Science 89; 1207-1221, 2006. 

- Meisel H. Overview on milk protein-derived peptides. Int Dairy J 1998;8:363-373. 

- Jauhiainen T., Korpela R.; Milk Peptides and Blood Pressure; J. Nutr. 2007 137: 825S-829S 

98 

98

Human Clinical Trials. 

- Aihara, K; Kajimoto, O; Hirata, H; Takahashi, R; Nakamura, Y. Journal of the American College 

of Nutrition (2005), 24(4), 257-265. Effect of powdered fermented milk with Lactobacillus 

helveticus on subjects with high-normal blood pressure or mild hypertension. (IPP: 4.7 mg/day 

and VPP: 8.3 mg/day) 

- Hata Y., Yamamoto M., Ohni M., Nakajima K., Nakamura Y., and Takano T. (1996) A placebocontrolled 

study of the effect of a sour milk on blood pressure in hypertensive subjects. Am. J. 

Clin. Nutr., 64, 767-771. (IPP: 1.1 mg/day and VPP: 1.5 mg/day) 

- Hirata H., Nakamura Y., Yada H., Moriguchi S., Kajimoto O.,and Takahashi T. (2002) Clinical 

effects of new sour milk drink on mild or moderate hypertensive subjects. J. New Rem. & Cli., 

51, 61-69. (IPP: 1.6 mg/day and VPP: 2.66 mg/day) 

- Itakura H., Ikemoto S., Terada S., and Kondo K. (2001) The effect of sour milk on blood 

pressure in untreated hypertensive and normotensive subjects. J Jpn. Soc. Clin. Nutr., 23, 26- 

31. (IPP: 1.1 mg/day and VPP: 1.5 mg/day) 

- Jauhiainen et al. Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive 

subjects in 24-h ambulatory blood pressure measurement. Am J Hypertens 2005;18:1600-5. 

(IPP: 22.5 mg/day and VPP: 30 mg/day) 

- Kaijmoto O., Nakamura Y., Yada H., Moriguchi S., Hirata H., and Takahashi T. (2001a) 

Hypotensive effects of sour milk in subjects with mild or moderate hypertension. J. Jpn. Soc. 

Nutr. Food Sci., 54, 347-354. (IPP: 1.52 mg/day and VPP: 2.53 mg/day) 

- Kajimoto O., Aihara K., Hirata H., Takahashi R., and Nakamura Y. (2001b) Hypertensive 

effects of the tablets containing “ Lactotripeptides (VPP, IPP)” . J. Nutr. Food, 4, 51-61. (IPP: 

1.64 mg/day and VPP: 2.52 mg/day) 

- Kajimoto, O; Kurosaki, T; Mizutani, J; Ikeda, N; Kaneko, K; Aihara, K; Yabune, M; Nakamura, 

Y. Journal of Nutritional Food (2002), 5(3), 55-66. Antihypertensive effects of liquid yogurts 

containing "lactotripeptides (VPP, IPP)" in mild hypertensive subjects. (IPP: 0.79 mg/day and 

VPP: 1.12 mg/day) 

- Mizuno S., Matsuura K., Gotoe T., Nishimura S., Kajimoto O., Yabune M., Kajimoto Y., and 

Yamamoto N. (2005) Antihypertensive effect of casein hydrolysate in a placebo-controlled 

study in subjects with high-normal blood pressure and mild hypertension. Br. J. Nutr., 94, 84- 

91. (IPP: 0.86, 1.2 and 1.76 mg/day and VPP: 0.89, 1.27 and 1.86 mg/day) 

- Mizushima et al. Randomized controlled trial of sour milk on blood pressure in borderline 

hypertensive men. Am J Hypertens 2004;17:701-706. (IPP: 1.15 mg/day and VPP: 1.98 

mg/day) 

- Nakamura Y., Kaijmoto O., Kaneko K., Aihara K., Mitzutani J., Ikeda N., Nishimura A., and 

Kaijmoto Y (2004) Effect of the liquid yoghurts containing “Lactotripeptide (VPP, IPP)” on highnormal 

blood pressure. J. Nutr. Food, 7, 123-137. (IPP: 0.74 mg/day and VPP: 1.13 mg/day) 

- Sano J, Ohki K, Higuchi T, Aihara K, Mizuno S, Kajimotot O, Nakagawa S, Kajimoto Y, 

Nakamura Y. Effect of casein hydrolyzate, prepared with protease derived from Aspergillus 

oryzae on subjects with high-normal blood pressure J Med Food 8 (4) 2005, 423-430 (IPP: 1.6 

mg/day and VPP: 1.47 mg/day) 

- Seppo L., Jauhiainen T., Poussa T., and Korpela R. (2003) A fermented milk high in bioactive 

peptides has a blood pressure-lowering effect in hypertensive subjects. Am. J. Clin. Nutr., 77, 

325-330 (IPP: 2.0 mg/day and VPP: 3.0 mg/day) 

- Seppo L., Kerojoki O., Suomalainen T., and Korpela R. (2002) The effect of a Lactobacillus 

helveticus LBK-16 H fermented milk on hypertension – a pilot study on humans. 

Milchwissenschaft 57, 124-127. (IPP: 2.25 mg/day and VPP: 3.0-3.75 mg/day) 

99 

99

- Tuomilehto et al. Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria 

producing tripeptides on blood pressure in subjects with mild hypertension. J Hum Hypertens 

2004;18:795-802. (IPP: 2.4-2.7 mg/day and VPP: 2.4-2.7 mg/day) 

Individual studies. 

- Foltz M, Meynen EE, Bianco V, van Platerink C, Koning TM, Kloek J. Angiotensin converting 

enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact 

into the circulation. J.Nutr. 2007;137:953-8. 

Animal studies. 

- Jauhiainen et al. Effect of long-term intake of milk peptides and minerals on blood pressure and 

arterial function in spontaneously hypertensive rats. Milchwissenschaft 2005;60:358-362. 

- Nakamura, Y; Yamamoto, N; Sakai, K; Takano, T. Journal of Dairy Science (1995) 78, 1253- 

1257. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to 

angiotensin I-converting enzyme. 

- Sipola, M; Finckenberg, P; Korpela, R; Vapaatalo, H; Nurminen, ML. Journal of Dairy Research 

(2002) 69, 103-111. Effect of long-term intake of milk products on blood pressure in 

hypertensive rats. 

- Sipola, M; Finckenberg, P; Santisteban, J; Korpela, R; Vapaatalo, H; Nurminen, ML. Journal of 

Physiology and Pharmacology (2001) 52, 745-754. Long-term intake of milk peptides 

attenuates development of hypertension in spontaneously hypertensive rats. 

- Masuda O, Nakamura Y, Takano T. Antihypertensive peptides are present in aorta after oral 

administration of sour milk containing these peptides to spontaneously hypertensive rats. J 

Nutr. 1996;126: 

Posters from Scientific meetings 

- Zander van der K, Jäkel M, Bianco V, Koning M. The effect of fermented dairy peptides on 

daytime blood pressure. J Hypertension 2006;24:S95. 

- Leeuw de P, Zander van der K, Kroon A, Rennenberg R, Koning M. Dairy peptides: a dose 

dependent effect on blood pressure. J Hypertension 2006;24:S95. 

- Visser F, Kocks M, Kluppel C, Zander van der K, Koning M, Navis G. Acute ACE inhibiting 

effects of the lactotripeptide IPP in rats. J Hypertension 2006;24:S373. 

- Jauhiainen T, Pilvi T, Jian C, Vapaatalo H, Korpela R, Mervaala E. Antihypertensive 

mechanism behind blood pressure lowering biological active tripeptides. J Hypertension 

2006;24:S345. 

- Jauhiainen T, Rönnback M, Vapaatalo H, Wuolle K, Kautiainen H, Groop P-H et al. 

Lactobacillus Helveticus fermented milk containing bioactive tripeptides improves arterial 

stiffness in hypertensive subjects. J Hypertension 2007;25:S60. 

- Neutel J, Nonaka M, Hendler M, Wuolle K. The use of Amealpeptide in the treatment of 

patients with stage I and stage II hypertension - data from the AHEAD Study. J Hypertension 

2006;24:S84. 

LIGNANS and Phyto-estrogenic properties 

Textbooks/Authoritative Reviews 

- British Nutrition Foundation. Soya and Health. Briefing Paper. BNF: 2002, UK. 

- British Nutrition Foundation. Plants: Diet and Health. Report of the BNF Task Force. Blackwell 

Publishing: 2003, UK. 

100 

100

- Rhodes M, Price KR. Phytochemicals. In Encyclopedia of Human Nutrition 1999, pgs 1543- 

1544. Academic Press, UK. 

- Committee on Toxicity. Phytoestrogens and Health. FSA: 2003, UK. 

- 

http://www.food.gov.uk/multimedia/pdfs/phytoreport0503 

Setchell KDR, Adlercreutz H. Mammalian lignans and phyto-estrogens - recent studies on their 

formation, metabolism and biological role in health and disease. In: Role of the Gut Flora in 

Toxicity and Cancer. Academic press Ltd 1988, 315-345. 

Reviews 

- Cassidy A, Faughnan M. Phyto-oestrogens through the life cycle. Proc Nut Soc 2000, 59: 489- 

496. 


- de Kleijn MJ, van der Schouw YT, Wilson PW et al. Intake of dietary phytoestrogens is low in 

postmenopausal women in the United States: the Framingham Study (1-4). 

LUTEIN and Eye health 


- Public statement issued in January 23, 2004 by the French National Food Safety Agency 

(AFSSA): Saisine Nr2003-SA-0205 – Available on the AFSSA website 

(http://www.afssa.fr/Object.asp?IdObj=22320&Pge=0&CCH=061017092217:26:4&cwSID=47C 

465D82DAD47F792CF6887E456A54C&AID=0) 

Recognized textbooks and monographs 

- Astley SB, Lindsay DG: European Research on the Functional Effects of Dietary Antioxidants 

(EUROFEDA). Conclusions. Mol Aspects Med 2002; 23(1-3): 287-91. 

- Augustin AJ: Nutrition and the Eye: Developments in Ophthalmology 2005; 38: 29-31, 70-88, 

129-131. 

- Shibamoto, Takayuki, Junji Terao, and Toshihiko Osawa. (1998) Functional Foods for Disease 

Prevention I. Oxford Press. Chapter 7 entitled Metabolism of Dietary Carotenoids and Their 

Potential Role in Prevention of Cancer and Age-Related Macular Degeneration written by F. 

Khachik, L.A. Cohen and Z. Zhao. 

- Firshein R: Lutein: sight for sore eyes. The nutraceutical revolution: 20 cutting-edge nutrients to 

help you design your own perfect whole-life program 1998; Chapter 16. 

- Krinsky NI, Mayne ST, Sies H: Discusses chemistry of lutein and zeaxanthin, relation to AMD, 

noninvasive assessment of carotenoids in the human eye, bioavailability, dietary sources, 

carotenoids in the skin, lutein and zeaxanthin in the human plasma, cataracts. Carotenoid in 

Health and Disease 2004. 

- Taylor A: Nutritional and environmental influences on the eye. CRC Press, Boca Raton 

1999(Chapters 11-13). 

- Joseph JA, Nadeau DA, Underwood A: Best sources of lutein and its relation to eye health. 

The Color Code: A Revollutionary Eating Plan for Optimum Health 2002. 

- Britton G, Liaaen-Jensen, Pfander H: Carotenoids Volume 3: Biosynthesis and Metabolism 

1998; 3: Chapter 6. 

- [No authors listed] Lutein and zeaxanthin. Monograph. Altern Med Rev. 2005 Jun;10(2):128-35. 

Critical review articles 

101 

101

- Landrum JT, Bone RA: Lutein, zeaxanthin, and the macular pigment. Arch Biochem Biophys 

2001; 385(1): 28-40. 

- Alves-Rodrigues A, Shao A: The science behind lutein. Toxicol Lett 2004; 150(1): 57-83. 

- Krinsky NI, Landrum JT, Bone RA: Biologic mechanisms of the protective role of lutein and 

zeaxanthin in the eye. Annu Rev Nutr 2003; 23: 171-201. 

- Nussbaum JJ, Pruett RC, Delori FC: Historic perspectives. Macular yellow pigment. The first 

200 years. Retina 1981; 1(4): 296-310. 

- Hammond BR, Wooten BR, Curran-Celentano J: Carotenoids in the retina and lens: possible 

acute and chronic effects on human visual performance. Arch Biochem Biophys 2001; 385(1): 

41-46. 

- Semba RD, Dagnelie G: Are lutein and zeaxanthin conditionally essential nutrients for eye 

health - Med Hypotheses 2003; 61(4): 465-72. 

- Shaban H, Richter C: A2E and blue light in the retina: the paradigm of age-related macular 

degeneration. Biol Chem 2002; 383(3-4): 537-45. 

- Schalch W. (1992) Carotenoids in the Retina – A Review of Their Possible Role in Preventing 

or Limiting Damage Caused by Light and Oxygen Free Radicals and Aging (I. Emerit, B. 

Chance, Eds.), Birkhäuser Verlag Basel, Exs 1992; 62: 280-98, 280-298 

- Ham WT, Jr.: Ocular hazards of light sources: review of current knowledge. J Occup Med 

1983; 25(2): 101-3. 

- Bartlett H, Eperjesi F: Age-related macular degeneration and nutritional supplementation: a 

review of randomised controlled trials. Ophthalmic Physiol Opt 2003; 23(5): 383-99. 

- Snodderly DM: Evidence for protection against age-related macular degeneration by 

carotenoids and antioxidant vitamins. Am J Clin Nutr 1995; 62(6 Suppl): 1448S-1461S. 

- Granado F, Olmedilla B, Blanco I: Nutritional and clinical relevance of lutein in human health. 

Br J Nutr 2003; 90(3): 487-502. 

- Stringham JM: Dietary lutein and zeaxanthin: possible effects on visual function. Nutritional 

Reviews 2005; 63(2): 59-64. 

- Wooten BR, Hammond BR: Macular pigment: influences on visual acuity and visibility. Prog 

Retin Eye Res 2002; 21(2): 225-40. 

- Whitehead AJ et al. Macular pigment: a review of current knowledge. Arch Ophthalmol. 2006 

Jul;124(7):1038-45 

Animal studies (in vitro) 

- Snodderly DM, Brown PK, Delori FC, Auran JD: The macular pigment. I. Absorbance spectra, 

localization, and discrimination from other yellow pigments in primate retinas. Invest 

Ophthalmol Vis Sci 1984; 25(6): 660-73. 

- Dachtler M., Kohler K., Albert K. (1998) Reversed-phase High-Performance Liquid 

Chromatographic Determination of Lutein and Zeaxanthin Stereoisomers in Bovine Retina 

using a C30 Bonded Phase J. Chromatogr. B, 720, 211-216 

- Khachik F., Bernstein P.S., Garland D.L. (1997) Identification of Lutein and Zeaxanthin 

Oxidation Products in Human and Monkey Retinas Invest. Ophthalmol. Vis. Sci., 38, 1802- 

1811 

In vitro studies (ex vivo studies) 

- Landrum JT, Bone RA, Kilburn MD: The macular pigment: a possible role in protection from 

age-related macular degeneration. Adv Pharmacol 1997; 38: 537-56. 

102 

102

- Bone RA, Landrum JT, Tarsis SL: Preliminary identification of the human macular pigment. 

Vision Res 1985; 25(11): 1531-5. 

- Yeum KJ, Taylor A, Tang G, Russell RM: Measurement of carotenoids, retinoids, and 

tocopherols in human lenses. Invest Ophthalmol Vis Sci 1995; 36(13): 2756-61. 

- Beatty S, Boulton M, Henson D, Koh HH, Murray IJ: Macular pigment and age related macular 

degeneration. Br J Ophthalmol 1999; 83(7): 867-77. 

- Sundelin SP, Nilsson SE: Lipofuscin-formation in retinal pigment epithelial cells is reduced by 

antioxidants. Free Radic Biol Med 2001; 31(2): 217-25. 

- Rapp LM, Maple SS, Choi JH: Lutein and zeaxanthin concentrations in rod outer segment 

membranes from perifoveal and peripheral human retina. Invest Ophthalmol Vis Sci 2000; 

41(5): 1200-9. 

- Stahl W, Junghans A, de Boer B, Driomina ES, Briviba K, Sies H: Carotenoid mixtures protect 

multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. 

FEBS Lett 1998; 427(2): 305-8. 

- Bhosale P, Bernstein PS: Synergistic effects of zeaxanthin and its binding protein in the 

prevention of lipid membrane oxidation. Biochim Biophys Acta 2005; 1740(2): 116-21. 

- Junghans A, Sies H, Stahl W: Macular pigments lutein and zeaxanthin as blue light filters 

studied in liposomes. Arch Biochem Biophys 2001; 391(2): 160-4. 

- Bernstein P.S., Yoshida M.D., Katz N.B., McClane R.W., Gellermann W. (1998) Raman 

Detection of Macular Carotinoid Pigments in Intact Human Retina Invest. Ophthalmol. Vis. Sci., 

39, 2003-2011 

- Bone R.A., Landrum J.T., Friedes L.M., Gomez C.M., Kilburn M.D. Menendez E., Vidal I., 

Wang W. (1997) Distribution of Lutein and Zeaxanthin Stereoisomers in the Human Retina 

Exp. Eye. Res., 64 211-218 

- Dachtler, M., Glaser, T., Kohler, K., Albert, K. (2001) Combined HPLC-MS and HPLC-NMR online 

coupling for the separation and determination of Lutein and Zeaxanthin Stereoisomers in 

Spinach and in retina. Anal. Chem. 73(3), 667-74 

- Pauleikhoff, D., van Kujik, F.J.G.M., and Bird, A.C. (2001) Makuläres Pigment und 

altersabhängige Makuladegeneration. Ophthalmologe 98, 511-19 

In vivo studies 

- Hammond BR, Jr., Wooten BR: CFF thresholds: relation to macular pigment optical density. 

Ophthalmic Physiol Opt 2005; 25(4): 315-9. 

- Curran Celentano J, Burke JD, Hammond BR, Jr.: In vivo assessment of retinal carotenoids: 

macular pigment detection techniques and their impact on monitoring pigment status. J Nutr 

2002; 132(3): 535S-539S 

Human studies 


- Broekmans WM, Berendschot TT, Klopping-Ketelaars IA, et al.: Macular pigment density in 

relation to serum and adipose tissue concentrations of lutein and serum concentrations of 

zeaxanthin. Am J Clin Nutr 2002; 76(3): 595-603. 

- Seddon JM, Ajani UA, Sperduto RD, et al.: Dietary carotenoids, vitamins A, C, and E, and 

advanced age-related macular degeneration. Eye Disease Case-Control Study Group. Jama 

1994; 272(18): 1413-20. 

- Mares-Perlman JA, Brady WE, Klein R, et al.: Serum antioxidants and age-related macular 

degeneration in a population- based case-control study. Arch Ophthalmol 1995; 113(12): 1518- 

23. 

103 

103

- Flood V, Smith W, Wang JJ, Manzi F, Webb K, Mitchell P: Dietary antioxidant intake and 

incidence of early age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology 

2002; 109(12): 2272-8. (Population-based cohort study) 

- Delcourt C, Carriere I, Delage M, Barberger-Gateau P, Schalch W; POLA Study Group.Plasma 

lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related 

maculopathy and cataract: the POLA Study. Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2329- 

35 

- Nolan JM, Stack J, O' Donovan O, Loane E, Beatty S. Risk factors for age-related maculopathy 

are associated with a relative lack of macular pigment. Exp Eye Res. 2007 Jan;84(1):61- 

74.Epub 2006 Nov 1. 

- Eye disease Case-Control Study Group (1993) Antioxidant Status and Neovascular Age- 

Related Macular Degeneration Arch. Ophthalmol., 111, 104-109 

Observational human studies 

- Bone RA, Landrum JT, Dixon Z, Chen Y, Llerena CM: Lutein and zeaxanthin in the eyes, 

serum and diet of human subjects. Exp Eye Res 2000; 71(3): 239-45. 

- Curran-Celentano J, Hammond BR, Jr., Ciulla TA, Cooper DA, Pratt LM, Danis RB: Relation 

between dietary intake, serum concentrations, and retinal concentrations of lutein and 

zeaxanthin in adults in a Midwest population. Am J Clin Nutr 2001; 74(6): 796-802. 

(Observational Cross-Sectional Study) 

- Snellen EL, Verbeek AL, Van Den Hoogen GW, Cruysberg JR, Hoyng CB: Neovascular agerelated 

macular degeneration and its relationship to antioxidant intake. Acta Ophthalmol Scand 

2002; 80(4): 368-71. (Observational/epidemiological case-control human study). 

- Bahrami H, Melia M, Dagnelie G: Lutein supplementation in retinitis pigmentosa: PC-based 

vision assessment in a randomized double-masked placebo-controlled clinical trial 

- 

[NCT00029289]. BMC Ophthalmol 2006; 6(1): 23. 

Bernstein PS, Zhao DY, Wintch SW, Ermakov IV, McClane RW, Gellermann W: Resonance 

Raman measurement of macular carotenoids in normal subjects and in age-related macular 

degeneration patients. Ophthalmology 2002; 109(10): 1780-7. 

- Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE: Macular pigment in 

donor eyes with and without AMD: a case-control study. Invest Ophthalmol Vis Sci 2001; 42(1): 

235-40 (Observational Case-Control Study). 

- Brown L, Rimm EB, Seddon JM, et al.: A prospective study of carotenoid intake and risk of 

cataract extraction in US men. Am J Clin Nutr 1999; 70(4): 517-24 (Observational prospective 

cohort study) 

- Chasan-Taber L, Willett WC, Seddon JM, et al.: A prospective study of carotenoid and vitamin 

A intakes and risk of cataract extraction in US women. Am J Clin Nutr 1999; 70(4): 509-16. 

(Prospective cohort study). 

- Richer S: ARMD--pilot (case series) environmental intervention data. J Am Optom Assoc 1999; 

70(1): 24-36. 

- Dagnelie G, Zorge IS, McDonald TM: Lutein improves visual function in some patients with 

retinal degeneration: a pilot study via the Internet. Optometry 2000; 71(3): 147-64. (prospective 

cohort study) 

- Hammond BR, Wooten BR, Snodderly DM: Preservation of visual sensitivity of older subjects: 

association with macular pigment density. Invest Ophthalmol Vis Sci 1998; 39(2): 397-406. 

- Hammond, B.R., Wooten, B.R., and Snodderly, M.R. (1996) Cigarette smoking and retinal 

carotenoids: implications for age-related macular degeneration Vision Res 36, 3003-3009 


104 

104

- Richer S, Stiles W, Statkute L, et al.: Double-masked, placebo-controlled, randomized trial of 

lutein and antioxidant supplementation in the intervention of atrophic age-related macular 

degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 

2004; 75(4): 216-30. 

- Johnson EJ, Hammond BR, Yeum KJ, et al.: Relation among serum and tissue concentrations 

of lutein and zeaxanthin and macular pigment density. Am J Clin Nutr 2000; 71(6): 1555-62. 

- Bone RA, Landrum JT, Guerra LH, Ruiz CA: Lutein and Zeaxanthin Dietary Supplements 

Raise Macular Pigment Density and Serum Concentrations of these Carotenoids in Humans. J 

Nutr 2003; 133(4): 992-8. 

- Duncan JL, Aleman TS, Gardner LM, et al.: Macular pigment and lutein supplementation in 

choroideremia. Exp Eye Res 2002; 74(3): 371-81. (Observation/Clinical Trial) 

- Koh HH, Murray IJ, Nolan D, Carden D, Feather J, Beatty S: Plasma and macular responses to 

lutein supplement in subjects with and without age-related maculopathy: a pilot study. Exp Eye 

Res 2004; 79(1): 21-7 

- Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, Sprague KE: A one year study of the 

macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res 1997; 65(1): 57- 

62. 

- Kvansakul J, Rodriguez-Carmona M, Edgar DF, et al.: Supplementation with the carotenoids 

lutein or zeaxanthin improves human visual performance. Ophthalmic Physiol Opt 2006; 26(4): 

362-71. 

- Olmedilla B, Granado F, Blanco I, Vaquero M: Lutein, but not alpha-tocopherol, 

supplementation improves visual function in patients with age-related cataracts: a 2-y doubleblind, 

placebo-controlled pilot study. Nutrition 2003; 19(1): 21-4. (Double blind placebo 

controlled pilot study) 

- Aleman TS, Duncan JL, Bieber ML, et al.: Macular pigment and lutein supplementation in 

retinitis pigmentosa and Usher syndrome. Invest Ophthalmol Vis Sci 2001; 42(8): 1873-81. 

- Schweitzer D, Lang GE, Beuermann B, et al.: Objektive bestimmung der optischen dichte von 

xanthophyll nach supplementation von lutein. Ophtalmologe 2002; 99: 270-275. 

- Falsini B, Piccardi M, Iarossi G, Fadda A, Merendino E, Valentini P: Influence of short-term 

antioxidant supplementation on macular function in age-related maculopathy. A pilot study 

including electrophysiologic assessment. Ophthalmology 2003; 110(1): 51-60. 

Single blinded trial 

- Hammond BR, Johnson EJ, Russell RM, et al.: Dietary modification of human macular pigment 

density. Invest Ophthalmol Vis Sci 1997; 38(9): 1795-801. 

Randomized, double-masked, placebo-controlled intervention clinical trial. 

- Richer S, Stiles W, Statkute L, et al.: Double-masked, placebo-controlled, randomized trial of 

lutein and antioxidant supplementation in the intervention of atrophic age-related macular 

degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 

2004; 75(4): 216-30. 

- Schalch W, Cohn W, Barker FM, et al.: Xanthophyll accumulation in the human retina during 

supplementation with lutein or zeaxanthin - the LUXEA (LUtein Xanthophyll Eye Accumulation) 

study. Arch Biochem Biophys 2006. (prospective, single-centred, randomized, placebocontrolled, 

one year pilot supplementation trial). 

- Berendschot TT, Goldbohm RA, Klopping WA, van de Kraats J, van Norel J, van Norren D: 

Influence of lutein supplementation on macular pigment, assessed with two objective 

techniques. Invest Ophthalmol Vis Sci 2000; 41(11): 3322-6. 

105 

105

- Cardinault N, Gorrand JM, Tyssandier V, Grolier P, Rock E, Borel P: Short-term 

supplementation with lutein affects biomarkers of lutein status similarly in young and elderly 

subjects. Exp Gerontol 2003; 38(5): 573-82. 

Other miscellaneous Peer-Reviewed articles 

- Garcia-Closas R, Berenguer A, Jose Tormo M, et al.: Dietary sources of vitamin C, vitamin E 

and specific carotenoids in Spain. Br J Nutr 2004; 91(6): 1005-11. 

- Khachik F, Bernstein PS, Garland DL: Identification of lutein and zeaxanthin oxidation products 

in human and monkey retinas. Invest Ophthalmol Vis Sci 1997; 38(9): 1802-11. 

LUTEIN and Skin health 

Textbooks 

- Elsner P, Maibach HI: Cosmeceuticals: Drugs vs. Cosmetics. 2000. 

- Aust LB: Cosmetic Claims Substantiation. 1998. 

- Frank HA, Young AJ, Britton G, Cogdell RJ: The Photochemistry of Carotenoids. 1999. 

- Freedberg IM, Eisen AZ, Wolff K, et al.: Fitzpatrick's Dermatology in General Medicine. 1999; I 

& II. 

Review articles 

- Alves-Rodrigues A, Shao A: The science behind lutein. Toxicol Lett 2004; 150(1): 57-83. 

Clinical trials 

- Randomized, placebo-controlled clinical trial 

- Palombo P, Fabrizi G, Ruocco V, et al.: Beneficial Long-Term Effects of Combined Oral/Topical 

Antioxidant Treatment with the Carotenoids Lutein and Zeaxanthin on Human Skin: A Double- 

Blind, Placebo-Controlled Study. Skin Pharmacology and Physiology 2007; 20(4): 199-210. 

- Morganti P, Bruno C, Guarneri F, Cardillo A, Del Ciotto P, Valenzano F: Role of topical and 

nutritional supplement to modify the oxidative stress. International J. Cosmetic Science 2002; 

24: 331-339. 

- Heinrich U, Tronnier H, Stahl W, Bejot M, Maurette JM: Antioxidant supplements improve 

parameters related to skin structure in humans. Skin Pharmacol Physiol 2006; 19(4): 224-31. 

- Morganti P, Fabrizi G, Bruno C: Protective effects of oral antioxidants on skin and eye function. 

Skinmed 2004; 3(6): 310-6. 

- Segger D, Shonlau F: Supplementation with Evelle improves skin smoothness and elasticity in 

a double-blind, placebo-controlled study with 62 women. Journal of Dermatological Treatment 

2004; 15: 222-226. 

- Case-control study 

- Millen AE: Diet and risk of malignant melanoma in a case-control study. Cancer Epidemiol 

Biomarkers Prev 2003; 12(11 Part 2): 1339s. 


- Taylor EJ, Evans FJ: Anti-psoriatic action of lutein demonstrated by inhibition of rat 

photodermatitis. J Pharm Pharmacol 1998; 50(Supplement): 78. 

- Lee EH, Faulhaber D, Hanson KM, et al.: Dietary lutein reduces ultraviolet radiation-induced 

inflammation and immunosuppression. J Invest Dermatol 2004; 122(2): 510-7. 

106 

106

- Gonzalez S, Astner S, An W, Goukassian D, Pathak MA: Dietary lutein/zeaxanthin decreases 

ultraviolet B-induced epidermal hyperproliferation and acute inflammation in hairless mice. J 

Invest Dermatol 2003; 121(2): 399-405. 

In vitro Studies 

- O'Connor I, O'Brien N: Modulation of UVA light-induced oxidative stress by beta-carotene, 

lutein and astaxanthin in cultured fibroblasts. J Dermatol Sci 1998; 16(3): 226-30. 

Human, ex-vivo studies 

- Lange BA, Buettner GR: Electron paramagnetic resonance detection of free radicals in UVirradiated 

human and mouse skin. Curr Probl Dermatol 2001; 29: 18-25. 

- Peng YM, Peng YS, Lin Y: A nonsaponification method for the determination of carotenoids, 

retinoids, and tocopherols in solid human tissues. Cancer Epidemiol Biomarkers Prev 1993; 

2(2): 139-44. 

- Peng YM, Peng YS, Lin Y, Moon T, Roe DJ, Ritenbaugh C: Concentrations and plasma-tissuediet 

relationships of carotenoids, retinoids, and tocopherols in humans. Nutr Cancer 1995; 

23(3): 233-46. 

- Hata TR, Scholz TA, Ermakov IV, et al.: Non-invasive raman spectroscopic detection of 

carotenoids in human skin. J Invest Dermatol 2000; 115(3): 441-8. 

- Greenway HT, Pratt S: Skin tissue levels of carotenoids, vitamin A, and antioxidants in 

photodamaged skin. La Jolla, Ca: Mohs Surgery Unit, Division of Dermatology & Cutaneous 

Surgury, Scripps Clinic, 1999. 

Others miscellaneous Peer-Reviewed articles 

- Garcia-Closas R, Berenguer A, Jose Tormo M, et al.: Dietary sources of vitamin C, vitamin E 

and specific carotenoids in Spain. Br J Nutr 2004; 91(6): 1005-11. 

LYCOPENE and Skin health 

Reviews 

- Stahl W, Heinrich U, Aust O, Tronnier H, Sies H. Lycopene-rich products and dietary 

photoprotection. Photochem Photobiol Sci. 2006 Feb;5(2):238-42. 


- Stahl W, Heinrich U, Wiseman S, Eichler O, Sies H, Tronnier H.. Dietary tomato paste protects 

against ultraviolet light-induced erythema in humans. J Nutr. 200May;131(5):1449-51. 

- Aust O, Stahl W, Sies H, Tronnier H, Heinrich U. Supplementation with tomato-based products 

increases lycopene, phytofluene, and phytoene levels in human serum and protects against 

UV-light-induced erythema. Int J Vitam Nutr Res. 2005 Jan;75(1):54-60. 


Gollnick H. Photoprotection of UV-irradiated human skin: an antioxidative combination of 


Physiol. 2002 Sep-Oct;15(5):307-15. 

- Heinrich U, Gartner C, Wiebusch M, Eichler O, Sies H, Tronnier H, Stahl W. Supplementation 

with beta-carotene or a similar amount of mixed carotenoids protects humans from UV-induced 

erythema. J Nutr. 2003 Jan;133(1):98-101. 

- Cesarini JP, Michel L, Maurette JM, Adhoute H, Bejot M. Immediate effects of UV radiation on 

the skin: modification by an antioxidant complex containing carotenoids. Photodermatol 

Photoimmunol Photomed. 2003 Aug;19(4):182-9. 

107 

107

- Ribaya-Mercado JD, Garmyn M, Gilchrest BA, Russell RM. Skin lycopene is destroyed 

preferentially over beta-carotene during ultraviolet irradiation in humans. J Nutr. 1995 

Jul;125(7):1854-9. 

In Vitro studies 

- Eichler O, Sies H, Stahl W. Divergent optimum levels of lycopene, beta-carotene and lutein 

protecting against UVB irradiation in human fibroblastst. Photochem Photobiol. 2002 

May;75(5):503-6. 

LYCOPENE and Prostate health 

References for antioxidant effect 


- Chen. Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based 

entrees as a whole-food intervention. J Natl Cancer Inst; 93: 1872-1879, 2001. 

- Pool-Zobel A, Muller H: Consumption of vegetables reduces genetic damage in humans: first 

results of a human intervention trial with carotenoid-rich foods. Carcinogenesis; 18: 1847-1850, 

1997. 

- Porrini. Lymphocyte lycopene concentration and DNA protection from oxidative damage is 

increased in women after a short period of tomato consumption. J Nutr; 130: 189-192, 1998. 

- Rao, Agarwal. Bioavailability and in vivo antioxidant properties of lycopene from tomato 

products and their possible role in the prevention of cancer. Nutrition and Cancer; 31: 199-203, 

1998. 

- Torbergsen. Recovery of human lymphocytes from oxidative DNA damage; the apparent 

enhancement of DNA repair by carotenoids is probably simply an antioxidant effect. Eur J Nutr; 

39: 80-85, 2000. 

Evidence from mechanistic studies and other evidence 

- [Böhm & Bitsch 1999] Intestinal absorption of lycopene from different matrices and interactions 

to other carotenoids, the lipid status, and the antioxidant capacity of human plasma. Eur J Nutr; 

38:118-25. 

- [Bowen 2002] Tomato sauce supplementation and prostate cancer: lycopene accumulation 

and modulation of biomarkers of carcinogenesis. Exp Biol Med; 27:886-893. 

- [Breemen 2005] How do intermediate endpoint markers respond to lycopene in men with 

prostate cancer or benign prostate hyperplasia? J Nutr; 135: 2062-2064. 

- [Cohen et al 2000] Kristal AR, Stanford JL: Fruit and vegetable intake and prostate cancer risk. 

J Natl Cancer Inst; 92: 61-68. 

- [Di Mascio et al 1989] Kaiser S, Sies H: Lycopene as the most efficient biological carotenoid 

singlet oxygen quencher Arch Biochem Biophys; 274:532-538. 

- [Matos 2000] Protective effect of lycopene on lipid peroxidation and oxidative DNA damage in 

cell culture. Arch Biochem Biophys; 383: 56-59. 

References for effects on androgen-metabolism 


- Ansari. Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer. 

Urologic Oncology: Seminars and original investigations; 22: 415-420, 2003. 

108 

108

- Kim, Bowen P, Chen L: Effects of tomato sauce consumption on apoptotic cell death in 

prostate benign hyperplasia and carcinoma Nutr Cancer; 47:40-47, 2003. 

- Omer Kucuk, Fazlul H Sarkar, Wael Sakr, Zora Djuric, Michael N. Pollak, Fred Khachik, Yi-Wei 

Li, Mousumi Banerjee, David Grignon, John S Bertram, John D Crissman, Edson J Pontes, and 

David P Wood. Phase II randomized clinical trial of lycopene supplementation before radical 

prostatectomy. Cancer Epidemiology, Biomarkers & Prevention, Vol 10: 861-868, 2001 (App 6- 

1). 

- Nayan Kumar Mohanty, Sunita Saxena, Uday Pratap Singh, Neeray K. Goyal, Rajender 

Prakash Arora. Lycopene as a chemopreventive agent in the treatment of high-grade prostate 

intraepithelial neoplasia. Urologic Oncology: Seminars and Original Investigations 23: 383-395 

(2005) (App 6-2). 

Evidence from animal studies 

- Siler, Herzog A, Spitzer V,: Lycopene effects on rat normal prostate and prostate tumor tissue. 

J Nutr; 135: 2050-2052, 2005. 

References for cell balance 

Evidence from mechanistic plausibility 

- Amir. Lycopene and 1, 25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle 

progression and induction of differentiation in HL-60 leukemic cells. Nutr Cancer; 33: 105-112, 

1999. 

- Karas. Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling 

in mammary cancer cells. Nutr Cancer; 36: 101-111, 2000. 

- Livny . Lycopene inhibits proliferation and enhances gap-junction communication of KB-1 

human oral tumor cells. J Nutr;132(12):3754-9, 1998. 

- Nahum, Hirsch K, Danilenko M: Lycopene inhibition of cell cycle progression in breast and 

endometrial cancer cells is associated with reduction in cyclin D levels and retention of 

p27(Kip1) in the cyclin E-cdk2 complexes. Oncogene; 20: 3428-3436, 2001. 

- Pastori . Lycopene in association with alpha-tocopherol inhibits at physiological concentrations 

proliferation of prostate carcinoma cells. Biochem Biophys Res Commun; 250: 582-585, 1998. 

- Stahl, von Laar J, Martin HD: Stimulation of gap junctional communication: comparison of 

acyclo-retinoic acid and lycopene. Arch Biochem Biophys; 373:271-274, 2000. 

Evidence from animal studie 

- Breinholt. Dose-response effects of lycopene on selected drug-metabolizing and antioxidant 

enzymes in the rat. Cancer Letters; 154: 201-210, 2000 

- Bhuvaneswari . Chemopreventive efficacy of lycopene on 7,12-dimethylbenz[a]anthraceneinduced 

hamster buccal pouch carcinogenesis. Fitoterapia; 72: 865-874, 2001. 

- Limpens J., Schröder FH, de Ridder CMA: Combined lycopene and vitamin E treatment 

suppresses the growth of PC-346C human prostate cancer cells in nude mice. J Nutr; 136: 

1287-1293, 2006. 

References for prostate health in general 

Evidence from epidemiological studies 

- Baldwin et al . The effect of nutritional and clinical factors upon serum prostate specific antigen 

and prostate cancer in a population of elderly California men. Annual Meeting of American 

Urological Association; 27,1997. 

109 

109

- Cerhan et al. A cohort study of diet and prostate cancer risk. Cancer Epidemiol Biomarkers 

Prev; 7: 175, 1998 . 

- Gann Ma J, Giovannucci E: Lower prostate cancer risk in men with elevated plasma lycopene 

levels: results of a prospective analysis. Cancer Res; 59: 1225-1230, 1999. 

- Giovannucci, Ascherio A, Rim BE: Intake of Carotenoids and retinol in relation to risk of 

prostate cancer. J Natl Cancer Inst; 87: 1767-76,1995. 

- Giovannucci. Tomatoes, tomato-based products, lycopene and cancer: review of the 

epidemiologic literature. J Natl Cancer Inst; 91: 317-33,1999. 

- Giovannucci, Rimm EB, Liu Y: A Prospective study of tomato products, lycopene, and prostate 

cancer risk J Natl Cancer Inst; 94: 391-398, 2002. 

- Hayes. Dietary factors and risks for prostate cancer among blacks and whites in the United 

States. Cancer Epidemiol Biomarkers & Prev; 8: 25-34, 1999. 

- Hsing, Comstock GW, Abbey H, Polk B: Serologic precursors of cancer. Retinol, carotenoids 

and tocopherol and risk of prostate cancer. J Natl Cancer Inst; 82:941-946, 1990. 

- Jain, Hislop GT, Howe GR, Ghadirian P: Plant foods, antioxidants, prostate cancer risk: 

findings from case-control studies in Canada. Nutr Cancer; 34: 173-84, 1999. 

- Key, Silcocks PB, Davey GK: A case-control study of diet and prostate cancer. Br J Cancer; 

76: 678-687, 1997. 

- Kirsh , Mayne ST, Peters U: A prospective study of lycopene and tomato product intake and 

risk of prostate cancer. Cancer Epidemiol Biomarkers Prev; 15: 92-98, 2006. 

- Kolonel, Hankin JH, Whittemore AS: Vegetables, fruits, legumes and prostate cancer: a 

multiethnic case-control study. Cancer Epidemiol Biomarkers & Prev; 9: 795-804, 2000. 

- Le Marchand, Hankin JH, Kolonel LN, Wilkens LR: Vegetable and fruit consumption in relation 

to prostate risk in Hawaii: a reevaluation of the effect of dietary beta-carotene. Am J Epidemiol; 

133: 215-219, 1991. 

- Lu , Hung JC, Heber D: Inverse Associations between plasma lycopene and other carotenoids 

and prostate cancer. Cancer Epidemiology, Biomarkers & Prevention; 10:749-756. 

- Mills. Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer; 64: 598-604, 

1989. 

- Nomura. Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. Cancer 

Epidemiol Biomarkers Prev; 6:487-491, 1997. 

- Schumann, Mandel JS, Radke A : Some selected features of the epidemiology of prostatic 

cancer: Minneapolis-St. Paul, Minnesota case-control study, 1976-1979, 1982. 

- Norrish, Jackson RT, Sharpe SJ: Prostate cancer and dietary carotenoids. Am J Epidemiol; 

151:119-123, 2000. 

- Schuurmann. Vegetable and fruit composition and prostate cancer risk: a cohort study in The 

Netherlands. Cancer Epidemiol Biomarkers Prev; 7: 673-680,1998. 

- Tzonzou, Signorello LB, Lagiou P: Diet and cancer of the prostate: a case-control study in 

Greece. Int J Cancer; 80: 704-708,1999. 

- Vogt. Serum lycopene, other serum carotenoids, and risk of prostate cancer in US blacks and 

whites. Am J Epidemiol; 155:1023-1032, 2002. 

- Wu. Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case-control 

study. Cancer Epid, Biomarkers & Prevention; 13:260-269,2004. 

110 

110

LYCOPENE and Antioxidant properties 

Review 

- Block G., Patterson B., Subar A., Fruit, vegetables, and cancer prevention: A review of the 

epidemiological evidence, Nutr. Cancer 18 (1992) 1-29. 

- Cooper D. A., Elridge A. L., Peters J. C., Dietary carotenoids and certain cancers, heart 

disease, and age-related macular degeneration: A review of recent research, Nutr. Rev. 57 

(1999) 201-214. 

Meta-Analysis 

- Vivekananthan D. P., Penn M. S., Sapp S. K., Hsu A., Use of antioxidant vitamins for the 

prevention of cardiovascular disease: meta-analysis of randomised trials, Lancet 36(2003) 

2017-2023. 

Clinical Trial 

- Pool-Zobel B. L., Bub A., Müller H., Wollowsky I., Rechkemmer G., Consumption of vegetables 

reduces genetic damage in humans: first results of a human intervention trial with carotenoidrich 

foods, Carcinogenesis 18 (1997) 1847-1850. 


- Bilton R., Gerber M., Grolier P., Leoni C. (eds), The White Book on antioxidants in tomatoes 

and tomato products and their health benefits, 2nd rev. edition 2001, CMITI Sarl Avignon, ISSN 

1145-9565. 

- Bowen P., Chen I., Stacewicz-Sapuntzakis M., Duncan C., Sharifi R., Ghosh L., Kim H. S., 

Christov-Tzelkov K., van Breemen R., Tomato sauce supplementation and prostate cancer: 

Lycopene accumulation and modulation of biomarkers of carcinogenesis, Exp. Biol. Med. 227 

(2002) 886-893. 

- Bradley S., Shinton R., Why is there an association between eating fruit and vegetables and a 

lower risk of stroke?, J. Human Nutr. Diet. 1(1998) 363-372. 

- Franceschi S., Parpinel M., La Vecchia C., Favero A., Talamini R., Negri E., Role of different 

types of vegetables and fruit in the prevention of cancer of the colon, rectum, and breast, 

Epidemiol. 9 (1998) 338-341. 

- Gaziano J. M. et al., Supplementation with b-carotene in vivo and in vitro does not inhibit low 

density lipoprotein oxidation, Atherosclerosis 112 (1995) 187-195. 

- Giovannucci E., Rimm E. B., Liu Y., Stampfer M. J., Willet W. C., A prospective study of tomato 

products, lycopene, and prostate cancer risk, J. Natl. Cancer Inst. 94 (2002) 391-398. 

- Kannel W. B., Wilson P. W. F., An update on coronary risk factors, Med. Clin. North Am. 79 

(1995) 951-971. 

- Kohlmeier L. et al., Lycopene and myocardial infarction risk in the EURAMIC study, Am. J. 

Epidemiol. 146 (1997) 618-626. 

- Matos H. R., Capelozzi V. I., Gomes O. F., di Mascio P., Medeiros M. H., Lycopene inhibits 

DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate, Arch. Biochem. 

Biophys. 396 (2001) 171-177. 

- Matos H. R., di Mascio P., Medeiros M. H., Protective effect of lycopene on lipid peroxidation 

and oxidative DNA damage in cell cultures, Arch. Biochem. Biophys. 383 (2000) 56-59. 

- Morris D. L., Kritchevsky S. B., Davis C. E., Serum carotenoids and coronary heart disease, J. 

Am. Med. Assoc. 272 (1994) 1439-1441. 

111 

111

- Neaton J. D., Wentworth D., Serum cholesterol, blood pressure, cigarette smoking, and death 

from coronary heart disease: overall findings and differences by age for 316.000 white men, 

Arch. Intern. Med. 152 (1992) 56-64. 

- Palace V. P., Khaper N., Qin Q., Singal P. K., Antioxidant potentials of vitamin A and 

carotenoids and their relevance to heart disease, Free Radical Biol. Med. 26 (1999) 746-761. 

- Riemersma R. A., Epidemiology and the role of antioxidants in preventing coronary heart 

disease: a brief overview, Proc. Nutr. Soc. 53 (1994) 59-65. 

- Sesso H. D., Buring J. E., Norkus E. P., Gaziano J. M., Plasma lycopene, other carotenoids, 

and retinol and the risk of cardiovascular disease in women, Am. J. Clin. Nutr. 79 (2004) 47-53. 

- Stahl W., Junghans B., de Boer E. S., Driomina E. S., Briviba K., Sies H., Carotenoid mixtures 

protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and 

lutein, FEBS Lett. 427 (1998) 305-308. 

- Willcox J. K., Catignani G. L., Lazarus S., Tomatoes and cardiovascular health, Crit. Rev. Food 

Sci. Nutr. 43 (2003) 1-18. 

- Woodall A. A., Britton G., Jackson M. J., Carotenoids and protection of phospholipids in 

solution or in liposomes against oxidation by peroxyl radicals: relationship between carotenoid 

structure and protective ability, Biochim. Biophys. Acta 1336 (1997) 575-586. 

LYCOPENE and Antioxidant properties / protection of DNA 

Individual human intervention studies: 

- Briviba, K., Kulling, S.E., Moseneder, J., Watzl, B., Rechkemmer, G., Bub, A. 2004. Effects of 

supplementing a low-carotenoid diet with a tomato extract for 2 weeks on endogenous levels of 

DNA single strand breaks and immune functions in healthy non-smokers and smokers. 

Carcinogenesis 25: 2373-2378. 

- Porrini, M., Riso, P., Brusamolino, A., Berti, C., Guarnieri, S., Visioli, F. 2005. Daily intake of a 

formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and 

improves cellular antioxidant protection. British Journal of Nutrition 93: 93-99. 

- Stacewicz-Sapuntzakis, M., Bowen, P.E. 2005. The role of lycopene and tomato products in 

prostate health Biochimica Biophysica Acta 1740: 202-205. 

- Torbergsen, A.C., Collins, A.R. 2004. Recovery of human lymphocytes from oxidative DNA 

damage; the apparent enhancement of DNA repair by carotenoids is probably simply an 

antioxidant effect. European Journal of Nutrition 39: 80-85. 

- Zhao, X., Aldini, G., Johnson, E.J., Rasmussen, H., Kraemer, K., Woolf, H., Musaeus, N., 

Krinsky, N.I., Russell, R.M., Yeum, K.J. 2006. Modification of lymphocyte DNA damage by 

carotenoid supplementation in postmenopausal women. American Journal of Clinical Nutrition 

83: 163-169. 

Evidence from Review articles: 

- Astley, S.B., Elliott, R.M. 2005. How strong is the evidence that lycopene supplementation can 

modify biomarkers of oxidative damage and DNA repair in human lymphocytes? Journal of 

Nutrition 135: 2071-2073 

- Moller, P., Loft, S. 2006. Dietary antioxidants and beneficial effect on oxidatively damaged 

DNA. Free Radical Biology & Medicine 41 (3): 388-415. 

- Stahl, W., Sies, H. 2005. Bioactivity and protective effects of natural carotenoids. Biochimica 

Biophysica Acta 1740 (2): 101-107. 

Evidence from experimental studies: 

112 

112

- Matos, H.R., Marques, S.A., Gomes, O.F., Silva, A.A., Heimann, J.C., Di Mascio, P., Medeiros, 

M.H. 2006. Lycopene and beta-carotene protect in vivo iron-induced oxidative stress damage 

in rat prostate. Brazilian Journal of Medical and Biological Research 39(2): 203-210. 

- Pan, H., Na, L., Shi, G., Li, X. 2004. [Effect of lycopene on DNA oxidative damage of cells in 

rats] Article in Chinese. Wei Sheng Yan Jiu 33: 189-191. 

LYCOPENE and Heart health 

References for myocardial incidences 


- Bansal. Cardioprotective effect of lycopene in the experimental model of myocardial ischemiareperfusion 

injury. Mol and Cell Biochem, 2006. 

- Gomez-Aracena . Association between townail scandium levels and risk of acute myocardial 

infarction in European men: the EURAMIC and Heavy Metals Study. Toxicology and industrial 

health; 18: 353-360, 2002. 

- Hak, Stampfer MJ, Campos H: Plasma carotenoids and tocopherols and risk of myocardial 

infarction in a low-risk population of US male physicians. J Am Heart Association 108:802-807, 

2003. 

- Kohlmeier, Kark JD, Gomez-Gracia E: Lycopene and myocardial infarction risk in the 

EURAMIC study. Am J Epidemiol 146: 618-625, 1997. 

- Sesso. Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease 

in men. Am J Clin Nutr; 81:990-997, 2005. 

- Street. Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alphatocopherol 

risk factors for myocardial infarction? Circulation; 90: 1154-61, 1994. 

References for intima media thickness 


- Jacopo Gianetti, Roberto Pedrinelli, et al. Inverse association between carotid intima-media 

thickness and the antioxidant lycopene in atherosclerosis. Am Heart J 2002; 143:467-74. 

- Iribarren , Folsom AR, Jacobs DR: Association of serum vitamin levels, LDL susceptibility to 

oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. Arterioscler 

Thromb Basc Biol; 17:1171-1177, 1997. 

- Klipstein-Grobusch. Serum carotenoids and atherosclerosis the Rotterdam study. 

- 

Atherosclerosis 148:49-56, 2000. 

Osganian, Stampfer MJ, Rimm E: Dietary carotenoids and risk of coronary artery disease in 

women. Am J Clin Nutr 77:1390-1399, 2003. 

- Polidori, Savino K, Alunni G, et al (2002) Plasma lipophilic antioxidants and malondialdehyde in 

congestive heart failure patients: relationship to disease severity. Free Rad Biol Med; 32: 148- 

152, 2002. 

- Rissanen, Voutilainen S, Nyyssönen K: Low plasma lycopene concentration is associated with 

increased intima-media thickness of the carotid artery wall. Arterioscler Thromb Vasc Biol 

20:2677-2681, 2000. 

- Rissanen, Voutilainen S, Nyyssönen K: Low serum lycopene concentration is associated with 

an excess incidence of acute coronary events and stroke: the Kuopio ischaemic heart disease 

risk factor study Br J Nutr 85:749-754, 2001. 

113 

113

- Rissanen, Voutilainen S, Nyyssönen K: Serum lycopene concentrations and carotid 

atherosclerosis: the Kuopio ischaemic heart disease risk factor study. Am J Clin Nutr 77:133- 

138, 2003. 

References for cardio vascular health 


- Ito. Cardiovascular disease mortality and serum carotenoid levels: a Japanese populationbased 

follow-up study. J of Epidemiology 16:154-160, 2006. 

- Kristenson , Zieden B, Kucinskiene Z: Antioxidant state and mortality from coronary heart 

disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50. 

BMJ 314:629-633. 1997. 

- Rissanen, Voutilainen S, Nyyssönen K: Lycopene, atherosclerosis, and coronary heart 

disease. Exp Biol Med 227:900-907, 2002. 

- Rowley. Inflammation and vascular endothelial activation in an aboriginal population: 

relationships to coronary disease risk factors and nutritional markers. MJA; 178: 495-500, 

2003. 

- Sesso. Dietary lycopene, tomato-based food products and cardiovascular disease in women. J 

Nutr; 133: 2336-2341, 2003. 

- Sesso. Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease 

in women. Am J Clin Nutr; 79: 47-53, 2004. 


- Arab & Steck. Lycopene and cardiovascular disease. Am J Clin Nutr; 71 (Suppl): 1691-1695, 

2000. 

- Peto, Collins R, Gray R (1995) Large-scale randomized evidence: large simple trials and 

overviews of trials. J Clin Epidemiol; 48:23-40, 1995. 

- Rao. Lycopene, tomatoes, and the prevention of coronary heart disease. Exp Biol Med; 

227:908-913, 2002. 

References for antioxidant effect 


- Sanjiv Agarwal and A. Venketeshwer Rao. Tomato lycopene and low density lipoprotein 

oxidation: a human dietary intervention study. Lipids, Vol. 33, No. 10 (1998) (App 6-3 of 

dossier). 

- Rao V. & Agarwal S. Role of antioxidant lycopene in cancer and heart disease. J Am Coll of 

Nutr;19:563-569, 2000.. 

References for lipid peroxidation 

- Esterbauer. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. 

Free Radic Biol Med; 13: 341-390, 1992. 

- Fuhrman, Elis A, Aviram M: Hypocholesterolemic effect of lycopene and beta-carotene is 

related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in 

macrophage. Biochem Biophys Res Communic; 233: 658-662, 1997. 

- Kita . Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipemic 

rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci USA; 84: 5928- 

5931, 1987. 

- Rao V & Agarwal S. Effect of diet and smoking on serum lycopene and lipid peroxidation. Nutr 

Res;18: 713-721,2000. 

114 

114

- Rissanen T, Voutilainen S, Nyyssönen K: Low serum lycopene concentration is associated with 

an excess incidence of acute coronary events and stroke: the Kuopio ischaemic heart disease 

risk factor study Br J Nutr 85:749-754, 2001. 

- Steinberg. Antioxidant vitamin supplementation and lipid peroxidation in smokers. Am J Clin 

Nutr; 68: 319-27, 1989. 

- Steinberg. Beyond cholesterol: modifications of low-density lipoprotein that increase its 

atherogenicity. N Engl J Med; 320: 915-924, 1989. 

LYCOPENES FROM TOMATO JUICES and Antioxidant properties 

Monographs 

- P. Grolier, C. Leoni, M. Gerber, R. Bilton (Chairmen of the Commissions) (2000) The White 

Book Of The European Commission Concerted Action: The Antioxidants In Tomatoes And 

Tomato Products And Their Health Benefits 

- [No author listed] (2003) Lycopene monograph. Altern Med Rev 8(3):336-342. 


- Clinton SK (1998) Lycopene : chemistry, biology and implications for human health and 

diseases. Nutr Rev 56,2:35-51. 

- Blum A, Monir M, Wirsansky I, Ben-Arzi S. (2005) The beneficial effects of tomatoes. Eur J 

Intern Med. 16(6):402-4. 

- Van Den Berg H (1999) Carotenoids interactions. Nutr Rev 57(1):1-10. 

- Dagnelie PC, Schuurman AG, Goldbohm RA, Van den Brandt PA. (2004) Diet, anthropometric 

measures and prostate cancer risk: a review of prospective cohort and intervention studies. 

BJU Int. 93(8):1139-50. 

- Banhegyi G. Semmelweis Egyetem, Altalanos Orvostudomanyi Kar, Orvosi Vegytani, 

Molekularis (2005) Lycopene—a natural antioxidant. Orv Hetil.146(31):1621-4. [Article in 

Hungarian] 

- Lecerf JM.(2006) Tomate, lycopène et prévention cardiovasculaire. Phytothérapie, numéro : 

HS34-HS39. 


- Paetau I, Khachik F, Brown Eldl and al. (1998) Chronic ingestion of lycopene-rich tomato juice 

or lycopene supplements significantly increases plasma concentrations of lycopene and related 

tomato carotenoids in humans. Am J Clin Nutr 68:1187-95. 

- Iribarren C, Folsom AR, Jacobs JR and al. (1997) Association of serum vitamins levels, LDL 

susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A 

case control study. Aterioscler Thromb Vasc Biol 1771-7. 

- Klipstein-Grobusch K, Launer LJ, Geleijnse JM and al. (2000) Serum carotenoids and 

atheriosclerosis. The Rotterdam study. Atherosclerosis 148:49-56. 

- Rissanen T, Voutilainen S, Nyyssonen K and al. (2003) Serum lycopene concentrations and 

carotid atherosclerosis : the kuopio ischaemic heart disease risk factor study. Am J Clin Nutr 

77:133-8. 

- Schmidt R, Faazekas F, Hayn M and al. (1997) Risk factors for microangiopathy – related 

cerebral damage in the austrian prevention stroke study. J Neurol Sci 152:15-2. 

- Agarwal S, Rao AV (1998) Tomato lycopene and low density lipoprotein oxidation : a human 

dietary intervention study. Lipids 33,10:981-3. 

115 

115


- D’orico A, Martines D, Kiechl S and al. (2000) High plasma levels of alpha and beta-carotene 

are associated with a lower risk of atherosclerosis : results from the Bruneck study. 

Atherosclerosis 153:231-9. 

- Rissanen T, Voutilainen S, Nyyssonen K and al. (2000) Low plasma lycopene concentration is 

associated with increased intima media thickness of the carotenoid artery wall. Aterioscler 

Thromb Vasc Biol 20:2677-81. 

- Rissanen T, Voutilainen S, Nyyssonen K and al. (2001) Low serum lycopene concentration is 

associated with an excess incidence of acute coronary events and stroke : the kuopio 

ischaemic heart. Risk Factor Study. Br J Nutr 85:749-54. 

- Street DA, Comstock GW, Salkeld RM and al. (1994) Serum antioxidants and myocardial 

infarction. Are low levels of carotenoids and alphatocopherol risk factors for myocardial 

infarction ? Circulation 90:1154-61. 

- Kohlmeier L, Kark JD, Gomez-Garcia E and al. (1997) Lycopene and myocardial infarction risk 

in the Euramic study. Am J Epidemiol 146:618-26. 

- Kristenson M, Zieden B, Kucinskiene Z and al. (1997) Antioxidant state and mortality from 

coronary heart disease in Lithuanian and Swedish men : concomitant cross sectional study of 

men aged 50. BMJ 314:629-33. 

- Gomez-Aracena J, Sloot SL, Garcia-Rodriguez A and al. (1997) Antioxidants in adipose tissue 

and myocardial infarction in a Mediterranean area. The Euramic study in Malaga. Nutr Metab 

Cardiovasc Disease 7:376-382. 

- Giovannucci E, Ascherio A, Rimm EB and al. (1995) Intake of carotenoids and retinol in 

relation to risk of prostate cancer. J Natl Cancer Inst 87:1767-76. 

- Clinton SK (2005) Tomatoes or lycopene : a role in prostate carcinogenesis ? J Nut 

135:2057S-2059S. 

- Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC (2002) A prospective study of tomato 

products, lycopene and prostate cancer risk. J Natl Cancer Inst 94,5:391-399. 

LYSINE and Body tissues 


- Encyclopedia of Human Nutrition (1st Edition) p 334. Editors: M. J. Sadler, J. J. Strain, B. 

Caballero 

Reviews 

- Pellett PL, Ghosh S, Lysine fortification: past, present, and future. Food Nutr. Bull. 2004; 25: 

107-113 


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J. Nutr. 1958; 66: 501-513 

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J. Nutr. 1960; 70 : 176-186 

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infants.Am. J. Clin. Nutr. 1969; 22: 1459-1468 

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indices of the nutritional status of predominantly cereal-eating families in Pakistan. Food Nutr. 

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supplementation with lysine, as determined from nitrogen balance indices in human subjects. J. 

Nutr. 1949; 38: 331-343. 

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stress in family members in economically weak communities in Northwest Syria. Proc. Natl. 

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acids I. J. Nutr. 1958; 66: 458-499 

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MEDIUM CHAIN TRIGLYCERIDES (MCT) and Weight management 

Text books 

- Elmadfa/Leitzmann. Ernährung des Menschen (3. Auflage)Verlag Eugen Ulmer Stuttgart,1998: 

112 

- Hahn A. Nahrungsergänzungsmittel. Wiisenschaftliche Verlagsgesellschaft mbH Stuttgard, 

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306 

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fancy? Journal of Lipid Research 1996; 37: 708-726 

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Ernährungsumschau 2003; 50 (Heft 1): 4-8 

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prevention of obesity. J Nutr 2002; 132: 329-332 

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Am J Clin Nutr 2005; 81: 7-15 


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triacylglycerols. American Journal of Clinical Nutrition 1998; 67: 595-601 

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consuming low-to-moderate amounts of medium chain triglycerides: a dose-response study in 

a human respiratory chamber. Eur J Clin Nutr 1996;50:152-158 

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Fat Balances. J. Clin. Invest. 1985;76: 1019-1024 

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Metabolism 1989; Vol 38, No 7: 641-648 

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in Humans. Journal of Atherosclerosis and Thrombosis 2003: Vol. 10, No. 5; 290-298 

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with medium-chain and long-chain triglycerides. Am J Clin Nutr 1991;53:1130-3. 

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1986;44:630-4. 

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Adiposity in Overweight Men. Obesity Research 2003; 11: 395-402 

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isoenergetically dense diets: effect on food intake in ad libitum feeding men. International 

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Double-Blind, Controlled Trial in Healthy Men and Women. American Society for Nutritional 

Sciences 2001; 2853-2859 

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food intake in men. American Journal of Clinical Nutrition 1998; 68: 226-234 

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attenuated after 14 d in premenopausal women. American Journal of Clinical Nutrition 1999; 

69: 883-889 

METHIONINE and Lipid metabolism 


- Borschel MW, Baggs GE, Cysteine and Methionine intakes associated with normal growth of 

healthy term infants fed casein hydrolyzate. FASEB J. 1998; 12: A848 

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polyarthrite rhumatoide. Rev. Rhum. Mal. Osteoartic 1988; 55: 995-997 

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to changes in sulfur amino acid intakes. J. Nutr. 2003; 133: 733-9 

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infants. Am. J.Clin. Nutr. 1979; 32: 2460- 2471 

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amino acids beyond protein. J. Nutr. 2006; 136: 1676S-1681S 

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79: 6-16 

Raguso C, Regan MM, Young VR, Cysteine kinetics and oxidation at different intakes of 

methionine and cystine in young adults. Am J. Clin. Nutr. 2000; 71: 491-499 

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NUCLEOTIDES and Immune health 

Review 

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Animal study 

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Pellis NR. Nutrition beyond nutrition: plausibility of immunotrophic nutrition for space travel. Clin 

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In vitro study 

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PAPAIN and Immune health 



Pharmaceutical Press, London (amylase 1675, bromelains 1681, chymotrypsin 1689 – 1690, 

papain 1738, trypsin 1763) 



532-537. 








119 

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Appl. Ther. 6 (1964), 323-325 

- Vallis,C.P., Lund,M.H.: Effect of treatment with Carica Papaya on re¬solution of edema and 

ecchymosis following rhinoplasty. Curr. therap. Res. 11 (1969) 356-359 

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PHENYLALANINE and Mental health 

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(1): 64-71; Feb (2000) 

- Fugh-Berman A, Cott JM. Dietary supplements and natural products as psychotherapeutic 

agents. Psychosom Med. 61 (5): 712-28; Sep-Out (1999) 


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of depression. 

J Neural Transm. 1984;59(1):81-7. 

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phenylalanine by schizophrenic patients, Neuropsychopharmacology. 1997 Feb;16(2):136-46 

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(1985) 

PHOSPHATIDYL CHOLINE / LECITHIN and Cholesterol / Heart health 

Overviews 

- Bonacker, Ursula, The significance of phosphatidylcholine for the lipid metabolism. Lucas 

Meyer Brochure, 1988 

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low-density lipoproteins. Biochim Biophys Acta, Vol. 751261:270, 1983 

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Diet 31,5Nutr, 1996 

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in normolipidemic subjects. Metab, Vol. Clin. Exp.42:13, 1993 

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rats by stimulation of biliary lipid secretion. BRITISH JOURNAL OF NUTRITION, Vol. 

75471:481, 1996 

- Hamada, Tadateru, Ikeda, Ikuo, Takashima, Kayoko, Kobayashi, Makoto, Kodama, Yoko, 

Inoue, Takashi, Matsuoka, Ryosuke, and Imaizumi, Katsumi, Hydrolysis of micellar 

phosphatidylcholine accelerates cholesterol absorption in rats and Caco-2 cells. Bioscience, 

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phosphatidylcholinein rabbits with heritable hypercholesterolemia. Artery, Vol. 22, Iss. 11, 1:23, 

1996 

- Jimenez, M. A., Scarino, M. L., Vignolini, F., and Mengheri, E., Evidence that polyunsaturated 

lecithin induces a reduction in plasma cholesterol level and favorable changes in lipoprotein 

composition in hypercholesterolemic rats. Journal of Nutrition, Vol. 120, Iss. 7, 659:667, 1990 

- Jonas, Ana, Lecithin cholesterol acyltransferase. Biochim Biophys Acta, Vol. 1529245:256, 

2000 

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of cholesterol and triglycerides in hypertriglyceridemic patients. American Journal of Clinical 

Nutrition, Vol. 4398:107, 1986 

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- Mastellone, I., Polichetti, E., Gres, S., de la Maisonneuve, C., Domingo, N., Marin, V., Lorec, 

A.-M., Farnarier, C., Portugal, Henri, Kaplanski, G., and Chanussot, Francoise, Dietary 

soybean phosphatidylcholines lower lipidemia: mechanisms at the levels of intestine, 

endothelial cell, and hepato-biliary axis. The Journal of nutritional biochemistry, Vol. 11, Iss. 9, 

461:466, 2000 

- Nagao, K. and Yamagita, T., Physiological Functions of Phospholipids. J Oleo Sci, Vol. 2, Iss. 

129, 2002 

- Plaskett, Phospholipids and the blood cholesterol. Lucas Meyer brochure, 1999 

- Polichetti, Diaconescu de La Porte Malli Portugal Pauli Lafont Tuchweber, Cholesterol-lowering 

effect of soyabean lecithin in normolipidaemic rats by stimulation of biliary lipid secretion. 

British Journal Of Nutrition, Vol. 75, Iss. 3, 471:481, 1996 

- Polichetti, E., Janisson, A., Lechene de la Porte, P., Portugal, Henri, Leonardi, Jeannie, Luna, 

A., La Droitte, P., and Chanussot, Francoise, Dietary polyenylphosphatidylcholine decreases 

cholesterolemia in hypercholesterolemic rabbits: role of the hepato-biliary axis. Life Sciences, 

Vol. 67, Iss. 21, 2563:2576, 2000 

- Polichetti, Janisson Iovanna Portugal Mekki Lorec Pauli Luna Lairon, Stimulation of the apo AIhigh 

density lipoprotein system by dietary soyabean lecithin in humans. J Nutr Biochem 9 659- 

664Nutr:664, 1998 

- Tsimikas, Sotirios, Brilakis, E. S., Miller, E. R., McConnell, J. P., Lennon, R. J., Kornman, K. S., 

Witztum, J. L., and Berger, P. B., Oxidized phospholipids, Lp(a) Lipoprotein and coronary 

artery disease. New England Journal of Medicine, Vol. 35346:57, 2005 

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Vol 9, 597-599Research, Vol:599, 1995 

- Wilson, Meservey, Soy lecithin reduces plasma lipoprotein cholesterol and early atherogenesis 

in hypercholesterolemic monkeys and hamsters: beyond linoleate. Atherosclerosis 140, 147- 

153, Vol. 140147:153, 1998 

PHOSPHATIDYL CHOLINE / LECITHIN and Cognitive function 


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dietary choline availability alters mitosis, apoptosis and the localization of TOAD-64 protein in 

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D. and Cacabelos, R. (1997). "Citicoline improves memory performance in elderly subjects." 

Methods Find Exp Clin PharmacoI19(3): 201-10. 

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prevention of impairment of memory function after electric convulsive therapy. A double- blind 

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- Blusztajn, J. K., Holbrook, P. G., Lakher, M., Liscovitch, M., Maire, J. C., Mauron, C., 

Richardson, U. I., Tacconi, M. and Wurtman, R. J. (1986). ""Autocannibalism" of membrane 

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221(4611): 614-620. 

- Brinkman, S. D., Smith, R. C., Meyer, J. S., Vroulis, G., Shaw, T., Gordon, J. R. and Allen, R. 

H. (1982). "Lecithin and memory training in suspected Alzheimer's disease." J Gerontol 37(1): 

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399-403. 

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double-blind, placebo-controlled multicenter study on efficiency of phosphatidylserine 

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Cennak, J. M., Blusztajn, J. K., Meck, W. H., Williarns, C. L., Fitzgerald, C. M., Rosene, D. L. 

and Loy, R. (1999). "Prenatal availability of choline alters the development of 

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acetylcholinesterase in the rat hippocampus." Dev Neurosci 21(2): 94-104. 

Chatellier, G. and Lacomblez, L. (1990). "Tacrine (tetrahydroaminoacridine; THA) and lecithin 

in senile dementia of the Alzheimer type: a multicentre trial. Groupe Francais d'Etude de la 

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- Cohen, B. M., Renshaw, P. F., Stoll, A. L., Wurtman, R. J., Yurgelun-Todd, D. and Babb, S. M. 

(1995). "Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance 

spectroscopy study." JAMA 274: 902-7. 

- Cohen, E. L. and Wurtman, R. J. (1975). "Brain acetylcholine: increase after systemic choline 

administration." Life Sci.16(7): 1095-102. 

- Cornford, E. M., Braun, L. D. and Oldendorf, W. H. (1978). "Carrier mediated blood-brain 

barrier transport of choline and certain choline analogs." J. Neurochem. 30(2): 299-308. 

- Corona, G. L., Cucchi, M. L., Frattini, P., Santagostino, G., Schinelli, S., Romani, A., Pola, A., 

Zerbi, F. and Savoldi, F. (1989). "Clinical and biochemical responses to therapy in Alzheimer's 

disease and multi-infarct dementia." Eur Arch Psvchiatrv Neurol Sci 239(2): 79-86. 

- Crook TH, Tinklenberg, Yesavage J, Petrie W, Nunzi MG, Massari DC Effects of 

phosphatidylserine in age-associated memory impairment. Neurology 1991;41(5):644-9. 

- Dani, S., Hori, A. and Walter, G., Eds. (1997). Principals of neural aging. Amsterdarn, Elsevier. 

- Davis, K. L., Mohs, R. C., Tinklenberg, J. R., Hollister, L. E., Pfefferbaum, A. and Kopell, B. S. 

(1980). "Cholinomimetics and memory. The effect of choline chloride." Arch. Neurol. 37(1): 49- 

52. 

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- Drachman, D. A., Glosser, G., Fleming, P. and Longenecker, G. (1982). "Memory decline in the 

aged: treatment with lecithin and physostigmine." Neurology 32(9): 944-50. 

- Duffy, F. H., McAnulty, G., Albert, M., Dwwen, H. and Weintraub, S. (1987). "Lecithin: absence 

of neurophysiologic effect in Alzheimer's disease by EEG topography." Neurology 37(6): 1015- 

9. 

- Fitten, L. J., Perryman, K. M., Gross, P. L.t Finet H., Cummins, J. and Marshallt C. (1990). 

"Treatment of Alzheimer's disease with short- and long-term oral THA and lecithin: a doubleblind 

study [see comments].tt Am J Psvchiatry 147(2): 239-42. 

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Rattan, P. (1980). "Choline bitartrate treatment of Alzheimer-type dementias." Commun 

PsvchonharmacoI 4(2): 141-5. 

- Garrow, T. (2001) Choline and carnitine; in Bowman BA, Russel RM (eds): Present knowledge 

in Nutrition, 8th edition. Washington, DC, ILSI Press, chapter 25, pp 261-270. 

- Gauthier, S., Bouchard, R., Lamontagne, A., Bailey, P., Bergman, H., Ratner, J., Tesfaye, Y., 

Saint-Martin, M., Bacher, Y., Carrier, L. and et al. (1990). "Tetrahydroaminoacridine-lecithin 

combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a 

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1272-6. 

- Goldberg, E., Gerstman, L. J., Mattis, S., Hughes, J. E., Sirio, C. A. and Bilder, R. M., Jr. 

(1982). "Selective effects of cholinergic treatment on verbal memory in posttraumatic amnesia." 

I Clin NeuronsvchoI 4(3): 219-34. 

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lecithin in the treatment of Alzheimer's disease." Neurobiol Aging 7(4): 269-76. 

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in normal adults." American Journal of Psvchiatrv 140(8): 1010-2. 

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acetylcholine induced by choline or deanol." Life Sci.17(6): 975-980. 

- Heyman, A., Schmechel, D., Wilkinson, W., Rogers, H., Krishnan, R., Holloway, D., Schultz, K., 

Gwyther, L., Peoples, R., Utley, C. and et al. (1987). "Failure oflong term high-dose lecithin to 

retard progression of early- onset Alzheimer's disease." J Neural Transm SuPl2124: 279-86. 

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A population pharmacodynarnic analysis of five clinical trials." Eur J Clin PharmacoI47(1): 17- 

23. 

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rats increases hippocampal phospholipase D activity of the offspring." FASEB J 10(14): 1653- 

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- Institute of Medicine and National Academy of Sciences USA (1998). Dietarv reference intakes 

For folate, thiamine, riboflavin, niacin, vitamin B12, panthothenic acid, biotin, and choline. 

Washington D.C., National Academy Press. 

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therapy with lecithin and ergoloid mesylates für Alzheimer's disease." J Clin Psvchiatrv 47(5): 

249-51. 

- Jones, J. P., Meck, W., Williarns, C. L., Wilson, W. A. and Swartzwelder, H. S. (1999). "Choline 

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Res Dev Brain Res 118(1-2): 159-67. 

- Kaye, W. H., Sitaram, N., Weingartner, H., Ebert, M. H., Smallberg, S. and Gillin, J. C. (1982). 

"Modest facilitation on memory in dementia with combined lecithin and anticholinerestase 

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- Ladd, S. L., Sommer, S. A., LaBerge, S. and Toscano, W. (1993). "Effect of 

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- Levin, H. S. (1991). "Treatment of postconcussional symptoms with CDP-choline." J Neurol Sci 

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memory." Life Sciences 37(2): 193-7. 

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Indicidual studies – in vivo studies 

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POLYPHENOLS DERIVED FROM RED WINE and Antioxidant properties 


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POLYPHENOLS FROM RED WINE and Vascular functions 

Critical review 

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Antithrombotic effect of polyphenols in experimental models: a mechanism of reduced vascular 

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- De Gaetano G, Cerletti C; European project. FAIR CT 97 3261 Project participants. Wine and 

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Mechanisms – in vitro studies 

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POLYPHENOLS FROM TEA and Antioxidant properties 

Review 

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studies (review). Int J Oncol 8; 221-38. 

- Tijburg LBM (1997) Tea flavonoids and cardiovascular diseases a review. Crit Rev Food Sci. 

Nutr 37; 771-85. 


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power in humans. Nutr and Cancer; 34(1): 83-87. 

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15. 

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drugs with oxidative metabolism of arachidonic acid by human platelets and neutraphils. 

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- De Whalley, et al (1990) Flavonoids inhibit the oxidative modification of Low Density 

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tea infusions. J Agric Food Chem; 49 (11): 5340-7. 

144 

144

- Benzie FF, et al (1999) Consumption of green tea causes rapid increase in plasma antioxidant 

power in humans. Nutr and Cancer; 34(1): 83-87. 

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drugs with oxidative metabolism of arachidonic acid by human platelets and neutraphils. 

Biochemica at Biophysica Acta 835; 315-321. 

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Lipoproteins by macrophages. Biochem Pharmacol 39; 1743-1750. 

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PROTEIN HYDROLYSATE and Insulin secretion and blood sugar levels 

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- Luc J.C. van Loon Amino Acids as Pharmaco-Nutrients for the Treatment of Type 2 Diabetes 

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- Luc JC van Loon, Wim HM Saris, Hans Verhagen, and Anton JM Wagenmakers Plasma insulin 

responses after ingestion of different amino acid or protein mixtures with carbohydrate Am J 

Clin Nutr 72: 96–105 (2000) 

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Wim H.M. Saris, Hans A. Keizer. Amino acid ingestion strongly enhances insulin secretion in 

patients with long-term type-2 diabetes Diabetes Care 26:625–630, 2003 

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Menheere, Nicolaas Schaper, Wim HM Saris, and Luc JC van Loon. Co-ingestion of a protein 

hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in 

patients with type 2 diabetes Am J Clin Nutr 82:76–83 (2005) 

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Wim H. Saris, Anton J. Wagenmakers, and Luc J. van Loon Co-ingestion of a protein 

hydrolysate with or without additional leucine effectively reduces postprandial blood glucose 

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QUERCETIN and Antioxidative properties 




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metabolism. Arch Biochem Biophys. 2003 Sep 1;417(1):12-7. Review. 

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Aug;16(2):275-8. Review. 

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chemicals: a review of the literature. Int J Clin Pharmacol Ther. 2004 Sep;42(9):488-95. 

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2003 Sep;78(3 Suppl):570S-578S. Review. 

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Rev Nutr. 2002;22:19-34. Epub 2002 Jan 4. Review. 

- Sengupta A, Ghosh S, Bhattacharjee S. Allium vegetables in cancer prevention: an overview. 

Asian Pac J Cancer Prev. 2004 Jul-Sep;5(3):237-45. Review. 

- Terao J. Dietary flavonoids as antioxidants in vivo: conjugated metabolites of (-)-epicatechin 

and quercetin participate in antioxidative defense in blood plasma. J Med Invest. 1999 

Aug;46(3-4):159-68. Review. 

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2001;47(4):299-306. Review. Polish. 

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bioavailability] Vopr Pitan. 2004;73(6):43-8. Review. Russian. 

- Valenzuela A, Sanhueza J, Nieto S. Cholesterol oxidation: health hazard and the role of 

antioxidants in prevention. Biol Res. 2003;36(3-4):291-302. Review. 

- Vitaglione P, Morisco F, Caporaso N, Fogliano V. Dietary antioxidant compounds and liver 

health. Crit Rev Food Sci Nutr. 2004;44(7-8):575-86. Review. 

- Walle T, Walle UK, Halushka PV. Carbon dioxide is the major metabolite of quercetin in 

humans. J Nutr. 2001 Oct;131(10):2648-52. 

- Weisburger JH. Mechanisms of action of antioxidants as exemplified in vegetables, tomatoes 

and tea. Food Chem Toxicol. 1999 Sep-Oct;37(9-10):943-8. Review. 

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Free Radic Biol Med. 2004 Apr 1;36(7):838-49. Review. 

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of 93 intervention studies. Am J Clin Nutr. 2005 Jan;81(1 Suppl):243S-255S. Review. 

- Wiseman H. The bioavailability of non-nutrient plant factors: dietary flavonoids and phytooestrogens. 

Proc Nutr Soc. 1999 Feb;58(1):139-46. Review. 

- Woodman OL, Chan ECh. Vascular and anti-oxidant actions of flavonols and flavones. Clin 

Exp Pharmacol Physiol. 2004 Nov;31(11):786-90. Review. 


- Beatty ER, O'Reilly JD, England TG, McAnlis GT, Young IS, Geissler CA, Sanders TA, 

Wiseman H. Effect of dietary quercetin on oxidative DNA damage in healthy human subjects. 

Br J Nutr. 2000 Dec;84(6):919-25. 

- Choi JS, Choi BC, Choi KE. Effect of quercetin on the pharmacokinetics of oral cyclosporine. 

Am J Health Syst Pharm. 2004 Nov 15;61(22):2406-9. 

- DiCenzo R, Frerichs V, Larppanichpoonphol P, Predko L, Chen A, Reichman R, Morris M. 

Effect of quercetin on the plasma and intracellular concentrations of saquinavir in healthy 

adults. Pharmacotherapy. 2006 Sep;26(9):1255-61. 

- Dupuy J, Larrieu G, Sutra JF, Lespine A, Alvinerie M. Enhancement of moxidectin 

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- Erlund I, Kosonen T, Alfthan G, Maenpaa J, Perttunen K, Kenraali J, Parantainen J, Aro A. 

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Clin Pharmacol. 2000 Nov;56(8):545-53. 

- Erlund I, Marniemi J, Hakala P, Alfthan G, Meririnne E, Aro A. Consumption of black currants, 

lingonberries and bilberries increases serum quercetin concentrations. Eur J Clin Nutr. 2003 

Jan;57(1):37-42. 

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Derendorf H, Veit M. Pharmacokinetics and bioavailability of quercetin glycosides in humans. 

J Clin Pharmacol. 2001 May;41(5):492-9. 

- Hempel J, Pforte H, Raab B, Engst W, Bohm H, Jacobasch G. Flavonols and flavones of 

parsley cell suspension culture change the antioxidative capacity of plasma in rats. Nahrung. 

1999 Jun;43(3):201-4. 

- Hubbard GP, Wolffram S, de Vos R, Bovy A, Gibbins JM, Lovegrove JA. Ingestion of onion 

soup high in quercetin inhibits platelet aggregation and essential components of the collagenstimulated 

platelet activation pathway in man: a pilot study. Br J Nutr. 2006 Sep;96(3):482-8. 

- Kim KA, Park PW, Kim HK, Ha JM, Park JY. Effect of quercetin on the pharmacokinetics of 

rosiglitazone, a CYP2C8 substrate, in healthy subjects. J Clin Pharmacol. 2005 Aug;45(8):941- 

6. 

- MacRae HS, Mefferd KM. Dietary antioxidant supplementation combined with quercetin 

improves cycling time trial performance. Int J Sport Nutr Exerc Metab. 2006 Aug;16(4):405-19. 

- Morrow DM, Fitzsimmons PE, Chopra M, McGlynn H. Dietary supplementation with the antitumour 

promoter quercetin: its effects on matrix metalloproteinase gene regulation. Mutat Res. 

2001 Sep 1;480-481:269-76. 

- O'Reilly JD, Sanders TA, Wiseman H. Flavonoids protect against oxidative damage to LDL in 

vitro: use in selection of a flavonoid rich diet and relevance to LDL oxidation resistance ex 

vivo? Free Radic Res. 2000 Oct;33(4):419-26. 

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of fresh and stored lettuce (Lactuca sativa) on plasma total antioxidant capacity and antioxidant 

levels in human subjects. Br J Nutr. 2002 Dec;88(6):615-23. 

- Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category III chronic 

prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology. 1999 

Dec;54(6):960-3. 

- Young JF, Nielsen SE, Haraldsdottir J, Daneshvar B, Lauridsen ST, Knuthsen P, Crozier A, 

Sandstrom B, Dragsted LO. [Polyphenolic antioxidants in fruit juice. Urinary excretion and 

effects on biological markers for antioxidative status] Ugeskr Laeger. 2000 Mar 

6;162(10):1388-92. Danish. 


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8. 

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200Sep 1;480-481:269-76. 

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RED YEAST RICE and Cholesterol 

Peer - Rewiews : 

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16;74(22):2675-83 

- Joanna S. Thompson Coon, PhD, BSc (Hons); Edzard Ernst, MD, PhD, FRCP (Edin); Herbs 

for serum cholesterol reduction: a systematic view. J Fam Pract. 2003 Jun;52(6):468-78 

Letters : 

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Feb; 69(2):175-6; 

152 

152

- Heber D; Dietary supplement or drug? The case for cholestin. Am J Clin Nutr. 1999 Feb; 

69(2):175-6; Am J Clin Nutr. 1999 Feb; 69(2):231-6 

- Richard Havel ; Reply to D Heber Am J Clin Nutr.Vol. 70, No. 1, 106A-108, July 1999 

- Bliznakov EG; More on the Chinese red-yeast-rice supplement and its cholesterol-lowering 

effect. Am J Clin Nutr. 1999, Feb; 69(2): 231-6 


- Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL. Cholesterol-lowering effects of a 

proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999 Jul; 70(1):106-8; 

Am J Clin Nutr. 2000 Jan1 70(1):152-4 

- Cicero AF, Brancaleoni M, Laghi L, Donati F, Mino M. Antihyperlipidaemic effect of a Monascus 

purpureus brand dietary supplement on a large sample of subjects at low risk for 

cardiovascular disease: a pilot study. Complement Ther. Med. 2005 Dec; 13(4):273-8 E pub 

2005 Sep 9 

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hyperlipidemia. Eur J Endocrinol 2005 Nov;153(5):679-86 

- Ricky Y.K. Man, Edward G. Lynn, Filly Cheung, Patricia S.Y. Tsang and O Karmin. Cholestin 

inhibits cholesterol synthesis and secretion in hepatic cells (HepG2). Mol Cell 

Biochem. 2002 Apr; 233(1-2): 153-8 

- Zhaoping Li, Ph.D., M.D, Navindra P. Seeram, Ph.D., Rupo Lee, M.Sc, Gail Thames, B.A., 

Chayo Minutti, He-Jing Wang, M.P.H., M.D., David Heber, Ph.D., M.D. Plasma 

Clearance of Lovastatin Versus Chinese Red Yeast Rice in Healthy Volunteers . 

The Journal of Alternative and Complementary Medicine Dec 2005, Vol. 11, No. 6 : 1031 – 

1038 


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long-term Cholestin (Monascus purpureus-fermented rice, red yeast rice) in cholesterol fed 

rabbits. J Nutr Biochem 2003 Jun;14(6):314-8. 

Evidence of Tradition of use: 

- Traditional Chinese Medicine (TCM) Could Make „Health for One“ True 

- Dr.Junying Fu, The TCM Strategy Study Team, Institute of Scientic and Technical Information 

of China, Ministry and Science and Technology of China 

RYE GRASS POLLEN EXTRACT and Prostate health 

Systematic Reviews 

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of benign prostatic hyperplasia. BJU Int 1999, 85: 836-841. 

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[German] 

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[Japanese] 

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Hinyokika Kiyo 1986, 32: 135-141 

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hyperplasia. Clin Ther 1995, 17: 82-87. 

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Nephrol 1996, 28: 49-53. 

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benign prostatic hypertrophy. Hinyokika Kiyo 1985, 31: 739-746 

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In Vitro Studies 

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SILICA / SILICIOUS EARTH and Essential part of the connective tissues, skin and hair 

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Clinical trials : 

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Animal studies : 

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Meta-Analysis 

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Maturitas 2002; 42:173-185. 

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proposed health effects of phyto-oestrogen exposure and recommendations for future 

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women. Proc of the Nutr Soc 2006; 65:76-92. 

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Obstet Gynecol 2004; 104:824-836. 

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Crisafulli A, Marini H, Bitto A, Altavilla D, Squadrito G, Romeo A, Adamo EB, Marini R, D'Anna 

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a single soy meal in humans. Am J Clin Nutr 1998, 67:867-872. 

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preventing and treating chronic diseases Nov2005 

- Uesugi T, et al (2002) Beneficial Effects of Soybean Isoflavone Supplementation on Bone 

Metabolism and Serum Lipids in Postmenopausal Japanese Women: A Four-Week Study. 

Journal of the American College of Nutrition, 21: 97–102. 

- Ye YB, Tang XY, Verbruggen MA, Su YX. Soy isoflavones attenuate bone loss in early 

postmenopausal Chinese women : A single-blind randomized, placebo-controlled trial. Eur J 

Nutr 2006. 

- Zhang X, Shu XO, Li H, Yang G, Li Q, Gao YT, Zheng W. Prospective cohort study of soy food 

consumption and risk of bone fracture among postmenopausal women.Arch Intern Med. 2005 

Sep 12;165(16):1890-5. 

STANDARDISED POTATO EXTRACT and Satiety / Weight management / Promotion of CCK 

release 

Critical review 

- Liddle RA: Regulation of cholecystokinin secretion by intraluminal releasing factors. Am J 

Physiol 1995; 269(3 Pt 1): G319-27. 

- Ritter RC, Covasa M, Matson CA: Cholecystokinin: proofs and prospects for involvement in 

control of food intake and body weight. Neuropeptides 1999; 33(5): 387-99. 

- Ludwig DS: The glycemic index: physiological mechanisms relating to obesity, diabetes, and 

cardiovascular disease. Jama 2002; 287(18): 2414-23. 

- Crawley JN, Corwin RL: Biological actions of cholecystokinin. Peptides 1994; 15(4): 731-55. 

- Jensen RT: Involvement of cholecystokinin/gastrin-related peptides and their receptors in 

clinical gastrointestinal disorders. Pharmacology & toxicology 2002; 91(6): 333-50. 

- Halford JC, Blundell JE: Pharmacology of appetite suppression. Prog Drug Res 2000; 54: 25- 

58. 

- Phillips WT, Schwartz JG, McMahan CA: Reduced postprandial blood glucose levels in 

recently diagnosed non- insulin-dependent diabetics secondary to pharmacologically induced 

delayed gastric emptying. Dig Dis Sci 1993; 38(1): 51-8. 

160 

160


- Matson CA, Reid DF, Cannon TA, Ritter RC: Cholecystokinin and leptin act synergistically to 

reduce body weight. Am J Physiol Regul Integr Comp Physiol 2000; 278(4): R882-90. 

- Herzig KH, Schon I, Tatemoto K, et al.: Diazepam binding inhibitor is a potent cholecystokininreleasing 

peptide in the intestine. Proc Natl Acad Sci U S A 1996; 93(15): 7927-32. 

- Woods SC, Schwartz MW, Baskin DG, Seeley RJ: Food intake and the regulation of body 

weight. Annu Rev Psychol 2000; 51: 255-77. 

- Gibbs J, Falasco JD, McHugh PR: Cholecystokinin-decreased food intake in rhesus monkeys. 

Am J Physiol 1976; 230(1): 15-18. 

- McLaughlin CL, Peikin SR, Baile CA: Food intake response to modulation of secretion of 

cholecystokinin in Zucker rats. The American journal of physiology 1983; 244(5): R676-85. 

- Gumbmann MR, Dugan GM, Spangler WL, Baker EC, Rackis JJ: Pancreatic response in rats 

and mice to trypsin inhibitors from soy and potato after short- and long-term dietary exposure. J 

Nutr 1989; 119(11): 1598-609. 

Evidence from individual references - Human studies 

- Hill AJ, Peikin SR, Ryan CA, Blundell JE: Oral administration of proteinase inhibitor II from 

potatoes reduces energy intake in man. Physiol Behav 1990; 48(2): 241-6. 

- Wolever TM, Jenkins DJ, Vuksan V, Jenkins AL, Wong GS, Josse RG: Beneficial effect of lowglycemic 

index diet in overweight NIDDM subjects. Diabetes care 1992; 15(4): 562-4. 

- Melton PM, Kissileff HR, Pi-Sunyer FX: Cholecystokinin (CCK-8) affects gastric pressure and 

ratings of hunger and fullness in women. The American journal of physiology 1992; 263(2 Pt 2): 

R452-6. 

- Peikin SR, Springer CJ, Dockray GJ, et. al.: Oral administration of protease inhibitor potato II 

stimulates the release of cholecystokinin in man (Abstract). Gastroenterology 1987; 92: A1570. 

- Vasselli JR, Greenfield D, Schwartz L, Heymsfield SB: Protease inhibitor from potatoes 

decreases hunger and increases fullness in overweight subjects following a meal (Abstract). 

North American Association for the study of obesity (NAASO) Annual Meeting, 1999. 

- Gutzwiller JP, Drewe J, Ketterer S, Hildebrand P, Krautheim A, Beglinger C: Interaction 

between CCK and a preload on reduction of food intake is mediated by CCK-A receptors in 

humans. Am J Physiol Regul Integr Comp Physiol 2000; 279(1): R189-95. 

- Miyasaka K, Funakoshi A: Luminal feedback regulation, monitor peptide, CCK-releasing 

peptide, and CCK receptors. Pancreas 1998; 16(3): 277-83. 

- Liddle RA: Regulation of cholecystokinin secretion in humans. J Gastroenterol 2000; 35(3): 

181-7. 

- Spreadbury D, Shao A, Essman M, Sheabar FS, Geletta S, Larsen B: A proteinase inhibitor 

extract from potatoes reduces post-prandial blood glucose in human subjects. JANA 2003; 6: 

29-38. 

- Owyang C: Discovery of a cholecystokinin-releasing peptide: biochemical characterization and 

physiological implications. Chin J Physiol 1999; 42(3): 113-20. 

- Schwartz JG, Guan D, Green GM, Phillips WT: Treatment with an oral proteinase inhibitor 

slows gastric emptying and acutely reduces glucose and insulin levels after a liquid meal in 

type II diabetic patients. Diabetes Care 1994; 17(4): 255-62. 

- Spiegel TA, Hubert C, Peikin SR: Effect of a premeal beverage containing a protease inhibitor 

from potatoes on satiety in dieting overweight women (Abstract). North American Association 

for the Study of Obesity (NAASO) Annual Meeting, 1999. 

161 

161

- Liddle RA, Rushakoff RJ, Morita ET, Beccaria L, Carter JD, Goldfine ID: Physiological role for 

cholecystokinin in reducing postprandial hyperglycemia in humans. The Journal of clinical 

investigation 1988; 81(6): 1675-81. 

- Dana S: An open label phase II study of Satise for appetite control and weight loss. Kemin 

Health Technical Literature KCCTL-012-006, KCCBB-012-002 2005. 

- Hu J, Dana S, Radosevich J: A randomized, double-blind, placebo-controlled clinical study 

demonstrates proteinase inhibitor II is a safe and effective tool for promoting weight reduction. 

Kemin Health Technical Literature 2004. 

STEARIC ACID and Lipid metabolism 

Monographs: 

- Joint WHO/FAO Expert Consultation (2003). Diet, Nutrition and the Prevention of Chronic 

Diseases, World Health Organization, Geneva. WHO Technical Report Series 916, pp. 147- 

148 (2003). 

- Total and LDL cholesterol levels. Institute of Medicine (2002). Dietary Reference Intakes for 

Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids 

(Macronutrients) , Chapter 8, National Academy Press, Washington, D.C. , p. 483 


- Kris-Etherton PM, Mustad VA (1994). Chocolate feeding studies: a novel approach for 

evaluating the plasma lipid effects of stearic acid. Am. J. Clin. Nutr. 60(Suppl.): 1029S – 36S. 

- Kris-Etherton PM, Yu S. Am J Clin Nutr. 1997 Individual fatty acid effects on plasma lipids and 

lipoproteins: human studies. May;65(5 Suppl):1628S-1644S 

- Kris-Etherton PM, Griel AE, Psota TL, Gebauer SK, Zhang J, Etherton TD (2005) Dietary 

stearic acid and risk of cardiovascular disease: intake, sources, digestion, and absorption. 

Lipids.;40:1193-2000.. 

- Mensink RP , Effects of stearic acid on plasma lipid and lipoproteins in humans. Lipids. 2005 

40(12):1201-5. 


- Yu S., et al. (1995) Plasma cholesterol-predictive equations demonstrate that stearic acid is 

neutral and monounsaturated fatty acids are hypocholesterolemic. Am. J. Clin. Nutr., 61 : 1129 

- 1139. 

- Tholstrup T et al. (1994) Fat High in Stearic Acid Favorably Affects Blood Lipids and Factor 

- Thijssen M.A., Mensink R.P. (2005). Small differences in the effects of stearic acid, oleic acid, 

and linoleic acid on the serum lipoprotein profile of humans. Am. J. Clin. Nutr., 82(3): 510-516. 

- Bonanome A & Grundy SM (1988). Effect of dietary stearic acid on plasma cholesterol and 

lipoprotein levels. New Eng. J. Med. 318: 1244-1248. 

- Grande, F, Anderson, JT, Keys A. (1970). Comparison of Effects of Palmitic and Stearic Acids 

in the Diet on Serum Cholesterol in Man. Am J. Clin. Nutr. 23 1184-1193 

- Denke, MA and Grundy SM (1991). Effects of fats high in stearic acid on lipid and lipoprotein 

concentrations in men Am. J. Clin. Nutr. 54 1036-1040. 

STEROLS / STANOLS AND THEIR ESTERS and Heart health and artery health because of 

LDL cholesterol loweringh 

Note: where conditions of use are recommended these are given after the reference 

162 

162


- AHA. Diet and lifestyle recommendations revision 2006: a scientific statement from the 

American Heart Association Nutrition Committee.. Lichtenstein AH et al. Circulation 2006; 114: 

82-96 [Recommend 2g Sterols/Stanols per day] 

- Australia – New Zealand. National Heart Foundation of Australia, Cardiac Society of Australia 

and New Zealand, Australian Atherosclerosis Society, National Stroke Foundation, Internal 

Medicine Society of Australia and New Zealand, The Royal Australian College of General 

Practitioners. The Medical Journal of Australia 2001, volume 175, supplement 

- 

http://www.heartfoundation.com.au/downloads/Guideline_Lipid_Mgt_2001.pdf [Recommend 2- 

3g Sterols per day] 

EU Regulation 608/2004 concerning the labelling of foods and food ingredients with added 

phytosterols, phytosterol esters, phytostanols and/or phytostanol esters. [For food labelling 

purposes up to 3 g Sterols/Stanols may be provided per portion or per 3 portions. NOTE This is 

a regulatory requirement and not a recommended level of intake] 

- FDA (2000). 21 CFR Part 101. Food labelling: health claims; plant sterol/stanol esters and 

coronary heart diseases. Federal Register: September 8, 2000 (Volume 65, Number 175); also 

FDA Letter of Discretion http://www.cfsan.fda.gov/~dms/ds-ltr30.html [Approved 800mg free 

phytosterols per day] 

- Flemish Dietetic Association. Intervention protocol for dyslipidemia published by the VVVD 

(Flemish Dietetic Association), 2002 [Recommend 2-3g Sterols/Stanols per day] 

- International Atherosclerosis Society Executive Board (IAS). International Atherosclerosis 

Society Harmonised Clinical Guidelines on Prevention of Atherosclerotic Vascular Disease. 

March 2003. [Recommend 2g Sterols/Stanols per day] 

- JHCI 2005 Approval of product specific claim in relation to plant sterols and blood cholesterol 

“Consuming 1.6g of plant sterols per day, as part of a healthy diet and lifestyle, is proven to 

help lower blood cholesterol” [Approved 1.6g sterols/stanols per day] 

- NCEP. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in 

Adults Executive Summary of the Third Report of the National Cholesterol Education Program 

(NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in 

Adults (Adult Treatment Panel III) JAMA, May 2001; 285: 2486 - 2497.[Recommend 2g 

Sterols/Stanols per day ] 

- SCF (Scientific Committee on Food) (2002). General view on the long-term effects of the intake 

of elevated levels of phytosterols from multiple dietary sources, with particular attention to the 

effects on β-carotene. Opinion adopted by the SCF on 26 September 2002. [opinion that 1-3g 

Sterols/Stanols per day was effective] 

- Swedish Nutrition Foundation. Product specific claims. 

- Voedingscentrum. Product specific claims. 

Meta-Analysis 

- Martijn B. Katan, Scott M. Grundy, Peter Jones, Malcolm Law, Tatu Miettinen and Rodolfo 

Paoletti, for the Stresa Workshop Participants. Efficacy and Safety of Plant Stanols and Sterols 

in the Management of Blood Cholesterol Levels Mayo Clin Proc. 2003;78:965-978. [Metaanalysis 

suggests 2g per day for 10% lowering of LDL cholesterol] 

TROXERUTIN and Vascular health 

Review 

- Bylka W, Kornobis J. Butcher's Broom, in the treatment of venous insufficiency. Pol Merkur 

Lekarski. 2005 Aug;19(110):234-6. 

163 

163

- Parodi MB. Medical treatment of retinal vein occlusions. Semin Ophthalmol. 2004 Mar- 

Jun;19(1-2):43-8. 

Human studies 

- Auteri A, Blardi P, Frigerio C, de Lillo L, di Perri T. Pharmacodynamics of troxerutine in patients 

with chronic venous insufficiency: correlations with plasma drug levels. Int J Clin Pharmacol 

Res. 1990;10(4):235-41. 

- Boisseau MR, Taccoen A, Garreau C, Vergnes C, Roudaut MF, Garreau-Gomez B. Fibrinolysis 

and hemorheology in chronic venous insufficiency: a double blind study of troxerutin efficiency. 

J Cardiovasc Surg (Torino). 1995 Aug;36(4):369-74. 

- Riccioni C, Sarcinella R, Izzo A, Palermo G, Liguori M. Effectiveness of Troxerutin in 

association with Pycnogenol in the pharmacological treatment of venous insufficiency. Minerva 

Cardioangiol. 2004 Feb;52(1):43-8. 

- Sumboonnanonda K, Lertsithichai P. Clinical study of the Ginko biloba-Troxerutin-Heptaminol 

Hce in the treatment of acute hemorrhoidal attacks. J Med Assoc Thai. 2004 Feb;87(2):137-42. 

- Carlsson K, Patwardhan A, Poullain JC, Gerentes I. Transport and localization of troxerutin in 

the venous wall. J Mal Vasc. 1996;21 Suppl C:270-4. 

- Patwardhan A, Carlsson K, Poullain JC, Taccoen A, Gerentes I. The affinity of troxerutin for the 

venous wall measured by laser scanning microscopy. J Cardiovasc Surg (Torino). 1995 

Aug;36(4):381-5. 

- Glacet-Bernard A, Coscas G, Chabanel A, Zourdani A, Lelong F, Samama MM. A randomized, 

double-masked study on the treatment of retinal vein occlusion with troxerutin. Am J 

Ophthalmol. 1994 Oct 15;118(4):421-9. 

- Lefebvre G, Lacombe C. Venous insufficiency in the pregnant woman. Rheological correction 

by troxerutin. Rev Fr Gynecol Obstet. 1991 Feb 25;86(2 Pt 2):206-8. 


- Krupinski K, Giedrojc J, Bielawiec M. Effect of troxerutin on laser-induced thrombus formation 

in rat mesenteric vessels, coagulation parameters and platelet function. Pol J Pharmacol. 1996 

May-Jun;48(3):335-9. 

- Adam BS, Pentz R, Siegers CP, Strubelt O, Tegtmeier M. Troxerutin protects the isolated 

perfused rat liver from a possible lipid peroxidation by coumarin. Phytomedicine. 2005 

Jan;12(1-2):52-61. 

ZEAXANTHIN and Eye health and vision 

References as to accumulation of zeaxanthin in the macula/ increase of Macular Pigment 

Optical Density 

Evidence from individual intervention studies 

- Aleman, T.S., Duncan J.L., Bieber M.L., et al., "Macular pigment and lutein supplementation in 

retinitis pigmentosa and Usher syndrome", Invest. Ophthalmol. Vis. Sci., 42 (8), 1873-1881 

(2001). 

- Berendschot, T.T., Goldbohm R.A., Klopping W.A., et al., "Influence of lutein supplementation 

on macular pigment, assessed with two objective techniques", Invest. Ophthalmol. Vis. Sci., 41 

(11), 3322-3326 (2000). 

- Bone, R.A., Landrum J.T., Guerra L.H., et al., "Lutein and zeaxanthin dietary supplements raise 

macular pigment density and serum concentrations of these carotenoids in humans", J. Nutr., 

133 (4), 992-998 (2003). 

164 

164

- Cardinault, N., Gorrand J., Tyssandier V., et al., "Short-term supplementation with lutein affects 

biomarkers of lutein status similarly in young and elderly subjects." Exp. Gerontol., 38 (5), 573- 

582 (2003). 

- Duncan, J.L., Aleman T.S., Gardner L.M., et al., "Macular pigment and lutein supplementation 

in choroideremia." Exp. Eye Res., 74 (3), 371-381 (2002). 

- Koepcke, W., Schalch W.and Group L.-S., "Changes in macular pigment optical density 

following repeated dosing with lutein, zeaxanthin, or their combination in healthy volunteers - 

results of the LUXEA-Study." ARVO 2005: Abstract Book on CDROM: Program#: 1765, (2005). 

- Koh, H.H., Murray I.J., Nolan D., et al., "Plasma and macular responses to lutein supplement in 

subjects with and without age-related maculopathy: a pilot study." Exp. Eye Res., 79 (1), 21-27 

(2004). 

- Liew, S.M., Gilbert C.E., Mellerio J., et al., "Effect of 6 Month Lutein Supplementation on 

Macular Pigment Levels, Measured by Two Methods, Fundus Autofluorescence & 

Heterochromatic Flicker Photometry", Invest. Ophthalmol. Vis. Sci., ARVO E-abstract 3794 

(2006) 

- Richer, S., Stiles W., Statkute L., et al., "Double-masked, placebo-controlled, randomized trial 

of lutein and antioxidant supplementation in the intervention of atrophic age-related macular 

degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial)." 

Optometry, 75 (4), 216-229 (2004). 

- Schweitzer, D., Lang G.E., Beuermann B., et al., "Objective determination of the optical density 

of xanthophyll after supplementation with lutein (original German title: "Objektive Bestimmung 

der optischen Dichte von Xanthophyll nach Supplementation von Lutein")", Ophthalmologe, 99 

270-275 (2002). 

- Trieschmann, M., Heimes B., Hense H.W., et al., "Macular Pigment: A Prospective 

Supplementation Study", Invest. Ophthalmol. Vis. Sci., ARVO E-abstract 2151 (2006). 

- Wenzel AJ, Gerweck C, Barbato D, Nicolosi RJ, Handelman GJ, Curran-Celentano J. A 12-wk 

egg intervention increases serum zeaxanthin and macular pigment optical density in women. J 

Nutr. 2006 Oct;136(10):2568-73 

- Yolton, D., DeRuyter B., Miller B., et al., "Failure of Oral Supplement Containing Lutein to 

Change Macular Pigment Density." Optometry and Vision Science, 79 (12), 104 (2002). 

References as to maintenance of eye health and vision in connection with AMD and ARD 


- Aleman, T.S., Duncan J.L., Bieber M.L., et al., "Macular pigment and lutein supplementation in 

retinitis pigmentosa and Usher syndrome", Invest. Ophthalmol. Vis. Sci., 42 (8), 1873-1881 

(2001). 

- Dagnelie, G., Zorge I.S.and McDonald T.M., "Lutein improves visual function in some patients 

with retinal degeneration: a pilot study via the Internet", Optometry, 71 (3), 147-164 (2000). 

- Delcourt C, Carriere I, Delage M, Barberger-Gateau P, Schalch W; POLA Study Group.Plasma 

lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related 

maculopathy and cataract: the POLA Study. Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2329- 

35 

- Duncan, J.L., Aleman T.S., Gardner L.M., et al., "Macular pigment and lutein supplementation 

in choroideremia." Exp. Eye Res., 74 (3), 371-381 (2002). 

- Falsini, B., Piccardi M., Iarossi G., et al., "Influence of short-term antioxidant supplementation 

on macular function in age-related maculopathy: a pilot study including electrophysiologic 

assessment." Ophthalmology, 110 (1), 51-60 (2003). 

165 

165

- Koh, H.H., Murray I.J., Nolan D., et al., "Plasma and macular responses to lutein supplement in 

subjects with and without age-related maculopathy: a pilot study." Exp. Eye Res., 79 (1), 21-27 

(2004). 

- Olmedilla, B., Granado F., Blanco I., et al., "Lutein, but not alpha-tocopherol, supplementation 

improves visual function in patients with age-related cataracts: a 2 year double-blind, placebocontrolled 

pilot study", Nutrition, 19 21-24 (2003). 

- Richer, S., Stiles W., Statkute L., et al., "Double-masked, placebo-controlled, randomized trial 

of lutein and antioxidant supplementation in the intervention of atrophic age-related macular 

degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial)." 

Optometry, 75 (4), 216-229 (2004) 

Other supportive evidence 

Monographs 

- [No authors listed] Lutein and zeaxanthin. Monograph. Altern Med Rev. 2005 Jun;10(2):128-35. 

Reviews 

- Ahmed, S.S., Lott M.N.and Marcus D.M., "The macular xanthophylls." Surv Ophthalmol., 50 

(2), 183-193 (2005). 

- Alves-Rodrigues, A.and Shao A., "The science behind lutein." Toxicol. Lett., 150 (1), 57-83 

(2004). 

- Comer, G.M., Ciulla T.A., Heier J.S., et al., "Future pharmacological treatment options for 

nonexudative and exudative age-related macular degeneration", Expert Opin Emerg Drugs, 10 

(1), 119-135 (2005). 

- Eter, N., Krohne T.U.and Holz F.G., "New pharmacologic approaches to therapy for agerelated 

macular degeneration", BioDrugs, 20 (3), 167-179 (2006). 

- Davies, N.P.and Morland A.B., "Macular pigments: their characteristics and putative role." 

Progress in Retinal and Eye Research, 23 (5), 533-559 (2004). 

- Granado, F., Olmedilla B.and Blanco I., "Nutritional and clinical relevance of lutein in human 

health." Br. J. Nutr., 90 (3), 487-502 (2003). 

- Krinsky, N.I., "Possible biologic mechanisms for a protective role of xanthophylls." J Nutr., 132 

(3), 540S-542S (2002). 

- Krinsky, N.I., Landrum J.T.and Bone R.A., "Biologic mechanisms of the protective role of lutein 

and zeaxanthin in the eye", Annu Rev Nutr., 23 171-201 (2003). 

- Krinsky, N.I.and Johnson E.J., "Carotenoid actions and their relation to health and disease." 

Mol Aspects Med., 26 (6), 459-516 (2005). 

- Stringham, J.M.and Hammond B.R.J., "Dietary lutein and zeaxanthin: possible effects on visual 

function." Nutr Rev., 63 (2), 59-64 (2005). 

- Whitehead, A.J., Mares J.A.and Danis R.P., "Macular pigment: a review of current knowledge", 

Arch Ophthalmol, 124 (7), 1038-1045 (2006). 

- Young, A.J.and Lowe G.M., "Antioxidant and prooxidant properties of carotenoids." Arch. 

Biochem. Biophys., 385 (1), 20-27 (2001) 

Other evidence in alphabetical order 

- Barker, F.M., Neuringer M., Johnson E.J., et al., "Dietary Zeaxanthin or Lutein Improves Foveal 

Photo-protection From Blue Light in Xanthopyhll-free Monkeys", ARVO 2005: Abstract Book on 

CDROM: Program#: 1770, (2005). 

166 

166

- Beatty, S., Murray I.J., Henson D.B., et al., "Macular pigment and risk for age-related macular 

degeneration in subjects from a Northern European population", Invest. Ophthalmol. Vis. Sci., 

42 (2), 439-446 (2001). 

- Bernstein, P.S., Khachik F., Carvalho L.S., et al., "Identification and quantitation of carotenoids 

and their metabolites in the tissues of the human eye", Exp. Eye Res., 72 (3), 215-223 (2001). 

- Bernstein, P.S., Zhao D.Y., Wintch S.W., et al., "Resonance Raman measurement of macular 

carotenoids in normal subjects and in age-related macular degeneration patients." 

Ophthalmology, 109 (10), 1780-1787 (2002). 

- Bone, R.A., Landrum J.T.and Tarsis S.L., "Preliminary identification of the human macular 

pigment", Vis. Res., 25 (11), 1531-1535 (1985). 

- Bone, R.A., Landrum J.T., Fernandez L., et al., "Analysis of the macular pigment by HPLC: 

retinal distribution and age study", Invest. Ophthalmol. Vis. Sci., 29 (6), 843-849 (1988). 

- Bone, R.A., Landrum J.T., Friedes L.M., et al., "Distribution of lutein and zeaxanthin 

stereoisomers in the human retina", Exp. Eye Res., 64 211-218 (1997). 

- Bone, R.A., Landrum J.T., Mayne S.T., et al., "Macular pigment in donor eyes with and without 

AMD: a case-control study", Invest. Ophthalmol. Vis. Sci., 42 (1), 235-242 (2001). 

- Chylack, L.T., Jr., Brown N.P., Bron A., et al., "The Roche European American Cataract Trial 

(REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant 

micronutrient mixture to slow progression of age-related cataract", Ophthalmic Epidemiology, 9 

(1), 49-80 (2002). 

- Congdon, N., Vingerling J.R., Klein B.E., et al., "Prevalence of cataract and 

- 

pseudophakia/aphakia among adults in the United States." Arch Ophthalmol, 122 (4), 487-494 

(2004). 

Davies, N.P.and Morland A.B., "Macular pigments: their characteristics and putative role." 

Progress in Retinal and Eye Research, 23 (5), 533-559 (2004). 

- Dorey, K.C., Granata L., Nichols C.R., et al., "Dietary modulation of lens zeaxanthin in quail." 

Exp. Eye Res., 81 464-477 (2005). 

- EDCC Study Group, "Antioxidant status and neovascular age-related macular degeneration", 

Arch. Ophthalmol., 111 104-109 (1993). 

- Fite, K.V., Bengston C.L.and Cousins F., "Drusen-like deposits in the outer retina of Japanese 

quail", Exp. Eye Res., 59 417-424 (1994). 

- Fletcher, A.E.and EUREYE S.G., "Sunlight Exposure, Antioxidants and AMD in a European 

Population: the EUREYE Study", ARVO Summer Eye Research Conference: toward the 

prevention of AMD, Ft. Myers, Jul 9-12, 2006; Abstracts at 

- 

http://www.arvo.org/eweb/startpage.aspx?site=serc; Presentation Number: 12, Abstracts online 

at http://www.arvo.org/, (2006). 

Friedman, D.S., O'Colmain B.J., Munoz B., et al., "Prevalence of age-related macular 

degeneration in the United States." Arch Ophthalmol., 122 (4), 564-572 (2004). 

- Gale, C.R., Hall N.F., Phillips D.I.W., et al., "Lutein and Zeaxanthin Status and Risk of Age- 

Related Macular Degeneration." Invest. Ophthalmol. Vis. Sci., 44 (6), 2461-2465 (2003). 

- Gass, J.D.M., "Müller cell cone, an overlooked part of the anatomy of the fovea centralis", Arch. 

Ophthalmol., 117 821-823 (1999). 

- Goralczyk, R., Barker F.M., Froescheis O., et al., "Ocular safety of lutein and zeaxanthin in a 

long-term study in cynomolgous monkeys", ARVO 2002, Abstracts Volume #1 Program # 2546 

(2002). 

- Gruszecki, W.I.and Strzalka K., "Carotenoids as modulators of lipid membrane physical 

properties." Biochim Biophys Acta, 1740 (2), 108-115 (2005). 

167 

167

- Hammond, B.R., Johnson E.J., Russell R.M., et al., "Dietary modification of human macular 

pigment density", Invest. Ophthalmol. Vis. Sci., 38 (9), 1795-1801 (1997). 

- Hammond, B.R., Wooten B.R.and Snodderly D.M., "Individual variations in the spatial profile of 

human macular pigment", J. Opt. Soc. Am., A 14 (6), 1187-1196 (1997). 

- Hammond, B.R., Jr., Wooten B.R.and Curran-Celentano J., "Carotenoids in the retina and lens: 

possible acute and chronic effects on human visual performance", Arch. Biochem. Biophys., 

385 (1), 41-46 (2001). 

- Handelman, G.J., Dratz E.A., Reay C.C., et al., "Carotenoids in the human macula and whole 

retina", Invest. Ophthalmol. Vis. Sci., 29 (6), 850-855 (1988). 

- Hart, W.M., "Adler's physiology of the eye." Ninth Edition, Mosby, St. Louis, Hart, W.M. editor 

(1992). 

- Hartmann, D., Thürmann P.A., Spitzer V., et al., "Plasma kinetics of zeaxanthin and 3'dehydro-lutein 

after multiple oral doses of synthetic zeaxanthin", Am. J. Clin. Nutr., 79 (3), 410- 

417 (2004). 

- Hope, G.M., Dawson W.W., Engel H.M., et al., "A primate model for age-related macular 

drusen", Br. J. Ophthalmol., 76 11-16 (1992). 

- Huang, K.C., "The pharmacology of chinese herbs", CRC Press, New York, 221-215 (1993). 

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