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As already described, almost any carbohydrate that reaches the large bowel will provide a substrate for the commensal microbiota, and will affect its growth and metabolic activities. This has been shown for NSP (Stephen and Cummings, 1980), and will occur with other substrates such as RS, sugar alcohols and lactose. However, stimulation of growth by these carbohydrates is a nonspecific, generalized effect, that probably involves many of the major saccharolytic groups, and associated cross-feeding species in the large bowel (Macfarlane and Cummings, 1991). The selective properties of prebiotics relate to the growth of bifidobacteria and lactobacilli at the expense of other groups of bacteria in the gut, such as bacteroides, clostridia, eubacteria, enterobacteria, enterococci, and so on. In practice, studies show that such selectivity is variable, and the extent to which changes in the microbiota allow a substance to be called prebiotic have not been established. There are also qualitative aspects of the concept of selectivity. Some investigations have shown increases in other bacterial genera such as Roseburia, Ruminococcus and Eubacterium, with established prebiotics like inulin (Duncan et al., 2003; Langlands et al., 2004). Moreover, it is now recognized that many bacteria inhabiting the large bowel have not yet been identified and are difficult to culture routinely (Macfarlane and Macfarlane, 2004; Eckburg et al., 2005). One consequence of this is that we do not know what the global effects of prebiotics are on the structure of the microbiota. Furthermore, prebiotics can only enhance the growth of bacteria that are already present in the gut and the composition of the microbiota can be affected by a variety of other factors, such as diet, disease, drugs, antibiotics, age, and so on. Nevertheless, prebiotic carbohydrates do have dramatic effects on the gut flora. Does this lead to any health benefits? Table 7 Effects of prebiotics on bowel habit Physiological aspects of energy metabolism M Elia and JH Cummings Prebiotics should be laxative but as Table 7 and Figure 7 show (Ito et al., 1990; Gibson et al., 1995; Alles et al., 1996; Bouhnik et al., 1997; Castiglia-Delavaud et al., 1998; van Dokkum et al., 1999; Gostner et al., 2005), they are not significantly so. Meta-analysis of the studies in Table 7 show that overall there is no significant change in faecal weight when a wide range of sources and doses of oligosaccharides are studied. Most of these papers do, however, report a clear bifidogenic effect, so this alone does not affect bowel habit. Subjects often report increased flatulence and bloating, a sign that fermentation is occurring, but there is no change in SCFA profile or bile acid output. Studies in constipated subjects (Teuri and Korpela, 1998; Chen et al., 2000; Den Hond et al., 2000), report increases in stool weight, which is surprising and should be followed up. Health benefits The main potential health benefit of prebiotics should be in strengthening gut barrier function against infection. So far, however, few randomised controlled trial (RCT) have been done and those that have, in traveller’s diarrhoea, IBS, inflammatory bowel disease and pouchitis, really do not show a clear benefit except, possibly, in well-being, although animal studies in inflammatory bowel disease are numerous and show reductions in inflammation. In antibioticassociated diarrhoea, three RCT have been reported, in one of which there was a benefit in reducing episodes of diarrhoea in patients with Clostridium difficile-associated symptoms treated with metronidazole and vancomycin. Again, it is too early to draw conclusions from these studies. (see review by Macfarlane et al., 2006). Type Amount (g/day) N MDSW/g/day Increase in stool weight (mean g/g ‘fibre’ fed) Control Prebiotic Oligomate 55 (GOS) 4.8 12 151 134 0 9.6 12 151 0 19.2 12 162 0.6 Oligofructose 15.0 8 134 154* 1.3 Inulin 15 4 92 123 2.1 Oligofructose 5 24 272 279 0 15 264 0 TOS 10 8 105 80 0 Inulin 31 9 129 204* 2.4 Inulin 15 12 129 155 1.7 Oligofructose 15 12 108 0 GOS 15 12 158 1.9 Isomalt a 30 19 99 111 0.4 Abbreviations: GOS, galacto-oligosaccharides; gram/gram increase, gram increase in stool weight per day per gram prebiotic fed; MDSW, mean daily stool weight; N, number of subjects; TOS, transgalacto-oligosaccharide. *Significantly different from control Po0.05. a Proposed as a prebiotic but not established as one. For data sources see Figure 7. S65 European Journal of Clinical Nutrition
S66 Study name Oloigosaccharide (OS) (g) Difference in means and 95% CI OS Control Ito et al 1990 GOS (10g) 12 12 Ito et al 1990 GOS (2.5g) 12 12 Ito et al 1990 GOS (5g) 12 12 Gibson et al 1990 FOS (15g) 8 8 Gibson et al 1990 Inulin (15g) 4 4 Alles et al 1996 FOS (5g) 24 24 Alles et al 1996 FOS (15g) 24 24 Bouhnik et al al 1997 TOS (10g) 8 8 Castiglia-Delavaud et al 1998 Inulin (22g) 9 9 van Dokkum et al 1999 FOS (15g) 12 12 van Dokkum et al 1999 GOS (15g) 12 12 van Dokkum et al 1999 Inulin (15g) 12 12 Gostner et al 2005 Isomalt (30g) 19 19 168 168 -200.00 -100.00 0.00 100.00 200.00 Favours control Favours OS Figure 7 Meta-analysis (fixed effect model) of various prebiotic carbohydrates on bowel habit (stool weight). Point estimate þ 12.6 g/day; 96% CI: 1.5 to þ 26.6 g/day. The test of overall effect was not significant (P ¼ 0.079) and nor was the test of heterogeneity (I 2 ¼ 21.6%; P ¼ 0.225). Table 8 Effect of prebiotics on calcium absorption in humans Subjects N Prebiotic Study design Absorption method Adolescents, M 14–16 years 12 FOS 15 g RCT feeding study. 9-day periods Adolescents, F 11–14 years 59 FOS 8 g FOS þ inulin 8 g Adolescents, F/M 9–13 years 100 Mixed long- and short-chain inulin 8 g M 20–30 years 12 Inulin 15 g, FOS 15 g, GOS 15 g An unexpected but potentially very important effect of prebiotics is that on calcium absorption and bone mineral density. Studies in animal models show clearly enhanced absorption of calcium, magnesium and iron with galacto- Randomized crossover feeding study. 3-week periods 1-year supplement to diet Randomized crossover feeding study. 21-day periods M 9 Inulin Latin square feeding study. 28-day periods Post menopausal women 12 FOS 10 g RCT feeding study. 5- 50–70 years week periods Post menopausal women 12 TOS 20 g RCT crossover. 9-day 55–65 years periods 8 men 7 women, 25–36 years 15 FOS 0.8–1.1 g Absorption from fortified milk drinks Abbreviations: FOS, fructo-oligosaccharides; TOS, transgalacto-oligosaccharides. For data sources see Macfarlane et al. (2006). European Journal of Clinical Nutrition Physiological aspects of energy metabolism M Elia and JH Cummings Result 44 Ca, 48 Ca Fractional absorption increased from 48717% to 60717% 46 Ca, 42 Ca FOS—effect FOS/inulin absorption increased from 32710% to 38710% 46 Ca Calcium absorption greater. Bone mineral density higher 44 Ca, 48 Ca No effect on calcium or iron absorption Balance Significant increase in absorption. No effect on magnesium, iron or zinc 44 Ca and balance No effect 44 48 Ca, Ca Ca absorption increased from 2177% to 2477% 42 43 44 Ca, Ca, Ca No effect oligosaccharides, fructooligosaccharides and inulin, and prevention of osteopenia following gastrectomy and ovariectomy. Table 8 summarizes the studies in humans in which five out of eight show a benefit, most importantly,
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Comision Federal de la mejora regul
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Subject: MEXICO - Comments on PROY
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Item of PROY‐ NOM‐051 A.3.1 & A
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Annex 1.1: Ziesenitz, S.C.; 1996;
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Volume 61 Supplement 1 December 200
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Volume 61, Supplement 1, December 2
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S1 S5 S19 S40 S75 S100 S112 S122 S1
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FAO/WHO Scientific Update on carboh
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cardiovascular diseases and cancer)
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REVIEW Carbohydrate terminology and
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Table 2 Energy and macronutrient in
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are inulin and fructo oligosacchari
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Table 3 Principal physiological pro
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National Academy of Sciences in 200
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Page 50 and 51: REVIEW Nutritional characterization
Page 52 and 53: Table 1 Nutritional characterizatio
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Page 56 and 57: Table 4 NSP in a selection of foods
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Page 66 and 67: similar to the situation with sugar
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Page 70 and 71: van Dam RM, Seidell JC (2007). Carb
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Table 3 Prospective studies of diet
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of sucrose-containing foods, such a
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Acrylamide Acrylamide is a chemical
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Nicodemus KK, Jacobs Jr DR, Folsom
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carbohydrate and fat may have a low
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Foods having very different nutrien
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esearch activities and food selecti
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highest satiety score was boiled po
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patients: a new basis for carbohydr
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and lipid levels, to a greater exte
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insufficient for the use of glycaem
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Dr Hans Englyst: Director and share
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Annex 1.4: US‐FDA GRAS Notificati
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FDA/CFSAN/OFAS: Agency Response Let
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Annex 1.5: US Health Claims Regulat
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jlentini on PROD1PC65 with RULES 30
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Annex 1.6: “PalatinoseTM (isomalt
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Isomaltulose is tooth friendly, unl
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CONFIDENTIAL Regulatory Affairs & N
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CONFIDENTIAL General or usual name:
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CONFIDENTIAL Plasma glucose change
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CONFIDENTIAL Rise in blood glucose
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CONFIDENTIAL References Regulatory
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Annex 1.8: Report from Imfeld (Univ
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Annex 2.2: Roberfroid, M.B., 1999;
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Annex 3.2: “Letter of no objectio
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1 Nutrition and Health Claims (CAC/
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Annex 3.2: “Letter of no objectio
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