Current Research on Functional Foods and Brain - Neuroscience ...

<strong>Current</strong> <strong>Research</strong> on Functional Foods and BrainAn Overview of Functional Foods and BrainFunctions: Nutritional Neuroscience and thePromotion of Brain FunctionsNaiphinich Kotchabhakdi, Ph.D.Neuro-Behavioural Biology Center,Institute of Molecular Biosciences,Mahidol University, SalayaNakornpathom 73170 Thailand,Email:scnkc@mahidol.ac.thWebsite: http://neuroscience.mahidol.ac.thhttp://neuroscience.mahidol.ac.thWhat is “Food” and what is “Nutrition”?Food is any edible material that provides energy,supports growth, repair and maintenance of thebody. Food also protects the body from infectionsand diseases.Nutrition is the process by which body utilizes foodfor growth and maintenance and healthy living.Food functions in the body through the nutrients itcontainsWhat are nutrients?Nutrients are substances found in food.These are:● Carbohydrates● Fats/Oils (lipids)● Proteins● Vitamins● MineralsSince Water is indispensable for life, it isconsidered both as a food and as a nutrient.Dietary Fiber and some Phytochemicals ofplant foods, although not nutrients as such, areneeded for good health.Functional foodFrom Wikipedia, the free encyclopediaFunctional food or medicinal food (Nutraceuticals) is any fresh orprocessed food claimed to have a health-promoting or disease-preventing property beyond the basic function of supplyingnutrients.The general category of functional foods includes processedfood or foods fortified with health-promoting additives, like"vitamin-enriched" products. Fermented foods with live culturesare considered as functional foods with probiotic benefits.Functional foods are an emerging field in food science due totheir increasing popularity with health-conscious consumers.The term was first used in Japan in the 1980s where there is agovernment approval process for functional foods called Foodsfor Specified Health Use (FOSHU).[1] What are Functional Foods and Nutraceuticals? Agriculture and Agri-FoodCanada, a, Health Canada 1998.

Scientific substantiation for claims…(Article 6)1. Nutrition and health claims shall be based onand substantiated by generally acceptedscientific evidence.2. A food business operator making a nutrition orhealth claim shall justify the use of the claim.3. The competent authorities of the Member Statesmay request a food business operator or aperson placing a product on the market toproduce all relevant elements and dataestablishing compliance with this Regulation.Understanding brainfunctions in relation to diet• Diet and cognitive functions• Brain conditioning• Mood and optimal performance• Prevention of cognitive decline• Food intake regulation and hunger/satiety• Nutrition and interorgan signalling - espgut-central nervous system interactionUnderstanding dietary effects onimmune and intestinal function• Modify systemic inflammatory activity bydiet• Dietary factors that t improve barrierfunctions• Biomarkers for intestinal health• Diet before and during pregnancy andlactation - immunefunction and allergy• Improved allergome database for foods

Understanding the link between dietand metabolic function (obesity andassociated metabolic disorders• Early biomarkers of metabolic syndrome• Individual variations in metabolic energy efficiency• Food components that regulate food intake andincrease termogenesis• Intervention strategies• Counteract age-associated associated muscle wasting• Low-grade inflammation - obesity/insulinresistance/metabolic syndrome• Epigenetic events - chronic disease• Maternal and infant recommendations for opt health• Meal composition and size - energy uptake, satietyUnderstanding consumer behaviourin relation to health and nutrition• Key determinants of food habits• Biological determinants in food choice• Methodology to understand and quantifydeterminants• Perception and determinants of ”healthy lifestyle”• Better tools for effective communication• Consumer knowledge - consumer understandingof health schemes, health claims, simplifiedlabelling - and personalised nutrition based onnutrigenomicsThe integrated picturesocietal needs• Low health costs• Healthy ageingg• Improved education onhealthy life style• Extend higher educationprogrammes along foodhealthchain• Measures of trust• Improved communicationabout food and healthissues• Involve SMEs in food andhealth areaconsumers needs• Premium taste andpleasure• Low salt, low fat foods• Improved packaging• Personalised foods• Increased intestinal andbone health• Improved immune andcognitive functions• Life style foods for eachlife cycle• Age-related diseasepreventionscience needs• Nutritional systems biology• New measures for foodintake and delivery systems• New imaging and minimallyinvasive techniques• Link databases anddatamining of (non) foodcomponents, intake andhealth parameters• Intestinal microbiotafunction and metagenomics• Consumer preference,acceptance and needs

Some natural food and their active antioxidant componentSurh, Y-J, Nature Rev. Cancer 2003, 768GeneticNutritionEnvironmentThe BrainStructural DevelopmentFunctional DevelopmentChemical DevelopmentEpigeneticProteomicReceptoromicGenomicTranscriptomicChannelomicMulti-omicapproachesBehavioural DevelopmentSynaptosomic

In developed countries, therehasbeenanexponentialgrowth in the awareness of“Health”and “Functional”foods, healthful eating habit,mood and lifestyle.This isclearly shown by the rapidgrowthintheseareasofnutrition andsupplementaryfood industries, and billions ofdollarsspent worldwideonnatural and functional foods,andfood additivesandsupplements.The old expression, “We arewhat we eat” has becomemore familiar and, althoughsometime controversial,gaining stronger scientificsupport.Recent progress of research in both fields ofNutrition and Neuroscience has providedample of scientific evidence that variousspecific nutrients can influence and modifybrain andmentalfunctions.The information and knowledge gained in theseareas of scientific investigation begins to havegreat impact in our future planning for humanand social and economic development.Furthermore,there havebeenincreasing number of reports on thedietarymodulation ofanimalandhuman behavioursand/or mentalfunctionsduring thelastdecade.Theseinclude, dietarysugarandhyperactivity in children, ameliorationofsymptomsof seasonalaffectivedisorder by dietary sugars, reductionof mental stress and fatigue by theessence of chicken, improvement ofmental well-beingin elderly subjectsbydehydroepiandrosteroned d (DHEA)supplement, improvement of memoryfunctions by extract from the leave ofGingko biloba etc..In recent years, asurvey of the annual publications on“Nutrition and Brain Development andFunction” yieldedover 500publications, and since 1998 there is apeer-reviewedreviewed professional journal for“NutritionalNeuroscience”.Scientific American : April 1982Synaptic formationon the pyramidalcell in the cerebralcortex

Diets and Serotonin level

Scientific American: January 1986ตอนนี้การโฆษณาขายอาหารเสริมกันมาก โดยเฉพาะนํ้ามันปลา ซึ ่งพบว่ามีกรดไขมันที ่มีผลดีต่อพัฒนาการของสมอง กรดไขมันที ่ได้รับการกล่าวถึงมากคือ กรดไขมันในกลุ ่มโอเมก้า 6 ได้แก่linoleic acid ซึ ่งใช้ในการสร้าง Arachidonic Acid และกรดไขมันในกลุ ่ม โอเมก้า 3(Omega-3) ได้แก่ linolenic acid หรือ Docosahexaenoic Acld (DHA) ซึ ่งกรดไขมันทั้งสองนี้ ้ ้ มีการสะสมมากในช่วงไตรมาสที่่สามของการตั้งครรภ์และในช่วง ้ ์ 18 เดือนหลังคลอดเพื ่อจะเป็ นส่วนประกอบของผนังเซลล์ของระบบประสาทในนมแม่มีสาร DHA ซึ ่งพบว่ามีส่วนช่วยในการเจริญเติบโตของสมองที ่เกี ่ยวกับการมองเห็นด้วยกรดไขมันสองตัวนี้มีมากในปลา เช่น ปลาทู ปลากระพง การกินอาหารปลาจากธรรมชาติอย่างเพียงพอจะช่วยให้ร่างกายได้รับกรดไขมันในปริมาณเพียงพอกับความต้องการของร่างกายด้วยไม่จําเป็ นต้องซื้อนํ้ามันปลาสําเร็จรูปมากินอีกEssential fatty acidThe term “essential” meansthat the fatty acids can not besynthesized in the body in an amountsufficient to meet the physiologicalneeds , must be supplied by way ofdiet

Visual Acuity Assesment in InfantBehavioral measurement FORCED CHOICE PREFERENTIALLOOKINGForced Choice Preferential LookingProcessing/IntegrationBehavioralresponseRetinaVisualCortexVisualStimulusDocosahexaenoic acid (DHA) is one of themajor compositions of membranephospholipids in mammalian central nervoussystemVisual Acuity Assesment in InfantElectrophysiologicmeasurementSweep Visual Evoked PotentialEEG/VEPresponse VisualCortexSweep VEPLog MAR1.210.8Control FDHA1.4 Behavioral measurementFPL acuity10.80.6DHA+AAHMElectrophysiologicmeasurementSweep VEP acuityVisualStimulusRetina0.60.40.20.40.206 wks 17 5206 wks 17 520.80.60.40.20.32LCPUFA effect on visual acuity of Terminfants by age of Behavioral evaluation* * *0.49Formula+DHA vs FBF vs Formula0.18 04 0.4LCPUFA effect on visual acuity of Terminfants by age of VEP evaluation1.2 Formula+ DHA vs F * 1.16* 1.03D AcuityBF vs Formula(octaves)0.8*0.370-0.2-0.4* p

Visual Acuity Relative Response in relation to DHA in For1,8(experimental/control1,61,41,210,80,6Number of studies = 12Number of subjects = 539y = 1,1014x + 0,7896R 2 = 0,30180 0,1 0,2 0,3 0,4DHA (% total fatty acids )Visual Acuity Relative Response in relation to DHA Eq in F1,81,61,41,210,80,6y = 3E-05x 2 - 0,0026x + 0,9491R 2 = 0,82740 50 100 150 200 250DHA Equivalents (mg per day ) 10 % conversion LNA1,81,61,41,20,80,6Visual Acuity Relative Response in relation to DHA Eq in Fo1y = 3E-05x 2 - 0,0032x + 1,0371R 2 = 0,75870 50 100 150 200 250DHA Equivalents (mg per day ) 5 % conversion LNA toVisual Acuity Relative Response in relation to DHA Eq in Fo1,8y = 3E-05x 2 - 0,0028x + 1,02241,6R 2 = 0,73871,41,210,80,60 50 100 150 200 250DHA Equivalents (mg per day ) 1 % conversion LNA toLTPResultLong-termPotentiation inHippocampus

Brain Aging is a multiphase processBlueberry

Antioxidant Diets ImproveCognitive FunctionTable 1. Antioxidant interventions improve cognitive function.Duration ofRef # Antioxidant Subjects Study Cognition[112] PBN gerbils 14 days improved spatial memory in radial arm maze[113] Blueberry, spinach 19 month old rats 8 weeks improved one-trial learning in the water maze&strawberryimproved vitaminElevels inthe hippocampus[114] PBN 24 month old rats 4-5 months improved memory retention on spatial memory taskvitamin Eimproved learning of a spatial memory task[115] Strawberry, spinach 6 month old rats 8 months enhanced retention in a spatial water maze taskAnd vitamin E[116] PBN 24 month old rats 9.5 months improved memory and learning on spatial memory taskfaster acquisition of a one-way activate avoidance task[117] PBN senescence 12 months significantly lengthened life spanaccelerated mice[118] Vitamin E Rats receiving 7 days reduced spatial memory impairments induced by Aintraventricular A[119] Vitamin E AD 2 years significantly delayed institutionalizationError r Scores250200150100500n=12ControlControlAoxn=13DietControln=6Control Aoxn=7DietYoungAgedA diet rich in antioxidantsimproves landmarkdiscrimination learning inoldbut not young dogs(p

<strong>Research</strong> on the Essence of Chicken:Responses of Human Brain Electrical Activities toDrinking of Essence of ChickenDeclaration of Conflict of Interest:Naiphinich Kotchabhakdi, Chittin Chindadoungratana,and William G.A. LongworthNeuro-Behavioural Biology Center,Institute of Science and Technology for <strong>Research</strong>and Development, Mahidol University, Salaya,Nakornpathom 73170 Thailand.Email: scnkc@mahidol.ac.thThe following research work wassupported by a research grant from:Cerebos (Thailand) Ltd.AndCerebos Pacific Ltd.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectBRAND’S Essence of Chicken (BEC)have been widely consumed, particularly in Chinesecommunities in Southeast Asia, as traditional remediesand promotion for several ailments. It was also known tobe beneficial in various conditions including:(A) Physical recovery from and nutritional supplement forthe sickness that often occurs in elderly and postpartumwomen;(B) the physical development of athletes;(C) recovery from physical and mental Stress; and(D) stimulating and enhancing mental efficiency ofstudents.Several scientific studies have been conducted over theyears to uncover the benefits of consuming BEC.In 1987, , research conducted by leadingnutritionists at King’s College in Londondemonstrated that 2 types of BEC substantiallyincrease mean metabolic rate by an average 8%and 12 % of above fasting baseline valuescompared to 2% % and 4% % increase with water orplacebo. The response was greater thanexpected from the total energy and proteincontent of the essence, and sustained longerthan three hours after consumption of BEC. Itwas concluded that the acute metabolicresponse may be due to the effects of particularamino acid composition, or other specificcomponents and/or a cephalic (brain) responseto taste.

Metabolic rateThermic effects of BECGeissler C et al Nutrition Reports International March 1989 Vol. 39 No. 3What are in BEC?BEC(Essence of Chicken)Protein content (%) 7.58Amino Acids (mg/100gm)Aspartic acid 387.63Threonine 163.85Serine 175.04Glutamic acid 848.64Proline 497.25Glycine 938.10Alanine 544.27Cystinenon-detect.Valine 162.01Methionine 84.78Isoleucine 125.04Leucine 269.19Tyrosine 47.24Phenylalanine 382.77Histidine 219.24Lysine 319.68Arginine 402.48Tryptophan 14.83Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCONTENT: 274 mg/100gm68.6 mg/100gmTaurine: 53 mg/100gm

In PlasmaIn Cerebral CortexIn HippocampusIn Hypothalamus

<strong>Research</strong> on the effects of Essence of Chickenby the Neuro-Behavioural Biology Center, Mahidol University, Salaya.We completed a clinical study on two groups of subjects.The first group of the Pilot study consisted of 15healthy volunteers university students who drank 2 bottlesof 70 ml., and we monitored the effects on brain electricalactivities (Electroencephalogram or EEG) 2 hours before,and 4 hours after drinking.The second group of 50 subjects followed theRandomized double-blind, blind, placebo-controlcontrol and crossoverstudy design. In the second group, data werecollected on the first day and after seven days of drinking 2bottles of either BEC or placebo daily.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Projectการศึกษานําร่อง (Pilot Study)Drinking BECone 70 cc. Bottle,2, or 3 BottlesContinuous Recording of EEGEC EO EC EO EC EO EC EO EC EOGroup ARandomized Double-blind,Placebo-Control withCross-over Study1st Day 7th Day 1st Day 7th Day1 HourBeforeEC = Eye Closed1 Hour 2 Hour 3 Hour 4 HourAfterEO = Eye OpenedDaily DrinkingBEC70 cc. X 23weeksBreakData Collection fromvolunteer subjectsDaily DrinkingPlacebo70 cc. X 2Randomized Double-blind,Placebo-Control withCross-over StudyGroup B1st Day 7th Day 1st Day 7th DayDaily DrinkingPlacebo70 cc. X 23weeksBreakData Collection fromvolunteer subjectsDaily DrinkingBEC70 cc. X 2Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project

BEC(Essence of Chicken)(Collagen)Protein content (%) 7.58 6.98Amino Acids (mg/100gm)Aspartic acid 387.63 332.32Threonine 163.85 119.68Serine 175.04 195.26Glutamic acid 848.64 678.13Proline 497.25 811.83Glycine 938.10 1,676.68Alanine 544.27 650.97Cystine non-detect. non-detect.Valine 162.01 144.77Methionine 84.78 35.07Isoleucine 125.04 87.15Leucine 269.19 180.35Tyrosine 47.24 18.98Phenylalanine 382.77 110.67Histidine 219.24 46.71Lysine 319.68 222.26Arginine 402.48 493.34Tryptophan 14.83 0.84Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectPlaceboPlaceboBEC(Essence of Chicken)(Collagen)L-Carnosine (mg/100ml) 73.0 non-detectL-Anserine (mg/100ml) 302.0 non-detectTaurine 53.0 non-detectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectDoes the subject feel anythingsubjectively after daily drinkingBEC?Subjective rating scale by visualanalog scale.14 itemsCompare BEC with placeboSubjective rating scale by visual analog scale:1. Physical strength and vigor2. Refreshing3. Stress-tensiontension-anxiety4. Depression5. Fatigue6. Confusion7. Concentration8. Drowsiness9. Alert10. Happiness11. Friendliness12. Pain and headache13. Sleep14. Better feeling compare to yesterday

All items were P < 0.05; N =5050 Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectInternational 10-20 Electrode Placement SystemCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectEEG Signal Recorded:EEG is the summation of the continuously-varyingbio-electrical activity of multiple neuronal ‘dipole’populations beneath the electrodes, and can beconsidered a composite waveform, comprised ofindividual components of various clinically usefulfrequencies:--- Delta (0.0 - 3.5Hz)--- Theta (4.0 - 7.5Hz)--- Alpha (8.0 - 13.0Hz)--- Beta (>13Hz)Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project

EYE OpenedCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectEye ClosedCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectTopographic Brain MappingCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectEyes-closed EEG sample taken 50 mins prior to BEC ingestion.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project

Eyes-closed EEG sample taken at the time of BEC ingestion.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectEyes-closed EEG sample taken 50 mins following BEC ingestion.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectEyes-closed EEG sample taken 2-1/2 hrs following BEC ingestion.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos <strong>Research</strong> ProjecCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos <strong>Research</strong> Project160.0140.0120.0100.080.060.040.020.00.0BEC-03 P3 Site EC-CARAbsolute Power ValuesCHICKEN SOUP #1 DATADelta Theta Alpha Beta TotalCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project-60-50-40-30-20-100102030405060708090100110120130140150160170180190200210

180.0160.0140.0120.0100.080.060.040.020.00.0BEC-03 P4 Site EC-CARAbsolute Power ValuesCHICKEN SOUP #1 DATADelta Theta Alpha Beta TotalCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project-60-50-40-30-20-100102030405060708090100110120130140150160170180190200210The effects of BEC on EEG power SpectraGroup data (N = 48)Electrodes: F3, F4, C3, C4, P3, P4Link to mandible groundsTime series analysis:Periods During Eye Opened(EO) During Eye Closed (EC)1. -85 min. (before BEC ingestion) -75 min.2. +5 min. (after BEC ingestion) +10 min.3. +25 min. +30 min.4. +45 min. +50 min.5. +65 min. +70 min.6. +115 min. +120 min.7. +165 min. +170 min.Data from Day one compare with Day SevenCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project20.0Day 1 Data: BEC minus PlaceboAbsolute Power Percent-Change Relative Difference: P3 site E/O LMRPositive numbers = BEC increased power > Placebo OR decreased power < PlaceboNegative numbers = Placebo increased power > BEC OR decreased power < BEC20.0Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectDay 1 Data: BEC minus PlaceboAbsolute Power Percent-Change Relative Difference: P4 site E/O LMRPositive numbers = BEC increased power > Placebo OR decreased power < PlaceboNegative numbers = Placebo increased power > BEC OR decreased power < BEC15.015.0ive Difference10.05.0ive Difference10.05.0Percent-Change Relati0.0-5.0-10.0Percent-Change Relati0.0-5.0-10.0-15.0-15.0-20.0Delta Theta Alpha Beta Total-20.0Delta Theta Alpha Beta TotalFrequency BandFrequency BandA bsolute PowerPercent-chang e ACopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project230.0220.0210.0200.0190.0180.0170.0160.0150.0140.0130.0120.0110.0100.090.080.0BEC - 2 bottles: Delta, Theta, Alpha, Beta and TotalFrequency Range activity from left parietal (P3) site (E/C, LMR)*** P < 0.0010 20 40 60 80 100 120 140 160 180 200Time post-ingestion (in minutes)Delta Theta Alpha Beta Total Geissler C et al Nutrition Reports International March 1989 Vol. 39 No. 3

Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectAbsolute PowerPercent-chang e in230.0220.0210.0200.0190.0180.0170.0160.0150.0140.0130.0120.0110.0100.090.0Comparison of BEC: 1 vs 2 bottles:Alpha activity from parietal electrodes (E/C, LMR)*** P < 0.001BEC-1 P3BEC-2 P3BEC-1 P4BEC-2 P480.00 20 40 60 80 100 120 140 160 180 200Time post-ingestion (in minutes)Effects of Drinking of the Essence of Chickenon the Event-Related Potentials (P300)Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectA representative sample (one subject)showing the differential effects of BECand Placebo substances on AuditoryP300 ERP latencies.From the beginning of the dosing cycle(Day 1, pre-ingestion) to the end (Day 7,post-ingestion), BEC tended to result ina shortening of the ‘P300‘ componentlatency, whereas Placebo resulted in aprolongation of same: opposite effects.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project

BEC Subject #04Substance: BECTesting Day: 1Pre-ingestion Auditory P300 ERPP300 Latency: 304 msCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectBEC Subject #04Substance: BECTesting Day: 7Post-ingestion Auditory P300 ERPP300 Latency: 290 msCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectBEC Subject #04Substance: PlaceboTesting Day: 1Pre-ingestion Auditory P300 ERPP300 Latency: 280 msCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project

BEC Subject #04Substance: PlaceboTesting Day: 7Post-ingestion Auditory P300 ERPP300 Latency: 304 msCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project340P300 Latency Comparison (Total Group n=45-49)between BEC and Placebo, and between Testing Days 1 and 7340P300 Latency Comparison (Total Group n=43-49)between BEC and Placebo, and between Testing Days 1 and 7330330y (msec's)P300 Latency320310300290e ncy (mse c)P300 Late320310300290280BEC Day 1 Pre-ingestion (n=49) BEC Day 7 Post-ingestion (n=48) Placebo Day 1 Pre-ingestion(n=46)P < 0.0505Placebo Day 7 Post-ingestion(n=45)280BEC Day 1Preingestion(n=49)BEC Day 1Postingestion(n=47)BEC Day 7Preingestion(n=47)BEC Day 7Postingestion(n=48)Placebo PlaceboDay 1 PreingestioingestionDay 1 Post-(n=46) (n=45)Placebo PlaceboDay 7 PreingestioingestionDay 7 Post-(n=43) (n=45)26Digit Span: Chicken SoupEffects of Drinking of the Essence of Chickenon Hormonal Levels in Normal Human Volunteers24oreSc222018prepostChittin Chindadoungratana, Naiphinich Kotchabhakdi,and William G.A. Longworth161412Neuro-Behavioural Biology Center,Institute of Science and Technology for <strong>Research</strong>and Development, Mahidol University, Salaya,Nakornpathom 73170 Thailand.10day1Day Samplingday7Email: scnkc@mahidol.ac.thCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project

CORTISOL25.01 st DAY BRANDWe completed the clinical study on the effects of Essence of Chicken(EC)on the level of serum cortisol. The subjects consisted of 40healthy male volunteers from university students who drank 2 bottlesof 70 ml. of the Essence of Chicken (EC). We monitored the level ofserum cortisol, and prolactin on day one and day seven after 7 days ofEC by radio-immuno-assay (RIA) technique before and 1, 2, and 3hours after consumption of EC. The samegroupalso tested with ih aplacebo, which composed of protein solution from collagen in adouble-blind placebo-control study design. Our data showed that afterdrinking 2 bottles of BEC, there were extremely significant decreasesin the level of serum cortisol while there were no significant changesin the group that consumed placebo. In our study, serum prolactin didnot change significantly. The levels of the serum cortisol have beenwidely used as indicators of the levels of physical and/orpsychological stresses and anxiety. The data provide solid evidencethat BEC produce a relaxation and recovery from stress and anxiety.Cortiso ol (mcg %)20.015.010.05.00.0Sampling Series*** P < 0.001Pre-ingestion Brand1 hr Post-Ingestion2 hrs Post-Ingestion3 hrs Post-IngestionCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project

Cortisol (mcg %)7th DAY BRAND16.014.012.0*** P < 0.00110.08.06.04.02.00.0Sampling SeriesCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectPre-Ingestion1 hr Post-Ingestion2 hrs Post-Ingestion3 hrs Post-IngestionCorti sol (mcg %)16.014.012.010.08.06.04.02.00.01 st Day PlaceboN.S.Sampling SeriesCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectPre-Ingestiion1 hr Post-Ingestion2 hrs Post-Ingestion3 hrs Post-Ingestion16.07 th Day Placebo14Cortisol (mcg %)14.012.0* P < 0.0110.0Pre-Ingestion1 hr Post-Ingestion8.02 hrs Post-Ingestion6.03 hrs Post-Ingestion4.02.00.0Sampling SeriesCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCortisol (mcg % )121086420** P < 0.01 N.S.1st Day Ingestion7th Day IngestionBrandBECPlaceboPlaceboCopyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> ProjectCONTENT: 274 mg/100gm68.6 mg/100gmAll items were P < 0.0505Taurine: 53 mg/100gm

CONCLUSION:Effects BEC on Brain FunctionsThe data from both groups show significant changes of the EEG. The alpha waves(8-13 Hz.) significantly increased and become more synchronized during bot theeye-closed and eye-opened periods over duration of 3 hours as compared to thecontrol period before drinking and after consumption of the placebo. The betawaves (>13 Hz.), on the other hand, significantly increased during the eye-openedthere seemed to be no statistically significant changes in the delta (0-3 Hz.) andtheta (4-7 Hz.) wavesThe increase in alpha waves and synchrony is well known to occur during variouspractice of mental relaxation and meditation which allow the subject a betterability to concentrate and organize their mental thinking processes. The increaseof beta wave during eye-opened period also indicated that BEC can enhancearousal state and alertness..These findings provide clear evidence that BEC can significantly and specificallyimprove brain functions since an increase in alpha wave activities during eyeclosedperiod can be interpreted as evidence that BEC produces a desirable stateof brain relaxation and reduction of stress and anxiety. The fact that there were nosignificant changes in the delta and the theta waves after drinking BEC indicatedthat BEC did not produce drowsiness or day-dreaming. Hence, the finding can beuse to support that BEC produces an increase in efficiency of brain functions, andalso correlated to findings in psychological studies which show improvement ofalertness, attention, and subjective feeling of reduced stress and anxiety.Copyright 2000 by N.Kotchabhakdi et al & Mahidol-Cerebos Collaborative <strong>Research</strong> Project