role of micronutrients and botanicals in enhancement of ... · bcl2 – anti-apoptotic protein bax,...
TRANSCRIPT
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Dr., Prof. Victor TutelyanFederalResearchCentreofNutrition,BiotechnologyandFoodSafety
Moscow,Russia
Roleof MicronutrientsandBotanicalsinEnhancementofHuman Adaptive
Potential
Seoul,16th ofMay17
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GenomeTranscriptome
ProteomePeptidome
Metabolome
Health(optimal functioning of human
body)
Optimalnutrition
Nutriome+
Nutri- microbiome
Signalpathways
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Chemicalcompoundsoffood(hundreds)
Foodsanddishes(∞ standsforinfinity)
Optimalnutritionformula- NUTRIOME
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OptimalNutritionFormula- NUTRIOMEMalesolderthan60 years,energyvalue- 2390 kcal)
Micronutrients
1
10
100
1000
10000
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OptimalNutritionFormula- NUTRIOMEMalesolderthan60years,energyvalue- 2390 kcal)
Micronutrients andBotanicalswithtargetphysiologicalactivity
1
10
100
1000
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Fundamental research in the field of evaluation of human requirements in various nutrients allows to make PhysiologicallevelsofenergyandessentialnutrientsforvariouspopulationgroupsintheRussian(МР2.3.1.2432-08) more precise.
This document provides a basis for numerous practical applications.
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Recommended daily allowances of over 100
nutrients and 60biologically active
substances for adults
Nutrients and biologically active
substances
Traditional food sources (food
products and raw materials)
Alternative sources of
nutrients and BASidentical to natural
Adequate consumption level
Maximum consumpti
on limit
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Adaptive PotentialAntioxidant
defense system
System of xenobioticmetabolism
enzymesImmune system
Apoptosis regulation
• Antioxidantactivityofbloodplasma
• Glutathionperoxidase• Glutathionereductase• Catalase• Exvivomicrosomal lipidperoxidation
•Malondialdehyde content• Xanthine oxydase
•CYP1A1•CYP1A2•CYP2B1
Cytokines•Interleukin2•Interleukin4•Interferon-gamma
•Lysosom membranestabilitydisorders•Releaseofhydrolases•Activationofcaspases
•Glutathionetransferase•Chinoin reductase•UDP-Glucoronosyltransferase•Epoxyhydrolase
Cell protection from oxydative and chemical stress
Forming of immunity
barrierCell survivability?
Homeostasismaintenance
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Hsp 90
Hsp 90
AhR
Keap1
Nrf2
AhR Nrf2
Hsp 90
Hsp 90
Arnt
mRNA mRNA
Ядро
CYP1A1, CYP1A2, CYP1B1,UDP-ГТ1А6, ГТ, ХР
UDP-ГТ1А6, ГТ, ХР, ГО,ГР, ГП-2
Усиление защиты от химического и окислительного стресса
Сохранение гомеостаза
ArntAhRXRE
Nrf2 MafАRE
Keap1
RoleofBotanicalsinRegulationofActivityofXenobioticMetabolismEnzymesandAntioxidantDefense
Indole
(indole-3-carbinol(I-3-C)
stilbenesstyrenes
isothiocyanatescurcuminphenolacidsindolescarotenoids
Homeostasismaintenance
Increasedprotectionfromchemicalandoxidativestress
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Fas-R
Bcl2
Spirulina,carotenoids,indole-3-carbinol
Lysosomotropic agents
Cytochromes c,AIF
TNF-R
КатепсиныB,D,L
Mitochondria
Bid tBid
Bax
AFC
Caspase8
Procaspase 9
Caspase 9
Procaspases3,6,7
Caspases 3,6,7
Apoptosis
Aminofurazan-carbonicacid
Bax
Hsp70
Lysosome
Catepsins B,D,L
PossibleRoleofLysosomes inApoptosis
Control I-3-C
Penetrability 100% 60%
Catepsin B 100% 75%
Apoptosis cells 6,9±0,5(100%)
4,1±0,3*
(60%)
- membrane stabilizer
Bcl2 – anti-apoptotic proteinBax, Bid – pro-apoptotic proteinsTNF-R, Fas-R – apoptosis receptors
- membrane destabilizer
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Foodproteins
Lys-Glu
Ala-Glu-Asp-Gluabsorption
Tissueproteinsdigestion
proteolysis
interleukins interferon troponins
biosinthesis
GItract
ExogenousPeptidesinRegulatoryProteinsSynthesis
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V. Havinson,2005
SchemeofLocalSeparationofChainsduetoBindingRegulatoryPeptideAla-Glu-Asp-Gly
inLargeGrooveofDNADoubleHelix
- hydrogenbondbetweenadenineandtimine (Watson-Crickmodel)
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Maf
Maf
Maf
AhR
Nrf2
Hsp90
Hsp90
Keap1
Arnt
Maf
Hsp90
CC
RP
p
XAP2 AhR
Nrf2
XREM
PBREM
RXR
RXR
PXR
PXR RXR
CAR
CAR RXR
Hsp90
Hsp90
XAP2
Keap1
Hsp90
CC
RP
p
Nucleus
Cytoplasm
CYP1A1,1А2,1B1;UDP-GT, glutathione-transferase, quinone reductaseparaoxonase-1
UDP-GT, glutathione-transferas,quinone reductase, heme-oxygenase-1,glutathione peroxidase,glutathione reductase, superoxide dismutase, et al.
CYP3А,UDP-GT,glutathione-transferas
CYP2В,UDP-GT,glutathione-transferas
XREAhR Arnt
?
CAR RXR
ROS
Nrf2
Nrf2
Nrf2
Nrf2
Nrf2
CARCAR
CAR
CAR
CARCAR
CAR
CARCAR
CARCAR
CARCAR
PXR
PXR
ArntArnt
Maf
RXR
Maf
Maf
RXRRXR
Maf
Maf
RXR
RXR
RXRRXR
Maf
Maf
RXR
RXR
RXRRXR
RXR
RXR
RXR
Maf
RXR
RXR
RXR
RXR
Maf
Maf
RXR
RXR
RXR
RXR
ARE
XRE
xenobiotic,BAS
Resultsofinvitroresearchoncellcultures
(Ligands/Activators)
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a
b
ab
b
CYP3
activity
,%ofcon
trol
a
bb
c
CYP1
A2activity
,%ofcon
trol
a
bc
ab
c
CYP1
A1activity
,%ofcon
trol
IncreasedactivityofCYP1A1(A),CYP1A2(B) andCYP3A(C)intheliverofratsafterseparateandcombinedactionof
Curcumin andQuercetin
Notes: Values marked with different letters (a, b, etc.) have statistically significant differences (p≤0.05).
А B С
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ResearchofChemicalCompositionfor2929VegetablesandFruits
(jointresearchprogramme withScienceCityMichurinsk)
Berries
ApplesCherryPrunusPearApricotCherryplum
Vegetables Fruits
RaspberryHawthornBlackcurrantGardenstrawberryGooseberryActinidiaHoneyberrySeabuckthornАrrowwoodCorneliancherryRedcurrantRosehipWhitecurrantBlackberrySunBerry
TomatoTopinamburPumpkinPumpkinseedsGarlicHotpepperSerpentrootSweetpepper
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FoodChemicalCompositionDatabasewww.ion.ru
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MedicinalandEdiblePlantsasaSourceofBotanicals
Ethnobotanical approachestotheselectionofmedicinalandedibleplantswhicharepromisingsourcesofphytonutrients
EnexampleofdevelopmentofFoodsupplementsandfoodsforspecialdietaryusesforpatientswith
type2diabetes
Project14-36-00041fundedbytheRussianScienceFoundation
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Theanalysisof200prescriptionreferencebooksofRussia,Ukraine,Belarushasbeendone.
Amongthem:• Leavesofblueberry– 100% ofprescriptions (flavonoids)
• Beansshell– 73% ofprescriptions (guanidines)
• Leavesofnettle– 65% ofprescriptions (complexofvitamins,flavonoids andphytosterols)
Thereare66 referencebookscontaining550antidiabetic prescriptions,whichincludes 237 medicinalplantsindifferentcombinations.
Project14-36-00041fundedbytheRussianScienceFoundation
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Analysisofallergyrisksofinclusionofextractsfromtheseplantsindietarysupplementsandspecializedfoodshasbeendone.Itisshownthattheextractofblueberryleaveshasminimalrisk.
Theefficacyoftheextractofblueberryleaveshasbeendemonstratedonthestreptozotocin induceddiabetesmodel(invivo).
Beneficialeffectsarehypoglycemicandantioxidant.
Formulationsoffoodsforspecialdietaryuseswithmodifiedcarbohydrateprofilehavebeendeveloped.
Theefficacyoftheseproductsintendedforpatientswithtype2diabetesmellitusisshowninclinicaltrial.
ThisclinicaltrialhasbeencarriedoutinClinicofFederalResearchCentreofNutrition,BiotechnologyandFoodSafety
Project14-36-00041fundedbytheRussianScienceFoundation
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Overconsumption of high energy foods and vitamins andmicronutrients deficiency lead to growth of obesityprevalence between adults (up to 23%) and children (up to7%) as well as decreasing adaptive potential of the popularmajority in the Russian Federation
Malnutrition in the RF population,
2005-2016 гг.
(Results of annual investigation of 15000 people)
Micronutrients deficiency
Requirements
FoodconsumptionpatternsinRussianpopulation
-60
-40
-20
0
20
40
60
80
100
ккал
белок
жир
НЖК
ПНЖК
n6ПНЖК
n3ПНЖК
холестерин
сахароза
этанол
ПВ
Са
Fe*
Se А В1
В2
С флавоноиды
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Кальциймг/сут.
555 to 562,8 (28)553 to 555 (11)551 to 553 (6)549,4 to 551 (16)509,1 to 549,4 (27)
CalciumIntake intheRussianAdult Populationin2016:510-560 mgperday
Recommended Daily Intake – 1000 mg
Calcium,mg/day
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Витамин Смг/сут.
65,4 to 65,4 (18)58,9 to 65,4 (12)57,9 to 58,9 (16)54 to 57,9 (15)49,8 to 54 (27)
VitaminCIntake intheRussianAdult Populationin2016:
50-65 mgperday
Recommended Daily Intake – 100 mg
VitaminCmg/day
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• Daily Intake Age• 61-70y.o. 71-80y.o. 81-90y.o. 91andabove
•• Protein,g 83,3 74,5 67,4 63,2• Proteinratio%E 14,1 14,1 13,94 13,8• Fat,g 100,0 81,5 72,1 67,9• Fatratio%E 37,4 34,2 32,9 32,9• Carbs,g 286,5 273,1 258,35 243,3• Energyvalue,kcal 2 390 2 129 1 953 1 838• vitanin А,mg 0,59 0,51 0,44 0,39• vitamin В1,mg 1,26 1,13 0,99 0,91• VitaminВ2,mg 1,40 1,32 1,23 1,17• vitamin С,mg 80,1 69,7 63,1 56,1• Calcium,mg 820,0 787,6 754,2 744,3
Requirements
6811,8773033523000,91,51,8901200
IntakeofVariousNutrientsinPopulationAged60andAbove
ActualIntake
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IntakeofMainGroupsofFoodsinPopulationAged60andAbove
• Daily Intake Age• 61-70y.o. 71-80y.o. 81-90y.o. 91andabove
•• BreadandBakery 251,6 241,2 226,4 211,4• Vegetables 288,7 243,3 197,5 168,1• Potato 188,8 170,8 152,7 127,8• Sugar 65,6 61,9 60,8 61,7• MeatandMeatProducts 217,9 171,4 146,4 133,3• FishandSeaFood 73,6 57,71 45,6 44,7• MilkandDairyproducts 800,0 776,634 777,9 762,5• Batter 11,8 11,0 10,4 9,0• Egges 24,5 20,1 17,1 12,7• Vegetableoil 25,6 19,0 13,6 11,6• FruitsandBerries 199,8 177,6 175,0 164,2•
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Overweight and Obesity Prevalence inPopulationAged60andAbove
GenderMale Female
Age
BMI%
˃25
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Obesity PrevalenceinPopulationAged60andAbove
GenderMale Female
BMI%
˃30
Age
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DetectionRateofVitaminDDeficiencyAssociatedwithVariousDiseases
(concentrationof25-ОНDinbloodserum)
2016,№1,Problemsofdietology.2016;6(2):22–29.
Patients: ELDERLY PEOPLE Region, year,quantity
Proportion of deficiency (inadequacy), %
chronic heart failure St. Petersburg, n=209 (>75)disseminated sclerosis St. Petersburg, n=33 81 (15)
psoriasis and psoriatic arthritis Irkutsk, n=123 (73,2) obesity and arterial
hypertension Moscow, 2015 г., n = 93 чел. 51
tuberculosis Kazan, 2015-2016 гг., n = 48 чел. 77
inflammatory disease of paradontium
Arkhangelsk, n=58 98,3
type 2 diabetes mellitus in postmenopause
Sverdlovskaya obl., 2015 г., n=15 femails
(93,3)
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Aim:TodevelopanInternet-basedsystemtoallowthequalityoflife,health,andnutritionmanagementthroughmonitoringoftheseacrosscountries,detectingNCDriskfactors,andprovidingpersonalizedfeedbackwithhealthpromotionanddiseasepreventionadviceandrecommendations.
Internationalresearchproject«Cross-CulturalQualityofLifeSurvey.HealthandNutrition»
Partners:• WHO• FederalResearchCentreofNutrition,BiotechnologyandFoodSafety(formerInstituteofNutritionoftheRussianAcademyofSciences)
• VisionInternationalPeopleGroup
Background:Implementationofthe2011MoscowDeclarationonNCDs,the2011PoliticalDeclarationonNCDsandthe2014RomeDeclarationonNutrition
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FoodConsumptionPatternsAcrossAgeGroups
WHOguidelines Underage Workingage Retirementage
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Plate:foodsintakeratioacrossagegroups
WHOguidelines Under35years
Above55yo35-55yo
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DietNutritiveandEnergyValueAcrossAgeGroups
RetirementageWorkingageUnderage
RetirementageWorkingageUnderage
proteinsfatscarbs
%E
Energyvalue,ccal
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HealthandFunctioningParametersAcrossAgeGroups:10yearsimprovement
2005 2015
RetirementageWorkingageUnderage Above55yo35-55yoUnder35yo
RetirementageWorkingageUnderage Above55yo35-55yoUnder35yo
Bodyfunctionsandactivity
Variousorganfunctions
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QualityofLifeParametersAcrossAgeGroups
2005 2015
Above55yo35-55yoUnder35yoRetirementageWorkingageUnderage
RetirementageWorkingageUnderage Above55yo35-55yoUnder35yo
Totalqualityoflife
Variouslifeparameters
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GlobalChallengesof21ST Century
Obesity
Micronutrientsdeficiency
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Traditional(natural)Foods Technologicalmodified(natural)foods
(Functionalfoods)
Geneticallymodified(natural)foods
DietarySupplements(micronutrients+Botanicals)
FOODSOF21STCENTURY
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MicronutrientsandBotanicals – MethodologicalBackground
Amodernmultilevelanalyticalbasehasbeensetupforspotting,identifyingandfindingoutthequantitativecontentofmacro- andmicronutrients,biologicallyactivesubstancesandcontaminants
160 methods of quality and safety control of food supplements have been developed, approved and implemented
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Fibers
Vitamins (C,D,group В)
Minerals(Ca,Fe)
PUFASn-3,n-6
Antioxidants (beta-carotene,tocopherols)
Oligosaccharidesandpolysaccharide(prebiotics)
Somespeciesofbeneficialmicroorganisms(probiotics)
MicronutrientsandBotanicalsforOptimisation ofPreventiveandTherapeutical Diets
Flavanoids (resveratrol,rutin,hesperidin,quercetine,epigallocatechin-3-gallate)
Indoles (indole-3-carbinol)
Phenolic acids
Caffeine
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PilotProject«EfficiencyEvaluationofProphilactic VitaminSupportingPatientsinHospitalsintheRepublicofTatarstan»
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COMPONENTSOFHEALTHYDIET
• FoodAvailability(pocket)
• FoodsAssortmentoffoodproducts(counter)
• Knowledgeandskillstobuildahealthydiet(education)
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Education- themosteffectiveandleastexpensive
waytooptimizingtheNation’shealththroughfoodand
nutrition
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Educationalprogrammes forthepopulationinthefieldofhealthnutritionповопросам
- Developmentofideology
РМАПО
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Thankyouforyourattention!
감사