Dr., Prof. Victor TutelyanFederalResearchCentreofNutrition,BiotechnologyandFoodSafety

Moscow,Russia

Roleof MicronutrientsandBotanicalsinEnhancementofHuman Adaptive

Potential

Seoul,16th ofMay17

GenomeTranscriptome

ProteomePeptidome

Metabolome

Health(optimal functioning of human

body)

Optimalnutrition

Nutriome+

Nutri- microbiome

Signalpathways

Chemicalcompoundsoffood(hundreds)

Foodsanddishes(∞ standsforinfinity)

Optimalnutritionformula- NUTRIOME

OptimalNutritionFormula- NUTRIOMEMalesolderthan60 years,energyvalue- 2390 kcal)

Micronutrients

1

10

100

1000

10000

OptimalNutritionFormula- NUTRIOMEMalesolderthan60years,energyvalue- 2390 kcal)

Micronutrients andBotanicalswithtargetphysiologicalactivity

1

10

100

1000

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.

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

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

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

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

Foodproteins

Lys-Glu

Ala-Glu-Asp-Gluabsorption

Tissueproteinsdigestion

proteolysis

interleukins interferon troponins

biosinthesis

GItract

ExogenousPeptidesinRegulatoryProteinsSynthesis

V. Havinson,2005

SchemeofLocalSeparationofChainsduetoBindingRegulatoryPeptideAla-Glu-Asp-Gly

inLargeGrooveofDNADoubleHelix

- hydrogenbondbetweenadenineandtimine (Watson-Crickmodel)

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)

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

ResearchofChemicalCompositionfor2929VegetablesandFruits

(jointresearchprogramme withScienceCityMichurinsk)

Berries

ApplesCherryPrunusPearApricotCherryplum

Vegetables Fruits

RaspberryHawthornBlackcurrantGardenstrawberryGooseberryActinidiaHoneyberrySeabuckthornАrrowwoodCorneliancherryRedcurrantRosehipWhitecurrantBlackberrySunBerry

TomatoTopinamburPumpkinPumpkinseedsGarlicHotpepperSerpentrootSweetpepper

FoodChemicalCompositionDatabasewww.ion.ru

MedicinalandEdiblePlantsasaSourceofBotanicals

Ethnobotanical approachestotheselectionofmedicinalandedibleplantswhicharepromisingsourcesofphytonutrients

EnexampleofdevelopmentofFoodsupplementsandfoodsforspecialdietaryusesforpatientswith

type2diabetes

Project14-36-00041fundedbytheRussianScienceFoundation

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

Analysisofallergyrisksofinclusionofextractsfromtheseplantsindietarysupplementsandspecializedfoodshasbeendone.Itisshownthattheextractofblueberryleaveshasminimalrisk.

Theefficacyoftheextractofblueberryleaveshasbeendemonstratedonthestreptozotocin induceddiabetesmodel(invivo).

Beneficialeffectsarehypoglycemicandantioxidant.

Formulationsoffoodsforspecialdietaryuseswithmodifiedcarbohydrateprofilehavebeendeveloped.

Theefficacyoftheseproductsintendedforpatientswithtype2diabetesmellitusisshowninclinicaltrial.

ThisclinicaltrialhasbeencarriedoutinClinicofFederalResearchCentreofNutrition,BiotechnologyandFoodSafety

Project14-36-00041fundedbytheRussianScienceFoundation

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

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

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

• 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

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•

Overweight and Obesity Prevalence inPopulationAged60andAbove

GenderMale Female

Age

BMI%

˃25

Obesity PrevalenceinPopulationAged60andAbove

GenderMale Female

BMI%

˃30

Age

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)

Aim:TodevelopanInternet-basedsystemtoallowthequalityoflife,health,andnutritionmanagementthroughmonitoringoftheseacrosscountries,detectingNCDriskfactors,andprovidingpersonalizedfeedbackwithhealthpromotionanddiseasepreventionadviceandrecommendations.

Internationalresearchproject«Cross-CulturalQualityofLifeSurvey.HealthandNutrition»

Partners:• WHO• FederalResearchCentreofNutrition,BiotechnologyandFoodSafety(formerInstituteofNutritionoftheRussianAcademyofSciences)

• VisionInternationalPeopleGroup

Background:Implementationofthe2011MoscowDeclarationonNCDs,the2011PoliticalDeclarationonNCDsandthe2014RomeDeclarationonNutrition

FoodConsumptionPatternsAcrossAgeGroups

WHOguidelines Underage Workingage Retirementage

Plate:foodsintakeratioacrossagegroups

WHOguidelines Under35years

Above55yo35-55yo

DietNutritiveandEnergyValueAcrossAgeGroups

RetirementageWorkingageUnderage

RetirementageWorkingageUnderage

proteinsfatscarbs

%E

Energyvalue,ccal

HealthandFunctioningParametersAcrossAgeGroups:10yearsimprovement

2005 2015

RetirementageWorkingageUnderage Above55yo35-55yoUnder35yo

RetirementageWorkingageUnderage Above55yo35-55yoUnder35yo

Bodyfunctionsandactivity

Variousorganfunctions

QualityofLifeParametersAcrossAgeGroups

2005 2015

Above55yo35-55yoUnder35yoRetirementageWorkingageUnderage

RetirementageWorkingageUnderage Above55yo35-55yoUnder35yo

Totalqualityoflife

Variouslifeparameters

GlobalChallengesof21ST Century

Obesity

Micronutrientsdeficiency

Traditional(natural)Foods Technologicalmodified(natural)foods

(Functionalfoods)

Geneticallymodified(natural)foods

DietarySupplements(micronutrients+Botanicals)

FOODSOF21STCENTURY

MicronutrientsandBotanicals – MethodologicalBackground

Amodernmultilevelanalyticalbasehasbeensetupforspotting,identifyingandfindingoutthequantitativecontentofmacro- andmicronutrients,biologicallyactivesubstancesandcontaminants

160 methods of quality and safety control of food supplements have been developed, approved and implemented

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

PilotProject«EfficiencyEvaluationofProphilactic VitaminSupportingPatientsinHospitalsintheRepublicofTatarstan»

COMPONENTSOFHEALTHYDIET

• FoodAvailability(pocket)

• FoodsAssortmentoffoodproducts(counter)

• Knowledgeandskillstobuildahealthydiet(education)

Education- themosteffectiveandleastexpensive

waytooptimizingtheNation’shealththroughfoodand

nutrition

Educationalprogrammes forthepopulationinthefieldofhealthnutritionповопросам

- Developmentofideology

РМАПО

Thankyouforyourattention!

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