RESVERATROL RESVERATROL

"S i tifi E id i H lth d Di " "ScientificEvidence inHealth andDisease"

Dr.RalFranciscoPastor Dr.RalFranciscoPastor
4CtedradeMedicinaInterna 4CtedradeMedicinaInterna
Hospital de Clnicas Hospital de Clnicas HospitaldeClnicas HospitaldeClnicas
JosdeSanMartn JosdeSanMartn
UniversidaddeBuenosAires UniversidaddeBuenosAires
Argentina Argentina gg
Evidence Evidence Based Medicine Based Medicine Evidence EvidenceBasedMedicine BasedMedicine
U ' id t th di l lit t II H t U ' id t th di l lit t II H t Users'guidestothemedicalliterature.II.Howtousean Users'guidestothemedicalliterature.II.Howtousean
articleabouttherapyorprevention.A.Aretheresultsof articleabouttherapyorprevention.A.Aretheresultsof
thestudyvalid? thestudyvalid? Evidence EvidenceBasedMedicineWorkingGroup. BasedMedicineWorkingGroup.
Guyatt GH, Sackett DL, CookDJ.
JAMA. 1993Dec1;270(21): 2598601
D f M di i M M U i i H il Departmentof Medicine,McMasterUniversity,Hamilton,
Ontario,Canada.
Globalise Globalise theevidence, theevidence,localise localise the thedecisin decisin
JohnEisemberg (1999)
AHCPR(AgencyforHealthCarePolicyandResearch)
Resveratrol Resveratrol
3,5,4transtrihidroxiestilbeno , ,
bioactive bioactive constituent constituent,non ,nonnutritional nutritional food food
Molecular Weight 228 24328 [g/mol] MolecularWeight228.24328[g/mol]
Roots
helboro helboro
((Veratrum Veratrum
Roots
Polygonum Polygonum
Cuspidatum Cuspidatum
(
Wine Wine
Cis Cis
Resveratrol Resveratrol
Wine Wine
Piceidos Piceidos
Resveratrol Resveratrol
Wine Wine
Trans Trans
Resveratrol Resveratrol
Grapes Grapes
Vitis Vitis
Vinifera Vinifera
Grapes Grapes
Piceido Piceido
Resveratrol Resveratrol
grandiflorum grandiflorum
O.Loes) O.Loes)
(Takaoka,1940)
(Nonomura et
al.,1963)
Jeandet Jeandet P. P.
etal1993 etal1993
Lamuela Lamuela
Ravents Ravents
R.1995 R.1995
Siemman Siemman
etal1992 etal1992
Vinifera Vinifera
Resveratol Resveratol
Langcake Langcake
P.etal P.etal
Waterhouse Waterhouse
A. A.Lamuela Lamuela
Ravents Ravents R. R.
1994 1994
1976 1976
1994 1994
Vaccinium
(arndanos)
Rimando et
Cava Cava
Andres Andres
Resorcinol
Veratrum
Rimandoet
al.2004. Lacueva Lacueva
etal. etal.
2001 2001
Veratrum
Ol oxhidrilo
Calorie Calorie Restriction Restriction == Resveratrol Resveratrol Calorie Calorie Restriction Restriction = =Resveratrol Resveratrol
McCay,etal1935.
Theeffectofretardedgrowthuponthelengthoflifeandupontheultimatebody
size. JournalofNutrition10,6379
Howitz,K.T.2003.
Smallmoleculeactivatorsofsirtuins extendSaccharomyces cerevisiae lifespan.
Nature425,191196.
JangMetal1997
CancerChemopreventive ActivityofResveratrol,aNaturalProductDerivedfrom
Grapes Science 10 January Vol 275 no 5297 pp 218 220 GrapesScience 10January Vol.275 no.5297 pp.218220
Renaud SC, etal1998
Alcohol and mortality in middle aged men from eastern France AlcoholandmortalityinmiddleagedmenfromeasternFrance.
Epidemiology.Mar;9(2):1848.
InthecaseofmiddleagedmenfromeasternFrance,amoderatedailyintakeof
wine (2232 g of alcohol) was associated with a lower risk of death due to CVDs wine(22 32gofalcohol)wasassociatedwithalowerriskofdeathduetoCVDs
(40%),cancer(22%),othercauses(42%),andallcauses(33%).
Calorie Calorie Restriction Restriction Calorie Calorie Restriction Restriction
Resveratrolandhealth N ofPapersandtrials
JangM,etal.Cancerchemopreventive
activityofresveratrol,anaturalproduct
derivedfromgrapes.
S i 1997 J 10 275(5297) 218 20 Science 1997Jan10;275(5297):21820.
MolecularNutrition&FoodResearch
Volume55,Issue8,pages11291141,20JUN2011DOI:10.1002/mnfr.201100143
http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201100143/full#fig1
Calorie Calorie Restriction Restriction == Resveratrol Resveratrol
d l d f l f d l d f l f
Calorie Calorie Restriction Restriction = =Resveratrol Resveratrol
Increasedqualityandspanoflife Increasedqualityandspanoflife
Reduced oxidative stress Reduced oxidative stress Reducedoxidativestress Reducedoxidativestress
Reducedriskofcancer Reducedriskofcancer
Reducedneurodegenerativedisorders Reducedneurodegenerativedisorders
Reduced autoimmune disease Reduced autoimmune disease Reducedautoimmunedisease Reducedautoimmunedisease
Reducedcardiovasculardisease Reducedcardiovasculardisease
ReducedTypeIIdiabetesmellitus ReducedTypeIIdiabetesmellitus
Resveratrolcontentofselectedfruits Resveratrolcontentofselectedfruits
and vegetables and vegetables andvegetables andvegetables
FoodsResveratrol FoodsResveratrol cupservinginmg cupservinginmg
1.Blueberry 1.Blueberry 32 32ng ng/gm /gm
2.Bilberries 2.Bilberries 16 16ng ng/g /g
3.Cranberryrawjuice 3.Cranberryrawjuice 0.2mg/L 0.2mg/L
4.Mulberry 4.Mulberry 0.0021 0.00210.0053mg/g 0.0053mg/g
5.Peanuts(raw) 5.Peanuts(raw) 0.01 0.01 0.26(perservingof146g) 0.26(perservingof146g)
6.Peanuts(boiled) 6.Peanuts(boiled) 0.32 0.321.28 1.28 (perservingof180g) (perservingof180g) p g g p g g
7.Peanutbutter 7.Peanutbutter 0.04 0.04 0.13(perservingof258g) 0.13(perservingof258g)
8.Redgrapes 8.Redgrapes 0.24 0.241.25 1.25 (perservingof160g) (perservingof160g) g p g p (p g g) (p g g)
9.Redgrapejuice(Spanish) 9.Redgrapejuice(Spanish) 0.17 0.17 1.30 1.30 (perservingof150ml) (perservingof150ml)
10. 10.Blackchocolate Blackchocolate 44 mg/L mg/L g/ g/
11. 11.Cocoaliquor Cocoaliquor 5 5mg/L mg/L
Resveratrolcontentofwines Resveratrolcontentofwines
Wi T t l Wi T t l T t l T t l t l t l WinesTotal WinesTotal Total Total resveratrol resveratrol
resveratrol(mg/L) resveratrol(mg/L) 150mlglass(mg) 150mlglass(mg)
1.Whitewine 1.Whitewine 0.05 0.051.80 1.80 0.01 0.01 0.27 0.27
2.Rosewine 2.Rosewine 0.43 0.433.52 3.52 0.06 0.06 0.53 0.53
3.Redwine(Spanish) 3.Redwine(Spanish) 1.92 1.9212.59 12.59 0.29 0.291.89 1.89
4.Red 4.Redwine wine (Global) (Global) 1.98 1.987.13 7.13 0.30 0.30 1.07 1.07
5.Pinotnoir 5.Pinotnoir 0.0 0.02.0 2.0 0.06 0.060.30 0.30
6.Red 6.Redwine wine ((Italian Italian) ) 0.05 0.05 0.008 0.008
7.Merlotswine(Chilean) 7.Merlotswine(Chilean) 2.25 2.25 0.35 0.35 ( ) ( )
Resveratrol Resveratrol Natural Sources Natural Sources Resveratrol Resveratrol NaturalSources NaturalSources
Resveratrolcontentofwines Resveratrolcontentofwines
Itisdifficulttoestimatethenormalhuman Itisdifficulttoestimatethenormalhuman
consumptionof consumptionofResveratrol Resveratrol astheintakeof astheintakeof pp
redwine(verifiedmainsourceof redwine(verifiedmainsourceofResveratrol Resveratrol) )
differs greatly in the population and the differs greatly in the population and the differsgreatlyinthepopulationandthe differsgreatlyinthepopulationandthe
contentof contentof
ff ll Averageof Averageof resveratrol resveratrol inwines inwines
mean 1.9 mean 1.9 1.7 mg/L 1.7 mg/L mean1.9 mean1.9 1.7mg/L 1.7mg/L
consumptionestimateddosemaybeupto consumptionestimateddosemaybeupto
4mg/person/day 4mg/person/day
Averagevaluesinwinesoftheisomers
ofResveratrol andPicedo
7,55mg/L 7,55mg/L 2,15mg/L 2,15mg/L, 0,48mg/L 0,48mg/L 0,67mg/L, 0,67mg/L,
Resveratrol Resveratrol
Bi il bili d M b li Bi il bili d M b li FF II BioavailabilityandMetabolism BioavailabilityandMetabolism Fase Fase II
Resveratrolhasahighabsorption Resveratrolhasahighabsorption
Reachesvariousorgans Reachesvariousorgans
Is metabolized mainly to Is metabolized mainly to glucuronide glucuronide and sulfate derivatives and sulfate derivatives Ismetabolizedmainlyto Ismetabolizedmainlytoglucuronide glucuronide andsulfatederivatives. andsulfatederivatives.
Hasasignificantroleinintestinal Hasasignificantroleinintestinalmicroflora microflora metaboliteproduction metaboliteproduction
dihidroresveratrol dihidroresveratrol
Resveratrolreachespeakplasmaconcentrationpeaksabout30minutes Resveratrolreachespeakplasmaconcentrationpeaksabout30minutes
afterintake,withthe afterintake,withtheglucuronide glucuronide andsulfate,whoseconcentration andsulfate,whoseconcentration
varies depending on the dose varies depending on the dose variesdependingonthedose variesdependingonthedose
Mainly,eliminationisbyurine Mainly,eliminationisbyurine
((Sulfate derivatives 37% Sulfate derivatives 37% Glucuronide Glucuronide derivatives 19% Traces of derivatives 19% Traces of ((Sulfatederivatives37%. Sulfatederivatives37%.Glucuronide Glucuronide derivatives19%Tracesof derivatives19%Tracesof
resveratrol resveratrol aglycone aglycone).Total56%. ).Total56%.
Ahigh44%Resveratrolwhosefateisunknown? Ahigh44%Resveratrolwhosefateisunknown?
Also,somemetabolitesremainunidentified? Also,somemetabolitesremainunidentified?
Meantotal(freeandconjugated) Meantotal(freeandconjugated) trans trans
t l i f f bj t i 25 t l i f f bj t i 25 resveratrolinserumoffoursubjectsgiven25 resveratrolinserumoffoursubjectsgiven25
mgof mgof trans transresveratrolinvariousmatrices. resveratrolinvariousmatrices.
Mean plasma concentrations of resveratrol (A), resveratrol-4-O-glucuronide (B), resveratrol-
3-O-glucuronide (C), and resveratrol-3-O-sulfate (D) versus time in healthy volunteers after
the last of between 21 and 28 daily doses of resveratrol at either 0.5 ... y
Brown V A et al. Cancer Res 2010;70:9003-9011
Clinicaltrialsofresveratrol
Resveratrol pharmacokinetics in healthy volunteers Resveratrolpharmacokineticsinhealthyvolunteers
followingmultipledosing.
AnnalsoftheNewYorkAcademyofSciences
Volume1215,Issue1,pages161169,24JAN2011DOI:10.1111/j.17496632.2010.05853.x
http://onlinelibrary.wiley.com/doi/10.1111/j.17496632.2010.05853.x/full#f1
Resveratrol Resveratrol
BioavailabilityandMetabolism BioavailabilityandMetabolism
Half Halflifeinbloodof lifeinbloodofresveratrol resveratrols s metabolites metabolites
h h d h h h d h approximatesthe9hours,indicatingthatexposureto approximatesthe9hours,indicatingthatexposureto
thesederivativesismuchhigherthanthatdueto thesederivativesismuchhigherthanthatdueto
resveratrol resveratrol aglycone aglycone resveratrol resveratrol aglycone aglycone..
Excretioninmanwithtimedependsonthe Excretioninmanwithtimedependsonthe
concentration of concentration of resveratrol resveratrol in plasma in plasma concentrationof concentrationofresveratrol resveratrol inplasma. inplasma.
Therefore,wheningestedsmallamountsof Therefore,wheningestedsmallamountsof
resveratrol resveratrol it is rapidly metabolized and eliminated it is rapidly metabolized and eliminated resveratrol resveratrol,itisrapidlymetabolizedandeliminated ,itisrapidlymetabolizedandeliminated
whereasiftheamountingestedislarge,thencanbe whereasiftheamountingestedislarge,thencanbe
detectedintissuesandcanpotentiallyenterthecells detectedintissuesandcanpotentiallyenterthecells p y p y
todisplaytheiraction. todisplaytheiraction.

Resveratrol
mg/day

mg/day

Intravascular Intracellular Intestinal

Intravascular
space
Intracellular
space
Intestinal
space
Mengetal.,2004).
Resveratrol Resveratrol
BioavailabilityandMetabolism BioavailabilityandMetabolism
I i i i I i i i i i i i h h h h Invivoactivity Invivoactivity issometimes issometimes greaterthanthat greaterthanthat
described described invitro, invitro, suggeststhatsomeform suggeststhatsomeform
conjugate conjugate generated generated invivo, invivo, ismorepotent ismorepotent
thanthe thanthe precursor( precursor(aglycone aglycone)) ingested. ingested. p ( p ( g y g y )) gg
Resveratrol Resveratrol
BioavailabilityandMetabolism BioavailabilityandMetabolism
Itwasshownthatresveratrolaccumulatesin Itwasshownthatresveratrolaccumulatesin
LDL i l h l d h i LDL i l h l d h i LDLparticles,mayhelpreducetheir LDLparticles,mayhelpreducetheir
susceptibilitytooxidationandthusstressing susceptibilitytooxidationandthusstressing
akeystepin akeystepinatherogenesis atherogenesis. .
DiversehealthbenefitsofResveratrol DiversehealthbenefitsofResveratrol
including includingcardioprotection cardioprotection
Resveratrolin Resveratrolinthe the health health and anddisease disease
Cancer Cancer
Resveratrolhasshownmuchpromiseintreating Resveratrolhasshownmuchpromiseintreating
cancerinlaboratoryanimalsandinvitrohumancell cancerinlaboratoryanimalsandinvitrohumancell
studies yet there is still a large void in human research studies yet there is still a large void in human research studies,yetthereisstillalargevoidinhumanresearch. studies,yetthereisstillalargevoidinhumanresearch.
Thismaysoonchange,assixoftheclinicaltrialscurrently Thismaysoonchange,assixoftheclinicaltrialscurrently
listedforresveratrolonwww.clinicaltrials.govinclude listedforresveratrolonwww.clinicaltrials.govinclude gg
cancerpatientsasatargetpopulation. cancerpatientsasatargetpopulation.
Acts Acts byinhibiting byinhibiting the3stages the3stages ofcarcinogenesis ofcarcinogenesis
1)initiation 1)initiation 2)promotion 2)promotion 3)progression 3)progression
Smoliga JM.,Baur JA.,Hausenblas HA.,(2011)Resveratrol andhealth A
comprehensivereviewofhumanclinicaltrials.
M l N t F d R 55 1129 1141 Mol.Nutr.FoodRes.55,11291141
Resveratrolin Resveratrolinthe the health health and anddisease disease
Cardiovasculareffects Cardiovasculareffects
Oneofthekey Oneofthekeycardioprotective cardioprotective mechanismsof mechanismsof
resveratrol stems from its ability to resveratrol stems from its ability to upregulate upregulate resveratrolstemsfromitsabilityto resveratrolstemsfromitsabilitytoupregulate upregulate
endothelialnitricoxide endothelialnitricoxidesynthase synthase ( (eNOS eNOS)which )which
ultimately increases nitric oxide (NO) mediated ultimately increases nitric oxide (NO) mediated ultimatelyincreasesnitricoxide(NO)mediated ultimatelyincreasesnitricoxide(NO)mediated
vasodilation vasodilation andincreasesblood andincreasesbloodow ow. .
Smoliga JM.,Baur JA.,Hausenblas HA.,(2011)Resveratrol andhealth A
comprehensivereviewofhumanclinicaltrials.
Mol.Nutr.FoodRes.55,11291141
Resveratrolin Resveratrolinthe the health health and anddisease disease
Oxidativestressand Oxidativestressandinammation inammation
Atherosclerosis diabetes mellitus chronic obstructive Atherosclerosis diabetes mellitus chronic obstructive Atherosclerosis,diabetesmellitus,chronicobstructive Atherosclerosis,diabetesmellitus,chronicobstructive
pulmonarydisease,andcancerareexamplesof pulmonarydisease,andcancerareexamplesof
di i t d ith ROS di i t d ith ROS i d d h i i d d h i diseasesassociatedwithROS diseasesassociatedwithROSinducedchronic inducedchronic
inammation inammation. .
Smoliga JM.,Baur JA.,Hausenblas HA.,(2011)Resveratrol andhealth A
comprehensivereviewofhumanclinicaltrials.
Mol.Nutr.FoodRes.55,11291141
Resveratrolin Resveratrolinthe the health health and anddisease disease
Obesityanddiabetes Obesityanddiabetes
Multiple mechanisms have been proposed to account Multiple mechanisms have been proposed to account Multiplemechanismshavebeenproposedtoaccount Multiplemechanismshavebeenproposedtoaccount
fortheinsulin fortheinsulinsensitizingeffectsofresveratrol, sensitizingeffectsofresveratrol,
including including antiinammatory antiinammatory effects effects including includingantiinammatory antiinammatory effects. effects.
S li JM B JA H bl HA (2011) R t l d h lth A Smoliga JM.,Baur JA.,Hausenblas HA.,(2011)Resveratrol andhealth A
comprehensivereviewofhumanclinicaltrials.
Mol. Nutr. Food Res. 55, 11291141 Mol.Nutr.FoodRes.55,1129 1141
Antidiabetic effects of Resveratrol AntidiabeticeffectsofResveratrol
AnnalsoftheNewYorkAcademyofSciences
Volume1215,Issue1,pages3439,24JAN2011DOI:10.1111/j.17496632.2010.05844.x
http://onlinelibrary.wiley.com/doi/10.1111/j.17496632.2010.05844.x/full#f1
Resveratrolin Resveratrolinthe the health health and anddisease disease
Neuroprotective Neuroprotective activity activity
250 mg trans 250 mg transresveratrol to increase cerebral blood resveratrol to increase cerebral blood 250mgtrans 250mgtransresveratroltoincreasecerebralblood resveratroltoincreasecerebralblood
ow ow comparedtoplacebobyFMD comparedtoplacebobyFMD
Smoliga JM.,Baur JA.,Hausenblas HA.,(2011)Resveratrol andhealth A
comprehensive review of human clinical trials comprehensivereviewofhumanclinicaltrials.
Mol.Nutr.FoodRes.55,11291141
Resveratrolin Resveratrolinthe the health health and anddisease disease
Longevity Longevity Longevity Longevity
Resveratrols Resveratrols abilitytocombatagingatthecellularlevel abilitytocombatagingatthecellularlevel
mayultimatelyleadtobreakthroughsingeriatricand mayultimatelyleadtobreakthroughsingeriatricand
anti antiaging medicine, but the data supporting this in aging medicine, but the data supporting this in anti anti agingmedicine,butthedatasupportingthisin agingmedicine,butthedatasupportingthisin
humansarescant. humansarescant.
Smoliga JM.,Baur JA.,Hausenblas HA.,(2011)Resveratrol andhealth A
h i i f h li i l t i l comprehensivereviewofhumanclinicaltrials.
Mol.Nutr.FoodRes.55,11291141
Numberofhealthyvolunteerswhoexperienced Numberofhealthyvolunteerswhoexperienced
adverseeventsdeemedintervention adverseeventsdeemedinterventionrelatedafter relatedafter
dailyingestionofresveratrolfor29d dailyingestionofresveratrolfor29d
Recommendationsfortheuseof Recommendationsfortheuseof
R t l R t l
Whichrelevant(overall)mechanismsofactionof Whichrelevant(overall)mechanismsofactionof
R l h b d d? R l h b d d?
Resveratrol Resveratrol
Modulation Modulationofcellproliferationandapoptosis ofcellproliferationandapoptosis
Modulation Modulation of angiogenesis of angiogenesis
Resveratrolhavebeendocumented? Resveratrolhavebeendocumented?
Modulation Modulationofangiogenesis ofangiogenesis
Inhibition Inhibitionofmetastasis ofmetastasis
Modulation Modulationof ofredox redox status status
Suppression Suppressionof ofadipogenesis adipogenesis andstimulationof andstimulationofadipocyte adipocyte
lipolysis lipolysis
Stimulation Stimulation of of osteogenesis osteogenesis Stimulation Stimulationof ofosteogenesis osteogenesis
Modulation Modulationofmitochondriaactivity ofmitochondriaactivity
Suppression Suppression of inflammation of inflammation Suppression Suppressionofinflammation ofinflammation
Modulation ModulationofDNAdamage ofDNAdamage
Modulation Modulationof ofxenobiotic xenobiotic metabolism metabolism
Modulation Modulationofglutamatemetabolism ofglutamatemetabolism
Estrogenic Estrogenicactivity/anti activity/antiestrogenic estrogenicactivity activity
Resveratrol Resveratrol
45 45InterventionStudies InterventionStudies inHumans inHumans
Resveratrol Resveratrol and and Wine Wine Resveratrol Resveratrol and andWine Wine
Isimportanttonotethattheresveratrol Isimportanttonotethattheresveratrol
concentrations in wine vary widely, even concentrations in wine vary widely, even concentrationsinwinevarywidely,even concentrationsinwinevarywidely,even
withinagivenvarietyofgrapeorgrowing withinagivenvarietyofgrapeorgrowing
ii region. region.
it is unclear if small doses of resveratrol on it is unclear if small doses of resveratrol on itisunclearifsmalldosesofresveratrolon itisunclearifsmalldosesofresveratrolon
aregularbasis(i.e.yearsofwine aregularbasis(i.e.yearsofwine
consumption)wouldhavethesame consumption)wouldhavethesame
physiological effect as the high physiological effect as the high Cmax Cmax physiologicaleffectasthehigh physiologicaleffectasthehighCmax Cmax
observedfromsupplementation. observedfromsupplementation.
Conclusion Conclusion Conclusion Conclusion
WW b li b li th th id id ii f i tl f i tl tt tt We We believe believe the the evidence evidence is is sufciently sufciently strong strong to to
conclude conclude that that a a single single dose dose of of resveratrol resveratrol is is able able to to
Induce Induce benecial benecial physiologic physiologic responses responses and and that that Induce Induce benecial benecial physiologic physiologic responses, responses, and and that that
either either weeks weeks or or months months of of resveratrol resveratrol supplementation supplementation
produces produces physiologic physiologic changes changes that that are are predictive predictive of of produces produces physiologic physiologic changes changes that that are are predictive predictive of of
improved improved health, health, especially especially in in clinical clinical populations populations with with
compromised compromised health health compromised compromised health health..
Resveratrol andhealth Acomprehensivereviewofhuman
clinicaltrials.
JamesM.Smoliga,JosephA.Baur andHeatherA.Hausenblas.
Mol Nutr Food Res 2011 55 1129 1141 Mol.Nutr.FoodRes.2011,55,11291141
Bibliografa Bibliografa
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Molecule?SystematicReviewandRecommendationsontheUseofResveratrol. Molecule?SystematicReviewandRecommendationsontheUseofResveratrol.PLoS PLoS
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juice.JournalofAgriculturalandFoodChemistry.52.pp:935 juice.JournalofAgriculturalandFoodChemistry.52.pp:935942. 942.
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InformedelComitCientficodelaAgenciaEspaoladeSeguridadAlimentariay
Nutricin(AESAN)enrelacinconlaaplicacindeluzUVCparalainduccinde
compuestos bioactivos en uvas . Documento aprobado por el Comit Cientfico en compuestosbioactivos enuvas.Documento aprobado por elComit Cientfico en
sesinplenariade14denoviembrede2007.Revista delcomit cientfico n7
Smoliga JM.,Baur JA.,Hausenblas HA.,(2011)Resveratrolandhealth A
comprehensivereviewofhumanclinicaltrials.Mol.Nutr.FoodRes.55,11291141
IRPrezetal. RevistadeEnologa,2001. Nivelesde resveratrol ypicedo envinosy
cavas
www.clinicaltrials.gov
Thanks for your attention Thanks foryourattention