Resveratrol and Its Effects On Human Health and Longevity

Truth Publishing International, LtdP. O.
Box 29-99 Taichung, Taichung City 40899 Taiwan

Resveratrol
and its Efects on Human Health
and Longevity - Myth or Miracle?
JaMEs BETz
Founder and CEO of Biotivia Bioceuticals, LLC
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medicine or most physicians. It is, however, the truth.
Contents
Introduction 1
Resveratrolversuspenicillin 3
Thescientificcommunityrecognizesresveratrolspotential 4
Vintagewineversusalowlyweed 6
Canamoleculethatprotectsplantsalsoprotecthumans? 9
Whysmallerisbetter 12
Resveratrolandaging,lifespanversushealthspan 13
Mostofwhatyouthinkyouknowaboutagingiswrong 15
Whyareweagingfasterbutlivinglonger? 22
Aprescriptionforlongevity 24
Whatthesciencesays 27
Resveratrolhumanclinicaltrials 27
Aguidetoselectingaqualityresveratrolsupplement 33
Gimmickstowatchourfor 39
Fiveessentialcriteriontopickaresveratrolprovider 41
FutureProspects 44
Scientificstudiesconfirmingstatementsandclaims 47
Resveratrol and its effects on human health and longevit] - N]th or miracle?
Distriouted o] www.haturalhews.com
1
Introduction
Is resveratrol, as many scientists believe, a breakthrough discovery
destinedtomakeagreatercontributiontohumanhealthandthepre-
vention and treatment of age-related disease than antibiotics; or is it
onlyanotherfalsepromisewhichistakingscarceresearchdollarsand
talentawayfromthedevelopmentofpharmaceuticalstheworldneeds
nowtotreatanagingpopulation?
With obesity, diabetes, coronary disease, Alzheimers disease and
cancerreachingnearpandemiclevelsinthedevelopedworld,surelya
compoundwiththeputativediseasepreventionandtreatmentpowers
of resveratrol cannot be dismissed without extensive scientific inves-
tigation. Only five years ago physicians, scientists and pharmaceuti-
cal companies had barely heard of this natural compound, and only a
handful of scientists and physicians possessed any real knowledge of
themoleculespotentialhealthandwellnessefects.
Thefirsthigh-strengthresveratrolsupplement,Bioforte,wasnoteven
ontheconsumersradar.Afewanimalstudieshadshownthepotential
for increases in life span, and a few hundred investigationsprimar-
ilybyresearchersatuniversitiesinJapan,IndiaandChinaelucidated
resveratrols chemoprotective properties, particularly with respect to
cancer and diabetes. However, the same could be said for hundreds
of other phytochemicals and synthetic drugs that had at one time or
another shown promising results in the lab, only to be shuttled of to
oblivion when scientists were unable to replicate the same efects in
mammals,especiallyhumans.
Oneintriguingandratheruniqueaspectofresveratrolthatcaughtthe
attention of both researchers and the public was its ability to extend
2
thelifespanofsomeanimals.Fishfedresveratrol,forexample,lived59
percentlongerthanthesamespecieswithoutresveratrol.Obesemice
lived 31 percent longer and managed to avoid all of the diseases nor-
mallyassociatedwithagingandobesity.
The big missing element in the resveratrol equation, however, was a
lack of published human clinical trials by major medical schools and
researchinstitutions.Verylittlewasthenknownalsoaboutthepoten-
tialtoxicityofresveratrolinhumansorwhatmightconstituteacorrect
dose; and there were concerns about the low bioavailability of resve-
ratrol,aswellasquestionsaboutitspossibleestrogenicefects.Some
scientists speculated that women might be best advised to avoid res-
veratrol for this reason. We now know that precisely the opposite is
true.Resveratrolhasbeenshowninawealthofstudiestobeapowerful
chemoprotectorantandchemotherapeuticagentagainstbreastcancer.
Itseemsthat,asmoreresourcesaredevotedtothestudyofthispotent
molecule,newmedicalandqualityoflifeapplicationscometolighton
aregularbasis.
As the results of the earlier studies were successfully replicated, and
new investigations by research teams around the world uncovered a
virtuallaundrylistofcriticaltranscriptionfactors,signalingpathways
and other important pharmacokinetic efects of this very small mole-
cule,interestinresveratrolincreasedexponentiallyinAsia,theUSand
Europe.Bylate2010,therewereover4,000publishedstudiesonres-
veratrol and a remarkable consensus was developing. Not only were
scientists finding unusually consistent and replicable positive results,
asoneinstitutionaftertheotherexaminedthemoleculeusingdiferent
approachesandtechnologies,butfundamentalnewefectsandmodes
of action were being discovered at an astonishing rate. Many of these
diversepropertiesofresveratrolhavepotentiallyhugeimplicationsfor
thepreventionandtreatmentofhumandisease.
8
Only time will tell if resveratrol manages to unseat antibiotics to take
the top spot as the most important contributor to human health, but
atthispointintimeitcannotbecountedout.Intermsofitsbeneficial
properties relative to chronic conditions such as diabetes, cardiovas-
cular diseases, many cancers and fitness, resveratrol is a strong con-
tenderandforresveratroltheracehasjustbegun.
Resveratrolversuspenicillin
Inaninterviewwithawell-knowninternationaltechnologymagazine
inMarch2009,Itoldthejournalist;Inmyopinion,resveratrolwill,in
thespaceof20or30years,cometoberegardedasamoreimportant
scientific development than penicillin. In this prediction I was refer-
ring to this small molecules potential to positively impact the health,
longevity,andqualityoflifeofthehumanrace.Sevenmonthsaftermy
interview,ascientistresearchingresveratrolatHarvardUniversitytook
thispredictiononestepfurtherbyproclaimingthatresveratrolwillbe
moreimportantthanallantibiotics.
Penicillin was discovered in 1928 and has been credited with saving
manythousands,ifnotmillions,oflives.Resveratrolwasfirstisolated
fromaplantsourcein1940intheWest,buthasbeenusedasatradi-
tionalmedicineinAsiaformorethan2,000years.In1970itwasfirst
characterizedasachemopreventive,asubstancethatprotectshealthy
humantissuefromthedisease-causingefectsofvariousagentssuchas
poordiet,bacteria,virusesandaging.Anexampleofachemopreventive
wouldbetheuseoflowdoseaspirintoprotectagainstheartattacks.
Bothpenicillinandresveratrol,likemostdrugswithalonghistoryofeffi-
cacy,arederivedfromnaturalsources;penicillincomesfromacommon
fungus,andresveratrolisfoundinavarietyofplantsincludinggrapes,
4
peanuts and cranberries, but most importantly in the Japanese Giant
Knotweed plant, also known as Polygonum-cuspidatum. Giant knot-
weedhasbeenusedinAsiaasatraditionalmedicinetotreatimmune
disorders, cancer, and neurological conditions. The plant acquired a
ratherunsavoryreputationasaforeigninvaderthroughoutSoutheast
AsiaandJapan,owingtoitsabilitytosurviveintheharshestconditions
andtocrowdoutotherplantsandcrops.FiveyearsagoaGooglesearch
forgiantknotweedwouldreturnhundredsofarticlesonhowtoexter-
minateit.Thesamesearchtodaywouldbefilledwithscientificstudies
elucidatingitsastonishingmedicalandhealthapplications.
Thescientificcommunityrecognizes
resveratrolspotential
InSeptember2010thefirstinternationalconferenceofresveratrolre-
searcherswasheldaboutaone-hourtrainrideoutsideofCopenhagen,
Denmark.Atthismilestoneevent,over120oftheworldsleadingsci-
entists from prestigious research institutions in the US, Asia, India,
EuropeandAustraliamettopresenttheirfindingsonresveratrol.After
attending this conference and listening to the presentations of these
distinguishedandhighlyaccomplishedscientists,Iamnowconvinced
that,ifanything,mycomparisonofresveratrolwithpenicillinwasex-
tremelyconservative.
Resveratrol and the drugs, treatments, supplements and functional
foodsthatcontainthistinybutincrediblypotentmolecule,willeclipse
penicillins importance within one generation. From 1940 until 2005,
thereweresome800publishedstudiesonresveratrolsbiologicalprop-
ertiesanditshealthbenefits.From2005untilthemiddleof2010,there
havebeenmorethan3,000newstudiesoncells,animals,andhumans.
New and surprising revelations are being announced almost weekly
5
nowbytheleadinguniversities,medicalschoolsandresearchorganiza-
tionsaroundtheworld.Allofthesediscoveriesaddtoourknowledgeof
resveratrolsremarkablerangeofhealthanddiseasepreventionefects
andgivesusnewideasonhowtoapplythisknowledgeforthegoodof
mankind.
The reservations expressed by some physicians and science journal-
ists a few years ago about possible side efects, or over estimation of
thebenefitsofresveratrol,havebeenalmostentirelyrefuted;andnew
previouslyunimaginedbenefitsarebeingrevealedasmorefundingis
devotedtoanimalandhumanclinicaltrialsofthisremarkablenatural
chemical. At a time when we face multiple drug resistant bacteria, an
explosion in the incidence of diabetes, pandemic levels of obesity, de-
bilitatingincreasesinAlzheimersdiseaseandotherformsofdementia,
andmanyotherdiseasesofaging,itisclearthatresveratrolisachemo-
preventivewhosetimehascome.
No single molecule or drug known to medical science has shown the
wide range of potential preventative, therapeutic, and quality of life
enhancement properties of resveratrol. It has been shown to inhibit
cancer, kill bacteria, viruses and fungal infections, extend life span in
animals, improve energy production in cells, quench damaging free
radicals,increaseglucosetoleranceindiabetics,improvecardiacfunc-
tion, enhance physical and mental fitness and concentration, repair
damagedDNA,preventcelldamagefromnuclearradiation,andmuch
more.
Penicillin has been shown to have one use: to combat bacterial infec-
tions.Itsefectivenesshasbeengreatlydiminishedoverthepasttwenty
yearsasmanystrainsofharmfulbacteriahaveacquiredresistancetoit.
Timewilltellifresveratroldoesfulfillitspromiseasaso-calledmiracle
molecule,butifitonlyprovestopossess10percentofthehealthand
medicalbenefitsresearchershaveattributedtoitsofar,itwillindeed
O
make a greater contribution to human health then penicillin, and
perhapsevenallantibiotics.
Vintagewineversusalowlyweed
Given all of the recent publicity about the health benefits of drinking
wine and the so-called French Paradox, one would naturally assume
thattheprincipalsourceofresveratrolusedbyscientistsandsupple-
ment makers is the red wine grape. Although the skin of red grapes
does contain small amounts of resveratrol, the concentration is much
toolowtomakegrapesaneconomicalsourceofthiscompound.
Anotherproblemwiththeextractionofresveratrolfromgrapesisthe
difficultyinremovingtheresiduesfrompesticides,fungicides,andother
agricultural chemicals needed to protect the fruit while it ripens. The
applicationofagriculturalchemicalsnotonlyposesaseriousproblem
fromcontaminationbytoxins,butalsotendstoreducethenaturalpro-
ductionofresveratrolandotherantioxidantsbythegrape.Thehighest
concentrationofresveratrolisfoundinorganicgrapesthatarestressed
byfungus,unfavorableweather,toolittleortoomuchwaterandalack
of pesticides. These conditions also lower the wine production levels
butoftenresultinawineofoutstandingquality.
If the amount of resveratrol in red wine is inadequate to explain the
French Paradox then what is the reason the French sufer 40 percent
less heart disease than the average westerner? As anyone who has
spent time in France knows, the typical French urban diet is high in
fatsandsaltandotherless-than-idealingredientsfromahealthstand-
point. In spite of this fact, the French people tend to have far lower
rates of cancer and cardiovascular disease than do Americans. Even
lungcancerratesarerelativelylowamongstthetobacco-lovingFrench
7
citizens.Furthermore,Francehasmorepeopleovertheageof100than
anyotherEuropeancountry.Manyscientistsnowbelievethatitisthe
fullrangeofpolyphenols,notonlyresveratrol,whichaccountsforthe
chemopreventiveefectsofdrinkingwine.
There is another paradox, which is called the American Paradox. The
American Paradox refers to the fact that even though Americans are
amongstthebestfedandmostaffluentpeopleintheworld,theirrate
of mortality from cancer and heart disease, and more recently, diabe-
tesandtheefectsofobesity,isextraordinarilyhighcomparedtomany
other developed countries. Wine consumption in the US is relatively
lowandthetypicalAmericanandUKdietisheavyonbadfats,redmeat
raisedonantibiotics,growthhormonesandotherchemicals,highfruc-
tosecornsyrup,processedfoodsandchemicalladenburgersandother
fastfoods.Thesefactors,alongwithtoolittleexercise,toomuchstress,
not enough sound sleep, and a heavy reliance on pharmaceuticals to
treatchronicconditions,surelyaccountformuchoftheseriousdiseas-
esintheUS.Theyalsoresultinashorterhealthspan.
Healthspanisthenumberofyearsapersonlivesfreeoftheso-called
diseasesofaging.Apersonwhodiesattheageof85whomanagesto
avoidcancer,diabetes,heartdiseaseandneurologicalconditionssuch
asAlzheimersanddementiahasafarlongerhealthspanthanaperson
whodiesatthesameageaftermanyyearsofintensivemedicaltreat-
mentandadramaticallyimpairedqualityoflifeduetochronicdisease
andincapacity.
So,ifgrapeskinsarenotthepreferredsourceofresveratrol,thenwhat
is?TheansweristheJapaneseGiantKnotweedplant,akaPolygonum-
cuspidatum.Iftherewereamasterninjaoftheplantkingdom,itwould
surelybeJapaneseGiantKnotweed.
8
This voracious predator is one of the toughest and most aggressive
plants in existence. Above the ground it appears to be much like any
otherdocilefloweringgreenperennialbutunderthesurfaceitsroots
tell a diferent story. If you can imagine a gnarly, hard, dense, thick
brownmassthatresemblestherootsofamatureoaktree,youhavea
goodideaofwhattherootsofthisplantlooklike.Itthrivesjustaswell
inhighandlowaltitudes,inhotandcold,andinwetoraridclimates.
Itseemstoactuallygrowstrongerinmorehostileenvironments.Itis
anaggressiveinvaderand,onceestablishedinanarea,willoverwhelm
existingvegetationwithinafewyears.Itissotoughithasbeenknown
togrowupthroughconcretebuildingfoundations.
In Japan and parts of Europe, a fierce battle is waged by farmers and
localcouncilstoeliminateoratleastcontrolit.Inmid-2010,thegovern-
mentoftheUnitedKingdomtooktheextrememeasureofapprovingthe
importationofawormknowntothriveontherootsofthePolygonum-
cuspidatum plant in a rather desperate attempt to rid England and
Walesoftheinvasive weed.BritishandAsianfarmerswhohavetried
toremoveinfestationsofJapaneseGiantKnotweedwilltellyouthatif
even one centimeter of the root of one plant is left in the ground the
plantwillreturnwithavengeancewithinayearortwo.
Thisobnoxiousplantistheprincipalsourceoftheresveratrolusedin
thousands of studies on cells, animals and humans. It is also a 2,000-
year-oldtraditionalmedicineinChinaandTibet.
Resveratrolfunctionsastheimmuneanddefensesystemsforthisplant
andmanyothers.Althoughresveratrolisfoundinpeanuts,blueberries,
and many other plants, the concentration of resveratrol is highest in
Knotweed.Notonlyistheplantrichinresveratrol,itisalsoasourceof
othernaturalprotectivecompoundswithnameslikepolydatin,pteros-
tilbene,andemodin,whichwesternscientistsareonlybeginningtoin-
vestigate.Someoftheseso-calledresveratrolanalogsappeartobeeven
9
morepotentthanresveratrolinfightingspecificdiseasesandimprov-
inghealth.
Pterostilbene, for example, a compound closely related chemically to
resveratrol, has been shown to reverse decline in mental function in
ratswhosecerebrumswerechemicallydamagedevenbetterthanres-
veratroloranypharmaceutical.Italsohaspotentcholesterollowering
properties.Manyscientistsbelievethattheoptimumhealthandmedical
efectswillfollowfromcombiningresveratrolwithotherchemopreven-
tiveplantextractssuchaspterostilbene,fruit-basedpolyphenols,and
otherphytochemicals.Asonephysicianandresearcherrecentlystated,
Antioxidantsarenotsoloacts,theyperformbestasplayersinadiverse
symphonyorchestra.
Canamoleculethatprotectsplants
alsoprotecthumans?
In 2006, scientists working at Harvard began referring to resveratrol
as a hormetic. A hormetic is a substance that is produced by a plant
inresponsetostressessuchasfungus,bacteria,insects,heat,andtoo
much sunlight, which protects the plant against damage or infection.
Thetheoryofzenohormesisisthatthesesubstancesalsoprovidepro-
tection and early warning of environmental threats to the animals in
theirvicinitywhoconsumethem,eitherbyeatingthewholeplantor,in
thecaseofhumans,aconcentratedformoftheplantcompounds,such
asinasupplement.
Hormetics, such as resveratrol, do not normally act directly on the
illnessorbiologicalstressor,asdomostdrugs.Theydonotfunctionlike
conventional medicines such as antibiotics, painkillers, cancer drugs,
andbloodpressureregulators;nordotheygenerallypossessthetoxic-
1O
ityofsyntheticdrugs.Thesenaturalplant-derivedcompoundsworkby
kick-startingprocesseswithintheanimalsowncellsandorgans,which
attackdiseaseorprotectagainstthestressandharmfulenvironmental
factors.
One example of a way in which resveratrol protects animals is its
abilitytopreventandreduceinflammationbysuppressingcertainpro-
teinsproducedbythebodyinresponsetoinfection, injury,and other
stresses.
It is now well known that inflammation, rather then simply being a
symptomofdiseaseasoncethought,isitselfthecauseofmanyhuman
afflictions.Wehaveverycompellingevidence,forexample,thatinflam-
mationplaysakeyroleinautoimmunediseasessuchasarthritis,aller-
gies and multiple sclerosis, as well as many other illnesses including
heartdisease,diabetesandAlzheimersdisease.
When resveratrol is consumed it does not directly reduce inflamma-
tion.Instead,itactivatessystemsinthebodyscellsandproteinsthat
reduceinflammationnaturally.Thisiswhyresveratroliscalledaregu-
latororapotentiator,andnotadrug.Aregulatorworksbyactivating
ordeactivatingvariousenzymes,proteinsandevengenestopreventor
treatthecauseofaproblem,notsimplymaskitssymptoms.
Whenisthelasttimeyouheardofasyntheticdrugthatactuallycured
any disease? Resveratrol inhibits inflammation by activating many of
thesameprocessesthatareactivatedbyanti-inflammatorydrugs,but
inamoresophisticatedandpreciselytargetedmanner.Comparingres-
veratrolwithNSAIDS,non-steroidalanti-inflammatorydrugs,isanalo-
gous to comparing a scalpel to a bread knife. Resveratrol reduces in-
flammationwithoutalsointerferingwiththebeneficialprocessesthat
theanti-inflammatorydrugsinhibit.Italsodoesnothavetheunwanted
11
sideefectsofdrugssuchasaspirin,ibuprofen,andthemorerecently
releasednextgenerationanti-inflammatorydrugs.
Themannerinwhichresveratrolattackscancerisanotherexampleof
itsselective,almostintelligentefectsoncells.Resveratrolinhibitsthe
growthofcancerouscellsthroughanumberofdiferentactions.Itin-
hibitsthegrowthofsmallbloodvesselsthatfeedatumor,butdoesnot
stimulatethespreadofthetumortootherareasofthebody,aprocess
referred to as metastasis, which is one side efect of the anti-cancer
drugs, which also inhibit the supply of blood to a cancerous tumor. It
alsoworksbyactivatingordeactivatingcertainproteinssuchasTumor
NecrosisFactor,TNF,animportantimmunesystemmoleculethatchar-
acterizes many tumors, and by suppressing NF-kB, a protein which is
linkedtoalmostallcancersinhumans.
Many of these anti-cancer efects of resveratrol are the same efects
thatthepharmaceuticalcompaniesarespendingbillionsofdollarsto
reproduceinnewpharmaceuticals.Unfortunately,manyofthemoreef-
fectivedrugsbeingusedtodayarealsohighlypoisonoustothepatient
aswellastothetumor.Oftenitisadeathraceforthepatientbetween
thedrugstoxicefectsandthegrowthandspreadofthecancer.
One oncologist I spoke to at M.D, Anderson Hospital in Houston said;
Veryfewpeopleareactuallydyingofcancerthesedays.Withaggres-
sive treatments such as chemo, radiation and surgery most die of the
therapyfirst,oriftheyareluckytheysurviveboththecancerandthe
treatment.
Thisisnottoproposetheuseofresveratrolasatreatmentforcancer,
oranyotherdiseaseforthatmatter.Weneedmuchmoreactualhuman
clinical data and confirmation of the results seen in the 4000 plus
studies,trialsandinvestigationsalreadycompletedbeforewecansay
withconfidencethatresveratrolisasefectiveasthelaboratorystudies
12
indicateitshouldbeagainstanyspecificdisease.Itmaywellturnout
thatsomecombinationofresveratrolandthemoreefectiveanti-cancer
drugswillbethebeststrategytopursue.Weknowforexamplethat,in
the case of some chemotherapy agents, resveratrol improves their ef-
fectiveness and reduces the severity of their side efects. It may also
turnoutthatsomeotherphytochemical,suchasPterostilbene,maybe
even more efective than resveratrol. There is presently an enormous
amountofresearchbeingundertakentoanswerthesequestions.
Whysmallerisbetter
The larger and more complex a molecule is, the harder it is for the
molecule,beitadrugornutrient,tobetakenupbythecell.Itsalso
veryoftenlessefectiveagainstthebasicprocessordiseasebeingtar-
geted. Larger molecules are also more likely to have unpredictable
sideefects.
Smallermoleculesarebetterabletopassthroughthecellmembranes,
whichactasbarrierssurroundingallcells.Theyarealsobetterableto
preciselytargetindividualdiseasecomponentsatthecellularlevel.The
efectsoflargemolecules,whichconstitutemostpharmaceuticaldrugs
onthemarkettoday,versussmallmolecules,suchasresveratrol,isthe
diference between using a laser to remove a tumor versus removing
theentireorganorlimbsurgically.
The major drug companies, such as Biotica and Genentech, as well as
researchorganizations,includingtheNationalInstitutesofHealth,con-
sidersmallmoleculedrugcandidatestohavethegreatestpotentialas
treatmentsfordiseasessuchasarthritis,Alzheimersdisease,cancer.In
theareasofgenetherapy,andneurologicaldiseasessuchasAlzheimers
disease,largermoleculesareessentiallyinefectiveduetotheirinabil-
18
itytopassthroughthebloodbrainbarrier,theprotectivebarrierwhich
preventspotentiallydamagingchemicalsfromenteringthebrain.Only
smallmoleculescanpassthroughthisprotectivefilter.
Resveratrol is an exceptionally small molecule that has shown aston-
ishingefectsinthousandsofanimalandlaboratorystudies.Inthepast
fewyears,manyofthehealthandlongevityefectsseeninthelabora-
tory have also been confirmedin human clinical trials. We now know
in much finer detail how resveratrol operates at the cellular level to
afect the bodys systems and functions. Going forward, the emphasis
ofresearcherswillshiftfromcellandanimaltrialstoclinicaltrialson
humans. Results from these limited human studies so far have been
nothingshortofastonishing.Itisexpectedthatprogressindiscovering
newmedicalandhealthenhancementapplicationsforresveratrolover
thecomingdecadewillberapidanddramatic.
Resveratrolandaging,lifespan
versushealthspan
Increasesinthemaximumandaveragelifespanofhumansfromthebe-
ginningofthetwentiethcenturyuntilnowhavenotbeenparticularly
impressive compared to the advances made in other areas of science
andtechnology;andinsomecountries,suchasRussia,lifespanshave
actuallydeclined.Predictionsbydemographersofadropintheaverage
USlifespaninthiscenturyarebaseduponcompellingevidenceofde-
clining health amongst the present generation of teens and twenty-
somethings,madeworsebytherisingcostofhealthcare.
Our poor record in extending maximum life span is attributable to
the fact that medical technologies and pharmaceutical research have
focused more on keeping sick people alive rather than on preventing
14
thediseasesanddisabilitiesrelatedtoaging.Drugcompaniesmakefar
more money selling drugs that treat disease than on cures to diseas-
es.Thisisonereasonwhyvirtuallynocureshavebeenoferedbyany
majorpharmaceuticalcompanyinthelast25years.
Oneresultofcorporategreed-drivenmedicinehasbeenthattheaverage
personspendsmorethan90percentofhisorherlifetimemedicalex-
pendituresduringthelastfiveyearsoflife.Althoughaveragelifespans
haveincreasedmoderatelyoverthepasttwodecades,healthspan,the
numberofyearsoneenjoysahealthy,independent,andproductivelife,
hasnotkeptpace.Infact,healthspanappearstobedecreasinginthe
US,theUKandinmuchofAsia,asthecitizensofthesecountriesforsake
traditionaldietandremediesforthewesternlifestyle.
Oneratheralarmingpredictionisthatparentsnowaged45to60may
commonly outlive their children for the first time in history. At the
currentrateofincreaseofmedicalcosts,thepolicyoftreatingdisease
ratherthenpreventingdiseaseisunsustainable.Atsomepointduring
the next ten to twenty years the result will be that health care, and
consequently life span, will be severely rationed, or national budgets
forhealthcarewillconsumemorethanthetotalgovernmentrevenues
for all public services. Preventable diseases such as type 2 diabetes,
manycancers,andcardiovasculardiseasesareincreasinginincidence
atunprecedentedratesinthedevelopedworld.Manyphysiciansand
scientists believe that resveratrol can play a critical strategic role in
reducingrunawayhealthcarecostsbypreventing,delayingortreat-
ing many of the health conditions associated with poor diet, lack of
exercise,andobesity.
15
Mostofwhatyouthinkyou
knowaboutagingiswrong
This applies whether you are a laymen, physician, political leader,
sciencejournalist,socialscientistorauthorofbooksandarticlesonthe
subject.Tobegintheprocessofdismantlingtheprevailingmythsand
misconceptionshereareafewfactstoconsider.
Aging and the widely recognized diseases of aging are
the inevitable consequences of living longer.
False:Agingisnotinitselfthecauseofdiabetes,obesity,heartdisease,
cancerorAlzheimers.Nordoesagingnecessarilyleadtoimpairmentof
emotionalhealth,physicalcapacity,libido,cognition,memoryorintel-
ligence.Agingismerelythenamegiventotheconstellationofadverse
health and medical conditions normally associated with the elapse of
time since one is born. The diseases and disabilities associated with
advancingageallhavespecificcauses.Onesageissimplyameasure-
ment of time lived, and time is not in itself a cause of any disease. By
modifyingonesdietanddailyroutine,stayingphysicallyandmentally
active,adoptingpreventativelifestylepractices,andseekingappropri-
atemedicalinterventionstorepair,replaceandrenovatedeteriorated
body parts and capabilities, virtually all of the diseases normally as-
sociatedwithchronologicalagingcanbeeitherdelayed,preventedor
evenreversed.
Adopting preventative strategies at the individual level can radically
lowerthemortalityratefromdisease,andonesuchstrategyisthein-
telligentuseofsupplementssuchasresveratrol.Unfortunately,thein-
stitutionalizedprofitmotivedrivingtheemphasisontreatmentversus
1O
preventiondeprivesthemajorityoftheworldspopulationoftheben-
efitsofincreasedlongevityandimprovedhealthduringlaterlife.Only
thoseindividualswhotakepersonalresponsibilityfortheirhealthcan
expecttoachieveimprovedhealthandlifespans.
An aging population will be a drag on society,
the young, and the economy.
False: Precisely the opposite scenario to this almost universally pre-
dictedcalamitywillactuallyensue.
The science commentators and social scientists who contend that an
increasedpopulationofoldercitizenswillbeaburdenontheyounger
members of society fail to understand one very simple fact; many
people will live longer because they are free of the disabling medical
conditionswhichpresentlydrainthewealth,vitality,andproductivity
fromsociety.
It is foolish to presume that people will somehow magically live sub-
stantiallylongerwithoutconcurrentimprovementsintheirhealthand
vitality. An elderly professional man or woman, for example, who is
stillhealthy,energetic,andmentallysharpisgreatlyadvantagedovera
youngercolleaguebyvirtueofhisorheradditionalyearsofworkexpe-
rience,judgment,andmaturity.
Thinkaboutit.Giventhechoicebetweentwosurgeons,bothofwhomare
fitandhealthy,wouldyoupreferthedoctorwith40yearsofexperience
and thousands of operations under his belt to remove your ruptured
appendixorthesurgeonwithfiveyearsandonly100operations?
Industryandtheprofessionsarealreadyseeingasurgeindemandfor
older workers over their less experienced colleagues in all developed
17
countries.Asaverage health span increaseswewill seepeopletaking
upnewcareersandstartinguniversityattheageof50andgreater,pro-
fessionalathletesintheir40sand50swillchallengecompetitorswho
aredecadesyounger,andtheaverageretirementagewillincreasedra-
matically,whichmeansthatmanymorepeoplewillbepayingtaxesand
contributingtotheeconomyforfivetotwentyyearslongerduringtheir
lifetimes.Importantly,manyfewerpeoplewillbedrawingretirement
anddisabilitypaymentsorrequiringcostlymedicaltreatments.
If prevention and personal responsibility for health become a reality,
theimprovementsinhealthspancouldbethesinglelargestcontribu-
tortotheUSandUKeconomiestwentyyearsfromnow.Resveratroland
othernaturalcompoundsrelatedtoresveratrolmayhavethepotential
to add many productive years to the life of westerners by extending
healthspanandinhibitingconditionssuchasdementia,diabetes,car-
diovasculardiseaseandcancer.
There is an intrinsic biological limit to the number of
years humans can live healthy, vital, independent lives.
False: Scientists have yet to identify a ticking biological clock that
predetermines the maximum life span for a human. Humans are not
programmed to die at a certain age. We know what the principal
causesofagingare,andwearerapidlyclosinginonsolutionstothese
causes.Some,suchasthecorruptionofonesDNA,anddecreasingtelo-
merelength,whichoccursascellsdivide,areabitmorecomplexthan
others, but none are impossible to solve given the application of suf-
ficientresources.
AManhattan Projectstyleattack onagingwouldprobablysolveall of
thesechallengesinfewerthantenyears.Nowthatthemedicalandre-
searchcommunitiesarebeginningtotreatagingasanyotherdisease,
18
rather then accepting it as inevitable, and simply focusing on making
olderpeoplemorecomfortable,wecanexpectdramaticbreakthroughs
inlifeextension.Eachnewbreakthroughwillgivehumansabitmore
timeduringwhichnewdiscoverieswillbemadethatwillcreatestep-
pingstonestothefinalgoalofindefinitelifespan.
Resveratrolisknowntobeachemoprotectiveagent,whichcanplaya
critical role in delaying or possibly even preventing the most serious
causes of mortality in the developed world. Serious consideration
shouldbegiventoincorporatingresveratrolandothernaturalchemo-
preventivesupplementsintoamorerational,humaneandefectivena-
tionalhealthplanineverydevelopedcountry.Unlessthepriorityshifts
from treatment to prevention, the health, wealth and life span of citi-
zenswill continuetodeclineandnational healthcarebudgetswill be
unabletokeeppace.
A silver bullet is just over the horizon that
will dramatically extend human life span.
False:Theincreaseinhumanlongevitywillcomeinsmallstepswhich
willturnagingfromadebilitatingterminaldiseaseintoatreatablecon-
dition just as the case has been with diseases such as diabetes, HIV-
AIDS,malaria,andmanyothers.
Resveratrolisnotamagicelixirthatwillpreventthediseasesofaging
or compensate for poor health habits. Like stem cell therapy, genetic
engineering,organreplacement,naturalandsyntheticdrugs,exercise,
dietandmedicaltechnology,ithasanimportantparttoplayinanylon-
gevityprogram.Aswecollectmoredatafromhumanclinicaltrialswe
willbebetterabletodefinejustwhatthisroleshouldbe.
19
Resveratrol isonlythefirstinwhatwill likelybealong listofsimilar
compoundswithextensivehealthbenefits.Othercompoundsrelatedto
resveratrol,suchasPterostilbene,Polydatin,andvariousotheranalogs
of resveratrol, will be intensively investigated over the coming few
years,anditisalmostcertainthatresearcherswillfindatreasuretrove
ofgeneticandotherbiologicalefectsevenmoreimpressivethanthose
ofresveratrol.
Pterostilbene, a natural compound found in blueberries, for example,
hasbeenshowninratstoactuallyreversedeclinesindecision-making
abilities and appears to improve intelligence. It also lowers LDL cho-
lesterolmoreefectivelythanresveratroldoes.Polydatinismoreefec-
tivethanresveratrolinpreventingthedamagetohearttissueoccurring
whenaheartattackvictimisresuscitatedoraheartisrestartedfollow-
ingsometypesofcardiacsurgery.Emodin,anantioxidantfoundinthe
JapaneseGiantKnotweedplant,isapotentanti-canceragent.
Themorewelearnabouttheseastonishingmolecules,themoreweare
awedbytheirbenefitstohumanhealth.Manyresearchershavenoted
asynergisticefectwhenresveratroliscombinedwithotherpolyphe-
nols such as curcumin, however not all combinations of polyphenols
are synergistic. For example, a negative efect on Sirt gene activation
hasbeenobservedwhenresveratroliscombinedwiththeantioxidant
quercetin.
Health span and life span will increase as discoveries are made and
knowledgeiscreatedthatwillleadtocuresandtherapiestotreatthe
so-calleddiseasesofaging.Naturalchemoprotectivessuchasresvera-
trol, curcumin and a wide range of other polyphenols may take over
muchoftherolesyntheticdrugsnowplayintreatingdiseaseafterthe
factratherthanfocusingonpreventingdiseasenaturally.
2O
Technology advances will lead to longer life spans
and elimination of many diseases.
True:Dr.SinclairatHarvardUniversitydiscoveredthegeneactivation
properties of resveratrol only because he had the help of a new com-
puterizedchemicalscreeningsystemthatcouldexaminethousandsof
moleculesfortheiranti-aginggeneactivationpropertiesinthetimeit
previouslytooktoinvestigateonlyahandfulofcompounds.
Advances in computing power are rapidly increasing our ability to
comprehendtheintricaciesofthemetabolicprocessandtorealistically
simulatecriticalbiologicalpathways.Thepastdecadesawthedevelop-
mentofgenomics.Thecomingtenyearswillconsolidatethisknowledge
andmoveontounravelingtheroleoftheproteinswhichareencoded
by our genes. This will represent an enormous advance in our ability
todesigndrugsthatturnonbeneficialgenesandswitchofthegenes
responsible for diseases such as multiple sclerosis, asthma, cystic fi-
brosis,thalassemia,mentalillnessandhundredsofotherdiseasesthat
arecausedbyeitheraspecificgeneticabnormalityoracombinationof
geneticfactors.
Wewillalsobegintosolvethemysteryofwhatfunctionthe95percent
of the genome which does not code for proteins plays in human de-
velopment. This will lead to the design of new strategies to prevent
or reverse aging and result in quantum leaps in human longevity. By
2020computersandothermedicaldeviceswillbepowerfulandcheap
enough to give scientists the tools they have needed to virtually stop
the aging process in animals. This goal has already been achieved in
thelab.
The convergence of thousands of independent discoveries and incre-
mental breakthroughs by dedicated professionals working in diverse
21
fieldsarecreatingsynergiesandmutuallyreinforcingdiscoveriesthat
arethekeytoextendinglifespanandeventuallyeliminatingagingal-
together. Developments in advanced prosthetics, stem cell therapy,
organreplacement,andthepreventionandtreatmentofcancer,heart
disease,andneurologicalconditionssuchasAlzheimersanddementia
willmeanthatthosepersonswhoarepresentlyunder60yearsofage
andinexcellenthealthwillhaveareasonablygoodchanceoflivingin-
definitely.Thisassumesthattheyarefinanciallyabletoafordthetreat-
ments,drugs,andtherapeuticprocedures,whichwillbecomeavailable
overthenext30years.
Beyond2040,agingwillbesimplyachronicconditiontreatableorpre-
ventableatareasonablecosttothepatient.Thetimingofonesdeath
will become for many people a matter of individual choice. Accidents
andneedlesswarsoverresourceswillbecomethemaincausesofdeath
inthedevelopedworld.Unlesswestopdestroyingourplanetthrough
theplunderingofitsresourcesandpoisoningitsairandwater,climate
changeandscarcityofusablewaterandbreathableairwillrenderany
increaseswemakeinaveragelifespansawasteoftimeandefort.Ifwe
destroythevitalbalance,whichsustainslifeonthisplanet,nothingelse
willmatter.
We must first fully understand the cells incredibly
complex metabolic process before we can develop effec-
tive drugs and other preventatives and treatments for
the disease we call aging.
False: Many of the safest and most successful drugs in use today
work by targeting unidentified biological processes they were
not initially designed to attack. Luck plays a big part in drug
discovery. Serendipity and persistence on the part of researchers and
physicians resulted in the discovery of penicillin, aspirin, pain killers
22
andmanyothervaluabledrugs.Partialknowledgeofthecellular-level
biologicalprocessesbeingtargeted,coupledwiththeintelligentappli-
cationoftrialanderror,isanefectiveandrationallifeextensionstrat-
egy. It probably ofers the greatest potential to conquer aging in the
near-tomid-term.
When Dr. Sinclair discovered the ability of resveratrol to activate the
so-called anti-aging genes, it was due to serendipity as much as to
science.Sinclairdiscoveredthispreviouslyunknownabilityofresvera-
trolbecausehewasabletoquicklyscreenthousandsofchemicalsfor
thispropertyduetoadvanceswhichhadjustbeenmadeinlaboratory
analysistechnology.Hisdiscoverydidnotcomeaboutbecausehehad
somereasontobelievethatresveratrolmightfitanyreceptoronacell
or it might have anti-inflammatory or antioxidant properties. In fact,
so called rational drug development, in which computers attempt to
matchchemicalstocellreceptorsinasearchfordrugcandidates,has
failedtoliveuptoitspromise.
Whyareweagingfasterbut
livinglonger?
The decline in the health status of the average British or American
citizenisnotprincipallyanaturalorinevitableconsequenceofhuman
evolutionnorisitduetotheriseofnewdiseasesorthedeteriorationof
thequalityoftheenvironmentinwhichwelive,althoughenvironmen-
tal factors do militate against increasing life spans. The fundamental
causesaresimpleandwellknown.
Life span increases so far have come about only because advances
in medical technology and pharmaceuticals are keeping sick people
alive longer, but at a very high and untenable cost, not because dis-
28
eases and disabilities are being prevented or that people are staying
healthylonger.Furtherincreasesinbothhealthspanandlifespanmust
come from adopting prevention as our primary focus. We have yet to
begintoexploittheadvantagesofpreventionattheinstitutionallevel.
Resveratrol is one molecule that may play an important part in both
preventionandtreatmentofdisease.
Obesityandlifestylefactors,notaging,aretheprincipalcauseofdiabe-
tes,hypertension,mostheartconditions,andmostcancers.Obesityis
alsoamajorcausalfactorforgastricrefluxdisease,gallbladderdisease,
degenerationofL-sacralspineandweight-bearingjoints,asthmaand
hundredsofotheradversemedicalconditions.Resveratrolwasshown
to increase the life span and health span in obese mammals. In Dr.
Sinclairs now famous study published in the journal Nature, obese
rats fed resveratrol lived 31 percent longer. When the vital organs of
the resveratrol-fed rats were examined by a pathologist they resem-
bledthoseofyoung,lean,healthyrats.
Lackofregularexercisecompoundsthenegativemedicalconsequences
ofobesity,andisariskfactorforosteoporosisaswellasawiderangeof
adversephysical,emotionalandneurologicalconditions.Mitochondria
are the cells energy factory. Resveratrol increases mitochondrial
density and enhances mitochondrial function. Rats fed resveratrol in
the study by Dr. Auer and published in the journal Cell, were able to
runtwiceasfarasratsnotfedresveratrol.Whenthemuscletissueof
resveratrol-fedanimalsisexaminedunderamicroscope,theincreased
numberandhealthofthemitochondriaisevident.
Probably the largest contributor to early aging and the diseases as-
sociated with aging is poor diet. Excessive consumption of red meat,
processedfoods,sugarsandhighfructosecornsyrup,aswellastrans
fats and the lack of omega-3 rich foods and polyphenols from fruits
and green leafy vegetables, and overeating in general are all enemies
24
of human health span and longevity. Resveratrol has been shown to
countermanyoftheadverseefectsofpoordiet.Weknowthatobese
ratsfedresveratrolinDr.Sinclairsstudyoutlivedtheratsnotfedresve-
ratrol,butitislesswellknownthattheresveratrol-fedratsalsoavoided
allofthenormaldiseasesassociatedwithagingandobesity.
Chronic unresolved stress results in endocrine imbalances, immune
system dysfunction, inflammation, sleep disorders and neurologi-
cal impairment. Resveratrol is a natural anti-inflammatory agent and
may have important neuroprotective properties. In a study done at
NorthumbriaUniversityintheUK,studentswhoweregiveneitherone
ortwoBiofortecapsulescontaining250mgoftrans-resveratrolexperi-
enceda100percenttoover200percentincreaseinbrainbloodflow.
Aprescriptionforlongevity
Anyone can substantially increase both health span and life span by
adoptingthefollowingmeasures:
Stopusingtobaccoproductsofalltypesandlimitalcoholusetono
morethanthreeglassesofwineorthreeouncesofspiritsperday.
Reduce,orbetteryeteliminate,allprocessedfoods,fastfoods,and
sweetened beverages. Make green leafy vegetables your primary
foodgroup.Reduceoreliminateredmeatfromyourdiet.
Takeapill.Addthebelowsupplementstoyourdailyroutine:
Biotiviaorotherqualityresveratrol,250mgto1,000mg
25
Pterostilbene, a molecule closely related to resveratrol, 100mg
daily.
Non-fish sourced omega-3, such as Green Omega 3, with EPA and
DHA,atleast500mg.
Amulti-antioxidant(notmultivitamin)complexsuchasBioQuench,
500mgto1,000mg
Vitamin D, 10,000 IU. Most people are deficient in this important
nutrient.
Acetyl L-Carnitine and Alpha Lipoic Acid supplements, 250 mg of
each.
Curcumin,alsoknownasthespiceturmeric,1to2gramsperday.
VitaminC,preferablytheoilsolubleformcalledascorbylpalmitate,
1gramperday.
Thereare,ofcourse,manyothersupplementsthatmayhaveabenefi-
cial impact on health span and longevity, but the published scientific
evidencebestsupportstheabovenutrients.Themajorityofover-the-
countersupplementsareofverylittlechemoprotectivevalue.
Inadditiontotheabovesupplementregime,incorporatethefollowing
intoyourdailyroutine:
Incorporateatleast30minutesofmoderatetointenseexercise,at
least three times each week, into your routine. Get up from your
computer,videogames,iPad,email,andFacebookaccountsanddo
somethingphysical,preferablyoutdoors.Evenifyouareoverweight
2O
youcanbefit.Infact,itishealthiertobefitandfatthenunfitand
thin.
Meditate,oratleasttakeaone-hourmentalandphysicalbreakfrom
yourdailygrind,onceeachday.Middaynapsof20to45minutesare
alsoextremelybeneficial.
Maintainahealthyweight,whichisbestmeasuredbydividingyour
heightininchesbyyourwaistcircumference.Theresultshouldbe
nolessthan2.0.ThepopularBMImeasurementisbasicallyworth-
less,asitmakesnodistinctionbetweenleanandfatbodymass.
Use high quality air and water purifiers in your home and office.
Lobbyyourpoliticalleaderstotakeenvironmentalprotectionand
cleanenergyseriously.Atsomepointthelimitonlifespanwillbe
thedeterminedbytheabilityoftheEarthsclimateandresourcesto
supporthumanlife.
See your physician at least once per year and repair failing parts
justasyoudowithyourautomobileoranyothercomplexmachine.
If your eyesight is deteriorating, consider having a corrective pro-
cedurebyaneyesurgeon,Ifyouhavedentalorperiodontalissues,
see your dentist and get them sorted before they lead to serious
disease.Teethandguminfectionscancausefatalheartdiseaseand
otherlifethreateningconditions.
Donotignoresymptomsofanunderlyingproblem.Yourchancesof
surviving cancer, as we all know, are dramatically enhanced if you
begintreatmentearly.Thesameruleappliestodiabetesandmost
otherchronicdiseases.
27
Drive sensibly, wear seat belts and control your stress. It would
be a pity to live a healthy life and then die at the age of 40 on the
motorway.
Use an advanced UV protection product to control photo aging of
the skin. Resveratrol has been shown to both prevent and reverse
theDNAdamage,whichagestheskin.Onecreamthatcontainsres-
veratrolinhighconcentrationalongwithotherpolyphenolsisCelle
byBiotivia.
Whatthesciencesays
Themostrecentresearchresultsbyscientistsandphysiciansworking
atprestigiousmedicalschoolsandotherinstitutionsaroundtheworld
werepresentedinSeptemberofthisyearattheResveratrol2010,the
firstinternationalscienceconferenceonresveratrolandhealth.There
isnotenoughspaceinthispapertodiscussalloftheremarkableresults
presentedby the experts at this conference. I have chosentosumma-
rizethehighpointsofsomeofthemoreinterestingandauthoritative
studiesbelow.Itshouldbenotedthatnostudywaspresentedinwhich
anytoxicorseriousadverseefectoforaladministrationofresveratrol
toanimalsorhumanswasobserved,andnostudyortrialwasstopped
duetothepresenceofsuchnegativeefects.
Resveratrolhumanclinicaltrials
Overthepastthreeyearsasubstantialnumberofmedicalschoolsand
researchinstitutionshaveundertakenstudiesofresveratrolsability
to prevent or treat disease in humans. The number of such clinical
28
trialsisincreasingweekly.Afewofthemoreimportantonesarede-
scribedbelow.
Diabetes
AlbertEinsteinMedicalCollegeconductedtwohumanclinicaltrialsin
whichtheabilityofresveratroltoenhancemitochondrialfunctionand
improve insulin sensitivity, two important functions the drug compa-
niesareattemptingtotargetwithanewgenerationofdiabetesdrugs.
The results of this study were extremely positive and it was recently
announcedthatthissmall-scalestudyusingBioforteresveratrolwillbe
expandedlaterthisyearbyAlbertEinsteinMedicalCollegeincollabora-
tionwiththeMayoClinic.Althoughthereareseveralotherhumanclini-
cal trials either underway or about to commence, the Einstein/Mayo
Clinicstudyistheonetolookoutfor.Theresultsofthisrelativelylarge-
scaledouble-blindtrialwilllikelyanswerthequestionofresveratrols
potentialusefulnessasanalternativetosomeofthepresentsideefect
ladenpharmaceuticals.
Onesuchnewgenerationdiabetesdrugannouncedattheannualscience
conference of the American Diabetes Association in Orlando Florida
warned that two adverse efects had been seen in the FDA mandated
drug trials of this compound. The first was that the drug can actually
cause someone who does not sufer from Type 2 Diabetes to contract
thedisease,andthesecondwasthatithadthenastytendencytolower
blood glucose levels so severely that the patient could die. Other dia-
betesdrugshavebeentakenofthemarketafterlife-threateningside
efectswerediscovered.
29
HeartDisease
Stony Brook University Medical Center, a renowned cardiac center in
NewYork,hasbegunalong-termhumanstudyofresveratrolspoten-
tialabilitytopreventpatientswhohavesuferedoneheartattackfrom
havingasecondone,orincreasingthechancesthat,ifthepatientdoes
haveasubsequentinfarct,heorshewillsurviveit.
Theabilityofresveratrolandpterostilbeneandpolydatin,analogsofres-
veratrol,topreventthecardiactissuedamagethatoccurswhenaheart,
which stopped beating due to a heart attack or open heart surgery, is
perfusedwithoxygen.Interestinglyenough,thetissuedamage,,which
heartattackvictimssufer,doesnothappenwhiletheheartisstopped,
evenforconsiderablelengthsoftime.Thedamageoccursduetoaflood
of destructive free radicals, which occurs when oxygen again flows
through the tissue. This finding suggests that paramedics might one
day be equipped with injectable resveratrol to administer to patients
whoseheartshavestoppedpriortoperfusingtheheartwithoxygen.
COPD,ChronicObstructivePulmonaryDisease
COPDisacommonbutseriousanddebilitatingconditioncausedbyin-
flammationofthetissuesofthelungandtheresultinginabilitytodeliver
sufficientamountsofoxygentothebloodandtoremoveaccumulated
carbondioxide.Suferersofthisconditionconstantlyfeelthattheyare
sufocating. COPD afects millions of people and is a common disease
of smokers and people who have worked for many years in a highly
polluted environment, such as a chemical factory or mine. Imperial
College of London has obtained an international patent on the use of
resveratroltotreatCOPD.Asofthispublicationnomedicinehasbeen
developedbyanypharmaceuticalcompanyonthebasisofthispatent,
howevertheUniversityofTorino,foundedin1404andthehomeoftwo
8O
recentNobelPrizewinners,isabouttoembarkonastudyofsmokers
to study resveratrols ability to alleviate the pulmonary inflammation
causedbytheirhabit.
Metabolicsyndrome,prediabetesandnon-alcoholic
fattyliverdisease
A study funded by the Danish government is about to begin in June
2011.TheleadresearcherisDr.SteenBnlkkePedersenfromAarhus
University. The project will include a one year randomized double-
blindedstudyof50subjects.AsidefromAarhusUniversityandFluxome,
the Aarhus University Hospital, University of Southern Denmark,
Roskilde University and Pennsylvania State University will contribute
totheclinicaltrial.This$3.5millionhumanclinicaltrialwillinvestigate
resveratrols potential to treat and prevent a constellation of human
health conditions which are known to accompany aging. This will be
the most extensive and best-funded long-term human clinical trial to
date.Theknowledgegleanedfromthisinvestigationwillbeinvaluable
inassessingthepotentialofresveratroltoalleviatearangeofadverse
healthconsequenceswhichafflictmillionsofpeopleworldwide.
Weexpecttoprovethatresveratrolinhumanscanneutralizethedet-
rimental efect of obesity on whole body metabolism, like low-grade
chronic inflammation, insulin resistance and lipid infiltration in liver
andskeletalmuscle,Dr.Pedersensaid.
Thalassemia
BetaThalassemiaisaninheriteddisorderinwhicheitherveryfewor
noredbloodcellsareproducedbythebonemarrowafterinfancy.The
treatment is monthly whole blood transfusions and the use of a drug
81
whichisextremelytoxicandcannotbeusedwithchildren.Thedisease
dramatically impacts the suferers quality of life and often results in
death around the age of puberty. Because it is more common in less
developed countries where it is virtually impossible for anyone other
thantheverywealthytoobtainregularsuppliesofcleanwholeblood
fortherequiredtransfusions,thefatalityrateishigh.Evenifthepatient
isabletoobtainmonthlytransfusionsandisabletoafordthedrugsto
treatthedisease,heorsheisconstantlyanemicandlackingofenergy.
Dr. Roberto Gambari, physician and molecular biologist, and well-
known authority on Beta Thalassemia, at the University of Ferrara,
discoveredthatTransmaxresveratrol,theconcentratedpureresvera-
trol supplement used by researchers in most clinical trials, was able
tostimulatetheproductionofembryonicredbloodcells,thetypethat
areproducedwhenababyisstillinthemotherswomb,butsoonafter
birth cease being produced. This is an extremely important finding
and one that has led to a human clinical trial now underway at the
UniversityofFerrara.Thesubjectsinthisclinicaltrialarehospitalized,
adolescentBetaThalassemiapatients.Hopefullyresveratrolwillgivea
newleaseonlifetothosewhosuferadiseasethatthepharmaceutical
companiesdonotconsiderpotentiallyprofitableenoughtodevelopa
newdrugfor.
Brainbloodflowandcognition
In2010NorthumbriaUniversity,locatedinnortheasternEngland,con-
ducted a human clinical trial in which university students were given
either one or two Bioforte capsules, each containing 250mg of trans-
resveratrol.Theobjectiveofthisstudywastoassesstheefectsoforal
resveratroloncognitiveperformanceandlocalizedcerebralbloodflow
variablesinhealthyhumanadults.
82
Inthisrandomized,double-blind,placebo-controlled,crossoverstudy,
22 healthy adults received placebo and 2 doses (250 and 500 mg) of
trans-resveratrol in counterbalanced order on separate days. After a
45-minuterestingabsorptionperiod,theparticipantsperformedase-
lection of cognitive tasks that activate the frontal cortex for an addi-
tional36minutes.Cerebralbloodflowandhemodynamics,asindexed
by concentration changes in oxygenated and deoxygenated hemoglo-
bin,wereassessedinthefrontalcortexthroughouttheposttreatment
periodwiththeuseofnear-infraredspectroscopy.Thepresenceofres-
veratrolanditsconjugatesinplasmawasconfirmedbyHPLCafterthe
samedosesinaseparatecohort(n=9).
Resveratroladministrationresultedindose-dependentincreasesince-
rebralbloodflowduringtaskperformance,asindexedbytotalconcen-
trationsofhemoglobin.Therewasalsoanincreaseindeoxyhemoglobin
afterboth dosesofresveratrol, whichsuggestedenhancedoxygen ex-
tractionthatbecameapparenttowardtheendofthe45-minuteabsorp-
tionphaseandwassustainedthroughouttaskperformance.Cognitive
function was not afected. Resveratrol metabolites were present in
plasmathroughoutthecognitivetaskperiod.Thesecondphaseofthis
trial is currently underway. In this human clinical study the students
will be given daily doses of Bioforte resveratrol over a period of one
monthversusthesingle doseregimenofthefirsttrial. Additional pa-
rameters,suchasresveratrolsefectonthestudentsweight,sleeppat-
ternsandmoodwillbeexaminedinthistrial.
Fitnessandphysicalperformance
TheUniversityofTexasisconductingahumantrialtoinvestigateresve-
ratrolsefectonhumanathleticperformanceandphysicalendurance.
The trial, also using Transmax, is presently underway and results are
expectedinabouttwomonths.DaveNoble,a64-year-oldAmericanwho
88
participated in competitive swimming events as a twenty something,
startedtocompeteagainaftera40-yearsabbaticalfromthesport.Dave
beganusingaresveratrolsupplement,thesameoneusedinmostofthe
medicalschooltrials,aftersixmonthsoftraining.Withintwomonths
ofbeginningsupplementationwithresveratrolDavewasbreakingper-
sonalrecordsthathesetwhenhewasinhisearlytwenties.Asof1May
2011 Dave was within the top five amateur swimmers worldwide for
hiseventandcategory.Davecreditsresveratrolforhisathleticimprove-
ment.Hetakes500mgofresveratrolabout45minutespriortotraining
andcompeting,andcreditsthecompoundforhissuccess.Hehasbeen
competingnowforaboutthreeyearssincestartingagainattheageof
61,andeachmonthhistimesimproveandhisendurance,asmeasured
bymaximumoxygenuptake,knownasVO2Max,isincreased.
Aguidetoselectingaquality
resveratrolsupplement
SincethestudybyDr.DavidSinclairwaspublishedinthejournalNature,
aplethoraofnewcompanieshavesprungintoexistenceoferingresve-
ratrol supplements. Evaluating resveratrol sellers and their products
hasbecomeaconfusingandfrustratingprocess.Thisguideismeantto
elucidatethemostimportantfactorsoneshouldusetodistinguishone
resveratrolsupplementfromanotherbasedupontheirrelativequality,
valueandlikelihoodofbeingefective.
Unlikemostdietarysupplements,thousandsofwellmanagedauthori-
tative scientific studies and trials have highlighted resveratrols po-
tentially critical health properties as a treatment for diabetes, cancer,
inflammatory and autoimmune diseases and neurological conditions.
Withoutpassingjudgmentonresveratrolsactualcurativepowers,itis
clearthatmanypeoplepurchaseresveratrolasapreventativeortreat-
84
mentforaseriousmedicalcondition.Iftheresveratroltheseconsumers
purchaseisnotahighquality,properlymanufactured,bioactivecom-
poundthentheyarenotonlywastingtheirmoneybutarealsofailing
toobtainwhateverbenefitsresveratrolmayoferforthepreventionor
treatmentofdisease.
The criteria below are based upon valid scientific principals and ac-
ceptedstandardsfortheevaluationofafunctionaldietarysupplement
such as resveratrol. The standards can also be used in judging other
supplements.
Yoursupplier
AftertheDr.SinclairstudywaspublishedinthejournalNature,aflood
ofnew,inexperiencedandillequippedonlineresveratrolsupplierssud-
denlystartedtopromotethiscompound.Manyofthesecompaniesand
individuals engaged in unethical and deceptive marketing campaigns,
whichluredcustomersinwithphoneyfreeofersandotherinduce-
ments. Their products often did not contain measurable amounts of
resveratroland,inmanycases,theoperatorsandownersofthesecom-
panieshadahistoryoffraud.Thelessonhereisthatoneiswelladvised
toselectacompanywithahistoryofatleasttenyearsintheindustry,
andonewhichspecializesinadvancednutraceuticals,versusageneric
supplementmaker.Resveratrolisadifficultcompoundtoprocessand,
unlessspecialcareistakenthroughoutthemanufacturingprocess,can
easilydegradeintoaworthlesspowder.
85
Ethicallabeling
Thelabelsofmanyresveratrolsuppliersdonotdisclosetheexactform
of resveratrol or the quantity contained in their supplement. Some
simplycalltheirmainingredientredwinecomplexoraproprietary
blend.Giventhatredwinecontainslessthan1percentresveratrol,it
seemsabitstrangethatacompanywouldusethisdescriptiontolabela
resveratrolproductunlessthepurposewastoconcealtheactualingre-
dientsintheproduct.Aproprietaryblendcanbealmostanything,but
isunlikelytoconsistofpureresveratrolgiventherelativelyhighcostof
qualityresveratrolversusotherpossibleingredients.
Resveratroliscomposedoftwoprincipalisomers:trans-resveratroland
cis-resveratrol.Onlythetrans-isomerhasbeenassociatedwithhealth
benefits.Thecisisomeractuallyactstonullifytheefectsoftrans-res-
veratrol.Unlessthesellerstatesonthelabelthattheproductconsists
entirelyofthetrans-resveratrolformitishighlylikelythatitcontains
eithersomeorallofcis-resveratrol,whichis,byanorderofmagnitude,
thelesscostlyformofresveratrol.
Dosage
The appropriate dosage of trans-resveratrol is a highly contentious
issue,withrespecttotherhetoricofresveratrolsuppliers,thatis.The
scienceregardingdosageisrelativelyclearhowever.Althoughdosesof
around50mgto100mgappearfromsomestudiestohavepotentially
importantpreventativeefects,theconsensusisthatatleast250mgis
required to reach the threshold for efficacy as demonstrated in most
animal and in vitro studies undertaken to date. This equates to the
humanequivalentofthedosageusedintheDr.Sinclairstudyandmany
otherstudies.Thedoserecommendedbymostcliniciansfortreatment
ofanexistingconditionrangesfrom1,000mgto4,000mg.Howeverit
8O
isrecommendedthatoneconsultaphysicianbeforetakingadoseover
1,000mgdaily.Notoxicityorseriousadverseefectswereobservedin
severalanimalandhumanstudiesinwhichupto5,000mgwasgivenon
adailybasisforanextendedperiodoftime.Inanimalstudies,dosages
uptothehumanequivalentof30,000mghavebeentoleratedwithonly
minor adverse efects. Products which ofer less than 250mg of pure
trans-resveratrolareofdubiousvalue.
Sourceofresveratrol
Although much of the news about resveratrol mentions the red wine
grapeasitssource,winegrapesarenotapracticalordesirablesource
ofresveratrolfortwoimportantreasons.Firstgrapesaresubjectedto
awiderange oftoxicchemicalsinthecultivation process.Fungicides,
pesticides, chemical fertilizers and many more chemicals are sprayed
directly on wine grapes. Since resveratrol comes from the skins, it is
verydifficulttoeliminatecontaminationintheresveratrolconcentrate.
The second reason wine grapes are not a good source of resveratrol
is that it is impossible to produce a high potency supplement using
grapeextract.Theconcentrationofresveratrolingrapeskinsissimply
toolow.Thisiswhy,invirtuallyalloftheanimalandtissuestudieson
thehealthbenefitsofresveratrol,thesourceoftheresveratrolwasthe
JapaneseGiantKnotweedplant,whichgrowswithoutfertilizersorag-
riculturalchemicalsinthewild.
Naturalversussynthetic
Synthetic resveratrol can be produced using one of two methods, fer-
mentationandchemicalengineering.Inthecaseoffermentation,ayeast
or bacteria is genetically modified to produce resveratrol. Chemically
engineeredresveratrolisconstructedfromabrothofcompoundsusing
87
organicchemistrytoengineerthemolecule.Bothprocessesarefraught
withpotentialpitfalls.
In the case of fermentation often what may occur is that bits of the
bacteriaoryeastDNAusedtoproducetheresveratrolshowupinthe
finishedmaterial.Thismeansthatifyouusethisproduct,youarecon-
suminganovelsubstanceacompoundthathasneverbeenpreviously
consumedbyahuman,withpotentiallytoxicorotherotherunknown
efects. In the case of a chemically engineered resveratrol product,
theissueiscontamination bysmall amountsofthechemicalsusedto
producethesyntheticresveratrol.
On a typical HPLC graph of a synthetic resveratrol there will almost
always be spikes on the chart of what are referred to as unknowns.
These trace chemicals are by-products of the creation of the resvera-
trol which are unidentified and assumed, or hoped, to be non-toxic.
Furthermore,naturallyextractedresveratrolfromthepolygonumcus-
pidatumplantisknowntobeefectiveandnon-toxic.Neitherproper-
ties have been definitively verified in regard to synthetic resveratrol.
When a natural compound such as resveratrol is copied using chemi-
cals,yeastorbacteriaoftenthefinalproductisnottrulyidenticaltothe
natural compound. There is only one reason why some suppliers use
synthetic resveratrol in place of natural resveratrol from polygonum
cuspidatum.Thereasonisthefarlowercostofsyntheticresveratrol.If
asupplierdoesnotdisclosewhichtypeofresveratroliscontainedinits
productsyoucannormallyassumethatitisthesyntheticvariety.
Capsulesize
Asizezerocapsuleisabletocontainabout500mgofresveratrol,but
onlyifthebasematerialisprocessedusingpharmaceuticaltechnology
andequipment.Thisisthelargestsizecapsulethatisquiteeasilyswal-
88
lowed by most people. Sellers who use larger capsules do so to com-
pensate for the fact that they are simply stuffing lower potency raw
materialintoacapsulewithoutgoingthroughthetimeandexpenseof
purifyingandgranulatingtheresveratrolextract.Alargercapsulesize
alsoallowsfortheuseofvariousfillersandchemicalssuchassilicon,
magnesiumsterate,celluloseandotheradditives.Thebestqualityres-
veratrolsupplementsarecontainedinasizezero,all-vegetablecapsule
and contain no additives or fillers at all. There is no reason why you
shouldhavetoconsumesand,chemicals,andotherunwantedingredi-
entsinyoursupplementsimplybecauseyoursuppliercannotbeboth-
eredwithusingmoresophisticatedprocessingandfillingtechnology.
Resveratrolishighlysusceptibletodeteriorationby
oxidationandexposuretoultravioletlight
A quality supplement will be protected from oxidation during man-
ufacture through the use of nitrogen gas-filled processing lines. The
bottle in which the supplement is contained should also use an inert
gastopreventoxidationduringshipment.Howeveroncethebottleis
openedoxygenisallowedtoenter.Ifactivepackagingtechnologyisnot
employed to protect against this damage, the shelf life of the product
willbeseriouslydegraded.Manyresveratrolsupplementsarealready
oxidizedwhenpurchased.Onlyonecompanyusesanactivepackaging
oxygenabsorbersystemtocapturetheoxygenwhichentersthebottle
whenacapsuleisretrieved.
Capsulesandpackaging
The capsules themselves should be made from high quality, all-veg-
etable materials such as Pfizer Vcaps. Cheaper clear gelatin capsules,
whicharemadefromanimalby-products,havenoplaceinaresveratrol
89
supplement.Notonlyisanall-vegetablecapsulehealthiertoconsume
thanagelatincapsule,butitisdesignedtobetterregulatetherelease
of the active ingredients into your digestive tract. What is the use of
takingahighqualitynaturalsupplementifthecapsuleitiscontainedin
ismadefromthecollageninsideanimalsskinandbones?
Gimmickstowatchourfor
Micronizedornanoresveratrol
Thereisabsolutelynopublishedscientificevidencethatshowsmicron-
izationimprovesthebioavailabilityofresveratrol.Infact,itmayhavea
negativeefectbyreducingthehalf-lifeofresveratrolinbloodplasma.
There is no reason to pay extra for a micronized resveratrol product,
whichofersnopracticaladvantagetotheuser,andmaynotbeasefec-
tiveasagoodqualitygranulatedresveratrol.
Resveratrolwithquercetin
Quercetin is a potent antioxidant in its own right, however it should
not be combined with resveratrol or even taken within at least eight
hoursoftakingaresveratrolsupplement.Thereason,whichwasonly
recentlydiscovered,isthatquercetinblocksthemetabolitesofresvera-
trolfromenteringyourbloodstream.Quercetinalsodeactivatessirtu-
ins,preciselytheoppositeefectofresveratrol.
Untilafewyearsagoitwasassumedthataddingquercetinwasagood
thing since the importance of the metabolites was not understood.
Before the latest studies revealed otherwise it was assumed that the
metaboliteswerenotresponsibleforthebiologicalandlongevitygene
4O
activation efects of resveratrol. Based upon several highly regarded
studies,wenowknowthatitisverylikelythatthebeneficialefectsof
resveratrol actually derive mainly from these metabolites rather than
fromthefreeresveratrol.
Thesemetabolitesarebioactiveproductsofthebreakdownofresvera-
trolbytheliverandlayerofcellsliningthesmallintestine.Byblocking
thesesulphatesandglucordinates,quercetininterfereswiththeability
of resveratrol to activate the sirtuins, specifically Sirt-1 and 2, the so
called anti-aging genes, and blocks other signaling pathways through
whichresveratroloperates,andwhichareresponsibleformanyofthe
desirablehealthefectsofresveratrol.Moreover,thehalf-lifeoftheme-
tabolitesinhumantissueisseveralhourswhereasthehalf-lifeoffree
resveratrolisonlyabout12minutes.
Ina2009studyofresveratrolsefectsoninducingthecreationofhe-
moglobin cells in patients blood it was found that quercetin totally
blocked the ability of resveratrol to create the new red blood cells.
Quercetin also nullified theanti-inflammatorypropertyofresveratrol
inaninformaltrialofresveratrolspalliativeefectonarthritis.Thereis
noscientificjustificationforaddingquercetintoaresveratrolsupple-
ment.Ifonewishestotakequercetinitisreadilyavailableasalowcost
supplementthatmaybetakenbyitself.
Redwinecomplex
Some supplement makers attempt to confuse the buyer into thinking
thatheisbuyingaresveratrolproductbyusingthismisleadingdescrip-
tion.ThereisnostandardforRedWineComplex.Redwinecontains
only very small amounts of resveratrol, less than 5 percent as a rule.
Companieswhodonotdisclosetheamountoftrans-resveratrolintheir
productsshouldbeavoided.
41
Dr. Oz or Oprah recommended resveratrol
Neither Dr. Oz nor Oprah recommend any brand of resveratrol. If you
areinterestedinknowingwhichbrandtheyuseintheirpresentations
on resveratrol you can find this by searching for resveratrol on their
respectivewebsites.Thelawyersforbothoftheserespectedpersonali-
tieshavetakenaggressivelegalactionagainstthecompaniesandindi-
vidualswhoclaimthattheyrecommendtheirproducts.
Fiveessentialcriteriontopicka
resveratrolprovider
Credentials
Themediacoverageofthestudiesdemonstratingthepotentialbenefits
ofresveratrolhasattractedafloodofnewandclearlydisreputableres-
veratrolsellerstothemarket.Thesecompanieshavenoexperiencein
producingafoodorhealthsupplement,noscientificstafs,testinglabs,
orothertechnicalresources.Mosthavenoestablishedqualitycontrol
standards and no history by which one can judge their reliability and
integrity.Manyofthesecompaniesuseaformofthewordresveratrol
intheirnamesandsellonlyviaawebsite.ThelawyersforDr.Mehmet
OzandOprahWinfreyrecentlyfiledfederallawsuitsagainstover50of
thesecompaniesforillegallyusingtheirtrademarksandmakingfalse
claimsthattheirproductswereendorsedbythesewell-knownperson-
alities. A copy of the litigation can be downloaded by visiting the fol-
lowinglink:
http://www.scribd.com/doc/19144074/Harpo-Productions-versus-
MonavieOprah-Dr-Oz-Suing-More-Than-50-Companies
42
Amanufacturerratherthansimplyareseller
Many suppliers buy raw material from Asian sources at the lowest
possible price and simply fill capsules, rather then collect the plant
and process it in their own GMP-certified facility. Legitimate resvera-
trol supplements will have passed Consumer Labs recently updated
evaluation of resveratrol brands, and its website should provide easy
methodstocontactthecompanyifyouhaveanyquestions,complaints
orarequestforarefund.
Tenyears,preferablymore,ofethicalbusiness
operationswithnounresolvedBetterBusiness
Bureaucomplaints
Itshouldoferarangeofproductsnotonlyoneortwovirtuallyidenti-
calproducts.Ifthecompanyofersamonthlyrecurringorderprogram
aclearandconvenientmeansofcancelingyoursubscriptionshouldbe
ofered.Beforeyougiveyourcreditcardinformationtoanonlineseller
besurethatthecompanyislegitimate.Thiscanusuallybeestablished
bycontactingyourlocalBBBanddoingabitofonlineduediligence.
Thesupplementissoldretailshops,notonly
throughwebsites
Ifthecompanysproductsarenotavailableinbrickandmortarstores
such as GNC, Walgreens, The Vitamin Shop and other reputable re-
sellers it should probably be avoided. Anyone can sell a product over
theInternetbuttohaveonesproductsacceptedbymajorHealthand
Supplement stores requires liability insurance, thorough testing of
the products quality and vetting of the company and its principals.
Shopsthatcarrysupplementscarryoutthoroughduediligenceofboth
48
the product itself and the company supplying and manufacturing the
product.Youhavenosuchassurancewithmostonlinesuppliers.
This is not to say that all online suppliers sell inferior quality supple-
ments.TherearesomeveryreputableandethicalInternetmerchants
and manufactures. Unfortunately however, with any new supplement
comes a raft of brand new suppliers with no history or experience in
manufacturingadvancednutritionalproductswhobuyfromlostcost,
lowqualitybrokersandwhoseproductsconsistentlyfailindependent
evaluation.Thesecompaniesusuallyemployhighlyunethicalbusiness
practicesorcompeteentirelyonthebasisofprice.Moreoftenthannot
theirproductsarevirtuallyworthless,theircustomerserviceisnonex-
istentandtheirlifespanismeasuredinmonthsifnotweeks.
Thegoldstandardisacceptancebythemedicaland
researchcommunities
Theresveratrolbrandusedinhumantrialsatinstitutionssuchasthe
AlbertEinsteinMedicalSchool,OttawaHospital,Harvard,theUniversity
ofFerrara,UniversityofQueenslandinAustraliaandtheNIHisbyne-
cessity the purest and most thoroughly tested supplements available
tothegeneralpublic.Theseinstitutionsmustputanyproductusedin
humantrialsthrougharigorousandextensiveseriesoftestsforpurity,
potencyandtoxicity.Theirendorsementisfarmorevaluablethanany
testdonebythemanufacturersthemselvesorbytheso-calledindepen-
dentlabs.
One company whose products satisfy all of these criteria, and which
have been used in National Institutes of Health, Health Canada and
other health ministry-funded studies is Biotivia, who introduced the
original resveratrol supplement over six years ago. The company has
beeninoperationintheUSandEuropeforover20years.
44
On the opposite end of the scale are the companies who have sprung
intoexistencetotakeadvantageofthehundredsofnewsarticlesabout
resveratrols potential health benefits. In mid-2010 Oprah Winfrey
hosted Dr. Mehmet Oz on her program to talk about extreme life ex-
tension. He extolled the virtues of resveratrol in his presentation and
shortlythereafterliterallydozensofnewsuppliersmaterializedofer-
ingfreebottlesofresveratrolandclaiminganendorsementbyDr.Oz.
Not only were they deceiving customers with their sleazy marketing
schemes,theirproductswerefound,inmanycases,nottocontainres-
veratrolatall.ThelawyersforDr.OzandOprahsproductioncompany
filed suit against most of these companies, and the states attorney
generalinseveralstateslaunchedcriminalinvestigations.Ifyouarein-
terestedinwhichbrandwasactuallyusedbyDr.Ozinhispresentation
ontheOprahsshowyoucansearchforthetermresveratrolonDr.Oz
orOprahswebsite.
FutureProspects
My prediction is that resveratrol will become both a stand-alone
preventative agent and an efective treatment for a variety of human
health conditions within five years. Perhaps more importantly, it will
gain widespread acceptance as a co-treatment to be used to enhance
theefficacyofexistingdrugsandnon-drugtreatmentsforawiderange
of conditions. Finally, resveratrol will, within the next year, become a
popular supplement and component in functional foods for its ability
toimprovetheoverallhealthandqualityoflifeofthosewhochooseto
takeadvantageofit.
Thepreponderanceofpeer-reviewedpublisheddatanowinthepublic
domainelucidatingthevariousbenefitsofresveratrolisverycompel-
lingevidenceofresveratrolsimportancetomedicalscienceandtocon-
45
sumersconcernedaboutimprovingandextendinghealthandlongev-
ity.Duringthisyearandthenext,alargenumberofhumanclinicaltrial
resultswillbepublishedbysomeoftheworldsmostrespectedscien-
tificinstitutions.Ibelievethatvirtuallyallofthesestudieswillconfirm
theresultsandconclusionssetforthinearlierinvitroandsmall-scale
humanclinicaltrials.Ifthisturnsouttobetrueitwillbeirresponsible
of the medical community to fail to incorporate resveratrol into their
recommendedtreatmentmodalities.
Medicalethicistssetaveryhighstandardforadoptionofanewdrug,
treatmentortechnology.Thisstandardiscalledtheprecautionaryprin-
cipal.OnedefinitionofthisprincipleissetforthinapapertitledThe
PrecautionaryPrincipleauthoredbyUNESCOsWorldCommissionon
theEthicsofScientificKnowledgeandTechnology.
Whenhumanactivitiesmayleadtomorallyunacceptableharmthatis
scienticallyplausiblebutuncertain,actionsshallbetakentoavoidor
diminishthatharm.
So how does resveratrol stack up against this rigid standard? Given
whatwenowknowaboutresveratrolsabilitytobeneficiallymodulate
somanybiologicalprocesses,anditsabsenceofanysignificanttoxicity
oradverseefectsinthethousandsofstudiesdonetodate,itisfairand
reasonabletocontendthatresveratrolhasmetthefirstcriterionofthis
standard. However this is only the first of two prerequisites which a
newdrugortreatmentmustsatisfytojustifyitsadoption.
Itisequallyimperativethatthetreatment,drugortechnologyofersa
legitimatebenefittoitsusersorconsumersthatoutweighstheforesee-
ablerisks.Somelevelofriskisacceptableandinevitable.Everyaction
wechoosetotakeortoavoidentailsrisk.Theprecautionaryprinciple
simply states that risks must be reasonable when considered in light
ofthebenefits.Resveratrolsbenefits,ifonlyjudgedintermsofitsan-
4O
tioxidantpropertiesandthefewhumanclinicaltrialstodate,satisfies
this second criterion as well. If I am correct, and the ongoing human
clinical trials confirm resveratrols safety and efficacy, not only will it
have justified its adoption by the medical community, it will have es-
tablisheditselfasacompoundwhosesafetyandimportancetohuman
health exceeds that of many of the pharmaceuticals commonly being
usedtodaytotreatdisease.
47
Scientificstudiesconfirmingstatements
andclaimsmadeinthispublication.
Anti-inflammatoryefectsofresveratrol
1. HuangZ,WangC,WeiL,WangJ,FanY,WangL,WangY,ChenT.,Resveratrol
inhibitsEMMPRINexpressionviaP38andERK1/2pathwaysinPMA-induced
THP-1cells.,BiochemBiophysResCommun.2008Sep26;374(3):517-21.
2. LuKT,KoMC,ChenBY,HuangJC,HsiehCW,LeeMC,ChiouRY,WungBS,Peng
CH,YangYL.,NeuroprotectiveEfectsofResveratrolonMPTP-InducedNeuron
LossMediatedbyFreeRadicalScavenging.,JAgricFoodChem.2008Jul11.
3. DoGM,KwonEY,KimHJ,JeonSM,HaTY,ParkT,ChoiMS.,Long-termefects
ofresveratrolsupplementationonsuppressionofatherogeniclesionforma-
tionandcholesterolsynthesisinapoE-deficientmice.,BiochemBiophysRes
Commun.2008Sep12;374(1):55-9.
4. HouX,XuS,Maitland-ToolanKA,SatoK,JiangB,IdoY,LanF,WalshK,
WierzbickiM,VerbeurenTJ,CohenRA,ZangM.,SIRT1regulateshepatocyte
lipidmetabolismthroughactivatingAMP-activatedproteinkinase.,JBiol
Chem.2008Jul18;283(29):20015-26.
5. ReiterE,AzziA,ZinggJM.,Enhancedanti-proliferativeefectsofcombinato-
rialtreatmentofdelta-tocopherolandresveratrolinhumanHMC-1cells.,
Biofactors.2007;30(2):67-77.
6. DasS,DasDK.,Resveratrol:atherapeuticpromiseforcardiovasculardiseases.
RecentPatentsCardiovascDrugDiscov.2007Jun;2(2):133-8.
7. MagroneT,TafaroA,JirilloF,PanaroMA,CuzzuolP,CuzzuolAC,PuglieseV,
AmatiL,JirilloE,CovelliV.,Redwineconsumptionandpreventionofathero-
sclerosis:aninvitromodelusinghumanperipheralbloodmononuclearcells.,
CurrPharmDes.2007;13(36):3718-25.
48
8. VivancosM,MorenoJJ.,Efectofresveratrol,tyrosolandbeta-sitosterolon
oxidisedlow-densitylipoprotein-stimulatedoxidativestress,arachidonicacid
releaseandprostaglandinE2synthesisbyRAW264.7macrophages.,BrJNutr.
2008Jun;99(6):1199-207.
9. AhnJ,LeeH,KimS,HaT.,ResveratrolinhibitsTNF-alpha-inducedchangesof
adipokinesin3T3-L1adipocytes.,BiochemBiophysResCommun.2007Dec
28;364(4):972-7.
10. TsouprasAB,FragopoulouE,NomikosT,IatrouC,AntonopoulouS,
DemopoulosCA.,Characterizationofthedenovobiosyntheticenzymeof
plateletactivatingfactor,DDT-insensitivecholinephosphotransferase,of
humanmesangialcells.,MediatorsInflamm.2007;2007:27683.
11. EkshyyanVP,HebertVY,KhandelwalA,DugasTR.,Resveratrolinhibitsrat
aorticvascularsmoothmusclecellproliferationviaestrogenreceptordepen-
dentnitricoxideproduction.,JCardiovascPharmacol.2007Jul;50(1):83-93.
12. BertelliAA.,Wine,researchandcardiovasculardisease:instructionsforuse.
Atherosclerosis.2007Dec;195(2):242-7.
13. CullenJP,MorrowD,JinY,vonOfenbergSweeneyN,SitzmannJV,Cahill
PA,RedmondEM.,Resveratrolinhibitsexpressionandbindingactivityof
themonocytechemotacticprotein-1receptor,CCR2,onTHP-1monocytes.,
Atherosclerosis.2007Nov;195(1):e125-33.
14. SchmittCA,HandlerN,HeissEH,ErkerT,DirschVM.,Noevidenceformodula-
tionofendothelialnitricoxidesynthasebytheoliveoilpolyphenolhydroxyty-
rosolinhumanendothelialcells.,Atherosclerosis.2007Nov;195(1):e58-64.
15. CruzMN,AgewallS,Schenck-GustafssonK,KublickieneK.,Acutedilata-
tiontophytoestrogensandestrogenreceptorsubtypesexpressioninsmall
arteriesfromwomenwithcoronaryheartdisease.,Atherosclerosis.2008
Jan;196(1):49-58.
49
16. FragopoulouE,NomikosT,KarantonisHC,ApostolakisC,PliakisE,Samiotaki
M,PanayotouG,AntonopoulouS.,Biologicalactivityofacetylatedphenolic
compounds.,JAgricFoodChem.2007Jan10;55(1):80-9.
17. ChowSE,HshuYC,WangJS,ChenJK.,ResveratrolattenuatesoxLDL-stimu-
latedNADPHoxidaseactivityandprotectsendothelialcellsfromoxidative
functionaldamages.,JApplPhysiol.2007Apr;102(4):1520-7.
18. BritoPM,MarianoA,AlmeidaLM,DinisTC.,Resveratrolafordsprotection
againstperoxynitrite-mediatedendothelialcelldeath:Aroleforintracellular
glutathione.ChemBiolInteract.2006Dec15;164(3):157-66.
19. JunHJ,ChungMJ,KimSY,LeeHJ,LeeSJ.,Non-radioactiveandcolorimetric
quantificationofmonocyteadhesiontoendothelialcellsinearlyatherogen-
esis.BiotechnolLett.2006Nov;28(22):1805-10.
20. SevovM,ElfinehL,CavelierLB.,Resveratrolregulatestheexpressionof
LXR-alphainhumanmacrophages.,BiochemBiophysResCommun.2006Sep
29;348(3):1047-54.
21. ZangM,XuS,Maitland-ToolanKA,ZuccolloA,HouX,JiangB,WierzbickiM,
VerbeurenTJ,CohenRA.,PolyphenolsstimulateAMP-activatedproteinkinase,
lowerlipids,andinhibitacceleratedatherosclerosisindiabeticLDLreceptor-
deficientmice.Diabetes.2006Aug;55(8):2180-91.
22. LeeKW,LeeHJ.,Therolesofpolyphenolsincancerchemoprevention.,
Biofactors.2006;26(2):105-21.
23. NorataGD,MarchesiP,PassamontiS,PirilloA,VioliF,CatapanoAL.,Anti-
inflammatoryandanti-atherogenicefectsofcathechin,cafeicacidand
trans-resveratrolinapolipoproteinEdeficientmice.,Atherosclerosis.2007
Apr;191(2):265-71.
24. LuKT,ChiouRY,ChenLG,ChenMH,TsengWT,HsiehHT,YangYL.,
Neuroprotectiveefectsofresveratroloncerebralischemia-inducedneuron
lossmediatedbyfreeradicalscavengingandcerebralbloodflowelevation.,J
AgricFoodChem.2006Apr19;54(8):3126-31.
5O
25. DasDK,MaulikN.,Resveratrolincardioprotection:atherapeuticpromiseof
alternativemedicine.,MolInterv.2006Feb;6(1):36-47.
26. KaurG,RobertiM,RaulF,PendurthiUR.,Suppressionofhumanmonocyte
tissuefactorinductionbyredwinephenolicsandsyntheticderivativesof
resveratrol.,ThrombRes.2007;119(2):247-56.
27. WungBS,HsuMC,WuCC,HsiehCW.,ResveratrolsuppressesIL-6-induced
ICAM-1geneexpressioninendothelialcells:efectsontheinhibitionofSTAT3
phosphorylation.,LifeSci.2005Dec12;78(4):389-97.
28. WangZ,ZouJ,CaoK,HsiehTC,HuangY,WuJM.,Dealcoholizedredwinecon-
tainingknownamountsofresveratrolsuppressesatherosclerosisinhyper-
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2005Oct;16(4):533-40.
29. SbarraV,RistorcelliE,Petit-ThveninJL,TeissedrePL,LombardoD,VrineA.,
Invitropolyphenolefectsonactivity,expressionandsecretionofpancreatic
bilesalt-dependentlipase.,BiochimBiophysActa.2005Sep5;1736(1):67-76.
30. VitracX,BornetA,VanderlindeR,VallsJ,RichardT,DelaunayJC,MrillonJM,
TeissdrePL.,Determinationofstilbenes(delta-viniferin,trans-astringin,
trans-piceid,cis-andtrans-resveratrol,epsilon-viniferin)inBrazilianwines.,J
AgricFoodChem.2005Jul13;53(14):5664-9.
31. MorrisBJ.,Aforkheadintheroadtolongevity:themolecularbasisoflifespan
becomesclearer.,JHypertens.2005Jul;23(7):1285-309.
32. Deby-DupontG,Mouithys-MickaladA,SerteynD,LamyM,DebyC.,Resveratrol
andcurcuminreducetherespiratoryburstofChlamydia-primedTHP-1cells.,
BiochemBiophysResCommun.2005Jul22;333(1):21-7.
33. DelmasD,JanninB,LatrufeN.,Resveratrol:preventingpropertiesagainst
vascularalterationsandageing.,MolNutrFoodRes.2005May;49(5):377-95.
51
34. AronisA,MadarZ,TiroshO.,Mechanismunderlyingoxidativestress-medi-
atedlipotoxicity:exposureofJ774.2macrophagestotriacylglycerolsfacilitates
mitochondrialreactiveoxygenspeciesproductionandcellularnecrosis.,Free
RadicBiolMed.2005May1;38(9):1221-30.
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36. LocatelliGA,SavioM,FortiL,ShevelevI,RamadanK,StivalaLA,VanniniV,
HbscherU,SpadariS,MagaG.,InhibitionofmammalianDNApolymerases
byresveratrol:mechanismandstructuraldeterminants.,BiochemJ.2005Jul
15;389(Pt2):259-68.
37. AugerC,TeissedrePL,GrainP,LequeuxN,BornetA,SerisierS,Besanon
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Cerebralbloodflowandcognition
DavidOKennedy,EmmaLWightman,JonathonLReay,GeorgLietz,EdwardJOkello,
AntheaWildeandCrystalFHaskell
FromtheBrainPerformanceNutritionResearchCentreNorthumbriaUniversity
NewcastleuponTyneUnitedKingdom(DOKELWJLRAWCFH)theSchoolof
AgricultureFoodRuralDevelopmentNewcastleUniversityNewcastleuponTyne
UnitedKingdom(GLEJO).
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