FLAVONOIDS/POLYPHENOLS

Flavonoids are polyphenolic compounds that are ubiquitous in nature and are
categorized, according to chemical structure, into flavonols, flavones, flavanones,
isoflavones, catechins, anthocyanidins and chalcones. Over 4,000 flavonoids have
beenidentified,manyofwhichoccurinfruits,vegetablesandbeverages(tea,coffee,
beer, wine and fruit drinks). The flavonoids have aroused considerable interest
recentlybecauseoftheirpotentialbeneficialeffectsonhumanhealththeyhavebeen
reported to have antiviral, antiallergic, antiplatelet, antiinflammatory, antitumor
andantioxidantactivities.

Antioxidants are compounds that protect cells against the damaging effects of
reactive oxygen species, such as singlet oxygen, superoxide, peroxyl radicals,
hydroxylradicalsandperoxynitrite.Animbalancebetweenantioxidantsandreactive
oxygen species results in oxidative stress, leading to cellular damage. Oxidative
stress has been linked to cancer, aging, atherosclerosis, ischemic injury,
inflammation and neurodegenerative diseases (Parkinson's and Alzheimer's).
Flavonoidsmayhelpprovideprotectionagainstthesediseasesbycontributing,along
with antioxidant vitamins and enzymes, to the total antioxidant defense system of
the human body. Epidemiological studies have shown that flavonoid intake is
inversely related to mortality from coronary heart disease and to the incidence of
heartattacks.

The recognized dietary antioxidants are vitamin C, vitamin E, selenium, and

carotenoids. However, recent studies have demonstrated that flavonoids found in
fruitsandvegetablesmayalsoactasantioxidants.Likealphatocopherol(vitaminE),
flavonoids contain chemical structural elements that may be responsible for their
antioxidant activities. The contribution of flavonoids to the antioxidant defense
system may be substantial considering that the total daily intake of flavonoids can
rangefrom50to800mg.Thisintakeishighcomparedtotheaveragedailyintakeof
other dietary antioxidants like vitamin C (70 mg), vitamin E (710 mg) or
carotenoids (23 mg). Flavonoid intake depends upon the consumption of fruits,
vegetables, and certain beverages, such as red wine, tea, and beer. The high
consumption of tea and wine may be most influential on total flavonoid intake in
certaingroupsofpeople.

Antioxidantflavonoids
(listedinorderofdecreasingpotency)

Quercetin(aflavonolinvegetables,fruitskins,onions)
Xanthohumol(aprenylatedchalconeinhopsandbeer)
Isoxanthohumol (a prenylated flavanone in hops and
beer)
Genistein(anisoflavoneinsoy)
 Prooxidantflavonoids

Chalconaringenin (a nonprenylated chalcone in citrus

fruits)
Naringenin(anonprenylatedflavanoneincitrusfruits)

The capacity of flavonoids to act as antioxidants depends upon their molecular

structure. The position of hydroxyl groups and other features in the chemical
structureofflavonoidsareimportantfortheirantioxidantandfreeradicalscavenging
activities. Quercetin, the most abundant dietary flavonol, is a potent antioxidant
becauseithasalltherightstructuralfeaturesforfreeradicalscavengingactivity.

Recently,chalconeandflavanone flavonoidswithprenylorgeranylsidechainshave
beenidentifiedinhopsandbeerbyDr.FredStevensandDr.MaxDeinzeratOregon
State University. Hops are used in beer for flavor. Xanthohumol (a chalcone) and
isoxanthohumoland6prenylnaringenin(flavanones)arethemajorprenylflavonoids
foundinbeer.Althoughtheantioxidantactivitiesofthesecompoundshavenotbeen
studied, these flavonoids may be responsible for the antioxidant activity of lager
beer, which is higher than that of green tea, red wine, or grape juice as reported
earlier by Dr. Joe A. Vinson from the University of Scranton in Pennsylvania.
Xanthohumolisfoundonlyinbeerbutinsmallconcentrations.

Toassesstheantioxidantactivityoftheprenylatedflavonoids,Dr.DonaldBuhlerand
Dr. Cristobal Mirand (The Linus Pauling Institute, Oregan, USA) evaluated the
capacityoftheseflavonoidstoinhibittheoxidationofLDLbycopper.Theantioxidant
propertiesoftheprenylflavonoidswerecomparedtothoseofquercetin(aflavonol),
genistein (the major isoflavone in soy), chalconaringenin (a nonprenylated
chalcone), naringenin (a nonprenylated flavanone), and vitamin E. The possible
interaction of xanthohumol, the major prenylchalcone in beer, with vitamin E to
inhibit LDL oxidation induced by copper was also examined.Their results showed
that the prenylchalcones and prenylflavones are effective in preventing LDL
oxidationinitiated by copper and that the prenylchalcones generally have greater
antioxidant activity than the prenylflavanones. Xanthohumol, the major
prenylchalconein hopsand beer,is a morepowerful antioxidantthanvitaminEor
genistein. However, xanthohumol was less potent than quercetin. The potency of
xanthohumol as an antioxidant is markedly increased when combined with an
equivalentamountofvitaminE.

Dr. Buhlers team also found that the prenyl group plays an important role in the
antioxidantactivityofcertainflavonoids.Aflavonoidchalcone(chalconaringenin)and
a flavanone (naringenin) with no prenyl groups act as prooxidants, i.e. they
promoterather thanlimittheoxidationofLDLbycopper.However,addingaprenyl
grouptotheseflavonoidmoleculescounteractedtheirprooxidantactivities.

Recentworksshowedthatthereareuniqueflavonoidsinhopsandbeerthatmaybe
potentially useful in the preventionof human disease attributed to free radical
damage.Theobservationthatprenylgroupsareimportantinconferringantioxidant
activity to certain flavonoids may lead to the discovery or synthesis of novel
prenylated flavonoids as preventive or therapeutic agents against human diseases
associated with free radicals. Recent results with xanthohumol suggest that this
prenylchalcone should be further studied for its antioxidant action and protective
effectsagainstfreeradicaldamageinanimalsandhumans.Preliminarystudieshave
shown that xanthohumol is absorbed from the digestive tract in rats, and more
studies are needed to evaluate the bioavailability of these interesting flavonoids in
people.

Further studies are also needed to establish the safety of xanthohumol or other
flavonoidsforuseasdietarysupplementssincehighdosesofthesecompoundsmay
produce adverse effects in humans, according to recent findings by Dr. Martyn
Smith,professoroftoxicology,UniversityofCaliforniaatBerkeley.