Vitamin C and DihydroquercetinCreating a

More Potent Vitamin CByMarkJ.Neveu, PhD

Every day, our bodies are under continual assault by danagents known as free radicals. Generally, both internal and dietaryancioxidants do an excellent job of keeping free radicals in check.However, once this balance is disrupted, lethal diseases such ascancer, heart disease, lung disease, diabetes, Parkinson's disease,arthritis, Alzheimer's disease, and stroke can be initiated.'"'

A wealth of scientific evidence has repeatedly demonstrated thatspecialized compounds in fresh fruits and vegetables exert criticalprotection against free-radical assault.^ Of these, vitamin C and plantsubstances known 2.'$, ftavonoids may be among nature's most potentnatural antioxidants.'•'"

Exciting new studies suggest that a flavonoid called dihydroquer-cetin, in combination with vitamin C, provides even more powerful,synergistic protection against oxidative stress than either substancealone. > > >

Free radicals (black stream, bottom left to center right) datnaging cellular DNA(wbite, cetiter nght). Tbe DNA tias origitiated trom tbe cell nucleus (ptirple, lowerright) and a sectioned cell membrane surrounds it. Vitamin C (blue particles)redtices ttiis damage. LDL particles (orange) are oxidized by tree radicals, andprotected by vitamin E (yellow bexagons). Oxidized LDL is removed by white bloodcells (pink/grey, upper center). These LDL-filled cells form atherosclerotic plaque(brown, upper right).

Collector's Edition 2007 UFE EXTENSION 119

Fiavonoids: Nature's' ' Response Modifiers''

Scientists have recently begunto attribute many of the beneficialeffects of fruits, vegetables, tea, andeven red wine to tbe flavonoid com-pounds they contain.''''

Flavonoids perform two impor-tant functions in tbe body. First,they strengthen tbe body's immuneresponse to attacks frotn allergens,viruses, and carcinogens. Second,they act as powerful antioxidants,protecting tbe body against the oxi-dative stress and free-radical damagethat underlie many cardiovascular,neurological, and diabetic diseases.Studies bave shown tbat tbose wbohave increased flavonoid intakeclearly demonstrate a decreasedincidence and mortality of beartdisease/ '"

One of tbe most important attri-butes of these flavonoids is tbeir abil-ity to enbatice the effects of vitamin C.Vitamin C's main function in bumansis to reduce tbe dangerous effects ofoxidative reactions throughout tbebody. Unfortunately, because vita-min C is water soluble, it stays in tbebody for only a very brief time beforebeing excreted. Tbis time frame lim-its vitamin C's efficacy.'" Until now,it has been recommended that

vitamin C be taken in severaldoses to maintain optimal benefits.However, flavonoids bave beensbown to improve tbe concentrationand efficacy of vitamin C tbrougb-out the body. Tbis important find-ing means tbat you can take lessvitamin C wbile it lasts longer andworks barder."

Dihydroquercetin

One flavonoid, dihydroquer-cetin, bas been found to beextremely beneficial in helpingvitamin C re-circulate tbrougb-out tbe body. Additionally, itlimits tbe inactivation or oxida-tion of vitamin C, wbicb enablesvitamin C to last longer in tbe

Tbe addition of tbis unique fla-vonoid creates an entirely new wayto deliver vitamin C to cells in needof its protection. Now, supplementusers can maximize tbeir benefitsfrom longer-lasting and more effec-tive vitamin C.

k Ejfects of Vltamhi Cand Dihydroquertetin

Unlike plants and most ani-mals, bumans cannot manufacturevitamin C witbin tbe body and

DIKYDROQUERCETIN FIGHTSCARDIOVASCULAR DISEASE

Dihydroquercetin acts in several waysto help avert cardiovascular disease.

Scientists have demonstrated thatdihydroquercetin inhibits lipid peroxida-tion, a process that often leads to athero-sclerosis,'""'^Mn an animal study, dihy-droquercetin inhibited the peroxidation ofserum and liver lipids tollowing exposureto toxic ionizing radiation.^^ Dihydroquer-cetin's inhibitory eftects on lipid peroxida-tion are enhanced by both vitamin C andvitamin E,̂ " By inhibiting the oxida-tion of harmful low-density lipoprotem(LDL), dihydroquercetin may help preventatherosclerosis,'^

Lowering high levels of low-den-sity lipoprotein {LOL) is one the the majorgoals of anti-cholesterol or statin therapyas used by mainstream physicians. Stud-ies suggest that dihydroquercetin may behelpful in therapeutic efforts to lower LDL byinhibiting the formation of apolipoprotein 8,one of the primary components of LDL.̂ ^

Other studies have shown that dihy-droquercetin lowers serum and liver lipidand cholesterol concentrations in rats.^' Aconjugated form of dihydroquercetin knownas astilbin inhibits the same enzymetargeted by popular cholesterol-lower-ing statin drugs such as Lipitor®, Zocor®,and Pravachol®.̂ ^

Attacking heart disease from anotherangle, animal studies showed that dihydro-quercetin lowers high blood pressure andnormalizes an electrical measure associ-ated with activation ofthe heart's pumpingchambers (ventricles),^

therefore must obtain it from exter-nal sources. Tbis bas led some sci-entists, including the late NobelPrize-winning chemist Linus Pauling,to propose that bumans wouldenjoy better health if tbey supple-mented tbeir diets witb an amountof tbe nutrient proportional to tbeamount produced in animal speciestbat manufacture tbeir own vitaminC. Moreover, aging adults experi-ence a decrease in vitamin C levels,wbicb may contribute to tbe devel-opment of several degenerative dis-eases, sucb as cardiovascular disease.

120 UFE EXTENSION Collector's Edition 2007

cancer, neurodegenerative condi-tions, and eye disorders." "'

Tbe combination of vitamin Cand dibydroquercetin offers suchtremendous promise in preservingand restoring bealtb tbat it bas beenapproved as a prescription drug insome parts ofthe worid.

In Russia, a drug known asAscovertin (a complex of dibydro-quercetin and vitamin C) is a populartreatment for many health condi-I ions that share oxidative stress as anunderlying mechanism. Since oxida-tive stress characterizes many ofthedegenerative conditions associatedwith aging,' ' Ascovertin's potentialapplications are quite broad.

For example, Ascovertin may haveapplications in the management ofstroke, a crippling, often fatal con-dition marked by a diminished sup-ply of blood and oxygen to the brain.Studies ofthe effects of oxygen depri-vation in rat brains demonstratedthat Ascovertin decreased the dam-age caused by lack of blood fiow.Additionally, Ascovertin restorednormal structure and electrochemi-cal activity to nerve synapses, thejunctions that allow nerve cells totransmit information.'''"

The Russian Academy of MedicalSciences recently conducted twoclinical studies of Ascovertin in52 patients with impaired bloodflow to tbe brain. Ascovertin wasadministered for 21 days. The result-ing decrease in blood viscosity andblood-clotting tendency improvedattention, memory, and mentalperformance, relieved vertigo, nor-malized sleep, relieved beadacbes,and decreased fatigue.'''̂ " No sucbchanges were observed in the age-matched control patients.

Ascovertin may also protectagainst some of the damaging con-sequences of heart attack. Studies inrats showed that Ascovertin inhibitsthe blood clotting and brain dam-age that can occur following a heartattack.-''̂ ^

The tissues of the eye may ben-efit from Ascovertin as well. Studiesin rats found that Ascovertin inhibitsdamage to the eye's retina inducedby high-intensity light.̂ ^

D'l/iydroqnerre/inS/ress and bijlammation

Because of its forceful antioxi-dant abilities, dihydroquercetin cansearch for and destroy two of themost dangerous types of free radi-cals in the body: the superoxide andperoxide radicals. Dihydroquercetinalso works overtime to protect redand white blood cells. Studies showthat it protects white blood cells fromenvironmental injury and preventsoxidative cell death in red blood cells.The result is a stronger, more vigor-ous immune systetn that can aggres-sively police and protect critical cellunits throughout the body.̂ -̂'̂

As Life Fxtension readers know,inflatiimation is a key culprit indegenerative diseases such as arthri-tis, cardiovascular disease, and can-cer. Dihydroquercetin bas shownits ability to reduce inflammation-producing enzymes such as cyclo-oxygenase-2 (COX-2) and to inhibitinflammatory mediators, includingcytokines.^' '" Tbe COX-2 enzymehas been the focus of extensivepharmaceutical research that hasproduced drugs such as Vioxx'̂ ' andCelebrex'. Tbese drugs went on to beimplicated in tbe creation of lethalheart disease. Dihydroquercetinmay provide a safe alternative tocertain pharmaceuticals used toaddress inflammatioti.

Inflammation also makes itspresence known through allergicreactions. Histamines are widelyrecognized as the trigger of mostallergic episodes. Dihydroquercetinsuppresses the release of hista-mines, thereby reducing the severityof allergic occurrences.- '̂

Studies ConfirmSafety and Effiraty

Studies indicate that dihydro-quercetin is highly safe and effica-cious. In fact, research suggests thatdihydroquercetin is even safer tbanits nutritional cousin, quercetin. '̂̂ ^No toxic effects were observed in ratstbat were treated with high levelsof dihydroquercetin for long periods

VitaminDihydrotuicnWhat)

A novel bioflavonoid. dihydroquercetin,offers exceptional benefits by enhanc-ing the heaith-promoting benefits ofvitamin C, Dihydroquercetin enhancesthe effectiveness of vitamin C byextending its period of bioactivity,enhancing its regeneration, andslowing its elimination from the body.Dihydroquercetin offers protectionagainst cardiovascular disease byinhibiting several steps m the diseaseprocess. Additionally, dihydroquercetinhelps guard nervous system health,prevents the complications of dia-betes, protects the liver against hepa-titis-inducing agents, fights infection,and quells inflammation that can leadto dermatitis, arthritis, and pam,

' Some of vitamin C's best-knownapplications are preventing viralinfection, enhancing cancer protection,and averting cardiovascular diseaseand stroke,

' In some parts of the world, a combina-tion of vitamin C and dihydroquercetinis available as a prescription drugknown as Ascovertin. Physiciansutilize Ascovertin to manage healthconditions that share oxidative stressas an underlying mechanism. Asco-vertin has demonstrated etficacy inprotecting against stroke, heart attack,and light-induced damage to the eye,

' Consumers in the United States canuse the benefits of a dietary supple-ment combining dihydroquercetin andvitamin C without a prescription.

COMMON APPLICATIONS OF VITAMIN C

Long considered essential to optimal health, vitamin C may offer targeted protectionagainst viral infections, cancer, cardiovascular disease, and stroke.

• Viruses. Vitamin C is widely used to support the immune system's protection againstcolds and flus. In adults and children, the preventive use of vitamin C reduced the durationof colds by up to 14%," In athletes and soldiers, daily vitamin C intake reduced the incidenceof colds by 50%, A recent study found mice that were deficient in vitamin C experiencedincreased lung tissue damage following infection with the influenza virus. Vitamin C-deficientmice also demonstrated increased expression of pro-inflammatory cytokines. These findingssuggest that vitamin C is required for an effective immune response to infection with theinfluenza virus,^^

• Cancer. Vitamin C may offer essential aid in fighting cancer. Higher intakes ofvitamin C are associated with a decreased incidence of cancers of the mouth, throat,esophagus, stomach, colon, and lung." In 2005, research by the National Institutes of Healthfound that vitamin C administered intravenously helped kill several strains of cancer cells.This led scientists to note that intravenous vitamin C may be an important tool in fightingcancer, which supports similar findings by Linus Pauling. '̂̂ Furthermore, a recent clinical trialdocumented the safety of high-dose vitamin C in advanced cancer patients,^' Several recentstudies indicate that the combination of tysine and proline with vitamin C more effectivelyinhibits cancer cells than vitamin C

• Cardiovascular Disease anti Stroke. Studies indicate that low or deficient intake ofvitamin C is associated with an increased risk of cardiovascular disease. Similarly, the riskof death from cardiovacular diseases was found to be 25-42% lower in adults who consumedplentiful amounts of vitamin C through diet and supplements compared to adults whowere deficient in vitamin C. Some research suggests that vitamin C supplements are moreprotective than dietary vitamin C in protecting against heart disease. Higher serum levelsof vitamin C have been found to diminish the risk of suffering a stroke by up to 29%. Dailysupplementation with vitamin C reduces high blood pressure, a contributor to cardiovascularand stroke risk."

cardiovascular, neurological, anddiabetic disorders. Incorporatingvitamin C and dihydroquercetin ina daily supplementation programis a simple, low-cost way to furtherstrengthen the body's natural anti-oxidant defenses. j |

While people in Russia requirea prescription to acquire tbe manybenefits of dihydroquercetin andvitamin C, this broad-spectrumnutrient combination is now read-ily available as a low-cost dietarysupplement to Americans seekingto enhance their health and well-being. By protecting and etihancingvitamin C as it courses througb tbebody, dihydroquercetin dramaticallyincreases the benefits of this impor-tant nutrient.

Substantial scientific evidencesuggests that this novel combina-tion of nutrients confers powerful,synergistic protection against someof tbe most common and danger-ous diseases of aging, including

122 LIFE EXTENSION Collector's Edition 2007

Kt'ierences

Kregel KC, Zhang HJ. An integrated view ofoxidatjve stress in aging; basic mechanisms,functional effects and pathologicalconsiderations. Am } Physiol Regul IntegrComp Physiol. 2006 Aug 17.Harman D. Free radical theory of aging: anupdate: increasing tlie functional life span.AnnNyAcfl^Sd. 2006 May;1067:10-21.Valko M, Leibfritz D, Moncol I, CroninMT, Mazur M, Telser I. Free radicals andantioxidants in normal physiologicalfunctions and human disease, tntj BiochemCeU Biol. 2006 Aug 4; lEpub ahead of print]

Halvorsen BL, Carlsen MH, Phillips KM,Bohn SK, Holte K, Jacobs DR |r, BlomhoffR. Content of redox-active compounds(ie. antioxidants) in foods consumed inthe United States, Am j Clin Nuir. 2006Iul;84(l):95-135.

Available at: hrtp://en.wikipedia.org/wiki/Bioflavonoids. Accessed October 10, 2006.Ross )A, Kasum CM, Dietary flavonoids:bioavailabiiity, metabolic effects, and safety,Anmi RevNuir. 2002;22\\%-M.Hertog MG, Kromhout D, Aravanis C. etal. Flavonoid intake and long-term risk ofcoronary heart disease and cancer in theseven countries study. Arch Intern Med. 1995Feb27;!55(4):381-6.

OIHYOROQUERCETIN SUPPORTSNERVOUS SYSTEM HEALTH

The brain and nervous system are par-ticularly sensitive to the damaging effectsof free radicals. As we age, free-radicaldamage can accumulate in the brain,leading to cognitive decline and other il l-nesses such as dementia and Alzheimer's.Maintaining optimal mental function isone of the leading goals of aging babyboomers. Fortunately, dihydroquercetinoffers essential protection to critical brainand nerve cells.

To examine methods to protect thebrain against injury, scientists used ananimal model of stroke. Dihydroquerce-tin inhibited the expression of enzymesthat lead to inflammation. Additionally,dihydroquercetin helped prevent inflam-matory white blood cells from attackingand adhering to vulnerable areas of thebrain. These actions help provide essen-tial neuroprotection against the free-radi-cat-induced oxidative damage that oftenoccurs when the brain does not receiveenough blood and oxygen,"•^^•'"'

In addition to the cognitive declinethat often accompanies aging, crit i-cal functions such perception, thinking,language, and consciousness can beadversely affected. Protecting the areas ofthe brain that oversee these functions isanother important benefit of dihydroquer-cetin. In one study, researchers found dihy-droquercetin prevented free radicals fromcausing oxidative damage to crucial nervecells that oversee these functions."'

By protecting the cells of the brain andcentral nervous system, dihydroquercetinmay help avert some of the most devastat-ing changes associated with aging.

DIHYOROQUERCETIN AVERTSCOMPLICATIONS OF DIABETES

One of the most dreaded of diseases,diabetes has particularly damaging con-sequences for the cardiovascular systemand the eyes. Dihydroquercetin may offermuch-needed support for people who aretrying to manage or reverse the effects oftype II diabetes.

Scientists have noted that people withtype II diabetes are at higher risk for arte-rial disease. This is partly because type IIdiabetes increases the capacity of certainwhite blood cells called neutrophils toadhere to the blood vessel lining, or endo-thelium,''''This may contribute to vasculardisease throughout the body, particularlyin the essential blood vessels of the heart,A Russian study found that dihydroquer-cetin inhibits the pro-inflammatory activ-ity of neutrophils in patients with type IIdiabetes,'-' and thus may help protect thevascular system against the damagingeffects of the disease.

In diabetics, dihydroquercetin hasbeen found to protect against two commoncauses of vision loss: macular degenera-tion and cataract. Macular degenerationoccurs when an area of the eye's retinathat is responsible for detailed visionbegins to deteriorate. Dihydroquercetinpromotes blood flow to this region of theeye, which offers protection against visionloss. Also, by inhibiting the activity of anenzyme in the eye lens, dihydroquercetinmay help to prevent cataract formation indiabetic patients.''^ ^̂

8. Knekt P Kumpulainen I, Jarvinen R, etal. Flavonoid intake and risk of chronicdiseases. Am I CUn Nutr. 2002 Sep;76{3):560-8.

9. Landrault N, Larronde F, Detaunay JC. et al.Levels of stilbene oligomers and astilbin inFrench varietal wines and in grapes duringnohle rot development. JAgric Food Chem.2002 Mar 27:50(7):2046-52.

10. Available at; http://en.wikipedia,org/wiki/Viiamin_c. Accessed October 10, 2006.

11. Vinson )A, Bose P. Comparativebioavailability to humans of ascorbic acidalone or in a citrus extract. Am / Clin Nutr.1988Sep:48(3):60l-4.

12. Har[)er Kv\, Morton AD, Rolfe Lil. PhenoUccompounds of black currant juice and theireffect on ascorbic acid. Ill Mechanism ofascorbic acid oxidation and its inhibition byilavonoids. J food Tech. 1969;4;255-67.

13. Nijveldt Rl, van NH, van Hoorn DE, etal. Flavonoids: a review of probablemechanisms of action and potentialapplications. Am ] Clin Nutr. 2001Oct;74(4):418-25.

14. vail der LB, BachschmidM.SpitzerV.etal. Decreased plasma and tissue levelsof vitamin C in a rat model of aging:implications for antioxidative defense.Biochem Biophys Res Commun. 2003 Apr4;303(21:483-7,

15. Jacob RA, Sotoudeh G. Vitamin C functionand status in chronic disease. Nutr ClinCare. 2002 Mar;5(2):66-74.

16. BsGLi! SA. Terezhalmy GT, Vitamin C inhealth and disease, j Contemp Dent Pract.2004 May 15;5(2}:1-13.

17. lx)gvinov SV, Pugachenko NV PotapovAV et al. Ischemia-induced cbanges insynaptoarchitectonics of brain cortexand their correction with ascovertin andLeuzea extract. Bull Exp Biol Med. 2001Oct;132(4):1017-20.

18. Plotnikov MB, Logvinov SV, Pugachenko NV,et al. Cerebroprotective effects of diquertinand ascorbic acid. Bull Exp Biol Med. 2000Nov;130(ll):1080-3.

19. Plotnikov MB, Plotnikov DM, Aliev 01. et al.Hemorheological and antioxidant effectsof Ascovertin in patients with sclerosis ofcerebral arteries. Clin Hemorheol Microcirc.2004;30(3-4):449'52.

20. Plotnikov MB, Plotnikov DM, AlifirovaVM, et al. Clinica! efficacy of a novelhemorheological drug ascovertin inpatients with vascular encephalopatby,Zh Nei'rot Psikhiatr Im SS Koraakova.2004;104(12):33-7.

21. Plotnikov MB, Aliev 01, MaslovMJ.VasilievAS. Tjukavkina NA, Correction ofthe highblood viscosity syndrome by a mixture ofDiquertin and ascorbic acid in vitro and invivo. PhytotherRes. 2003 Mar;17(3!:276-8.

22. Plotnikov MB, Aliev OI.Maslov MI,Vasiliev AS, Tjukavkina NA, Correctionof haemorheological disturbances inmyocardial infarction by diquertinand ascorbic acid. Phytother Res. 2003Jan;17(l):86-8.

23. Logvinov SV. Plotnikov MB, Varakuta EY, etal. Effect of ascovertin on morphologicalchanges in rat retina exposed to high-intensity light. Bull Exp Biol Med. 2005Nov;140[5):578-81.

24. Potapovich Al, KostyukVA. Comparativestudy of antioxidant properties andcytoprotective activity of flavonoids.Biochemistry (Mosc). 2003 May;68(5):514-9.

25. Haraguchi H, Mochida Y, Sakai S, et al.Protection against oxidative damagebydihydroflavonols in Engelhardtiachrysolepis. Biosci Biotechnol Biochem. 1996Jun;60(6):945-8.

26. KostyukVA. Potapovich Al. Antiradical andcheiating effects in flavonoid protectionagainst silica-induced cell injury. ArchBiochem Biophy.^. 199H lul l;355(l):43-8.

27. WangYl I, Wang WY. c;hang CC, et al.Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through itsanti-oxidative effect and modulation ofNF-kappa B activation. / Biomed Sci. 2006Janil3(l):127-41.

28. Solinian KF, Mazzio EA. In vitro attenuationof nitric oxide prodtiction in C6 astrocytecell culture by various dietary compounds.Proc Soc E.rp Biol Med. 1998 Sep;218(4)::i90-7.

29. BitoT. Roy S, Sen C,K otal. I-lavonoidsdifferentially regtilate IFN gamma inducedlCAM-1 expression in human keratinocytes:molecular mecbanisms of action. FEBS Lett.2002 Jun 5;520(l-3):145-52,

DIHYDROQUERCETIN 1"PROTECTS AGAINST LIVER DAMAGE ^

r AND HEPATITIS J

Many chemicals used for industrialand commercial purposes^such as diox-ins, dJbenzofurans, and carbon tetrachlo-ride—act like poisons in the liver. Somecan induce liver toxicity and hepatitis bypromoting the peroxidation of lipids.'^Through its powerful antioxidant effects,dihydroquercetin may protect the liveragainst both toxic exposure and viralinfection. When rats were supplementedwith dihydroquercetin for four days beforebeing exposed to a chemical formerlyused in the dry cleaning and refrigerationindustries, they were protected against thetoxin's hepatitis-Inducing effects,"'

Moreover, in a mouse model of liverinjury, dihydroquercetin was more effectivethan vitamin E in inhibiting the biochemi-cal changes that can lead to hepatitis.Specifically, dihydroquercetin blocked pro-duction of pro-inflammatory tumor necro-sis factor-alpha as well as the infiltrationof immune system cells,'"'"^''

Dihydroquercetin also shows promisein fighting virally induced hepatitis A. Thehepatitis A virus is typically contractedthrough eating unsanitary food. In thelaboratory, dihydroquercetin inhibited thereplication and pathogenic effects of thehepatitis A virus.'''

Supplementation with dihydroquer-cetin thus offers important benefits forthe liver by helping to protect against thedamaging effects of exposure to toxins andviral hepatitis infection.

Collector's Edition 2007 LIFE EXTENSION 123

OIHYOROQUERCETIN ALLEVIATESARTHRITIS PAIN, INFUMMATIQN

The most common types of arthritisresult from either inflammation-induceddeterioration of the cartilage in joints(osteoarthritis) or the body's autoim-mune attack against its own joint tissues(rheumatoid arthritis). Dihydroquerce-tin may offer benefits for both types ofarthritis." 53

One of the important ways in whichdihydroquercetin may limit the onset ofarthritis is by blocking the expression ofinflammatory biochemicals. This actionhas been shown to avert the developmentof autoimmune-induced arthritis.^-' Addi-tionally, dihydroquercetin inhibits the for-mation of activated immune cells, whichcould be effective in treating a variety ofautoimmune disorders, including rheuma-toid arthritis."'^^

Furthermore, dihydroquercetin mayoffer natural pain relief. In a study inmice, dihydroquercetin was more potentthan aspirin or acetaminophen (Tylenol®)in inhibiting pain and inflammation.^^

Dihydroquercetin may thus hold prom-ise in averting the inflammation and auto-immune activity that contribute to arthritis.In existing instances of pain and inflam-mation, dihydroquercetin may offer naturalrelief from the discomfort of arthritis.

30. Devi MA, Das NR In vitro effects of naturalplant polyphenols on the proliferation ofnormal and abnormal human lymphocytesand their secretions of interleukin-2. Cancerle/f. 1993 May 14;69(3):l91-6.

31. BronnerC.LandryV. Kinetics oftheinhibitory effect of flavonoids on histaminesecretion from mast cells. Agents Actions.1985Apr;16(3-4):l47-51.

32. Kravchenko LV. Morozov SV, Tutel'yanVA. Effects of flavonoids on the resistanceof microsomes to lipid peroxidation invitro and ex vivo. Btill Exp Biol Med. 2003Dec:136(6):572-5.

33. Teselkin YO. Babenkova IV, Tjukavkina NA,et al. Influence of dibydroquercetin onthe lipid peroxidation of mice during post-radiation period. Phytotherapy Research.1998:12:517-9.

34. Vasiljeva OV Lyubitsky OB, Klebanov GI,Vladimirov YA. Effect of the combinedaction of flavonoids. ascorbate and alpha-tocopherol on peroxidation of phospholipidliposomes induced by Fe2+ ions, Membra>//K[o/.2000:I4(l):47-56.

35. KostyukVA, KraemerT, Sies H, ScheweT.Myeloperoxidase/nitrite-mediated lipidperoxidation of low-density lipoprotein asmodulated by flavonoids. FEBS Lett. 2003Feb27;5.37(l-3):146-50.

36. Casaschi A, Rubio BK, Maiyoh GK, TheriauitAG. Inhibitory activity of diacylglycerolacyltransferase [DGAT) and microsomaltriglyceride transfer protein (MTP)by the fiavonoid, taxifolin, in HepG2cells: potential role in tbe regulation ofapolipoprotein B secretion. Atherosclerosis.2004Oct;176(2):247-53.

37. Igarashi K, Uchida Y, Murakami N, MizutanlK, Masuda H. Effect of astilbin in teaprocessed from leaves of Engelhardtiachrysolepis on the serum and liver lipidconcentrations and on the erythrocyteand liver antioxidative etizyme activitiesof rats. Biosci Biotechnol Biochem. 1996Mar;60(3):513-5,

38. ChenTH, Uu JC, Chang Jl, et al. The in vitroinhibitory effect of flavonoid astilbin on3-hydroxy-3-methylglutaryl coenzyme Areductase on Vero cells. ZhonghuaYi Xue ZaZhi (Taipei). 2001 iuI;64(7):382-7.

39. TikhonovVRMakarovaMN,ZajtsevaMA,MakarovVG. Efficacy of (±)-taxifolin fromLarix sibirica (Munchh.) Ledeb. on bloodpressure in experiments in vivo. Planta Med.2006;72:174.

40. WangYH, Wang WY, Uao JF, et al. Preventionof macrophage adhesion molecule-l(Mac-l)-dependentneutropbil firmadbesion by taxifolin througb impairmentof protein kinase-dependent NADPHoxidase activation and antagonism of Gprotein-mediated calcium influx. BiochemP/fflrmflfro/. 2004 lun ]5;67(12):225l-62.

41. Dok-Go H, Lee KH, Kim HI, et al.Neuroprotective effects of antioxidativeflavonoids, quercetin, (+)-dihydroquercetinand quercetin 3-methyl ether, isolated fromOpuntia ficus-indica var. saboten. Brain Res.2003 Mar 7;965[12):130-6.

42. van Oostrom Al, van Wijk IP SijmonsmaTP Rabelink TJ, Castro CM. Increasedexpression of activation markers onmonocytes and neutrophils in type 2diabetes. Neth J Med. 2004 Oct;62 [9) :320-5.

43. Fedosova NF, Alisievich SV Lyadov KV, etal. Mechanisms underlying diquertin-mediated regulation of neutropbil functionin patients with non-insulin-dependentdiabetes mellitus. Bull Exp Biol Med. 2004Feb;137(2):143-6,

44. Haraguchi H, Ohtni 1, Fukuda A, etal. Inhibition of aldose reductase andsorbito! accumtilation by astilbin andtaxifolin dihydroflavonols in Engelhardtiachrysolepis. Biosci Biotechnol Biochem. 1997Apr;61[4):65I-4.

45. Haraguchi H,Ohmi I, Masuda H,etal. Inhibition of aldose reductaseby dihydrofiavonols in Engelhardtiachrysolepis anti effects on other enzymes.Experientia. 1996|un 15;52(6):564-7.

46. Batt AM, Ferrari L. Manifestations ofchemically induced liver damage. ClinChem. 1995 Dec;4U12Pt 2): 1882-7.

47. Teselkin YO, Babenkova IV KolhirVK.et al. Dihydroquercetin as a meansof antioxidative defence in rats withtetrachlorometliane hepatitis. Phytother Res.2000May;14(3):160-2.

48. Wang I. Zhao Y, Xu Q. Astilbin preventsconcanavalin A-induced liver injury byreducingTNF-alpha production and Tlymphocytes adhesion.} Pharm Pharmacol.2004Apr;56(4):495-502.

49. Xu Q, Wti F, Cao J, et al. Astilbin selectivelyinduces dysfunction of liver-infiltratingcells^novel protection from liver damage.Eur ] Pharmacol 1999 Jul 14;377(l):93-I00.

50. Closa D. Torres M, Hotter G, et al.Prostanoids and free radicals in C14C-induced bepatotoxicity in rats: effect ofastilbin. Prostagtandins Leukot Essent FattyAcids. 1997Apr:56(4):331-4.

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52. Gupta MB, Bhalla TN. Gupta GP MitraCR, Bhargava KP Anti-inflammatoryactivity of taxifolin. ]pn J Pharmacol. 1971Jun;21(3):377-82.

OIHYOROQUERCETINPROVIOES

IMMUNE SUPPORT IExciting studies indicate that dihydro-

quercetin may support the fight againsttwo types of serious infection: pneumoniaand HIV.

Investigators examined dihydro-quercetin's effects in patients sufferingfrom acute pneumonia. When individualsundergoing standard therapy supplement-ed with an antioxidant formula featuringdihydroquercetin, they recovered fasterfrom symptoms of lung inflammationcompared to patients who underwent tra-ditional therapy alone. '̂'

Preliminary studies may suggest arole for dihydroquercetin in fighting theHIV virus. Dihydroquercetin was recentlyisolated as the active component in thestem bark of Chinese walnut, a plantextract that selectively kills cells infectedwith the human immunodeficiency virus."Moreover, dihydroquercetin was foundto inhibit the activity of an enzyme thatviruses such as HIV use to replicate theirgenetic material.^*

124 LIFE EXTENSION Collectors Edition 2007

OIHYOROQUERCETINSOOTHES

IRRITATED SKIN

In a human study of skin inflammation,dihydroquercetin blocked various biochem-icals that contribute to dermatitis.^^ Dihy-droquercetin alleviates skin inflammationby stimulating a powerful, anti-intlamma-tory cytokine molecule known as IL-IO,^''^"IL-10 helps reduce the skin's hypersensi-tivity reactions to external agents, an all-too-common cause of dermatitis.

53, Cai Y Chen T Xu 0- Astilbin suppressescollagen-induced arthritis via thedysftmction of lymphocytes. Inflamm Res.2003Aug;52[8):334-40.

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