BY WILLIAM FALOON

American Medical AssociationDiscovers Gamma Tocopherol

The Journal of the American Medical Association(JAMA) is one of world's leading scientific publi-

eations. Since the early 1990s, JAMA has publishedarticles about the benefits of dietary supplements,including folic acid, ginkgo, vitamins E, B6, and B12,among others.'" JAMA has also published studiesshowing that vitamin E (alpha tocopherol) by itself hasnot always reduced heart-attack risk factors.^

In January 1998, the Life Extension Foundationintroduced the world to the multiple benefits of gammatocopherol/ Until that time, the only form of vitamin Ethat consumers knew about was alpha tocopherol.

On August 11, 2004, JAMA published an extensivereview article extolling the benefits of gamma toco-pherol.'' While there were similarities to the LifeExtension and JAMA articles, the big difference is thatreaders of JAMA had to wait six years longer than LifeExtension members to find out about the virtues ofgamma tocopherol.

Vitamin E Alone Is Not Enough

In its •dit'idc, JAMA discusses the inconsistent findingsabout alpha tocopherol and presents compelling evi-dence that gamma tocopherol is the form of vitamin Emost likely to reduce the risk of degenerative disease."

The JAMA article reviewed the scientific basis forvitamin E's cardioprotective effects. It then went on todescribe why studies that showed no efficacy to vitaminE supplementation might have been flawed. The rea-sons cited for why these studies failed to provide reliableresults include selection of subjects, stage of disease,end points, dosage, and source of the vitamin E.

Another issue raised in the JAMA review is that vita-min E's mechanism of preventing heart disease is mostlikely related to its ability to suppress LDL oxida-tion. A more targeted approach, X4M/4 asserts, wouldbe to include only patients with enhanced levels ofoxidative stress and low plasma levels of vitamin E inorder to determine those most likely to benefit fromantioxidant treatment.

As Life Extension members are well aware, a widerange of toxic factors—including excess blood levels ofhomocysteine, C-reactive protein, flbrinogen, insulin,glucose, and triglycerides—causes atherosclerotic heartdisease.'" It is impractical to expect vitamin E by itself toprevent atherosclerosis. If healthy arteries are to bemaintained, other pathological mechanisms have to beaddressed as well.̂

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Gamma TocopherolsCancer-Preventive Effects

The JAMA article notes thatmost clinical trials designed toexamine vitamin E's ability to pre-vent disease have used alpha toco-pherol. The article then considersrecent molecular and epidemiolog-ical studies that have promptedresearchers to examine the poten-tial benefits of the gamma toco-pherol form of vitamin E.

One study cited by JAMAshowed that increased levels ofgamma tocopherol were associat-ed with a significantly reduced riskof prostate cancer." The JAMAarticle goes on to note that theanti-cancer effects of high concen-trations of selenium and alphatocopherol were observed whengamma tocopherol concentrationswere also high.

Another group of researchersinterviewed by JAMA are investi-gating whether gamma tocopherolcan inhibit the growth of colon can-cer. These researchers hypothesizethat vitamin E levels inside cells aremore important than blood levels

in protecting DNA genes againstmutations that can lead to cancer.Part of this rationale is that coloncancer cells take up gamma toco-pherol much more effectively thanalpha tocopherol. Furthermore,according to the JAMA article,when alpha and gamma toco-phero! are taken up together intocells, the presence of gamma toco-pherol increases the level of alphatocopherol.

The researchers interviewed byJAMA point out that gamma toco-pherol has unique properties thatalpha tocopherol does not have,including the ability to neutralizecertain free radicals and suppressexpression of a gene {ras-p21) thatis known to cause cancer.'"

The JAMA article reports on arat study that showed gamma toco-pherol provides antioxidant pro-tection to the cells lining tbe colonand to fecal material (possiblydecreasing the production ofmutagens).

Another study cited by JAMAexamined the influence of gammatocopherol on the expression ofanother gene called peroxisomeproliferator activated receptor y(PPARy). This gene (PPARy) is apromising target for the preventionand treatment of colon and othercancers." Activation of PPARy withcertain drugs such as Rezulin^ theJAMA article points out, can reducetumor growth by inhibiting cellularproliferation and inducing pro-grammed eel! death (apoptosis).

Life Extension members mayremember that Rezulin® was takenoff the market because of fatal livertoxicity. Other drugs in its classsuch as Avandia* and Actos®, how-ever, have not demonstrated thistype of liver toxicity.'̂ The comfort-ing news is that gamma tocopherolmay function safely in a mannersimilar to these drugs, favorablyinfluencing PPAR-y and therebyreducing cancer risk.

Others Journals RecognizeGamma Tocopherol

In addition to the JAMA article,other scientific journals publishedfavorable studies in 2004 concern-ing gamma tocopherol's effects ondisease prevention and treatment.

In March, the Archives ofBiochemistry Biophysicia reportedon a study that compared theeffects of alpha tocopherol, gammatocopherol, and other forms ofvitamin E in inhibiting the spreadof prostate cancer cells." Gammatocopherol and its metabolite werethe most effective inhibitors of theproliferation of prostate cancercells. Other forms of vitamin Ewere much less effective.

In July, the Annals of NutritionMetabolism published an article("Gamma tocopherol—an underes-timated vitamin?") showing thatgamma tocophero! has higher trap-ping activity against dangerousnitrogen radicals than does alphatocopherol.'" The study authorsnote that low-level gamma toco-pherol correlates with increasedrisks of cardiovascular disease and

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cancer, and that gamma toco-pherol—but not alpha toco-pherol—provides beneficial natri-uretic activity. Natriuretic agentsenhance renal excretion of sodiumand can help facilitate pressure/vol-ume homeostasis in multiple tis-sues. Natriuretic agents may thushave applications in managing con-ditions such as hypertension andcongestive heart failure.

In January 2004, the journal FreeRadical Biology and Medicine report-ed on "new and unexpected bio-logical activities" with regard togamma tocopherol.'^ The scientistsstated that ''these other tocopheroLs"possess anti-inflammatory, anti-can-cer, and natriuretic functions.Epidemiological data were citedsuggesting that gamma tocopherolhelps prevent certain types of can-cer and heart attack better thanalpha tocopherol. The scientistsconcluded by warning that the:

". . . potential public health implica-tions are immense, given the extremepopularity of alpha tocopherol supple-mentation which can unintentionallydeplete the body of eamma toco-pherol."''

What DoctorsDon't Yet Know

While doctors are slowly beingeducated about the value of gammatocopherol, Life Extension has dis-covered a method to increase theantioxidant and anti-inflammatoryproperties of gamma tocopherol. Itturns out that when sesame seed lig-nans are added to gamma toco-pherol in controlled laboratorystudies, lipid peroxidation ratesare lowered by 50% compared togamma tocopherol alone.'̂ ""

Equally important are stud-ies showing that sesame lignansincrease tissue levels of gammatocopherol as much as 833%

compared to no sesame.-' The sig-nificance of this finding is thatwhile gamma tocopherol in theblood can help protect againstLDL-induced oxidation in thearterial wall, free-radical damagecan still run rampant in the brain,kidneys, and other organs. Increas-ing tissue levels of gamma toco-pherol is critical to neutralizingdestructive free radicals generatedin cells outside the vascular sys-tem. Sesame lignans have beenshown to specifically increase tis-sue levels of gamma tocopherol.

In a brief, two-week study onhuman subjects. Life Extensionmeasured various indicators offree radical and inflammatorydamage. Gamma tocopherol plussesame lignans was shown tobe 25% more effective on averagethan the same amount of gammatocopherol combined with toco-trienols. The significance of thisfinding is that tocotrienols are oneof nature's most potent antioxi-dants, yet low-cost sesame wasfound to work even better.

While progressive doctorsmight soon be recommendinggamma tocopherol-tocotrienolsupplements to their patients,data uncovered by Life Extensionindicate that the combination of

gamma tocopherol and sesamelignans is a more effective anti-oxidant and anti-inflammatoryapproach to preventing degener-ative disease.

How Much IsYour Life Worth?

If you wanted to learn about thelifesaving benefits of gamma toco-pherol back in 1998, you needed tobe a member of the Life ExtensionFoundation. No one else offeredthe benefits of gamma tocopherolback then.

Dedicated supplement usershave been consuming lots of alphatocopherol and thinking they wereprotecting themselves against des-tructive free radicals. The LifeExtension Foundation, on the otherhand, long ago warned that thosewho take regular vitamin E supple-ments should also take gamma toco-pherol, since alpha tocopherol candisplace gamma tocopherol in thebody.' The most prestigious scientif-ic journals in the world now agreewith what Life Extension advocatedmore than six years ago.

Each month, members read aboutnew ways of staving off aging anddeath in Life Extension magazine.

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It costs $75 a year to be amember of the Life ExtensionFoundation. Some people thinkthat is a lot of money, but if theonly benefit of membership werefinding out about the criticalimportance of gamma tocopherol,this alone would have been wellworth the membership fee.

The good news for price-con-scious consumers is that gammatocopherol with sesame lignanscosts a lot less than gamma toco-pherol-tocotrienols and has beenshown to better fend off toxicoxidative and inflammatory reac-tions in the body.

Life Extension AwardedNIH Research Grant

Every time you purchase a sup-plement that might add years ofhealthy life, you help support theworld's most ambitious scientificresearch program to abolish thescourge of age-related disease.

I want to personally thank our100,000-1- members who have sogenerously supported our scientificefforts. The Life Extension Found-ation funded a record-breaking

amount of research in 2004, andhas been awarded a $900,000 grantfrom the National Institutes ofHealth to further our pioneeringscientific endeavors. I

For longer life,

William Faioon

References

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10. Faioon W What the news media did notreveal about Bill Clinton's heart problem.Life Extension. November 2004:9-16.

11. Helzlsouer KJ. Huang HY. Alberg AJ. et al.Association between alpha-tocopherol.gamma tocopherol. selenium, and subse-quent prostate cancer. J Nail Cancer Inst.2000 Dec 20:92(24):2018-23.

12. Stone WL. Papas AM. LeClair IO. Qui M.Ponder T. The influence of dietary iron andtocopherols on oxidative stress and ras-p21levels in the colon. Cancer Delect Prev.2002; 26( 1); 78-84.

13. Campbell SE. Stone WL, Whaley SG, QuiM. Krishnan K. Gamma (gamma) toco-pherol upregulates peroxisomc proliferatorsactivated receptor (PPAR) gamma (gamma)expression in SW 480 human colon cancercell lines. BMC Cancer. 2003 Oct 1;3(1):25.

14. Bae MA. Rhee H. Song BJ. Troglitazone butnot rosiglitazone induces Gl cell cycle arrestand apoptosis in human and rat hepatomacell lines. Toxicol Lett. 2003 Mar20;139(l):67-75.

L5. Gain F. Stabile AM, Betti M. et al. The effectof alpha- and gamma-tocopherol and theircarboxyethyl hydroxychroman metaboliteson prostate cancer cell proliferation. ArchBiochem Biophys. 2(H)4 Mar l;423(l):97-102.

16. Wagner KH. Kamal-Eldin A, Elmadfa 1.Gamma-tocopherol—an underestimatedvitamin./4nn NulrMelab. 2004;48(3): 169-88.

17. Hensley K, Benaksas EJ, Bolli R, et al. Newperspectives on vilamin E: gamma-toco-pherol and carboxyelthylhydroxychromanmetabolites in biology and medicine. FreeRadic Biol Med. 2004'Jan 1:36(1):1-15.

18. Kang M. Katsuzaki H. Osawa T Inhibitionof 2.2'-azobis[2.4-dimethylvaleronitrile)-induced lipid peroxidation by sesaminols.Lipids. 1998 Oct;33(10):103l-6.

19. Yamashita K, Lizuka Y, Imai X Namiki M.Sesame seed and its lignans produce markedenhancement of vitamin E activity in rats feda low a-tocopherol diet. Lipids. 1995Nov;30(ll):1019-28.

20. Yamashita K. Nohara Y. Katayama K,Namiki M. Sesame seed lignans and gamma-tocopherol act synergistically to produce vita-min E aelivily in rats. Nutr. 1992Dec;122(l2):2440-6.

21. Ikeda S, Tohyama T Yamashita K. Dietarysesame seed and its lignans inhibit 2.7.8-trimcthyl-2[2'-carboxyethyl]-6-hydr(x:hromanexcretion into urine of rats fed gamma-toco-pherol.yM*?/: 2002 May:132(5):961-6.

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