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LE Magazine April 2006
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What Makes Gamma Tocopherol Superior to Alpha Tocopherol

By Lyle MacWilliam, MSc, FP

Gamma’s Cancer-Preventive Properties

While human and animal prevention trials are lacking, several studies support gamma tocopherol’s potential role in cancer prevention, having demonstrated that it inhibits cancer cell growth even more effectively than alpha tocopherol.43 Gamma tocopherol’s actions appear multifactorial, and include the ability to:

  • destroy reactive nitrogen species1,16
  • prevent the formation of mutagens (DNA-damaging agents) in the colon2
  • induce apoptosis (programmed cell death) in cancerous cell lines4,5
  • regulate the expression of genetic factors that can influence cancerous growth.44-46

Colorectal cancer. As the second most common cause of cancer death in North America, colorectal cancer is a silent but deadly enemy. Gamma tocopherol may play an important role in arresting its development.

Prostate cancer cell division. Colored scanning electron micrograph of two prostate cancer cells in the final stage of cell division (cytokinesis).

While both gamma and alpha tocopherol appear to act as gene regulators,44 recent epidemiological and experimental evidence suggests that gamma tocopherol may be a more potent chemopreventive agent than alpha tocopherol against this disease.45 New evidence from tissue culture studies shows that both tocopherols, and gamma tocopherol in particular, can shield colon cells through a mechanism that enhances the expression of genetic factors that protect against cancerous growth. Scientists suggest that these findings hold relevance not only for cancer prevention, but also for the management of diabetes, inflammatory disorders, and cardiovascular disease.46

The ratio of gamma tocopherol to alpha tocopherol appears higher in the bowel than in the blood,47,48 which may explain gamma tocopherol’s protective effect against colorectal cancer. Gamma tocopherol may help prevent colon cancer by inhibiting the formation of mutagens arising from the oxidation of fecal lipids, as well as by diminishing oxidative stress in the cells lining the colon.24,45,49

Prostate cancer. Both alpha tocopherol and gamma tocopherol may guard against prostate cancer.3-5 Gamma tocopherol effectively inhibits cell proliferation and DNA synthesis in colon and prostate cancer cells.50 In one study, researchers found that gamma tocopherol—but not alpha tocopherol—induced apoptosis (programmed cell death) in both prostate and lung cancer cells.50 Similar effects have been observed with gamma-tocopheryl quinone, a metabolite of gamma tocopherol that demonstrates powerful chemotherapeutic and cell-killing properties in human leukemia cells.51

One study revealed an intriguing association between prostate cancer and plasma and toenail concentrations of alpha tocopherol, gamma tocopherol, and selenium. Men with the highest concentrations of gamma tocopherol had a fivefold lower risk of developing prostate cancer than men with the lowest levels. Moreover, the protective effect observed for high levels of selenium and alpha tocopherol was observed only when gamma tocopherol levels were also high, leading the authors to recommend the use of mixed tocopherol supplements in future prevention trials.52

Other cancers. Blood levels of both alpha tocopherol and gamma tocopherol appear to be substantially lower in women at risk for cervical cancer.53 In addition, epidemiological evidence indicates that women who consume the most dietary vitamin E (which consists primarily of gamma tocopherol) have a 60% lower risk of breast cancer than women with low dietary vitamin E intake.12 Finally, gamma tocopheryl quinine, the gamma tocopherol metabolite, has been found to kill leukemia and breast cancer cells in the laboratory.51,54

Gamma May Guard Against Dementia

Some of the most promising protective benefits of gamma tocopherol involve Alzheimer’s disease. Scientists believe that oxidative stress and inflammation are major contributing factors in the development of Alzheimer’s, and that reactive nitrogen oxides play a role in the disease process. The results of one study suggest that gamma tocopherol offers greater protection than alpha tocopherol in subduing oxidative stress in the brain related to reactive nitrogen oxides, thus helping to protect the brain against inflammatory processes related to Alzheimer’disease.55

GAMMA TOCOPHEROL EXCLUDED FROM DIETARY REFERENCE INTAKES

Until recently, scant attention has been paid to the biological importance of gamma tocopherol and the other tocopherol forms. In fact, they are not even included in the new dietary reference intakes recently established by the US Food and Nutrition Board.

Under the current dietary reference intake definition for vitamin E activity, the daily intake requirement can be met only with alpha tocopherol. This is not the case in the European Union, where gamma tocopherol is considered an integral component of the nutrient-based recommendations in many EU member countries.

The US Food and Nutrition Board’s decision has failed to consider the cumulative results of more than three decades of research, which consistently point to a unique nutritional role for gamma tocopherol. This underestimated nutrient—the most prevalent form of vitamin E in nature—may contribute significantly to human health in ways yet fully recognized.

British researchers recently found that dietary vitamin E, mainly comprising gamma tocopherol, strongly affects the expression of an array of genes involved in the clearance of amyloid beta proteins.7 The accumulation of amyloid beta plaques is a hallmark of the oxidation and inflammation that occurs in the brains of Alzheimer’s sufferers. Fighting beta amyloid tangles is believed to be essential in slowing the progression of this incapacitating disease.

Moreover, vitamin E appears to help regulate other genes associated with nerve growth, the transmission of nerve signals, and the clearance of advanced glycation end products, which are pro-inflammatory sugar-protein complexes that result from oxidative damage to biological molecules.7 Such evidence of vitamin E’s role as a gene regulator indicates an important protective role for dietary vitamin E against the progression of Alzheimer’s disease.

Alpha tocopherol, more so than gamma tocopherol, suppresses the degeneration of neurons caused by oxidative stress.56 This has led some researchers to dismiss gamma tocopherol’s importance in protecting against neurodegenerative decline. However, research conducted in 2005 provides strong evidence that gamma tocopherol may play just such a protective role. The study authors found that increased consumption of a mixture of tocopherols from food, rather than alpha tocopherol alone, was associated with a lower risk of Alzheimer’s-related cognitive decline.6 Their findings are consistent with several other recent studies that validate vitamin E’s importance in preventing the onset of Alzheimer’s disease.7,57-59

The Future of Vitamin E Supplementation

As recent investigations show, gamma tocopherol is quickly gaining recognition within the medical research community and is emerging as an important partner to alpha tocopherol in the science of preventive health.

While both forms of vitamin E have disease-preventive actions that reflect their individual chemistries, it is their combination that likely accounts for the powerful preventive effects observed in epidemiological, retrospective, and laboratory studies. Consequently, to highlight one form and exclude the other is to sell both forms short. We may soon find that the other tocopherol forms of vitamin E pack even more preventive punch in ways not yet revealed.

STUDY FLAWS FUEL VITAMIN E CONTROVERSY

Life Extension members and other health-conscious adults have expressed concern about recent headlines that question the safety and effectiveness of vitamin E supplements. In fact, findings from several clinical trials of alpha tocopherol have been ambiguous, failing to show consistent results due to the way the trials were structured and conducted.60-64

For example, a recent meta-analysis of seven clinical trials of antioxidant vitamins concluded that the data do not support the use of vitamin E supplements for preventing heart disease.65 Likewise, a number of large prospective studies examining vitamin E’s cancer-preventive effects have produced inconsistent results.14

Several plausible explanations may account for this ambiguity. At a recent conference on vitamin E and health sponsored by the New York Academy of Sciences, researchers noted that the various clinical trials of vitamin E differed markedly in ways that contribute to the inconsistent findings.14 For one thing, many of the studies focused on supplementation with vitamin E alone rather than with a broad spectrum of antioxidants. It is well known that nutrients work best when they work synergistically; consequently, the inconsistent findings may simply reflect the fact that no single nutrient is a “magic bullet.”

In addition, many of the clinical studies involved elderly adults who were seriously ill, rather than healthy individuals. The results of such studies would not, therefore, reflect the preventive nature of nutritional supplementation. Moreover, virtually all of the clinical trials used alpha tocopherol, the primary form of vitamin E in dietary supplements, and most used synthetic vitamin E—which is known to cause adverse effects at high dosage—rather than the mixed tocopherols found in natural dietary sources.46 According to researchers at Johns Hopkins, the benefits of alpha tocopherol may in fact be compromised by a decrease in the levels of gamma and other tocopherols that is known to occur with high-dose alpha tocopherol supplementation.36

To explain these inconsistencies, scientists are now looking beyond alpha tocopherol to other forms of vitamin E, particularly gamma tocopherol. To date, relatively few clinical studies have examined gamma tocopherol’s role in the context of prevention. Those few, however, concur that gamma tocopherol may be every bit as important as alpha tocopherol in preventing chronic diseases.25,39 These findings may prelude a paradigm shift in scientific thinking on vitamin E.

Nevertheless, it is important to keep in mind that most research to date consists of laboratory studies and that further human clinical trials are needed to reveal the true powers of gamma tocopherol and other forms of vitamin E. Researchers have called for such trials to employ a mixture of tocopherols that better reflects the ratio found in the diet. Others urge a review of international dietary standards that to date have considered only the alpha tocopherol form.

Given the widespread popularity of vitamin E supplementation, the potential public health implications of using mixed tocopherols are immense. According to Dr. Kenneth Hensley of the Oklahoma Medical Research Foundation, recent findings may signal a major paradigm shift in free radical biology and medicine, and argue for a thorough reappraisal of the role of gamma tocopherol and other tocopherol forms, especially within the context of cardiovascular disease and cancer biology.66

Dr. Stephan Christen of the University of California, Berkeley, contends that consumers taking vitamin E supplements containing an imbalance of the two principal forms of vitamin E are depriving themselves of the protective value afforded by a mixture of tocopherols. His views are based on joint investigations by US and Australian researchers that confirm previous findings—namely, that gamma tocopherol possesses distinctive and protective biochemical properties not seen in alpha tocopherol, and plays an equally important but complementary role in limiting cell damage and disarming toxic metabolites.26 Accordingly, he and other scientists contend that vitamin E supplements should contain a ratio of alpha tocopherol to gamma tocopherol that is closer to what is found in nature.

In the meantime, consumers of dietary supplements committed to optimal nutrition should seriously consider the inclusion of mixed tocopherols in their daily regimens. Johns Hopkins scientists initially recommended that at least 20% of supplemental vitamin E be in the form of gamma tocopherol,52 while researchers at Berkeley just this year have proposed a 50-50 blend of alpha tocopherol and gamma tocopherol.67 For optimal supplementation, it would appear logical to consume at least 200 mg of gamma tocopherol each day, in addition to around 400 IU of alpha tocopherol.

Editor’s note: Individuals who use the medication warfarin (Coumadin®) or have a history of bleeding disorder or hemorrhagic stroke should consult a physician before supplementing with vitamin E.

References

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