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Which Form of Vitamin E, Alpha- or Gamma-Tocopherol, is Better?

Maret G. Traber, Ph.D.
Professor of Nutrition
LPI Principal Investigator

Despite the numerous antioxidant and anti-inflammatory properties of alpha-tocopherol, results of large clinical trials assessing vitamin E efficacy in heart disease have been disappointing. We know that oxidative stress and inflammation play pivotal roles in heart disease. Recent clinical trials even suggest that markers of inflammation, such as C-reactive protein, may be better indicators of heart disease risk than the old standby, cholesterol. So many scientists are asking, why didn't vitamin E work?

It is surprising that alpha-tocopherol wasn't effective in the clinical trials because it appears to have potent effects on cellular functions that may modulate heart attack risk. Alpha-tocopherol can modulate the inflammatory responses in white blood cells. It also can decrease blood clotting by platelets—an important reason to let your physician know that you are taking vitamin E. Another key function regulated by alpha-tocopherol is vascular tone. Normal vascular function requires responsiveness to nitric oxide (NO). Alpha-tocopherol not only mediates NO production, but alpha-tocopherol supplementation in hypercholesterolemic patients and in smokers maintains normal artery wall flexibility. In clinical trials, vitamin C has also been found to exert vasodilatory effects, probably through a different mechanism.

Unfortunately, most of the studies designed to demonstrate specific alpha-tocopherol functions have been test-tube studies or are a result of ex vivo treatment, i.e., plasma removed from subjects. Very few measurements have been carried out in supplemented humans. Moreover, all of the intervention studies evaluating the role of vitamin E in heart disease were carried out using supplements containing alpha-tocopherol. This has led to the concept that only alpha-tocopherol has been well studied and that other members of the vitamin E family, including gamma-tocopherol, have been neglected. But that is not true.

It is well known that alpha-tocopherol supplements decrease plasma gamma-tocopherol concentrations. What is less well appreciated is that the body intentionally retains alpha-tocopherol. A special protein in the liver, the alpha-tocopherol transfer protein, preferentially maintains blood levels of alpha-tocopherol by incorporating only alpha-tocopherol into low-density lipoprotein (LDL) for tissue distribution. Our studies, currently in progress, show that the body retains alpha-tocopherol three times longer than gamma-tocopherol.

Mechanisms of gamma-tocopherol action

Very few studies have evaluated gamma-tocopherol in the body, but those that have suggest that it may have potent physiological actions. While both alpha- and gamma-tocopherol are potent antioxidants, gamma-tocopherol has a unique function. Because of its different chemical structure, gamma-tocopherol scavenges reactive nitrogen species, which, like reactive oxygen species, can damage proteins, lipids, and DNA. 5-Nitro-gamma-tocopherol, which is formed from these scavenging reactions, may be a useful in vivo marker for estimating the physiological relevance of such reactions. My laboratory has just developed methods for measuring this marker, and we plan to use these to assess gamma-tocopherol activity in humans under various kinds of oxidative and inflammatory stress.

The RDA is only for alpha-tocopherol

The recommended dietary allowance (RDA) for vitamin E was set in 2000 as 15 mg of alpha-tocopherol per day. A diet rich in fruits and vegetables and low in fat probably contains less than 15 mg of alpha-tocopherol. Moreover, dietary alpha-tocopherol has probably decreased over the past 50 years, not by losses in food processing, but because of changes in recipes! Responding to concerns about the relationship between certain dietary fats and heart disease, food manufacturers have increased the vegetable oil content of processed foods. Vegetable oils rich in polyunsaturated fats from, for example, corn and soybeans, are also rich in gamma-tocopherol. Consuming these oils as the major source of fat in the diet increases gamma-tocopherol intakes to as much as 50 to 100 mg per day.

Gamma-tocopherol concentrations in the blood have been reported to be significantly lower in coronary heart disease (CHD) patients compared to healthy subjects, suggesting that the low Gamma-tocopherol concentrations increased the risk of CHD. But Gamma-tocopherol may simply be an indicator that the patients did not eat a diet low in saturated fat and high in polyunsaturated fat. Higher vegetable oil intakes in healthy subjects may have raised Gamma-tocopherol concentrations. Although the beneficial effect may have been due to the intake of polyunsaturated fat, Gamma-tocopherol itself may have some benefit.

Prior to 2000, the RDA was expressed in “alpha-tocopherol equivalents,”and Gamma-tocopherol was estimated to have 10% of the activity of alpha-tocopherol. In contrast, the 2000 RDA defines that the vitamin E requirement can only be met by alpha-tocopherol and further specifies that the activity of synthetic (dl) alpha-tocopherol is half that of natural (d) alpha-tocopherol. Thus, the 2000 RDA for vitamin E is not based on antioxidant activities of the various dietary forms of vitamin E (tocopherols and tocotrienols), but rather on the observation that alpha-tocopherol is maintained in the circulation and therefore must be required for some specific, as yet undefined, function.

Key to establishing human vitamin E requirements is the identification of alpha-tocopherol function. An important functional role of alpha-tocopherol in human nutrition as an antioxidant is difficult to justify because there are a variety of dietary antioxidants that are more potent than alpha-tocopherol. However, only alpha-tocopherol has a protein that regulates its plasma concentrations. This observation argues for a unique and important physiological role for alpha-tocopherol. The goal of the Traber lab is to discover that function!

Last updated May, 2003

Micronutrient Research for Optimum Health

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