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Alpha-tocopherol Supplementation Reduces Gamma and Delta-tocopherol Levels

Researchers at Johns Hopkins University in Baltimore, Maryland have found a possible reason for the conflicting results obtained from vitamin E supplementation in cardiovascular and cancer trials.

Clinical research has most often utilized alpha-tocopherol. Yet alpha tocopherol is only one of four tocopherols that combined with four tocotrienols, form the full complement of vitamin E isomers. Although the major form of vitamin E found in the blood is alpha-tocopherol, a typical American diet provides over two-thirds of its vitamin E in the form of gamma-tocopherol. Recent research has found that the other tocopherols and tocotrienols, particularly gamma-tocopherol, have disease preventive benefits. In the current study, Dr. Han-Yao Huang and Dr. Lawrence J Appel found that supplementation with alpha-tocopherol lowered concentrations of both gamma and delta-tocopherols.

One hundred eighty-four (184) adult nonsmokers were randomized to receive 400 international units (IU) alpha-tocopherol or a placebo daily for a two-month period. Study participants who were regular users of vitamin E supplements were asked to stop supplementing during the two months prior to the trial. Even with a washout period of 2 months, this group had higher serum levels of alpha-tocopherol and lower levels of gamma-tocopherol than those who had not used Vitamin E supplements prior to the study's onset.

Predictably, alpha-tocopherol supplementation increased serum levels of the vitamin in the group that received it. However, at the study's conclusion, participants who received alpha-tocopherol experienced a reduction in serum gamma-tocopherol blood levels of approximately 58 percent. While delta-tocopherol concentrations were detectable in half of the subjects in each group at the study's onset, alpha-tocopherol supplementation for two months reduced detectable levels to 13 percent.

The researchers suggest that alpha-tocopherol supplements may compete with gamma and delta-tocopherols for hepatic transfer, thereby lowering their blood concentrations. Although they did not test for beta-tocopherols or the tocotrienols, serum levels of these fractions may also be reduced by supplementing with only alpha-tocopherol. Thus people who obtain the full compliment of tocopherols and tocotrienols (from food or supplements) may be more protected than those who just obtain alpha tocopherol supplementation.

Maximum Vitality contains all the tocopherol and tocotrienol forms of Vitamin E.


Despite promising evidence from in vitro experiments and observational studies, supplementation of diets with alpha-tocopherol has not reduced the risk of cardiovascular disease and cancer in most large-scale clinical trials. One plausible explanation is that the potential health benefits of alpha-tocopherol supplements are offset by deleterious changes in the bioavailability and/or bioactivity of other nutrients.

We studied the effects of supplementing diets with RRR-alpha-tocopheryl acetate (400 IU/d) on serum concentrations of gamma- and delta-tocopherol in a randomized, placebo-controlled trial in 184 adult nonsmokers. Outcomes were changes in serum concentrations of gamma- and delta-tocopherol from baseline to the end of the 2-mo experimental period.

Compared with placebo, supplementation with alpha-tocopherol reduced serum gamma-tocopherol concentrations by a median change of 58% [95% CI = (51%, 66%), P < 0.0001], and reduced the number of individuals with detectable delta-tocopherol concentrations (P < 0.0001). Consistent with trial results were the results from baseline cross-sectional analyses, in which prior vitamin E supplement users had significantly lower serum gamma-tocopherol than nonusers.

In view of the potential benefits of gamma- and delta-tocopherol, the efficacy of alpha-tocopherol supplementation may be reduced due to decreases in serum gamma- and delta-tocopherol levels. Additional research is clearly warranted.


Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr. 2003 Oct;133(10):3137-40. PMID: 14519797 [PubMed - indexed for MEDLINE]

Key concepts: Vitamin E, alpha-tocopherol, gamma-tocopherol, delta-tocopherol