The vitamin E debate rumbles on

By Stephen Daniells

- Last updated on GMT

Related tags Tocopherol

Gamma-tocopherol, the major form of vitamin E consumed in the
American diet, and becoming more popular in dietary supplements,
produces metabolites that are toxic to cells, claims a new study.

The results of the study, published in the Early Edition of the Proceedings of the National Academy of Sciences​ (Vol. 103, pp. 3604-3609), were released two days before the Mayo Clinic recommended that consumers take most of their vitamin E from the diet and not from supplements.

The consumer is receiving yet more mixed messages that will lead to more confusions about this antioxidant. In the past 18 months there has been considerable debate over the safety of vitamin E from the industry and media, much of which was spurred by a widely publicised meta-analysis at the tail end of 2004 that linked vitamin E with an increased risk of all-cause mortality (Annals of Internal Medicine​2005 Jan 4;142(1):37-46).

There are eight forms of vitamin E: four tocopherols (alpha, beta, gamma, delta) and four tocotrienols (alpha, beta, gamma, delta). Alpha-tocopherol (alpha-Toc) is the main source found in supplements and in the European diet, while gamma-tocopherol (gamma-Toc) is the most common form in the American diet.

Gamma-Toc is consumed from vegetable oils such as corn and soybean, and also from nuts. Sources of alpha-Toc include olive oil and sunflower seeds.

Most of the stored form of vitamin E in the body is also alpha-Toc. Previous studies have estimated that more than half of the ingested gamma-Toc is converted to a water soluble metabolite called 2,7,8-(beta-carboxylethyl)-6-hydroxychroman (gamma-CEHC) and then excreted.

The new in vitro​ study claims that the reason the gamma-Toc is excreted is because in its fully metabolised form, proposed to be gamma-tocopherol quinone, it is toxic to cells.

The corresponding alpha-Toc quinone is not toxic, say the researchers, which is why we naturally store alpha-Toc.

In a communication from Ohio State University, entitled "Vitamin E: Nutritional friend or foe?" study co-leader David Cornwell explained: "In the United States we tend to eat a diet rich in corn and soybean oil, so we consume much greater amounts of gamma-tocopherol than alpha-tocopherol.

But most of the vitamin E coursing through our veins is alpha-tocopherol - the body selects for this version. We want to know why that is, and whether the selection of the alpha-tocopherol confers an evolutionary benefit in animal cells."

The study looked at the effect of alpha-Toc, gamma-Toc and the corresponding quinones on possible poisoning of rodent cells, as well as stress induced on the endoplasmic reticulum (ER), an organelle found in eukaryotic cells that is responsible for, amongst other things, protein modification.

"As little as five micromoles of gamma-Toc quinone is sufficient to cause 70 per cent of cells to lose viability,"​ reported the researchers.

In contrast, the alpha-Toc, gamma-Toc and alpha-Toc quinone were not toxic to cells, even at concentrations as high as 50 micromoles.

The gamma-Toc quinone was also linked to inducing ER stress, and by doing so prevents the proper folding of proteins in the cell.

Although the researchers limited their studies to mice brain and skin cells, as well as kidney cells from monkeys, study co-leader Jiyan Ma said: "We think that gamma-tocopherol may have this kind of damaging effect on nearly every type of cell in the body."

"Animals selectively retain the only phenolics antioxidant precursor in the vitamin E family that produces a nonarylating quinone, alpha-Toc, as about 85 per cent of tissue tocopherol,"​ concluded the researchers.

No comparison was made by the researchers with actual​ tocopherol concentrations that could be found in human cells.

In a review by Bruce Ames and colleagues (American Journal of Clinical Nutrition​, 2001, Vol. 74, pp. 714-722), gamma-Toc concentrations in various human tissues with respect to rats and mice are given.

The typical concentration of gamma-Toc found in rodent skin is only three nanomoles per gram, while human skin typically contains 180 nanomoles per gram.

"Gamma-tocopherol concentrations are substantially higher in human than in rodent tissues,"​ wrote Ames and colleagues.

Despite the researchers not having considered the health effects for humans, Ohio State University's statement maintained that there are 'mixed messages' about vitmain E.

Moreover the researchers failed to consider that previous human studies have linked increased levels of gamma-Toc in faeces to the elimination of faecel mutagens and a reduced risk of colon cancer (Journal of National Cancer Institute​ 1997 Vol. 89, pp. 1006-1014).

Ames and colleagues reported that gamma-Toc was superior to alpha-Toc for removing species like reactive nitrogen oxides that cause cell damage, as well having anti-inflammatory activity.

"A nascent body of epidemiological data suggests that gamma-Toc is a better negative risk factor for certain types of cancer and myocardial infarction than is alpha-Toc,"​ wrote Kenneth Hensley, from the Oklahoma Medical Research Foundation, in Free Radical Biology and Medicine (2004, Vol. 36, pp. 1-15).

The Mayo Clinic also issued a statement entitled: "Vitamin E: No disease prevention benefit, possible risks",​ which could further confuse consumers.

Ames and colleagues said: "Controlled intervention studies in humans are required to clearly establish the benefits of gamma-tocopherol supplementation… Potential synergistic effects between alpha-tocopherol and other antioxidants should also be explored."

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