SATURDAY September 22, 2007 (Foodconsumer.org) --Many early trials on vitamin E are flawed, said researchers from Oregon State University and Tufts University after they researched and found the doses used in early trials fell largely into the range that does not reduce the oxidative stress, which is linked to numerous conditions including cancer and heart disease.

The new research published in Free Radical Biology and Medicine has demonstrated that the levels of vitamin E necessary to reduce oxidative stress are far much higher than those that have been used in previous clinical trials.

To be specific, the researchers said as high as 1,600 to 3,200 International Units daily are needed to reduce oxidative stress measured by accepted biomarkers of lipid peroxidation.   The effective doses are four to eight times higher than those used in almost all previous clinical trials.

Dr. Balz Prei, professor and director of the Linus Pauling Institute at Oregon State and Dr. Jeffrey Blumberg from Tufts University said in a commentary that the results of their study explain why early studies on vitamin E resulted in inconsistent conclusions.

“The methodology used in almost all past clinical trials of vitamin E has been fatally flawed,” said Frei, one of the world’s leading experts on antioxidants and disease.

“These trials supposedly addressed the hypothesis that reducing oxidative stress could reduce cardiovascular disease. But oxidative stress was never measured in these trials, and therefore we don’t know whether it was actually reduced or not. The hypothesis was never really tested.”

The effective levels of vitamin E, which exceed the tolerable upper intake level, 1000 IU as set by the Institute of Medicine, can be not obtained through use of any diet, according to the researchers who did not recommend consumers use such high levels for now. However, the researchers said high levels should be used in controlled clinical trials which aim to explore a preventive effect of the vitamin.

Vitamin E has proved in lab, animal or human studies to reduce oxidative stress, inhibit formation of atherosclerotic lesions, slow aortic thickening, lower inflammation and reduce platelet adhesion.  

Some studies showed doses of vitamin E at 100 to 400 IU per day reduced cardiovascular disease risk while others did not.   The consistency in the results from early studies has been ill-understood as most studies did not measure the effect of vitamin E on oxidative stress, which is the main mechanism through which researchers believe the vitamin protects against certain chronic diseases.

“What’s now clear is that the amount of vitamin E than can conclusively be shown to reduce oxidative stress is higher than we realized,” Frei said. “And almost none of the studies done with vitamin E actually measured the beginning level or reduction of oxidative stress.”

The researchers said proper studies of vitamin E must consider the newest findings about this micronutrient. For instance, they should decide which form of vitamin E to use in a trial.   It has been known that the natural forms of the vitamin are far more readily absorbed than synthetic forms.   Also, supplementation of vitamin E will have an effect only when a fat-containing diet is used because vitamin E is oil-soluble and can be absorbed only through fat or oil.

The effect of vitamin E also depends on the subject’s health status.   Trials aiming to determine reduction of oxidative stress should enlist patients with conditions such as hear disease risk factors such as obesity, poor diet, hypertension or other health problems, the authors suggested, which lead to high oxidative stress.

“A pill count simply isn’t enough to determine the value of vitamin E,” Frei said. “We need to select people for trials properly, make sure they are taking the right form of the vitamin, at the right levels and at the right time, and then verify the metabolic results with laboratory testing.”

“Only when we do these studies right will we answer questions about the value of vitamin E in addressing cardiovascular disease,” he said. “So far we’ve been flying blind.”

A scientist affiliated with foodconsumer.org who was not involved in the new research commented that the significance of this research is beyond the protective effect of vitamin E.   He said when a study was designed to determine the effects of certain micronutrient supplements, often a single small dose was used.  

Editor’s note: This research is significant not only because it found that most of vitamin E studies are flawed, but also because it pointed out the potential problems with other similar types of studies.   Consumers should know that both a risk and benefit of a physiologically active substance depends on its dose.   When we read a news story on a study of vitamin E or whatever substance, which claims that the substance is useless, or risky or beneficial for certain condition, we need to know what dose was used in the study and how it was used.   We noticed similar flaws in many studies of vitamin C and potentially many other studies.