Food Insight
July/August 2005

A recent study in the Journal of the American Medical Association (JAMA) looked at major studies cited by scientists over a 13-year period and found that, because of the developing nature of science and research, 16 percent of the time these studies were contradicted by subsequent research findings. The JAMA study underscores the fact that science is, and should be, evolutionary in order to enhance our understanding of an issue.

One of the latest debates in nutrition research involves the use of vitamin E possibly to reduce the risk of or delay chronic disease. Evidence has suggested that this potent antioxidant may lower the risk for various diseases, including heart disease, some types of cancer, cataracts, age-related macular degeneration, Parkinson’s disease, and Alzheimer's disease.

Yet, some recent research has cast doubt on the safety and efficacy of vitamin E dietary supplements—once heralded as a “golden child” of antioxidants—causing debate among scientists as to the merits of supplemental vitamin E.

Antioxidant Abilities

The theory behind the role of antioxidants in good health is well known. Certain nutrients are believed to slow or prevent oxidative damage in the body, which is implicated in the development of many diseases. Dr. Jeffrey Blumberg, a professor in the Friedman School of Nutrition Science and Policy and Director of the Antioxidants Research Laboratory at Jean Mayer USDA Human Nutrition Research Center on Aging, believes that the antioxidant theory related to disease prevention is strong, yet not definitive. “There is provocative evidence from animal studies and observational studies with humans that antioxidants such as vitamin E may be helpful in preventing disease,” says Blumberg. “But current research does not support the use of antioxidants in a therapeutic role.”

Herein lies the challenge with communicating the results of vitamin E research. According to Dr. Takayuki Shibamoto, a professor in the Department of Environmental Toxicology at the University of California, Davis, one reason that recent studies with vitamin E have produced discouraging results is because some overestimate the power of vitamin E. “Antioxidants do not have drug-like abilities,” says Shibamoto. Rather, he explains that antioxidants are better suited to help reduce the risk or slow the progression of disease so other body processes or medications can better fight the disease.

Vitamin E is a case in point—illustrating that with any research, new evidence needs to be considered carefully before making generalized recommendations or discounting the results of previous well-conducted research. This article will help to put today’s knowledge of vitamin E into context.

Background on Vitamin E

This fat-soluble vitamin found in plants exists in eight different forms. The forms vary in their biological activity, or potency, in the body. In its natural form of alpha-tocopherol, vitamin E is most biologically active in humans and also functions as an antioxidant.

Many vitamin E supplements are synthetic and derived from petroleum, while the natural form comes mainly from soybean oil. On a dietary supplement label, the simplest way to determine which form is used is to look at the ingredients: “dl”-alpha-tocopherol means synthetic; “d” instead of “dl” means it’s natural.

The Institute of Medicine (IOM) established a Recommended Dietary Allowance (RDA) for vitamin E as part of the Dietary Reference Intakes (see Table 1). The RDA for vitamin E is provided as “alpha-tocopherol equivalents” or ATEs, to account for the different biological activities of the varying forms of vitamin E. Foods and some supplements that label vitamin E will list the amount in International Units (IU) because the Daily Value for vitamin E is measured in IUs. The Daily Value for vitamin E is 30 IUs (or 20 mg ATE).

The IOM set a Tolerable Upper Intake Level (UL) for vitamin E at 1000 mg per day (1,500 IU natural vitamin E; 1,000 IU synthetic vitamin E) of supplementary alpha-tocopherol for adults. The UL is the highest daily intake likely to pose no risk of adverse health effects to almost all individuals in the general population. Due to its anticoagulant properties, bleeding problems were the adverse health effect or “critical endpoint” on which to base the UL for vitamin E.

Common food sources of vitamin E include vegetable oils, nuts, green leafy vegetables, and fortified cereals. National surveys suggest that the diets of most Americans do not meet the recommended intake for vitamin E. The Dietary Guidelines for Americans identify vitamin E as a nutrient for concern because intake levels are believed to be low in adults and children.

Evidence for Vitamin E

Related to heart disease, vitamin E is believed to inhibit oxidative changes to LDL (“bad”) cholesterol that promote blockages in blood vessels leading to heart attack and stroke. Observational and clinical studies support this hypothesis.

An observational study of approximately 90,000 nurses suggested that incidence of heart disease was 30% to 40% lower among nurses with the highest intake of vitamin E from diet and supplements. The apparent benefit was mainly derived from vitamin E supplements because high intake of vitamin E from food alone was not associated with cardiac risk reduction. Similarly, a 1993 study of 40,000 male health professionals found those who took at least 100 IUs daily for two years had a third fewer cases of heart disease than those receiving no vitamin E supplements. A 1996 study from the National Institutes on Aging followed 11,000 elderly people for seven years and found the death rate for vitamin E users was a third of that of nonusers.

In an intervention study, the Cambridge Heart Antioxidant Study (CHAOS), researchers assigned 2,002 participants with established heart disease to receive either 800 IU or 400 IU of vitamin E or a placebo for a median of 510 days. Treatment with vitamin E substantially reduced the rate of non-fatal heart attack, with beneficial effects apparent after one year. Over a three-year period of vitamin E and vitamin C supplementation in men and postmenopausal women 45-69 years with elevated blood cholesterol levels, researchers in Finland observed a 74% reduction of atherosclerotic progression in men.

Vitamin E may also play a role in cancer risk reduction by protecting against free radicals implicated in cancer, blocking the formation of cancer-promoting nitrosamines, and helping to enhance immune function. Although research is limited, some studies associate higher intakes of vitamin E with a decreased incidence of specific types of cancer, such as prostate, breast, bladder, and colon. Evidence for a link between vitamin E and prostate cancer was compelling enough to be investigated in a large ongoing clinical trial of 35,000 men. The National Institutes of Health launched the SELECT study (Selenium and Vitamin E Cancer Prevention Trial) to examine whether one or both of these dietary supplements may help reduce risk of prostate cancer. Other studies are underway to examine the potential benefits of vitamin E in reducing the risk of developing cataracts, age-related macular degeneration, Parkinson’s disease, and Alzheimer’s disease. For example, the National Eye Institute launched a new study following the release of promising findings from the Age-Related Eye Disease Study (AREDS), a study of nearly 5,000 participants that found slower progression of age-related macular degeneration with a daily dose of vitamin E (400 IU), beta-carotene, vitamin C, zinc, and copper. The new study will examine if vitamin E, together with lutein and omega-3 fats, can slow the onset of age-related macular degeneration.

Questions Raised about Vitamin E

Recent data from the Women’s Health Study, in which nearly 20,000 healthy, middle-aged women were given 600 international units of vitamin E every other day for roughly 10 years, suggest that vitamin E provides no overall benefit for major cardiovascular-related events or cancer, nor does it affect total mortality or decrease cardiovascular-related deaths in healthy women. However, this double-blind, placebo-controlled trial also found that although overall there was no statistically significant cardiovascular benefit to vitamin E, there was a 24 percent reduction in cardiovascular deaths and a 26 percent reduction in major cardiovascular events among a sub-group of women who were 65 or older.

Another randomized clinical trial known as the Heart Outcomes Prevention Evaluation (HOPE) Study found a lack of protection with vitamin E supplements. This study followed nearly 10,000 patients 55 years and older with vascular disease or diabetes. After about five years, the study was extended and renamed HOPE-TOO (HOPE- The Ongoing Outcomes) with nearly 7,000 patients for four more years. The subjects who received 400 IU of vitamin E daily did not experience fewer major cardiovascular events or differences in cancer incidence, but were 13 percent more likely to develop heart failure compared to those not taking vitamin E. Researchers speculated that higher doses of vitamin E may disturb the balance of beneficial, naturally occurring antioxidants.

A review of 19 clinical trials conducted between 1993 and 2004 also found a lack of benefit associated with vitamin E supplements, especially at higher doses. With vitamin E supplements above 400 IU per day, researchers concluded that there was an increased risk for death among older, high-risk patients. This review may be somewhat limited in that it excluded studies reporting fewer than 10 deaths and did not consider the results of epidemiologic observational studies.

Not the Final Word on Vitamin E

Experts suggest there is good reason to be cautious about generalizing the findings of recent vitamin E studies. Blumberg points out that many studies with negative results were secondary prevention trials where study participants were older with existing disease. “The evidence simply does not support the use of vitamin E in reversing disease,” says Blumberg. Yet the effects on younger and healthier individuals may be more promising.

Despite a substantial amount of research on vitamin E, Shibamoto advises that there is still much to learn—about how vitamin E works with other antioxidants and food components and, particularly, the optimal amount of vitamin E and other antioxidants for specific individuals that may produce favorable health outcomes.

Until more is known, Blumberg and Shibamoto agree with other experts who believe it may be premature to make sweeping recommendations about whether to supplement with vitamin E. Yet, Blumberg adds it is reasonable to suggest that the potential benefits of vitamin E seem to outweigh the risk (if any), especially for at-risk individuals. Studies suggesting greater risk with vitamin E supplements containing more than 400 IU observed no harm at lower levels, such as 100 IU per day.

The IFIC Foundation and Institute of Food Technologists (IFT) Guidelines for Communicating the Emerging Science of Dietary Components for Health suggest that consumers should be guided to make lifestyle changes based on consensus science, rather than emerging science. To do so, communicators are advised to:

• Convey emerging science on a continuum, based on the strength of the overall evidence as opposed to isolated studies
• Provide context when new or emerging scientific evidence adds to and supports the body of research currently available or when the emerging science contradicts previous research, questioning established dietary guidance

(For more information on the Guidelines, please visit the IFIC Foundation Web site at: http://www.ific.org/nutrition/functional/guidelines. For more information on how to critically review scientific studies, see the IFIC Review: How to Understand and Interpret Food and Health-Related Scientific Studies http://ific.org/ publications/reviews/scientificir.cfm).

The latest findings pose some perplexing questions about vitamin E, but do not revoke the body of evidence that supports the safety and potential benefits of vitamin E supplements for a healthy population, as well as at-risk individuals, at the most common daily doses (100-400 IU) found in vitamin E supplements. One conclusion researchers can agree on: vitamin E, or any food component by itself, cannot match the most effective ways to reduce disease risk—not smoking, getting regular exercise, maintaining a healthy weight, and eating an overall healthful diet.

• IFIC Foundation and Institute of Food Technologists' (IFT) Guidelines for Communicating the Emerging Science of Dietary Components for Health