Vitamin E - Risks and Benefits

 Risks

Increased prostate cancer risk from vitamin E supplements

Men who took 400 international units (I.U.) of vitamin E daily had more prostate cancers compared to men who took a placebo, according to an updated review of data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The findings showed that, per 1,000 men, there were 76 prostate cancers in men who took only vitamin E supplements, vs. 65 in men on placebo over a seven-year period, or 11 more cases of prostate cancer per 1,000 men. This represents a 17 percent increase in prostate cancers relative to those who took a placebo. This difference was statistically significant and therefore is not likely due to chance. The results of this update appeared Oct. 12, 2011, in the Journal of the American Medical Association.

SWOG, an international network of research institutions, carried out SELECT at more than 400 clinical sites in the United States, Puerto Rico, and Canada. SELECT was funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health.

The crystalline structure of Vitamin E“Based on these results and the results of large cardiovascular studies using vitamin E, there is no reason for men in the general population to take the dose of vitamin E used in SELECT as the supplements have shown no benefit and some very real risks,” said Eric Klein, M.D., a study co-chair for SELECT, and a physician at the Cleveland Clinic. “For now, men who were part of SELECT should continue to see their primary care physician or urologist and bring these results to their attention for further consideration.”

The SELECT study began in 2001 and included over 35,000 men. It was started because earlier research had suggested that selenium or vitamin E might reduce the risk of developing prostate cancer. However, based on an independent safety monitoring review in autumn 2008, participants were told to stop taking their study supplements because it had become clear that the trial would never produce the 25 percent reduction in prostate cancer the study was designed to show with the use of these supplements. In 2010, the study sites were closed and over half of the participants consented to have their health monitored via mail questionnaires. Now, because of this latest finding, researchers are encouraging all participants to consider taking part in long-term study follow-up so investigators can continue to track outcomes.

SELECT was undertaken to substantiate earlier, separate findings from studies in which prostate cancer risk was not the primary outcome. A 1998 study of male smokers in Finland who took 50 I.U. of vitamin E daily to prevent lung cancer, showed 32 percent fewer prostate cancers in men who took the supplement. A 1996 study of men and women with a history of skin cancer who took selenium for prevention of disease recurrence showed that men who took the supplement had 52 percent fewer prostate cancers than men who did not take the supplement.

Based on these and other findings, men were recruited to participate in SELECT. They were randomly assigned to take one of four sets of supplements or placebos, with more than 8,000 men in each group. One group took both selenium and vitamin E; one took selenium and a placebo that looked similar to vitamin E; one took vitamin E and a placebo that looked similar to selenium; and the final group received placebos of both supplements. Men who took selenium alone or vitamin E and selenium together were also more likely to develop prostate cancer than men who took a placebo, but those increases were small and possibly due to chance.

“SELECT has definitively shown a lack of benefit from vitamin E and selenium supplements in the prevention of prostate cancer and has shown there is the potential for harm,” said Lori Minasian, M.D., study co-author and acting director of NCI’s Division of Cancer Prevention. “Nevertheless, this type of research has been critically important to understanding the potential benefits and risks from supplements.”

SELECT researchers are now measuring the amount of vitamin E, selenium, and other nutrients in the blood of participants when they joined the trial, to see if the effect of the supplements depended upon this baseline level of micronutrient. Other researchers are looking at single nucleotide polymorphisms, which are DNA changes known as SNPs, to see if a change in one or more genes could affect cancer risk or perhaps increase a man’s risk of developing prostate cancer while taking vitamin E.

The participant samples come from the study biorepository of blood and toe nail clippings which, when coupled with the extensive clinical information on participants, is a vital resource for further study. “SWOG is soliciting proposals from researchers nationwide to use the SELECT biorepository to help answer the biological question of why vitamin E increased risk instead of decreasing it,” said Laurence Baker, D.O., study co-author and chairman of SWOG. “There are many more questions raised by these study results than we have answers for, and thus the need for further investigation.”

Except for skin cancer, prostate cancer is the most common type of cancer in men in the United States. The current lifetime risk of prostate cancer for American men is 16 percent. In 2011, there will be an estimated 240,890 new cases of prostate cancer and 33,720 deaths from this disease in the United States. 

Vitamin E supplements hamper endurance training

Vitamin C and E supplements may blunt the improvement of muscular endurance – by disrupting cellular adaptions in exercised muscles – suggests a new study published February 2014 in The Journal of Physiology.

As vitamin C and E supplements are widely used, understanding if they interfere with cellular and physiological adaptations to exercise is of interest to people exercising for health purposes as well as to athletes.

Dr Gøran Paulsen, who led the study at the Norwegian School of Sport Sciences, explains:

"Our results show that vitamin C and E supplements blunted the endurance training-induced increase of mitochondrial proteins, which are needed to improve muscular endurance."

In the 11-week trial, 54 young, healthy men and women were randomly allocated to receive either 1000mg vitamin C and 235mg vitamin E (consistent with amounts found in shop supplements), or a placebo (a pill containing no active ingredients). Neither the subjects nor the investigators knew which participant received the vitamins or placebos.

The participants completed an endurance training programme, consisting of three to four sessions per week, of primarily running. Fitness tests, blood samples and muscle biopsies were taken before and after the intervention.

Whilst the supplements did not affect maximal oxygen uptake or the results of a 20 metre shuttle test, the results showed that markers for the production of new muscle mitochondria – the power supply for cells – increased only in the group without supplements.

The National Health Service (NHS) says taking less than 540mg vitamin E and 1000mg vitamin C supplements per day is unlikely to cause any harm.

Dr Paulsen says:

"Our results indicate that high dosages of vitamin C and E – as commonly found in supplements – should be used with caution, especially if you are undertaking endurance training."

A significant trend has been identified, but the molecular processes requires further research. Dr Paulsen says:

"Future studies are needed to determine the underlying mechanisms of these results, but we assume that the vitamins interfered with cellular signalling and blunted expression of certain genes."

Previous studies show that exercising increases muscle oxidant production, which participates in the signalling processes leading to muscle adaption. It is possible that high doses of vitamins C and E act as antioxidants and take away some of this oxidative stress, hence blocking muscular endurance development.

Benefits/Risks

Vitamin E may decrease and increase mortality of male smokers

Six-year vitamin E supplementation decreased mortality by 41% in elderly male smokers who had high dietary vitamin C intake, but increased mortality by 19% in middle-aged smokers who had high vitamin C intake, according to a study published in the American Journal of Epidemiology.

Large-scale controlled trials have not found any overall effects of vitamin E supplementation on the mortality of participants. Nevertheless, the effect of vitamin E on respiratory infections has significantly diverged between different population groups suggesting that the effects of vitamin E may not be uniform over all the population.

Dr. Harri Hemila, and Professor Jaakko Kaprio, of the University of Helsinki, Finland, studied whether the effect of vitamin E supplementation on mortality might diverge between different population groups. They analyzed the data of the large randomized trial (Alpha-Tocopherol Beta-Carotene Cancer Prevention Study) which was conducted in Finland between 1985-1993 and included male smokers aged 50-69 years. There were 3571 deaths in 29,133 participants during the 6-year supplementation of 50 mg/day of vitamin E.

Although vitamin E had no overall effect on mortality, its effect was modified by age and dietary vitamin C intake. Vitamin E had no effect on participants who had low dietary vitamin C intake, less than 90 mg/day. However, in those who had high vitamin C intake, over 90 mg/day, the effect of vitamin E diverged so that it increased mortality in young participants (50-62 years), but decreased mortality in old participants (66-69 years).

The US nutritional recommendations, issued by the prestigious Institute of Medicine, consider that vitamin E is safe in doses up to 1000 mg/day. This new study gives further evidence indicating that in some population groups vitamin E may be harmful in a substantially lower dose, 50 mg/day.

The researchers concluded that "in people younger than 65 years, taking vitamin E supplements should be strongly discouraged, until clear evidence emerges that some population groups of younger or middle-aged people benefit". They also concluded that the effect of vitamin E on elderly people should be further investigated.

Benefits 

Vitamin E may increase the life expectancy of older men

Depending on the level of smoking and dietary vitamin C intake, vitamin E supplementation may extend the life-span of restricted groups of men, according to a study published in the Age and Ageing.

Several large randomized trials of humans found that vitamin E supplementation does not reduce mortality. However, the average effect on mortality in a group of people with a wide age range may mask an effect of vitamin E on the life-span.

Dr. Harri Hemila, and Professor Jaakko Kaprio, of the University of Helsinki, Finland, studied the age-dependency of vitamin E effect on mortality in the large randomized trial (Alpha-Tocopherol Beta-Carotene Cancer Prevention Study) which was conducted in Finland between 1985-1993. Their study was restricted to follow-up period over 65 years and 10,837 participants contributed to the analysis.

Among all analyzed participants, vitamin E had no effect on mortality when participants were 65 to 70 years old, but reduced mortality by 24% when participants were 71 or older.

Among 2,284 men with dietary vitamin C intake above the median who smoked less than a pack of cigarettes per day, vitamin E extended life-span by two years at the upper limit of the follow-up age span. In the other participants, consisting of 80% of the cohort, vitamin E did not affect mortality, which shows that vitamin E is no panacea for extending life expectancy.

The researchers concluded that "if vitamin E influences the life-span, it is possible that a benefit on the oldest participants might be camouflaged by the large middle-aged majority of study participants". Therefore, they propose that it might be useful to analyze the effect of vitamin E supplementation in large controlled trials by the age of the participant at the follow-up and not just by the time after randomization that has been customary.