Should You Take Vitamin E Supplements?

Randomized controlled trials show that daily vitamin D supplementation appears to reduce the risk of acute respiratory infections in children and adolescents, but it does not seem to make a difference in adults. Nor does vitamin D appear effective for boosting antibody responses to influenza vaccination.

What about vitamin E? In most places, you’ll read that there are eight different tocopherols and tocotrienols that are collectively known as vitamin E, but only alpha-tocopherol has been shown to protect against human vitamin E deficiency. So, alpha-tocopherol is the only bona fide vitamin E and is the one found in vitamin E supplements.

There are observational data suggesting those self-reporting supplementation with vitamin E have, for example, better pneumonia outcomes. But only interventional trials can prove if this is the case. Compared to placebo supplements, vitamin E was able to significantly boost immunity to hepatitis B and tetanus vaccinations (though not to diphtheria or pneumonia). One randomized controlled trial found that vitamin E supplementation of the elderly did not cut down on lower respiratory tract infections (like pneumonia), but did reduce the incidence of upper respiratory tract infections (like the common cold) by about 20 percent over one year. But another study using the same dose found no preventive benefit, and vitamin E supplementation actually made the infections they did get even worse––with a greater number and severity of symptoms, including a greater likelihood of fever and activity restriction.

By far the largest study on vitamin E and respiratory infections was the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study that randomized nearly 15,000 smokers to vitamin E or placebo for about five years. No overall effect was found either way between the vitamin E and placebo groups. But upon subgroup analysis, it appeared that while lighter smokers living in cities appeared to benefit with about a 50 percent lower risk of catching the common cold, vitamin E appeared to be a detriment to heavier smokers living outside of cities––resulting in about a 50 percent increased risk. “Accordingly,” concluded the investigators, “caution should be maintained in public health recommendations on vitamin E supplementation until its effects are better understood.”

The pneumonia results from the same study took a similar turn. No overall effect of vitamin E compared to placebo, but upon further analysis, vitamin E appeared to decrease pneumonia risk among lighter smokers who exercised, yet it increased pneumonia risk among heavier smokers who did not. Higher pneumonia rates were also noted in those randomized to vitamin D and were either low or high body weight––but only, apparently, among those with high dietary vitamin C intake. Heavy smokers who got a lot of vitamin C also seemed to have higher tuberculosis rates on vitamin E compared to placebo. This kind of slicing and dicing of data is frowned upon, as it can spawn spurious connections, and so these findings are regarded only as exploratory for further research directions.

Overall mortality in the ATBC study was similar between the vitamin E and placebo groups, though again there were subgroups that appeared to have their lives cut short or extended. There have been dozens of controlled clinical trials on vitamin E, and most meta-analyses found a small but apparent real increase in the risk of mortality among those randomized to vitamin E. In other words, those who buy vitamin E supplements may be in effect paying to live a shorter life. Across 46 trials, 12 percent died in the vitamin E groups, versus about 10 percent in the placebo groups. (This is similar to the increase in mortality seen with beta carotene supplementation—approximately 14 percent versus 11 percent across 26 randomized trials.)

The goal of the ATBC was to see if taking antioxidant supplements, like vitamin E or beta carotene, could help prevent lung cancer in smokers. Vitamin E had no effect on lung cancer, and beta-carotene unexpectedly actually increased lung cancer rates. But vitamin E did, incidentally, appear to reduce incident prostate cancer rates. This helped inspire the SELECT study, the largest cancer prevention trial ever performed. More than 35,000 men were randomized to take vitamin E, selenium, both, or neither (just placebos). The selenium didn’t appear to matter, but those randomized to the straight vitamin E group ended up with a 17 percent greater risk of developing prostate cancer. If 100 men took vitamin E for a decade, we would expect to see one or two of them be diagnosed with prostate cancer that they otherwise wouldn’t have gotten had they wasted their money on sugar pills instead.

Oxidative stress from free radicals is the one of the pathways implicated in the development and deterioration of Alzheimer’s brains, given the evidence of excess of oxidative DNA damage on autopsy. So, what about trying an antioxidant? Vitamin E levels tend to be lower in the bloodstreams of those with cognitive impairment or dementia, but which came first? Maybe Alzheimer’s disease led to poor eating, rather than poor eating leading to Alzheimer’s disease. Greater vitamin E intake from foods is clearly associated with lower risk of developing Alzheimer’s, but greater vitamin E intake from supplements is not. But that didn’t stop researchers from including a vitamin E arm in the largest primary prevention study of Alzheimer’s disease to date.

The Prevention of Alzheimer’s Disease by Vitamin E and Selenium trial randomized more than 7,500 older men to take vitamin E, selenium, both, or neither—just placebos—for five years. To quote from the conclusion: “Neither supplement prevented dementia.” A separate long-term vitamin E supplementation trial of older women similarly found no protection against cognitive decline. Neither did vitamin E appear to benefit those with mild cognitive impairment. But the trials on Alzheimer’s patients themselves started to get more interesting.

The first trial, published in the New England Journal of Medicine, randomized more than 150 Alzheimer’s patients to vitamin E or placebo to see if vitamin E could slow the progression of the disease. The primary outcome was the number of days until of one of any of the following happened: death, institutionalization, loss of the ability to perform basic activities of daily living, or sliding into severe dementia, where you suffer a complete loss of sense of time or place. On first analysis, vitamin E flopped: no significant slowing of progression. Digging deeper, the researchers realized that despite the random allotment, the placebo group just by chance ended up with patients with milder disease. After taking that into account, the difference in outcomes between the vitamin E and placebo groups widened substantially. Now, this kind of unplanned post-hoc analysis is heavily frowned upon, but the effect seemed so sizable they went ahead and published it. In the placebo group, the adjusted time to death or loss of independence was 440 days. But in the vitamin E group, after the baseline cognition was normalized, it was 670 days––more than seven months later. However, given the unorthodox analysis, the scientific world waited for the study to be replicated.

And here we go: more than 600 patients with mild to moderate Alzheimer’s disease were subsequently randomized to vitamin E supplements, the drug memantine, both, or neither (just placebos) for two years. Although there was no slowing of cognitive decline after adjusting for multiple comparisons, there was a slowing of functional decline, in terms of managing daily activities like bathing and dressing. The vitamin E group appeared to only suffer about 1.5 years of functional deterioration in the two years’ time, resulting in approximately two hours less caregiver time required each day compared to the drug group.

If those were the only two clinical vitamin E trials, I would give vitamin E serious consideration for those with Alzheimer’s disease. But, there’s a third, a six-month trial, that suggested vitamin E may be detrimental to cognition in some Alzheimer’s patients. Obviously, more research needs to be done.