Do antioxidant supplements really work?

Naveed Saleh, MD, MS | July 29, 2021

What do vitamin C, vitamin E, selenium, and carotenoids, such as beta-carotene, lycopene, and lutein, have in common? They are all antioxidants. While often touted for their health benefits, research reveals that these antioxidants may offer little health benefit, according to the NIH.

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Antioxidant supplements are touted for their health benefits, but here's what the science says about their efficacy.

“Rigorous scientific studies involving more than 100,000 people combined have tested whether antioxidant supplements can help prevent chronic diseases, such as cardiovascular diseases, cancer, and cataracts,” explained the NIH. “In most instances, antioxidants did not reduce the risks of developing these diseases.”

Although official US nutritional guidance promotes eating antioxidant-rich fruits and vegetables for their health benefits, and those who eat healthy amounts of these foods exhibit lower rates of several illnesses, it’s unclear what role antioxidants play in disease prevention. It could be that other components of fruits and vegetables, or covariates, such as other lifestyle choices, actually prevent illness.

Let’s take a closer look at a few studies that the NIH cites to support its conclusion that antioxidant supplements may not be all they are cracked up to be. Please note that although some of these studies date back several years, the NIH still values them and labels them “recent.” Furthermore, many of these clinical trials were funded by the NIH to compare the effects of antioxidant supplements vs placebo on diseases such as cancer and heart disease. 

Woman’s antioxidant cardiovascular study 

In this earlier trial from 2004, researchers tested whether antioxidant vitamins and a folic acid/vitamin B6/vitamin B12 combination decreased risk for future cardiovascular events in 8,171 women with preexisting cardiovascular disease (CVD) or CVD risk factors. 

“Although a definitive conclusion regarding generalizability requires additional trials in diverse populations, there is little biological basis for supposing that the benefit-risk balance differs in other high-risk women,” the authors concluded.

Physicians’ health study II

Multivitamins are the most frequently taken dietary supplement in the United States. In this randomized trial, 14,641 male physicians aged 50 years or more took either multivitamins or placebo, with follow-up from 1997 to 2011. Endpoints in this study included nonfatal myocardial infarction (MI), nonfatal stroke, and CVD mortality.

“Among this population of US male physicians, taking a daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up,” concluded the authors. 

Vitamin E and vitamin C supplements failed to decrease the risk of heart attack, stroke, or death due to heart disease. Furthermore, vitamin E supplementation was tied to a higher risk of hemorrhagic stroke, among other findings.

SELECT trial

Researchers in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) examined whether these supplements could prevent prostate cancer when compared with placebo. The trial was funded by the National Cancer Institute, with more than 35,000 men aged 50 years and older participating at hundreds of clinical sites.

Not only did these supplements fail to prevent prostate cancer, on longer follow-up, they actually predicted risk of prostate cancer. “The additional data show that the men who took vitamin E alone had a 17 percent relative increase in numbers of prostate cancers compared to men on placebo,” the authors wrote.

Although NIH researchers didn’t reject the null hypothesis, they did suggest certain reasons why the selenium supplements failed to decrease cancer risk, including excessive dosing and decreased bioactivity. Furthermore, the NIH noted, “it may be that selenium only reduces the risk of prostate cancer in selenium-deficient men and not in the general population.”

Bottom line

In the aggregate, antioxidant supplements may do little to facilitate better health. In fact, they may actually be unhealthy in certain situations. (In addition to the aforementioned examples, high-dose beta-carotene supplementation may increase the risk of lung cancer.)

These findings are unfortunate because antioxidants have shown so much promise in preclinical studies, where they readily stabilize free radicals. Ultimately, not all research translates from bench to bedside, and in the case of antioxidants—unless deficiency is an issue—it may be best to secure them from a balanced diet.

Read more about potential adverse effects of antioxidants and other supplements at MDLinx.

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