Most science journalism is negative about “antioxidant supplements.” You’ve probably heard that antioxidant supplements have a host of negative effects ranging from impaired training adaptations in response to exercise, extreme hypoglycemia, and even increased cancer. At their best, these reports say, antioxidants are merely useless and totally ineffective. The implicit and explicit message is to avoid antioxidant supplements. A “waste of money.”
So, is this true? Are antioxidants harmful? Are they effective? What do they do?
The biggest problem with the popular research on antioxidant supplements is the lack of specificity. These reporters just talk about “antioxidants” as if they are a monolithic entity. In reality, there are thousands of different antioxidant compounds, most of which have specific and unique effects—and these compounds are rarely the subject of the popular studies.
“Antioxidant” is so broad as to be almost useless.
Why Most Antioxidant Supplement Studies are Misleading
If you dig a little deeper, you find that the majority of studies researching the effects of “antioxidant supplements” are looking at just three: vitamin E, vitamin C, and beta-carotene. Furthermore, they’re looking at synthetic, incomplete forms of these vitamins, like single spectrum synthetic vitamin E alpha-tocopherol rather than the full spectrum form we’re more likely to get from food.
Don’t believe me?
Let’s examine some of the studies that purport to show how useless they are and look at the specific antioxidants used.
Metabolic syndrome: A study found that “long term antioxidant supplementation” had no effect on metabolic syndrome risk in adults. For over seven years, a group of adults was randomly chosen to take “antioxidants” to see how it affected their rate of metabolic syndrome—hypertension, high cholesterol, overweight, all the bad things. The antioxidant supplement? Vitamin C, vitamin E, beta-carotene, zinc, and selenium.1
Fasting blood glucose: In another study, taking “antioxidants” for 7.5 years had no effect on fasting blood glucose, an important marker for diabetes risk. The antioxidant supplement? Vitamin C, vitamin E, beta-carotene, zinc, and selenium.2
Cancer: A study found no benefit of “antioxidant supplementation” in cancer prevention. Those taking “antioxidant supplements” had no reduction in cancer incidence or mortality. The supplement? Vitamin C, vitamin E, and beta-carotene.3
Exercise: A study found that “antioxidant supplements” hampered training adaptations in the muscles of human subjects after exercising. Except there are two problems: the antioxidants were just vitamin C and vitamin E; and the actual performance markers measured did not suffer, only some biomarkers related to training adaptations.4
Mortality: A study found that “antioxidant supplements” appear to increase mortality.5 “Science-based” blogs love to cite this one. The antioxidants in question? Beta carotene and vitamin E. Again.
So why do “antioxidant supplement” studies get this so wrong? Why are they looking at these specific nutrients, and these alone?
For one, they’re some of the most common. Your garden variety supplement down at the drug store checkout line will contain these. It’s what your average person who doesn’t really read the literature or keep up with the latest advances in nutritional science takes. In that sense, it’s a realistic line of inquiry.
Two, because observational studies have by and large found that higher levels of these nutrients in the serum of populations can predict better health outcomes. That is, people with higher levels of vitamin C, vitamin E, and beta-carotene tend to live longer and better. Unfortunately, that’s just an observation and doesn’t mean taking the nutrients themselves in isolated form will confer the same effect.
The reality is that serum levels of these nutrients are a good barometer for two important things:
Overall intake of colorful plants, herbs, and spices containing the nutrients in question along with hundreds of other beneficial compounds that supplementation studies aren’t examining.
Overall low inflammation and oxidative stress. Low levels of vitamin E, C, and other compounds in the serum are a marker of inflammation.
When you look at studies on antioxidant supplements that account for these factors—by including other beneficial antioxidant compounds or controlling for baseline inflammation and oxidative stress—antioxidant supplements look much more effective.
Antioxidant Supplements and Exercise
The relationship between antioxidant supplements and exercise adaptations is entirely contextual. Whether it helps or hinders you depends on several factors.
Baseline oxidative stress and inflammation: Giving antioxidant supplements to heart disease patients on an exercise regimen did not reduce the benefits of exercise.6 CHD patients typically have elevated oxidative stress markers.7
Age: In elderly exercisers, taking a green tea and vitamin E supplement actually enhanced the effects of exercise.8 They improved body composition, glucose tolerance, and oxidative stress load to a greater degree upon antioxidant supplementation, probably because older people are more susceptible to oxidative stress induced by exercise.9
Obesity: Obese subjects lose more weight and have better body composition results from exercise when they take green tea extract, a potent antioxidant supplement.10 They have worse results without the supplement, meaning the supplement is undoubtedly helpful.
Exercise intensity: The more antioxidants you take, the higher your tolerance for greater intensities. You’ll likely “need” more intensity. That may be why giving antioxidants to people engaged in high intensity interval training does not reduce the benefits—they’re going hard enough.11
And regardless of the context, the effect of antioxidant supplements on training adaptations to exercise is never a deal-breaker. The effects the negative studies find are very small.
Antioxidant Supplements and Diabetes
You’ll read a report that “antioxidant supplements increase diabetes,” but that’s based on a mouse study and a contrived mix of supplements. The reality in humans is different.
Most antioxidants are insulin-sensitizing agents. They increase the effects of insulin, a primary one of which is the removal of glucose from the blood, so you need less insulin to remove the same amount of glucose. Or put another way, the same amount of insulin removes even more glucose.
Alpha lipoid acid, an antioxidant supplement rarely studied in the mainstream reports, has been shown to prevent the descent from glucose intolerance into full-blown type 2 diabetes and increase insulin sensitivity in type 2 diabetics.1213
Curcumin, from turmeric, can reduce insulin resistance and improve blood lipids and even reduce the incidence of type 2 diabetes diagnoses in people at high risk of diabetes.1415 In other words, it helps the people who need the help.
Purified anthocyanins (the same antioxidant compound found in blueberries and purple potatoes) actually reduce inflammation, improve blood lipids, and prevent insulin resistance in type 2 diabetics.16
Antioxidant Supplements and Cancer
A headline like “Antioxidants Could Increase Cancer Rates” implies that supplements are increasing the incidence of cancer in the population. Looking at the study it draws upon, you realize that vitamin E and NAC “only” accelerated tumor growth in mice with pre-existing tumors rather than spurred the formation of new ones.17
Meanwhile, other evidence shows that NAC is chemopreventive (inhibits cancer from starting), especially when combined with other antioxidants like green tea extract. 1819It’s also safe to assume that the vitamin E used in this study was alpha tocopherol, whereas broad-spectrum vitamin E that includes tocotrienols tends to slow the progression of cancer.20
Certain antioxidants may very well spur progression of (some) existing cancers, but that’s not the same as increasing the incidence of cancer.
Antioxidant Supplements in the Context of Inflammation
Healthy people are not the same as unhealthy people. They respond differently to medications, foods, exercise regimens, and yes, antioxidants.
In healthy men, grape polyphenol extracts don’t improve vascular function. In men with metabolic syndrome, grape polyphenol extracts lower blood pressure and increase flow-mediated dilation.2122 Even the classic vitamin C/beta-carotene/vitamin E cocktail that performs so poorly in so many studies reduces LDL oxidation in diabetics (who are more susceptible to LDL oxidation and under more oxidative stress).23 The antioxidant supplement is getting the inflamed, metabolically-unhealthy man back closer to baseline; there’s not as much to improve in the healthy man.
This concept applies to almost any high quality antioxidant supplement you can find:
A combination of glycine and NAC is helpful for increasing glutathione and improving health in older people, who have more oxidative stress and a higher baseline demand for glutathione.24
In patients with fatty liver—an inflammatory disease—pomegranate extract supplementation improves blood lipids, waist circumference, body weight, and blood pressure compared to placebo.25
In patients with chronic heart failure, CoQ10 supplementation reduces mortality, cardiovascular events, and improves quality of life.26 How much more clear can it get?
And despite that, antioxidants even work in generally healthy populations if you use the good stuff rather than just vitamin E/vitamin C/beta-carotene; a complex of quercetin, curcumin, catechins, and selenium improved cardiovascular disease markers after two months. 27
Notice a trend? Antioxidant supplements are generally beneficial for unhealthy people with high baseline levels of oxidative stress and systemic inflammation, while they can be neutral or unhelpful for people who are already healthy with low levels of oxidative stress and systemic inflammation. Unfortunately, most people fall into the former category.
The bottom line of all this? Use quality antioxidant supplements and figure out where you stand.
A severely obese person might benefit from more regular usage. An extremely active, high-performing, daily-training athlete with a high exposure to induced acute stress would probably benefit from semi-regular usage. A heart disease patient or a smoker might look into supplementation. And I imagine a person working 15 hour days at a high-stress job could probably benefit from antioxidant supplementation. Anyone over 50, even healthy, is going to have higher baseline oxidative stress. These are people who are inflamed, who are coming into the game with a hefty load of oxidative stress. They can probably use the extra help.
Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.