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Are Antioxidant Supplements Effective?

Posted By Mark Sisson On March 18, 2014 @ 8:00 am In Supplements | 37 Comments

If you pay attention to science journalism, you’ve probably heard tell that antioxidant supplements have mostly negative effects on health markers, ranging from impaired training adaptations in response to exercise, extreme hypoglycemia, and even cancer. At their best, these reports say, antioxidants are merely useless and totally ineffective.

So, is this true? Are antioxidants harmful? Are they effective?

Let’s examine some of the specific claims made about antioxidant supplements.

Do antioxidants erase the beneficial effects of exercise?

Sometimes they reduce them, sometimes they enhance them, and sometime they have a neutral effect. It depends on several factors.

It depends on your baseline oxidative stress status. Giving antioxidant supplements to heart disease patients on an exercise regimen did not reduce the benefits of exercise [7]. CHD patients typically have elevated oxidative stress markers [8].

It depends on your age. In elderly exercisers, taking a green tea and vitamin E supplement actually enhanced the effects of exercise [9]. 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 [10].

It depends on your body composition. One of the more recent [11] “antioxidants cancel out exercise” studies actually suggests that obese people enjoy improved body fat loss when supplementing and exercising. And even though the healthy trainees who supplemented showed biomarkers that normally indicate impaired training adaptations, their V02 max and running performance compared favorably to those who did not supplement.

It depends on the nature of the exercise. 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 [12].

Do antioxidants cause hypoglycemia?

Pick an antioxidant, any antioxidant, and you’ll find people online complaining about it causing low blood sugar. How can this be if antioxidants are “good for you”?

Many (and perhaps most) antioxidants are insulin-sensitizing agents. They increase the effects of insulin, a primary one of which is the removal of glucose [13] from the blood, so you need less insulin to remove the same amount of glucose. Or put another way, the same amount of insulin [14] removes even more glucose. If you’re lean, if you’re perfectly insulin sensitive, if you’re walking around with optimal blood glucose levels, consuming an insulin-sensitizing agent may be too much of a good thing. It may make you hypoglycemic.

What if you’re not healthy? If you’re a type 2 diabetic, if you’re completely sedentary, if you’re obese and insulin resistant, if you’re hyperglycemic, more insulin sensitivity will improve your health. Context matters. Always.

That’s why the same alpha lipoic acid that might cause hypoglycemia has also been shown to prevent the descent [15] from glucose intolerance into full-blown type 2 diabetes and increase insulin sensitivity in type 2 diabetics [16]. Or why the curcumin that may cause low blood sugar in healthy people can reduce the incidence of type 2 diabetes [17] diagnoses in an at-risk cohort. In other words, it helps the people who need the help.

Do antioxidants increase cancer?

A headline like “Antioxidants Could Increase Cancer Rates [18]” implies that supplements are increasing the incidence of cancer in the population. Looking at the study [19] it draws upon, you realize that vitamin E and NAC [20] “only” accelerated tumor growth in mice with pre-existing tumors rather than spurred the formation of new ones. That’s understandable, as cancer patients undergoing radiation or chemo therapy are usually told not to discontinue any antioxidant supplementation.

Meanwhile, other evidence shows that NAC is chemopreventive [21] (inhibits cancer from starting), especially when combined with other antioxidants like green tea extract [22]. It’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 [23] of cancer.

Certain antioxidants may very well spur progression of (some) existing cancers, but that’s not the same as increasing the incidence of cancer.

Why do so many studies show that antioxidants don’t work?

They’re studying the wrong populations. 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 [24]. In men with metabolic syndrome, grape polyphenol extracts lower blood pressure and increase flow-mediated dilation [25]. Similar differences have been observed with resveratrol [26], too. And despite that, antioxidants sometimes do work, even in generally healthy populations; a complex of quercetin, curcumin, catechins, and selenium improved [27] cardiovascular disease markers after two months.

Notice a trend? Antioxidant supplements are generally beneficial for unhealthy people with high baseline levels of oxidative stress [28] and systemic inflammation [29], while they can be unhelpful for people who are already healthy with low levels of oxidative stress and systemic inflammation. Unfortunately, most people fall into the former category.

Take me, for example.

Back when I first got started on the Primal road to better health, I was a mess. Overtraining, chronic stress, inflammation – the years of abusing my body in the pursuit of elite endurance performance had not been kind. I designed my antioxidant supplement (Damage Control Master Formula [30]) to counter all that oxidative stress I was subjecting myself to. And, in concert with smarter (less) training, a better (more Primal) way of eating, and other lifestyle interventions (stress [31], sleep [32], play [33], etc.), it seemed to help. It was actually a very selfish endeavor – I just wanted to get healthier, faster, so I put together a spectrum of safe, natural compounds and extracts that satisfied my criteria:

  • Moderate doses that reflect the ongoing research.
  • Able to pass through the body if not needed.
  • Takes advantage of synergistic interactions between nutrients and antioxidant recycling (for example, since vitamin E alone as alpha tocopherol actetate becomes a pro-oxidant when it donates an electron, Master Formula has a spectrum of mixed tocopherols and tocotrienols and vitamin C to help recycle the various forms of E back to antioxidant state).

Nowadays, I’ve got my health dialed in. I eat right, move correctly, sleep well, and kinda-sorta handle stress adequately. I don’t need to take an antioxidant supplement on a daily basis, so I take it intermittently. One pill after breakfast one day, three the next day, and none for half a week. Then I’ll take it every other day at varying dosages, then back off for another half week. That’s just an example, not a prescription. I jump around, basically. What’s funny is that because I’m fairly healthy, taking Master Formula every day could conceivably offer diminishing, or even negative returns. The same negative effects you see bandied about. Taking it the way I do now has a hormetic effect [34], the phenomenon whereby a moderate stressor upregulates your own antioxidant mechanisms to make you healthier and more robust.

The bottom line of all this? Figure out where you stand.

A severely obese [35] person might benefit from more regular usage. An extremely active, high-performing, daily-training athlete would probably benefit from semi-regular usage. A heart disease [36] patient might look into supplementation. And I imagine a person working 15 hour days at a high-stress job could probably benefit from antioxidant supplementation. 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.

If you’re eating well [37], exercising intelligently [38], getting as much sleep [39] as you need, and not suffering from any obvious maladies, you don’t “need” to take an antioxidant supplement. You might benefit from the occasional hormetic dose – as I believe I do – especially if you don’t eat enough phytonutrient-rich plant food [40], but you’ll be okay without it.

See how it works? Rather confusingly. There are no easy answers, only choices – often hard ones – we must make based on our personal situations.

Let’s hear from you guys. Do you take any antioxidants? Why or why not?


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[6] supplements: http://primalblueprint.com/categories/Store/Supplements/?utm_source=mda_wwsgd&utm_medium=link&utm_campaign=mda_wwsgd_supplements

[7] did not reduce the benefits of exercise: http://www.ncbi.nlm.nih.gov/pubmed/21427602

[8] elevated oxidative stress markers: http://www.ncbi.nlm.nih.gov/pubmed/19656058

[9] enhanced the effects of exercise: http://www.ncbi.nlm.nih.gov/pubmed/24015697

[10] more susceptible to oxidative stress induced by exercise: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0090420

[11] more recent: http://jp.physoc.org/content/early/2014/01/31/jphysiol.2013.267419.abstract

[12] does not reduce the benefits: http://www.ncbi.nlm.nih.gov/pubmed/21487150

[13] glucose: http://www.marksdailyapple.com/how-much-glucose-does-your-brain-really-need/

[14] insulin: http://www.marksdailyapple.com/diabetes/

[15] prevent the descent: http://www.ncbi.nlm.nih.gov/pubmed/24361606

[16] increase insulin sensitivity in type 2 diabetics: http://www.ncbi.nlm.nih.gov/pubmed/17178700

[17] reduce the incidence of type 2 diabetes: http://www.ncbi.nlm.nih.gov/pubmed/22773702

[18] Antioxidants Could Increase Cancer Rates: http://news.sciencemag.org/biology/2014/01/antioxidants-could-increase-cancer-rates

[19] study: http://stm.sciencemag.org/content/6/221/221ra15.abstract

[20] NAC: http://www.marksdailyapple.com/glutathione-cartilage-regeneration/

[21] NAC is chemopreventive: http://www.ncbi.nlm.nih.gov/pubmed/23104176?dopt=AbstractPlus

[22] green tea extract: http://www.ncbi.nlm.nih.gov/pubmed/18206665?dopt=AbstractPlus

[23] slow the progression: http://www.ncbi.nlm.nih.gov/pubmed/23963802

[24] grape polyphenol extracts don’t improve vascular function: http://www.ncbi.nlm.nih.gov/pubmed/20702747

[25] lower blood pressure and increase flow-mediated dilation: http://www.ncbi.nlm.nih.gov/pubmed/22810991

[26] resveratrol: http://www.impactaging.com/papers/v5/n7/full/100579.html

[27] improved: http://www.ncbi.nlm.nih.gov/pubmed/23331204

[28] oxidative stress: http://www.marksdailyapple.com/dear-mark-sleep-and-oxidative-stress/

[29] systemic inflammation: http://www.marksdailyapple.com/inflammation/

[30] Damage Control Master Formula: http://www.primalblueprint.com/product/Damage_Control_Master_Formula/Supplements

[31] stress: http://www.marksdailyapple.com/rethinking-stress-it-could-save-your-life/

[32] sleep: http://www.marksdailyapple.com/how-to-get-fitter-faster-and-stronger-with-quality-sleep/

[33] play: http://www.marksdailyapple.com/15-concrete-ways-to-play/

[34] hormetic effect: http://www.marksdailyapple.com/hormesis-how-certain-kinds-of-stress-can-actually-be-good-for-you/

[35] obese: http://www.marksdailyapple.com/is-obesity-a-disease/

[36] heart disease: http://www.marksdailyapple.com/how-might-inflammation-cause-heart-disease/

[37] eating well: http://www.marksdailyapple.com/definitive-guide-to-the-primal-eating-plan/

[38] exercising intelligently: http://www.marksdailyapple.com/the-best-exercise-there-is-hands-down/

[39] getting as much sleep: http://www.marksdailyapple.com/how-to-manufacture-the-best-night-of-sleep-in-your-life/

[40] phytonutrient-rich plant food: http://www.marksdailyapple.com/do-you-really-need-to-eat-vegetables-to-be-healthy/

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