Are Antioxidant Supplements Effective?

VitaminsIf 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. CHD patients typically have elevated oxidative stress markers.

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

It depends on your body composition. One of the more recent “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.

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 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. 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 from glucose intolerance into full-blown type 2 diabetes and increase insulin sensitivity in type 2 diabetics. Or why the curcumin that may cause low blood sugar in healthy people can reduce the incidence of type 2 diabetes 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” 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. 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 (inhibits cancer from starting), especially when combined with other antioxidants like green tea extract. 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 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. In men with metabolic syndrome, grape polyphenol extracts lower blood pressure and increase flow-mediated dilation. Similar differences have been observed with resveratrol, too. And despite that, antioxidants sometimes do work, even in generally healthy populations; a complex of quercetin, curcumin, catechins, and selenium improved cardiovascular disease markers after two months.

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 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) 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, sleep, play, 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, 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 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 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, exercising intelligently, getting as much sleep 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, 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?

About the Author

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.

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39 thoughts on “Are Antioxidant Supplements Effective?”

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  1. I love the recommendation of OCCASIONAL usage for the hormetic response. I have a lot of patients I need to talk out of obsessively supplementing daily after switching them to a paleo/primal diet.

    1. This is something I need to consider. I have ME/cfs and I take a number of supplements…. I also eat a primal diet and load of veggies. I guess I should rotate each out for a period and observe effects. Difficult sometimes to know what is best.

      1. Really the best thing would track blood work, sleep, how you feel with/without supplementation. If things are going in the right direction, then it is probably the right choice for you.

    2. I’ve been reading about the use of food grade diatomaceous earth for people to use to ride themselves of parasites etc. in the gut. It’s like a flour that can be made into baked, albeit carb, goods.

      Does Primal or any one else have any experience with use of diatomaceous earth?

  2. Thanks for the idea of occasional usage. I started taking Vit E a month or so ago for menopause symptoms – initially, it helped alot. I ve noticed symptoms creeping back up again. Think I will try taking it occasionally and see how it goes.

    1. I dunno, the snuggie is a pretty awesome onesize-fits-all. (Is it a blanket? Is it a moo-moo? Is it an fuzzy poncho? Is it machine washable? Yes! Thank heavens because it has its own Snuggie Sutra.)

  3. Great post. There’s also nothing wrong with getting your antioxidants from diet – those that do might already have high levels of antioxidants to begin with – also skewing research results.

  4. Supplements can be very helpful. The studies done on vitamins often are designed to fail, based on what outcome the people funding the study want. In many cases they don’t use a high enough dose to show that vitamins are effective. Often the quality of the vitamin given is lacking.The RDA for vitamin C is 90 mg but that will only prevent scurvy. it isn’t enough to create vibrant health. Getting it from food is ideal. I think we are far from ideal in the way the soil is managed.
    I find Mark’s point very helpful – that supplements make a big difference depending on the health of the individual and what stress that person faces.

    1. I believe Mark is emphasizing antioxidant supplements because no one’s talking me out of my daily vitamin D3, fish oil, and K2 and cod liver oil.

    2. I think you need to bear in mind that the supplement industry is a multi-billion dollar money machine. As such, it pays the consumer to question some of the marketing hype that has gotten passed around as being factual, such as poor soil quality, RDA recommendations being too low, diet alone being insufficient, etc., and to know which supplements, if any, are really necessary.

      I know people who are so tied to their supplement regimen that they think they will die if they don’t take them. Yet those same people aren’t particularly healthy. In fact some of them have numerous health issues. The reason being is that they eat crap, they don’t exercise, and they are throwing their natural body chemistry off-kilter with all the lab-manufactured isolates they take in megadoses. They are literally making themselves ill by buying into marketing propaganda.

  5. One thing you left out, Mark–your age. The older you get, the more oxidization you build up in your cells NO MATTER HOW YOU EAT OR EXERCISE. Proof of that is in the gray hair we all get–gray hair is oxidization turning into hydrogen peroxide, which bleaches our hair from the inside. Keep oxidation down, and you keep gray hair from forming (and you can supplement that with catalase from food sources–the supplements don’t work).

    Sources of catalase:
    1. Beef liver–the best source
    2. Vegetables–potatoes (both kinds), avocados, leeks, onions, radishes, kale, carrots, spinach, cucumbers, parsnips, celery, red cabbage. Zucchini contains a smaller amount.
    3. Fruit–pineapple, cherries, apricots, bananas, watermelon, kiwi, and peaches (all to be eaten fresh and raw–cooking causes a decrease in catalase activity).
    4. Other–sprouts, clover, Brussels sprouts, lentil, and the sprouts of dark green leafy plants. Sunflower seeds, yeast, and dairy products contain some catalase.
    5. Supplements–manganese. copper, zinc, and selenium. DO NOT BUY CATALASE SUPPLEMENTS, AS THEY GET DESTROYED IN THE STOMACH, AND END UP USELESS.

    If you can combine any of these foods in one meal, that is the best catalase delivery system going. If your blood sugar can’t handle it, you can eat the liver, and make a salad out of the radishes (sliced) and sprouts (cut up)–both are Atkins induction-friendly.

    This is what we do at home.

    1. In my experience greying hair (and timing of such) is genetic and not dietary or stress-related apart from the rare case where hair turns white (or falls out) after a severe trauma.

      Both my parents have been white haired for 20 years (now early 70s) and had been becoming white for the previous 20 just as had their relatives. My hair started to gain white hairs from 19 and I’m now completely white-haired aged 46 – the difference in lifestyles between me and my parents is great, as is all of ours from the lifestyles of our forebears.

      1. My mom went WHITE when she was 22 and my dad didn’t start until he was 35. I am going to be 31 next week and I have only occasional gray hairs. Maybe I take after my dad, but my husband’s parents turned early too, and at 35, he doesn’t even have a gray hair in his beard. We thank the primal/paleo diet, lifestyle, astaxanthin, and coQ10.

    2. Gray/white hair is a result of copper deficiency. Read or listen to “Dead Doctors Don’t Lie.”

  6. You need a variety of antioxidants that work together, so a study that uses a large quantity of just one may show negative results. It can take several antioxidants working together to quench a free radical. For example That is why pine bark and grape seeds provide such good antioxidant protection they are a complex of antioxidants. If supplements made from them work as well I don’t know although many people have had good results.

  7. I eat wild blueberries 5-6 times a week. They have an incredibly high anti-oxidant content.

  8. Antioxidants and other supplements work! I tested on myself several time and got great results.

  9. I tend to view supplements as the name implies. They supplement my Primal Blueprint lifestyle. I’m not counting on them MAKE me healthy but rather to KEEP me healthy. Exception: Vitamin C. It takes some reading to appreciate the necessity for regular supplementation. Best source: There you will find “The Healing Factor” by Irwin Stone, “Clinical Guide” by Dr. Frederick Klenner, and information from Dr. Linus Pauling. Also check for some great videos on vitamin C.
    GROK ON!

  10. Thank you Mark for not apologizing that you sell supplements. Your Primal Blueprint has taken my health and weight to places I haven’t seen in 25 years. I love taking your Damage Control Formula and the feeling of vitality being Primal.

  11. Hmmmm. So I’m treating tumors, which seems to indicate that I shouldn’t supplement with antioxidants. But I’m following Seyfried’s diet, where the goal is the get my blood glucose levels down to really rock-bottom levels. After three months they’re low, but not nearly as low as they need to be, except for a few hours at the end of a multi-day fast. This seems to indicate that the hypoglycemic effect would be good for me and I should take the antioxidants. It’s a conundrum.

  12. Why MDA is such a great resource–no one-size-fit-all generalizations, an objective approach to find what works for each individual.

  13. Terry Wahls MD found that when she supplemented, her Multiple Sclerosis symptoms got a bit better, but when she instead put lots of variety of foods in her diet to try to get the same micronutrients she got a lot better. As I recall she thought this must be evidence of a lot of so-far undiscovered nutritional factors in real food. The fundamental error in unthinking supplementation is thinking that science has discovered all the nutrients we need; we in science have NEVER discovered everything about ANYTHING. I do use supplements, especially vitamin D, glucosamine, vitamin K2, but I don’t count on them to do it all. I also eat a lot of green, color, organ meat, sulfur-containing vegies, etc. I also try to get sun but in Colorado in the winter that can be a bit challenging!

    Doc Jim the PaleoPathologist

    1. I got the worst sunburn of my life skiing at Keystone during Easter vacation. Couldn’t even put in my contact lenses for 2 days. Go to the mountains Doc! ?

  14. I think if possible always sticking with whole food sources are your best bets for antioxidants like blueberries, broccoli, garlic etc
    That along with backing off a bit on the exercise and plugging in more rest periods was a good formula for me


  15. I view supplements as the name implies; they supplement my Primal Blueprint diet and lifestyle. I don’t expect them to MAKE me healthy, rather to help KEEP me healthy. The “heavy lifting” (pun intended) is done by following the PB guidelines.

    Exception: Vitamin C. Since, unlike nearly all other mammals, we are lacking the necessary enzyme to fully convert glucose into vitamin C we must supplement. Refer to the work of Irwin Stone, Dr. Frederick Klenner and Dr. Linus Pauling.
    GROK ON!

  16. Thanks on the antioxidant info Mark. You could have sold us a bill of goods but you are being as honest as you can and this only adds to your integrity. I’m 56 years old and have been primal/paleo for oh.. a year now. I take alpha lipoic acid in cycles and really can’t tell if it’s helping. I also supplement with cod liver oil, vitamin D3, K2, and iodine on a daily basis. I don’t expect to feel results from my supplementation because I have my diet and exercise for that. I guess when you start to get up in age you start thinking preservation.

  17. I like how Mark shows both (or more) sides of the story with this post and states taking too much of his supplement might be deleterious when a relentless capitalist would explain away any negative effects of antioxidants and give full support to them. That’s something to respect. I was thinking of getting some Master Formula lately but ran out of money and recently read that vitamin supplements, even from whole foods, can be overall harmful (unless perhaps you have a deficiency) so I’ve changed my mind. I read that when you take vitamins on a regular basis your body stops making its own.
    I’m still confused about antioxidants. I used to know practically nothing about them and think more = better, then read the post here about hormesis and learned they can be poisonous, and figure I could use some but don’t know where to draw the limit with them. I don’t supplement or plan to but I probably get plenty from my diet, which includes liberal amounts of coffee and tea and fair amounts of plant food when available. Lately I’ve also been thinking about anti-nutrients and toxins in plants but have also been reading about studies that show the more of certain vegetables (like carrots) you eat, the healthier you should be. It’s bewildering.

    1. I should also have mentioned another major source of antioxidants in my diet – herbs and spices. I use plenty. I like to use natural sweeteners, often in my coffee or homemade eggnog, and when I do I’ll usually add cinnamon to help control my blood sugar.

      1. I can buy into taking time off from supplements, say for a weekend, but I am not sure about the idea that the body will stop making them as a reason to worry about it. My body doesn’t make C, D3 (unless I sunbathe), K2, or the Omega 3s (essentially). I do not produce copper, zinc, selenium, magnesium, etc. Also, if I eat broccoli everyday is that going to reduce the benefit of eating broccoli?
        Trying to intake all my micro-nutrients on a somewhat consistent basis has been a preoccupation and supplementing safely has been a next step. I do focus on not breaching upper limits, which seems easy enough to do.
        I have heard the anecdotal “the body will get lazy” meme a few times and would appreciate any solid links to help me embrace this concern.

  18. Mark– I hadn’t taken vites and such for years! One of your posts finally convinced me to use supplements.
    Over the last three months using both the Primal Fuel and Master Formula I have truly felt the difference! I work a 0-45 hour week (standing all day) with a sprint session and/or walk at lunch. Then I work around the house–I also preach on Sundays (and I do it standing of course) after teaching Bible study Saturday nights.

    By Sunday pm I used to be dragging– but now I have enough energy to come home and get in a good workout!

    It works!

  19. I feel like this goes for things like colostrum as well. Research shows that it’s great for treating for attenuating post workout gut permeability and recovery from the flu, but in relatively healthy people I don’t seem to find much benefit. I’ve also found research showing that it “increased” gut permeability in moderate exercise (Jogging). It seems that unless the body perceives stress and needs extra substrates to recover, the supplements “can” become a stressor in an of themselves.

  20. I take Cytogreens and I have asked myself “do I really need to?”. I eat like a champ 97% of the time, lift and love my sprint runs. But I have gone from using it regularly to when I have a sense inside to take it….not sure if it is fear because I have heard that antioxidants can do more harm then good, or because I’m listening to my “inner voice”! Too bad we could push a button, say our belly button, and get a print out about what is going on inside of us….wait, I think someone is working on an app for that! lol

  21. Mark, the other day I was all set to order your “Damage Control” supplement. It sounded perfect, and easier than my several different bottles. Then, I saw it contains Folic Acid. From what I’ve been reading lately from many sources, including from Chris Kresser, we should avoid Folic Acid. Instead, if we are going to supplement this it should be the Metfolin brand, or list “5-methyltetrahydrofolate” or “5-MTHF.” Any plans to update your formula, or can you address this issue, please? Thanks.

  22. What about “whole foods” supplements (not the store brand) versus the traditional/synthetic forms. “Whole food” forms seem to contain smaller dosages, and are more expensive. According to the “whole food” supplement people the smaller dosages are more effective than the synthetics, thus you don’t need so much. Then there’s the issue of binders & fillers, stearates, etc…, and on, and on, and on. Even eating a really clean diet I do supplement a bit, and thus am a tad concerned about these issues.

  23. Anti-oxidant supplements is very effective for weight loss. I’ve few experience on it. Although I’m always trusted on natural ways like to do exercise, food control etc.

  24. I’m 62 years old and many years post-menopausal. The hormones are shot (no libido at all). The Paleo diet cured acid reflux, bloating and digestive issues and fixed my weight, but it hasn’t touched osteoarthritis or the progress of tenosynovitis (trigger finger) in both hands. My body is hypermobile – it’s a genetic trait – and the fingers naturally bend backwards when I stiffen them. Now that I’m working out with weights to protect my bones, which I enjoy very much, my hands are getting worse and worse. I wake up in the morning and either can’t bend my fingers or open them if I make a fist. I don’t want to stop working out, because it has many immediate as well as long-term benefits. Lately I’ve also developed floaters in my eyes and my nose is running all the time. Obviously something is seriously out of whack and I assume I’ve got inflammation that is exacerbating the structural defect of hypermobility. In order to address it I’ve taking Vit. C, Vit. D3, alpha-lipoic acid, cod liver oil, magnesium, cal/mag and Vit. B6. But I’m seeing no improvement; in fact, my hands continue to deteriorate. I’m sensitive to nightshades and avoid white potatoes because overnight I get swelling, stiffness and pain in the hands. Similar issues with dairy and I avoid them. I’m strict with Paleo, I don’t eat sweets or junk food, and I haven’t eaten wheat products in over 30 years. I tried an anti-inflammatory Paleo diet and it didn’t help. I hate to just increase supplement doses or throw more antioxidants, like turmeric, into the mix. Anybody have any ideas on what to explore next?