The Downside of Antioxidants

Free radicals and antioxidants

Antioxidants are natural or chemical substances that quench free radicals and therefore, in theory, prevent damage to cells, improve health, and fight aging. The most well-known antioxidants are vitamins C and E. While these two are required nutrients, they have a downside and may not be as healthy as imagined.

Free radicals, or more technically, reactive oxygen species, are molecules created inside cells as a result of metabolism, and that can cause damage.

For a long time, free radicals were thought to be a primary driver of aging; this is the free radical theory of aging as formulated by the late scientist Denham Harman. (Harman lived to the age of 98, so he was doing something right.)

The free radical theory of aging is no longer widely held, since it’s been discovered that free radicals act as signaling molecules in cells and are therefore necessary for health. Another objection to the theory is that some animals have high levels of free radical damage, but die from other causes.

As signaling molecules, free radicals are important in exercise and in other forms of stress that cause hormesis, the upgrading of cellular defense mechanisms caused by a stress or toxin.

Antioxidants blunt the healthful effects of exercise

Blunting or abolishing free radicals produced by exercise means blunting or abolishing its healthful effects. Exercise absolutely depends on the generation of free radicals to improve health. Vitamins C and E, when taken regularly and/or around exercise, can completely negate exercise health benefits. (Research on this topic is ongoing, some researchers not having found this effect; nevertheless, as we’ll see below, there are good reasons to believe that it occurs.)

It doesn’t take large amounts of vitamins C and E to hamper the effects of exercise either; 1000 mg of vitamin C and 235 mg of vitamin E will do the job.

Many athletes and others who exercise a lot often take these vitamins, and that doesn’t seem like a great idea.

Furthermore, a meta-analysis of antioxidant trials found that taking antioxidant supplements was associated with an increased risk of death.1 While vitamin C had no association with increased risk, vitamins A, E, and beta carotene did.

What could be going on here? Evidently, free radicals are so necessary for health that quenching results in worse health and higher risk of death.

Antioxidants inhibit autophagy

Antioxidants inhibit autophagy too, and this could well be behind the increased risk of death found in the meta-analysis.2 (Thanks to reader Ole Pedersen for bringing this article to my attention.)

Autophagy is the cellular self-cleansing process that rids cells of junk, and thus repairs damage. It is extremely important to the aging process. The rate of autophagy declines with age, and keeping the rate at high levels is critical for slowing aging. This can be done with intermittent fasting, a low-carbohydrate diet, and autophagy boosters.

The study cited above found that the efficacy of drugs that induce autophagy, including rapamycin and trehalose, can be impaired by antioxidants.

Not only that, but the ability of fasting to induce autophagy is impaired by antioxidants.

This could very well be the reason why antioxidants supplementation is associated with a higher risk of death.

Does this mean you should never take antioxidants? No, it doesn’t, but caution is in order.

Up to 22% of apparently healthy people in the United States are deficient in vitamin C, and provision of vitamin C at 1,000 mg daily increases the level of physical activity and reduces the incidence and duration of the common cold by almost 50%. Those are not small effects.

The effects of mild vitamin C deficiency can be manifested as fatigue, malaise, and depression. So if you have any of these symptoms, or you get colds with unusual frequency, vitamin C may be worth taking.

Another of the antioxidants that inhibited autophagy was n-acetylcysteine (NAC). This cysteine pro-drug replenishes glutathione, the body’s most abundant internal antioxidant, which is necessary for good health. While NAC has many uses in the treatment of mental and physical disorders, apparently having too much glutathione may be as detrimental as too little. Caution is in order when taking NAC as well.

If you need to take vitamins C, E, or NAC for any reason, don’t take them immediately before or after exercise, and do not take them while fasting. They should be taken, if needed, during the fed state.

Dose is another consideration. If you have the symptoms of vitamin C deficiency and want to supplement with it, smaller doses, say a couple hundred milligrams daily, may be better. Don’t megadose unless you have good reason, such as a serious illness or infection.

Antioxidants as a misnomer

The notion of antioxidants as healthful has been so ingrained in us, and the idea that healthful effects of various foods are due to antioxidants so established, that we’re often told that something is good for us due to high levels of antioxidants.

That is not the case.

Plant foods such as blueberries, broccoli, red wine, chocolate, and coffee have health benefits not because of antioxidant content, which is low, but because they contain phytochemicals that upgrade stress defense mechanisms. In effect, low-dose toxins.

So next time you read, e.g. “coffee is the biggest source of antioxidants for Americans”, or “eat these high-antioxidant blueberries”, realize that these statements are nonsense.

They contain low levels of antioxidants. They contain high levels of phytochemicals that promote hormesis.

By all means include them in your diet, because they promote health, but they don’t do so because of antioxidants.

Antioxidants are not nearly as health-promoting as we’ve been led to believe, and may in some cases be harmful to health.

PS: Check out my Supplements Buying Guide for Men.

  1.  Bjelakovic, Goran, et al. “Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.” JAMA 297.8 (2007): 842-857.
  2.  Underwood, Benjamin R., et al. “Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease.” Human Molecular Genetics 19.17 (2010): 3413-3429.
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36 comments
Jer says August 1, 2016

Hi PD
Another great article. I was feeling a degree of “paralysis from analysis” hitting me until I rationalised my thinking while writing this post (this sentence has been rewritten since I began writing this post) …I am doing a fast at the moment (18 hours and counting) and have had a couple of cups of coffee. Why coffee? I thought it was healthy based on your other cutting edge article on Coffee, Tea and Red Wine – I still think it is having thought about it more (linked below for others). However, I googled “coffee biggest source of antioxidants” (because it was within authoritative quotation marks!) and lo and behold, it really is the biggest source. I would be disappointed if I was self sabotaging the benefits of my fast as a result of a few cups of Joe.

It’s at times like these when I have to calm down and remember: “The perfect is the enemy of the good.” It’s the trait which makes people chuck in the towel if they think they’re not doing it right and say “what’s the point, I’m just getting it wrong”. Wikipedia cites Confucius who said it better: “”Better a diamond with a flaw than a pebble without.””

Fundamental point: fasting is good – if not for autophagy, then for losing weight! and if you’re not eating, you’re not eating sugar or other junk.
Other point: coffee chelates iron. another plus.
if there is some antioxidant collateral damage, so what. It’s a lot better place to be in than where you were. Eating a bread sandwich has never been a recommended source of nutrition. The less of that, the better.

http://roguehealthandfitness.com/coffee-tea-red-wine-prevent-disease/
https://authoritynutrition.com/coffee-worlds-biggest-source-of-antioxidants/

On a more philosophical level – the new theories on antioxidants (especially Vit C) and that SATURATED fat to be good for you, is remarkable. This is a Kuhnian paradigm shift right before our eyes. At a larger level, this must affect faith in science as a whole – purportedly fool-proof scientific-method apolitical science can be junk as well and gets thing 180 degrees wrong. Why follow your recommendations then…well, I’m now more skeptical…but you reach conclusions I agree a priori!

Best
J

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    P. D. Mangan says August 1, 2016

    Thanks, Jer, glad you liked it. I want to emphasize that coffee is *low* in antioxidants, and I’ve changed the wording in the article slightly to make it clearer that when most people say “antioxidants”, they’re using the word wrongly.

    There certainly is a paradigm shift in health and fitness. I’m thinking that for good health you should be like George Costanza in that Seinfeld episode: “Do the opposite!”

    Reply
    bigmyc says August 2, 2016

    Just want to say that your citation of “new” theories such as sat. fat being good for the physiology is curious. I guess I say this because I’ve been a Paleo apprecianado for a while and well, that tidbit is fairly common knowledge there. Of course, this blog, while related, is not exactly straight out of the “Paleosphere” so information such as that might not be the most forth coming. By contrast however, I will admit that I have come across information on this particular blog site that I do not recall seeing on other Paleo oriented sites.

    I just thought that the demonization of saturated fat was just about dispelled by now.

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Jer says August 1, 2016

Thanks PD. That new text is (i) in bold, (ii) written down, (iii) written by you, (iv) confirms my past practices, and is therefore reassuring. Much appreciated – I’m glad a Costanza-like outburst has had a small impact!

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Ole says August 1, 2016

Jer, please do enjoy your black coffee, as long as you don’t add cream to it.

In fact, chlorogenic acid, which is the primary polyphenol in coffee, is a well know autophagy inducer (achieved via the inhibition of mTORC1).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111762/

The study, which showed that antioxidants inhibit autophagy was done with vitamin C and E supplements and not polyphenols. Supplementing with vitamin C and E is not a good idea anyway. Get your vitamins from real foods instead.

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    Jer says August 1, 2016

    Thanks Ole
    Read PD’s article on a ketogenic diet – cream is fine, so long as it’s full fat!! The carbs are the killer to autophagy and piling on weight! If you can take liquefied fat intravenously, it comes HIGHLY recommended!

    Reply
      Ole says August 1, 2016

      Jer, it’s just that milk/cream will somewhat counteract the kickstart of autophagy, since it inhibits the bioavailability of chlorogenic acid. But I suppose a few ml won’t hurt. Enjoy!

      http://www.ncbi.nlm.nih.gov/pubmed/21627318

      Reply
      Ole says August 1, 2016

      Before going full ketonic, please take a look at this one:

      http://nutritionfacts.org/video/telomeres-cap-it-all-off-with-diet/

      a LCHF keto-diet may not be optimal for your telomeres. Saturated fat seems to be toxic to cells, thereby shortening telmomere length. Generally, our telomeres prefer a non-inflammatory environment,, which means a diet primarily based on vegetables and fruit.

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        P. D. Mangan says August 2, 2016

        Uh-oh, you’re not a vegan mole, are you Ole? 😉

        Reply
          Ole says August 2, 2016

          He.he.. Dennis, 🙂 No, not at all. But I do eat a lot of vegetables, especially leafy greens. They provide good saturation, and I have yet to find a single study, which points to any side effects. Chlorophyll has extremely many benefits and is a very potent anti-inflammatory.

          Generally, I think there is a sad tendency that food is becoming the next religion. Either you are muslim, protestant etc. No-one is better than the other However, having said that, I’m leaning towards ketogenic, although fat will never become my primary fuel.

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          bigmyc says August 2, 2016

          Quick question if I may?….If you are leaning toward the ketogenic side of metabolism and fat isn’t going to be your primary fuel, what then would?

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          Ole says August 2, 2016

          I’m just not convinced that a 100% ketonic diet is the best choice for me. Eat saturated fat, and you hamper your telomeres. Eat carbonhydrates and you generate mitochondrial ROS and cell garbage. Breathing is the single biggest contributor to oxidative stress and mitochondrial damage, but we still keep doing it for a good reason. I try to listen to my body and at the same time keep the latest research in the back of my mind. Yesterday I enjoyed a fantastic homemade lasagne with lots of pasta and meat in it, knowing that mTOR and, insulin level probably went through the roof 😮

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          bigmyc says August 3, 2016

          Well, you gotta enjoy things…acute insulin spikes aren’t going to do you much damage. chronic carb intake will. Sounds like you are on top of your diet and physical health anyhow. I would proof your belief about sat. fat, however. I wouldn’t think that they are terrible for telomeres. If the research clearly says so, then I’ll be proven incorrect. Until I find cross referenced sources that verify that notion, I’m going to believe that it’s baloney (pun intended).

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        bigmyc says August 2, 2016

        Admittedly, I have yet to watch the video but I would be careful about what you heed from Dr. Ornish….the guy seems to have an agenda concerning his health advice. Also, have you SEEN the guy? Does he look healthy to you?

        “Robust health” is not a phrase that I would ascribe to him.

        Reply
        Drifter says August 6, 2016

        Ole,

        I haven’t watched the video (i’m trying to stay in a fairly zen state right now) but I strongly suspect it confuses blood levels of Saturated fat and dietary Saturated fat. Both logic and evidence have shown (to the best of my knowledge) that eating a “low fat” diet actually produces higher levels of sat fat in the blood as a result of the liver’s conversion of sugars to fats, that a low carb, higher fat diet. There are other things involved as well such as the likelihood for a LCHF person to burn the blood fats for fuel rather than having them stored in harmful ways. Volek has spoken about this and done metabolic ward studies, Mark Hyman talks about it in his latest book, and Dr. Kendrick has a post called “what happens to the carbs” that talks about this, Chris Masterjohn had a post called something like ” Why a low fat diet is a high saturated fat diet” among many others.

        On another note, I don’t remember all the science, but I don’t think the telomere length theory has been shown to be a valid predictor of aging. I could be mis-remembering that however.

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          P. D. Mangan says August 6, 2016

          You’re right: dietary sat fat does not raise blood sat fat; carbs do.

          Reply
          Ole says August 6, 2016

          Thanks Drifter. I’ll study this further.

          Reply
Arren Brandt says August 1, 2016

Phil Goetz wrote a good criticism of multivitamin studies:
http://lesswrong.com/lw/20i/even_if_you_have_a_nail_not_all_hammers_are_the/

What would be found if aspirin was trialed in dosages of 1-50g/day?

Personally I’m looking at mitochondrially targeted antioxidants as a lot more beneficial. MitoQ stopped 100 % of metastasis in one trial. SkQ1 also seems very potent and I suspect they will not have that negative effect on physical because they won’t end up in parts of the cell where their presence disturbs redox signaling.

Other effective antioxidants are PEG-HCC which protects brains from traumatic reperfusion injury after trauma.
Cerium oxide (added to diesel it protects lungs against pollution, is recycled again and again as an antioxidant)
SS-31 which interfers with overproduction of suoperoxide.
C60-olive oil, very effective antioxidant but seems to easily turn toxic if production and storage is not carried out in a very specific way.

Ideally we would fund the SENS initiative of allotopic expression, to port the mt-DNA to the nuclear DNA where it is better protected and doing so clear up the issue of degenerative radical stress. They have already succeeded with some genes.

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    P. D. Mangan says August 1, 2016

    Thanks, Arren. I was taking MitoQ for awhile, but the antioxidant aspect made me rethink. Apparently animals that have ubiquinone genetically deleted actually live longer. However, I’m certainly open to everything you point out here.

    Is this the study you were referring to: Paving the way for therapeutic prevention of tumor metastasis with agents targeting mitochondrial superoxide.

    Then, there’s the opposite: Hitting the Bull’s-Eye in Metastatic Cancers—NSAIDs Elevate ROS in Mitochondria, Inducing Malignant Cell Death

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      Arren Brandt says August 1, 2016

      The field of antioxidants is plagued by scientific confusion in general. Cancer cells cannot maintain themselves the way normal cells do although they can adapt. There is a growing suspicion that the most effective therapies versus cancer will be lots of combinations.
      Perhaps a cycle of quality mito-antioxidants followed by one that elevates ROS. I have seen studies where traditional antibiotics were used with good result versus cancer.
      Certainly most existing chemo works by elevating ROS, seems cancer can usually overcome that.
      I agree with you, the term antioxidant is close to useless. It’s about as specific as “vehicle”.

      Reply
George Henderson says August 1, 2016

Some thoughts here; when I suffered from overt hepatitis, antioxidant supplements were unarguably beneficial, measured by all objective and subjective parameters. There is no shortage of evidence to back this up; when an organ is under severe oxidative stress, its function can be rescued by antioxidants.

Fast forward to today, thanks to keto diet, IF, and antiviral drugs I’m not at risk of hepatitis. I notice no benefit from antioxidants beyond those supplied by my diet,, except that I think an extra 500mg vitamin C daily keeps my gums tougher than they might otherwise be.

The interesting thing about vit C is that its proper function in the body is equally antioxidant and pro-oxidant. In fact, its antioxidant function can largely be replaced by other molecules such as uric acid, but its pro-oxidant function (essential to produce collagen, creatine, and carnitine) cannot.

The antioxidant trials that (very debatebly in some cases) increased mortality involved high doses of single vitamins. But there is an antioxidant trial that reduced mortality, and it’s probably not a co-incidence that this long-term trial used low doses of a mixture of antioxidants (zinc ACE) and that the effect was due to reduced cancer mortality (consistent with the work of Bruce Ames) and only seen in those subjects with poor diets (measured with the inflammatory diet score, which involves some assumptions but is probably a reasonable proxy for antioxidant-deficient, high-GI and refined food diets).

http://www.ncbi.nlm.nih.gov/pubmed/26864363

I suggest that there is an a priori benefit from antioxidant supplementation in the general population, but that this can in many cases be more-or-less easily transcended through other factors, including diet and exercise, in which case supplementation will tend to become a liability.

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bigmyc says August 2, 2016

I suppose that you submitted this post while realizing it might stir a hornets nest of objections…I don’t object so much as question some of what you have just asserted. Nutritional information, like anything that is of nebulous and interlocking nature, is constantly evolving as are the contexts from which we derive this information. However, the idea that vitamins A, E and C, for instance, can hamper our health in such areas as muscle hypertrophy, is curious. Hormesis is, of course, behind anabolic processes so I still fail to see the relevant role of free radical “signalling.” I understand that they would play a role but if there is muscle “damage” to be repaired, would the body not naturally take the necessary steps to facilitate this repair if sufficient amino acids and calories were available? Perhaps I over estimate the dosages involved in interfering with general health but I can’t see that consuming a bunch of peppers and organ meats could put the whammy on muscle replenishment.

Secondly, the idea that food items should be held in value due to their phytonutrients and not their anti-oxidants is interesting. However once more, I understand how, in theory that anti-oxidants might benefit health, I would like to hear a more clear explanation as to how flavanoids and polyphenols, through hormesis, would confer health benefits. Basically, my question here is this; By “getting over” the phytochemicals that are present in the tannins of a blueberry, how exactly does that benefit our health outside of being able to eat more blueberries?

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    P. D. Mangan says August 2, 2016

    No, consuming a bunch of peppers – or tomatoes, or similar – won’t do anything bad for health or hinder muscle development. We’re talking large doses of vitamins C and E that may hamper exercise benefits, although whether they inhibit muscle hypertrophy I don’t know, and may not. Phytochemicals increase stress defense mechanisms and thus lead to overall stronger cells and tissues – they will be more resistant to ischemic injury for example, and have increased numbers of mitochondria, increased detox enzymes like superoxide dismutase, catalase, and glutathione.

    I wasn’t expecting to stir up a hornet’s nest because this post is strictly factual; the healthful substances in plants are not antioxidants, and when journalists keep repeating that, someone should say so.

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      bigmyc says August 3, 2016

      Gotcha. No, I was only referring to one of the most recent gospels in “new health” and that is the role of anti-oxidants in our diet. I wasn’t asserting that you were being provocative for its own ends. Just simply that dietary anti-oxidants are more for the benefit of the plant/fruit than they are for our health. This is a fairly new paradigm, after all.

      All good to know….which is the main reason I follow your blog. Great work.

      Reply
James says August 2, 2016

Some oxidation is good… but why, then, is iron oxidation bad? Is it simply the case that moderate to high iron in the body creates free radicals at a rate beyond what is useful for the body? Therefore, while low levels of iron still create free radicals, this is at a level that is useful for the body?

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    P. D. Mangan says August 2, 2016

    Good question, James. In the case of iron, it seems that it creates a form of free radical that’s especially damaging the OH- radical, formed from the so-called Fenton reaction.

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José Carlos says August 2, 2016

P. D.

This is probably a bit off-topic in the thread, but I found the article (and the site as well) intriguing and I felt like sharing.

http://www.diagnosisdiet.com/food/vegetables/

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    P. D. Mangan says August 2, 2016

    Great article, JC, thanks.

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Ole says August 2, 2016

Although highly anecdotal, I find dr. Walsh’s personal experience quite facinating. What seems to be one person’s miracle cure is another persons poison:

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    bigmyc says August 3, 2016

    I didn’t have the time to watch the video but I’m fairly familiar with Dr. Wahls and her recuperation from MS. What did you think was so polar about her protocol?…I mean, in reference to one man’s poison being another’s miracle cure? It’s not the inclusion of saturated fat into the diet again, is it?

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Ole Pedersen says August 3, 2016

bigmyc, I am not on a crusade against SFAs, but there are a number of studies, which COULD indicate that a diet entirely based on SFA’s can overwhelm cells due to excessive inflammation leading to oxidative stress. Instead of burning purely SFAs, one could alternate with e.g. olive oil or get at least some of the fuel from carbs.

About the cure/poison thing, this was just a comment to José’s link about vegetables not being good for us at all. It was kind of a big contrast to Whals’ recovery story 😉

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Jim says August 16, 2016

A few weeks ago you tweeted something about a chemical in pomegranates that helped increase stamina/endurance. Since I can find pomegranates only seasonally where I live, do you know if drinking pomegranate juice will help just as well with stamina? Also, any thoughts on how long before a competition (I do MMA) you should take pomegranates/pomegranate juice to get the best impact?

Thanks!

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    P. D. Mangan says August 16, 2016

    Jim, I believe that was urolithin. Only animal experiments have been done, but it looks like chronic ingestion is the way to go, daily perhaps.

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George Ironthumb says August 17, 2016

Very true! Just want to add, yes vitamin C is very important for collagen formation and vitamin E increases the risk of death because they are fat soluble (A,D,E, k) which means they don’t get eliminated quickly but get stuck in your fat cells. For that reason it is not needed to take them regularly because the body stores them unlike water soluble vitamins like vitamin C which the body just washes away with your urine and its very easy to be deficient on vitamin C.

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    bigmyc says August 17, 2016

    Very interesting and thanks very much for sharing that information. I wonder though, if Vitamin E can be indicted for its implications in shortening lifespan, might not the same be said for the other vitamins that you cited? If so, this is very interesting considering how vital that vitamin D is for our existence, in general.

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Chris says March 19, 2017

A website with intelligent, considerate commenters! I’m subscribing on the basis of that alone – takes a lot of skill to foster that kind of following.

I’ve never really thought too much about antioxidants, but did think they were good for me. I appreciate learning that I may have been wrong.

Reply
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