Exercise, Reactive Oxygen Species, and Antioxidants

I was slowly planning to write something about a recent study that shows antioxidant supplements blocking (one part of) the mechanism by which exercise produces (some of its) health benefits. Here I am instead reaping the benefits of procrastination. If you leave a blog post percolating for long enough, someone else will do part of your job for you:

So, what actually causes [the beneficial effects of exercise on metabolism]? There has to be a signal (or set of signals) down at the molecular level that tells your cells what’s happening, and initiates changes in their metabolism. One good candidate is the formation of reactive oxygen species (ROS) in the mitochondria. Exercise most certainly increases a person’s use of oxygen, and increases the work load on the mitochondria (since that’s where all the biochemical energy is coming from, anyway). Increased mitochondrial formation of ROS has been well documented, and they have a lot of physiological effects.


as it turns out, antioxidant supplements appear to cancel out many of the beneficial effects of exercise. Soaking up those transient bursts of reactive oxygen species keeps them from signaling. Looked at the other way, oxidative stress could be a key to preventing type II diabetes.

By way of a reminder, you should recall that mitochondria produce ROS as a side effect of their normal operation as the cell's power plants. When they do more work, you get more ROS. It's a sort of pollution, and like other forms of pollution it can also be interpreted as a call to action.

This study is very interesting - given the importance of exercise to health and longevity, this could be the mechanism by which some studies of rodents found a negative effect on healthy life span through antioxidant supplements, one item that immediately springs to mind. However, as for all such studies, beware of ascribing all the benefits to the one new mechanism that has come to light. I think it's a fair bet, for example, that some percentage of the long-term metabolic benefits of exercise arise from shedding visceral fat:

We have previously demonstrated that surgical removal of visceral fat (VF) in rats improves insulin action, thus, we set out to determine if VF removal affects longevity. ... these observations provide the most direct evidence to date that a reduction in fat mass, and specifically VF, may be one of the possible underlying mechanisms of the anti-aging effect of [calorie restriction].

Though that said, this study was conducted over a period of a few weeks; hardly long enough to shed a significant amount of weight. Here's a link to the original paper if you'd like to follow up at your own pace - it's open access so the full PDF is available.

Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.

For the layperson, probably quite confused by the conflicting messages (and propaganda in some cases) about antioxidants, some important things to recognize about our biochemistry are:

  • A chemical compound can be good, indifferent, or bad for health and the operation of your cells and tissues depending on both a) how much of it there is and b) exactly where it is in your cells.
  • This is because evolution in complex systems - such as mammalian biochemistry - leads to a promiscuous reuse of components. Any given common biochemical might be important in tens of different mechanisms in different amounts, at different times, or under different circumstances. This is one of the reasons that manipulating our metabolism is so hard: the only levers that are easy to pull are each connected to a dozen different parts of the machinery and will each accomplish a dozen different (and probably undesirable) results when moved. I exaggerate for effect, but not by much.
  • Hormesis in particular is one characteristic of this sort of evolved system with a lot of overlapping machinery - a small amount of a particular chemical can be much better for you than either none at all or a large amount.

So it is with reactive oxgen species (or free radicals) and the many mechanisms in the body that either generate or make use of them. Thus all of the following are well-supported by science:

Don't expect any of this to daunt the magical thinkers who are out there selling and consuming vast quantities of antioxidants based on the science of 20 years ago, of course. Large industries change slowly, buoyed to the end by their own inertia.

Ristow, M., Zarse, K., Oberbach, A., Kloting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C., & Bluher, M. (2009). Antioxidants prevent health-promoting effects of physical exercise in humans Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0903485106


When you say:

"Taking antioxidant supplements doesn't do anything for longevity, since those compounds don't end up near the mitochondria where the problem lies."

How about melatonin ? I've read that this is one anti-oxidant that does make its way to mitochondria.

The results from Spain last year on mice were encouraging.

Posted by: jay at May 14th, 2009 5:25 AM

"Unless you have cleverly engineered an antioxidant that does end up in the mitochondria, of course, in which case you can boost mouse life spans by 30% or so. Not that we humans can buy that in a store yet." NOT true.

There are several antioxidants which protect mitochondria, all of which are avaliable as supplements:

1. CoQ10 http://dx.doi.org/10.1016/j.expneurol.2005.07.012

2. Chlorophyllin http://dx.doi.org/10.1016/S0300-483X(00)00278-X

3. Carnitine and Lipoic Acid http://pmid.us/16802113

4. Quercetin http://www.wellnessresources.com/studies/entry/quercetin_protects_mitochondria

Posted by: Jeff at May 14th, 2009 7:42 AM

None of which extend life notably in healthy mice. e.g. see this null result for CoQ10:


Posted by: Reason at May 14th, 2009 9:18 AM

I take a full gram of vitamin C (every day) along with beta alanine, before I work out (every day). Although high blood sugar and type 2 diabetes runs in my family, my blood sugar is 70 (low side of normal). So I question the above assertion that antioxidants are so counterproductive regarding blood sugar.

Posted by: Otto J Hunt at May 18th, 2009 6:19 AM

We have been tracking the VO2MAX and heartrate variability of boomers in our age reversal program.These biomarkers together with fat free mass and energy system assessments have provided reliable benchmarks.The adaptation of the three ANAEROBIC SYSTEMS dominate the revesal of transcriptional signature of aging in our opinion. Mark

Posted by: Mark at June 17th, 2009 7:53 AM

Using a mitochondrially targeted endogenous antioxidant stimulator has helped speed up fast twitch remodelling,contactile intensity,VO2MAX,and sympathetic response in previously untrained boomers Mark

Posted by: Mark OConnor at August 20th, 2009 11:58 AM

So would a ROS supplement be best??

Posted by: fran P at June 6th, 2017 1:25 AM

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