Walk through the aisles of any health food or grocery store, and the word is ubiquitous — antioxidants.
Food culture went through (and is perhaps still going through) a phase where our food, supplements, even our water, is being “enhanced” with antioxidants that are supposed to boost our health, optimize our athletic performance, and ward off or cure many chronic diseases. Likely beneficiaries of this antioxidant hysteria include Dr. Oz and #BigPomegranate.
Along with the addition of “superfood” to the nutrition nomenclature, antioxidant supplements became increasingly popular — many of them loaded with extracts and micronutrients from exotic plant species —most unpronouncable and all claiming to be a panacea for your ailments.
Antioxidants have been touted as medicine and consumed in heavy doses without much consideration about what they actually do or any potential consequences of consuming them ad libidum. We take for granted that antioxidant equals good and more antioxidants equals better. It turns out, that might not be the case.
The theoretical basis of antioxidant supplementation is founded on the premise that they fight off cellular damage in the body caused by molecules known as reactive oxygen species — or ROS.
As the name suggests, ROS are molecules containing oxygen and an unpaired electron — making them highly reactive with proteins, DNA, and other cellular components in our body.
There are several different ROS; including superoxide, hydrogen peroxide, hydroxyl radical, and peroxynitrite. ROS are formed through normal metabolic processes in the body by the mitochondria. The process of being alive and breathing leads to a small amount of ROS production.
In addition, ROS production can increase during exercise and pathological events like exposure to toxic chemicals, radiation or high blood glucose levels.
What makes ROS potentially harmful? Due to their highly reactive nature, ROS can inactivate several beneficial molecules in our body. One such molecule is nitric oxide (NO) — which helps our blood vessels relax and regulates blood pressure. High levels of ROS can decrease NO levels and promote cardiovascular dysfunction.
ROS can also react with DNA and proteins, causing dysregulated gene expression or enzyme dysfunction. ROS have even been implicated in the process of aging through a mechanism involving DNA oxidation and the accumulation of cells that no longer function — what are known as senescent cells. This process even has a name — the “free radical theory of aging.”
If ROS are so bad, then why do we naturally produce them? What purpose do they serve other than wreaking havoc on our cellular machinery?
In reality, ROS, while toxic at higher doses and with chronic exposure, have several necessary physiological roles in the body. ROS are signaling molecules — “cellular messengers” that tell the body to turn on and off certain genes, activate certain pathways, or behave a certain way due to environmental conditions. As an example, it is known that a certain amount of ROS are needed inside the muscle to regulate force production. While they can contribute to muscular fatigue during exercise, ROS are also needed for muscular performance during exercise and adaptation after. A double-edged sword, in a way.
This brings us to antioxidants. As the name suggests, antioxidants are the opposite of “prooxidants” (i.e. ROS) — they neutralize or “quench” ROS and prevent cellular damage they might cause. Antioxidants prevent “oxidative stress” — which is an imbalance of oxidants and antioxidants, in favor of the former. Chronic oxidative stress is a bad thing. When the see-saw tips in the direction of prooxidants, problems ensue.
To prevent this imbalance, our body makes antioxidants naturally — including enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). Each of these can reactive with superoxide, hydrogen peroxide and other ROS to prevent them from reacting with other molecules.
Other antioxidants we can ingest through our diet— these include things like vitamin E (alpha-tocopherol), vitamin C (ascorbic acid), and beta-carotene.
Endogenous (internally produced) antioxidants are protective. In the case of a large increase in ROS (exercise or an injury, for example), our body responds by activating a counter-attack, upregulating antioxidant gene expression to cope with the oxidative insult — bringing us back to homeostasis (baseline).
If naturally-occurring antioxidants are good for us, then consuming external sources of antioxidants in food and supplements must be even better. We should do all that we can to prevent ROS and oxidative stress in order to help us live longer, perform better, and be healthier.
That’s the theory — a theory that evidence has failed to support.
That oxidative stress is causative in diseases like hypertension and cardiovascular disease is well-supported by the literature. A valid approach to this issue would seem to be supplementing with antioxidants. Stop the disease at its source.
Unfortunately, clinical trials of antioxidant supplementation have failed to show any benefit for disease outcomes. A 2004 position statement from the American Heart Association concluded that “the scientific data do not justify the use of antioxidant vitamin supplements for CVD risk reduction.” Furthermore, they note that “no consistent data support that consuming micronutrients (i.e. antioxidants) at levels exceeding those provided by a dietary pattern…will confer additional benefit with regard to CVD risk reduction.”
Why antioxidants show no benefit for CVD and other diseases is an interesting question with a few explanations. It’s pretty evident that consuming a diet high in nutrient-rich plant and animal foods is the ideal first-line prevention against disease. Oxidative stress and inflammation can be manged through lifestyle interventions including diet and exercise, along with limiting exposure to environmental toxins.
Saturating our body with external sources of antioxidants doesn’t help improve disease prognosis. In fact, it might even interfere with our natural antioxidant production. Perhaps this is another reason for null results of supplementation.
On the other side of the coin is the belief that antioxidant supplementation might have benefits for athletes. Promoting recovery by reducing oxidative damage, preventing muscle soreness, and reducing the development of ROS-induced fatigue during exercise are all cited mechanisms.
Antioxidants have not only failed to provide these benefits, but have been recently shown to have negative effects for exercise adaptations.
There is zero evidence to support that antioxidant supplementation in athletes enhances adaptations to exercise. Whether you lift, run, or swim, popping a polyphenol post-workout isn’t going to help you. In fact, it might hurt you.
In particular, antioxidant supplementation has been consistently reported to prevent or attenuate many of the exercise-induced adaptations in response to overload stress and high-intensity training. You’re better off hitting it hard in the gym and skipping out on the antioxidant smoothie afterward.
While this seems like a contradiction, it makes perfect sense. ROS released during exercise serve a huge purpose. Muscle contraction produces ROS, and these go on to induce stress-activated proteins in the muscle, which then lead to the transcription of genes responsible for making our body stronger and more resilient. That’s how exercise training works. Stress + rest = adaptation
When we take antioxidants before/during/after exercise, this beneficial stress response is prevented. Without the signaling effects of ROS, exercise-activated genes can’t be expressed, and we lose out on many of the adaptations we’re looking for — whether it’s enhanced muscle growth, more mitochondria, or better glucose and fat metabolism.
This isn’t a manifesto against antioxidants — they’re necessary and beneficial for proper physiological function. But, the antioxidants we manufacture naturally and those we obtain by eating a nutrient-rich diet likely provide us with more than enough protection.
Similar to vitamin supplementation, antioxidant supplements might have one profound effect — producing more nutrient-rich and expensive urine.
Eat your veggies, exercise, and relax.
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82(1):47–95.
Kris-etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL. Antioxidant vitamin supplements and cardiovascular disease. Circulation. 2004;110(5):637–41.
Merry TL, Ristow M. Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?. J Physiol (Lond). 2016;594(18):5135–47.