Physiology Friday #129: Do Antioxidants Interfere with the Mitochondrial Benefits of Exercise?

Endurance athletes who supplemented with flavanol-rich cocoa may have missed out on some key training adaptations.

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Quick finding of the week: Artificial sweeteners not so “sweet” for the heart? A recent population-based study of over 103,000 individuals found that artificial sweetener intake was associated with an increased risk of cardiovascular disease (CVD). Aspartame, acesulfame potassium (Sunette, Sweet One), and sucralose (Splenda) were associated with a greater CVD risk, in particular a higher risk for cerebrovascular disease and coronary heart disease.¹

Should you ditch the antioxidant supplements during training?

Dietary antioxidants — which come primarily from fruits and vegetables — have been promoted for their health benefits, sold as supplements, and heavily researched for their ability to prevent and cure disease. Their popularity is based on the theory that several major ailments are associated with elevated levels of reactive oxygen species (ROS), molecules in the body that, when overproduced, can cause damage to cells and proteins. This process is known as oxidative stress.

Since antioxidants “scavenge” free radicals and prevent oxidative stress, the theory goes that supplementing with antioxidants should prevent free radical-associated diseases. While dietary antioxidants (i.e., those from fruit and vegetable intake) have been associated with reductions in all-cause mortality, there is little evidence to support that supplementing with antioxidants has any measurable effect on most disease-related health outcomes.

What about athletes — can they benefit from antioxidants?

Antioxidants have similarly been promoted to athletes for their ability to reduce exercise-associated muscle damage, prevent soreness, and enhance recovery and training adaptability.

However, new research, including today’s study, suggests that antioxidant supplementation may have unintended consequences for endurance training improvements.²

The study enrolled 42 endurance-trained males who took part in a 10-week endurance exercise training program. One group received a placebo supplement, and the other group received 5 grams per day of a cocoa supplement. Cocoa is rich in antioxidants called flavanols and is often used as an antioxidant supplement in research studies.

The study also included 60 male mice who completed a 5-day treadmill training program. Mice were split into exercise and no-exercise groups. Within those two groups, the mice were further divided into those who received a placebo, those who received a low-dose cocoa supplement, and those who received a high-dose cocoa supplement.

Results

At the end of the study, both groups had significantly increased their exercise ventilatory threshold (an indicator of submaximal exercise performance) and improved their VO2max. However, the placebo group also increased their maximal aerobic speed, while the cocoa supplement group didn’t experience an improvement in this outcome.

The amount of mitochondrial DNA increased in the control group after training. However, in the cocoa supplement group, no changes in mitochondrial DNA were observed. The mouse study confirmed this finding: cocoa supplementation prevented the increase in mitochondrial DNA after endurance training. A non-significant blunting of biomarkers related to mitochondrial biogenesis was also observed in the cocoa-supplemented exercising mice.

When biomarkers of inflammation and oxidative stress were compared between groups, the control group, but not the cocoa group, had significantly elevated levels of several of these key signaling molecules. In addition, while antioxidant levels increased in the control group after exercise, they were unchanged in the cocoa supplement group.

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Even though cocoa supplementation did not seem to negatively impact performance parameters in this study, the finding that antioxidants seem to prevent the increase in mitochondrial biogenesis (or key indicators of it) is “alarming.” 

One of the primary adaptations to endurance exercise training is an increase in the number and density of mitochondria — the so-called “powerhouses of the cell”. This is what allows us to become more metabolically efficient and perform better.

What explains the lack of an improvement in the antioxidant supplement group?

If you recall, the control group displayed elevated levels of inflammation and oxidative stress at the end of the training program. As it turns out, not all inflammation and oxidative stress is harmful, and some is necessary. ROS are released during exercise and play a crucial role in signaling for the body to adapt to the “stress” that is being imposed upon it. 

The body adapts to increased levels of ROS by building more mitochondria and scaling up the production of the body’s natural antioxidant defenses. Classis “hormesis” (what doesn’t kill us makes us stronger).

Supplementing with high-dose antioxidants likely prevents this process from happening! It’s a way to tell the body: “Hey, we’ve got this, no need to build up the defenses for later.”

This isn’t the only study to demonstrate a detrimental effect of antioxidants on exercise adaptations. There is a consensus building in the exercise field that antioxidant supplementation may blunt several favorable adaptations to endurance and strength training.³

Source: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP270654 

Should you be worried that your love for dark chocolate or high consumption of fruits and veggies could be harming your training gains? Not so fast. The high doses of antioxidants used in studies like the one above are likely unachievable through dietary means. The potential risk may only arise when you consciously consume antioxidant compounds in high doses.

The “antioxidant myth” is just another example that, when it comes to exercise — or most health outcomes for that matter — there are no shortcuts. In fact, sometimes those shortcuts may be cutting short our benefits.

Thanks for reading. 

See you next Friday.

~Brady~

1. Debras C, Chazelas E, Sellem L, et al. Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. BMJ. Published online September 7, 2022:e071204.

2. García-Merino JA, de Lucas B, Herrera-Rocha K, et al. Flavanol-rich cocoa supplementation inhibits mitochondrial biogenesis triggered by exercise. Antioxidants. 2022;11(8):1522.

3. Merry TL, Ristow M. Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?: Antioxidants and skeletal muscle adaptation. J Physiol. 2016;594(18):5135-5147.