The Emerging Case Against Antioxidant Supplements
New studies suggest exercise and healthy diet combined are the elusive magic bullet.
We think of muscles as our primary source of movement, but on a deeper level they are intricate molecular machines. During intense exercise, muscle cells manufacture troublemaking molecules called free radicals that can harm biological tissues.
Though free radicals also have helpful effects, their potential to do harm draws a lot more attention. Some experts advise exercisers to take antioxidant supplements—including vitamin C, vitamin E and carotenoids—to protect against free radicals. Newer research suggests that supplementation is wrong-headed and may actually discourage favorable adaptation in muscle (Merry & Ristow 2015).
This column explores the processes of oxidation, free-radical formation and antioxidant defenses against free-radical damage. Understanding these processes provides a backdrop for critical new findings on the efficacy of antioxidant supplementation.
What Are Oxidation and Reduction?
It's helpful to review the role of electrons, the negatively charged particles that orbit an atom. The movement of electrons is crucial because it leads to the formation or breaking of chemical bonds. One of the most crucial bond-breakers is oxidation, which happens when an atom loses one or more of its electrons.
In the human body, oxidation coincides with a chemical process called reduction, which happens when a molecule gains one or more electrons. Therefore, in an oxidation-reduction reaction (also called a redox reaction), an atom or molecule will transfer one or more electrons to another molecule.
What Is a Free Radical or Reactive Oxygen Species?
Free radicals form when chemical reactions in the body leave a molecule with an odd, unpaired electron. Free radicals are very unstable and will assault (or react with) other compounds, trying to capture a needed electron to gain stability and become less reactive. A molecule that falls under attack and loses an electron becomes a free radical itself, beginning a chain reaction.
Once the process starts, it can create a cascade of damage to cell membranes, enzymes and DNA (Steinbacher & Eckl 2015).
Free radicals from oxygen atoms are called reactive oxygen species, or ROS. They are formed in the mitochondria (a cell's energy powerhouse) and in various enzyme reactions as part of normal aerobic life. It is important to note that not all ROS are bad. Some ROS help to fight off viruses, bacteria and unwanted microbes in cells.
Nevertheless, if too many ROS form, they may contribute to serious health conditions such as heart disease and cancer. Alas, free radicals can come from the sun (or any type of radiation), the environment (including cigarette smoke and pollution), household chemicals (such as pesticides), unhealthy fats and stress.
What Are Antioxidants and Oxidative Stress?
When ROS are the villains, antioxidants are the heroes because they can neutralize or disarm ROS, interrupting the ROS chain of reactions. Antioxidants can donate an electron to ROS to stabilize them without becoming free radicals themselves.
The body's own cells manufacture many of these antioxidants to ward off invading organisms. Antioxidants also occur naturally in plant-based foods. Some of the well-known antioxidant compounds are flavanols (found in chocolate), resveratrol (wine), catechins (tea) and lycopene (tomatoes). Other popular antioxidants include vitamins A (beta-carotene), C and E.
Oxidative stress is the unbalanced cellular state that happens when ROS overwhelm the body's antioxidant defenses. Oxidative stress is associated with the development of numerous ailments, including cancer, cardiovascular disease, diabetes and neurodegenerative diseases (Merry & Ristow 2015).
The Antioxidant Role of Exercise
Merry & Ristow (2015) explain that exercise increases the production of many antioxidants—a natural mechanism that could help explain the health benefits of regular exercise. From their research review, the scientists argue that oversupplementation with antioxidants may be potentially harmful to the functions and signaling mechanisms of ROS. Merry & Ristow add that exercise helps to regulate antioxidant responses in a more specific manner, counteracting the unwanted effects of scavenging ROS.
Should We Take Antioxidant Supplements?
Merry & Ristow (2015) note that we are just beginning to understand the cellular effects of antioxidant supplementation on exercise-induced alterations to the body.
Cumming et al. (2014) investigated the effects of vitamin C and E supplementation and endurance training on adaptations in endogenous antioxidants and heat shock proteins. Thirty-seven men and women were randomly assigned to receive vitamins C and E (C: 1,000 milligrams daily, E: 235 mg daily) or a placebo during an 11-week endurance-training regimen.
The study found that vitamin C and E supplementation had no effect on the activation of several metabolic pathways measured. However, the vitamin group showed indications of inhibited capacity to tolerate exercise-induced stress, an effect that could in the long run, or during periods of very intense exercise, delay recovery and prevent optimal gains in physical performance.
In another recent investigation (Paulsen et al. 2014), 54 young women and men were randomly allocated to receive either 1,000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, participants did endurance training consisting of three to four running sessions per week, divided into high-intensity interval sessions—at more than 90% of maximal heart rate—and steady-state continuous sessions.
Maximal oxygen uptake, submaximal running and a 20-meter shuttle-run test were assessed, as were several biomarker adaptations to cardiovascular exercise. Results showed that the daily vitamin C and E supplementation minimized specific markers of mitochondria creation after endurance training. The authors concluded, "Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise."
In a recent review article, Steinbacher & Eckl (2015) said it is well-understood that muscle contractions during exercise lead to elevated levels of reactive oxygen species in skeletal muscle. ROS, as discussed, can have several negative effects. However, Steinbacher & Eckl pointed out that some exercise-produced ROS are involved in very positive signaling messages that promote muscle development. The researchers also noted that regular endurance training enhances the development (in cells) of specific antioxidants that ward off some of the ROS damage.
They determined that "a diet supplemented with exogenous antioxidants such as vitamins appears to prevent health-promoting effects of physical exercise in humans."
In the Merry & Ristow review (2015), the authors concluded that a growing body of literature suggests antioxidant supplementation may hinder or prevent the activation of important adaptations such as muscle mitochondria creation, insulin sensitivity and hypertrophy.
The new research clearly shows that some ROS, particularly some produced during endurance exercise, are beneficial to cellular processes (see Figure 1). Furthermore, it is well understood that exercise develops and enhances a very specific team of antioxidants that defend against harmful ROS. For now, there is no meaningful evidence suggesting that exercise enthusiasts should use antioxidant supplements for exercise performance.
Also, since antioxidants occur naturally in plant-based molecules, the research indicates that a diet should include recommended levels of vegetables, fruits and whole-grain foods to help combat or balance out cellular ROS production.
Cumming, K.T., et al. 2014. Effects of vitamin C and E supplementation on endogenous antioxidant systems and heat shock proteins in response to endurance training. Physiological Reports, 2 (10), 1-14.
Merry, T.L., & Ristow, M. 2015. Do antioxidant supplements interfere with skeletal muscleadaptation to exercise training? Journal of Physiology, 1-13.
Paulsen, G., et al. 2014. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: A double–blind, randomised, controlled trial. Journal of Physiology, 592 (8), 1887-1901.
Steinbacher, P., & Eckl, P. 2015. Impact of oxidative stress on exercising skeletal muscle. Biomolecules, 5 (2), 356-77.
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