Antioxidants are molecules that neutralize (fight) free radicals in your body and reactive oxygen species (ROS) in the cell, which may play a role in preventing heart disease, cancer, and other diseases. Free radicals are compounds that can cause harm if their levels become too high in your body. However, as research has progressed, it has become evident that antioxidants (especially in larger-than-usual amounts) may not always be beneficial. Hard to believe, but it’s true!
One of these situations is related to strenuous exercise and muscle growth. While there is little evidence to suggest that antioxidant supplementation affects training‐induced improvements in endurance performance, several studies have reported a detrimental effect of antioxidant supplementation on high‐intensity exercise performance and muscle growth (muscle hypertrophy).
Antioxidants – a double-edged sword
Various portals and advertisements often label oxidative stress and free radicals as exclusively bad and promote antioxidants as a panacea – a solution or remedy for all difficulties or diseases. On the other hand, others post that “antioxidants cause cancer” with the inevitable and famous phrase “research has shown.” Is there a clear answer and what do we know so far?
A consequence of the very fact that we are alive and breathing is the formation of reactive oxygen radicals (ROS) during the oxidation of fuel molecules in the mitochondria to obtain energy. Oxidative stress occurs as a result of excessive production of these radicals and inadequate antioxidant defense. Since 1950, more than 100 disorders (mainly chronic inflammatory diseases) have been associated with oxidative stress.
However, today it is well known that free radicals are essential for defense against pathogens, cell signaling, and numerous metabolic processes. Their levels are controlled by endogenous antioxidants that we create ourselves (glutathione), and there are also essential ones that we must consume (vitamins A, C, E).
One review paper nicely describes that the principle of a double-edged sword refers not only to the importance of maintaining an adequate level of radicals but also of antioxidants, whose excessive level in the body also has harmful consequences for health because it leads to the other extreme – reductive stress.
Do antioxidants really cause cancer?
The effect of antioxidant supplementation is highly context-dependent because the concept of antioxidant is not one, but includes numerous vitamins and compounds with different properties.
For example, supplementation with high doses of beta carotene, which is converted to vitamin A in the body, significantly increased the incidence of lung cancer in smokers compared to placebo. Namely, it has been shown that beta-carotene breaks down into fragments that damage DNA in the highly oxidizing environment of the lungs of smokers. The same outcome was not shown in non-smokers.
Furthermore, the SELECT study showed that megadosing with alpha-tocopherol (a form of vitamin E) increases the incidence of prostate cancer during 7.5 years. The fact is that high doses of the alpha form greatly reduce the gamma form of vitamin E, which is normally found in food, and has a strong effect against reactive nitrogen radicals. When subjects were given selenium, which has an effect similar to the gamma form of vitamin E, along with alpha-tocopherol, there was no increase in the incidence of cancer.
Other available studies have found no effect of antioxidant supplements on cancer incidence in healthy people, and the latest systematic review concluded that there is no clear evidence of their usefulness in cancer prevention.
Antioxidants and disease prevention?
A systematic review of the literature from the Cochrane Library (Cochrane Database of Systematic Reviews) concluded that current evidence does not support the use of antioxidant supplements in the primary and secondary prevention of disease.
The conclusion of many authors is that most studies on antioxidant supplements are very poorly designed. The reasons for this are as follows:
- First of all, the level of antioxidants in the plasma of people was not measured at the beginning or at the end of the study,
- Very high doses (10-12 times the recommended) of only one isolated antioxidant were used in most studies;
- They don’t take into account individual genetic polymorphisms (influence the bioavailability of antioxidants), etc.
Based on this, current evidence suggests that antioxidant supplements will only be effective when the right antioxidant is given to the right individual in the right dose at the right time.
Antioxidants and training & muscle hypertrophy and recovery
Free radicals are created in muscles during exercise and help them generate force and adapt to training. Studies suggest that it is best to skip taking antioxidant supplements in the hours around training time as they have been shown to have a negative effect on recovery and muscle growth. It may also be wise to avoid daily very-high-dose antioxidant supplements if you’re aiming for maximum muscle growth.
A recent study sheds some new light on how exactly (by which mechanism of action) antioxidants may interfere with muscle building, potentially by suppressing the ability of muscle cells to repair their cell membranes after exposure to a heavy load. We have to accept the fact that oxidation is also required to repair (and thus build) damaged muscle cells. That is why antioxidant supplements could hamper your muscle-building efforts and/or delay recovery.
If you’re interested in more details, the story goes like this. Although it has been known for some time that mitochondria are particularly important in the muscle repair process, the mechanism has been a mystery. The researchers found that upon damage to the cell membrane, calcium, which exists in a much higher concentration outside of cells, floods into the cell cytosol. While calcium is important for healthy teeth and bones, it is also an important signaling molecule and like ROS, can be toxic at high levels. After rushing into the cell through damaged cell membranes, the extra calcium was quickly absorbed by mitochondria. The researchers found that this helped to prevent cytosolic calcium from becoming too high and killing the cell, and also sent signals to the mitochondria, to increase ROS production.
Muscle cell membrane damage causes calcium to rush inside of the cell. This is absorbed by mitochondria, which triggers increased ROS production.
What the researchers found next has important implications in the gym: the increase in mitochondrial ROS production was essential to repair the membranes of muscle and other cell types after injury. The mechanism works via ROS-activation of the enzyme RhoA, which triggers the formation of actin fibers around the injury site. In this case, the actin fibers act as a sort of molecular scaffold that helps the cell to patch up holes in the plasma membrane. An easy way to think about this is to picture the repair of a big hole in the roof of a house. The damage can’t simply be fixed by throwing another layer of shingles on top – the underlying rafters need to be rebuilt first. This is precisely what happens when a cell membrane is damaged. Actin fibers form around the hole (i.e. rafters), which is then patched by laying down more lipid membranes (i.e. shingles) on top of the actin framework. ROS promotes the formation of actin fibers around cell membrane damage (which occurs during exercise). This acts as a scaffold to patch the hole.
The researchers took their studies one step further by isolating intact muscle fibers from mice, where they demonstrated that inhibiting mitochondrial ROS production both limited force production during muscle contractions and also crippled the ability of the muscle fibers to repair themselves. Preventing ROS levels from increasing limited the ability of isolated muscle fibers to repair cell membrane damage, and also limited force production.
What studies agree on is that if you eat fruits and vegetables rich in antioxidants, you can never go wrong. In fact, in addition to antioxidants, plant compounds (phytochemicals) are present here, which have an anti-inflammatory effect, protect the immune system and the heart, maintain healthy blood flow, and even raise the levels of our own antioxidants. Also, the fibers from vegetables and fruits will contribute to a healthy microbiome that contributes to vitamin synthesis and mineral absorption and reduces the risk of type 2 diabetes and cardiovascular diseases.
Final Thoughts: Antioxidant supplements could hamper your muscle-building efforts
There are potential harms of supplementation with high doses of antioxidants in athletes (especially in the hours around training time). High-intensity exercise generates large amounts of reactive oxygen species (ROS) as a result of the consumption of large volumes of O2 in athletes, causing some athletes to consume antioxidants in the erroneous belief that this will counteract the damaging effects of ROS.
There is currently no convincing evidence to support the benefits of antioxidant supplementation in acute physical exercise and exercise training. On the contrary, exogenous antioxidants prevent some physiological functions of free radicals that are needed for cell signaling, causing higher dosages of antioxidants to hamper or prevent performance-enhancing and health-promoting training adaptation such as mitochondrial biogenesis, skeletal and cardiac muscle hypertrophy, and improved insulin sensitivity.
However, there remains the perception that antioxidants can counterbalance oxidative stress and benefit exercise adaptation and performance in athletes. It is likely that the negative effects of high doses of antioxidant supplementation exceed their potential benefits.
If you eat predominantly nutritionally poor food, make an effort to change that and eat more vegetables and fruits. Only in exceptional cases you should take supplements and you should do so in the best way – after you have determined the levels of antioxidants in the plasma.