The benefits of resveratrol for athletes: the evidence base

After mice on resveratrol ran twice the distance in 2006, this substance earned the reputation of an "endurance pill." Since then a series of randomized studies has been conducted in humans — and their results turned out to be far less optimistic. The editorial team gathered the key data to answer whether an athlete should spend money on resveratrol.

Where the reputation of an "endurance pill" came from

The starting point was the work of Lagouge and co-authors (2006) in the journal Cell. Mice that received high doses of resveratrol against a background of a high-calorie diet had more mitochondria in their muscles, oxidized fats better and ran significantly longer on the treadmill. The mechanism was linked to activation of SIRT1 and PGC-1α — key regulators of energy metabolism.

The logic that "a supplement activates the same pathways as endurance training" looked attractive to the sports industry. Resveratrol began to be positioned as an exercise mimetic — a substance that partially reproduces training adaptations.

It is important to remember the conditions under which these results were obtained. The mice were on a metabolically harmful diet, received doses that, scaled to a human, would amount to grams per day, and did not train on a special program. That is, resveratrol compensated for a worsening of metabolism rather than improving the result of an already trained organism.

It is precisely this difference between "correcting disturbances" and "improving the norm" that explains most of the discrepancies between animal and human studies discussed below.

Animal studies: convincing but limited

Besides the work of Lagouge, positive results were obtained by other groups too. Dolinsky and co-authors (2012) showed that in rats that trained on a treadmill and received resveratrol, the gains in endurance, skeletal muscle strength and heart function were greater than in animals that only trained.

At the same time, even in animals the data are not unanimous: some experiments found no additional benefit or showed that the effect depends on age, sex and the animals' baseline metabolic state. Doses in most positive studies were very high.

A separate problem is bioavailability. Walle and co-authors (2004) showed that in humans free resveratrol is present in the blood at very low concentrations due to intensive metabolism in the intestine and liver. Rodent metabolism differs, so transferring their doses and effects directly to humans is impossible.

Thus, animal data are a rationale for human studies but not proof of efficacy for athletes. The real answer can be given only by randomized controlled trials in people who train.

Young trained people: no effect

In young active people the study results are mostly negative. Scribbans and co-authors (2014) studied resveratrol in combination with high-intensity interval training in young men. The supplement did not enhance gains in aerobic and anaerobic performance, and by some muscle measures the adaptations in the resveratrol group were even less pronounced than in the placebo group.

For young trained people this picture is logical. Their mitochondrial system is already well adapted, and the AMPK–SIRT1–PGC-1α signaling pathways are activated by the training itself. Additional pharmacological stimulation, even if it occurs, adds little.

Data on the effect of resveratrol on strength, speed-strength measures or muscle mass growth in young people are practically absent. Claims about an "anabolic" effect of resveratrol have no confirmation in human studies.

The number of studies in young athletes is generally small, and the samples are small. Nevertheless, none of them showed convincing benefit, so there are no grounds to recommend resveratrol to this group.

Older people: conflicting results

The most high-profile study was conducted by Gliemann and co-authors (2013) in Denmark. Older men performed high-intensity training for 8 weeks and received 250 mg of resveratrol per day or placebo. Unexpectedly, in the resveratrol group the training produced a smaller increase in maximal oxygen uptake, and the positive changes in blood pressure and lipid profile were weakened or absent.

In a subsequent analysis of the same cohort, Olesen and co-authors (2014) concluded that it was the training, not resveratrol, that improved the metabolic and inflammatory status of skeletal muscle. The supplement added no benefit.

At the same time, Alway and co-authors (2017) obtained a different result in older men and women: resveratrol at a dose of 500 mg per day together with training improved some measures of muscle function and mitochondrial density compared with placebo. Polley and co-authors (2016) found no substantial additional benefit in a similar population.

Such heterogeneity may be explained by different doses, types of training, the participants' baseline state and small samples. For older people the question remains open, but there is no unequivocal evidence of benefit, and the signal about a possible weakening of adaptations cannot be ignored.

Why resveratrol may interfere with adaptation

Training adaptation is largely triggered by stress: during exertion reactive oxygen species are formed, the cell's energy balance changes, and these signals switch on the genes responsible for new mitochondria, capillaries and antioxidant defense. Ristow and co-authors (2009) showed that vitamins C and E can dampen part of these beneficial signals.

Resveratrol, as a polyphenol with antioxidant and anti-inflammatory properties, can theoretically act similarly. It was exactly this explanation that the authors of the Gliemann study proposed when they saw the weakening of cardiovascular adaptations. The mechanism is not definitively proven, but the hypothesis is consistent with data on other antioxidants.

• Training in itself activates AMPK, SIRT1 and PGC-1α — the very pathways that resveratrol "targets."
• Excessive suppression of oxidative signals can reduce the stimulus for adaptation.
• The effects of supplements are most noticeable under conditions of disturbed metabolism, not in a healthy trained organism.

The IOC consensus on supplements (Maughan et al., 2018) does not include resveratrol among agents with proven efficacy for athletes. Given the available data, the editorial team agrees: for people whose goal is to improve fitness, resveratrol has no justification.

It is also worth remembering that resveratrol can interact with anticoagulants and affect the enzymes of drug metabolism. Those taking prescription medications should coordinate its use with a doctor.

Editorial conclusions

Resveratrol's reputation as an "endurance pill" is based on studies in rodents with disturbed metabolism and very high doses.

In young people who train, randomized studies showed no benefit, and in older people the results are contradictory: from a weakening of training adaptations to a moderate improvement of individual measures.

For an athlete whose goal is maximal adaptation to training, resveratrol has no evidence-based justification and may theoretically hinder it.

We also recommend reading "Resveratrol: what it is and how it works," "The benefits of quercetin for athletes: the evidence base" and "Myths about quercetin."

References

1. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127(6):1109–1122.
2. Dolinsky VW, Jones KE, Sidhu RS, et al. Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats. J Physiol. 2012;590(11):2783–2799.
3. Gliemann L, Schmidt JF, Olesen J, et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol. 2013;591(20):5047–5059.
4. Olesen J, Gliemann L, Biensø R, et al. Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. J Physiol. 2014;592(8):1873–1886.
5. Scribbans TD, Ma JK, Edgett BA, et al. Resveratrol supplementation does not augment performance adaptations or fibre-type-specific responses to high-intensity interval training in humans. Appl Physiol Nutr Metab. 2014;39(11):1305–1313.
6. Alway SE, McCrory JL, Kearcher K, et al. Resveratrol enhances exercise-induced cellular and functional adaptations of skeletal muscle in older men and women. J Gerontol A Biol Sci Med Sci. 2017;72(12):1595–1606.
7. Ristow M, Zarse K, Oberbach A, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009;106(21):8665–8670.
8. Maughan RJ, Burke LM, Dvorak J, et al. IOC consensus statement: dietary supplements and the high-performance athlete. Br J Sports Med. 2018;52(7):439–455.