Resveratrol, Mitochondrial Efficiency, and Exercise
The human body is amazing. It is remarkably resilient to stress, malnutrition, physical inactivity, and exposure to toxic substances, e.g. smoking. Nevertheless, oxidative stress and inflammation are hypothesized to accelerate aging. Consuming a high-sugar, high-fat diet, especially when sedentary, can lead to weight gain and increase risk cardiovascular risk factors. Increasing the omega-3 to omega-6 polyunsaturated fatty acid (LCPUFA) balance of our diet can reduce inflammation and lower atherosclerotic lipids. But LCPUFA are more susceptible to reactive oxygen species (ROS) and oxidation than saturated fats. Having an adequate intake of antioxidant vitamins (C and E) and compounds is also important.
Resveratrol, a natural antioxidant compound found in grapes and red wine, has been shown to alter mitochondrial function and energy metabolism in obese, healthy males. Levels of inflammatory markers, glucose, and insulin were reduced with 150 mg resveratrol daily. In a new study published in Diabetes, Fiori and colleagues provide insights into the mechanism of action. Adult rhesus monkeys (N=24) were randomized to a healthy standard diet, high-fat/high-sugar diet with or without 80 mg resveratrol daily for 1 year and then 240mg resveratrol twice daily for the 2nd year. Serum resveratrol concentrations rose with treatment from undetectable to 28 ng/mL. Monkeys consuming high-fat/high-sugar diet gained weight (not controls) and serum glucose levels and insulin resistance increased relative to baseline. Resveratrol helped protect β-cell function.
One of the proposed mechanisms of action for resveratrol is blood vessel dilation which can allow for increased blood flow. Improved blood flow can be cardioprotective, and may be beneficial to overweight individuals with cardiovascular risk factors.
In a new study, Gliemann and colleagues tested the effects of resveratrol supplementation in 27 healthy men (60-72y) randomized to 8 wk of high-intensity exercise training with or without resveratrol (250 mg/day). Intensive training increased maximal oxygen uptake (P<0.03). After training, maximal oxygen uptake and interstitial vasodilator prostacyclin concentrations were greater in the placebo than the resveratrol-treated group.
The interpretation by the authors was that resveratrol abolished the positive effects of exercise. That is one interpretation. Alternatively, their bodies may have become more efficient. Other scientists report that resveratrol reduces energy expenditure and lowers energy expenditure. Prostaglandin is a known vasodilator. Reduced levels of prostaglandin, as seen with resveratrol supplementation, should be associated with less vasodilation and higher blood pressure. If resveratrol helps a muscle become more efficient, it may not need as much blood flow or metabolize as much oxygen to the same amount of work.
Scientists often summarize with the statement ‘more research is needed’. In the case of resveratrol, this is true. We still have things to learn about the human body.
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Fiori JL, Shin Y-K, Kim W, Krzysik-Walker SM, Gonzalez-Mariscal I, Carlson OD, Moaddel R, Farhang K, Gadkaree SK, Doyle ME, Pearson KJ, Mattison JA, de Cabo R, Egan JM. Resveratrol prevents β-cell dedifferentiation in non-human primates given a high fat/high sugar diet. 2013 Diabetes doi:10.2337/db13-0266
Gliemann L, Schmidt JF, Olesen J, Beinso RS, Peronard SL, Grandjean SU, Mortensen SP, Nyberg M, Bangsbo J, Pilegaard H, Hellsten Y. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. 2013 J Physiol doi:10.1113/jphysiol.2013.258061
Wong RH, Howe PR, Buckley JD, Coates AM. Berry NM. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. 2011 Nutr Metab Cardiovasc Dis. doi:10.1016/j.numecd.2010.03.003