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Should Willy Wonka have been a sports nutritionist?

2011; Wiley; Volume: 589; Issue: 19 Linguagem: Inglês

10.1113/jphysiol.2011.218438

1469-7793

Andrew Philp,

Antioxidant Activity and Oxidative Stress

The seminal studies from Holloszy and colleagues in the 1960s were the first to demonstrate that endurance exercise training can increase skeletal muscle mitochondrial content (Holloszy, 1967). Since then, many of the molecular cues translating this exercise stimulus to mitochondrial adaptation have been defined (Yan et al. 2011). Physical activity is a key modulator of skeletal muscle oxidative capacity and mitochondrial content, as is the balance between nutrient supply and utilization (Yan et al. 2011). Importantly, reductions in chronic activity levels and nutrient excess are associated with the development of obesity, inflammation and chronic disease, whilst exercise in combination with appropriate nutritional practice leads to a enhanced training response (Hawley et al. 2011). In fact, the nutritional status of skeletal muscle is now understood to play a key role in facilitating, or negating, training adaptations (Hawley et al. 2011). This has led to a number of recent studies examining the effect of dietary supplements, nutrients and pharmacological activators, alone or in combination with exercise, on skeletal muscle oxidative capacity and mitochondrial biogenesis. In a recent issue of The Journal of Physiology, Nogueira and colleagues (2011) examined the effects of the flavanoid (–)-epicatechin (Epi), a naturally occurring constituent of cocoa found in dark chocolate, on skeletal muscle mitochondrial biogenesis and function. To achieve this aim, the authors gave Epi (1.0 mg (kg body weight)−1) to 1-year-old mice for 14 days and examined whether Epi alone or in combination with mild endurance treadmill training (30 min day−1, five times a week at 50% of maximal running speed) improves skeletal muscle capillarisation, oxidative capacity and mitochondrial biogenesis. Using an elegant combination of electron microscopy, physiological testing and biochemical analysis, the authors demonstrate that Epi supplementation alone increases skeletal muscle capillary density and mitochondrial abundance as compared to water supplementation. This adaptation resulted in improved fatigue resistance in isolated skeletal muscle, an increase in the protein abundance of components of the electron transport chain (ETC), and an increase in mitochondrial volume and cristae surface area. Mechanistically, these adaptations in the Epi treated mice may have been driven by increases in the protein content of mitochondrial transcription factor A, mitofilin and porin, proteins that are involved in mitochondrial gene and structural adaptations (Scarpulla, 2008). Interestingly, when Epi was administered in combination with mild exercise, the authors observed an additive effect on skeletal muscle capillarity and ETC protein content. To probe the mechanisms for this adaptation, the authors measured the phosphorylation status of neuronal nitric oxide synthase (nNOS), a protein that has previously been associated with aspects of angiogenesis and mitochondrial adaptation in skeletal muscle (Yan et al. 2011). In accordance with their hypothesis, exercise alone, Epi alone and Epi+exercise all increased the amount of phosphorylated nNOS, although the increase was comparable between groups. These data would suggest that whilst nNOS may play a role in the adaptive response, it does not explain the observed differences between the exercise, Epi and Epi+exercise groups. One way to address this might be to conduct Epi studies in mice lacking nNOS, although NOS inhibition does not appear to impair the mitochondrial adaptive response to exercise training, suggesting that alternative pathways are important (Yan et al. 2011). As with any novel study, there are a number of additional questions that arise. Whether or not these findings can translate to human skeletal muscle is not apparent at this time and without a clear mechanism for the positive effects of Epi, it is hard to predict how successful Epi will be when given to athletic or clinical populations. Little is known about how flavanoids, such as Epi, bring about signalling changes, and what is specific about Epi with regard to skeletal muscle that makes it so potent. Equally important, questions regarding optimal dose, Epi retention capacity and timing of administration with regard to exercise remain unexplored. Finally, it needs to be stressed that the most potent effects of Epi occurred when it was administered in addition to exercise training. Just as with other proposed exercise mimetics (Narkar et al. 2008), these compounds are only moderately effective when administered in sedentary conditions. Ironically, this means that exercise mimetics still require an exercise stimulus to maximise their effects (Richter et al. 2008). Looking at the broader implications of this research, we certainly do not think of individuals that eat a substantial amount of chocolate as great endurance athletes, nor view chocolatiers, such as Willy Wonka, as sports nutritionists. Obviously this is because most of the chocolate we eat contains a high percentage of energy dense ingredients such as fats and sugars, and a small amount of the cocoa that contains (–)-epicatechin. This unfortunately means that if we wanted to use chocolate alone to enhance our training adaptation, we are more likely to end up like Augustus Gloop than discover the golden ticket. So, before you trade in your exercise regime for a bar of dark chocolate, it is important that more studies such as the one by Nogueira et al. are conducted, so we can understand what makes (–)-epicatechin, the ‘golden’ ingredient in dark chocolate.