Beetroot juice supplementation reduces the oxygen cost of exercise without improving mitochondrial efficiency: but how?
Dietary inorganic nitrate is a popular sports nutrition supplement, and has possible therapeutic applications. Nitrate is abundant in foods such as leafy vegetables and beetroot. Ingested nitrate is reduced by oral bacteria to nitrite, which enters the circulation where it can be further reduced to nitric oxide this in turn has many vascular and metabolic effects. Supplementation can be with pure sodium nitrate preparations, or more conveniently beetroot juice, in which nitrate is the main active ingredient. One remarkable effect of inorganic nitrate supplementation is a decrease in the oxygen cost of submaximal exercise, with consequent improvements in exercise tolerance and performance. The effect is robust, at least in young healthy subjects, but its physiology is by no means well understood. A paper by Whitfield et al. (2016) in this issue of The Journal of Physiology addresses this by studying the effects of beetroot juice supplementation on skeletal muscle mitochondria ex vivo. In general terms there are two possible explanations of a decreased oxygen cost of muscular work: first, a decrease in the oxygen cost of ATP synthesis, i.e. an increase in its reciprocal, the mitochondrial P:O ratio, which can be thought of as 'mitochondrial efficiency' second, a decrease in the ATP cost of contraction, i.e. an increase in its reciprocal, 'contractile efficiency' What Whitfield et al. found, in marked contrast to the earlier study of sodium nitrate ingestion by Larsen et al. (2011) was no change in a variety of measures of mitochondrial efficiency. This leaves decreased ATP cost of work as the only remaining explanation of the decreased oxygen cost of work. As the authors note, this is consistent with the conclusion of a recent P magnetic resonance spectroscopy study of beetroot juice supplementation (Bailey et al. 2010) in which pH and phosphocreatine changes during exercise were smaller in the supplementation group. However, there is no reason a priori why both effects should not operate. What next? Why these ex vivo results differ from those of Larsen et al. (2011) is unclear. It is hard to see how it could result from the different supplements used (sodium nitrate vs. beetroot juice) but this cannot be ruled out. P magnetic resonance spectroscopy can in principle be used to distinguish the two possible effects in vivo: the initial rate of phosphocreatine depletion in exercise is a direct measure of the ATP cost of contraction (Jubrias et al. 2008) post exercise phosphocreatine recovery kinetics reflect 'mitochondrial capacity' a concept that encompasses many aspects of mitochondrial function (Kemp et al. 2014) and although PCr recovery kinetics do not directly reflect P:O, a combination of near infrared spectroscopy and P magnetic resonance spectroscopy can be used to estimate mitochondrial coupling efficiency in vivo (Conley et al. 2013) What would be useful now, I suggest, is a study comparing beetroot juice and sodium nitrate supplementation directly, measuring submaximal VO2 in vivo along with mitochondrial function and coupling ex vivo (Larsen et al. 2011) but combined with P MRS based measurements (Bailey et al. 2010) focusing specifically on contractile efficiency (Jubrias et al. 2008) mitochondrial function (Kemp et al. 2014) and coupling efficiency (Conley et al. 2013) in vivo. If it turns out that, indeed, nitrate supplementation has its main effect by decreasing the ATP cost of contraction, then we have a fascinating problem to solve: how? References
The Journal of physiology