Characterizing the plasma metabolome during 14 days of live‐high, train‐low simulated altitude: A metabolomic approach

Abstract

New Findings What is the central question of this study?Does 14 days of live‐high, train‐low simulated altitude alter an individual's metabolomic/metabolic profile? What is the main finding and its importance?This study demonstrated that ∼200 h of moderate simulated altitude exposure resulted in greater variance in measured metabolites between subject than within subject, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate that altitude alters multiple metabolic pathways, and the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information on the acute adaptation response to altitude. Abstract The purpose of this study was to determine the influence of 14 days of normobaric hypoxic simulated altitude exposure at 3000 m on the human plasma metabolomic profile. For 14 days, 10 well‐trained endurance runners (six men and four women; 29 ± 7 years of age) lived at 3000 m simulated altitude, accumulating 196.4 ± 25.6 h of hypoxic exposure, and trained at ∼600 m. Resting plasma samples were collected at baseline and on days 3 and 14 of altitude exposure and stored at −80°C. Plasma samples were analysed using liquid chromatography–high‐resolution mass spectrometry to construct a metabolite profile of altitude exposure. Mass spectrometry of plasma identified 36 metabolites, of which eight were statistically significant (false discovery rate probability 0.1) from baseline to either day 3 or day 14. Specifically, changes in plasma metabolites relating to amino acid metabolism (tyrosine and proline), glycolysis (adenosine) and purine metabolism (adenosine) were observed during altitude exposure. Principal component canonical variate analysis showed significant discrimination between group means (P < 0.05), with canonical variate 1 describing a non‐linear recovery trajectory from baseline to day 3 and then back to baseline by day 14. Conversely, canonical variate 2 described a weaker non‐recovery trajectory and increase from baseline to day 3, with a further increase from day 3 to 14. The present study demonstrates that metabolomics can be a useful tool to monitor metabolic changes associated with altitude exposure. Furthermore, it is apparent that altitude exposure alters multiple metabolic pathways, and the time course of these changes is different over 14 days of altitude exposure.

Blood Biomarker Profiling and Monitoring for High-Performance Physiology and Nutrition: Current Perspectives, Limitations and Recommendations

“…There are early signs of new ‘-omics’ science in sport [91, 138], but these are a long way from becoming the norm. Similarly, new technology that analyses an athlete’s blood without the need for traditional venepuncture is in existence and could eventually become commonplace in sport.…”

A role for metabolomics in the antidoping toolbox?

“…Furthermore, we should take into account the fact that a modified metabolic profile could also be the result of specific training (e.g. high altitude training 136 ), specific food supplements, 131 metabolic illnesses, 42 authorized medication, and because athletes participating in different sports have different cardiovascular demands that determine different metabolic profiles 131,137,138 . This fact could mask the markers of effect of the PEDs identified in the research frame.…”

Metabolomics for the mountains; bring on the biomarkers!

“…In this issue of Experimental Physiology , Lawler et al. () characterize changes in the plasma metabolome of endurance‐trained athletes performing LHTL having clocked up to as much as 200 h simulated altitude exposure to 3000 m, to provide important insight into the mechanisms underpinning metabolic adaptation to (albeit normobaric) hypoxia (Lawler et al., ). Given that the respiring mammalian cell has evolved to be dependent entirely on molecular O 2 (because it serves as the terminal electron acceptor in mitochondrial oxidative phosphorylation), a more informed understanding of how we humans adapt (or indeed fail to adapt) to hypoxia is important, not simply from a performance perspective, but equally from a clinical one, because numerous diseases affecting the human circulation are characterized by marked hypoxaemia (Bailey, ).…”

“…Lawler et al. () used liquid chromatography–high‐resolution mass spectrometry, with parts per million mass determination sensitivity. Just wrap your brain around what this means; it is equivalent to detecting one granule of sugar among 273 sugar cubes, a technological marvel in and of itself!…”

“…What does the study by Lawler et al. () add to the mixing pot? Several findings are worthy of mention, but let's start with the most fundamental.…”