Effects of Exercise on Metabolism: More Extensive Than Previously Reported

by Anna Jellema-Butler

Regular physical activity is known to have cardiovascular-protective action mediated by improvements in lipid profiles, blood pressure, body fat, and insulin sensitivity (1). However, a recent study in Cardiovascular Research suggests that the magnitude and extent of the metabolic benefits of exercise are much more profound than previously reported. These findings have important implications for the prevention of heart disease, type II diabetes, and other cardiometabolic diseases which, together, account for over 30% of worldwide mortality (2).

In this unique study, Koay et al. (3) invited a group of 52 male military recruits of similar age and body mass index to participate in an 80-day program of daily aerobic and strength exercise. Critically, the soldiers were housed in the same domicile, allowing for careful – and previously unprecedented – control of lifestyle factors such as diet, sleep, work environment, stress, and tobacco and alcohol use.

To track changes in metabolic health, the authors compared post-exercise levels of 201 plasma metabolites to their baseline values. Global metabolism was dramatically shifted in the trained soldiers (Figure 1), with changes observed across numerous metabolic pathways and at magnitudes and significance levels heretofore unforeseen.

The largest change was a significant reduction in various fatty acid and ketone body intermediates – two substrate classes that serve as key muscle fuel. This indicates an increased capacity for and efficiency of muscular fatty acid metabolism, and to an extent that has never previously been captured. In addition to improved lipid metabolism, elevated levels of arginine and related metabolites in the post-exercise metabolomic profiles signify increased vasodilation and blood flow, reflecting improved vascular health in response to exercise.  

The scale and scope of shifts in several other metabolite classes, including gut microbiome-derived metabolites, markers of proteolysis, substrates of coagulation, endocannabinoids, nucleotides, and markers of redox stress, were similarly unanticipated and may provide novel insights into the metabolic adaptation to exercise.

However, not all the soldiers experienced the same metabolic benefits as their peers. Interestingly, an attenuated or maladaptive metabolic response was associated with increased levels of dimethylguanidino valeric acid (DMGV). This result supports a building hypothesis that DMGV, a poorly characterized metabolite, may serve as an early biomarker of subclinical metabolic dysfunction and allow for early intervention in individuals who will require strategies other than exercise to improve their cardiovascular risk (4).

As the most highly controlled metabolomic analysis of exercise to date, this study reveals the true range and magnitude of the effects of exercise across diverse metabolic pathways. Regular exercise significantly improved the overall metabolic health of young males in just three months. This result solidifies physical activity as a cornerstone of cardiovascular risk-reduction regimes. Furthermore, considered alongside demonstrated benefits for fitness, body fat, sleep, mental health, and non-communicable disease risk (5), these findings reinforce the prioritization of daily exercise for the average individual in pursuit of longevity and quality of life.


1.       Nystoriak MA, Bhatnagar A. Cardiovascular Effects and Benefits of Exercise. Vol. 5, Frontiers in Cardiovascular Medicine. Frontiers Media S.A.; 2018.

2.       Bhatnagar P, Wickramasinghe K, Williams J, Rayner M, Townsend N. The epidemiology of cardiovascular disease in the UK 2014. Vol. 101, Heart. BMJ Publishing Group; 2015. p. 1182–9.

3.       Koay YC, Stanton K, Kienzle V, Li M, Yang J, Celermajer DS, et al. Effect of chronic exercise in healthy young male adults: A metabolomic analysis. Cardiovasc Res. 2021 Feb 1;117(2):613–22.

4.       Robbins JM, Herzig M, Morningstar J, Sarzynski MA, Cruz DE, Wang TJ, et al. Association of Dimethylguanidino Valeric Acid with Partial Resistance to Metabolic Health Benefits of Regular Exercise. JAMA Cardiol. 2019 Jul 1;4(7):636–43.

5.       Ruegsegger GN, Booth FW. Health Benefits of Exercise. Cold Spring Harb Perspect Med [Internet]. 2018 [cited 2022 Aug 31];8. Available from: http://perspectivesinmedicine.cshlp.org/

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