Lactate dwarfs other markers of exercise stress

Everyone recognises fatigue subjectively, but measuring it objectively in body fluids has proved stubbornly hard. Sports science and wearable technology both want a blood, sweat or saliva marker that reliably indexes how fatigued someone is, yet studies use different exercise protocols, different sample types and different analytical machines, which makes results difficult to compare. Before any marker can be trusted, someone has to establish which candidates actually move consistently after exercise and by how much. This work set out to do exactly that across the published literature.

The team ran three complementary analyses. First, a systematic review and random-effects meta-analysis of quantitative biomarkers measured in body fluids including blood, plasma, serum, saliva, sweat, urine and interstitial fluid, comparing pre-exercise with post-exercise time points. Eligible studies used apparently healthy participants free of acute or chronic disease, major injury, pregnancy or diagnosed pathological fatigue, performing endurance, resistance, high-intensity interval or mixed protocols. Markers reported in at least 10 independent comparisons were pooled using log-transformed post/pre response ratios. Second, a descriptive fold-change synthesis of exercise metabolomics studies. Third, an exploratory paired plasma-saliva liquid chromatography-mass spectrometry pilot in seven apparently healthy young male volunteers.

The meta-analysis covered 110 articles, 129 experiments and 1,826 participants. Lactate showed the strongest pooled post-exercise response, with a response ratio of 4.43 (95% CI 3.74-5.25), followed by IL-6 at 2.15 (95% CI 1.50-3.07), creatine kinase at 1.70 (95% CI 1.56-1.86) and LDH at 1.23 (95% CI 1.11-1.35). Heterogeneity was very high throughout, with I² values of 98%, 87%, 90% and 93% respectively. The metabolomics synthesis flagged lactate, pyruvate, hypoxanthine and xanthine as frequently reported exercise-responsive metabolites tied to glycolysis and purine degradation, and the small LC-MS pilot showed directionally consistent changes in both plasma and saliva.

This confirms that these four conventional markers reliably rise with exercise, and adds purine-pathway metabolites as candidates worth pursuing. Crucially, it does not show that any of them measure fatigue as opposed to simply measuring that exercise happened. The authors are explicit that fatigue specificity remains unestablished and would require validation against independent fatigue criteria, non-fatiguing exercise controls, matrix-specific analyses and adequately powered diverse cohorts. The extreme heterogeneity also means the pooled numbers describe an average across very different protocols rather than what any one session would produce.

If you have ever seen a single blood or saliva marker sold as a readout of your fatigue or readiness, this is a reason for scepticism: a marker that rises after any exercise is not the same as a marker that tells you how tired you are. Lactate responds most dramatically to acute exercise, which is why it dominates discussion of exercise intensity, but its size of response varies enormously between protocols. The saliva findings are intriguing because they hint at less invasive sampling, though seven men is nowhere near enough to build on. For now, subjective and performance-based measures of fatigue remain the reference point.