Breath Hydrogen Reflects a Cellular Bioenergetic Phenotype in Sedentary Adults with Metabolic Syndrome

Background: Metabolic syndrome is associated with early impairments in cellular bioenergetics that are not fully captured by conventional body composition measures. Molecular hydrogen, produced endogenously through gut microbial fermentation and measurable in breath, has been implicated in redox and mitochondrial regulation. Whether breath hydrogen relates to preservation of intracellular, metabolically active tissue in metabolic syndrome remains unclear. Objectives: To examine the association between breath hydrogen concentration and an integrated cellular bioenergetic phenotype derived from intracellular body composition indices in sedentary adults with metabolic syndrome. Methods: Twenty-eight sedentary, middle-aged adults (51.2 ± 7.9 years, 19 females) with metabolic syndrome underwent fasting breath hydrogen assessment and multifrequency bioelectrical impedance analysis. A composite cellular bioenergetic phenotype was derived using principal component analysis of body cell mass, intracellular water, total body potassium, and glycogen. Associations between breath hydrogen and the composite phenotype were evaluated using Spearman correlation with bootstrapped confidence intervals, Theil-Sen regression, and Bayesian linear regression adjusted for age, sex, and waist circumference. Sensitivity analyses included fat-free mass. Results: A single principal component explained 98.6% of the variance across intracellular variables, indicating a highly coherent cellular bioenergetic phenotype. Breath hydrogen concentration was positively associated with this phenotype (ρ = 0.43, p = 0.021; BCa 95% CI 0.07–0.70). Theil-Sen regression confirmed a robust positive association (β = 0.017 per ppm hydrogen; 95% CI 0.002–0.046). Bayesian models showed posterior distributions centered on positive effect sizes, independent of central adiposity. In contrast, the association with fat-free mass alone was borderline. Conclusions: Breath hydrogen concentration reflects an integrated intracellular bioenergetic phenotype in sedentary adults with metabolic syndrome, tracking cellular quality rather than lean mass quantity. Breath hydrogen may serve as a non-invasive biomarker of cellular bioenergetic integrity and a potential tool for phenotype-guided metabolic interventions.