Hydrogen-Rich Water as a Dietary Activator of Brown Adipose Tissue and UCP1?

Abstract

Molecular hydrogen (dihydrogen or hydrogen gas) is a small bioactive molecule involved in various metabolic pathways, from redox-sensitive reactions and cell signaling to bioenergetics and gut microbiota biology. Drinking hydrogen-rich water (HRW) has been suggested as a safe, novel, and promising nutritional strategy to attenuate metabolic disorders and burdensome and highly prevalent conditions that negatively affect populational health. Several recent studies demonstrate that HRW ameliorates lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance [1] and metabolic syndrome [2], reduces liver fat accumulation in non-alcoholic fatty liver disease [3], and improves body composition and metabolic profiles in obesity [4]. Above so-called pro-metabolic effects of HRW are usually attributed to suppressing oxidative stress, inflammation, and adipogenesis [5] (Fig. 1). However, HRW might also act as an activator of thermogenic respiration in adipose tissue, thereby promoting energy dissipation and regulation. An interesting preclinical trial by a Japanese group [6] reported that drinking HRW for 2 weeks promoted the histological conversion of hypertrophy to hyperplasia in brown adipose tissues (BAT) with the upregulation of uncoupling protein 1 (UCP1, thermogenin), a critical thermogenic factor in BAT mitochondria. Specifically, HRW was associated with a 1.63-fold increase in UCP1 expression in the BAT of high-fat diet-induced obesity mice. This was accompanied by a significant increase in the percentage of BAT mass to body weight, implying the possible HRW-driven browning (or beigeing) of white adipose tissue. Interestingly, HRW administered in this study was a low-saturation solution (hydrogen levels 0.88 ± 0.25 ppm) which is comparatively lower than HRWs used in human trials where hydrogen concentrations were ∼3 ppm. Thermogenic effects of supplemental HRW could thus complement conventional obesity treatment, with HRW-mediated UCP1 upregulation that might stimulate whole-body energy expenditure. A recent clinical trial corroborated better energy balance and mitochondrial function in overweight women supplemented with HRW [4]. However, no trials so far evaluated the thermogenic potential of HRW administration in human BAT, neither assessed changes in BAT volume and total energy expenditure during the intervention. Although BAT in humans is scarce and can contribute up to 5% of resting metabolic rate, a sustained activation (and enlargement) of BAT by HRW may alleviate obesity and associated disorders. Whether these effects are dose-dependent and clinically relevant remains to be addressed. Hypothetically, supersaturated HRW currently available for human use might hyperactivate BAT thermogenesis and/or browning of white adipose tissue, and perhaps forge ahead increased energy expenditure phenotypes. Since current FDA-approved BAT stimulators for obesity treatment are accompanied by severe side effects (e.g., adrenergic stimulation), HRW (if proven) might offer a safe and effective alternative.

Study details

Article type

Letter

Disease / injury model

Obesity, Metabolic Syndrome, Type 2 Diabetes, Non-alcoholic Fatty Liver Disease

Dose comparison

The article notes that the preclinical mouse study used a lower hydrogen concentration (0.88 ppm) than human trials (~3 ppm), suggesting possible dose-dependent effects.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Hydrogen-rich water (HRW) may activate brown adipose tissue (BAT) and upregulate UCP1, potentially promoting thermogenesis and energy expenditure, with possible benefits for obesity and metabolic disorders. Preclinical evidence in mice shows increased UCP1 expression and BAT mass after HRW, but clinical relevance and dose-dependence in humans remain unproven.