Hydrogen inhalation positively affects cardiometabolic risk factors in men and women aged 65 years or older: a preliminary report

Abstract

Molecular hydrogen (H2) has been recently introduced as an experimental medical gas in clinical medicine [1]. Beneficial effects of H2 are attributed to its antioxidant, anti-apoptotic and anti-inflammatory properties, with H2 administered via oral, parenteral or inhalational route found beneficial in cardiometabolic disorders [2]. However, no information is currently available concerning its efficacy and safety to affect cardiometabolic risk factors in elderly. This population faces the highest risk for cardiometabolic morbidity [3], and any intervention that would help improve cardiometabolic profiles is highly required. In this pilot study, we evaluated the impact of short-term H2 inhalation on the American Heart Association (AHA) cardiovascular risk scores, health-related physical fitness, and cardiometabolic biomarkers in men and women aged 65 years or older. Sixteen (n = 16) community-dwelling aged adults (14 women and 2 men; age 68.1 ± 5.3 years; BMI 27.6 ± 5.3 kg/m2) volunteered to participate in this open-label interventional trial (extension of trial NCT02830854, clinicaltrials.gov) conducted according to the Declaration of Helsinki and approved by the local IRB. All participants inhaled 4% gaseous H2 (MIZ Company Ltd, Kanagawa, Japan) for 20 min once per day for 4 weeks, supervised by research staff. Assessment of cardiometabolic outcomes and adverse events was performed at baseline and at 4-week follow-up. Participants were strongly encouraged not to change their diet and physical activity routine during the study period. Cumulative AHA risk scores significantly dropped at follow-up from 4.4 ± 1.7 to 3.7 ± 2.1 points (P = 0.05). Cardiorespiratory fitness and handgrip strength increased at post-administration for 22.4% (95% confidence intervals 7.6 to 37.2%; P = 0.01) and 4.6% (95% confidence intervals − 0.3 to 9.5%; P = 0.05), respectively. H2 inhalation tended to reduce total serum cholesterol from 6.3 ± 0.9 to 5.4 ± 2.1  mmol/L (P = 0.13), and fasting glycemia from 5.7 ± 0.7 to 4.6 ± 1.9  mmol/L (P = 0.12). Blood pressure at rest remained unaffected by the intervention (121 ± 78 mmHg at baseline vs. 125 ± 80 mmHg at follow-up; P = 0.88). No participants reported any adverse events of H2 inhalation. Although these are preliminary data and this is not a full research study, short-term inhalation of gaseous H2 appeared to favorably affect various cardiometabolic risk factors in older men and women. This perhaps happened due to beneficial effects of H2 on lipid utilization and proinflammatory factors [2], and mitochondrial bioenergetics [4] toward activating metabolic pathways in energy-demanding tissues, including the skeletal muscle, liver and adipose tissue. Hydrogen pointedly reduced AHA risk score, a cumulative proxy for cardiometabolic health that accounts for history of relevant diseases, patient-reported outcomes, and cardiovascular risk factors. Driving lower AHA scores at post-administration, along with augmented health-related physical fitness attributes, seems to nominate inhalational H2 as a possible candidate agent in the primary and secondary prevention of cardiometabolic morbidity in elderly. However, several limitations must be considered when study findings are interpreted. The lack of control group (e.g., patients with and without AHA risk score and cardiometabolic risk factors) is a major deficiency of this pilot trial that calls into question does changes observed after H2 intervention are due to the treatment itself or other factors. In addition, before–after design employed here is not a satisfactory study model and cannot ‘design-out’ potential bias, unlike randomized controlled trials. The enrolled population includes only a small sample of senior individuals with risk factors for cardiometabolic diseases, which limits the generalizability of the results; it remains unknown whether H2 affects cardiometabolic disease itself or other conditions. Although there was an instruction not to change the diet and the physical activity during the study period, there was no tool to monitor the subjects’ compliance. Many potential confounders that are not accounted for in this study, including possible comorbidities, the medications of the studied population, and the subjects’ bias, should be addressed in future H2 interventional trials. Finally, with a limited number of clinical tests employed here, the safety of H2 inhalation could not be reliably determined. Possible safety concerns associated with H2 intervention should be addressed in the future through laboratory screening that includes kidney and liver function monitoring (e.g., serum creatinine, clinical enzymes) at the minimum. Therefore, further studies are highly warranted to further investigate the effectiveness and safety of exogenous H2 in clinical environment via long-term well-powered randomized controlled trials.

Study details

Article type

Letter

Disease / injury model

Cardiometabolic risk factors in elderly adults

Duration

4 weeks

Dose-dependent effect

No

Outcome

Positive

Findings

Short-term inhalation of 4% hydrogen gas for 20 minutes daily over 4 weeks in elderly adults (≥65 years) led to a significant reduction in AHA cardiovascular risk scores, increased cardiorespiratory fitness and handgrip strength, and trends toward reduced serum cholesterol and fasting glycemia, with no adverse events reported.