The effect of a low dose hydrogen-oxygen mixture inhalation in midlife/older adults with hypertension: A randomized, placebo-controlled trial

Objective: To explore the effect of a low-dose hydrogen-oxygen (H2-O2) mixture inhalation in midlife/older adults with hypertension. Methods: This randomized, placebo-controlled trial included 60 participants with hypertension aged 50-70 years who were randomly divided into Air group (inhaled placebo air) or H2-O2 group [inhaled H2-O2 mixture (66% H2/33% O2)]. Participants in both groups were treated 4 h per day for 2 weeks. Four-limb blood pressure and 24-h ambulatory blood pressure were monitored before and after the intervention, and levels of plasma hormones related to hypertension were determined. Results: A total of 56 patients completed the study (27 in the Air group and 29 in the H2-O2 group). The right and left arm systolic blood pressure (SBP) were significantly decreased in H2-O2 group compared with the baseline levels (151.9 ± 12.7 mmHg to 147.1 ± 12.0 mmHg, and 150.7 ± 13.3 mmHg to 145.7 ± 13.0 mmHg, respectively; all p < 0.05). Meanwhile, the H2-O2 intervention significantly decreased diastolic nighttime ambulatory blood pressure by 2.7 ± 6.5 mmHg (p < 0.05). All blood pressures were unaffected in placebo group (all p > 0.05). When stratified by age (aged 50-59 years versus aged 60-70 years), participants in the older H2-O2 group showed a larger reduction in right arm SBP compared with that in the younger group (p < 0.05). In addition, the angiotensin II, aldosterone, and cortisol levels as well as the aldosterone-to-renin ratio in plasma were significantly lower in H2-O2 group compared with baseline (p < 0.05). No significant differences were observed in the Air group before and after the intervention. Conclusion: Inhalation of a low-dose H2-O2 mixture exerts a favorable effect on blood pressure, and reduces the plasma levels of hormones associated with hypertension on renin-angiotensin-aldosterone system and stress in midlife/older adults with hypertension.

A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide with increasing incidence consistent with obesity, type 2 diabetes and cardiovascular diseases. No approved medication was currently available for NAFLD treatment. Molecular hydrogen (H2 ), an anti-oxidative, anti-inflammatory biomedical agent is proved to exhibit therapeutic and preventive effect in various diseases. The purpose of this study was to investigate the effect of hydrogen/oxygen inhalation on NAFLD subjects and explore the mechanism from the perspective of hepatocyte autophagy. We conducted a randomized, placebo-controlled clinical trial of 13-week hydrogen/oxygen inhalation (China Clinical Trial Registry [#ChiCTR-IIR-16009114]) including 43 subjects. We found that inhalation of hydrogen/oxygen improved serum lipid and liver enzymes. Significantly improved liver fat content detected by ultrasound and CT scans after hydrogen/oxygen inhalation was observed in moderate-severe cases. We also performed an animal experiment based on methionine and choline-deficient (MCD) diet-induced mice model to investigate effect of hydrogen on mouse NASH. Hydrogen/oxygen inhalation improved systemic inflammation and liver histology. Promoted autophagy was observed in mice inhaled hydrogen/oxygen and treatment with chloroquine blocked the beneficial effect of hydrogen. Moreover, molecular hydrogen inhibited lipid accumulation in AML-12 cells. Autophagy induced by palmitic acid (PA) incubation was further promoted by 20% hydrogen incubation. Addition of 3-methyladenine (3-MA) partially blocked the inhibitory effect of hydrogen on intracellular lipid accumulation. Collectively, hydrogen/oxygen inhalation alleviated NAFLD in moderate-severe patients. This protective effect of hydrogen was possibly by activating hepatic autophagy. Keywords: MCD-induced NASH; NAFLD; autoph

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

We have found hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9-1.0 L/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome. Serum analysis showed that consumption of H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels. Western blot analysis revealed a marked decrease of apolipoprotein B100 (apoB100) and apoE in serum. Besides, we found H2 significantly improved high-density lipoprotein (HDL) functionality assessed in four independent ways, namely (i) protection against LDL oxidation, (ii) inhibition of TNF-α induced monocyte adhension to endothelial cells, (iii) stimulation of cholesterol efflux from macrophage foam cells, (iv) protection of endothelial cells from TNF-α induced apoptosis. Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water appear to decrease serum LDL-C and apoB levels, improve dyslipidemia injured HDL functions, and reduce the oxidative stress and may have a beneficial role in prevention of potential metabolic syndrome.