Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo and Improves High-Density Lipoprotein Function in Patients With Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial

Abstract:

Context We have found that hydrogen (dihydrogen; H2) decreases plasma low-density lipoprotein cholesterol (LDL-C) levels and improves high-density lipoprotein (HDL) function in patients with potential metabolic syndrome in a before-after self-controlled study. Objective To further characterize the effects of H2-rich water (0.9 L/day) on the content, composition, and biological activities of plasma lipoproteins on patients with hypercholesterolemia and their underlying mechanisms in a double-blinded, randomized and placebo-controlled trial. Design Case control study. Setting Zhoudian community, Taian. Patients A total of 68 patients with untreated isolated hypercholesterolemia were randomly allocated to either drinking H2-rich water (n=34) or placebo water (n=34) for 10 weeks. Results HDL isolated from H2 group showed an increased ability to promote ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux ex vivo. Plasma pre-β-HDL levels were upregulated although there were no changes in plasma HDL-cholesterol levels. Moreover, other HDL functions, assessed in protection against LDL oxidation, inhibition of oxidized-LDL induced inflammation, and protection of endothelial cells from oxidized-LDL induced apoptosis, were all significantly improved by H2 treatment. In addition, H2 treatment increased effective rate in down-regulating plasma levels of total-cholesterol (47.06% versus 17.65%) and LDL-cholesterol (47.06% versus 23.53%). Western blot analysis revealed a marked decrease of apolipoprotein B100 and an increase of apolipoprotein M in plasma of H2 group. Finally H2 treatment resulted in a significant reduction in the levels of several inflammatory and oxidative stress indicators in whole plasma and HDL particles. Conclusions H2 activates ATP-binding cassette transporter A1-dependent efflux, enhances HDL anti-atherosclerotic functions, and has beneficial lipid-lowering effects. The present finding may highlight the potential role of H2 in the regression of hypercholesterolemia and atherosclerosis.