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 (LDL) cholesterol levels and improves high-density lipoprotein (HDL) function in patients with potential metabolic syndrome in a before-after self-controlled study.

OBJECTIVE:

The purpose of this study was 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:

This was a case-control study.

SETTING:

The setting was the Zhoudian community, Tai'an, China.

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 the H2 group showed an increased ability to promote the ATP-binding cassette transporter A1-mediated cholesterol efflux ex vivo. Plasma pre-β-HDL levels were up-regulated 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 the effective rate in down-regulating plasma levels of total cholesterol (47.06% vs 17.65%) and LDL cholesterol (47.06% vs 23.53%). Western blot analysis revealed a marked decrease in apolipoprotein B100 and an increase in apolipoprotein M in plasma of the 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 antiatherosclerotic functions, and has beneficial lipid-lowering effects. The present findings highlight the potential role of H2 in the regression of hypercholesterolemia and atherosclerosis.

• Authors: Guohua Song, Quanqiang Lin, Hui Zhao, Meiyuan Liu, Fenglong Ye, Yujuan Sun, Yang Yu, Shoudong Guo, Peng Jiao, Yun Wu, Guoyong Ding, Qiang Xiao, Shucun Qin
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 100 Issue 7 Pg. 2724-33 (Jul 2015) ISSN: 1945-7197 [Electronic] United States
• PMID: 25978109 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• Lipoproteins, HDL
• Placebos
• Hydrogen

Topics

• ATP Binding Cassette Transporter 1 (metabolism)
• Adult
• Animals
• Biological Transport (drug effects)
• Case-Control Studies
• Cells, Cultured
• China
• Double-Blind Method
• Humans
• Hydrogen (pharmacology)
• Hypercholesterolemia (blood, metabolism)
• Lipoproteins, HDL (metabolism, physiology)
• Macrophages (drug effects, metabolism)
• Mice
• Middle Aged
• Oxidative Stress (drug effects)
• Placebos