title: 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: BACKGROUND
  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.
  
  
  METHODS
  This was a case-control study.
  
  
  METHODS
  The setting was the Zhoudian community, Tai'an, China.
  
  
  METHODS
  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.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Guohua
authors.initials: G
authors.lastname: Song
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Quanqiang
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Meiyuan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Fenglong
authors.initials: F
authors.lastname: Ye
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Shoudong
authors.initials: S
authors.lastname: Guo
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiao
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Ding
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis (G.S., Q.L., H.Z., Y.Y., S.G., P.J., S.Q.), TaiShan Medical University, Tai'an, China 271000; Heart Center of TaiShan Medical University (G.S., Q.L., Y.W., Q.X., S.Q.), Tai'an, China 271000; Zhoudian Community (M.L., Y.S.), Daiyue District, Tai'an, China 271021; Tai'an He Ren Tang Hospital (F.Y.), Tai'an, China 271021; Department of Cardiology (Y.W., Q.X., S.Q.), Affiliated Hospital of Taishan Medical University, Tai'an, China 271000; and Institute of Public Health (G.D.), TaiShan Medical University, Tai'an, China 271000.
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000328:Adult; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016022:Case-Control Studies; D002478:Cells, Cultured; D002681:China; D004311:Double-Blind Method; D006801:Humans; D006859:Hydrogen / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010919:Placebos
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D008075:Lipoproteins, HDL; D010919:Placebos; D006859:Hydrogen