title: Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study.
abstract: The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Patients were randomized 1:1 to receive 500 ml of either H2-saline or placebo-saline, which was drop infused intravenously (DIV) daily for 5 days. The disease activity score in 28 joints (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks. Therapeutic effects of H2-saline on joint inflammation were estimated by measuring serum biomarkers for RA, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8-hydroxydeoxyguanosine (8-OHdG). In the H2-infused group, average DAS28 decreased from 5.18 ± 1.16 to 4.02 ± 1.25 immediately post infusion and reached 3.74 ± 1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo group throughout the study. IL-6 levels in the H2 group significantly decreased in 4 weeks by 37.3 ± 62.0% compared to baseline, whereas it increased by 33.6 ± 34.4% in the placebo group. TNFα levels did not change remarkably in the H2 or placebo groups in 4 weeks post-infusion compared to baseline. The relative ratio of 8-OHdG in the H2 group also significantly decreased by 4.7%. After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H2 group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H2 safely and effectively reduced RA disease activity.
authors.affiliation: Haradoi Hospital, Department of Rheumatology and Orthopaedic Surgery, 6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan. Electronic address: toruishi@haradoi-hospital.com.
authors.forename: Toru
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: MiZ Company, 16-5 Zengyo 1-chome, Fujisawa, Kanagawa 251-0871, Japan. Electronic address: b_sato@e-miz.co.jp.
authors.forename: Bunpei
authors.initials: B
authors.lastname: Sato
authors.affiliation: Haradoi Hospital, Department of Rheumatology and Orthopaedic Surgery, 6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan. Electronic address: s_shibata@haradoi-hospital.com.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Haradoi Hospital, Department of Cardiology, Japan. Electronic address: sakai@haradoi-hospital.com.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Haradoi Hospital, Department of Internal Medicine, Japan. Electronic address: hara@eos.ocn.ne.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Haradoi Hospital, Department of Rheumatology and Orthopaedic Surgery, 6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan. Electronic address: naritomi@haradoi-hospital.com.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naritomi
authors.affiliation: Haradoi Hospital, Department of Cardiology, Japan. Electronic address: info@haradoi-hospital.com.
authors.forename: Samon
authors.initials: S
authors.lastname: Koyanagi
authors.affiliation: Haradoi Hospital, Department of Internal Medicine, Japan. Electronic address: hara@haradoi-hospital.com.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
authors.affiliation: Midorino Clinic, 7-26-1 Aoba, Higashi-ku, Fukuoka 813-0025, Japan. Electronic address: wakabanonagao@yahoo.co.jp.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Nagao
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006859:Hydrogen / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D010865:Pilot Projects; D012965:Sodium Chloride / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012965:Sodium Chloride; D006859:Hydrogen; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019278:Matrix Metalloproteinase 3; D003849:Deoxyguanosine
keywords: H(2)-Saline; IL-6; MMP-3; Molecular hydrogen; Reactive oxygen species; Rheumatoid arthritis