PMID- 24929023 OWN - NLM STAT- MEDLINE DCOM- 20150409 LR - 20220318 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 21 IP - 2 DP - 2014 Aug TI - Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study. PG - 468-73 LID - S1567-5769(14)00212-4 [pii] LID - 10.1016/j.intimp.2014.06.001 [doi] AB - 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-alpha (TNFalpha), 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. TNFalpha 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. CI - Copyright (c) 2014. Published by Elsevier B.V. FAU - Ishibashi, Toru AU - Ishibashi T AD - Haradoi Hospital, Department of Rheumatology and Orthopaedic Surgery, 6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan. Electronic address: toruishi@haradoi-hospital.com. FAU - Sato, Bunpei AU - Sato B AD - MiZ Company, 16-5 Zengyo 1-chome, Fujisawa, Kanagawa 251-0871, Japan. Electronic address: b_sato@e-miz.co.jp. FAU - Shibata, Shinji AU - Shibata S AD - 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. FAU - Sakai, Takaaki AU - Sakai T AD - Haradoi Hospital, Department of Cardiology, Japan. Electronic address: sakai@haradoi-hospital.com. FAU - Hara, Yuichi AU - Hara Y AD - Haradoi Hospital, Department of Internal Medicine, Japan. Electronic address: hara@eos.ocn.ne.jp. FAU - Naritomi, Yuji AU - Naritomi Y AD - Haradoi Hospital, Department of Rheumatology and Orthopaedic Surgery, 6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan. Electronic address: naritomi@haradoi-hospital.com. FAU - Koyanagi, Samon AU - Koyanagi S AD - Haradoi Hospital, Department of Cardiology, Japan. Electronic address: info@haradoi-hospital.com. FAU - Hara, Hiroshi AU - Hara H AD - Haradoi Hospital, Department of Internal Medicine, Japan. Electronic address: hara@haradoi-hospital.com. FAU - Nagao, Tetsuhiko AU - Nagao T AD - Midorino Clinic, 7-26-1 Aoba, Higashi-ku, Fukuoka 813-0025, Japan. Electronic address: wakabanonagao@yahoo.co.jp. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20140611 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 451W47IQ8X (Sodium Chloride) RN - 7YNJ3PO35Z (Hydrogen) RN - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - G9481N71RO (Deoxyguanosine) SB - IM MH - 8-Hydroxy-2'-Deoxyguanosine MH - Adult MH - Aged MH - Aged, 80 and over MH - Arthritis, Rheumatoid/*drug therapy/metabolism/urine MH - Deoxyguanosine/analogs & derivatives/urine MH - Double-Blind Method MH - Female MH - Humans MH - Hydrogen/adverse effects/*therapeutic use MH - Inflammation/drug therapy/metabolism/urine MH - Interleukin-6/metabolism MH - Joints/drug effects/metabolism MH - Male MH - Matrix Metalloproteinase 3/metabolism MH - Middle Aged MH - Pilot Projects MH - Sodium Chloride/*therapeutic use MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - H(2)-Saline OT - IL-6 OT - MMP-3 OT - Molecular hydrogen OT - Reactive oxygen species OT - Rheumatoid arthritis EDAT- 2014/06/15 06:00 MHDA- 2015/04/10 06:00 CRDT- 2014/06/15 06:00 PHST- 2014/05/06 00:00 [received] PHST- 2014/05/30 00:00 [revised] PHST- 2014/06/01 00:00 [accepted] PHST- 2014/06/15 06:00 [entrez] PHST- 2014/06/15 06:00 [pubmed] PHST- 2015/04/10 06:00 [medline] AID - S1567-5769(14)00212-4 [pii] AID - 10.1016/j.intimp.2014.06.001 [doi] PST - ppublish SO - Int Immunopharmacol. 2014 Aug;21(2):468-73. doi: 10.1016/j.intimp.2014.06.001. Epub 2014 Jun 11.