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.

Molecular hydrogen suppresses activated Wnt/β-catenin signaling

“…Development and aggravation of OA are associated with abnormal activation of Wnt/β-catenin signaling8910. H 2 is beneficial for musculoskeletal diseases including inflammatory and mitochondrial myopathies11, microgravity-induced bone loss12, post-ovariectomy osteopenia13, rheumatoid arthritis (RA)1415, and psoriasis-associated arthritis16. However, no study has demonstrated the effect of H 2 on OA to the best of our knowledge.…”

Hydrogen Molecular Biology and Medicine

“…Among the ROS, the hydroxyl radical is the most harmful, and molecular hydrogen (H 2 ) is a selective scavenger. It was demonstrated that consumption of water with a high concentration of molecular hydrogen significantly improves the disease activity and reduces the oxidative stress in RA for this species [61,62]. It has been shown that H 2 is useful when administered along with the conventional therapy in RA as it acts to reduce oxidative stress in the patients.…”

Effect of H2 treatment in a mouse model of rheumatoid arthritis‐associated interstitial lung disease

“…In addition to these immunogenic factors, reactive oxygen species (ROS) are important therapeutic targets because they occur upstream of cytokine‐mediated inflammatory cascades . The synovial fluid and peripheral blood of patients with RA contain high levels of ROS and ROS‐induced molecules such as superoxide, hydroxyl radicals (•OH) and peroxynitrite (ONOO − ) …”

“…10 In addition to these immunogenic factors, reactive oxygen species (ROS) are important therapeutic targets because they occur upstream of cytokine-mediated inflammatory cascades. 11 The synovial fluid and peripheral blood of patients with RA contain high levels of ROS and ROS-induced molecules such as superoxide, hydroxyl radicals (•OH) and peroxynitrite (ONOO − ). 1,[12][13][14][15][16][17] Molecular hydrogen (H 2 ) only quenches harmful ROS, including •OH and ONOO − , and permeates cell membranes; thus, it can easily target organelles, including mitochondria and nuclei.…”