Table 2.
The effects of H2 intervention on metabolic diseases in clinical trials.
| Disease/Objective | Subjects No. | Routes of H2 Delivery | H2 Concentration | Duration | Main Effects | Clinical Registration No. | Reference | |
|---|---|---|---|---|---|---|---|---|
| Male | Female | |||||||
| T2DM/IGT | 18 | 18 | drinking HRW | ~0.6 mM | 8 weeks | sdLDL, emLDL, u-IsoP: ↓, oxLDL: ⇓ glucose tolerance in 4 of 6 IGT patients: ↑ TG, TC, LDL, HDL, FBG, HbA1C, insulin: NSC |
NA | [39] |
| T2DM | 25 | 20 | drinking ERW | NA | 12 weeks | lactate: ↓, FBG, insulin, HOMA-IR: NSC the rate of change in lactate was positively correlated with the rate of change in HOMA-IR, FBG and insulin in the HOMA-IR ≥1.73 group, in the FBG ≥6.1 mM group: insulin: ↓, FBG: ⇓ |
UMIN000019032 | [40] |
| T2DM | 15 | 15 | drinking ERW | NA | 12 days | TC, TG, LDL: ↓, HDL: ↑ FBG: ⇓ |
NA | [41] |
| MS | 10 | 10 | drinking HRW | 0.55–0.65 mM | 8 weeks | SOD: ↑, TBARS in urine: ↓ HDL: ↑ (week 4) LDL, TC/HDL: ↓ (week 4) TC, TG, FBG: NSC |
NA | [42] |
| MS | 12 | 8 | drinking HRW | 0.2–0.25 mM | 10 weeks | TC, LDL, apoB100, apoE: ↓ TG, HDL, FBG: NSC MDA: ↓, SOD: ↑ TNF-α, IL-6: NSC |
NA | [43] |
| MS | 30 | 30 | drinking high-concentration HRW (>5.5 mM) | >5.5 mmol H2 per day | 24 weeks | BMI, WHC, TG, TC, LDL, HDL, FBG, HbA1c: ↓ TNF-α, IL-6, CRP: ↓ MDA: ↓, TBARS: NSC Vitamin E, Vitamin C: ↑ |
NA | [44] |
| NAFLD | 5 | 7 | drinking HRW | 3 mM | 4 weeks | liver fat, AST: ↓ BW, BMI, body composition, lipid profiles, FBG: NSC |
NCT03625362 | [45] |
| NAFLD | 13 | 17 | drinking HRW | >2 mM | 8 weeks | BW, BMI, SBP, AST, ALT, LDH, NF-κB, HSP70, MMP-9: ⇓ CRP, ALB, ALP, TG, TC, HDL, LDL, TG/HDL ratio, 8-OHdG, MDA: ⇑ |
NCT05325398 | [46] |
| NAFLD | 24 | 19 | Hydrogen/oxygen inhalation | 66% | 13 weeks | TC, TG, HDL: NSC LDL, AST, ALT, MDA, TNF-α, IL-6: ↓ SOD: ↑ liver fat in moderate–severe cases: ↓ |
ChiCTR-IIR-16009114 | [47] |
| Vascular endothelial function |
18 | 16 | drinking high-concentration HRW (3.5 mM) | >3.5 mM | 1 time | the ratio of the changes in FMD of the BA: ↑ | NA | [48] |
| Vascular endothelial function |
24 | 44 | drinking high-concentration HRW (3.5 mM) | >3.5 mM | 2 weeks | Ln_RHI value in the low Ln_RHI group: ↑ Ln_RHI value in the high Ln_RHI group: NSC |
NA | [49] |
| Obesity | 0 | 10 | oral intake of H2 generating minerals |
~6 ppm of H2 per day | 4 weeks | body fatness, arm fat index, TG, insulin: ↓ ghrelin: ⇑, lactate: ↓ BW, FBG, other lipid parameters: NSC |
NCT02832219 | [50] |
| Obesity | 2 | 2 | HRW bath (41 °C, 0.15 mM) | ~0.15 mM | 4–24 weeks | visceral fat, LDL in two women: ↓ | NA | [51] |
Abbreviations: IGT, impaired glucose tolerance; sdLDL, small dense LDL; emLDL, electronegative charge of modified LDL; u-IsoP, urinary 8-isoprostanes; oxLDL, oxidized LDL; HbA1C, hemoglobin A1c; HOMA-IR, homeostasis model assessment of insulin resistance; TBARS, thiobarbituric acid reactive substances; apoB100, apolipoprotein B100; apoE, apolipoprotein E; TNF-α, tumor necrosis factor alpha; IL-6, interleukin-6; BMI, body mass index; WHC, waist–hip circumference; CRP, C-reactive protein; MDA, malondialdehyde; AST, aspartate aminotransferase; BW, body weight; SBP, systolic blood pressure; ALT, alanine transferase; LDH, lactate dehydrogenase; NF-κB, nuclear factor kappa B; HSP70, heat shock protein 70; MMP-9, matrix metalloproteinase-9; ALB, albumin; ALP, alkaline phosphatase; 8-OHdG, 8-hydroxydeoxyguanosine; FMD, flow-mediated dilation; BA, brachial artery; Ln_RHI, the natural logarithmic transformed value of the RH-PAT (reactive hyperemia-peripheral arterial tonometry) index; ⇓, decrease without significance; ⇑, increase without significance; NSC, no significant change; NA, not available.