The Science of Hydrogen and Health


Oral hydrogen water prevents chronic allograft nephropathy in rats
Chronic allograft nephropathy is a disease that occurs after kidney transplant.  It is the most prevalent cause of transplant failure.  Scientists discovered that drinking hydrogen-rich water improved functioning of kidney transplants, slowed the progression of chronic allograft nephropathy and improved overall survival after kidney transplantation in rats. 
Download this article from Kidney International  (Cardinal et al 2009)

Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice
Nephrotoxicity is the poisonous effect of some medications on the kidneys.  Cisplatin is a drug used for chemotherapy that can cause kidney damage as a side effect (it is a nephrotoxin.)  This study showed that drinking hydrogen rich water reduces the side effects of cisplatin by reducing oxidative stress in the kidneys.  It reduced death rate, weight loss and kidney damage in mice.  However it did not reduce the beneficial anti-tumor activity of the cisplatin.  The paper notes that many antioxidants have been reported to protect against cisplatin toxicity, however, extremely high doses were required, higher than the amount humans could safely take.  Hydrogen has the advantage over other antioxidants, in that it is able to protect kidney cells within a safe dosage. 

Another important aspect of this paper is that the authors compared inhalation of hydrogen gas to ingestion of hydrogen rich water.  They found both equally effective, but noted that drinking hydrogen rich water may be more convenient.  They concluded, "Hydrogen has potential for improving the quality of life of patients during chemotherapy by effectively mitigating the side effects of cisplatin."
Download this article from Cancer Chemotherapy and Pharmacology  (Nakashima-Kamimura et al 2009)

Experimental verification of protective effect of hydrogen-rich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT
This study is similar to Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice (listed above.) Rats were used in this study, rather than mice, and instead of measuring oxidative stress markers, death rate, weight loss, and blood tests to indicate kidney damage, the scientists in this study used dynamic contrast-enhanced CAT scans.  Rats in the treatment group were given free access to hydrogen rich water starting 7 days before being treated with cisplatin.  The results strongly supported the previous study, demonstrating that hydrogen rich water improves kidney dysfunction due to side-effects of cisplatin. 
Download this article from British Journal of Radiology  (Kitamura et al 2010)

Protective effect of hydrogen-rich water against Gentamicin-induced nephrotoxicity in rats using blood oxygenation level-dependent MR imaging
Gentamicin is a common antibiotic which can cause kidney damage (nephrotoxicity.)

   Purpose: We assessed intrarenal oxygenation in gentamicin-induced nephrotoxicity (GIN) and the protective effect of hydrogen-rich water (HW) against GIN using blood oxygenation level-dependent Magnetic resonance (MR) imaging.
   Materials and Methods: We acquired T2*-weighted images (T2*WI) of 21 rats on Days 0, 2, 4, and 7 using a 1.5-tesla MR imaging system.  The rats were divided into 3 groups of seven each: control rats had free access to standard water and no gentamicin (GM) injection; rats designated the GM group had free access to standard water and were injected with GM (80 mg/kg/day) subcutaneously for 7 days; and the third group, designated the GM+HW group, had free access to HW and were injected with GM. R2* (=1/T2*) was estimated from T2*WI. 
   Results: R2* values in the cortex were significantly decreased on Days 2, 4, and 7 compared with those on Day 0 in the GM group but not significantly changed in the control and GM+HW groups. R2* values in the medulla did not change significantly in any group. 
  Conclusions: Our findings suggested reduced oxygen utility, mainly in the cortex, in gentamicin-induced nephrotoxicity and an ameliorative effect of hydrogen-rich water against GIN. 
Download this article from Magnetic Resonance in Medical Sciences  (Matsushita et al 2011)

Hydrogen-rich water inhibits glucose and α,β-dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney
Background: Reactive oxygen species (ROS) production induced by α,β-dicarbonyl compounds and advanced glycation end products causes renal dysfunction in patients with type 2 diabetes and metabolic syndrome. Hydrogen-rich water (HRW) increases the H2 level in blood and tissues, thus reducing oxidative stress in animals as well as humans. In this study, we investigated the effects of HRW on glucose- and α,β-dicarbonyl compound-induced ROS generation in vitro and in vivo.
Methods: Kidney homogenates from Wistar rats were incubated in vitro with glucose and α,β-dicarbonyl compounds containing HRW, following which ROS levels were measured. In vivo animal models of metabolic syndrome, SHR.Cg-Leprcp/NDmcr rats, were treated with HRW for 16 weeks, following which renal ROS production and plasma and renal α,β-dicarbonyl compound levels were measured by liquid chromatograph mass spectrometer.
Results: HRW inhibited glucose- and α,β-dicarbonyl compound-induced ROS production in kidney homogenates from Wistar rats in vitro. Furthermore, SHR.Cg-Leprcp/NDmcr rats treated with HRW showed a 34% decrease in ROS production. Moreover, their renal glyoxal, methylglyoxal, and 3-deoxyglucosone levels decreased by 81%, 77%, and 60%, respectively. Positive correlations were found between renal ROS levels and renal glyoxal (r = 0.659, p = 0.008) and methylglyoxal (r = 0.782, p = 0.001) levels.
Conclusion: These results indicate that HRW inhibits the production of α,β-dicarbonyl compounds and ROS in the kidneys of SHR.Cg-Leprcp/NDmcr rats. Therefore, it has therapeutic potential for renal dysfunction in patient with type 2 diabetes and metabolic syndrome.
Download this article from Medical Gas Research  (Katakura et al 2012)

Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats
Background: Hydrogen (H2) reportedly produces an anti-oxidative effect by quenching cytotoxic oxygen radicals. We studied the biological effects of water with dissolved H2 on ischemia-induced cardio-renal injury in a rat model of chronic kidney disease (CKD).
Methods: Dahl salt-sensitive rats (7 weeks old) were allowed ad libitum drinking of filtered water (FW: dissolved H2, 0.00 ± 0.00 mg/L) or water with dissolved H2 produced by electrolysis (EW: dissolved H2, 0.35 ± 0.03 mg/L) for up to 6 weeks on a 0.5% salt diet. The rats then underwent ischemic reperfusion (I/R) of one kidney and were killed a week later for investigation of the contralateral kidney and the heart.
Results: In the rats given FW, unilateral kidney I/R induced significant increases in plasma monocyte chemoattractant protein-1, methylglyoxal and blood urea nitrogen. Histologically, significant increases were found in glomerular adhesion, cardiac fibrosis, number of ED-1 (CD68)-positive cells and nitrotyrosine staining in the contralateral kidney and the heart. In rats given EW, those findings were significantly ameliorated and there were significant histological differences between rats given FW and those given EW.
Conclusion: Consumption of EW by ad libitum drinking has the potential to ameliorate ischemia-induced cardio-renal injury in CKD model rats. This indicates a novel strategy of applying H2 produced by water electrolysis tech- nology for the prevention of CKD cardio-renal syndrome.
Download this article from Nephrology Dialysis Transplantation  (Zhu et al 2010)
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