Hydrogen inhalation, patients with Parkinson’s diseaseScientific Research

Inhalation of hydrogen gas elevates urinary 8-hydroxy-2′-deoxyguanine in Parkinson’s disease

Masaaki Hirayama,1 Mikako Ito,2 Tomomi Minato,1 Asako Yoritaka,3 Tyler W. LeBaron,4,5 and Kinji Ohno, MD, PhD2,*

Abstract

Hypoemia is one of the earliest and most common symptoms in Parkinson’s disease (PD). The benefits of hydrogen water on motor deficits have been reported in PD animal models and PD patients, but the effects of hydrogen on PD patients have not been studied. We conducted an 8-week washout study in 20 PD patients in a randomized, double-blind, placebo-controlled, crossover study. Patients inhaled approximately 1.2-1.4% hydrogen-air mixture or placebo for 10 minutes twice a day for 4 weeks. Low-dose hydrogen inhalation did not significantly affect clinical PD parameters, but increased urinary 8-OHdG concentrations by 16%. This increase in 8-OHdG was significantly lower than the over 300% increase in diabetes and more comparable to the increase after vigorous exercise. Although elevated reactive oxygen species are often associated with toxicity and disease, they also play an important role in mediating cytoprotective cellular adaptations in a process known as excitability. Increased hydrogen-induced oxidative stress and its ability to activate Nrf2, the NF-κB pathway, and the heat shock response have been previously reported. Although we did not observe any beneficial effects of hydrogen in our brief experiments, we believe that increased 8-OHdG and other reported hydrogen stress responses may suggest that its beneficial effects are partly or largely mediated by excitatory mechanisms. This study was approved by the Ethics Committee of the Nagoya University Graduate School of Medicine (approval number 2015-0295). This clinical study is registered with the University Hospital’s Medical Information Network (ID UMIN000019082).

Results

A randomized, double-blind, placebo-controlled, crossover study of 20 Parkinson’s disease patients inhaling approximately 1.2-1.4% hydrogen-air mixture or placebo for 10 minutes twice a day for 4 weeks found that OSIT- J (p = 0.77), UPDSR1 (P = 0.84) and UPDRS2 (P = 0.15) were not affected by hydrogen (Table 1). In contrast, 4 weeks of hydrogen inhalation increased urinary 8-OHdG excretion by 16%, which was statistically significant (P=0.02) (Table 1 and Figure 2).

Table 1

Metrics before and after inhalation of true and placebo hydrogen gas for 4 weeks

HydrogenPlacebo
BeforeAfterPBeforeAfterP
OSIT-J4.7±2.04.85±1.90.774.55±2.44.6±2.20.92
UPDRS12.2±1.62.3±1.90.842.7±2.42.4±1.90.41
UPDRS213.7±9.015.9±7.00.1516.6±9.116.8±6.30.93
8-OHdG/Cr (ng/mg Cr)9.5±9.711.0±5.90.029.2±6.99.7±6.80.59

Note: Date are expressed as the mean ± SD. P values are calculated by paired t-test. 8-OHdG: 8-Hydroxy-2′-deoxyguanine; Cr: creatine; UPDRS: Unified Parkinson’s Disease Rating Scale.

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Urinary 8-OHdG/Cr before and after inhalation of true and placebo hydrogen gas for 4 weeks.

Note: (A) Twenty Parkinson’s disease (PD) patients. P value by Student’s paired t-test is indicated. (B) Ten PD patients who inhaled hydrogen first. (C) Ten PD patients who inhaled placebo first. (B, C) No statistical significance by one-way analysis of variance. Date are expressed as the mean ± SE. 8-OHdG: 8-Hydroxy- 2′-deoxyguanine; Cr: creatine.

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