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hydrogen-rich water protects LIVER function of colorectal CANCER patients during CHEMOTHERAPY

The study published in 2017  was conducted to investigate the protective effect of hydrogen-rich water on the liver function of colorectal cancer (CRC) patients treated with mFOLFOX6 chemotherapy.

A controlled, randomized, single-blind clinical trial was designed.

A total of 152 patients with colorectal cancer were recruited by the Department of Oncology of Taishan Hospital (Taian, China) between June 2010 and February 2016, among whom 146 met the inclusion criteria. Subsequently, 144 patients were randomized into the treatment with hydrogen water(n=80) and placebo (n=64) groups. At the end of the study, 76 patients in the hydrogen water treatment group and 60 patients in the placebo group were included in the final analysis.

The 80 patients group started drinking hydrogen-rich water 1 day prior to chemotherapy until the end of the cycle, for a total of 4 days, with a total intake of 1,000 ml hydrogen-rich water per day in 4 doses (250 ml hydrogen-rich water each). Hydrogen-rich water was consumed 0.5 h after a meal and before bedtime.

The patients did not discontinue consuming hydrogen-rich water during the entire course of chemotherapy.

The other 64 placebo patients consumed distilled water, with a daily intake of 1,000 ml in 4 doses (250 ml each).

The changes in liver function after the chemotherapy, such as altered levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase, indirect bilirubin (IBIL) and direct bilirubin, were observed. The damaging effects of the mFOLFOX6 chemotherapy on liver function were mainly represented by increased ALT, AST and IBIL levels. The hydrogen-rich water group exhibited no significant differences in liver function before and after treatment, whereas the placebo group exhibited significantly elevated levels of ALT, AST and IBIL. Thus, hydrogen-rich water appeared to alleviate the mFOLFOX6-related liver injury

 

 

PMID:29142752
PMCID:PMC5666661
DOI:10.3892/mco.2017.1409
 2017 Nov;7(5):891-896. doi: 10.3892/mco.2017.1409. Epub 2017 Sep 1.
Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy.
Yang Q1Ji G1Pan R1Zhao Y2Yan P3.

Author information

1
Department of Oncology, Shandong Provincial Taishan Hospital, Taian, Shandong 271000, P.R. China.
2
Department of Pathology, Taishan Medical University, Taian, Shandong 271000, P.R. China.
3
Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.

Hydrogen-rich water for improvements of MOOD,ANXIETY and AUTONOMIC NERVE FUNCTION in daily life

Abstract

Health and a vibrant life are sought by everyone. To improve quality of life (QOL), maintain a healthy state, and prevent various diseases, evaluations of the effects of potentially QOL-increasing factors are important. Chronic oxidative stress and inflammation cause deteriorations in central nervous system function, leading to low QOL. In healthy individuals, aging, job stress, and cognitive load over several hours also induce increases in oxidative stress, suggesting that preventing the accumulation of oxidative stress caused by daily stress and daily work contributes to maintaining QOL and ameliorating the effects of aging. Hydrogen has anti-oxidant activity and can prevent inflammation, and may thus contribute to improve QOL. The present study aimed to investigate the effects of drinking hydrogen-rich water (HRW) on the QOL of adult volunteers using psychophysiological tests, including questionnaires and tests of autonomic nerve function and cognitive function. In this double-blinded, placebo-controlled study with a two-way crossover design, 26 volunteers (13 females, 13 males; mean age, 34.4 ± 9.9 years) were randomized to either a group administered oral hydrogen-rich water HRW (600 mL/d) or placebo water (PLW, 600 mL/d) for 4 weeks. Change ratios (post-treatment/pre-treatment) for K6 score and sympathetic nerve activity during the resting state were significantly lower after hydrogen-rich water HRW administration than after PLW administration. These results suggest that hydrogen-rich water HRW may reinforce QOL through effects that increase central nervous system functions involving mood, anxiety, and autonomic nerve function.

Introduction

Health and a vibrant life are much craved by everyone. To improve quality of life (QOL), maintain a healthy state, and prevent the onset of various diseases, evaluation of interventional effects for improving QOL is important. The high metabolic rate of the brain results in the generation of disproportionate amounts of reactive oxygen and nitrogen species, leading to increased oxidative stress. Increased oxidative stress and lipid peroxidation initiate a cascade of proinflammatory signals, leading to inflammation. Altered homeostasis of oxidation, inflammation, and protein aggregation has been suggested to contribute to the death of neurons, which is directly related to impairments in various cognitive domains. As such, chronic oxidative stress and inflammation may cause deteriorations in the function of the central nervous system, leading to reductions in QOL. Hydrogen has antioxidant activity and can prevent inflammation.,, The distribution of hydrogen throughout the brain and body indicates actions both in the central and peripheral nervous systems. Previous clinical studies have shown that hydrogen-rich water (HRW) reduces concentrations of markers of oxidative stress in patients with metabolic syndrome,,improves lipid and glucose metabolism in patients with type 2 diabetes, improves mitochondrial dysfunction in patients with mitochondrial myopathies, and reduces inflammatory processes in patients with polymyositis/dermatomyositis. In another study, exercise-induced declines in muscle function among elite athletes were also improved by administering hydrogen-rich water HRW. Although such findings suggest that hydrogen-rich water HRW may help alleviate symptoms of several diseases and increase the physical performance of athletes, the effects of prolonged  hydrogen-rich water HRW ingestion on the QOL of individuals in the general population remain unknown.

Some reports have demonstrated that oxidative stress is associated with QOL in patients with chronic obstructive pulmonary disease and cervical cancer., During oncological treatment among patients with cervical cancer, antioxidant supplementation was found to be effective in improving QOL. In addition, Kang et al. reported that treatment with hydrogen-rich water HRW for patients receiving radiotherapy for liver tumors decreased oxidative stress and improved QOL. Although the association between oxidative stress and QOL in healthy individuals is still unclear, aging, job stress, and cognitive load over the course of several hours in healthy individuals have also been found to induce increases in oxidative stress,,,, suggesting that preventing the accumulation of oxidative stress caused by daily stress and daily work may contribute to the maintenance of QOL and amelioration of the effects of aging. Continuous hydrogen-rich water HRW intake might therefore be expected to reduce accumulation of oxidative stress, thus helping to prevent decreases in QOL.

The aim of the present study was to investigate the effects of drinking 600 mL of hydrogen-rich water HRW per day for 4 weeks on the QOL of adult volunteers using questionnaires for sleep, fatigue, mood, anxiety, and depression, an autonomic function test, and a higher cognitive function test.

Subjects and Methods

Subjects

Thirty-one adult volunteers between 20 and 49 years old participated in this double-blinded, randomized, placebo-controlled study with a two-way crossover design. Exclusion criteria comprised: history of chronic illness; chronic medication or use of supplemental vitamins; employment in shift work; pregnancy; body mass index ≤ 17 or ≥ 29 kg/m2; food allergy; history of smoking; or history of drinking excessive amounts of alcohol (≥ 60 g/day). Shift workers were excluded because the water was administered at breakfast and dinner, the timings of which are irregular among shift workers. In addition, the mental and physical conditions of shift workers can be greatly affected by the shift schedule for the preceding 2 days, which may impact the results obtained from the questionnaires used in this study. Before each experiment, participants were asked to refrain from drinking alcohol, since drinking excessive amounts of alcohol carries significant risks of fluctuations in physical condition. All experiments were conducted in compliance with national legislation and the Code of Ethical Principles for Medical Research Involving Human Subjects of the World Medical Association (the Declaration of Helsinki) and registered to the UMIN Clinical Trials Registry (No. UMIN000022382). The study protocol was approved by the Ethics Committee of Osaka City University Center for Health Science Innovation (OCU-CHSI-IRB No. 4), and all participants provided written informed consent for participation in the study.

Study design

We used a double-blinded, placebo-controlled study with a two-way crossover design, as summarized in Figure 1. After admission to the study, participants were randomized in a double-blinded manner to receive hydrogen-rich water HRW in an aluminum pouch (0.8–1.2 ppm of hydrogen, 300 mL/pouch; Melodian Corporation, Yao, Japan) or placebo water (PLW), representing mineral water from the same source (i.e., same components without hydrogen) in an aluminum pouch (0 ppm of hydrogen, 300 mL/pouch; Melodian Corporation) twice a day for 4 weeks. Fifteen participants were administered PLWfirst, and then hydrogen-rich water HRW. The remaining 16 participants were administered HRW hydrogen-rich water first, and then PLW. Participants consumed water within 5 minutes twice a day, at breakfast and dinner in their home, and confirmed the water intake at breakfast and dinner in a daily journal for 4 weeks. We assessed the intake rate of water by checking the daily journal every 4 weeks, on the 2nd and 4th experimental days. No participants reported any difference in taste between hydrogen-rich water HRW and PLW. Previous studies have reported interventional effects of administering hydrogen-rich water HRW to humans at hydrogen concentrations under 1.3 ppm., We therefore used a similar concentration of 0.8–1.2 ppm in the present study. Absolute volumes (600 mL) of  hydrogen-rich water HRW and PLW were provided to participants rather than a volume proportional to body mass, based on previously reported results.,,, The duration of supplementation was set based on previous findings with hydrogen-rich water HRW administration for 2–8 weeks.,, A 4-week washout period was provided between hydrogen-rich water HRW and PLW administrations based on a previous study.The day before starting each experiment, participants were told to finish dinner by 21:00, and were required to fast overnight to avoid any influence of diet on concentrations of measured parameters (markers of inflammation and oxidative stress) in blood samples. At 09:00 the next day, participants completed the questionnaires after confirming that they had refrained from drinking alcohol, had finished dinner by 21:00, and had fasted overnight. Autonomic nerve function was measured at 09:30. Cognitive function testing was conducted at 09:45. Blood samples were collected at 10:00. These measurements were performed a total of four times for each participant, before (pre) and after (post) each of the two 4-week administration periods. From 24 hours (the day before the visit day) before each visit for measurements, participants were told to refrain from drinking alcohol or performing strenuous physical activity and to follow their normal diets, drinking habits, and sleeping hours. During the 4-week PLW or hydrogen-rich water HRW administration periods, daily daytime activity (amount of physical exertion) of participants was measured using a pedometer and participants kept a daily journal to record drinking volume and times of PLW or HRW intake, physical condition (e.g., pain, lassitude, and indefinite complaints), sleeping times, etc.

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Time course of the experiments.

Note: Participants were randomly divided into two study groups. The experiment consisted of 4 weeks of hydrogen-rich water (HRW) administration or placebo water (PLW) administration, a 4-week washout period, and then another 4 weeks of PLW administration or hydrogen-rich water HRW administration. Before (pre) and after (post) each period of hydrogen-rich water HRW or PLW administration, subjective and objective measurements for quality of life were obtained, such as results for sleep, mood, anxiety, feelings of depression, autonomic nerve function, and cognitive function.

Questionnaire

Severity of fatigue was measured using the Chalder Fatigue Scale (CFS) and a modified version of the Osaka City University Hospital Fatigue Scale. Mood and anxiety were evaluated using the K6 scale.Symptoms of depression were measured using the Center for Epidemiologic Studies Depression Scale.General sleepiness and daytime sleepiness scores were calculated using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale, respectively. The reliability and validity of the Japanese versions of these questionnaires have been confirmed.,,,,,

Autonomic function test

Participants underwent simultaneous electrocardiography and photoplethysmography using a Vital Monitor 302 system (Fatigue Science Laboratory, Osaka, Japan) while sitting quietly with their eyes closed for 3 minutes. These data were analyzed using MemCalc software (GMS, Tokyo, Japan). Frequency analyses for R-R interval variation from electrocardiography and a-a interval variation as the second derivative of photoplethysmography (accelerated plethysmography) were performed using the maximum entropy method, which is capable of estimating the power spectrum density from short time series data, and is adequate for examining changes in heart rate variability under different conditions of short duration.,The power spectrum resolution was 600 Hz. For frequency analyses, the low-frequency component power (LF) was calculated as the power within a frequency range of 0.04–0.15 Hz, and the high-frequency component power (HF) was calculated as that within a frequency range of 0.15–0.4 Hz. HF is vagally mediated,,, whereas LF originates from a variety of sympathetic and vagal mechanisms., Some review articles,, mentioned that LF reflects sympathetic nerve activity and is used as a marker of sympathetic nerve activity in original articles. Before autonomic nerve function testing was conducted for 3 minutes, a practice test was conducted for a period of 1 minute, in accordance with previous studies.,, The reliability of these tests has been confirmed.,

Cognitive function test

Since previous studies have revealed that a switching attention task is useful for evaluating reduced performance under fatigue conditions,,, we used task E of the modified advanced trail making test (mATMT) as a switching attention task for evaluating executive function., Circles with numbers (from 1 to 13) or kana (Japanese phonograms, 12 different letters) were shown in random locations on a screen, and participants were required to use a computer mouse to alternately touch the numbers and kana; this task thus required switching attention. When participants touched a target circle, it remained in the same position, but its color changed from black to yellow. Participants were instructed to perform the task as quickly and correctly as possible, and continuously performed this task for 5 minutes. We evaluated three indices of task performance: the total count of correct responses (number of correctly touched numbers and letters); the total count of errors (number of incorrectly touched numbers and letters); and the motivational response (reaction time from a finished trial to the next trial). Based on our previous study, before participants performed task E of the mATMT on each experimental day, they practiced for a period of 1 minute. The reliability of this test has been confirmed.,

Blood sample analyses

Blood samples were collected from the brachial vein. The amount of blood sampled was 13 mL per experimental day. We thus collected blood samples on four occasions (once per experimental day) in the study. Blood samples for serum analyses were centrifuged at 1,470 × g for 5 minutes at 4°C. The concentration of high-sensitivity C-reactive protein (hs-CRP) in each serum sample was assessed by particle-enhanced immunonephelometry using a BNII analyzer (BN II ProSpec; Siemens, Munich, Germany). Oxidative activity in each serum sample was assessed with the reactive oxygen metabolites-derived compounds (d-ROMs) test (Diacron International, Grosseto, Italy), while anti-oxidative activity was measured with the biological anti-oxidant potential (BAP) test (Diacron International) using a JCABM1650 automated analyzer (JEOL, Tokyo, Japan). The concentrations of ROMs are expressed in Carratelli units (1 CARR U = 0.08 mg of hydrogen peroxide/dL). The oxidative stress index (OSI) was calculated using the following formula: OSI = C × (d-ROMs/BAP), where C denotes a coefficient for standardization to set the mean OSI in healthy individuals at 1.0 (C = 8.85). All supernatants were stored at -80°C until analyzed. Assays for hs-CRP were performed at LSI Medience Corporation (Tokyo, Japan) and those for serum d-ROMs and BAP were performed at Yamaguchi University Graduate School of Medicine.

Daily daytime activity and daily journal

Daily daytime activity, representing the expenditure of calories and amount of physical activity (METs × time) was recorded using an Active style Pro HJA-350IT pedometer (OMRON, Kyoto, Japan). A daily journal was kept for 4 weeks, and included information on fatigue (based on a visual analogue scale from 0, representing “no fatigue”, to 100, representing “total exhaustion”) just after waking up and before bedtime, sleeping times, physical condition (1, good; 2, normal; or 3, bad), and special events (if the day was different from a usual day: 1, no; or 2, yes). We carefully checked the daily journal every four weeks, on the 2nd, 3rd, and 4th experimental days.

Statistical analyses

First, we tested the normality (parametric or non-parametric distributions) of each measured parameter using the Kolmogorov-Smirnov test. Values are presented as the mean ± standard deviation or median and interquartile range based on the results of Kolmogorov-Smirnov test. The Wilcoxon signed-rank test for non-parametric parameters and paired t-test for differences between hydrogen-rich water HRW and PLW administrations after two-way repeated-measurement analysis of variance for parametric parameters were conducted. If significant changes were observed by comparisons within each condition (pre- vs. post-HRW; pre- vs. post-PLW) or between post-treatment values (post-HRW vs. post-PLW), then we compared change ratios between post-HRW/pre-HRW and post-PLW/pre-PLW using the Wilcoxon signed-rank test or paired t-test. All P values were two-tailed, and those less than 0.05 were considered statistically significant. Statistical analyses were performed using IBM SPSS Statistical Package version 20.0 (IBM, Armonk, NY, USA).

Results

General results

During the study, we excluded five participants from data analyses due to symptoms of hay fever, prolonged medication use because of a cold, insufficient intake of hydrogen-rich water HRW or PLW intake (≥ 85%), or a frequency of special events ≤ 15% as recorded in the daily diary. We thus analyzed data from a total of 26 participants (13 females, 13 males; mean age, 34.4 ± 9.9 years; mean body mass index, 21.5 ± 2.6 kg/m2). No side, order, and carry-over effects were observed from the oral administrations of hydrogen-rich water HRW and PLW in any participant.

Questionnaire results

Results from the questionnaires are summarized in Table 1. No questionnaire scores at baseline (pre) showed any significant differences between hydrogen-rich water HRW and PLW administration groups. With HRW administration, scores for K6, CFS, and PSQI were significantly decreased after the 4-week administration period. In addition, the change ratio (post/pre) for K6 score was significantly lower in the hydrogen-rich water HRW administration group than in the PLW administration group (Figure 2). No significant changes were seen in any other questionnaire scores (modified version of the Osaka City University Hospital Fatigue Scale, Center for Epidemiologic Studies Depression Scale or Epworth Sleepiness Scale) after hydrogen-rich water HRW administration and no significant changes in any of the scores were seen after PLW administration. Likewise, these scores did not differ significantly between HRW and PLW after administration.

Table 1

Changes in parameters related to quality of life due to hydrogen-rich water (HRW) or placebo water (PLW) administration

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Comparison of change ratios (post-treatment/pre-treatment) for parameters related to quality of life with administration of hydrogen-rich water (HRW) or placebo water (PLW) for 4 weeks.

Note: Change ratios for K6 score for mood (A) and anxiety and the low-frequency component power (LF) for autonomic nerve function (B). *P < 0.05.

Autonomic function results

Results for the autonomic nerve function are summarized in Table 1. LF, HF, and LF/HF ratio at baseline (pre) did not differ significantly between hydrogen-rich water HRW and PLW administrations, indicating similar autonomic nerve function in the two groups before water intake. Although the HF and LF/HF ratio were not significantly affected by 4-week administrations of hydrogen-rich water HRW or PLW, LF after hydrogen-rich water HRW administration was significantly lower than that after PLW administration. The change ratio (post/pre) for LF was also significantly lower in the hydrogen-rich water HRW administration group than in the PLW administration group (Figure 2).

Cognitive function results

Results for the cognitive function test are shown in Table 1. Motivational response and total counts of correct responses and errors at baseline (pre) did not differ significantly between hydrogen-rich water HRW and PLW administrations, indicating similar cognitive function between groups before water intake. Motivational response after hydrogen-rich water HRW administration was significantly faster than that before hydrogen-rich water HRW administration. The change ratio (post/pre) for motivational response was not significantly different in the hydrogen-rich water HRW administration group than in the PLW administration group. No significant differences in motivational response, total counts of correct responses, or errors after water administration were seen between hydrogen-rich water HRW- and PLW-administered conditions.

Blood sample results

No significant differences were seen in any blood parameters (hs-CRP, d-ROMs, BAP, and OSI) before hydrogen-rich water HRW or PLW administration (Table 1), indicating the comparability of the two groups before water intake. After hydrogen-rich water HRW and PLW administrations, we again found no significant differences in these blood parameters.

Daily daytime activity and daily journal results

The daily expenditure of calories and amount of physical activity during the 4-week administration periods did not differ significantly between hydrogen-rich water HRW and PLW administration conditions (Table 2). Similarly, visual analogue scale scores for fatigue just after waking and before bedtime, sleeping times, physical condition, and counts of special events were comparable between hydrogen-rich water HRW and PLW administration conditions (Table 2), indicating that living habits were successfully controlled during the experimental period in the two groups.

Table 2

Daily daytime activity and data recorded in the daily journal during the hydrogen-rich water (HRW) or placebo water (PLW) administration period (4 weeks)

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Discussion

The present findings suggest that hydrogen-rich water HRW administration for 4 weeks may have improved the QOL of adult volunteers in terms of improved mood and anxiety and reduced activity of the sympathetic nervous system at rest.

In terms of associations between hydrogen and the central nervous system, a report by Ohsawa et al. was the first to demonstrate that molecular hydrogen acts, at least in part, as an anti-oxidant as it binds to hydroxyl ions produced in central nervous system injuries. Previous studies have proposed that hydrogen-rich water HRW administration has neuroprotective effects and anti-aging effects on periodontal oxidative damage in healthy aged rats. In a rat model of Alzheimer’s disease, hydrogen-rich saline prevented neuroinflammation and oxidative stress, and improved memory function. In terms of the association between hydrogen-rich water HRW and QOL, only one study reported that HRW hydrogen-rich water administration for 6 weeks improved QOL scores in patients treated with radiotherapy for liver tumors. Although reports on the effects of HRW hydrogen-rich water administration in healthy populations have not been accumulated, job stress, and acute fatigue caused by mental and physical loading for several hours, have been shown to enhance oxidative stress. As for physical fatigue, in order to alleviate acute physical fatigue in healthy volunteers not including athletes, we have previously demonstrated that treatment with antioxidant supplements is effective.,, The present study provided new findings that HRW hydrogen-rich water affects not only physical condition but also mental conditions such as mood, anxiety, and autonomic nerve function. One of the advantages of HRW hydrogen-rich water is the ability to cross the blood-brain barrier, offering high potential to reduce oxidative stress in the brain. A previous study in rats found that levels of malondialdehyde, a marker of oxidative stress, were around 4.8-fold higher in the brain than in the blood (plasma). These results suggest that HRW hydrogen-rich water may be effective for reducing accumulated oxidative stress in the brain in daily life, potentially contributing to the maintenance of central nervous system activity and preventing decreases in QOL.

In the present study, mood and anxiety levels improved after HRW hydrogen-rich water administration. These negative emotions are also known to be involved in conditions related to oxidative stress; social phobia,,depression, anxiety,, and other neuropsychiatric disorders have been shown to be associated with increased oxidative stress. Neuroinflammation is also related to fatigue, mood, anxiety, and sleep.,,, In older mice, HRW hydrogen-rich water administration succeeded in suppressing depression-like behaviors. These findings suggest that administration of HRW hydrogen-rich water for 4 weeks may be effective for controlling such negative emotions by reducing oxidative stress and inflammation of the central nervous system. Increasing evidence suggests that oxidative stress and inflammation in neurons are involved in the pathological manifestations of many neurological and neuropsychiatric disorders, and HRW hydrogen-rich water administration may thus help alleviate the symptoms of these disorders. Previous study revealed that oxidative stress of the brain causes cognitive and motivational deficits in a mouse model of neuropsychiatric disorder (schizophrenia). In the present study, motivational response of cognitive function test was improved by prolonged HRW hydrogen-rich water intake, suggesting that a reduction of oxidative stress in the brain by the intake of HRW hydrogen-rich water may increase motivational performance of cognitive task.

Stressors can enhance sympathetic hyperactivity, promote oxidative stress, and boost pro-inflammatory cytokine production.,, Autonomic nerve function is thus closely associated with oxidative stress and inflammation. Attenuation of sympathetic nervous system activity during the resting state in adult volunteers may therefore be the result of decreases in inflammation and oxidative stress as an effect of prolonged HRW hydrogen-rich water administration. However, the lack of changes in oxidative stress markers noted in the present study after HRW intake for 4 weeks could be due to the low severity of oxidative stress in the participants. Actually, serum d-ROMs (307.1 ± 49.4 CARR U) and BAP (2,549 ± 194 µM) concentrations at the first measurement point in the present study were within normal ranges based on the results of serum d-ROMs (286.9 ± 100.2 CARR U) and BAP (2,541 ± 122 µM) concentrations measured in 312 healthy participants in our previous study. However, levels of oxidative stress fluctuate depending on daily work load and stress. In addition, the rat study by García-Niño et al. that found malondialdehyde levels around 4.8-fold higher in the brain than in plasma indicate that oxidative stress in the brain is more severe. Daily administration of HRW hydrogen-rich water for 4 weeks may thus contribute to attenuation of and prevention from the cumulative oxidative stress in the brain. Mood, anxiety, and autonomic nerve function could thus potentially be improved. Although the range of sympathetic nerve activity in the present study considers to be normal based on our previous studies,, sympathetic nerve activity also fluctuates depending on daily work load and stress. Therefore, lower sympathetic nerve activity of resting state may contribute to suppress an excessive increase in sympathetic nerve activity after the daily work load and stress.

We conducted this study with a limited number of participants. Before our results can be generalized, studies involving larger numbers of participants are essential.

Although we mainly examined the effects of HRW hydrogen-rich water on the central nervous system, we did not directly evaluate the dynamics of inflammation and oxidation in the brain. Neuroimaging studies using positron emission tomography and magnetic resonance imaging are thus underway in our laboratory to identify the mechanisms underlying the effects of HRW intake on the central nervous system that can improve QOL.

In conclusion, HRW hydrogen-rich water administration for 4 weeks in adult volunteers improved mood, anxiety, and autonomic nerve function, suggesting that HRW hydrogen-rich water administration may offer an effective method to reinforce QOL and maintain good health. In a further study, we will try to identify the effects of HRW hydrogen-rich water administration in participants with ongoing stress or chronic fatigue.

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Link to Publisher's site
. 2017 Oct-Dec; 7(4): 247–255.
Published online 2018 Jan 22. doi:  [10.4103/2045-9912.222448]
PMCID: PMC5806445
PMID: 29497485
Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life

Acknowledgments

We would like to thank Ms. Mika Furusawa for her excellent technical assistances and Forte Science Communications for editorial help with this manuscript.

Footnotes

Conflicts of interest

This work was presented at Japanese Society of Fatigue Science, Yamaguchi City, Japan on May 16, 2016. Yasuyoshi Watanabe received funding for the present study from Melodian Corporation. The other authors have no conflicts of interest to declare.

Research ethics

All experiments were conducted in compliance with national legislation and the Code of Ethical Principles for Medical Research Involving Human Subjects of the World Medical Association (the Declaration of Helsinki) and registered to the UMIN Clinical Trials Registry (UMIN000022382). The study protocol was approved by the Ethics Committee of Osaka City University Center for Health Science Innovation (OCU-CHSI-IRB No. 4).

Declaration of participant consent

The authors certify that they have obtained all appropriate participant consent forms. In the form the participants have given their consent for their images and other clinical information to be reported in the journal. The participants understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Data sharing statement

Datasets analyzed during the current study are available from the corresponding author on reasonable request.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

Open peer reviewers

Lei Huang, Loma Linda University, USA; Qin Hu, Shanghai Jiao Tong University, China.

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Hydrogen-rich water affected blood alkalinity in physically active men

Abstract

Possible appliance of effective and safe alkalizing agent in the treatment of metabolic acidosis could be of particular interest to humans experiencing an increase in plasma acidity, such as exercise-induced acidosis.

In the present study we tested the hypothesis that the daily oral intake of 2L of hydrogen-rich water (HRW) for 14 days would increase arterial blood alkalinity at baseline and post-exercise as compared with the placebo.

This study was a randomized, double blind, placebo-controlled trial involving 52 presumably healthy physically active male volunteers. Twenty-six participants received hydrogen-rich water HRW and 26 a placebo (tap water) for 14 days.

Arterial blood pH, partial pressure for carbon dioxide (pCO2), and bicarbonates were measured at baseline and postexercise at the start (day 0) and at the end of the intervention period (day 14).

Intake of hydrogen-rich water HRW significantly increased fasting arterial blood pH by 0.04 (95% confidence interval; 0.01 – 0.08; p < 0.001), and postexercise pH by 0.07 (95% confidence interval; 0.01 – 0.10; p = 0.03) after 14 days of intervention.

Fasting bicarbonates were significantly higher in the hydrogen-rich water HRW trial after the administration regimen as compared with the preadministration (30.5 ± 1.9 mEq/L vs. 28.3 ± 2.3 mEq/L; p < 0.0001).

No volunteers withdrew before the end of the study, and no participant reported any vexatious side effects of supplementation.

These results support the hypothesis that hydrogen-rich water HRW administration is safe and may have an alkalizing effect in young physically active men.

 2014;22(1):49-60. doi: 10.1080/15438627.2013.852092.
PMID: 24392771
Hydrogen-rich water affected blood alkalinity in physically active men.
1 a Center for Health, Exercise and Sport Sciences , Stari DIF , Belgrade , Serbia.

hydrogen water , SPORTS , ANTIOXIDANTS and GUT FLORA

Abstract

Expending a considerable amount of physical energy inevitably leads to fatigue during both training and competition in football. An increasing number of experimental findings have confirmed the relationship between the generation and clearance of free radicals, fatigue, and exercise injury. Recently, hydrogen was identified as a new selective antioxidant with potential beneficial applications in sports. The present study evaluated the effect of 2-month consumption of hydrogen-rich water on the gut flora in juvenile female soccer players from Suzhou. As demonstrated by enzyme linked immunosorbent assay and 16S rDNA sequence analysis of stool samples, the consumption of hydrogen-rich water for two months significantly reduced serum malondialdehyde, interleukin-1, interleukin-6, tumour necrosis factor-α levels; then significantly increased serum superoxide dismutase, total antioxidant capacity levels and haemoglobin levels of whole blood. Furthermore, the consumption of hydrogen-rich water improved the diversity and abundance of the gut flora in athletes. All examined indices, including the shannon, sobs, ace, and chao indices, were higher in the control group than those proposed to result from hydrogen-rich water consumption prior to the trial, but these indices were all reversed and were higher than those in the controls after the 2-month intervention. Nevertheless, there were some differences in the gut flora components of these two groups before the trial, whereas there were no significant changes in the gut flora composition during the trial period. Thus, the consumption of hydrogen-rich water for two months might play a role modulating in the gut flora of athletes based on its selective antioxidant and anti-inflammatory activities. The study protocol was approved by the ethics committee of the Suzhou Sports School (approved number: SSS-EC150903).

Introduction

A number of studies have confirmed that the occurrence of exercise-induced fatigue is closely related to the level of oxidative stress in the body., The lipid peroxidative damage caused by the accumulation of free radicals in the body and the corresponding chain reaction are considered important factors responsible for decreased function of the body.,,

The antioxidant capacity of professional athletes is much higher than that of ordinary people, and athletes develop a greater ability to withstand the accumulation of free radicals and oxidative damage generated in sports. However, there are still many problems regarding protection against and alleviation and removal of the oxidative stress reaction induced by free radical accumulation in the aftermath of exercise and sports. Currently, the effects of antioxidants used in exercise practice vary, and studies have indicated that some of these substances may induce more significant skeletal muscle injury in athletes.,, Therefore, the search for safe and effective selective antioxidants has become an important research endeavour.

The selective antioxidant activity of hydrogen was first reported in 2007 by Ohsawa et al. Thereafter, a significant number of studies confirmed that hydrogen-rich water, prepared by dissolving hydrogen in water, shows selective antioxidant activity. Currently, sports science researchers are paying increasing attention to the selective antioxidant, anti-inflammatory, and anti-apoptotic effects of hydrogen and its regulation of the alkalinizing environment of the body., The beneficial protective effect of hydrogen-rich water has gradually been confirmed in both animal and human experiments.

The human symbiotic gut flora, considered the body’s “second genome”, has significant effects on human health., In recent years, studies have confirmed that imbalance of the intestinal flora is directly related to oxidative stress., The results of human experiments on athletes have shown that a greater exercise intensity results in increased oxidative stress in the body and, thus, a higher incidence of gastrointestinal stress symptoms. Therefore, in the training process, athletes should drink a sufficient amount of selective antioxidant hydrogen-rich water to regulate their gut flora, which might have a protective effect on the gastrointestinal tract and reduce stress reactions.

Participants and Methods

Participants and grouping

Thirty-eight juvenile female football players from the Suzhou Sports School showing a healthy status and absence of sports injury, without any obvious food preference, and with no significant reported intake of nutritional supplements and antibiotics for 3 months were randomly divided into two groups: the control group (n = 10) and the hydrogen-rich water treatment group (n = 28) (Figure 1). Written informed consent was obtained from each participant prior to admission to the protocol, and the study protocol was approved by the ethics committee of the Suzhou Sports School (approved number: SSS-EC150903). This study follows the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During the experiment, the athletes in the hydrogen-rich water treatment group drank hydrogen-rich water in an amount equivalent to the amount of normal water they had previously consumed daily, while athletes in the control group continued to drink standard water in amounts consistent with their previous habits. The experiment lasted for 2 months. The basic information of the subjects is shown in Table 1.

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Trial flow chart.

Table 1

Characteristics of all subjects

Characteristics Control group (n = 10) Hydrogen-rich water treatment group (n = 28)
Age (year) 13.7±1.06 12.18±0.86
Height (cm) 159.1±5.51 149.32±8.69
Body weight (kg) 48.97±4.56 40.15±7.56
Training period (year) 3.4±1.51 1.21±0.6

Note: Data as expressed as the mean ± SD.

Sample collection

During the experiment, the athletes followed their previous dietary and resting regimes and other aspects of their normal daily routine. The training content, exercise intensity, frequency of exercise, and other parameters were consistent with the routine training regimen of the athletes.

Blood sample test

We collected 5 mL samples of venous blood (fasting) from all 38 athletes at a predetermined time in the morning, and 100 μL of whole blood was sampled for the measurement of haematological parameters in a blood cell analyser. The remaining blood samples were centrifuged at 3000 × g for 5 minutes. The serum samples were then collected and analysed with an automatic biochemical analysis apparatus to determine hemoglobin (HGB), blood urea nitrogen (BUN) and creatine kinase (CK). Then, the serum samples were analysed for oxidative response indices (malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) and inflammatory indices (interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α)) using enzyme linked immunosorbent assay.

16S rDNA sequencing analysis of gut flora samples

Faecal flora samples were collected from all 38 athletes according to the specifications for stool sampling and stored at –80°C. The subsequent DNA sample extraction and 16S rDNA sequencing analysis were performed with the assistance of the Novagene Genomics Institute.

Statistical analysis

SPSS 19.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. The results were expressed as the mean ± SD. Significant differences between the two groups were analysed with repeated measured one-way analysis of variance, and the significance level was set at P < 0.05.

Results

Effects of long-term consumption of hydrogen-rich water on routine indices of juvenile female football players

Hemoglobin

After 4 weeks, HGB decreased from 134.3 ± 12.95 g/L to 124.00 ± 17.75 g/L in the control group, while that in the hydrogen-rich water treatment group decreased from 138.74 ± 9.38 g/L to 129.59 ± 8.57 g/L. After 8 weeks, HGB increased from 124.00 ± 17.75 g/L to 131.6 ± 25.31 g/L in the control group, while that in the hydrogen-rich water treatment group increased from 129.59 ± 8.57 g/L to 139.89 ± 7.02 g/L (Figure 2A). The increasing trend and amplitude of HGB were more significant in the hydrogen-rich water treatment group (P = 0.032).

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Changes in HGB, BUN and CK before and after hydrogen-rich water consumption.

Note: (A) The shift of HGB before and after hydrogen-rich water consumption; (B) The shift of BUN before and after hydrogen-rich water consumption; (C) The shift of CK before and after hydrogen-rich water consumption. HGB: Hemoglobin; BUN: blood urea nitrogen; CK: creatine kinase.

Blood urea nitrogen

After 4 weeks, the level of BUN increased from 4.73 ± 0.88 to 4.83 ± 0.81 mM in the control group, while that in the hydrogen-rich water treatment group changed from 5.19 ± 0.85 to 5.17 ± 1.03 mM. After 8 weeks, the level of BUN in the control group continued to increase, from 4.83 ± 0.81 to 5.29 ± 0.97 mM, while that in the hydrogen-rich water treatment group decreased from 5.17 ± 1.03 to 4.42 ± 0.95 mM (Figure 2B). There was a more distinct difference between the two groups (P = 0.887).

Creatine kinase

After 4 weeks, CK in the control group increased from 157.3 ± 17.37 to 171.3 ± 31.96 IU, while that in the hydrogen-rich water treatment group decreased from 149.3 ± 30.43 to 135.85 ± 24.44 IU (Figure 2C). After 8 weeks, CK decreased from 171.3 ± 31.96 to 129.7 ± 30.05 IU in the control group and from 135.85 ± 24.44 to 119.85 ± 29.93 IU in the hydrogen-rich water treatment group (P = 0.061).

Compared with HGB and BUN, CK was more sensitive to changes in the exercise load. These results suggest that the hydrogen-rich water treatment exerted a somewhat effect to enhance the whole blood HGB level of the athletes.

Effects of long-term consumption of hydrogen-rich water on oxidative response indices of juvenile female football players

Malondialdehyde

After 4 weeks, serum MDA decreased from 24.77 ± 7.32 to 16.67 ± 4.19 μM in the control group, while that decreased from 22.39 ± 6.20 to 13.80 ± 3.33 μM in the hydrogen-rich water treatment group. After 8 weeks, serum MDA changed from 16.67 ± 4.19 to 15.79 ± 3.07 μM in the control group and from13.80 ± 3.33 to 12.69 ± 1.94 μM in the hydrogen-rich water treatment group, with significant differences being observed between the two groups (P = 0.000; Figure 3A).

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Changes in MDA, SOD and T-AOC before and after hydrogen-rich water consumption.

Note: (A) The shift of MDA before and after hydrogen-rich water consumption; (B) The shift of SOD before and after hydrogen-rich water consumption; (C) The shift of T-AOC before and after hydrogen-rich water consumption. MDA: Malondialdehyde; SOD: superoxide dismutase; T-AOC: total antioxidant capacity.

Superoxide dismutase

After 4 weeks, the serum SOD level increased from 10.14 ± 2.60 to 13.14 ± 2.18 U/mL in the control group and from 11.09 ± 3.17 to 14.07 ± 1.91 U/mL in the hydrogen-rich water treatment group. After 8 weeks, the serum SOD level in the control group decreased from 13.14 ± 2.18 to 13.01 ± 1.08 U/mL, while that in the hydrogen-rich water treatment group decreased from 14.07 ± 1.91 to 13.69 ± 2.10 U/mL, with significant differences between the two groups (P = 0.027; Figure 3B).

Total antioxidant capacity

After 4 weeks, serum T-AOC increased from 0.8 ± 0.08 to 1.11 ± 0.17 μM in the control group, while serum T-AOC in the hydrogen-rich water treatment group changed from 0.87 ± 0.11 to 1.17 ± 0.13 μM. After 8 weeks, T-AOC changed from 1.17 ± 0.13 to 0.84 ± 0.09 μM in the control group and from 1.17 ± 0.13 to 0.9 ± 0.13 μM in the hydrogen-rich water treatment group, with significant differences between the two groups (P = 0.004, Figure 3C).

These results suggest that the hydrogen-rich water treatment exerted an anti-oxidative effect.

Effects of long-term consumption of hydrogen-rich water on inflammatory indices of juvenile female football players

Interleukin-1

After 4 weeks, the level of serum IL-1 in the control group increased from 24.77 ± 7.32 to 32.56 ± 7.61 μM, and that in the hydrogen-rich water treatment group increased from 24.79 ± 8.94 to 29.32 ± 7.09 μM. After 8 weeks, the IL-1 level increased from 32.56 ± 7.61 to 42.94 ± 6.24 μM in the control group and from 29.32 ± 7.09 μM to 34.47 ± 6.22 μM in the hydrogen-rich water treatment group, with significant differences between the two groups (P = 0.002, Figure 4A).

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Changes in IL-1, IL-6 and TNF-α before and after hydrogen-rich water consumption.

Note: (A) The shift of IL-1 before and after hydrogen-rich water consumption; (B) The shift of IL-6 before and after hydrogen-rich water consumption; (C) The shift of TNF-α before and after hydrogen-rich water consumption. IL: Interleukin; TNF-α: tumour necrosis factor alpha.

Interleukin-6

After 4 weeks, the level of serum IL-6 decreased from 19.48 ± 2.16 to 10.53 ± 1.62 ng/L in the control group and from 17.72 ± 2.1 to 8.74 ± 2.57 ng/L in the hydrogen-rich water treatment group. After 8 weeks, the level of serum IL-6 in the control group increased from 10.53 ± 1.62 ng/L to 24.88 ± 6.11 ng/L, while that in the hydrogen-rich water treatment group increased from 8.74 ± 2.57 to 12.37 ± 3.2 ng/L, with significant differences between the two groups (P = 0.000, Figure 4B).

Tumour necrosis factor-α

After 4 weeks, serum TNF-α increased from 20.04 ± 7.99 to 60.57 ± 10.09 μM in the control group and increased from 20.44 ± 7.75 to 49.46 ± 11.59 μM in the hydrogen-rich water treatment group. After 8 weeks, serum TNF-α increased from 60.57 ± 10.09 to 132.24 ± 10.46 μM in the control group and from 49.46 ± 11.59 to 107.00 ± 13.89 μM in the hydrogen-rich water treatment group, with significant differences between the two groups (P = 0.000, Figure 4C).

These results suggest that the hydrogen-rich water treatment exerted an anti-inflammatory effect.

Effects of long-term consumption of hydrogen-rich water on gut flora components of juvenile female football players

Classification by phylum

In the samples collected from the athletes after pre-treatment with hydrogen-rich water, the number of Actinobacteria in the control group was higher than that in the treatment group, and the number of Bacteroides in the control group was slightly lower than that in the hydrogen-rich water treatment group. Moreover, the number of Clostridia in the control group was slightly higher than that in the hydrogen-rich water treatment group. However, there were no significant differences in the numbers of these bacterial groups after 2 months of hydrogen-rich water treatment.

Classification by class

In samples collected from the athletes after pre-treatment with hydrogen-rich water, the number of Actinobacteria in the control group was higher than that in the hydrogen-rich water treatment group, while the number of Bacteroides in the control group was slightly lower than that in the hydrogen-rich water treatment group, and the numbers of ClostridiaCoriobacteria, and Erysipelotrichia in the control group were higher than those in the hydrogen-rich water treatment group. However, there was no significant difference in the numbers of these bacterial groups after 2 months of hydrogen-rich water treatment.

Classification by order

In samples collected from the athletes after pre-treatment with hydrogen-rich water, the number of Actinobacteria in the control group was higher than that in the hydrogen-rich water treatment group, while the number of Bacteroides in the control group was slightly lower than that in the hydrogen-rich water treatment group, and the numbers of Clostridia and Coriobacteria in the control group were higher than those in the hydrogen-rich water treatment group. The number of Erysipelotrichia in the control group was higher than that in the hydrogen-rich water treatment group, although this difference was not significant. Nevertheless, there were no significant differences in the numbers of related bacteria after 2 months of hydrogen-rich water treatment.

Classification by family

In samples collected from the athletes after pre-treatment with hydrogen-rich water, the numbers of Acidaminococcaceae, Bacteriodaceae, Bifidobacteriaceae, Coriobacteriaceae, Desulforibrionaceae, Erysipelotrichaceae and Ruminococcaceae were higher than those in the hydrogen-rich water treatment group, with differences being observed in the number of Bifidobacteriaceae, Ruminococcaceae, Coriobacteriaceae and Erysipelotrichaceae. There was no difference in the number of Lachnospiraceae between the two groups. The number of Prevotellaceae in the hydrogen-rich water treatment group was higher than that in the control group. However, there were no significant differences in the number of these bacterial groups after 2 months of hydrogen-rich water treatment.

Classification by genus

In samples collected from the athletes after pre-treatment with hydrogen-rich water, the numbers of Bifidobacterium and Oscillibacter in the control group were higher than those in the hydrogen-rich water treatment group, with a difference being observed in the number of Bifidobacteriaceae. The number of Prevotella in the hydrogen-rich water treatment group was higher than that in the control group, although this difference was not significant. There were no significant differences in the number of these bacterial groups after 2 months of hydrogen-rich water treatment.

Effects of long-term consumption of hydrogen-rich water on gut flora diversity and abundance in juvenile female football players

The actual number of operational taxonomic units (sobs) and the ace, chao and shannon indices were determined, and then a dilution curve was drawn. The recorded changes indicated that the sobs, ace, chao and shannon indices of the control group were all higher than those of the hydrogen-rich water treatment group, suggesting that the abundance and diversity of the gut flora in the control group were higher than those in the hydrogen-rich water treatment group.

After 1 month of hydrogen-rich water treatment, the sobs, ace, and chao indices were higher in the hydrogen-rich water treatment group than those in the control group. The trend was slightly reversed, indicating that the abundance of gut flora was higher in the hydrogen-rich water treatment group than in the control group. The shannon index of the treatment group at that time was essentially the same as that in the control group, indicating that treatment with hydrogen-rich water could also enhance the diversity of the gut flora. After 2 months of hydrogen-rich water treatment, the sobs, ace, chao and shannon indices were much higher than those in the control group (P = 0.479, P = 0.710, P = 0.369, P = 0.369). Indicating that treatment with hydrogen-rich water can enhance the gut flora abundance and diversity of the gut flora (Figure 5).

An external file that holds a picture, illustration, etc. Object name is MGR-8-135-g005.jpg

Changes in gut flora diversity and abundance before and after hydrogen-rich water consumption.

Note: (A) The shift of sobs before and after hydrogenrich water consumption; (B) The shift of ace index before and after hydrogen-rich water consumption; (C) The shift of chao index before and after hydrogen-rich water consumption; (D) The shift of shannon index before and after hydrogen-rich water consumption.

Discussion

The existing experimental and clinical studies have shown that animals or humans need only to breathe hydrogen or drink or inject hydrogen-rich water to protect the heart, brain, liver, kidney, lung, and small intestine from ischaemia/reperfusion oxidative injury or inflammatory injury after cardiac organ transplantation.,

The potential biological effects of hydrogen in sports have drawn much attention from researchers in sports science. The beneficial protective effects of hydrogen-rich water on the body have been gradually confirmed in both animal and human experiments. Ostojic summarized the current applications of hydrogen in the field of sports, emphasizing that hydrogen

1) can effectively remove a large number of harmful free radicals generated through movement, thus enhancing the antioxidant capacity;

2) is an effective alkalizing agent in the internal environment that can effectively inhibit blood acidification induced by lactic acid accumulation in sports; and

3) is an important gas signalling molecule that can participate in physiological regulatory processes such as anti-inflammatory, anti-apoptotic, and anti-autophagy processes., This regulation does not involve the same signalling pathway as antioxidative stress.

Analysis of the effect of long-term consumption of hydrogen-rich water on routine indices of juvenile female football players

HGB is one of the classic indicators reflecting the level of endurance exercise. The shift of HGB after 4 weeks was caused by increases in the amount or intensity of exercise and seasonal factors during winter training. The HGB level began to gradually increase, suggesting that the athletes had adapted well to the winter training load. The increase in the HGB level was higher overall in the hydrogen-rich water treatment group suggested that long-term hydrogen-rich water treatment could help increase the HGB level.

Urea nitrogen is the final product of protein metabolism. The participation of protein catabolism in the energy supply is enhanced during long-term and high-intensity exercise, thus increasing the amount of urea nitrogen in the blood and urine with increased decomposition of proteins and amino acids. The shift of the BUN level of all 38 athletes increased slightly due to winter training and seasonal factors. After 8 weeks, the decrease in the serum urea nitrogen level and the increase in the HGB level indicated that long-term hydrogen-rich water treatment has beneficial effects on the physiological functions of athletes.

CK is the key enzyme in energy metabolism in skeletal muscle cells, whose activity directly affects the short-term maximum intensity of the exercise capacity. After a high-intensity muscle load, muscle soreness and serum CK levels are highly and positively correlated. Clarke et al. found that the level of CK in the serum of professional rugby athletes is markedly high. CK is an important index reflecting the exercise load, particularly that suffered by the skeletal muscle. Thus, CK could indirectly reflect the levels of injury and active repair of the skeletal muscle ultrastructure.

After 8 weeks, the level of serum CK in both the control and hydrogen-rich water treatment groups continued to decrease.

Analysis of the effect of long-term consumption of hydrogen-rich water on the serum oxidative response of juvenile female football players

Tsubone et al. compared the effects of drinking hydrogen-rich water on the levels of oxidative stress and antioxidant metabolites in the serum of British thoroughbred horses and found that hydrogen-rich water treatment had a beneficial antioxidant effect. Aoki et al. conducted studies on football players and showed that drinking hydrogen-rich water for 1 week could reduce exercise fatigue and lactic acid accumulation after exercise but had no significant effect on the oxidative response index.

Li et al. showed that hydrogen-rich water could significantly prolong the duration of exercise before exhaustion in rats and improve their exercise capacity, indicating a significant anti-fatigue effect.

Zhao and Zhang showed that supplementation of hydrogen-rich water at different times before, during, and after exercise exerted significant protective effects against oxidative stress injury in swimming athletes during high-intensity exercise. This supplementation of hydrogen-rich water can reduce the production of excessive free radicals and enhance the activity of antioxidant enzymes and the antioxidant capacity of the body, thereby promoting physical recovery after high-intensity exercise. Hu and Zhang showed that high-intensity intermittent training increases the concentration of O2 , •OH and H2O2. Hydrogen-rich water can significantly enhance the body’s inhibition of O2  and •OH, showing a higher rate of •OH inhibition, fully reflecting its selective antioxidant effect.

Li et al. found that hydrogen-rich water treatment could effectively reduce oxidative stress injury induced in skeletal muscle by severe exercise while improving the muscle ultrastructure.

Wang et al. reported that hydrogen-rich water treatment could up-regulate the expression of SIRT3, enhance the activity of antioxidant enzymes, and reduce the inflammatory response after centrifugal exercise.

MDA is one of the classic indicators reflecting the level of lipid peroxidation. After 8 weeks, the difference of serum MDA between the two groups was significant, it suggested that long-term hydrogen-rich water treatment exerts an antioxidant effect.

SOD is one of the classic indicators reflecting the free radical-scavenging antioxidant capacity. The SOD levels of both the control and hydrogen-rich water treatment groups slightly increased after 4 weeks. And the mean serum SOD level of the hydrogen-rich water treatment group was consistent higher than the control group after 8 weeks.

Serum antioxidant substances can be divided into the enzymatic antioxidant system and the non-enzymatic antioxidant system. The enzymatic antioxidant system mainly involves substances such as SOD, glutathione peroxidase, glutathione reductase, and catalase. The non-enzymatic antioxidant system mainly involves water-soluble substances, such as vitamin C, bilirubin, fat-soluble vitamin E, coenzyme Q, carotenoids, and flavonoid antioxidants. In terms of their function, serum antioxidant substances can be divided into three types: preventive antioxidants; capture-type antioxidants; and repair and regeneration antioxidants. The total antioxidant capacity represents the sum of the above substances and functions.

The observed changes in serum T-AOC suggested that 4 weeks of hydrogen-rich water treatment group indeed improved the free radical-scavenging ability of antioxidants. These results suggest that long-term hydrogen-rich water treatment exerts an antioxidant effect.

Analysis of the effect of long-term consumption of hydrogen-rich water on serum inflammatory indices of juvenile female football players

Inflammatory factors will increase, and inflammation will intensify during exercise due to increases in energy consumption, free radicals, and intensification of oxidative stress. However, there are three anti-inflammatory mechanisms that may be deployed in the course of exercise.

1) Exercise can increase energy consumption, thereby reducing visceral fat volume and alleviating the infiltration of fat into inflammatory lymphocytes.

2) Exercise can effectively increase the production and release of muscle-derived anti-inflammatory cytokines during skeletal muscle contraction; skeletal muscle accounts for 35–45% of the total body weight, and the regulatory effects of this major endocrine organ on human homeostasis cannot be ignored.

3) Exercise can effectively reduce toll-like receptor expression on the membrane surface of monocytes and macrophages, which may lead to a decreased downstream response, including reduced secretion of inflammatory agents, decreased expression of compatibility complexes in major organs, and decreases in co-stimulatory Mecules.,

These three effects can ensure that the levels of inflammatory agent factors in athletes participating in strenuous exercise will not increase and may even decrease. However, the effect of oxidative stress on the body will not be weakened. After 8 weeks of hydrogen-rich water treatment, the levels of IL-1, IL-6 and TNF-α in the hydrogen-rich water treatment group were lower than those in the control group and with significant differences between the two groups. Compared with the abovementioned changes in the oxidative stress indices, long-term hydrogen-rich water treatment showed a stronger anti-inflammatory effect in addition to an antioxidant effect.

Analysis of the effect of long-term consumption of hydrogen-rich water on gut flora components of juvenile female football players

Analysis of the structural components of the gut flora at different levels of classification in the two groups showed some differences between the two groups at different stages of the experiment. However, there were no significant changes in the structural components of flora between the two groups in terms of the oxidative response and the anti-inflammatory effect. These results suggest that two months of hydrogen-rich water treatment did not significantly change the structural components of the gut flora of the juvenile female football players. Differences in the composition of the flora between the two groups are an expected result of differences in age, particularly regarding the number of training years.

In 2007, Ohsawa et al. suggested that the selective antioxidant activity of hydrogen-rich water, and particularly its selective elimination of •OH, is superior to that of traditional antioxidants, while its overall antioxidant capacity is much lower than that of traditional antioxidants. Therefore, the effect of 2 months of hydrogen-rich water treatment on the regulation of gut flora was also much lower than that of established supplements such as resveratrol, grape antioxidant dietary fibre, selenium supplements, anthocyanin, and pomegranate peel polyphenols.,,,,,

Analysis of the effect of long-term consumption of hydrogen-rich water on gut flora diversity and abundance in juvenile female football players

As a complex and variable micro-ecological system, the gut flora is constantly undergoing changes in its dynamic equilibrium. The richness and diversity of its components are important indicators of the health of this ecological system. The richness of the gut flora in patients with inflammatory bowel disorder is decreased in elderly and obese individuals. Le Chatelier et al. compared the composition of the gut flora of 123 non-obese and 169 obese Danes and found that the gut flora richness of these two groups differed, as did the number of genes in their gut flora. Individuals with lower gut flora richness were found to exhibit more significant obesity characteristics, insulin resistance, and lipid metabolic disorders as well as more severe inflammatory phenotypes.,

As a strong stressor, long-term and high-intensity professional sports training eventually has a corresponding impact on the gut flora. Clarke et al. found that professional rugby athletes exhibited a more abundant gut flora in their intestines compared with control groups of individuals with a body mass index (BMI) < 25 or BMI > 28. In samples from the professional rugby athletes, the total microorganisms identified came from 22 phyla, 68 families, and 113 genera. In the control group with a BMI < 25, a total of 11 phyla, 33 families, and 65 genera of microorganisms were detected, whereas the microorganisms in the control group with a BMI > 28 came from 9 phyla, 33 families, and 61 genera. The richness and diversity of the gut flora were lowest in obese individuals, while the professional athletes exhibited the highest richness and diversity levels.

Before treatment with hydrogen-rich water, the richness and diversity of the gut flora were higher in the control group (3.4 ± 1.51 years of training) than in the treatment group (1.21 ± 0.6 years of training), and the training period was the main factor leading to this difference. Individuals who had a longer training period exhibited a higher richness and diversity in their gut flora; this trend is consistent with the results of Clarke et al.

After 4 weeks of treatment with hydrogen-rich water, the trend was slightly reversed. The richness and diversity of the gut flora were higher in athletes who had a shorter training period than those who had a longer training period. This finding indicated that drinking hydrogen-rich water for a long period of time may plays an important role in enhancing the richness and diversity of the gut flora. At the same time, the levels of serum MDA, IL-1, IL-6 and TNF-α decreased in the treatment group, and the SOD, T-AOC level increased. Such changes are closely related to changes in the richness and diversity of the gut flora.

After 8 weeks of treatment with hydrogen-rich water, the richness and diversity of the gut flora were still higher in athletes who had a shorter training period than in control individuals who had a longer training. Additionally, the serum levels of MDA, IL-1, IL-6 and TNF-α decreased, and the levels of HGB SOD, T-AOC level increased to various degrees in the hydrogen-rich water treatment group. The trend of favourable changes of motor function indices, the oxidative response index, and inflammatory factor indices were almost consistent with the changes in the richness and diversity of the gut flora.

The above results showed that long-term consumption of hydrogen-rich water not only exerts certain antioxidant and anti-inflammatory effects but also enhances the diversity and abundance of the gut flora of the subjects.

Footnotes

Funding: The study was supported by the National Basic Research Project of China (973 Program), No. 2012CB518200 (to ZCG), the General Program of the Natural Science Foundation of China, No. 81371232, 81573251 (to ZCG), and the Special Key Programs for Science and Technology of China, No. 2012ZX09102301-016 and 2014ZX09J14107-05B (to ZCG).

Conflicts of interest

There is no conflict of interest.

Financial support

The study was supported by The National Basic Research Project of China (973 Program), No. 2012CB518200, the General Program of the Natural Science Foundation of China, No. 81371232, 81573251, and the Special Key Programs for Science and Technology of China, No. 2012ZX09102301-016, 2014ZX09J14107-05B.

Institutional review board statement

The institutional review board approval of Suzhou Sports School was obtained for this study.

Declaration of participant consent

The authors certify that they have obtained participant consent forms. In the form, participants have given their consent for their images andother clinical information to be reported in the journal. The participants understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Reporting statement

This study follows the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

Biostatistics statement

The statistical methods of this study were reviewed by the biostatistician of the State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing, China.

Copyright license agreement

The Copyright License Agreement has been signed by all authors before publication.

Data sharing statement

Datasets analyzed during the current study are available from the corresponding author on reasonable request.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

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Link to Publisher's site
. 2018 Oct-Dec; 8(4): 135–143.
Published online 2019 Jan 9. doi: 10.4103/2045-9912.248263
PMCID: PMC6352569
PMID: 30713665
Effects of the long-term consumption of hydrogen-rich water on the antioxidant activity and the gut flora in female juvenile soccer players from Suzhou, China
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