Hydrogen-rich water to improve mood, anxiety and autonomic nerve function in everyday lifeScientific Research

Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life

Kei Mizuno¹, Akihiro T Sasaki², Kyoko Ebisu³, Kanako Tajima⁴, Osami Kajimoto⁵, Junzo Nojima⁶, Hirohiko Kuratsune⁷, Hiroshi Hori⁸, Yasuyoshi Watanabe M.D., Ph.D. ⁹

DOI: 10.4103/2045-9912.222448

 

Abstract

Everyone strives for a healthy and vibrant life. In order to improve quality of life (QOL), maintain health, and prevent various diseases, it is important to assess the impact of potential QOL-increasing factors. Chronic oxidative stress and inflammation lead to worsening central nervous system function, resulting in poor quality of life. In healthy individuals, aging, work stress, and multiple hours of cognitive load also contribute to increased oxidative stress, suggesting that preventing the build-up of daily stress and work-induced oxidative stress contributes to the maintenance of quality of life and contributes to Improve aging. Hydrogen has antioxidant properties that prevent inflammation, which can help improve quality of life. This study aimed to investigate the effect of drinking hydrogen-rich water (HRW) on quality of life in adult volunteers through psychophysiological tests including questionnaires and tests of autonomic and cognitive function. In this double-blind, placebo-controlled, two-way crossover study, 26 volunteers (13 women, 13 men; mean age 34.4 ± 9.9 years) were randomized to oral HRW (600 mL/day) or placebo Water (PLW, 600 ml/day) for 4 weeks. The rate of change in K6 score and resting-state sympathetic activity (post-treatment/pre-treatment) after HRW administration was significantly lower than after PLW administration.

 

Results

These results suggest that HRW may improve quality of life by increasing the effects of central nervous system function, including mood, anxiety, and autonomic function.

References

Starke RM, Chalouhi N, Ali MS, et al. The role of oxidative stress in cerebral aneurysm formation and rupture. Curr Neurovasc Res. 2013;10:247-255.
2.	Buchholz BM, Kaczorowski DJ, Sugimoto R, et al. Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am J Transplant. 2008;8:2015-2024.
3.	Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res. 2010;44:971-982.   [PUBMED]
4.	Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13:688-694.   [PUBMED]
5.	Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr. 2010;46:140-149.
6.	Song G, Li M, Sang H, et al. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. J Lipid Res. 2013;54:1884-1893.   [PUBMED]
7.	Kajiyama S, Hasegawa G, Asano M, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res. 2008;28:137-143.
8.	Ito M, Ibi T, Sahashi K, Ichihara M, Ito M, Ohno K. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med Gas Res. 2011;1:24.
9.	Aoki K, Nakao A, Adachi T, Matsui Y, Miyakawa S. Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Med Gas Res. 2012;2:12.
10.	Ben Moussa S, Rouatbi S, Ben Saad H. Incapacity, handicap, and oxidative stress markers of male smokers with and without COPD. Respir Care. 2016;61:668-679.
11.	Fuchs-Tarlovsky V, Rivera MA, Altamirano KA, Lopez-Alvarenga JC, Ceballos-Reyes GM. Antioxidant supplementation has a positive effect on oxidative stress and hematological toxicity during oncology treatment in cervical cancer patients. Support Care Cancer. 2013;21:1359-1363.   [PUBMED]
12.	Kang KM, Kang YN, Choi IB, et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res. 2011;1:11.
13.	Inal ME, Kanbak G, Sunal E. Antioxidant enzyme activities and malondialdehyde levels related to aging. Clin Chim Acta. 2001;305:75-80.   [PUBMED]
14.	Casado Á, Castellanos A, López-Fernández ME, et al. Determination of oxidative and occupational stress in palliative care workers. Clin Chem Lab Med. 2011;49:471-477.
15.	Ishihara I, Nakano M, Ikushima M, et al. Effect of work conditions and work environments on the formation of 8-OH-dG in nurses and non-nurse female workers. J UOEH. 2008;30:293-308.
16.	Fukuda S, Nojima J, Motoki Y, et al. A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity. Biol Psychol. 2016;118:88-93.
17.	Ostojic SM, Stojanovic MD. Hydrogen-rich water affected blood alkalinity in physically active men. Res Sports Med. 2014;22:49-60.
18.	Chalder T, Berelowitz G, Pawlikowska T, et al. Development of a fatigue scale. J Psychosom Res. 1993;37:147-153.
19.	Fukuda S, Takashima S, Iwase M, Yamaguchi K, Kuratsune H, Watanabe Y. Development and validation of a new fatigue scale for fatigued subjects with and without chronic fatigue syndrome. In: Watanabe Y, Evengård B, Natelson BH, Jason LA, Kuratsune H, eds. Fatigue Science for Human Health. New York: Springer. 2008:89-102.
20.	Kessler RC, Andrews G, Colpe LJ, et al. Short screening scales to monitor population prevalences and trends in non-specific psychological distress. Psychol Med. 2002;32:959-976.
21.	Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385-401.
22.	Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193-213.
23.	Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540-545.
24.	Doi Y, Minowa M, Uchiyama M, et al. Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects. Psychiatry Res. 2000;97:165-172.   [PUBMED]
25.	Furukawa TA, Kawakami N, Saitoh M, et al. The performance of the Japanese version of the K6 and K10 in the World Mental Health Survey Japan. Int J Methods Psychiatr Res. 2008;17:152-158.
26.	Takegami M, Suzukamo Y, Wakita T, et al. Development of a Japanese version of the Epworth Sleepiness Scale (JESS) based on item response theory. Sleep Med. 2009;10:556-565.
27.	Tanaka M, Fukuda S, Mizuno K, et al. Reliability and validity of the Japanese version of the Chalder Fatigue Scale among youth in Japan. Psychol Rep. 2008;103:682-690.   [PUBMED]
28.	Shima S, Shikano T, Kitamura T. New self-rating scales for depression. Clin Psychiatry. 1985;27:717-723.
29.	Kanaya N, Hirata N, Kurosawa S, Nakayama M, Namiki A. Differential effects of propofol and sevoflurane on heart rate variability. Anesthesiology. 2003;98:34-40.   [PUBMED]
30.	Takusagawa M, Komori S, Umetani K, et al. Alterations of autonomic nervous activity in recurrence of variant angina. Heart. 1999;82:75-81.
31.	Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981;213:220-222.   [PUBMED]
32.	Pomeranz B, Macaulay RJ, Caudill MA, et al. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol. 1985;248:H151-153.   [PUBMED]
33.	Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84:482-492.
34.	Appel ML, Berger RD, Saul JP, Smith JM, Cohen RJ. Beat to beat variability in cardiovascular variables: noise or music? J Am Coll Cardiol. 1989;14:1139-1148.   [PUBMED]
35.	Tanaka M, Tajima S, Mizuno K, et al. Frontier studies on fatigue, autonomic nerve dysfunction, and sleep-rhythm disorder. J Physiol Sci. 2015;65:483-498.
36.	Montano N, Porta A, Cogliati C, et al. Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior. Neurosci Biobehav Rev. 2009;33:71-80.
37.	Perini R, Veicsteinas A. Heart rate variability and autonomic activity at rest and during exercise in various physiological conditions. Eur J Appl Physiol. 2003;90:317-325.
38.	Tajima K, Tanaka M, Mizuno K, Okada N, Rokushima K, Watanabe Y. Effects of bathing in micro-bubbles on recovery from moderate mental fatigue. Ergonomia IJE&HF. 2008;30:134-145.
39.	Mizuno K, Tanaka M, Tajima K, Okada N, Rokushima K, Watanabe Y. Effects of mild-stream bathing on recovery from mental fatigue. Med Sci Monit. 2010;16:Cr8-14.   [PUBMED]
40.	Mizuno K, Tanaka M, Yamaguti K, Kajimoto O, Kuratsune H, Watanabe Y. Mental fatigue caused by prolonged cognitive load associated with sympathetic hyperactivity. Behav Brain Funct. 2011;7:17.
41.	Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93:1043-1065.   [PUBMED]
42.	Kume S, Nishimura Y, Mizuno K, et al. Music improves subjective feelings leading to cardiac autonomic nervous modulation: a pilot study. Front Neurosci. 2017;11:108.
43.	Kajimoto O. Development of a method of evaluation of fatigue and its economic impacts. In: Watanabe Y, Evengård B, Natelson BH, Jason LA, Kuratsune H, eds. Fatigue Science for Human Health. New York: Springer. 2008:33-46.
44.	Mizuno K, Watanabe Y. Neurocognitive impairment in childhood chronic fatigue syndrome. Front Physiol. 2013;4:87.
45.	Mizuno K, Tanaka M, Fukuda S, Imai-Matsumura K, Watanabe Y. Relationship between cognitive functions and prevalence of fatigue in elementary and junior high school students. Brain Dev. 2011;33:470-479.
46.	Kawatani J, Mizuno K, Shiraishi S, et al. Cognitive dysfunction and mental fatigue in childhood chronic fatigue syndrome–a 6-month follow-up study. Brain Dev. 2011;33:832-841.
47.	Mizuno K, Tanaka M, Fukuda S, Sasabe T, Imai-Matsumura K, Watanabe Y. Changes in cognitive functions of students in the transitional period from elementary school to junior high school. Brain Dev. 2011;33:412-420.
48.	Trotti R, Carratelli M, Barbieri M. Performance and clinical application of a new, fast method for the detection of hydroperoxides in serum. Panminerva Med. 2002;44:37-40.
49.	Nojima J, Motoki Y, Tsuneoka H, et al. ‘Oxidation stress index’ as a possible clinical marker for the evaluation of non-Hodgkin lymphoma. Br J Haematol. 2011;155:528-530.   [PUBMED]
50.	Li J, Wang C, Zhang JH, Cai JM, Cao YP, Sun XJ. Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer’s disease by reduction of oxidative stress. Brain Res. 2010;1328:152-161.   [PUBMED]
51.	Matsumoto A, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H. Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice. Sci Rep. 2013;3:3273.   [PUBMED]
52.	Tomofuji T, Kawabata Y, Kasuyama K, et al. Effects of hydrogen-rich water on aging periodontal tissues in rats. Sci Rep. 2014;4:5534.   [PUBMED]
53.	Watanabe Y, Kuratsune H, Kajimoto O. Desmond Biochemical indices of fatigue for anti-fatigue strategies and products. In: Matthews G, Desmond PA, Neubauer C, Hancoc PA, eds. The Handbook of Operator Fatigue. CRC Press. 2012:209-224.
54.	Ataka S, Tanaka M, Nozaki S, et al. Effects of Applephenon and ascorbic acid on physical fatigue. Nutrition. 2007;23:419-423.
55.	Mizuno K, Tanaka M, Nozaki S, et al. Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition. 2008;24:293-299.
56.	Mizuma H, Tanaka M, Nozaki S, et al. Daily oral administration of crocetin attenuates physical fatigue in human subjects. Nutr Res. 2009;29:145-150.
57.	García-Niño WR, Zatarain-Barrón ZL, Hernández-Pando R, Vega-Garcia CC, Tapia E, Pedraza-Chaverri J. Oxidative stress markers and histological analysis in diverse organs from rats treated with a hepatotoxic dose of Cr(VI): effect of curcumin. Biol Trace Elem Res. 2015;167:130-145.
58.	Atmaca M, Tezcan E, Kuloglu M, Ustundag B, Tunckol H. Antioxidant enzyme and malondialdehyde values in social phobia before and after citalopram treatment. Eur Arch Psychiatry Clin Neurosci. 2004;254:231-235.   [PUBMED]
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63.	Pandya CD, Howell KR, Pillai A. Antioxidants as potential therapeutics for neuropsychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:214-223.
64.	Nakatomi Y, Mizuno K, Ishii A, et al. Neuroinflammation in patients with chronic fatigue syndrome/myalgic encephalomyelitis: an (1)(1)C-(R)-PK11195 PET study. J Nucl Med. 2014;55:945-950.   [PUBMED]
65.	Castanon N, Luheshi G, Laye S. Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity. Front Neurosci. 2015;9:229.
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68.	Tian Y, Guo S, Zhang Y, Xu Y, Zhao P, Zhao X. Effects of hydrogen-rich saline on hepatectomy-induced postoperative cognitive dysfunction in old mice. Mol Neurobiol. 2017;54:2579-2584.   [PUBMED]
69.	Johnson AW, Jaaro-Peled H, Shahani N, et al. Cognitive and motivational deficits together with prefrontal oxidative stress in a mouse model for neuropsychiatric illness. Proc Natl Acad Sci USA. 2013;110:12462-12467.   [PUBMED]
70.	Bierhaus A, Wolf J, Andrassy M, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci USA. 2003;100:1920-1925.   [PUBMED]
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72.	Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun. 2007;21:901-912.
73.	Mizuno K, Tajima K, Watanabe Y, Kuratsune H. Fatigue correlates with the decrease in parasympathetic sinus modulation induced by a cognitive challenge. Behav Brain Funct. 2014;10:25.
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Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life

Kei Mizuno¹, Akihiro T Sasaki², Kyoko Ebisu³, Kanako Tajima⁴, Osami Kajimoto⁵, Junzo Nojima⁶, Hirohiko Kuratsune⁷, Hiroshi Hori⁸, Yasuyoshi Watanabe M.D., Ph.D. ⁹

DOI: 10.4103/2045-9912.222448

 

Abstract

Everyone strives for a healthy and vibrant life. In order to improve quality of life (QOL), maintain health, and prevent various diseases, it is important to assess the impact of potential QOL-increasing factors. Chronic oxidative stress and inflammation lead to worsening central nervous system function, resulting in poor quality of life. In healthy individuals, aging, work stress, and multiple hours of cognitive load also contribute to increased oxidative stress, suggesting that preventing the build-up of daily stress and work-induced oxidative stress contributes to the maintenance of quality of life and contributes to Improve aging. Hydrogen has antioxidant properties that prevent inflammation, which can help improve quality of life. This study aimed to investigate the effect of drinking hydrogen-rich water (HRW) on quality of life in adult volunteers through psychophysiological tests including questionnaires and tests of autonomic and cognitive function. In this double-blind, placebo-controlled, two-way crossover study, 26 volunteers (13 women, 13 men; mean age 34.4 ± 9.9 years) were randomized to oral HRW (600 mL/day) or placebo Water (PLW, 600 ml/day) for 4 weeks. The rate of change in K6 score and resting-state sympathetic activity (post-treatment/pre-treatment) after HRW administration was significantly lower than after PLW administration.

 

Results

These results suggest that HRW may improve quality of life by increasing the effects of central nervous system function, including mood, anxiety, and autonomic function.

References

Starke RM, Chalouhi N, Ali MS, et al. The role of oxidative stress in cerebral aneurysm formation and rupture. Curr Neurovasc Res. 2013;10:247-255.
2.	Buchholz BM, Kaczorowski DJ, Sugimoto R, et al. Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am J Transplant. 2008;8:2015-2024.
3.	Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res. 2010;44:971-982.   [PUBMED]
4.	Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13:688-694.   [PUBMED]
5.	Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr. 2010;46:140-149.
6.	Song G, Li M, Sang H, et al. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. J Lipid Res. 2013;54:1884-1893.   [PUBMED]
7.	Kajiyama S, Hasegawa G, Asano M, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res. 2008;28:137-143.
8.	Ito M, Ibi T, Sahashi K, Ichihara M, Ito M, Ohno K. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med Gas Res. 2011;1:24.
9.	Aoki K, Nakao A, Adachi T, Matsui Y, Miyakawa S. Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Med Gas Res. 2012;2:12.
10.	Ben Moussa S, Rouatbi S, Ben Saad H. Incapacity, handicap, and oxidative stress markers of male smokers with and without COPD. Respir Care. 2016;61:668-679.
11.	Fuchs-Tarlovsky V, Rivera MA, Altamirano KA, Lopez-Alvarenga JC, Ceballos-Reyes GM. Antioxidant supplementation has a positive effect on oxidative stress and hematological toxicity during oncology treatment in cervical cancer patients. Support Care Cancer. 2013;21:1359-1363.   [PUBMED]
12.	Kang KM, Kang YN, Choi IB, et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res. 2011;1:11.
13.	Inal ME, Kanbak G, Sunal E. Antioxidant enzyme activities and malondialdehyde levels related to aging. Clin Chim Acta. 2001;305:75-80.   [PUBMED]
14.	Casado Á, Castellanos A, López-Fernández ME, et al. Determination of oxidative and occupational stress in palliative care workers. Clin Chem Lab Med. 2011;49:471-477.
15.	Ishihara I, Nakano M, Ikushima M, et al. Effect of work conditions and work environments on the formation of 8-OH-dG in nurses and non-nurse female workers. J UOEH. 2008;30:293-308.
16.	Fukuda S, Nojima J, Motoki Y, et al. A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity. Biol Psychol. 2016;118:88-93.
17.	Ostojic SM, Stojanovic MD. Hydrogen-rich water affected blood alkalinity in physically active men. Res Sports Med. 2014;22:49-60.
18.	Chalder T, Berelowitz G, Pawlikowska T, et al. Development of a fatigue scale. J Psychosom Res. 1993;37:147-153.
19.	Fukuda S, Takashima S, Iwase M, Yamaguchi K, Kuratsune H, Watanabe Y. Development and validation of a new fatigue scale for fatigued subjects with and without chronic fatigue syndrome. In: Watanabe Y, Evengård B, Natelson BH, Jason LA, Kuratsune H, eds. Fatigue Science for Human Health. New York: Springer. 2008:89-102.
20.	Kessler RC, Andrews G, Colpe LJ, et al. Short screening scales to monitor population prevalences and trends in non-specific psychological distress. Psychol Med. 2002;32:959-976.
21.	Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385-401.
22.	Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193-213.
23.	Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540-545.
24.	Doi Y, Minowa M, Uchiyama M, et al. Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects. Psychiatry Res. 2000;97:165-172.   [PUBMED]
25.	Furukawa TA, Kawakami N, Saitoh M, et al. The performance of the Japanese version of the K6 and K10 in the World Mental Health Survey Japan. Int J Methods Psychiatr Res. 2008;17:152-158.
26.	Takegami M, Suzukamo Y, Wakita T, et al. Development of a Japanese version of the Epworth Sleepiness Scale (JESS) based on item response theory. Sleep Med. 2009;10:556-565.
27.	Tanaka M, Fukuda S, Mizuno K, et al. Reliability and validity of the Japanese version of the Chalder Fatigue Scale among youth in Japan. Psychol Rep. 2008;103:682-690.   [PUBMED]
28.	Shima S, Shikano T, Kitamura T. New self-rating scales for depression. Clin Psychiatry. 1985;27:717-723.
29.	Kanaya N, Hirata N, Kurosawa S, Nakayama M, Namiki A. Differential effects of propofol and sevoflurane on heart rate variability. Anesthesiology. 2003;98:34-40.   [PUBMED]
30.	Takusagawa M, Komori S, Umetani K, et al. Alterations of autonomic nervous activity in recurrence of variant angina. Heart. 1999;82:75-81.
31.	Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981;213:220-222.   [PUBMED]
32.	Pomeranz B, Macaulay RJ, Caudill MA, et al. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol. 1985;248:H151-153.   [PUBMED]
33.	Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84:482-492.
34.	Appel ML, Berger RD, Saul JP, Smith JM, Cohen RJ. Beat to beat variability in cardiovascular variables: noise or music? J Am Coll Cardiol. 1989;14:1139-1148.   [PUBMED]
35.	Tanaka M, Tajima S, Mizuno K, et al. Frontier studies on fatigue, autonomic nerve dysfunction, and sleep-rhythm disorder. J Physiol Sci. 2015;65:483-498.
36.	Montano N, Porta A, Cogliati C, et al. Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior. Neurosci Biobehav Rev. 2009;33:71-80.
37.	Perini R, Veicsteinas A. Heart rate variability and autonomic activity at rest and during exercise in various physiological conditions. Eur J Appl Physiol. 2003;90:317-325.
38.	Tajima K, Tanaka M, Mizuno K, Okada N, Rokushima K, Watanabe Y. Effects of bathing in micro-bubbles on recovery from moderate mental fatigue. Ergonomia IJE&HF. 2008;30:134-145.
39.	Mizuno K, Tanaka M, Tajima K, Okada N, Rokushima K, Watanabe Y. Effects of mild-stream bathing on recovery from mental fatigue. Med Sci Monit. 2010;16:Cr8-14.   [PUBMED]
40.	Mizuno K, Tanaka M, Yamaguti K, Kajimoto O, Kuratsune H, Watanabe Y. Mental fatigue caused by prolonged cognitive load associated with sympathetic hyperactivity. Behav Brain Funct. 2011;7:17.
41.	Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93:1043-1065.   [PUBMED]
42.	Kume S, Nishimura Y, Mizuno K, et al. Music improves subjective feelings leading to cardiac autonomic nervous modulation: a pilot study. Front Neurosci. 2017;11:108.
43.	Kajimoto O. Development of a method of evaluation of fatigue and its economic impacts. In: Watanabe Y, Evengård B, Natelson BH, Jason LA, Kuratsune H, eds. Fatigue Science for Human Health. New York: Springer. 2008:33-46.
44.	Mizuno K, Watanabe Y. Neurocognitive impairment in childhood chronic fatigue syndrome. Front Physiol. 2013;4:87.
45.	Mizuno K, Tanaka M, Fukuda S, Imai-Matsumura K, Watanabe Y. Relationship between cognitive functions and prevalence of fatigue in elementary and junior high school students. Brain Dev. 2011;33:470-479.
46.	Kawatani J, Mizuno K, Shiraishi S, et al. Cognitive dysfunction and mental fatigue in childhood chronic fatigue syndrome–a 6-month follow-up study. Brain Dev. 2011;33:832-841.
47.	Mizuno K, Tanaka M, Fukuda S, Sasabe T, Imai-Matsumura K, Watanabe Y. Changes in cognitive functions of students in the transitional period from elementary school to junior high school. Brain Dev. 2011;33:412-420.
48.	Trotti R, Carratelli M, Barbieri M. Performance and clinical application of a new, fast method for the detection of hydroperoxides in serum. Panminerva Med. 2002;44:37-40.
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