Effectiveness of hydrogen-rich water in individuals with potential metabolic syndromeScientific Research

Effectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome—An Open Label Pilot Study

Abstract

Metabolic syndrome is characterized by cardiometabolic risk factors, including obesity, insulin resistance, hypertension, and dyslipidemia. It is well known that oxidative stress plays an important role in the pathogenesis of metabolic syndrome. The purpose of this study was to investigate the effectiveness of hydrogen-enriched water (1.5-2 L/day) in an 8-week open-label study in 20 subjects with underlying metabolic syndrome. Hydrogen-rich water is prepared by placing metallic magnesium rods in drinking water (hydrogen concentration; 0.55-0.65 mM) through the following chemical reaction; Mg + 2H2O → Mg(OH)2 + H2. After drinking hydrogen-rich water for 8 weeks, the antioxidant enzyme superoxide dismutase (SOD) in urine increased by 39% (p<0.05) and thiobarbituric acid reactive substances (TBARS) decreased by 43% (p<0.05) ). In addition, subjects showed an 8% increase in high-density lipoprotein (HDL) cholesterol from baseline to week  4 and a 13% decrease in total cholesterol/HDL cholesterol. Fasting blood glucose levels did not change during the 8-week study. In conclusion, drinking hydrogen-rich water represents a potential metabolic syndrome treatment and prevention strategy. Portable magnesium bars are a safe, simple, and effective way to provide study participants with hydrogen-rich water for daily drinking.

References

• • [1] Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., and Shimomura, I.: Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest., 114, 1752–1761, 2004.

• • [2] Holvoet, P., Lee, D.H., Steffes, M., Gross, M., and Jacobs, D.R.Jr.: Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA, 299, 2287–2293, 2008.

• • [3] Ford, E.S., Giles, W.H., and Dietz, W.H.: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA, 287, 356–359, 2002.

• • [4] Grundy, S.M., Brewer, H.B. Jr., Cleeman, J.I., Smith, S.C.Jr., and Lenfant, C.: Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation, 109, 433–438, 2004.

• • [5] Dean, R.T., Fu, S., Stocker, R., and Davies, M.J.: Biochemistry and pathology of radical-mediated protein oxidation. Biochem. J., 324, 1–18, 1997.

• • [6] Halliwell, B., Gutteridge, J.M., and Cross, C.E.: Free radicals, antioxidants, and human disease: where are we now?. J. Lab. Clin. Med., 119, 598–620, 1992.

• • [7] Ford, E.S., Mokdad, A.H., Giles, W.H., and Brown, D.W.: The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. Diabetes, 52, 2346–2352, 2003.

• • [8] Villeponteau, B., Cockrell, R., and Feng, J.: Nutraceutical interventions may delay aging and the age-related diseases. Exp. Gerontol., 35, 1405–1417, 2000.

• • [9] Halliwell, B.: Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am. J. Med., 91, 14S–22S, 1991.

• • [10] Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., Katsura, K., Katayama, Y., Asoh, S., and Ohta, S.: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med., 13, 688–694, 2007.

• • [11] Buchholz, B.M., Kaczorowski, D.J., Sugimoto, R., Yang, R., Wang, Y., Billiar, T.R., McCurry, K.R., Bauer, A.J., and Nakao, A.: Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am. J. Transplant., 8, 2015–2024, 2008.

• • [12] N.A.S.A.: Safety Standard for Hydrogen and Hydrogen Systems. National Aeronautics and Space Administration, 2005.

• • [13] Ohsawa, I., Nishimaki, K., Yamagata, K., Ishikawa, M., and Ohta, S.: Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem. Biophys. Res. Commun., 377, 1195–1198, 2008.

• • [14] Nakashima-Kamimura, N., Mori, T., Ohsawa, I., Asoh, S., and Ohta, S.: Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer. Chemother. Pharmacol., 64, 753–761, 2009.

• • [15] Sato, Y., Kajiyama, S., Amano, A., Kondo, Y., Sasaki, T., Handa, S., Takahashi, R., Fukui, M., Hasegawa, G., Nakamura, N., Fujinawa, H., Mori, T., Ohta, M., Obayashi, H., Maruyama, N., and Ishigami, A.: Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem. Biophys. Res. Commun., 375, 346–350, 2008.

• • [16] Cardinal, J.S., Zhan, J., Wang, Y., Sugimoto, R., Tsung, A., McCurry, K.R., Billiar, T.R., and Nakao, A.: Oral administration of hydrogen water prevents chronic allograft nephropathy in renal transplantation. Kidney Int., 2009, in press.

• • [17] Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., Kitawaki, J., Imai, S., Nakano, K., Ohta, M., Adachi, T., Obayashi, H., and Yoshikawa, T.: Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr. Res., 28, 137–143, 2008.

• • [18] Yagi, K.: Simple procedure for specific assay of lipid hydroperoxides in serum or plasma. Methods. Mol. Biol., 108, 107–110, 1998.

• • [19] Loft, S., Fischer-Nielsen, A., Jeding, I.B., Vistisen, K., and Poulsen, H.E.: 8-Hydroxydeoxyguanosine as a urinary biomarker of oxidative DNA damage. J. Toxicol. Environ. Health., 40, 391–404, 1993.

• • [20] Kinnula, V.L. and Crapo, J.D.: Superoxide dismutases in the lung and human lung diseases. Am. J. Respir. Crit. Care. Med., 167, 1600–1619, 2003.

• • [21] Noor, R., Mittal, S., and Iqbal, J.: Superoxide dismutase—applications and relevance to human diseases. Med. Sci. Monit., 8, RA210–215, 2002.

• • [22] Fukai, T., Folz, R.J., Landmesser, U., and Harrison, D.G.: Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc. Res., 55, 239–249, 2002.

• • [23] Batiste, M.C. and Schaefer, E.J.: Diagnosis and management of lipoprotein abnormalities. Nutr. Clin. Care, 5, 115–123, 2002.

• • [24] Whitfield, J.B.: Gamma glutamyl transferase. Crit. Rev. Clin. Lab. Sci., 38, 263–355, 2001.

• • [25] Lee, D.H., Blomhoff, R., and Jacobs, D.R.Jr.: Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic. Res., 38, 535–539, 2004.

• • [26] Schwertner, H.A., Jackson, W.G., and Tolan, G.: Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin. Chem., 40, 18–23, 1994.

• • [27] Madhavan, M., Wattigney, W.A., Srinivasan, S.R., and Berenson, G.S.: Serum bilirubin distribution and its relation to cardiovascular risk in children and young adults. Atherosclerosis, 131, 107–113, 1997.

• • [28] Tenhunen, R., Marver, H.S., and Schmid, R.: The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. U.S.A., 61, 748–755, 1968.

• • [29] Otterbein, L.E., Soares, M.P., Yamashita, K., and Bach, F.H.: Heme oxygenase-1: unleashing the protective properties of heme. Trends. Immunol., 24, 449–455, 2003.

• [30] Dilsiz, N., Olcucu, A., Cay, M., Naziroglu, M., and Cobanoglu, D.: Protective effects of selenium, vitamin C and vitamin E against oxidative stress of cigarette smoke in rats. Cell Biochem. Funct., 17, 1–7, 1999.

Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., and Shimomura, I.: Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest., 114, 1752–1761, 2004.

[2] Holvoet, P., Lee, D.H., Steffes, M., Gross, M., and Jacobs, D.R.Jr.: Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA, 299, 2287–2293, 2008.

[3] Ford, E.S., Giles, W.H., and Dietz, W.H.: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA, 287, 356–359, 2002.

[4] Grundy, S.M., Brewer, H.B. Jr., Cleeman, J.I., Smith, S.C.Jr., and Lenfant, C.: Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation, 109, 433–438, 2004.

[5] Dean, R.T., Fu, S., Stocker, R., and Davies, M.J.: Biochemistry and pathology of radical-mediated protein oxidation. Biochem. J., 324, 1–18, 1997.

[6] Halliwell, B., Gutteridge, J.M., and Cross, C.E.: Free radicals, antioxidants, and human disease: where are we now?. J. Lab. Clin. Med., 119, 598–620, 1992.

[7] Ford, E.S., Mokdad, A.H., Giles, W.H., and Brown, D.W.: The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. Diabetes, 52, 2346–2352, 2003.

[8] Villeponteau, B., Cockrell, R., and Feng, J.: Nutraceutical interventions may delay aging and the age-related diseases. Exp. Gerontol., 35, 1405–1417, 2000.

[9] Halliwell, B.: Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am. J. Med., 91, 14S–22S, 1991.

[10] Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., Katsura, K., Katayama, Y., Asoh, S., and Ohta, S.: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med., 13, 688–694, 2007.

[11] Buchholz, B.M., Kaczorowski, D.J., Sugimoto, R., Yang, R., Wang, Y., Billiar, T.R., McCurry, K.R., Bauer, A.J., and Nakao, A.: Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am. J. Transplant., 8, 2015–2024, 2008.

[12] N.A.S.A.: Safety Standard for Hydrogen and Hydrogen Systems. National Aeronautics and Space Administration, 2005.

[13] Ohsawa, I., Nishimaki, K., Yamagata, K., Ishikawa, M., and Ohta, S.: Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem. Biophys. Res. Commun., 377, 1195–1198, 2008.

[14] Nakashima-Kamimura, N., Mori, T., Ohsawa, I., Asoh, S., and Ohta, S.: Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer. Chemother. Pharmacol., 64, 753–761, 2009.

[15] Sato, Y., Kajiyama, S., Amano, A., Kondo, Y., Sasaki, T., Handa, S., Takahashi, R., Fukui, M., Hasegawa, G., Nakamura, N., Fujinawa, H., Mori, T., Ohta, M., Obayashi, H., Maruyama, N., and Ishigami, A.: Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem. Biophys. Res. Commun., 375, 346–350, 2008.

[16] Cardinal, J.S., Zhan, J., Wang, Y., Sugimoto, R., Tsung, A., McCurry, K.R., Billiar, T.R., and Nakao, A.: Oral administration of hydrogen water prevents chronic allograft nephropathy in renal transplantation. Kidney Int., 2009, in press.

[17] Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., Kitawaki, J., Imai, S., Nakano, K., Ohta, M., Adachi, T., Obayashi, H., and Yoshikawa, T.: Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr. Res., 28, 137–143, 2008.

[18] Yagi, K.: Simple procedure for specific assay of lipid hydroperoxides in serum or plasma. Methods. Mol. Biol., 108, 107–110, 1998.

[19] Loft, S., Fischer-Nielsen, A., Jeding, I.B., Vistisen, K., and Poulsen, H.E.: 8-Hydroxydeoxyguanosine as a urinary biomarker of oxidative DNA damage. J. Toxicol. Environ. Health., 40, 391–404, 1993.

[20] Kinnula, V.L. and Crapo, J.D.: Superoxide dismutases in the lung and human lung diseases. Am. J. Respir. Crit. Care. Med., 167, 1600–1619, 2003.

[21] Noor, R., Mittal, S., and Iqbal, J.: Superoxide dismutase—applications and relevance to human diseases. Med. Sci. Monit., 8, RA210–215, 2002.

[22] Fukai, T., Folz, R.J., Landmesser, U., and Harrison, D.G.: Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc. Res., 55, 239–249, 2002.

[23] Batiste, M.C. and Schaefer, E.J.: Diagnosis and management of lipoprotein abnormalities. Nutr. Clin. Care, 5, 115–123, 2002.

[24] Whitfield, J.B.: Gamma glutamyl transferase. Crit. Rev. Clin. Lab. Sci., 38, 263–355, 2001.

[25] Lee, D.H., Blomhoff, R., and Jacobs, D.R.Jr.: Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic. Res., 38, 535–539, 2004.

[26] Schwertner, H.A., Jackson, W.G., and Tolan, G.: Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin. Chem., 40, 18–23, 1994.

[27] Madhavan, M., Wattigney, W.A., Srinivasan, S.R., and Berenson, G.S.: Serum bilirubin distribution and its relation to cardiovascular risk in children and young adults. Atherosclerosis, 131, 107–113, 1997.

[28] Tenhunen, R., Marver, H.S., and Schmid, R.: The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. U.S.A., 61, 748–755, 1968.

[29] Otterbein, L.E., Soares, M.P., Yamashita, K., and Bach, F.H.: Heme oxygenase-1: unleashing the protective properties of heme. Trends. Immunol., 24, 449–455, 2003.

[30] Dilsiz, N., Olcucu, A., Cay, M., Naziroglu, M., and Cobanoglu, D.: Protective effects of selenium, vitamin C and vitamin E against oxidative stress of cigarette smoke in rats. Cell Biochem. Funct., 17, 1–7, 1999.