{"id":27740,"date":"2024-01-03T21:52:28","date_gmt":"2024-01-03T19:52:28","guid":{"rendered":"https:\/\/hho-bulgaria.com\/h2-rich-water-and-antioxidant-status-in-metabolic-syndrome\/"},"modified":"2024-01-29T21:37:38","modified_gmt":"2024-01-29T19:37:38","slug":"h2-rich-water-and-antioxidant-status-in-metabolic-syndrome","status":"publish","type":"post","link":"https:\/\/hho-bulgaria.com\/en\/h2-rich-water-and-antioxidant-status-in-metabolic-syndrome\/","title":{"rendered":"H2-rich water and antioxidant status in metabolic syndrome"},"content":{"rendered":"<div class=\"jig-ncbiinpagenav\" data-jigconfig=\"smoothScroll: false, allHeadingLevels: ['h2'], headingExclude: ':hidden,.nomenu'\" id=\"ui-ncbiinpagenav-1\">\n<div class=\"fm-sec half_rhythm no_top_margin\">\n<div class=\"fm-flexbox\">\n<div class=\"fm-citation\">\n<div class=\"citation-default\">\n<div class=\"part1\"><span role=\"menubar\"><a href=\"#\" role=\"menuitem\" aria-expanded=\"false\" aria-haspopup=\"true\">J Clin Biochem Nutr.<\/a><\/span> 2010 Mar; 46(2): 140\u2013149. <\/div>\n<div class=\"part2\"><span class=\"fm-vol-iss-date\">Published online 2010 Feb 24. <\/span>  <span class=\"doi\"><span>doi:&nbsp;<\/span><a href=\"\/\/doi.org\/10.3164%2Fjcbn.09-100\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=2831093&amp;issue-id=185380&amp;journal-id=548&amp;FROM=Article%7CFront%20Matter&amp;TO=Content%20Provider%7CCrosslink%7CDOI\">10.3164\/jcbn.09-100<\/a><\/span><\/div>\n<\/div>\n<\/div>\n<div class=\"fm-ids\">\n<div class=\"fm-citation-pmcid\"><span class=\"fm-citation-ids-label\">PMCID: <\/span><span>PMC2831093<\/span><\/div>\n<div class=\"fm-citation-pmid\">PMID: <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/20216947\">20216947<\/a><\/div>\n<\/div>\n<\/div>\n<h1 class=\"content-title\">Effectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome\u2014An Open Label Pilot Study<\/h1>\n<div class=\"half_rhythm\">\n<div class=\"contrib-group fm-author\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Nakao%20A%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139663024256368\" co-class=\"co-affbox\">Atsunori Nakao<\/a>,<sup>1,<\/sup><sup>*<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Toyoda%20Y%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139663024689536\" co-class=\"co-affbox\">Yoshiya Toyoda<\/a>,<sup>1<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sharma%20P%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139663024687264\" co-class=\"co-affbox\">Prachi Sharma<\/a>,<sup>2<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Evans%20M%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139663027896352\" co-class=\"co-affbox\">Malkanthi Evans<\/a>,<sup>2<\/sup> and  <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Guthrie%20N%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm139663027894080\" co-class=\"co-affbox\">Najla Guthrie<\/a><sup>2<\/sup><\/div>\n<div style=\"display:none\" class=\"contrib-group aff-tip\">\n<div id=\"_co_idm139663024256368\">\n<h3 class=\"no_margin\">Atsunori Nakao<\/h3>\n<p><sup>1<\/sup>Heart, Lung and Esophageal Surgery Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15213, USA<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Nakao%20A%5BAuthor%5D\">Atsunori Nakao<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139663024689536\">\n<h3 class=\"no_margin\">Yoshiya Toyoda<\/h3>\n<p><sup>1<\/sup>Heart, Lung and Esophageal Surgery Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15213, USA<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Toyoda%20Y%5BAuthor%5D\">Yoshiya Toyoda<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139663024687264\">\n<h3 class=\"no_margin\">Prachi Sharma<\/h3>\n<p><sup>2<\/sup>KGK Synergize, Inc., London, ON, postal code, Canada, N6A 5R8<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sharma%20P%5BAuthor%5D\">Prachi Sharma<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139663027896352\">\n<h3 class=\"no_margin\">Malkanthi Evans<\/h3>\n<p><sup>2<\/sup>KGK Synergize, Inc., London, ON, postal code, Canada, N6A 5R8<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Evans%20M%5BAuthor%5D\">Malkanthi Evans<\/a><\/div>\n<\/div>\n<div id=\"_co_idm139663027894080\">\n<h3 class=\"no_margin\">Najla Guthrie<\/h3>\n<p><sup>2<\/sup>KGK Synergize, Inc., London, ON, postal code, Canada, N6A 5R8<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Guthrie%20N%5BAuthor%5D\">Najla Guthrie<\/a><\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"half_rhythm\">\n<div class=\"togglers fm-copyright-license\"><a href=\"#\" class=\"pmctoggle\" rid=\"idm139663033331216_ai\">Author information<\/a> <a href=\"#\" class=\"pmctoggle\" rid=\"idm139663033331216_an\">Article notes<\/a> <a href=\"#\" class=\"pmctoggle\" rid=\"idm139663033331216_cpl\">Copyright and License information<\/a> <a href=\"\/pmc\/about\/disclaimer\/\" style=\"margin-left: 1em\">PMC Disclaimer<\/a><\/div>\n<div class=\"fm-authors-info hide half_rhythm\" id=\"idm139663033331216_ai\" style=\"display:none\">\n<div class=\"fm-affl\" id=\"aff1\"><sup>1<\/sup>Heart, Lung and Esophageal Surgery Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15213, USA<\/div>\n<div class=\"fm-affl\" id=\"aff2\"><sup>2<\/sup>KGK Synergize, Inc., London, ON, postal code, Canada, N6A 5R8<\/div>\n<div id=\"cor1\">*To whom correspondence should be addressed.    Tel: 1-412-648-9547    Fax: 1-412-624-6666    E-mail: <a href=\"mailto:dev@null\" data-email=\"ude.ttip.pami@oakana\" class=\"oemail\">ude.ttip.pami@oakana<\/a><\/div>\n<\/div>\n<div class=\"fm-article-notes hide half_rhythm\" id=\"idm139663033331216_an\" style=\"display:none\">\n<div class=\"fm-pubdate half_rhythm\">Received 2009 Oct 15; Accepted 2009 Nov 6.<\/div>\n<\/div>\n<div class=\"permissions half_rhythm hide\" id=\"idm139663033331216_cpl\" style=\"display:none\">\n<div class=\"fm-copyright half_rhythm\"><a href=\"\/pmc\/about\/copyright\/\">Copyright<\/a>  \u00a9 2010 JCBN<\/div>\n<div class=\"license half_rhythm\">This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.<\/div>\n<\/div>\n<\/div>\n<div id=\"pmclinksbox\" class=\"links-box whole_rhythm hidden\" role=\"complementary\" aria-label=\"Related or updated information about this article.\"><\/div>\n<\/div>\n<div class=\"sec\"><\/div>\n<div id=\"abstract-a.k.b.q\" lang=\"en\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><span role=\"menubar\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"menuitem\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/span><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"abstract-a.k.b.qtitle\">Abstract<\/h2>\n<p><!--article-meta--><\/p>\n<div>\n<p class=\"p p-first-last\">Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5\u20132&nbsp;L\/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55\u20130.65 mM), by the following chemical reaction; Mg&nbsp;+&nbsp;2H<sub>2<\/sub>O \u2192 Mg (OH)<sub>2<\/sub>&nbsp;+&nbsp;H<sub>2<\/sub>. The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (<em>p<\/em>&lt;0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (<em>p<\/em>&lt;0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol\/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.<\/p>\n<\/div>\n<div class=\"sec\"><strong class=\"kwd-title\">Keywords: <\/strong><span class=\"kwd-text\">hydrogen, drinking water, magnesium, oxidative stress, metabolic syndrome<\/span><\/div>\n<\/div>\n<div id=\"sec-a.l.a\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.l.atitle\">Introduction<\/h2>\n<p class=\"p p-first\">Metabolic syndrome is characterized by a constellation of metabolic and anthropometric abnormalities, which include excess weight, hyperglycemia, hypertension, low concentration of high density lipoprotein (HDL) cholesterol and hypertriglyceridemia [<a href=\"#B1\" rid=\"B1\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">1<\/a>\u2013<a href=\"#B3\" rid=\"B3\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">3<\/a>]. Metabolic disease remains a serious concerns in the United States and people with metabolic syndrome are at increased risk of developing cardiovascular disease and type II diabetes [<a href=\"#B3\" rid=\"B3\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">3<\/a>, <a href=\"#B4\" rid=\"B4\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">4<\/a>].<\/p>\n<p>Free radicals and other reactive oxygen species (ROS) are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants and industrial chemicals [<a href=\"#B5\" rid=\"B5\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">5<\/a>]. Disturbance of the balance between production of oxygen free radicals (or some other radical species) and activity of the antioxidant system of protection causes oxidative stress [<a href=\"#B6\" rid=\"B6\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">6<\/a>]. Recent evidence implicated oxidative stress in the pathogenesis of metabolic syndrome [<a href=\"#B1\" rid=\"B1\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">1<\/a>, <a href=\"#B2\" rid=\"B2\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">2<\/a>, <a href=\"#B7\" rid=\"B7\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">7<\/a>]. Oxidative stress and nutritional changes also contribute to the aging process and to many age-related diseases and may affect cardiovascular function by either involving the long-term development of atherosclerosis or causing immediate damage during a heart attack or stroke [<a href=\"#B8\" rid=\"B8\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">8<\/a>]. Typically, ROS reacts with lipids causing lipid peroxidation leading to oxidative destruction of unsaturated fatty acids and damage of cell membranes with indirect damage to other cell constituents [<a href=\"#B9\" rid=\"B9\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">9<\/a>]. Therefore mitigating oxidative stress may have a significant impact for people in pre-metabolic syndrome status.<\/p>\n<p>Hydrogen has been identified as having therapeutic antioxidant properties by selectively reducing cytotoxic ROS in tissues [<a href=\"#B10\" rid=\"B10\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">10<\/a>, <a href=\"#B11\" rid=\"B11\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">11<\/a>]. As hydrogen is a gaseous molecule, inhaled hydrogen might be an easy delivery strategy. Although it is safe at a concentration lower than its threshold of 4.6% in air, the translational applicability of inhaled hydrogen gas is limited to medical care facilities as it is an inflammable gas and cannot be realistically and safely administered [<a href=\"#B12\" rid=\"B12\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">12<\/a>]. Oral intake of liquid containing hydrogen represents a novel and easily translatable method of delivery of hydrogen gas. Previous animal studies have linked daily consumption of hydrogen rich water, generated by bubbling or direct contact with hydrogen gas, with reduced atherosclerosis in apolipoprotein E knockout mice [<a href=\"#B13\" rid=\"B13\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">13<\/a>], alleviated cisplatin-induced nephrotoxicity [<a href=\"#B14\" rid=\"B14\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">14<\/a>], improved vitamin C deficiency-induced brain injury [<a href=\"#B15\" rid=\"B15\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">15<\/a>] and prevented chronic allograft nephropathy after renal transplantation [<a href=\"#B16\" rid=\"B16\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">16<\/a>]. In addition, the beneficial effects of consuming hydrogen rich water in the prevention of adult onset diabetes and insulin resistance has been reported in a human study [<a href=\"#B17\" rid=\"B17\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">17<\/a>].<\/p>\n<p class=\"p p-last\">We hypothesized that oral intake of hydrogen rich water generated <em>via<\/em> a magnesium stick may reduce oxidative stress in human subjects with potential metabolic syndrome. As metabolic syndrome is a disease closely associated with lifestyle-related habits, oral intake of hydrogen on a daily basis via drinking water may be ideal, for people without complicating or changing their life style. The administration of hydrogen rich water <em>via<\/em> a portable magnesium stick was considered to be a safe and feasible method of delivery and was investigated in an open label study, on subjects with potential metabolic syndrome.<\/p>\n<\/div>\n<div id=\"sec-a.l.b\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.l.btitle\">Materials and Methods<\/h2>\n<div id=\"sec-a.l.b.b\" class=\"sec sec-first\">\n<h3 id=\"sec-a.l.b.btitle\">Subjects and Design<\/h3>\n<p class=\"p p-first\">This study was an open label pilot study conducted at a single site with an 8 week treatment period. Twenty subjects \u226540 years, males (<em>n<\/em>&nbsp;=&nbsp;10) and females (<em>n<\/em>&nbsp;=&nbsp;10) were enrolled from existing patient databases or by advertisement. In order to qualify, subjects were required to have one or more of the following conditions: body mass index (BMI) between 25.0 and 34.9&nbsp;kg\/m<sup>2<\/sup>, waist circumference of \u2265100&nbsp;cm for males and \u226588&nbsp;cm for females, pre-hypertension (diastolic blood pressure of 80\u201389&nbsp;mmHg and systolic blood pressure of 139&nbsp;mmHg or lower), pre-diabetes (fasting plasma glucose from 5.2 to 6.9&nbsp;mmol\/L), total cholesterol &gt;5.18&nbsp;mmol\/L and\/or low density lipoprotein (LDL) &gt;2.59&nbsp;mmol\/L. At screening, subjects provided written informed consent and, inclusion and exclusion criteria, medical history and prior use of concomitant medications were reviewed.<\/p>\n<p>Subjects were required to be weight stable (for 3 months prior to study) and those subjects that were smokers were encouraged not to change their smoking habits. Subjects were required to discontinue other natural health products three weeks prior to randomization and during the study and to maintain their current level of physical activity and dietary habits during the course of the study. Subjects were excluded from participating if they were pregnant, breastfeeding, or planning to become pregnant, had uncontrolled hypertension, or history of diagnosed disease or condition including diabetes (Type I or II), cardiovascular disease, cancer, renal and\/or liver disease, history of psychiatric disorder or drug\/alcohol abuse, used prescription or over the counter products for vasodilation, erectile dysfunction, weight loss, and\/or hypercholesterolemia, use of anticoagulants or had participated in a clinical research trial within 30 days prior to randomization.<\/p>\n<p class=\"p p-last\">This study was conducted at KGK Synergize, Inc., London ON, Canada. The study was conducted in accordance with Good Clinical Practice Guidelines and the ethical principles of the Declaration of Helsinki (2000). The study protocol and materials were approved by the Institutional Review Board Services (Aurora, Ontario), and all subjects gave written informed consent prior to participation.<\/p>\n<\/div>\n<div id=\"sec-a.l.b.c\" class=\"sec\">\n<h3 id=\"sec-a.l.b.ctitle\">Investigational products (Production of hydrogen water)<\/h3>\n<p class=\"p p-first\">A plastic shelled product consisting of metallic magnesium (99.9% pure) and natural stones in the polypropylene containers combined with ceramics (Doctor SUISOSUI\u00ae, Friendear, Tokyo, Japan) was used to produce hydrogen. The product was capable of generating hydrogen when placed in drinking water by the following chemical reaction; Mg&nbsp;+&nbsp;2H<sub>2<\/sub>O \u2192 Mg (OH)<sub>2<\/sub>&nbsp;+&nbsp;H<sub>2<\/sub> (Fig.&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/figure\/F1\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"F1\" rid-ob=\"ob-F1\" co-legend-rid=\"lgnd_F1\" rel=\"noopener\"><span>1<\/span><\/a>). Hydrogen water sticks were dispensed at baseline and week 4 and used sticks were collected at week 4 and week 8 and compliance calculated.<\/p>\n<p><!--fig ft0--><!--fig mode=article f1--><\/p>\n<div class=\"fig iconblock whole_rhythm\" id=\"F1\" co-legend-rid=\"lgnd_F1\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/figure\/F1\/\" target=\"figure\" rid-figpopup=\"F1\" rid-ob=\"ob-F1\" rel=\"noopener\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/a><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm139663071530416\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/figure\/F1\/\" target=\"figure\" rid-figpopup=\"F1\" rid-ob=\"ob-F1\" rel=\"noopener\"><\/a><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=2831093_jcbn09-100f01.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is jcbn09-100f01.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/jcbn09-100f01.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm139663071530416\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/figure\/F1\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"icnblk_cntnt\" id=\"lgnd_F1\">\n<div><a class=\"figpopup\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/figure\/F1\/\" target=\"figure\" rid-figpopup=\"F1\" rid-ob=\"ob-F1\" rel=\"noopener\">Fig.&nbsp;1<\/a><\/div>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>A. Magnesium stick and the methods to generate hydrogen water in 500&nbsp;ml bottles of drinking water. A plastic shelled product consisting of metallic magnesium (99.9% pure) and natural stones in the polypropylene containers combined with ceramics (Doctor SUISOSUI\u00ae, Friendear, Tokyo, Japan) was used to produce hydrogen. The product was capable of generating hydrogen when placed in drinking water by the following chemical reaction; Mg&nbsp;+&nbsp;2H<sub>2<\/sub>O \u2192 Mg (OH)<sub>2<\/sub>&nbsp;+&nbsp;H<sub>2<\/sub>. B. Hydrogen concentrations in the water bottle (<em>n<\/em>&nbsp;=&nbsp;3). The hydrogen concentration in a water bottle was maintained between 0.55 and 0.65&nbsp;mM over an 8 week period.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<p class=\"p p-last\">In a retrospective study conducted at the University of Pittsburgh, in a setting similar to the study procedures followed in the current study, the hydrogen concentration in a water bottle was sequentially monitored using a hydrogen needle sensor (DHS-001, ABLE, Tokyo, Japan). It was determined that the hydrogen concentration was maintained between 0.55 and 0.65&nbsp;mM and pH between 7.9 and 8.1 over a 12 to 36&nbsp;h period. When monitored twice a day at weekly intervals for 4 weeks, it was further documented, that the magnesium stick maintained the hydrogen concentration in the water bottles for the desired length of the study. The concentration of magnesium and calcium in the water were also measured using a standard test method (ASTM D511-09, ASTM International, West Conshohocken, PA, conducted at University of Pittsburgh) and found to be &lt;1.0&nbsp;mg\/L and &lt;1.0&nbsp;mg\/L, respectively.<\/p>\n<\/div>\n<div id=\"sec-a.l.b.d\" class=\"sec\">\n<h3 id=\"sec-a.l.b.dtitle\">Study protocols (dose and mode of administration)<\/h3>\n<p class=\"p p-first-last\">Subjects were provided with 500&nbsp;ml bottles of drinking water and instructed to place two magnesium sticks in each of five bottles of water at the end of each day in preparation for consumption the following day. Participants were asked to drink 300\u2013400&nbsp;ml from bottle one, each morning, one hour before breakfast; 300\u2013400&nbsp;ml from bottle two, one hour before lunch; 300\u2013400&nbsp;ml from bottle three, two hours after lunch; 300\u2013400&nbsp;ml from bottle four, one hour before supper; and 300\u2013400&nbsp;ml from bottle five, one-half hour before bedtime as per instructions provided in the informed consent form. Subjects were instructed to reuse the magnesium sticks by transferring the sticks to a new bottle of water after use. In summary, subjects were expected to consume 300\u2013400&nbsp;ml of hydrogen rich water 5 times\/day for a total minimum consumption of 1500&nbsp;ml (1.5&nbsp;L) to a maximum consumption of 2000&nbsp;ml (2.0&nbsp;L).<\/p>\n<\/div>\n<div id=\"sec-a.l.b.e\" class=\"sec\">\n<h3 id=\"sec-a.l.b.etitle\">Assessment of health and physiological parameters<\/h3>\n<p class=\"p p-first-last\">The study included 4 clinic visits, which occurred at screening, baseline, week 4 and week 8. At baseline, week 4 and week 8, blood pressure, heart rate, waist circumference and concomitant therapies were assessed, weight measurements were recorded and fasting peripheral blood was collected to determine glucose and lipid profile. Serum chemistry and hematology were repeated at week 4 and week 8 and first morning void urine samples from two consecutive days were pooled for urinalysis at baseline, week 4 and week 8. A treatment diary was dispensed at baseline and week 4 and included forms to record daily product use, changes in concomitant therapies and adverse events and was returned and reviewed at week 4 and week 8. Adverse events were reviewed at week 4 and week 8.<\/p>\n<\/div>\n<div id=\"sec-a.l.b.f\" class=\"sec\">\n<h3 id=\"sec-a.l.b.ftitle\">Analysis of oxidative stress markers<\/h3>\n<p class=\"p p-first-last\">Laboratory tests for routine health markers such as complete blood count (CBC), creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT), bilirubin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and fasting glucose were conducted using standardized procedures at Life Labs Medical Laboratory Services in London, ON. Concentration of 8-hydroxy-2&#8242;-deoxyguanosine (8-OHdG) was analyzed by enzyme immunoassay (EIA) (Caymen Chemical, Ann Arbor, MI, Cat. #589320), 8-isoprostane by EIA (Caymen Chemical, Cat. #516351.1), superoxide dismutase (SOD) by enzyme colorimetric assay (Caymen Chemical, Cat. #706002) and thiobarbituric acid reactive substances (TBARS) was analyzed spectrophotometrically using TBARS ASSAY (Caymen Chemical, Cat. #10009055).<\/p>\n<\/div>\n<div id=\"sec-a.l.b.g\" class=\"sec sec-last\">\n<h3 id=\"sec-a.l.b.gtitle\">Statistical analysis<\/h3>\n<p class=\"p p-first-last\">As this was a pilot study, no formal sample size calculation was performed. Repeated measures analysis of variance (ANOVA) was used to compare pre- and post-treatment measurements of effectiveness and general health markers. Probability values less than 0.05 were considered to be statistically significant. The change from baseline to week 4, and week 8 were compared using Tukey\u2019s multiple comparisons test for 8-OHdG, 8-isoprostane, TBARS, and SOD, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and fasting glucose. Adverse events were summarized descriptively using frequencies, and categorizing by intensity and body system. A post hoc sub analysis was also conducted on female and male subjects to determine any differences in response according to gender and on subjects who were current smokers for effectiveness. SAS version 9.1 was used to perform the statistical analysis.<\/p>\n<\/div>\n<\/div>\n<div id=\"sec-a.l.c\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.l.ctitle\">Results<\/h2>\n<div id=\"sec-a.l.c.b\" class=\"sec sec-first\">\n<h3 id=\"sec-a.l.c.btitle\">Subject characteristics<\/h3>\n<p class=\"p p-first\">All subjects completed treatment with mean compliance of 98.7&nbsp;\u00b1&nbsp;3.3 and were included in the analysis. The baseline demographics of subjects are presented in Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T1\/\" target=\"table\" class=\"fig-table-link figpopup\" rid-figpopup=\"T1\" rid-ob=\"ob-T1\" co-legend-rid=\"\" rel=\"noopener\"><span>1<\/span><\/a>. Subjects enrolled in the study included those who were pre-hypertensive (<em>n<\/em>&nbsp;=&nbsp;3), pre-diabetic (<em>n<\/em>&nbsp;=&nbsp;7), and had total cholesterol &gt;5.18&nbsp;mmol\/L (<em>n<\/em>&nbsp;=&nbsp;12), LDL-c &gt;2.59&nbsp;mmol\/L (<em>n<\/em>&nbsp;=&nbsp;17), BMI 25\u201334.9 (<em>n<\/em>&nbsp;=&nbsp;10), and\/or smokers (<em>n<\/em>&nbsp;=&nbsp;4). All subjects showed mean normal clinical levels of baseline biometric parameters, clinical chemistry and hematology.<\/p>\n<p><!--table ft1--><!--table-wrap mode=\"anchored\" t5--><\/p>\n<div class=\"table-wrap anchored whole_rhythm\" id=\"T1\">\n<h3>Table&nbsp;1<\/h3>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Characteristics of subjects Biometrics, Lipid panel and clinical chemistry for all subjects and by gender at baseline<\/p>\n<\/div>\n<div class=\"xtable\">\n<table frame=\"hsides\" rules=\"groups\" class=\"rendered small default_table\">\n<thead>\n<tr>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">Variable<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">All (<em>n<\/em>&nbsp;=&nbsp;20)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Female (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Male (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Age (years)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">*50.8&nbsp;\u00b1&nbsp;9.6<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">50.0&nbsp;\u00b1&nbsp;9.7<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">51.5&nbsp;\u00b1&nbsp;10.0<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Gender-Female<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">**10\/20 (50.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">10\/10 (100.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">0\/10 (0.0)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Gender-Male<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">10\/20 (50.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">0\/10 (0.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">10\/10 (100.0)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Mean Systolic BP (mmHg)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">*114.4&nbsp;\u00b1&nbsp;9.5<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">110.8&nbsp;\u00b1&nbsp;10.8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">117.9&nbsp;\u00b1&nbsp;6.7<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Mean Diastolic BP (mmHg)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">72.2&nbsp;\u00b1&nbsp;7.5<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">69.8&nbsp;\u00b1&nbsp;7.2<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">74.5&nbsp;\u00b1&nbsp;7.4<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Mean Heart Rate (bpm)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">69.1&nbsp;\u00b1&nbsp;6.9<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">70.0&nbsp;\u00b1&nbsp;6.1<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">68.2&nbsp;\u00b1&nbsp;7.8<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Height (cm)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">171.9&nbsp;\u00b1&nbsp;7.7<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">167.3&nbsp;\u00b1&nbsp;5.9<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">176.5&nbsp;\u00b1&nbsp;6.5<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Weight (kg)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">84.6&nbsp;\u00b1&nbsp;17.7<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">80.3&nbsp;\u00b1&nbsp;19.1<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">88.8&nbsp;\u00b1&nbsp;16.1<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Waist Circumference (cm)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">97.8&nbsp;\u00b1&nbsp;11.5<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">94.2&nbsp;\u00b1&nbsp;10.1<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">101.5&nbsp;\u00b1&nbsp;12.3<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">BMI (kg\/m<sup>2<\/sup>)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.6&nbsp;\u00b1&nbsp;5.8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.7&nbsp;\u00b1&nbsp;6.9<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.5&nbsp;\u00b1&nbsp;4.7<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">Fasting Glucose (mmol\/L)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.9&nbsp;\u00b1&nbsp;0.5<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.6&nbsp;\u00b1&nbsp;0.6<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.9&nbsp;\u00b1&nbsp;0.4<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><strong>Alcohol Use<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Daily<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">**2\/20 (10.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">0\/10 (0.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">2\/20 (10.0)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Occasional<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">14\/20 (70.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">6\/10 (60.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">8\/10 (30.0)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Weekly<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4\/20 (20.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4\/10 (40.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">0\/10 (0.0)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><strong>Tobacco Use<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Current<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4\/20 (20.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1\/10 (10.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3\/10 (30)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Former<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">7\/20 (35.0 )<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3\/10 (30.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4\/10 (40.0)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003None<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">9\/20 (45.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">6\/10 (60.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3\/10 (30.0)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm139663071527776\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T1\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"tblwrap-foot\">\n<p>* Mean&nbsp;\u00b1&nbsp;SD, **f\/n (%)&nbsp;=&nbsp;Number of subjects\/Total Number of subjects (percent). BP, indicates blood pressure; BMI, body mass index.<\/p>\n<\/div>\n<\/div>\n<p class=\"p p-last\">The proportion of male smokers was greater (<em>n<\/em>&nbsp;=&nbsp;3) than that of the female smokers (<em>n<\/em>&nbsp;=&nbsp;1) however all subjects were occasional smokers. The compliance with respect to reporting the number of cigarettes smoked in all the visits was 100%. In two subjects the number of cigarettes smoked remained the same throughout the visits (10 and 20).<\/p>\n<\/div>\n<div id=\"sec-a.l.c.c\" class=\"sec\">\n<h3 id=\"sec-a.l.c.ctitle\">Oxidative stress biomarkers<\/h3>\n<p class=\"p p-first-last\">Oxidative stress is a well-recognized mechanism playing an important role in pathological conditions seen in metabolic syndrome [<a href=\"#B1\" rid=\"B1\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">1<\/a>]. The effect of hydrogen rich water on markers of oxidative stress is presented in Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T2\/\" target=\"table\" class=\"fig-table-link figpopup\" rid-figpopup=\"T2\" rid-ob=\"ob-T2\" co-legend-rid=\"\" rel=\"noopener\"><span>2<\/span><\/a>. TBARS are a marker of lipid peroxidation which is indicative of malondialdehyde formation and lipid damage and is a well-established method for screening and monitoring lipid peroxidation [<a href=\"#B18\" rid=\"B18\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">18<\/a>]. The concentration of urinary TBARS decreased significantly (<em>p<\/em>&lt;0.05) from baseline to week 4 and week 8. Subjects demonstrated a significant increase (<em>p<\/em>&lt;0.05) in SOD from baseline to week 8. Subjects demonstrated increasing trends in 8-isoprostane from baseline to week 4 and week 8. When a post hoc sub analysis by gender was conducted, male subjects demonstrated a significant decrease in urinary TBARS from baseline to week 8 and a significant increase (<em>p<\/em>&lt;0.05) in SOD from baseline to week 8. During oxidative damage to DNA, damaged products are usually eliminated by repair enzymes and detected as nucleoside derivatives. Urinary 8-OHdG is one adduct of this reaction and has been proposed as a sensitive biomarker of oxidative DNA damage and repair [<a href=\"#B19\" rid=\"B19\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">19<\/a>]. In subjects who were current smokers, there was a trend toward a decrease in urinary 8-OHdG and TBARS levels from baseline to week 4 and week 8. Subjects demonstrated increasing trends in SOD from baseline to week 8 and 8-isoprostane from baseline to week 4 and week 8. Urinary 8-OHdG, 8-isoprostane, TBARS and SOD were higher in subjects who were current smokers (data not shown).<\/p>\n<p><!--table ft1--><!--table-wrap mode=\"anchored\" t5--><\/p>\n<div class=\"table-wrap anchored whole_rhythm\" id=\"T2\">\n<h3>Table&nbsp;2<\/h3>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Urinary oxidative stress markers and by gender at baseline and after 4 and 8 weeks of treatment with hydrogen rich water.<\/p>\n<\/div>\n<div class=\"xtable\">\n<table frame=\"hsides\" rules=\"groups\" class=\"rendered small default_table\">\n<thead>\n<tr>\n<th rowspan=\"1\" colspan=\"1\"><\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">All (<em>n<\/em>&nbsp;=&nbsp;20)<\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">Female (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">Male (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<\/tr>\n<tr>\n<th rowspan=\"1\" colspan=\"1\"><\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>Urine 8-OHdG (ng\/mg creatinine)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">31.8&nbsp;\u00b1&nbsp;16.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">34.6&nbsp;\u00b1&nbsp;16.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.9&nbsp;\u00b1&nbsp;17.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">31.7&nbsp;\u00b1&nbsp;10.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">33.4&nbsp;\u00b1&nbsp;11.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">30.0&nbsp;\u00b1&nbsp;10.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.9, 7.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22121.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221213.4, 11.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(1.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221210.2, 12.5)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">31.1&nbsp;\u00b1&nbsp;12.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">31.1&nbsp;\u00b1&nbsp;16.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">31.0&nbsp;\u00b1&nbsp;9.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22128.5, 7.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.6)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221215.8, 8.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(2.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22129.2, 13.5)<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>8-Isoprostane (ng\/mmol creatinine)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">122.9&nbsp;\u00b1&nbsp;33.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">125.9&nbsp;\u00b1&nbsp;29.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">120.0&nbsp;\u00b1&nbsp;39.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">130.0&nbsp;\u00b1&nbsp;43.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">122.8&nbsp;\u00b1&nbsp;38.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">137.2&nbsp;\u00b1&nbsp;48.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(7.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221217.7, 31.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221234.6, 28.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(17.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221224.8, 59.2)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">140.3&nbsp;\u00b1&nbsp;32.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">138.2&nbsp;\u00b1&nbsp;20.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">142.4&nbsp;\u00b1&nbsp;42.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(17.4)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.4, 42.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(12.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221219.2, 43.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(22.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221219.5, 64.5)<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>TBARS (\u00b5mol\/g creatinine)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">7.7&nbsp;\u00b1&nbsp;5.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">8.4&nbsp;\u00b1&nbsp;5.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">7.1&nbsp;\u00b1&nbsp;4.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.0&nbsp;\u00b1&nbsp;3.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.7&nbsp;\u00b1&nbsp;4.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.3&nbsp;\u00b1&nbsp;2.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22122.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22124.9, \u22120.6)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22122.6)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22125.7, 0.4)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22122.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22126.2, 0.6)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.5&nbsp;\u00b1&nbsp;2.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.4&nbsp;\u00b1&nbsp;3.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.6&nbsp;\u00b1&nbsp;2.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22125.4, \u22121.1)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22126.1, 0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22126.9, \u22120.2)*<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>SOD (U\/mmol creatinine)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">122.1&nbsp;\u00b1&nbsp;106.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">155.9&nbsp;\u00b1&nbsp;122.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">88.3&nbsp;\u00b1&nbsp;80.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">129.8&nbsp;\u00b1&nbsp;62.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">153.6&nbsp;\u00b1&nbsp;61.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">106.1&nbsp;\u00b1&nbsp;56.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(7.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221225.3, 40.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22122.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221259.6, 55.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(17.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221222.4, 58.0)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">169.7&nbsp;\u00b1&nbsp;94.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">208.2&nbsp;\u00b1&nbsp;106.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">131.3&nbsp;\u00b1&nbsp;64.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(47.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(14.6, 80.7)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(52.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22125.0, 109.6)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(43.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(2.8, 83.2)*<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm139663024428832\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T2\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"tblwrap-foot\">\n<p>* denotes statistically significant differences (<em>p<\/em>&lt;0.05), 95% confidence intervals about the mean difference between baseline and week 4 and baseline and week 8 were obtained via Tukey\u2019s multiple comparisons test. ** Change in urinary oxidative stress markers from baseline to week 4. <sup>\u2020<\/sup> Change in urinary oxidative stress markers from baseline to week 8 of treatment. 8-OHdG, indicates 8-hydroxy-2&#8242;-deoxyguanosine; TBARS, thiobarbituric acid; SOD, superoxide dismutase.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"sec-a.l.c.d\" class=\"sec\">\n<h3 id=\"sec-a.l.c.dtitle\">Lipid profile and fasting glucose<\/h3>\n<p class=\"p p-first\">Subjects demonstrated a significant increase in HDL-cholesterol from baseline to week 4 and week 8 and a decrease in total cholesterol\/HDL ratio from baseline to week 4 (Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T3\/\" target=\"table\" class=\"fig-table-link figpopup\" rid-figpopup=\"T3\" rid-ob=\"ob-T3\" co-legend-rid=\"\" rel=\"noopener\"><span>3<\/span><\/a>). Post hoc sub analysis by gender demonstrated that female subjects had a significant increase (<em>p<\/em>&lt;0.05) in HDL-cholesterol from baseline to week 4, and a significant decrease (<em>p<\/em>&lt;0.05) in LDL-cholesterol and total cholesterol\/HDL-cholesterol ratio from baseline to week 4. There were no changes in HDL cholesterol, cholesterol\/HDL ratio and triglycerides from baseline to week 8. Male subjects demonstrated a significant increase in HDL-cholesterol from baseline to week 4 and week 8 and significant decrease in total cholesterol\/HDL ratio from baseline to week 4 (<em>p<\/em>&lt;0.05) (Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T3\/\" target=\"table\" class=\"fig-table-link figpopup\" rid-figpopup=\"T3\" rid-ob=\"ob-T3\" co-legend-rid=\"\" rel=\"noopener\"><span>3<\/span><\/a>).<\/p>\n<p><!--table ft1--><!--table-wrap mode=\"anchored\" t5--><\/p>\n<div class=\"table-wrap anchored whole_rhythm\" id=\"T3\">\n<h3>Table&nbsp;3<\/h3>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Blood lipid profile of all subjects and by gender at baseline and after 4 and 8 weeks of treatment with hydrogen rich water.<\/p>\n<\/div>\n<div class=\"xtable\">\n<table frame=\"hsides\" rules=\"groups\" class=\"rendered small default_table\">\n<thead>\n<tr>\n<th rowspan=\"1\" colspan=\"1\"><\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">All (<em>n<\/em>&nbsp;=&nbsp;20)<\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">Female (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">Male (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<\/tr>\n<tr>\n<th rowspan=\"1\" colspan=\"1\"><\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>Total Cholesterol (mmol\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.3&nbsp;\u00b1&nbsp;1.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.6&nbsp;\u00b1&nbsp;1.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.1&nbsp;\u00b1&nbsp;0.7<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.3&nbsp;\u00b1&nbsp;0.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.4&nbsp;\u00b1&nbsp;1.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.3&nbsp;\u00b1&nbsp;0.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><sup>\u2020<\/sup>(\u22120.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.3, 0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.6, 0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.1, 0.5)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.5&nbsp;\u00b1&nbsp;1.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.8&nbsp;\u00b1&nbsp;1.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.3&nbsp;\u00b1&nbsp;0.7<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><sup>\u2020\u2020<\/sup>(0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.1, 0.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2, 0.6)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.1, 0.5)<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>LDL Cholesterol (mmol\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.4&nbsp;\u00b1&nbsp;0.9**<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.6&nbsp;\u00b1&nbsp;1.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.2&nbsp;\u00b1&nbsp;0.5***<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.2&nbsp;\u00b1&nbsp;0.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.2&nbsp;\u00b1&nbsp;1.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.2&nbsp;\u00b1&nbsp;0.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.4, 0.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.4)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.8, \u22120.0)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.3, 0.3)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.5&nbsp;\u00b1&nbsp;0.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.7&nbsp;\u00b1&nbsp;1.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.3&nbsp;\u00b1&nbsp;0.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.1, 0.4)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.3, 0.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2, 0.4)<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>HDL Cholesterol (mmol\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.2&nbsp;\u00b1&nbsp;0.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.4&nbsp;\u00b1&nbsp;0.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.1&nbsp;\u00b1&nbsp;0.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.4&nbsp;\u00b1&nbsp;0.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.5&nbsp;\u00b1&nbsp;0.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.3&nbsp;\u00b1&nbsp;0.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1, 0.3)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1, 0.3)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1, 0.3)*<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.3&nbsp;\u00b1&nbsp;0.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.4&nbsp;\u00b1&nbsp;0.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.2&nbsp;\u00b1&nbsp;0.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.0, 0.2)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.0, 0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.0, 0.2)*<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>Cholesterol\/HDL Ratio<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.5&nbsp;\u00b1&nbsp;1.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.1&nbsp;\u00b1&nbsp;1.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">5.0&nbsp;\u00b1&nbsp;1.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.9&nbsp;\u00b1&nbsp;1.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">3.6&nbsp;\u00b1&nbsp;0.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.3&nbsp;\u00b1&nbsp;1.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.6)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.9, \u22120.4)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.6)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.9, \u22120.2)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22121.0, \u22120.4)*<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.4&nbsp;\u00b1&nbsp;1.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.1&nbsp;\u00b1&nbsp;1.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">4.7&nbsp;\u00b1&nbsp;1.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.4, 0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.3, 0.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.7, 0.0)<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>Triglycerides (mmol\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Baseline (Week 0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.6&nbsp;\u00b1&nbsp;1.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.3&nbsp;\u00b1&nbsp;0.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.9&nbsp;\u00b1&nbsp;1.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.5&nbsp;\u00b1&nbsp;0.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.3&nbsp;\u00b1&nbsp;0.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.7&nbsp;\u00b1&nbsp;1.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.3, 0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2, 0.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.7, 0.4)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.5&nbsp;\u00b1&nbsp;0.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.3&nbsp;\u00b1&nbsp;0.7<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">1.6&nbsp;\u00b1&nbsp;0.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.4, 0.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2, 0.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.8, 0.3)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm139663027011904\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T3\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"tblwrap-foot\">\n<p>* denotes statistically significant differences (<em>p<\/em>&lt;0.05), 95% confidence intervals about the mean difference between baseline and week 4 and baseline and week 8 were obtained via Tukey\u2019s multiple comparisons test. **N&nbsp;=&nbsp;19, ***N&nbsp;=&nbsp;9. <sup>\u2020<\/sup>Change in lipid profile of subjects from baseline to week 4. <sup>\u2020\u2020<\/sup>Change in lipid profile of subjects from baseline to week 8. LDL, indicates low density lipoprotein; HDL, high density lipoprotein.<\/p>\n<\/div>\n<\/div>\n<p>The effects of hydrogen rich water on the lipid profile in subjects who were current smokers demonstrated that there was a significant decrease in the total cholesterol\/HDL ratio from baseline to week 4 (data not shown) and a significant increase in HDL from baseline to week 4 (<em>p<\/em>&lt;0.05).<\/p>\n<p class=\"p p-last\">Results showed that there were no statistical differences from baseline to week 8 for fasting glucose in participants after consumption of hydrogen rich water (data not shown).<\/p>\n<\/div>\n<div id=\"sec-a.l.c.e\" class=\"sec\">\n<h3 id=\"sec-a.l.c.etitle\">Biometric parameters, clinical chemistry and hematology<\/h3>\n<p class=\"p p-first\">There were no significant differences in blood pressure, heart rate, weight and BMI assessed at any time point (data not shown). Analysis of clinical chemistry parameters demonstrated that ALT and creatinine were significantly decreased (<em>p<\/em>&lt;0.05) from baseline to week 4 and week 8 in all subjects (Table&nbsp;<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T4\/\" target=\"table\" class=\"fig-table-link figpopup\" rid-figpopup=\"T4\" rid-ob=\"ob-T4\" co-legend-rid=\"\" rel=\"noopener\"><span>4<\/span><\/a>). Further analysis demonstrated that 80% of subjects (9 females and 7 males) had a decrease in ALT from baseline to week 8 and 95% of subjects (10 females and 9 males) had a decrease in creatinine from baseline to week 8.<\/p>\n<p><!--table ft1--><!--table-wrap mode=\"anchored\" t5--><\/p>\n<div class=\"table-wrap anchored whole_rhythm\" id=\"T4\">\n<h3>Table&nbsp;4<\/h3>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Clinical Chemistry of all subjects and by gender at screening and after 4 and 8 weeks of treatment with hydrogen rich water.<\/p>\n<\/div>\n<div class=\"xtable\">\n<table frame=\"hsides\" rules=\"groups\" class=\"rendered small default_table\">\n<thead>\n<tr>\n<th rowspan=\"1\" colspan=\"1\"><\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">All (<em>n<\/em>&nbsp;=&nbsp;20)<\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">Female (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<th colspan=\"2\" align=\"center\" rowspan=\"1\">Male (<em>n<\/em>&nbsp;=&nbsp;10)<\/th>\n<\/tr>\n<tr>\n<th rowspan=\"1\" colspan=\"1\"><\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<th align=\"center\" rowspan=\"1\" colspan=\"1\">Mean&nbsp;\u00b1&nbsp;SD (Difference between means)<\/th>\n<th align=\"left\" valign=\"middle\" rowspan=\"1\" colspan=\"1\">(95% CI)<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><strong>AST (U\/L)<\/strong><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 0<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">26.3&nbsp;\u00b1&nbsp;6.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">24.1&nbsp;\u00b1&nbsp;5.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.5&nbsp;\u00b1&nbsp;7.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">21.9&nbsp;\u00b1&nbsp;6.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">19.7&nbsp;\u00b1&nbsp;6.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">24.0&nbsp;\u00b1&nbsp;5.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">**(\u22124.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221210.3, 1.4)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22124.4)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.8, \u22121.0)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22124.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221216.4, 7.4)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">23.6&nbsp;\u00b1&nbsp;12.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">19.2&nbsp;\u00b1&nbsp;4.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.0&nbsp;\u00b1&nbsp;15.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\"><sup>\u2020<\/sup>(\u22122.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22128.5, 3.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22124.9)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22128.3, \u22121.5)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221212.4, 11.4)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><strong>ALT (U\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 0<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">32.2&nbsp;\u00b1&nbsp;11.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.4&nbsp;\u00b1&nbsp;9.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">35.9&nbsp;\u00b1&nbsp;11.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">24.7&nbsp;\u00b1&nbsp;9.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">21.3&nbsp;\u00b1&nbsp;10.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.1&nbsp;\u00b1&nbsp;7.7<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221211.9, \u22123.0)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221211.8, \u22122.4)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221216.1, 0.5)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">26.1&nbsp;\u00b1&nbsp;10.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">21.2&nbsp;\u00b1&nbsp;7.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">30.9&nbsp;\u00b1&nbsp;10.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22126.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221210.6, \u22121.6)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221211.9, \u22122.5)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22125.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221213.3, 3.3)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><strong>GGT (U\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 0<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">25.7&nbsp;\u00b1&nbsp;14.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">24.8&nbsp;\u00b1&nbsp;16.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">26.5&nbsp;\u00b1&nbsp;12.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">30.0&nbsp;\u00b1&nbsp;16.2<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">25.9&nbsp;\u00b1&nbsp;13.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">34.0&nbsp;\u00b1&nbsp;18.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(4.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.6, 9.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(1.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.2, 5.4)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(7.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22121.7, 16.7)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">31.8&nbsp;\u00b1&nbsp;20.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">28.0&nbsp;\u00b1&nbsp;19.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">35.5&nbsp;\u00b1&nbsp;21.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(6.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(1.2, 11.0)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(3.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22121.1, 7.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(9.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.2, 18.2)<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>Total Bilirubin (umol\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 0<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">8.1&nbsp;\u00b1&nbsp;3.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">6.7&nbsp;\u00b1&nbsp;3.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">9.4&nbsp;\u00b1&nbsp;3.7<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">10.4&nbsp;\u00b1&nbsp;4.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">9.5&nbsp;\u00b1&nbsp;3.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">11.2&nbsp;\u00b1&nbsp;5.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(2.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.8, 3.8)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(2.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.9, 4.7)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(1.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.8, 4.4)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">10.1&nbsp;\u00b1&nbsp;3.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">8.8&nbsp;\u00b1&nbsp;3.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">11.3&nbsp;\u00b1&nbsp;3.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.5, 3.5)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(2.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(0.2, 4.0)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(1.9)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.7, 4.5)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><strong>Creatinine (umol\/L)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 0<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">83.6&nbsp;\u00b1&nbsp;14.1<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">76.2&nbsp;\u00b1&nbsp;11.8<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">90.9&nbsp;\u00b1&nbsp;12.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">76.3&nbsp;\u00b1&nbsp;12.0<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">68.4&nbsp;\u00b1&nbsp;8.7<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">84.2&nbsp;\u00b1&nbsp;9.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221211.2, \u22123.3)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22127.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221212.8, \u22122.8)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22126.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221213.4, \u22120.0)*<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">73.8&nbsp;\u00b1&nbsp;14.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">64.7&nbsp;\u00b1&nbsp;9.4<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">82.9&nbsp;\u00b1&nbsp;12.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22129.8)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221213.7, \u22125.8)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221211.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221216.5, \u22126.5)*<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22128.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221214.7, \u22121.3)*<\/td>\n<\/tr>\n<tr>\n<td colspan=\"2\" align=\"left\" rowspan=\"1\"><strong>eGFR (mL\/min\/1.73&nbsp;m<sup>2<\/sup>)<\/strong><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 0<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">86.2&nbsp;\u00b1&nbsp;14.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">83.2&nbsp;\u00b1&nbsp;15.6<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">89.2&nbsp;\u00b1&nbsp;12.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 4<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">82.7&nbsp;\u00b1&nbsp;12.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">80.9&nbsp;\u00b1&nbsp;14.7<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">84.5&nbsp;\u00b1&nbsp;9.9<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22129.1, 2.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22122.3)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22129.6, 5.0)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22124.7)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221213.9, 4.5)<\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\">\u2003Week 8<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">85.7&nbsp;\u00b1&nbsp;15.5<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">86.1&nbsp;\u00b1&nbsp;13.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">85.3&nbsp;\u00b1&nbsp;18.3<\/td>\n<td rowspan=\"1\" colspan=\"1\"><\/td>\n<\/tr>\n<tr>\n<td align=\"left\" rowspan=\"1\" colspan=\"1\"><\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22120.5)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22126.1, 5.1)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(2.9)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22124.4, 10.2)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u22123.9)<\/td>\n<td align=\"center\" rowspan=\"1\" colspan=\"1\">(\u221213.1, 5.3)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm139663070701328\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2831093\/table\/T4\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"tblwrap-foot\">\n<p>* denotes statistically significant differences (<em>p<\/em>&lt;0.05), 95% confidence intervals about the mean difference between baseline and week 4 and baseline and week 8 were obtained via Tukey\u2019s multiple comparisons test. **Change in clinical chemistry parameters of subjects from baseline to week 4, <sup>\u2020<\/sup>Change in clinical chemistry parameters of subjects from baseline to week 8. AST, indicates aspartate aminotransferase; ALT, alanine transaminase; GGT, gamma glutamyl transferase; eGFR, estimated glomerular filtration rate.<\/p>\n<\/div>\n<\/div>\n<p class=\"p p-last\">The decrease in ALT was significant (<em>p<\/em>&lt;0.05) from baseline to week 4 and week 8 in female subjects but not male subjects. Creatinine was significantly decreased (<em>p<\/em>&lt;0.05) in both genders from baseline to week 4 and week 8. Significant increases were demonstrated from baseline to week 4 and week 8 for bilirubin in subjects on hydrogen rich water. Eight females and seven males demonstrated an increase in bilirubin from baseline to week 8. This increase was significant in female subjects, but not in male subjects. GGT was significantly increased (<em>p<\/em>&lt;0.05) from baseline to week 8 with 85% of all subjects demonstrating an increase during this period (8 females and 9 males). Ninety percent of all subjects demonstrated a decrease in AST from baseline to week 8 (9 females and 9 males). This decrease was significant from baseline to weeks 4 and week 8 in female subjects but not in male subjects. The mean values for these parameters were within the normal acceptable reference range for male and female subjects. In subjects who were current smokers, significant increases were demonstrated from baseline to week 8 for bilirubin and this increase was within normal acceptable reference ranges (data not shown).<\/p>\n<\/div>\n<div id=\"sec-a.l.c.f\" class=\"sec sec-last\">\n<h3 id=\"sec-a.l.c.ftitle\">Adverse events<\/h3>\n<p class=\"p p-first-last\">A total of 28 adverse events were experienced by 13 of the 20 subjects (65.0%) enrolled in the study. Overall, 6 adverse events, experienced by 4 subjects (20.0%) were assessed by the investigator as having a possible relationship to the test article. These adverse events included loose stools (3 subjects), increase in frequency of bowel movement (1 subject) heartburn (1 subject), and headache (1 subject). These adverse events having \u201cpossible\u201d relationship to the test article were classified as mild in intensity. There were no serious adverse events which occurred during the study.<\/p>\n<\/div>\n<\/div>\n<div id=\"sec-a.l.d\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec-a.l.dtitle\">Discussion<\/h2>\n<p class=\"p p-first\">In this study, we demonstrated that drinking hydrogen rich water increased urinary anti-oxidant enzyme SOD, an endogenous defensive system against ROS-induced cellular injury, associated with reduction of oxidative stress markers, in subjects with metabolic syndrome [<a href=\"#B7\" rid=\"B7\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">7<\/a>]. SOD plays an important role in the antioxidant defense system against superoxide anion (O<sub>2<\/sub><sup>\u2212<\/sup>) generated <em>in vivo<\/em> and is involved in defense against many diseases [<a href=\"#B20\" rid=\"B20\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">20<\/a>\u2013<a href=\"#B22\" rid=\"B22\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">22<\/a>]. Our data demonstrated that subjects consuming hydrogen rich water for 8 weeks showed significantly increased SOD levels from baseline to week 8, suggesting that hydrogen rich water is capable of inducing SOD activity. Although the detailed mechanisms are undefined an increase in SOD levels correlated with decreasing trends in 8-OHdG levels, and thus supported our hypothesis that oxidative stress is reduced by consuming hydrogen rich water.<\/p>\n<p>Oxidative modification of LDL in the arterial wall plays a key role in the pathogenesis of atherosclerosis [<a href=\"#B2\" rid=\"B2\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">2<\/a>]. A high level of HDL-cholesterol is reported to protect against cardiovascular disease, and low HDL-cholesterol levels (less than 40&nbsp;mg\/dL) increase the risk of heart disease [<a href=\"#B23\" rid=\"B23\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">23<\/a>]. Results of the current study demonstrated a significant increase in HDL-cholesterol leading to a significant decrease in total cholesterol\/HDL ratio by week 4. Decreasing trends were also seen for LDL-cholesterol from baseline to week 4, and triglycerides from baseline to week 8. Though there was an increase in total cholesterol and LDL-cholesterol in subjects consuming hydrogen rich water from baseline until week 8, these values were not clinically significant and were still within a normal acceptable range. The increasing trends may possibly be associated with higher saturated fat consumption, individual food habits and physical activity of subjects. It is possible that the hypolipidemic effect of hydrogen rich water may be due to its ability to prevent lipid peroxidation, as demonstrated by the significant decrease in TBARS, resulting in lower total cholesterol\/ HDL ratio, triglycerides and an increase in HDL-cholesterol. Although an improvement of lipid and glucose metabolism after supplementation with hydrogen rich water have been observed in patients with type II diabetes [<a href=\"#B17\" rid=\"B17\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">17<\/a>], our results showed that there were no statistical differences in fasting glucose in pre-diabetic participants from baseline to week 8. These results are supported by a previous study where hydrogen water was found to lower the blood glucose level of participants with abnormally high blood glucose levels and did not induce a reduction of a normal blood glucose level [<a href=\"#B17\" rid=\"B17\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">17<\/a>].<\/p>\n<p>GGT is an enzyme widely distributed in the human body, especially in the kidney and liver [<a href=\"#B24\" rid=\"B24\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">24<\/a>]. The results of the present study demonstrated that there was a significant increase in GGT (<em>p<\/em>&lt;0.05) within group from baseline to week 8. However this increase was still within the normal acceptable clinical range for these values for both females and males.<\/p>\n<p>Previous studies have showed that there is a positive association between dietary factors and GGT levels [<a href=\"#B25\" rid=\"B25\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">25<\/a>]. Alcohol and meat consumption are reported to increase GGT levels in a dose dependant manner. However as food records were not maintained in this study we were unable to confirm that the increases in the GGT levels were related to these factors. As the other liver markers such as AST and ALT were not impacted it is possible to suggest that hydrogen water did not have a negative effect on liver function. In this study we found that AST decreased from baseline to week 4 and week 8 in both female and male subjects and these decreases attained significance in the female subjects. The levels of ALT decreased significantly from week 4 to week 8 and in the subgroup analysis this significance was also seen in the female subjects.<\/p>\n<p>Taken together it is possible to suggest that the increases in GGT may reflect changes associated with food intake and alcohol consumption of the participants. The values for GGT remained within an acceptable clinical range for this parameter.<\/p>\n<p>Interestingly, subjects demonstrated a significant increase in total bilirubin from baseline to week 4 and week 8. These increases remained within normal clinically acceptable range. Serum ALT and AST decreased with hydrogen rich water consumption and the elevation of bilirubin levels seen in this study may be a specific effect afforded by hydrogen. Schwertner <em>et al.<\/em> previously reported that there was a significant inverse correlation between bilirubin concentration and the prevalence of cardiovascular disease and lower serum bilirubin concentrations were correlated with the presence of ischemic heart disease [<a href=\"#B26\" rid=\"B26\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">26<\/a>]. Madhavan <em>et al.<\/em> showed that plasma bilirubin concentration is positively correlated with HDL-cholesterol and confirms the results demonstrated in our study [<a href=\"#B27\" rid=\"B27\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">27<\/a>]. Thus, the elevations of serum bilirubin levels, below toxic levels, are likely to be protective for cardiovascular disease.<\/p>\n<p>The exact mechanisms involved in bilirubin elevation in the subjects treated with hydrogen rich water are not fully understood, however, the antioxidant effects of hydrogen may not be the sole explanation for this increase and other as yet undefined mechanisms may be involved, such as a role in signaling pathways or perhaps other physiological functions. There is a possibility that the higher bilirubin levels are associated with the degradation of heme by heme oxygenase into equimolar quantities of biliverdin (bilirubin) and carbon monoxide (CO), while the central iron is released [<a href=\"#B28\" rid=\"B28\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">28<\/a>]. The induction of heme oxygenase (HO-1), which is the rate-limiting enzyme, catalyzes the degradation of heme [<a href=\"#B29\" rid=\"B29\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">29<\/a>]. Further studies are required to determine if hydrogen can induce HO-1. As our hematological data was not altered by hydrogen water consumption and as the elevations in serum bilirubin remained within the normal acceptable range, it is not likely that hemolysis contributed to the increase of serum bilirubin levels.<\/p>\n<p>Mean values of all hematological parameters were within normal clinically acceptable ranges. Biometric parameters assessed as a measure of safety remained unchanged during the 8 week period of the study. Results also showed that there were no changes in blood pressure, BMI and weight in subjects after consuming hydrogen rich water for 8 weeks.<\/p>\n<p>A sub analysis was conducted on subjects who were smokers as previous documentation has established that smokers are likely to have more oxidative stress [<a href=\"#B30\" rid=\"B30\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">30<\/a>] and thus may show a greater benefit from an antioxidant intervention. Subjects who smoked demonstrated a decrease in urinary creatinine, urinary 8-OHdG and TBARS with hydrogen rich water. Further subjects who smoked demonstrated increasing trends in SOD from baseline to week 8 and 8-isoprostane from baseline to week 4 and week 8, and higher urinary 8-OHdG, 8-isoprostane, TBARS and SOD. There was a statistically significant and a clinically important decrease in total cholesterol\/HDL ratio from baseline to week 4 and a statistically significant increase in HDL from baseline to week 4. These results demonstrated that oxidative stress was perhaps impacted more significantly in subjects who smoked.<\/p>\n<p class=\"p p-last\">In conclusion, consumption of hydrogen rich water generated <em>via<\/em> a magnesium stick demonstrated improvement in the levels of oxidative stress markers associated with metabolic syndrome and boosted the body\u2019s antioxidant activity. Hydrogen rich water represents a potentially novel therapeutic and preventive strategy for the treatment of metabolic syndrome. This method of delivery was advantageous as magnesium sticks are portable and proved to be an easy and safe administration of hydrogen rich water for daily consumption.<\/p>\n<\/div>\n<div id=\"ack-a.m.a\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"ack-a.m.atitle\">Acknowledgments<\/h2>\n<div class=\"sec\">\n<p>We would like to thank the volunteers of this study for their willingness and diligence in complying with the protocol. This study was managed by KGK Synergize Inc. London, ON, Canada, under the supervision of the medical directors, David Crowley, MD and Dale Wilson, MD. Statistical guidance and analysis was provided by Larry Stitt, Assistant Director of the Biostatistical Support Unit, University of Western Ontario, London, ON, Canada. We acknowledge the technical contribution of Joshua Baisley and thank Sonya Barss for overseeing the conduct of the study. This study was supported by Friendear Inc. (Decoupage Minami Aoyama 4F, 5-10-13 Minami Aoyama, Minato-ku, Tokyo 107-0062, Japan).<\/p>\n<\/div>\n<\/div>\n<div id=\"glossary-a.m.b\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"glossary-a.m.btitle\">Abbreviations<\/h2>\n<div class=\"bk-sec\">\n<div>\n<table class=\"default-table glossary\">\n<tbody>\n<tr>\n<td>8-isoprostane<\/td>\n<td>15-F<sub>2t<\/sub>-15-isoprostane (8-isoprostane F<sub>2<\/sub><sub>\u03b1<\/sub>)<\/td>\n<\/tr>\n<tr>\n<td>8-OHdG<\/td>\n<td>8-hydroxy-2&#8242;-deoxyguanosine<\/td>\n<\/tr>\n<tr>\n<td>ALT<\/td>\n<td>alanine transaminase<\/td>\n<\/tr>\n<tr>\n<td>ANOVA<\/td>\n<td>analysis of variance<\/td>\n<\/tr>\n<tr>\n<td>AST<\/td>\n<td>aspartate aminotransferase<\/td>\n<\/tr>\n<tr>\n<td>BMI<\/td>\n<td>body mass index<\/td>\n<\/tr>\n<tr>\n<td>DNA<\/td>\n<td>deoxyribonucleic acid<\/td>\n<\/tr>\n<tr>\n<td>GCP<\/td>\n<td>Good Clinical Practices<\/td>\n<\/tr>\n<tr>\n<td>GGT<\/td>\n<td>gamma glutamyl transferase<\/td>\n<\/tr>\n<tr>\n<td>HDL<\/td>\n<td>high density lipoproteins<\/td>\n<\/tr>\n<tr>\n<td>LDL<\/td>\n<td>low density lipoprotein<\/td>\n<\/tr>\n<tr>\n<td>IRB<\/td>\n<td>institutional review board<\/td>\n<\/tr>\n<tr>\n<td>MCH<\/td>\n<td>mean corpuscular hemoglobin<\/td>\n<\/tr>\n<tr>\n<td>Mg<\/td>\n<td>Magnesium metal<\/td>\n<\/tr>\n<tr>\n<td>Mg (OH)<sub>2<\/sub><\/td>\n<td>Magnesium hydroxide<\/td>\n<\/tr>\n<tr>\n<td>ROS<\/td>\n<td>reactive oxygen species<\/td>\n<\/tr>\n<tr>\n<td>SD<\/td>\n<td>standard deviation<\/td>\n<\/tr>\n<tr>\n<td>SOD<\/td>\n<td>superoxide dismutase<\/td>\n<\/tr>\n<tr>\n<td>TBARS<\/td>\n<td>Thiobarbituric Acid Reactive Substances<\/td>\n<\/tr>\n<tr>\n<td>eGFR<\/td>\n<td>estimated glomerular filtration rate<\/td>\n<\/tr>\n<tr>\n<td>HO-1<\/td>\n<td>heme oxygenase<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"ref-list-a.m.c\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"ref-list-a.m.ctitle\">References<\/h2>\n<div class=\"ref-list-sec sec\" id=\"reference-list\">\n<div class=\"ref-cit-blk half_rhythm\" id=\"B1\">1. <span class=\"mixed-citation\">Furukawa S., Fujita T., Shimabukuro M., Iwaki M., Yamada Y., Nakajima Y., Nakayama O., Makishima M., Matsuda M., Shimomura I. 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Scholar<\/a>]<\/span><\/span><\/div>\n<\/div>\n<\/div>\n<div style=\"display: none; width: 200px; top: -100px; left: -100px;\" aria-live=\"assertive\" aria-hidden=\"true\" class=\"ui-helper-reset ui-ncbipopper-wrapper ui-ncbilinksmenu\">\n<ul id=\"ui-ncbiinpagenav-2\">\n<li><a href=\"#abstract-a.k.b.qtitle\">Abstract<\/a><\/li>\n<li><a href=\"#sec-a.l.atitle\">Introduction<\/a><\/li>\n<li><a href=\"#sec-a.l.btitle\">Materials and Methods<\/a><\/li>\n<li><a href=\"#sec-a.l.ctitle\">Results<\/a><\/li>\n<li><a href=\"#sec-a.l.dtitle\">Discussion<\/a><\/li>\n<li><a href=\"#ack-a.m.atitle\">Acknowledgments<\/a><\/li>\n<li><a href=\"#glossary-a.m.btitle\">Abbreviations<\/a><\/li>\n<li><a href=\"#ref-list-a.m.ctitle\">References<\/a><\/li>\n<\/ul>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study<\/p>\n","protected":false},"author":1,"featured_media":17899,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[130],"tags":[],"disease":[896],"body-organ":[1022],"applications":[680],"test_subjects":[1519],"report-topic":[1280],"class_list":["post-27740","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-hydrogen-health","disease-metabolic-syndrome-2","body-organ-whole-body-2","applications-ingestion-2","test_subjects-human-2","report-topic-oxidative-stress-2"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>H2-rich water and antioxidant status in metabolic syndrome<\/title>\n<meta name=\"description\" content=\"Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label 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