氢气：健康与医学治疗潜力
HYDROGEN: THERAPEUTIC POTENTIAL IN WELLNESS AND MEDICINE
译文简介
氢气医学研究论文翻译，不推荐作为健康指导
正文翻译
HYDROGEN: THERAPEUTIC POTENTIAL IN WELLNESS AND MEDICINE
原文标题：氢气：健康与医学治疗潜力
原创翻译：龙腾网 http://www.ltaaa.cn 转载请注明出处
原文标题：氢气：健康与医学治疗潜力
原创翻译：龙腾网 http://www.ltaaa.cn 转载请注明出处
M. Lemaire1, F. Barbier2
1. Air Liquide Sante International, Paris Saclay Research Center, Jouy-en-Josas, France, 2. Air Liquide R&D, Paris Saclay Research Center, Jouy-en-Josas, France.
Corresponding Author: Marc Lemaire, Air Liquide Sante International, Paris Saclay Research Center, 1, route de la porte des loges, Les Loges-en-Josas, 78354, Jouy-en-Josas, France. Tel: +33139076212; Fax:+33139076199; email: Marc.lemaire@airliquide.com
J Aging Res Clin Practice 2017;6:14-22
Published online January 6, 2017, http://dx.doi.org/10.14283/jarcp.2017.2
Abstract
Persistent oxidative stress plays an important role in a variety of pathologies, and the search for an effective and well tolerated antioxidant agent continues. Molecular hydrogen acts as a therapeutic antioxidant by sextively reducing cytotoxic oxygen radicals. The non-specific mechanism of hydrogen as a therapeutic antioxidant gives it broad therapeutic potential across a wide range of medical applications, as has been shown by a substantial volume of preclinical data, as well as a growing body of clinical evidence. This review provides an overview of the therapeutic potential of hydrogen, in ageing and wellness applications as well as medical applications, including acute ischemia/reperfusion injury, inflammation and ulceration, metabolic disorders, neurodegenerative disorders, and cancer (anti-cancer effects, radiation toxicities, and side effects of cisplatin) with an emphasis on clinical data. Overall, this review shows that hydrogen is an effective antioxidant, anti-inflammatory and cytoprotective agent.
摘要
持续性氧化应激在各种病理学中起着重要作用，人们继续寻找有效且耐受性良好的抗氧化剂。分子氢通过选择性地减少细胞毒氧自由基作为治疗性抗氧化剂。氢作为治疗性抗氧化剂的非特异性机制在医学应用中具有广泛治疗潜力，大量的临床数据以及越来越多临床证据都证明了这一点。本摘要概述了氢气在衰老和健康应用以及医疗应用中的治疗潜力，包括急性缺血/再灌注损伤、炎症和溃疡、代谢紊乱、神经退行性疾病和癌症(抗癌作用、辐射毒性和顺铂的副作用)，重点关注相关临床数据。总的来说，这次研究表明氢是一种有效的抗氧化、抗炎和细胞保护剂。
1. Air Liquide Sante International, Paris Saclay Research Center, Jouy-en-Josas, France, 2. Air Liquide R&D, Paris Saclay Research Center, Jouy-en-Josas, France.
Corresponding Author: Marc Lemaire, Air Liquide Sante International, Paris Saclay Research Center, 1, route de la porte des loges, Les Loges-en-Josas, 78354, Jouy-en-Josas, France. Tel: +33139076212; Fax:+33139076199; email: Marc.lemaire@airliquide.com
J Aging Res Clin Practice 2017;6:14-22
Published online January 6, 2017, http://dx.doi.org/10.14283/jarcp.2017.2
Abstract
Persistent oxidative stress plays an important role in a variety of pathologies, and the search for an effective and well tolerated antioxidant agent continues. Molecular hydrogen acts as a therapeutic antioxidant by sextively reducing cytotoxic oxygen radicals. The non-specific mechanism of hydrogen as a therapeutic antioxidant gives it broad therapeutic potential across a wide range of medical applications, as has been shown by a substantial volume of preclinical data, as well as a growing body of clinical evidence. This review provides an overview of the therapeutic potential of hydrogen, in ageing and wellness applications as well as medical applications, including acute ischemia/reperfusion injury, inflammation and ulceration, metabolic disorders, neurodegenerative disorders, and cancer (anti-cancer effects, radiation toxicities, and side effects of cisplatin) with an emphasis on clinical data. Overall, this review shows that hydrogen is an effective antioxidant, anti-inflammatory and cytoprotective agent.
摘要
持续性氧化应激在各种病理学中起着重要作用，人们继续寻找有效且耐受性良好的抗氧化剂。分子氢通过选择性地减少细胞毒氧自由基作为治疗性抗氧化剂。氢作为治疗性抗氧化剂的非特异性机制在医学应用中具有广泛治疗潜力，大量的临床数据以及越来越多临床证据都证明了这一点。本摘要概述了氢气在衰老和健康应用以及医疗应用中的治疗潜力，包括急性缺血/再灌注损伤、炎症和溃疡、代谢紊乱、神经退行性疾病和癌症(抗癌作用、辐射毒性和顺铂的副作用)，重点关注相关临床数据。总的来说，这次研究表明氢是一种有效的抗氧化、抗炎和细胞保护剂。
Key words: Hydrogen, ageing, wellness, inflammation, antioxidant.
关键词：氢气、衰老、健康、炎症、抗氧化
关键词：氢气、衰老、健康、炎症、抗氧化
Introduction
Hydrogen, a single proton and a lone electron, is the lightest and most abundant element in the universe. On Earth, hydrogen generally exists in compounds with other elements, and is not found by itself. The most common sources of hydrogen are hydrocarbons, water and carbohydrates from which molecular hydrogen can be produced (1).
With more than 50 million tons produced globally each year, hydrogen is one of the oldest known molecules that is used extensively by many industries. Most of its uses are based on its physical properties, such as its very low molecular weight (2.0159 g/mol H2) and density (0.084 g/l at 20°C and 1 atm), and its chemical properties such as its reactivity, forming compounds or preventing oxidation of metals due to its reducing properties (1). Hydrogen has the potential to become an important future energy solution due its high calorific value and its environmentally friendly properties, generating only water vapor when used in fuel cells to produce electricity. The benefits of molecular hydrogen in therapeutic applications have been discovered relatively recently, and remain to be completely elucidated. Many consider hydrogen to have healing properties, with its role as the fundamental antioxidant for every cell. Reactive oxygen species (ROS) are generated in the bodies of all aerobic organisms as by-products of energy metabolism via oxidative phosphorylation (2). Excess production of ROS or impaired endogenous antioxidant capacity result in a build-up of ROS, known as oxidative stress (2). It is widely accepted that persistent oxidative stress plays an important role in a variety of pathologies, including lifestyle-related diseases such as atherosclerosis and diabetes mellitus, hypertension, chronic inflammation, neurodegenerative diseases, cancer, decreased vascular function and the ageing process (2-7). However, the majority of prospective controlled clinical trials of antioxidant therapy to prevent oxidative stress-related diseases, mostly cardiovascular indications, have failed (8). Therefore, the search for an effective and well tolerated antioxidant agent continues.
氢，由一个质子和一个电子组成，是宇宙中最轻和最丰富的元素。在地球上，氢通常存在于其他元素的化合物中，氢气单质并不存在。最常见的氢气来源是碳氢化合物、水和碳水化合物，从中可以产生分子氢(1)。
全球每年生产超过5000万吨氢气，是已知最古老的分子之一，被许多行业广泛使用。它的大部分用途是基于其物理特性，如其非常低的分子量(2.0159克/摩尔H2)和密度(0.084克/升，在20°C和1atm)，其化学性质，如其反应性，形成化合物或防止金属氧化，由于其减少特性(1)。氢气具有高热值和环保无污染的特性，在燃料电池中发电时只产生水蒸气，因此有可能成为未来重要的能源解决方案。分子氢在治疗应用中的用处最近被发现，还有待完全阐明。许多人认为氢具有愈合作用，其作用机理是每个细胞的基本抗氧化剂。反应性氧自由基(ROS)在所有有氧生物体内生成，是氧化磷酸化体反应产生能量代谢的副产品(2)。过量生产 ROS 或受损的内源性抗氧化能力会导致 ROS 的积累，称为氧化应激(2)。人们普遍认为，持续的氧化应激在各种病理学中起着重要作用，包括与生活方式有关的疾病，如动脉粥样硬化和糖尿病、高血压、慢性炎症、神经退行性疾病、癌症、血管功能下降和衰老过程(2-7)。然而，大多数潜在的以防止氧化应激相关疾病，主要是心血管适应症为目的的抗氧化治疗对照临床试验都失败了(8)。因此，人们一直在继续寻找有效和耐受性良好的抗氧化剂。
Hydrogen, a single proton and a lone electron, is the lightest and most abundant element in the universe. On Earth, hydrogen generally exists in compounds with other elements, and is not found by itself. The most common sources of hydrogen are hydrocarbons, water and carbohydrates from which molecular hydrogen can be produced (1).
With more than 50 million tons produced globally each year, hydrogen is one of the oldest known molecules that is used extensively by many industries. Most of its uses are based on its physical properties, such as its very low molecular weight (2.0159 g/mol H2) and density (0.084 g/l at 20°C and 1 atm), and its chemical properties such as its reactivity, forming compounds or preventing oxidation of metals due to its reducing properties (1). Hydrogen has the potential to become an important future energy solution due its high calorific value and its environmentally friendly properties, generating only water vapor when used in fuel cells to produce electricity. The benefits of molecular hydrogen in therapeutic applications have been discovered relatively recently, and remain to be completely elucidated. Many consider hydrogen to have healing properties, with its role as the fundamental antioxidant for every cell. Reactive oxygen species (ROS) are generated in the bodies of all aerobic organisms as by-products of energy metabolism via oxidative phosphorylation (2). Excess production of ROS or impaired endogenous antioxidant capacity result in a build-up of ROS, known as oxidative stress (2). It is widely accepted that persistent oxidative stress plays an important role in a variety of pathologies, including lifestyle-related diseases such as atherosclerosis and diabetes mellitus, hypertension, chronic inflammation, neurodegenerative diseases, cancer, decreased vascular function and the ageing process (2-7). However, the majority of prospective controlled clinical trials of antioxidant therapy to prevent oxidative stress-related diseases, mostly cardiovascular indications, have failed (8). Therefore, the search for an effective and well tolerated antioxidant agent continues.
氢，由一个质子和一个电子组成，是宇宙中最轻和最丰富的元素。在地球上，氢通常存在于其他元素的化合物中，氢气单质并不存在。最常见的氢气来源是碳氢化合物、水和碳水化合物，从中可以产生分子氢(1)。
全球每年生产超过5000万吨氢气，是已知最古老的分子之一，被许多行业广泛使用。它的大部分用途是基于其物理特性，如其非常低的分子量(2.0159克/摩尔H2)和密度(0.084克/升，在20°C和1atm)，其化学性质，如其反应性，形成化合物或防止金属氧化，由于其减少特性(1)。氢气具有高热值和环保无污染的特性，在燃料电池中发电时只产生水蒸气，因此有可能成为未来重要的能源解决方案。分子氢在治疗应用中的用处最近被发现，还有待完全阐明。许多人认为氢具有愈合作用，其作用机理是每个细胞的基本抗氧化剂。反应性氧自由基(ROS)在所有有氧生物体内生成，是氧化磷酸化体反应产生能量代谢的副产品(2)。过量生产 ROS 或受损的内源性抗氧化能力会导致 ROS 的积累，称为氧化应激(2)。人们普遍认为，持续的氧化应激在各种病理学中起着重要作用，包括与生活方式有关的疾病，如动脉粥样硬化和糖尿病、高血压、慢性炎症、神经退行性疾病、癌症、血管功能下降和衰老过程(2-7)。然而，大多数潜在的以防止氧化应激相关疾病，主要是心血管适应症为目的的抗氧化治疗对照临床试验都失败了(8)。因此，人们一直在继续寻找有效和耐受性良好的抗氧化剂。
*From Young C.L., 1981 (18).
Hydrogen is an odorless, tasteless gas that has demonstrated many biological effects against oxidative stress in almost all organs (9, 10). Molecular hydrogen acts as a therapeutic antioxidant by sextively reducing cytotoxic oxygen radicals (11). Hydrogen has a number of characteristics that suggest it might be an ideal antioxidant agent for use in humans. These include its ability to neutralize hydroxyl radicals (·OH) in living cells (including penetration into organelles such as mitochondria) and to cross the blood-brain barrier, as well as its stability at room temperature and low solubility in water (1.9 mL H2/100 mL H2O at 20°C and 1 atm, Table 1) and a favorable tolerability profile (2, 10, 12). The advantageous physical and chemical properties of hydrogen, in relation to its therapeutic benefits are summarized in Table 2. Therefore, hydrogen may be potentially useful in the many human diseases known to be associated with oxidative stress, and may have an important role in the prevention of ageing and in many wellness applications.
氢气是一种无色无味气体，在几乎所有器官中表现出许多针对氧化应激的生物效应(9, 10)。分子氢通过选择性地减少细胞毒氧性自由基作为治疗性抗氧化剂(11)。氢有许多特征，表明它可能是一种理想的可作用于人体的抗氧化剂。这些特性包括能够中和活细胞中的羟基自由基(·OH)(包括渗透到线粒体等细胞器中)和穿过血脑屏障的能力，以及它在室温下的稳定性和水中的低溶血性(1.9 mL H2/100 mL H2O ，在 20°C 和 1 atm，表 1)和广泛的生物耐受性 (2, 10, 12)。氢气相对于其治疗益处的有利物理和化学特性，总结于表2。因此，氢气在已知与氧化应激相关的许多人类疾病中可能具有潜在用途，在预防衰老和许多健康应用中可能具有重要作用。
·OH = hydroxyl radical; ROS = reactive oxygen species; ●O2- = superoxide; H2O2: hydrogen peroxide; ONOO-: peroxynitrite
In addition to its role as an anti-oxidant, there is also evidence to suggest that molecular hydrogen has anti-inflammatory properties, via its reaction with the hydroxyl radical (·OH), which is generated during inflammation (13, 14). There is also evidence to suggest that hydrogen acts more directly on inflammation, via the inhibition of lipopolysaccharide/interferon γ-induced nitric oxide production, via modulation of signal transduction in macrophages (15). Hydrogen may therefore also be therapeutically useful in the many inflammatory human diseases. Moreover, hydrogen has also been shown to prevent apoptosis, possibly via its ability to reduce or eliminate the hydroxyl radical (·OH) and peroxynitrite (ONOO-) (16).
Importantly, there are a wide variety of options for the administration of hydrogen, including inhalation as a medical gas, drinking of hydrogen-enriched water (dissolved hydrogen gas, created by exposing water to magnesium, by dissolving electrolyzed hydrogen into water, or by using high pressure to dissolve molecular hydrogen in water (16, 17)), taking a hydrogen bath, injection of hydrogen-enriched saline and use of hydrogen-enriched saline eye drops (12).
It is important to note that due to the low solubility of hydrogen in water (18), the resulting concentration of hydrogen less than 2 % v/v is much lower than the concentration of hydrogen (4% v/v) needed to react with oxygen (1). As a result, hydrogen can be considered as safe and inert within the human body.
This review provides an overview of the therapeutic potential of hydrogen. Ageing and wellness applications are discussed first, followed by a variety of medical applications.
除了作为一种抗氧化剂的作用外，还有证据表明，分子氢通过与炎症期间产生的羟基自由基(·OH)发生反应，具有抗炎特性(13, 14)。还有证据表明，氢气通过调节巨噬细胞的信号转导，抑制脂多糖/γ干扰素诱导的一氧化氮产生，更直接地作用于炎症 (15)。因此，在许多炎症性疾病中，氢也可能有治疗作用。此外，氢气也被证明可以防止细胞凋亡，可能是通过其减少或消除羟基自由基(·OH)和过氧亚硝酸盐(ONOO-)的能力(16)。
重要的是，施用氢气有多种方式，包括作为医用气体吸入、饮用富氢水(溶解氢气，通过将水暴露在镁中、将电解氢溶解到水中或使用高压将分子氢溶解在水中而产生的溶解氢气)(16, 17)、洗氢气浴、注射富氢盐水和使用富氢盐水滴眼液(12)。
值得注意的是，由于氢气在水中的溶解度很低(18)，所产生的氢气浓度低于2% v/v，远远低于与氧气反应所需的最低氢气浓度(4% v/v)。因此，氢气是一种被认为在人体中安全和惰性的气体。
这篇评论概述了氢气的治疗潜力。首先讨论了在老龄化和健康方面的应用，然后是各种医疗应用。
原创翻译：龙腾网 http://www.ltaaa.cn 转载请注明出处
Ageing
Free radicals and reactive oxygen species (ROS) produced by aerobic metabolism play important roles in signal transduction, but also cause damage in biological systems (19). These free radicals and ROS are known to play a role in many human diseases and to be involved in premature ageing (Sun X, 2015).
The search for a simple method to delay or halt the ageing process has been going on for centuries based on efficient anti-oxidant products. Growing evidence of the ability of hydrogen, either as a gas or solution, to scavenge and sextively inactivate ROS suggest that it could exert protective effects (20). Bathing every day for 3 months in waters containing molecular hydrogen (N=18) has been shown to decrease the oxidation-reduction potential (ORP) and increased the elasticity of human skin (21, 22).
The ORP of the skin is increased by sun exposure and by ageing (23), suggesting that a reduction in the ORP might have anti-ageing effects.
对抗老化的应用
有氧代谢产生的自由基和活性氧物种(ROS)在信号转导中起着重要作用，但也对生物系统造成损害 (19)。众所周知，这些自由基和ROS在许多人类疾病中发挥作用，并参与过早衰老(Sun X, 2015)。
几个世纪以来，人们一直在寻找一种简单的方法来延缓或停止老化过程，这种方法的基础是研发出有效的抗氧化产品。越来越多的证据表明氢气作为气体或溶液能够清除和选择性地灭活ROS，这表明它能够发挥保护作用(20)。每天在含有分子氢(N=18)的水中沐浴3个月，可降低氧化还原电位(ORP)，并增加人体皮肤的弹性 (21, 22)。
皮肤的ORP随着接受阳光照射和衰老而增加(23)，这表明ORP的减少可能具有抗衰老作用。
Free radicals and reactive oxygen species (ROS) produced by aerobic metabolism play important roles in signal transduction, but also cause damage in biological systems (19). These free radicals and ROS are known to play a role in many human diseases and to be involved in premature ageing (Sun X, 2015).
The search for a simple method to delay or halt the ageing process has been going on for centuries based on efficient anti-oxidant products. Growing evidence of the ability of hydrogen, either as a gas or solution, to scavenge and sextively inactivate ROS suggest that it could exert protective effects (20). Bathing every day for 3 months in waters containing molecular hydrogen (N=18) has been shown to decrease the oxidation-reduction potential (ORP) and increased the elasticity of human skin (21, 22).
The ORP of the skin is increased by sun exposure and by ageing (23), suggesting that a reduction in the ORP might have anti-ageing effects.
对抗老化的应用
有氧代谢产生的自由基和活性氧物种(ROS)在信号转导中起着重要作用，但也对生物系统造成损害 (19)。众所周知，这些自由基和ROS在许多人类疾病中发挥作用，并参与过早衰老(Sun X, 2015)。
几个世纪以来，人们一直在寻找一种简单的方法来延缓或停止老化过程，这种方法的基础是研发出有效的抗氧化产品。越来越多的证据表明氢气作为气体或溶液能够清除和选择性地灭活ROS，这表明它能够发挥保护作用(20)。每天在含有分子氢(N=18)的水中沐浴3个月，可降低氧化还原电位(ORP)，并增加人体皮肤的弹性 (21, 22)。
皮肤的ORP随着接受阳光照射和衰老而增加(23)，这表明ORP的减少可能具有抗衰老作用。
Wellness
Hydrogen has been shown to be alkaline in water (24, 25). Hydrogen-rich alkaline water obtained by adding H2 to electrolyzed water reduces the pH, but the hydrogen itself that can be expected to be of benefit (26). This has important implications for the wellness industry leading to the development of a beverage or food supplement that is able to take advantage of this hydrogen-associated alkalinity.
健康方面的应用
氢气已被证明在水中是碱性的(24, 25)。通过向电解水添加H2获得的富氢碱性水降低了水的pH值，但可以认为氢气本身是有好处的 (26)。这对健康产业具有重要意义，有利于开发一种能够利用这种与氢有关的碱性饮料或食品补充剂。
Hydrogen has been shown to be alkaline in water (24, 25). Hydrogen-rich alkaline water obtained by adding H2 to electrolyzed water reduces the pH, but the hydrogen itself that can be expected to be of benefit (26). This has important implications for the wellness industry leading to the development of a beverage or food supplement that is able to take advantage of this hydrogen-associated alkalinity.
健康方面的应用
氢气已被证明在水中是碱性的(24, 25)。通过向电解水添加H2获得的富氢碱性水降低了水的pH值，但可以认为氢气本身是有好处的 (26)。这对健康产业具有重要意义，有利于开发一种能够利用这种与氢有关的碱性饮料或食品补充剂。
Exercise performance and sports injury
Exercise-induced production of free radicals is now a well-known phenomenon (27). The increased oxidative stress associated with exercise has the potential to diminish the overall beneficial effects that exercise has on wellbeing.
An open-label pilot study in 19 young, healthy men showed that daily intake of 2 L of hydrogen-enriched water (1.1 mM of dissolved hydrogen) for 7 days increased fasting and post-exercise blood pH, reflecting a reduction in exercise-associated acidosis, with no adverse effects (28). Athletes receiving 1 L of hydrogen water daily showed a significant decrease in the rates of perceived exertion during exercise testing (29), and an attenuation of increases in blood lactate levels and prevention of the post-exercise decrease in peak torque, an indicator of muscle fatigue (30).
To investigate the effects of hydrogen in the management of sports injuries, 12 professional athletes presenting within the first 24 hours after a muscle and tendon strain were randomized in a double-blind study to receive standard care alone (control) or in combination with oral hydrogen tables (2 g/day) and topical hydrogen-enriched packs (6 times per day for 20 minutes). Follow-up after 7 days showed that the addition of hydrogen significantly reduced plasma viscosity (p=0.002) and limb circumference (p=0.04). These results indicate that the addition of oral and topical molecular hydrogen to traditional first-line treatment is effective in the management of musculotendinous injuries (31).
提高运动成绩和治疗运动损伤的作用
运动引起的自由基增多是一个众所周知的现象 (27)。与运动相关的氧化应激增加有可能减少运动对健康的总体有益影响。
一项针对19岁年轻健康男性的开放标签试验研究表明，7天内每天摄入2升富氢水(1.1mM溶解氢)会增加禁食时长和运动后血液pH值，反映出运动相关的酸中毒减少，没有不良反应(28)。每天摄入1升氢水的运动员显示，在运动测试中人体感觉到的消耗率明显下降(29) ，劳累感明显下降，血乳酸水平增多值也有所减小，并防止运动后峰值扭矩的下降——这是肌肉疲劳的指标 (30)。
为了研究氢气在运动损伤管理中的效果，在一项双盲研究中，对12名在肌肉和肌腱拉伤后头24小时内出现的专业运动员进行了随机调查，以单独接受标准护理(对照)或结合口服氢气片(2克/天)和外用富氢包(每天6次，每次20分钟)。7天后的随访显示，添加氢气后，血浆粘度(p=0.002)和肢体围度(p=0.04)明显降低。这些结果表明，在传统的一线治疗中加入口服和外用分子氢气对处理肌肉肌腱损伤是有效的(31)。
Exercise-induced production of free radicals is now a well-known phenomenon (27). The increased oxidative stress associated with exercise has the potential to diminish the overall beneficial effects that exercise has on wellbeing.
An open-label pilot study in 19 young, healthy men showed that daily intake of 2 L of hydrogen-enriched water (1.1 mM of dissolved hydrogen) for 7 days increased fasting and post-exercise blood pH, reflecting a reduction in exercise-associated acidosis, with no adverse effects (28). Athletes receiving 1 L of hydrogen water daily showed a significant decrease in the rates of perceived exertion during exercise testing (29), and an attenuation of increases in blood lactate levels and prevention of the post-exercise decrease in peak torque, an indicator of muscle fatigue (30).
To investigate the effects of hydrogen in the management of sports injuries, 12 professional athletes presenting within the first 24 hours after a muscle and tendon strain were randomized in a double-blind study to receive standard care alone (control) or in combination with oral hydrogen tables (2 g/day) and topical hydrogen-enriched packs (6 times per day for 20 minutes). Follow-up after 7 days showed that the addition of hydrogen significantly reduced plasma viscosity (p=0.002) and limb circumference (p=0.04). These results indicate that the addition of oral and topical molecular hydrogen to traditional first-line treatment is effective in the management of musculotendinous injuries (31).
提高运动成绩和治疗运动损伤的作用
运动引起的自由基增多是一个众所周知的现象 (27)。与运动相关的氧化应激增加有可能减少运动对健康的总体有益影响。
一项针对19岁年轻健康男性的开放标签试验研究表明，7天内每天摄入2升富氢水(1.1mM溶解氢)会增加禁食时长和运动后血液pH值，反映出运动相关的酸中毒减少，没有不良反应(28)。每天摄入1升氢水的运动员显示，在运动测试中人体感觉到的消耗率明显下降(29) ，劳累感明显下降，血乳酸水平增多值也有所减小，并防止运动后峰值扭矩的下降——这是肌肉疲劳的指标 (30)。
为了研究氢气在运动损伤管理中的效果，在一项双盲研究中，对12名在肌肉和肌腱拉伤后头24小时内出现的专业运动员进行了随机调查，以单独接受标准护理(对照)或结合口服氢气片(2克/天)和外用富氢包(每天6次，每次20分钟)。7天后的随访显示，添加氢气后，血浆粘度(p=0.002)和肢体围度(p=0.04)明显降低。这些结果表明，在传统的一线治疗中加入口服和外用分子氢气对处理肌肉肌腱损伤是有效的(31)。
Endothelial function
The results of a study in healthy volunteers suggest that hydrogen might contribute to wellness via modulation of vascular vasomotor function secondary to suppression of subclinical vascular inflammation (32). Thirty minutes after drinking 530 mL of hydrogen-enriched water (each 500 mL containing 3.5 mg of H2), healthy volunteers showed significantly improved flow-mediated dilation in the brachial artery compared with subjects who drank placebo water (p=0.0221). Potential mechanisms proposed for this effect were neutralization of ROS to preserve NO bioavailability, and suppression of inflammatory pre-atherosclerotic events.
调节血管内皮功能
一项对健康志愿者的研究结果表明，氢可能通过调节血管运动功能继而抑制亚临床血管炎症来促进健康 (32)。在饮用530ml富含氢气的水(每500毫升含3.5毫克H2)30分钟后，健康志愿者与饮用安慰剂水的受试者相比，肱动脉血流介导的扩张得到改善(P=0.0221)。这种效果的潜在机制是中和ROS以保持NO(一氧化氮)的生物利用率，以及抑制炎症性动脉硬化前事件。
The results of a study in healthy volunteers suggest that hydrogen might contribute to wellness via modulation of vascular vasomotor function secondary to suppression of subclinical vascular inflammation (32). Thirty minutes after drinking 530 mL of hydrogen-enriched water (each 500 mL containing 3.5 mg of H2), healthy volunteers showed significantly improved flow-mediated dilation in the brachial artery compared with subjects who drank placebo water (p=0.0221). Potential mechanisms proposed for this effect were neutralization of ROS to preserve NO bioavailability, and suppression of inflammatory pre-atherosclerotic events.
调节血管内皮功能
一项对健康志愿者的研究结果表明，氢可能通过调节血管运动功能继而抑制亚临床血管炎症来促进健康 (32)。在饮用530ml富含氢气的水(每500毫升含3.5毫克H2)30分钟后，健康志愿者与饮用安慰剂水的受试者相比，肱动脉血流介导的扩张得到改善(P=0.0221)。这种效果的潜在机制是中和ROS以保持NO(一氧化氮)的生物利用率，以及抑制炎症性动脉硬化前事件。
Medical applications
Major syndromes
Acute ischemia/reperfusion injury
Stroke and myocardial infarction
For both stroke and myocardial infarction the successful treatment strategies to restore blood flow to ischemic tissue are associated with reperfusion injury. One mechanism thought to contribute to this negative outcome is the generation of ROS (33).
In an animal model, inhalation of 2% hydrogen prior to reperfusion has been shown to attenuate ischemia/reperfusion injury (IRI) occurring during coronary artery reperfusion, with a significant reduction in infarct size, (41.6% vs 21.2%: p<0.05) (34). Hydrogen-rich saline (0.6 mM) reduced the apoptosis IRI, (TUNEL-positive cells: 15% vs 24%: p<0.05), decreased infarct size (9.8% vs 32.1%: p<0.01) and improved heart function parameters 24 hours after reperfusion (35). Hydrogen-enriched saline (0.6 mM) has also been shown to decrease infarct size (p<0.05) as well as both oxidative stress and inflammation (36). In mice, inhalation of hydrogen (2%), alone and in combination with nitric oxide (NO), reduced infarct size after IRI. The hydrogen/NO combination was also associated with preservation of cardiac function after IRI (37). These findings suggest that patients may benefit from hydrogen inhalation as an add-on to percutaneous coronary intervention procedures.
ROS are generated during cerebral IRI and contribute significantly to brain injury. Inhalation of hydrogen at 2% to 4% during reperfusion decreased infarct volume in rats after middle cerebral artery occlusion and reperfusion (p<0.001); inhalation of hydrogen during ischemia had no effect on infarct size in this model (11), hence to have an effect, hydrogen must be used following reperfusion, as is the case for all organ protective molecules.
In experimental hepatic IRI, inhalation of hydrogen (1% to 4%) and intraperitoneal injection of hydrogen-enriched saline (2.5, 5 or 10 mL/kg) have both been associated with reductions in the severity of liver injury, improved liver function and decreases in markers of lipid peroxidation and inflammation (38, 39). Similar findings have been reported after treatment with hydrogen-rich saline (>0.6 mM) in rats subjected to renal IRI (40).
In a clinical setting, the addition of intravenous hydrogen-rich saline (>250 μmol/L) to treatment with the hydroxyl radical scavenger/neuroprotective agent edaravone in acute brainstem infarction patients was associated with incremental improvements in magnetic resonance imaging (MRI) findings compared with the natural course: relative diffusion-weighted images (rDWIs), regional apparent diffusion coefficients (rADCs), and pseudo-normalization time of rDWI and rADC were all improved with the combined infusion of hydrogen and edaravone (41).
医疗应用
主要综合征
急性缺血/再灌注损伤
中风和心肌梗塞
对于中风和心肌梗死，恢复缺血组织血流的成功治疗策略都与再灌注损伤有关。一个被认为有助于这种负面结果的机制是ROS的产生(33)。
在一个动物模型中，再灌注前吸入2%的氢气已被证明可以减轻冠状动脉再灌注过程中发生的缺血/再灌注损伤(IRI)，梗塞面积明显减少，(41.6% vs 21.2%：P<0.05)(34)。富氢盐水(0.6mM)减少了IRI的凋亡，(TUNEL阳性细胞：15% vs 24%：p<0.05)，减少了梗死面积(9.8% vs 32.1%：p<0.01)，改善了再灌注后24小时的心脏功能参数(35)。富氢盐水(0.6mM)也被证明可以减少梗塞的大小(p<0.05)，以及氧化应激和炎症(36)。在小鼠中，吸入氢气(2%)，单独或与一氧化氮(NO)结合使用，可以减少IRI后的梗塞大小。氢气/一氧化氮组合也与IRI后心脏功能的保护有关(37)。这些发现表明，作为经皮冠状动脉介入手术的补充，患者可能从氢气吸入中受益。
ROS在大脑缺血/再灌注损伤期间产生，对脑损伤有很大的影响。在再灌注期间吸入2%至4%的氢气可以减少大脑中动脉闭塞和再灌注后大鼠的梗塞体积(P<0.001)；在缺血期间吸入氢气对该模型的梗塞大小没有影响(11)，因此要产生效果，氢气必须在再灌注后使用，所有器官保护分子的情况都是如此。
在实验性肝脏缺血/再灌注损伤中，吸入氢气(1%到4%)和腹腔注射富含氢气的生理盐水(2.5，5或10mL/公斤)都与肝脏损伤的严重程度降低、肝功能改善以及脂质过氧化和炎症标志物的减少有关(38，39)。用富氢盐水(>0.6mM)处理肾脏缺血/再灌注损伤的大鼠后也有类似的发现(40)。
在临床上，急性脑干梗塞患者在使用羟基自由基清除剂/神经保护剂——依达拉奉治疗的同时，静脉注射富氢盐水(>250μmol/L)，与自然过程相比，磁共振成像(MRI)结果有了增量改善。相对扩散加权图像(rDWIs)、区域表观扩散系数(rADCs)以及rDWI和rADC的伪正常化时间都因联合输注氢气和依达拉奉而得到改善(41)。
Major syndromes
Acute ischemia/reperfusion injury
Stroke and myocardial infarction
For both stroke and myocardial infarction the successful treatment strategies to restore blood flow to ischemic tissue are associated with reperfusion injury. One mechanism thought to contribute to this negative outcome is the generation of ROS (33).
In an animal model, inhalation of 2% hydrogen prior to reperfusion has been shown to attenuate ischemia/reperfusion injury (IRI) occurring during coronary artery reperfusion, with a significant reduction in infarct size, (41.6% vs 21.2%: p<0.05) (34). Hydrogen-rich saline (0.6 mM) reduced the apoptosis IRI, (TUNEL-positive cells: 15% vs 24%: p<0.05), decreased infarct size (9.8% vs 32.1%: p<0.01) and improved heart function parameters 24 hours after reperfusion (35). Hydrogen-enriched saline (0.6 mM) has also been shown to decrease infarct size (p<0.05) as well as both oxidative stress and inflammation (36). In mice, inhalation of hydrogen (2%), alone and in combination with nitric oxide (NO), reduced infarct size after IRI. The hydrogen/NO combination was also associated with preservation of cardiac function after IRI (37). These findings suggest that patients may benefit from hydrogen inhalation as an add-on to percutaneous coronary intervention procedures.
ROS are generated during cerebral IRI and contribute significantly to brain injury. Inhalation of hydrogen at 2% to 4% during reperfusion decreased infarct volume in rats after middle cerebral artery occlusion and reperfusion (p<0.001); inhalation of hydrogen during ischemia had no effect on infarct size in this model (11), hence to have an effect, hydrogen must be used following reperfusion, as is the case for all organ protective molecules.
In experimental hepatic IRI, inhalation of hydrogen (1% to 4%) and intraperitoneal injection of hydrogen-enriched saline (2.5, 5 or 10 mL/kg) have both been associated with reductions in the severity of liver injury, improved liver function and decreases in markers of lipid peroxidation and inflammation (38, 39). Similar findings have been reported after treatment with hydrogen-rich saline (>0.6 mM) in rats subjected to renal IRI (40).
In a clinical setting, the addition of intravenous hydrogen-rich saline (>250 μmol/L) to treatment with the hydroxyl radical scavenger/neuroprotective agent edaravone in acute brainstem infarction patients was associated with incremental improvements in magnetic resonance imaging (MRI) findings compared with the natural course: relative diffusion-weighted images (rDWIs), regional apparent diffusion coefficients (rADCs), and pseudo-normalization time of rDWI and rADC were all improved with the combined infusion of hydrogen and edaravone (41).
医疗应用
主要综合征
急性缺血/再灌注损伤
中风和心肌梗塞
对于中风和心肌梗死，恢复缺血组织血流的成功治疗策略都与再灌注损伤有关。一个被认为有助于这种负面结果的机制是ROS的产生(33)。
在一个动物模型中，再灌注前吸入2%的氢气已被证明可以减轻冠状动脉再灌注过程中发生的缺血/再灌注损伤(IRI)，梗塞面积明显减少，(41.6% vs 21.2%：P<0.05)(34)。富氢盐水(0.6mM)减少了IRI的凋亡，(TUNEL阳性细胞：15% vs 24%：p<0.05)，减少了梗死面积(9.8% vs 32.1%：p<0.01)，改善了再灌注后24小时的心脏功能参数(35)。富氢盐水(0.6mM)也被证明可以减少梗塞的大小(p<0.05)，以及氧化应激和炎症(36)。在小鼠中，吸入氢气(2%)，单独或与一氧化氮(NO)结合使用，可以减少IRI后的梗塞大小。氢气/一氧化氮组合也与IRI后心脏功能的保护有关(37)。这些发现表明，作为经皮冠状动脉介入手术的补充，患者可能从氢气吸入中受益。
ROS在大脑缺血/再灌注损伤期间产生，对脑损伤有很大的影响。在再灌注期间吸入2%至4%的氢气可以减少大脑中动脉闭塞和再灌注后大鼠的梗塞体积(P<0.001)；在缺血期间吸入氢气对该模型的梗塞大小没有影响(11)，因此要产生效果，氢气必须在再灌注后使用，所有器官保护分子的情况都是如此。
在实验性肝脏缺血/再灌注损伤中，吸入氢气(1%到4%)和腹腔注射富含氢气的生理盐水(2.5，5或10mL/公斤)都与肝脏损伤的严重程度降低、肝功能改善以及脂质过氧化和炎症标志物的减少有关(38，39)。用富氢盐水(>0.6mM)处理肾脏缺血/再灌注损伤的大鼠后也有类似的发现(40)。
在临床上，急性脑干梗塞患者在使用羟基自由基清除剂/神经保护剂——依达拉奉治疗的同时，静脉注射富氢盐水(>250μmol/L)，与自然过程相比，磁共振成像(MRI)结果有了增量改善。相对扩散加权图像(rDWIs)、区域表观扩散系数(rADCs)以及rDWI和rADC的伪正常化时间都因联合输注氢气和依达拉奉而得到改善(41)。
Cardiac arrest and hemorrhagic shock
Intraperitoneal injection of hydrogen (10 or 20 mL/kg) reduced neuronal injury and inhibited neuronal apoptosis in a rabbit model of cardiac arrest; these effects appeared to occur via reductions in oxidative stress indicators and enhanced antioxidant enzyme activity (42). Similar beneficial effects have been observed with inhalation of hydrogen (2% H2 and 98% O2) during cardiopulmonary resuscitation in a rat model of cardiac arrest, with treated animals having improved survival and fewer neurological deficits compared with animals who underwent therapeutic hypothermia (43).
The anti-inflammatory, antioxidant and beneficial effects of hydrogen have also been documented in a number of other acute oxidative stress settings, including a rat model of uncontrolled hemorrhagic shock, where hydrogen-rich saline (>0.6 mM) had better activity when administered via the intravenous versus intraperitoneal route (44).
心脏骤停和失血性休克
腹腔注射氢气(10或20mL/公斤)减少了神经元的损伤，并抑制了心脏骤停的兔子模型中的神经元凋亡；这些影响似乎是通过减少氧化应激指标和增强抗氧化酶的活性而发生(42)。在心脏骤停的大鼠模型中，在心肺复苏期间吸入氢气(2%的H2和98%的O2)也观察到类似的有益效果，与接受治疗性低温的动物相比，接受氢气治疗的动物生存率提高，神经功能障碍减少(43)。
氢气的抗炎、抗氧化和有益作用在其他一些急性氧化应激环境中也有记载，包括失控失血性休克大鼠模型，富氢盐水(>0.6mM)通过静脉注射与腹腔注射途径的活性效果更佳(44)。
Intraperitoneal injection of hydrogen (10 or 20 mL/kg) reduced neuronal injury and inhibited neuronal apoptosis in a rabbit model of cardiac arrest; these effects appeared to occur via reductions in oxidative stress indicators and enhanced antioxidant enzyme activity (42). Similar beneficial effects have been observed with inhalation of hydrogen (2% H2 and 98% O2) during cardiopulmonary resuscitation in a rat model of cardiac arrest, with treated animals having improved survival and fewer neurological deficits compared with animals who underwent therapeutic hypothermia (43).
The anti-inflammatory, antioxidant and beneficial effects of hydrogen have also been documented in a number of other acute oxidative stress settings, including a rat model of uncontrolled hemorrhagic shock, where hydrogen-rich saline (>0.6 mM) had better activity when administered via the intravenous versus intraperitoneal route (44).
心脏骤停和失血性休克
腹腔注射氢气(10或20mL/公斤)减少了神经元的损伤，并抑制了心脏骤停的兔子模型中的神经元凋亡；这些影响似乎是通过减少氧化应激指标和增强抗氧化酶的活性而发生(42)。在心脏骤停的大鼠模型中，在心肺复苏期间吸入氢气(2%的H2和98%的O2)也观察到类似的有益效果，与接受治疗性低温的动物相比，接受氢气治疗的动物生存率提高，神经功能障碍减少(43)。
氢气的抗炎、抗氧化和有益作用在其他一些急性氧化应激环境中也有记载，包括失控失血性休克大鼠模型，富氢盐水(>0.6mM)通过静脉注射与腹腔注射途径的活性效果更佳(44)。
Organ transplantation
Preclinical data show that the antioxidant effects of hydrogen therapy are evident in organ transplantation models. In a rat model of renal transplant, treatment with hydrogen-enriched water versus regular water reduced chronic allograft nephropathy and improved overall post-transplant survival; these effects appeared to be secondary to reductions in oxidative stress-induced tissue damage (45). Hydrogen-enriched water (0.5 or 0.6 mM) has also been shown to protect rat cardiac allografts from oxidative injury and inflammation-associated deterioration, with significant reductions in markers of oxidative injury and of inflammation (p<0.05), thereby increasing allograft survival (46). Moreover, hydrogen-enriched water (0.55–0.65 mM) inhibited intimal hyperplasia and reduced oxidative damage in arterialized vein grafts in rats (47). Inhaled hydrogen (2%) appears to have beneficial effects in models of lung and intestinal transplantation, including improved spontaneous muscle contractile activity, reduced expression of inflammatory mediators and oxidative injury, prevention of IRI and improved graft survival (48, 49).
器官移植
临床前数据显示，氢气疗法的抗氧化作用在器官移植模型中很明显。在大鼠的肾移植模型中，富氢水与普通水相比可以减少慢性移植物肾病，并提高移植后的总体存活率；这些效果似乎是由于氧化应激引起的组织损伤的减少(45)。富氢水(0.5~0.6 mM)也被证明可以保护大鼠心脏异体移植免受氧化损伤和炎症相关的恶化影响，氧化损伤和炎症标志物明显减少(P<0.05)，从而提高异体移植的存活率(46)。此外，富含氢气的水(0.55~0.65mM)抑制了大鼠动脉化静脉移植物的内膜增生并减少了氧化损伤(47)。吸入氢气(2%)似乎对肺和肠移植模型有好处，包括改善自发的肌肉收缩活动，减少炎症介质的表达和氧化损伤，预防急性缺血/再灌注损伤和改善移植物存活率(48，49)。
Preclinical data show that the antioxidant effects of hydrogen therapy are evident in organ transplantation models. In a rat model of renal transplant, treatment with hydrogen-enriched water versus regular water reduced chronic allograft nephropathy and improved overall post-transplant survival; these effects appeared to be secondary to reductions in oxidative stress-induced tissue damage (45). Hydrogen-enriched water (0.5 or 0.6 mM) has also been shown to protect rat cardiac allografts from oxidative injury and inflammation-associated deterioration, with significant reductions in markers of oxidative injury and of inflammation (p<0.05), thereby increasing allograft survival (46). Moreover, hydrogen-enriched water (0.55–0.65 mM) inhibited intimal hyperplasia and reduced oxidative damage in arterialized vein grafts in rats (47). Inhaled hydrogen (2%) appears to have beneficial effects in models of lung and intestinal transplantation, including improved spontaneous muscle contractile activity, reduced expression of inflammatory mediators and oxidative injury, prevention of IRI and improved graft survival (48, 49).
器官移植
临床前数据显示，氢气疗法的抗氧化作用在器官移植模型中很明显。在大鼠的肾移植模型中，富氢水与普通水相比可以减少慢性移植物肾病，并提高移植后的总体存活率；这些效果似乎是由于氧化应激引起的组织损伤的减少(45)。富氢水(0.5~0.6 mM)也被证明可以保护大鼠心脏异体移植免受氧化损伤和炎症相关的恶化影响，氧化损伤和炎症标志物明显减少(P<0.05)，从而提高异体移植的存活率(46)。此外，富含氢气的水(0.55~0.65mM)抑制了大鼠动脉化静脉移植物的内膜增生并减少了氧化损伤(47)。吸入氢气(2%)似乎对肺和肠移植模型有好处，包括改善自发的肌肉收缩活动，减少炎症介质的表达和氧化损伤，预防急性缺血/再灌注损伤和改善移植物存活率(48，49)。
Inflammation and ulceration
The anti-inflammatory effect of hydrogen is related to the inhibition of the production of ROS and the release of pro-inflammatory cytokines.
In a rat model of ulcerative colitis (UC), intraperitoneal injection of hydrogen-enriched saline (0.6 mM) was shown to reduce weight loss and diarrhea, as well as alleviate colonic mucosal damage (50). Furthermore, hydrogen-enriched saline was also associated with inhibition of the increased expression of vascular endothelial growth factor seen in this UC model.
In another study, four patients with acute erythematous skin disease were found to experience rapid and significant improvements in symptoms after intravenous treatment with 500 mL of hydrogen-enriched water, with no subsequent recurrence (51).
Hydrogen enriched water (600 mL/day: 0.8–1.3 ppm) improved pressure ulcers in 12/22 (55%) of hospitalized elderly patients. The responders had a significant reduction in hospital stay (113.3 days vs 155.4 days; p<0.05) and in the number of pressure ulcers (28.1% reduction) compared with the subgroup of patients for whom hydrogen treatment was not effective. Both groups of hydrogen-treated patients showed a significant reduction in wound size from baseline, which was greater in the effective group. The results of parallel in vitro studies led study investigators to suggest that the beneficial effects of hydrogen therapy were secondary to type-I collagen construction in dermal fibroblasts and/or promoted mitochondrial reducing ability and ROS repression in epidermal keratinocytes (52).
Twenty patients with rheumatoid arthritis (RA), drank 530 mL of hydrogen-rich water (4–5 ppm) every day for 4 weeks in addition to regular RA medication. This treatment period was followed by a 4-week washout then another 4 weeks of treatment (53). There was a mean decrease of 14.3% from baseline in 8-hydroxyguanine (8-OHdG is a standard biomarker for oxidative stress) during the first 4 weeks of treatment (p<0.01) and after the second period of hydrogen-enriched water therapy the reduction in 8OHdG levels was 15.1% (p<0.01 vs baseline). Disease activity scores significantly decreased in 18/20 patients during the first 4-weeks (p<0.01) and remained lower than baseline levels at the end of the 4-week washout phase. At study end, 16 patients had improved disease activity scores and nine patients achieved remission. Four patients had not received any previous RA treatment and all achieved remission during the 12-week study. Apart from increased urinary frequency due to an increased fluid intake, no adverse effects of hydrogen were observed, suggesting that hydrogen water might be a useful addition to conventional therapy in patients with RA (53, 54).
炎症和溃疡
氢气的抗炎作用与抑制ROS的产生和促炎症细胞因子的释放有关。
在溃疡性结肠炎(UC)的大鼠模型中，腹腔注射富氢盐水(0.6mM)被证明可以减少体重减轻和腹泻，以及减轻结肠粘膜损伤(50)。此外，富氢盐水还与抑制该UC模型中观察到的血管内皮生长因子的表达增加有关。
在另一项研究中，发现四名急性红斑性皮肤病患者在静脉注射500毫升富氢水治疗后，症状迅速明显改善，而且随后没有复发(51)。
饮用富氢水(600毫升/天：0.8~1.3ppm)改善了12/22(55%)住院老年患者的褥疮。与氢气治疗无效的患者亚组相比，反应者的住院时间明显减少(113.3天对155.4天；P<0.05)，褥疮数量也明显减少(减少28.1%)。两组接受氢气治疗患者的伤口大小都比对照组明显减少，而有效组的减少幅度更大。平行体外研究的结果使研究人员认为，氢气治疗的有益作用是继发于真皮成纤维细胞的I型胶原蛋白构建和促进线粒体还原能力和表皮角质细胞的ROS抑制(52)。
20名患有类风湿性关节炎(RA)的病人，除了常规RA药物治疗外，每天喝530毫升富含氢气的水(4~5ppm)，为期4周。这个治疗期之后是4周清洗期，然后再进行4周的治疗(53)。在治疗的前4周，8-羟基鸟嘌呤(8-OHdG是氧化压力的标准生物标志物)比基线平均下降了14.3%(P<0.01)，在富氢水治疗的第二个时期后，8OHdG水平下降了15.1%(P<0.01与基线相比)。 在前4周，18/20名患者的疾病活动评分明显下降(P<0.01)，在4周的冲洗阶段结束时仍低于基线水平。在研究结束时，16名患者的疾病活动评分得到改善，9名患者达到缓解。4名患者以前没有接受过任何RA治疗，在12周的研究中都实现了症状缓解。除了因液体摄入量增加而导致尿频外，没有观察到氢气的不良影响，这表明氢水可能是RA患者常规治疗外的有益补充(53，54)。
The anti-inflammatory effect of hydrogen is related to the inhibition of the production of ROS and the release of pro-inflammatory cytokines.
In a rat model of ulcerative colitis (UC), intraperitoneal injection of hydrogen-enriched saline (0.6 mM) was shown to reduce weight loss and diarrhea, as well as alleviate colonic mucosal damage (50). Furthermore, hydrogen-enriched saline was also associated with inhibition of the increased expression of vascular endothelial growth factor seen in this UC model.
In another study, four patients with acute erythematous skin disease were found to experience rapid and significant improvements in symptoms after intravenous treatment with 500 mL of hydrogen-enriched water, with no subsequent recurrence (51).
Hydrogen enriched water (600 mL/day: 0.8–1.3 ppm) improved pressure ulcers in 12/22 (55%) of hospitalized elderly patients. The responders had a significant reduction in hospital stay (113.3 days vs 155.4 days; p<0.05) and in the number of pressure ulcers (28.1% reduction) compared with the subgroup of patients for whom hydrogen treatment was not effective. Both groups of hydrogen-treated patients showed a significant reduction in wound size from baseline, which was greater in the effective group. The results of parallel in vitro studies led study investigators to suggest that the beneficial effects of hydrogen therapy were secondary to type-I collagen construction in dermal fibroblasts and/or promoted mitochondrial reducing ability and ROS repression in epidermal keratinocytes (52).
Twenty patients with rheumatoid arthritis (RA), drank 530 mL of hydrogen-rich water (4–5 ppm) every day for 4 weeks in addition to regular RA medication. This treatment period was followed by a 4-week washout then another 4 weeks of treatment (53). There was a mean decrease of 14.3% from baseline in 8-hydroxyguanine (8-OHdG is a standard biomarker for oxidative stress) during the first 4 weeks of treatment (p<0.01) and after the second period of hydrogen-enriched water therapy the reduction in 8OHdG levels was 15.1% (p<0.01 vs baseline). Disease activity scores significantly decreased in 18/20 patients during the first 4-weeks (p<0.01) and remained lower than baseline levels at the end of the 4-week washout phase. At study end, 16 patients had improved disease activity scores and nine patients achieved remission. Four patients had not received any previous RA treatment and all achieved remission during the 12-week study. Apart from increased urinary frequency due to an increased fluid intake, no adverse effects of hydrogen were observed, suggesting that hydrogen water might be a useful addition to conventional therapy in patients with RA (53, 54).
炎症和溃疡
氢气的抗炎作用与抑制ROS的产生和促炎症细胞因子的释放有关。
在溃疡性结肠炎(UC)的大鼠模型中，腹腔注射富氢盐水(0.6mM)被证明可以减少体重减轻和腹泻，以及减轻结肠粘膜损伤(50)。此外，富氢盐水还与抑制该UC模型中观察到的血管内皮生长因子的表达增加有关。
在另一项研究中，发现四名急性红斑性皮肤病患者在静脉注射500毫升富氢水治疗后，症状迅速明显改善，而且随后没有复发(51)。
饮用富氢水(600毫升/天：0.8~1.3ppm)改善了12/22(55%)住院老年患者的褥疮。与氢气治疗无效的患者亚组相比，反应者的住院时间明显减少(113.3天对155.4天；P<0.05)，褥疮数量也明显减少(减少28.1%)。两组接受氢气治疗患者的伤口大小都比对照组明显减少，而有效组的减少幅度更大。平行体外研究的结果使研究人员认为，氢气治疗的有益作用是继发于真皮成纤维细胞的I型胶原蛋白构建和促进线粒体还原能力和表皮角质细胞的ROS抑制(52)。
20名患有类风湿性关节炎(RA)的病人，除了常规RA药物治疗外，每天喝530毫升富含氢气的水(4~5ppm)，为期4周。这个治疗期之后是4周清洗期，然后再进行4周的治疗(53)。在治疗的前4周，8-羟基鸟嘌呤(8-OHdG是氧化压力的标准生物标志物)比基线平均下降了14.3%(P<0.01)，在富氢水治疗的第二个时期后，8OHdG水平下降了15.1%(P<0.01与基线相比)。 在前4周，18/20名患者的疾病活动评分明显下降(P<0.01)，在4周的冲洗阶段结束时仍低于基线水平。在研究结束时，16名患者的疾病活动评分得到改善，9名患者达到缓解。4名患者以前没有接受过任何RA治疗，在12周的研究中都实现了症状缓解。除了因液体摄入量增加而导致尿频外，没有观察到氢气的不良影响，这表明氢水可能是RA患者常规治疗外的有益补充(53，54)。
Metabolic disorders
Oxidative stress plays a role in the development of type 2 diabetes mellitus, suggested by accumulation of molecular hydrogen in the liver with glycogen after oral administration of hydrogen water in rats (55), making this another possible target for hydrogen therapy. The consumption of hydrogen-enriched water reduced oxidative stress in the liver, improved fatty liver in mice with diabetes and in those with diet-induced obesity reduced plasma glucose and triglyceride levels, attenuated body weight gain, and stimulation of energy metabolism (55).
Patients with type 2 diabetes or impaired glucose tolerance were included an 8-week randomized, double-blind, crossover study of hydrogen-enriched water (1.2 ± 0.1 mg/L) (56). Hydrogen was associated with significant reductions in levels of modified LDL cholesterol, small dense LDL and urinary 8-isoprostanes, plus smaller reductions in serum levels of oxidized LDL and free fatty acids and increased plasma levels of adiponectin and extracellular-superoxide dismutase (56).
Hydrogen-enriched water or saline (>0.6 mM) has been shown to contribute to atherosclerosis prevention in apolipoprotein-E knockout mice (57, 58) and improved plaque stability (59). Additionally, ad libitum access to hydrogen-enriched water (>0.8 mM) ameliorated pulmonary arterial hypertension in a rat model (60), and intraperitoneal administration of hydrogen-enriched saline (>0.6 mM) reduced oxidative stress and attenuated left ventricular hypertrophy in spontaneously hypertensive rats (61).
Three clinical trials have assessed the effects of hydrogen treatment in the metabolic syndrome setting. After 10 weeks of hydrogen water (0.2–0.25 mM), significant reductions from baseline were seen in serum levels of total and low-density lipoprotein (LDL) cholesterol, apolipoproteins B and E, and malondialdehyde (MDA; an indicator of lipid peroxidation). Improvements were also seen in oxidation of LDL and high-density lipoprotein (HDL), and in LDL-mediated inflammation (62). In a similar group of potential metabolic syndrome patients, consumption of 1.5–2L of hydrogen-enriched water (0.55–0.65 mM) per day for 8 weeks increased HDL cholesterol levels and decreased the total cholesterol/HDL cholesterol ratio compared with baseline (63).
代谢紊乱
氧化应激在2型糖尿病的发展中起到关键作用，大鼠口服氢水后，肝脏中的分子氢与糖原的积累表明了这一点(55)，使之成为氢气治疗的另一个可能目标。饮用富氢水可以减少肝脏中的氧化应激反应，改善糖尿病小鼠的脂肪肝症状。在那些由饮食引起的肥胖症小鼠中降低血浆葡萄糖和甘油三酯水平，抑制体重增加，并刺激能量代谢(55)。
2型糖尿病或糖耐量受损的患者被纳入一项为期8周的随机、双盲、交叉富氢水(1.2±0.1毫克/升)(56)研究。发现氢气摄入与改良的低密度脂蛋白胆固醇、小密度脂蛋白和尿液中的8-异丙醇水平的显著降低有关，另外，氧化的低密度脂蛋白和游离脂肪酸的血清水平也有较小的降低，血浆中的脂联素和细胞外超氧化物歧化酶的水平也有增加(56)。
富氢水或生理盐水(>0.6mM)已被证明有助于预防脂蛋白-E基因敲除小鼠的动脉粥样硬化(57，58)并改善斑块稳定性(59)。此外，自由饮用富氢水(>0.8mM)可改善大鼠模型中的肺动脉高压(60)，腹腔注射富氢盐水(>0.6mM)可减少氧化应激并减轻自发性高血压大鼠的左心室肥大症状(61)。
三项临床试验评估了氢气治疗在代谢综合征环境中的效果。使用氢水(0.2~0.25mM)10周后，总胆固醇和低密度脂蛋白(LDL)、载脂蛋白B和E以及丙二醛(MDA；一种脂质过氧化的指标物)的血清水平比基线明显下降。在低密度脂蛋白和高密度脂蛋白(HDL)的氧化，以及低密度脂蛋白介导的炎症方面也有改善(62)。在一组类似的潜在代谢综合征患者中，与基线相比，每天饮用1.5~2L富氢水(0.55~0.65毫摩尔)8周，可提高高密度脂蛋白胆固醇水平，并降低总胆固醇/高密度脂蛋白胆固醇比率(63)。
Oxidative stress plays a role in the development of type 2 diabetes mellitus, suggested by accumulation of molecular hydrogen in the liver with glycogen after oral administration of hydrogen water in rats (55), making this another possible target for hydrogen therapy. The consumption of hydrogen-enriched water reduced oxidative stress in the liver, improved fatty liver in mice with diabetes and in those with diet-induced obesity reduced plasma glucose and triglyceride levels, attenuated body weight gain, and stimulation of energy metabolism (55).
Patients with type 2 diabetes or impaired glucose tolerance were included an 8-week randomized, double-blind, crossover study of hydrogen-enriched water (1.2 ± 0.1 mg/L) (56). Hydrogen was associated with significant reductions in levels of modified LDL cholesterol, small dense LDL and urinary 8-isoprostanes, plus smaller reductions in serum levels of oxidized LDL and free fatty acids and increased plasma levels of adiponectin and extracellular-superoxide dismutase (56).
Hydrogen-enriched water or saline (>0.6 mM) has been shown to contribute to atherosclerosis prevention in apolipoprotein-E knockout mice (57, 58) and improved plaque stability (59). Additionally, ad libitum access to hydrogen-enriched water (>0.8 mM) ameliorated pulmonary arterial hypertension in a rat model (60), and intraperitoneal administration of hydrogen-enriched saline (>0.6 mM) reduced oxidative stress and attenuated left ventricular hypertrophy in spontaneously hypertensive rats (61).
Three clinical trials have assessed the effects of hydrogen treatment in the metabolic syndrome setting. After 10 weeks of hydrogen water (0.2–0.25 mM), significant reductions from baseline were seen in serum levels of total and low-density lipoprotein (LDL) cholesterol, apolipoproteins B and E, and malondialdehyde (MDA; an indicator of lipid peroxidation). Improvements were also seen in oxidation of LDL and high-density lipoprotein (HDL), and in LDL-mediated inflammation (62). In a similar group of potential metabolic syndrome patients, consumption of 1.5–2L of hydrogen-enriched water (0.55–0.65 mM) per day for 8 weeks increased HDL cholesterol levels and decreased the total cholesterol/HDL cholesterol ratio compared with baseline (63).
代谢紊乱
氧化应激在2型糖尿病的发展中起到关键作用，大鼠口服氢水后，肝脏中的分子氢与糖原的积累表明了这一点(55)，使之成为氢气治疗的另一个可能目标。饮用富氢水可以减少肝脏中的氧化应激反应，改善糖尿病小鼠的脂肪肝症状。在那些由饮食引起的肥胖症小鼠中降低血浆葡萄糖和甘油三酯水平，抑制体重增加，并刺激能量代谢(55)。
2型糖尿病或糖耐量受损的患者被纳入一项为期8周的随机、双盲、交叉富氢水(1.2±0.1毫克/升)(56)研究。发现氢气摄入与改良的低密度脂蛋白胆固醇、小密度脂蛋白和尿液中的8-异丙醇水平的显著降低有关，另外，氧化的低密度脂蛋白和游离脂肪酸的血清水平也有较小的降低，血浆中的脂联素和细胞外超氧化物歧化酶的水平也有增加(56)。
富氢水或生理盐水(>0.6mM)已被证明有助于预防脂蛋白-E基因敲除小鼠的动脉粥样硬化(57，58)并改善斑块稳定性(59)。此外，自由饮用富氢水(>0.8mM)可改善大鼠模型中的肺动脉高压(60)，腹腔注射富氢盐水(>0.6mM)可减少氧化应激并减轻自发性高血压大鼠的左心室肥大症状(61)。
三项临床试验评估了氢气治疗在代谢综合征环境中的效果。使用氢水(0.2~0.25mM)10周后，总胆固醇和低密度脂蛋白(LDL)、载脂蛋白B和E以及丙二醛(MDA；一种脂质过氧化的指标物)的血清水平比基线明显下降。在低密度脂蛋白和高密度脂蛋白(HDL)的氧化，以及低密度脂蛋白介导的炎症方面也有改善(62)。在一组类似的潜在代谢综合征患者中，与基线相比，每天饮用1.5~2L富氢水(0.55~0.65毫摩尔)8周，可提高高密度脂蛋白胆固醇水平，并降低总胆固醇/高密度脂蛋白胆固醇比率(63)。
Neurodegenerative diseases
Evidence of increased levels of ROS have been found in post-mortem samples of brain tissue samples from patients with neurodegenerative diseases (3). There are a number of factors that make the brain particularly susceptible to oxidative stress, including its high metabolic rate and reduced capacity for cellular regeneration compared with other organs (3, 64).
Consumption of hydrogen-enriched water (>0.6 mM) ad libitum suppressed increases in oxidative stress markers and improved the proliferation of neural progenitor cells in a mouse chronic physical restraint model (65). Hydrogen-enriched saline reduced oxidative stress, inflammatory responses and amyloid-beta-induced astrocyte activation while improving learning and memory in a rat model of Alzheimer’s disease (66).
In Parkinson’s disease addition of hydrogen to drinking water (>0.4 mM or 0.08–1.5 ppm) prevented the development and progression of nigrostriatal degeneration and dopaminergic neuron loss (67, 68).
The efficacy of hydrogen-enriched water was assessed in a randomized, placebo-controlled, double-blind, parallel clinical trial conducted as a pilot study in levodopa-treated patients with Parkinson’s disease (69). Participants drank 1 L per day of hydrogen-enriched water (prepared by dissolving 0.8 mM H2; n=9) or placebo water (n=8) for 48 weeks. Total Unified Parkinson’s Disease Rating Scale (UPDRS) scores in the hydrogen-enriched water group improved during the study, whereas UPDRS scores in the placebo group worsened (p<0.05 at 48 weeks). Hydrogen-enriched water was well tolerated during the study and no adverse events were reported.
神经退行性疾病
在神经退行性疾病患者的死后脑组织样本中发现了ROS水平增加的证据(3)。有许多因素使大脑特别容易受到氧化应激的影响，包括其高代谢率和与其他器官相比细胞再生能力的降低(3，64)。
随意饮用富氢水(>0.6 mM)可以抑制氧化应激标志物的增加，并改善小鼠慢性身体束缚模型中神经祖细胞的增殖(65)。富氢盐水减少了氧化应激、炎症反应和淀粉样-β-诱导的星形细胞激活，同时改善了阿尔茨海默病大鼠模型的学习和记忆症状(66)。
在帕金森病中，在饮用水中加入氢气(>0.4mM或0.08~1.5ppm)可以防止黑质变性和多巴胺能神经元损失的发展(67，68)。
在一项随机、安慰剂对照、双盲、平行的临床试验中，对左旋多巴治疗的帕金森病患者评估了富氢水的疗效(69)。参与者每天喝1升富氢水(通过溶解0.8mM H2制备；n=9)或安慰剂水(n=8)，持续48周。在研究期间，富氢水组的统一帕金森病评分表(UPDRS)总分有所改善，而安慰剂组的UPDRS评分则有所恶化(48周时P<0.05)。在研究期间，富氢水的人体耐受性良好，没有不良事件报告。
Evidence of increased levels of ROS have been found in post-mortem samples of brain tissue samples from patients with neurodegenerative diseases (3). There are a number of factors that make the brain particularly susceptible to oxidative stress, including its high metabolic rate and reduced capacity for cellular regeneration compared with other organs (3, 64).
Consumption of hydrogen-enriched water (>0.6 mM) ad libitum suppressed increases in oxidative stress markers and improved the proliferation of neural progenitor cells in a mouse chronic physical restraint model (65). Hydrogen-enriched saline reduced oxidative stress, inflammatory responses and amyloid-beta-induced astrocyte activation while improving learning and memory in a rat model of Alzheimer’s disease (66).
In Parkinson’s disease addition of hydrogen to drinking water (>0.4 mM or 0.08–1.5 ppm) prevented the development and progression of nigrostriatal degeneration and dopaminergic neuron loss (67, 68).
The efficacy of hydrogen-enriched water was assessed in a randomized, placebo-controlled, double-blind, parallel clinical trial conducted as a pilot study in levodopa-treated patients with Parkinson’s disease (69). Participants drank 1 L per day of hydrogen-enriched water (prepared by dissolving 0.8 mM H2; n=9) or placebo water (n=8) for 48 weeks. Total Unified Parkinson’s Disease Rating Scale (UPDRS) scores in the hydrogen-enriched water group improved during the study, whereas UPDRS scores in the placebo group worsened (p<0.05 at 48 weeks). Hydrogen-enriched water was well tolerated during the study and no adverse events were reported.
神经退行性疾病
在神经退行性疾病患者的死后脑组织样本中发现了ROS水平增加的证据(3)。有许多因素使大脑特别容易受到氧化应激的影响，包括其高代谢率和与其他器官相比细胞再生能力的降低(3，64)。
随意饮用富氢水(>0.6 mM)可以抑制氧化应激标志物的增加，并改善小鼠慢性身体束缚模型中神经祖细胞的增殖(65)。富氢盐水减少了氧化应激、炎症反应和淀粉样-β-诱导的星形细胞激活，同时改善了阿尔茨海默病大鼠模型的学习和记忆症状(66)。
在帕金森病中，在饮用水中加入氢气(>0.4mM或0.08~1.5ppm)可以防止黑质变性和多巴胺能神经元损失的发展(67，68)。
在一项随机、安慰剂对照、双盲、平行的临床试验中，对左旋多巴治疗的帕金森病患者评估了富氢水的疗效(69)。参与者每天喝1升富氢水(通过溶解0.8mM H2制备；n=9)或安慰剂水(n=8)，持续48周。在研究期间，富氢水组的统一帕金森病评分表(UPDRS)总分有所改善，而安慰剂组的UPDRS评分则有所恶化(48周时P<0.05)。在研究期间，富氢水的人体耐受性良好，没有不良事件报告。
Spinal cord and brain injury
Intraperitoneal administration of hydrogen-enriched saline (0.6 mM) to rats at the time of spinal cord injury, and at 24 and 48 hours after injury was associated with a reduction in the number of apoptotic cells, decreased oxidative stress, increased release of brain-derived neurotrophic factor, and improved locomotor function (70). Similar beneficial effects were observed in a rat model of traumatic brain injury (TBI) after treatment with 2% inhaled hydrogen in air (71). Hydrogen was administered from 5 minutes to 5 hours after TBI, and significantly attenuated TBI-induced increases in blood-brain barrier permeability, brain edema, lesion volume and neurological dysfunction. These effects were thought to occur via increases in endogenous antioxidant enzyme activities (71). Reduction in brain edema and protection from the neurodegenerative changes associated with TBI has also been documented when hydrogen is added to drinking water (>1.6 mM), starting 24 hours before TBI. In particular, expression of genes relating to oxidation, neuroinflammation and carbohydrate metabolism was effectively reversed by hydrogen water (72).
脊髓和脑损伤
在脊髓损伤时和损伤后24小时和48小时对大鼠进行腹腔注射富氢盐水(0.6mM)，与减少凋亡细胞的数量、减少氧化应激、增加脑源性神经营养因子的释放和改善运动功能有关(70)。类似的有益影响在大鼠创伤性脑损伤(TBI)的大鼠模型中，在空气中吸入2%的氢气治疗后，也观察到了类似的有益效果(71)。氢气在TBI后5分钟至5小时内给药，明显减弱了TBI引起的血脑屏障通透性、脑水肿、病变体积和神经功能障碍的增加。这些影响被认为是通过内源性抗氧化酶活性的增加而发生的(71)。在TBI前24小时开始，在饮用水中加入氢气(>1.6mM)，也记录了脑水肿的减少和与TBI相关的神经退行性变化的保护。特别是与氧化、神经炎症和碳水化合物代谢有关的基因的表达被氢水有效逆转(72)。
原创翻译：龙腾网 http://www.ltaaa.cn 转载请注明出处
Intraperitoneal administration of hydrogen-enriched saline (0.6 mM) to rats at the time of spinal cord injury, and at 24 and 48 hours after injury was associated with a reduction in the number of apoptotic cells, decreased oxidative stress, increased release of brain-derived neurotrophic factor, and improved locomotor function (70). Similar beneficial effects were observed in a rat model of traumatic brain injury (TBI) after treatment with 2% inhaled hydrogen in air (71). Hydrogen was administered from 5 minutes to 5 hours after TBI, and significantly attenuated TBI-induced increases in blood-brain barrier permeability, brain edema, lesion volume and neurological dysfunction. These effects were thought to occur via increases in endogenous antioxidant enzyme activities (71). Reduction in brain edema and protection from the neurodegenerative changes associated with TBI has also been documented when hydrogen is added to drinking water (>1.6 mM), starting 24 hours before TBI. In particular, expression of genes relating to oxidation, neuroinflammation and carbohydrate metabolism was effectively reversed by hydrogen water (72).
脊髓和脑损伤
在脊髓损伤时和损伤后24小时和48小时对大鼠进行腹腔注射富氢盐水(0.6mM)，与减少凋亡细胞的数量、减少氧化应激、增加脑源性神经营养因子的释放和改善运动功能有关(70)。类似的有益影响在大鼠创伤性脑损伤(TBI)的大鼠模型中，在空气中吸入2%的氢气治疗后，也观察到了类似的有益效果(71)。氢气在TBI后5分钟至5小时内给药，明显减弱了TBI引起的血脑屏障通透性、脑水肿、病变体积和神经功能障碍的增加。这些影响被认为是通过内源性抗氧化酶活性的增加而发生的(71)。在TBI前24小时开始，在饮用水中加入氢气(>1.6mM)，也记录了脑水肿的减少和与TBI相关的神经退行性变化的保护。特别是与氧化、神经炎症和碳水化合物代谢有关的基因的表达被氢水有效逆转(72)。
原创翻译：龙腾网 http://www.ltaaa.cn 转载请注明出处
Cancer
Anti-cancer effects
The production of ROS by human cancer cells is higher than that for normal cell lines (73). In addition, elevated levels of ROS appear to play a role in the signaling cascades that trigger and maintain the oncogenic phenotype of cancer cells (74), and may contribute to DNA damage, and cell proliferation, migration and survival (75). Therefore, the possible anticancer effects of hydrogen, alone or in combination with traditional therapy, are the subject of growing research (76).
In an in vitro study, hydrogen-enriched water (1.0–1.3 ppm) supplemented with platinum nanocolloid showed rapid antioxidant effects and preferentially inhibited clonal growth of human tongue carcinoma cells compared with normal cells (77). Hydrogen-enriched water has also been shown to increase the inhibitory effects of the chemotherapy agent fluorouracil on colon cancer cells (76). In a mouse model of colon cancer, hydrogen-enriched water (≈0.8 mM) significantly increased survival compared with placebo water treatment, and survival was increased to an even greater extent when hydrogen-enriched water was combined with fluouracil (76).
癌症
抗癌效果
人类癌细胞产生的ROS高于正常细胞系(73)。此外，升高的ROS水平似乎在触发和维持癌细胞致癌表型的信号级联中起作用(74)，并可能促成DNA损伤，以及细胞增殖、迁移和生存(75)。因此，氢气可能的抗癌作用，单独或与传统疗法相结合是越来越多的研究课题的关注重点(76)。
在体外研究中，与正常细胞(77)相比，富氢水(1.0~1.3ppm)辅以铂纳米胶体，显示出快速的抗氧化作用，并优先抑制人类舌头癌细胞的克隆生长。氢富集水也已被证明可以增加化疗剂氟酸对结肠癌细胞(76)的抑制作用。在结肠癌小鼠模型中，富氢水(≈0.8mM)与安慰剂水处理相比，病人存活率显著提高，当富氢水与氟酸(76)结合使用时，存活率进一步提高。
Anti-cancer effects
The production of ROS by human cancer cells is higher than that for normal cell lines (73). In addition, elevated levels of ROS appear to play a role in the signaling cascades that trigger and maintain the oncogenic phenotype of cancer cells (74), and may contribute to DNA damage, and cell proliferation, migration and survival (75). Therefore, the possible anticancer effects of hydrogen, alone or in combination with traditional therapy, are the subject of growing research (76).
In an in vitro study, hydrogen-enriched water (1.0–1.3 ppm) supplemented with platinum nanocolloid showed rapid antioxidant effects and preferentially inhibited clonal growth of human tongue carcinoma cells compared with normal cells (77). Hydrogen-enriched water has also been shown to increase the inhibitory effects of the chemotherapy agent fluorouracil on colon cancer cells (76). In a mouse model of colon cancer, hydrogen-enriched water (≈0.8 mM) significantly increased survival compared with placebo water treatment, and survival was increased to an even greater extent when hydrogen-enriched water was combined with fluouracil (76).
癌症
抗癌效果
人类癌细胞产生的ROS高于正常细胞系(73)。此外，升高的ROS水平似乎在触发和维持癌细胞致癌表型的信号级联中起作用(74)，并可能促成DNA损伤，以及细胞增殖、迁移和生存(75)。因此，氢气可能的抗癌作用，单独或与传统疗法相结合是越来越多的研究课题的关注重点(76)。
在体外研究中，与正常细胞(77)相比，富氢水(1.0~1.3ppm)辅以铂纳米胶体，显示出快速的抗氧化作用，并优先抑制人类舌头癌细胞的克隆生长。氢富集水也已被证明可以增加化疗剂氟酸对结肠癌细胞(76)的抑制作用。在结肠癌小鼠模型中，富氢水(≈0.8mM)与安慰剂水处理相比，病人存活率显著提高，当富氢水与氟酸(76)结合使用时，存活率进一步提高。
Radiation toxicities
Radiotherapy is associated with radiolysis of H2O to ·OH, which contributes to a range of adverse effects (33). The results of one preclinical study showed that hydrogen-enriched saline (>0.6 mM) protects cells against radiation-induced toxicity and ameliorates intestinal injury caused by radiation (78). Another showed that hydrogen-enriched saline (>0.6 mM) markedly reduced ROS levels after radiation and protected against radiation-induced immune dysfunction (79), while a third indicated that treatment with hydrogen-enriched saline (0.6 mM) before ionizing radiation could provide partial protection of both spermatogenesis and hematopoiesis (80). Hydrogen has been proposed as a possible preventive strategy for radiation pneumonitis because of its ability to quickly scavenge free radicals produced by irradiation of the lungs (81).
The effects of drinking hydrogen-enriched water were investigated in a randomized, placebo-controlled study of patients receiving radiotherapy for liver tumors (82). Treatment with 1.5–2L hydrogen-enriched (0.55–0.65 mM) or placebo water was started on the first day of radiation treatment and continued for 6 weeks. Drinking hydrogen-enriched water prevented the marked increase in total serum hydroperoxide associated with radiotherapy, and attenuated the radiation-related reduction in serum antioxidant activity. Patients in the hydrogen-enriched water group reported significantly less loss of appetite and fewer taste disorders compared with those receiving placebo. Importantly, hydrogen-enriched water had no effect on the efficacy of radiotherapy (82).
辐射毒性
放疗损伤与H2O的放射性分解为·OH有关，这导致了一系列的不良反应(33)。一项临床前研究的结果显示，富氢盐水(>0.6mM)可以保护细胞免受辐射引起的毒性，并改善辐射引起的肠道损伤(78)。另一个表明，富氢盐水(>0.6mM)明显减少了辐射后的ROS水平，并保护了辐射引起的免疫功能障碍(79)，而第三个表明，在电离辐射前用富氢盐水(0.6mM)处理可以对精子生成和造血功能提供部分保护(80)。由于氢气能够迅速清除肺部辐照产生的自由基，氢气已被提议作为一种可能的辐射性肺炎的预防治疗手段(81)。
在一项针对接受肝脏肿瘤放射治疗的病人的随机、安慰剂对照研究中，调查了饮用富氢水的效果(82)。在放射治疗的第一天开始用1.5~2L富氢水(0.55~0.65mM)或安慰剂水治疗，并持续6周。饮用富氢水可以防止与放疗有关的血清总过氧化氢的明显增加，减弱了与辐射有关的血清抗氧化活性的降低。与接受安慰剂的病人相比，富氢水组的病人报告食欲不振和味觉障碍明显减少。重要的是，富氢水对放疗的疗效没有影响(82)。
Radiotherapy is associated with radiolysis of H2O to ·OH, which contributes to a range of adverse effects (33). The results of one preclinical study showed that hydrogen-enriched saline (>0.6 mM) protects cells against radiation-induced toxicity and ameliorates intestinal injury caused by radiation (78). Another showed that hydrogen-enriched saline (>0.6 mM) markedly reduced ROS levels after radiation and protected against radiation-induced immune dysfunction (79), while a third indicated that treatment with hydrogen-enriched saline (0.6 mM) before ionizing radiation could provide partial protection of both spermatogenesis and hematopoiesis (80). Hydrogen has been proposed as a possible preventive strategy for radiation pneumonitis because of its ability to quickly scavenge free radicals produced by irradiation of the lungs (81).
The effects of drinking hydrogen-enriched water were investigated in a randomized, placebo-controlled study of patients receiving radiotherapy for liver tumors (82). Treatment with 1.5–2L hydrogen-enriched (0.55–0.65 mM) or placebo water was started on the first day of radiation treatment and continued for 6 weeks. Drinking hydrogen-enriched water prevented the marked increase in total serum hydroperoxide associated with radiotherapy, and attenuated the radiation-related reduction in serum antioxidant activity. Patients in the hydrogen-enriched water group reported significantly less loss of appetite and fewer taste disorders compared with those receiving placebo. Importantly, hydrogen-enriched water had no effect on the efficacy of radiotherapy (82).
辐射毒性
放疗损伤与H2O的放射性分解为·OH有关，这导致了一系列的不良反应(33)。一项临床前研究的结果显示，富氢盐水(>0.6mM)可以保护细胞免受辐射引起的毒性，并改善辐射引起的肠道损伤(78)。另一个表明，富氢盐水(>0.6mM)明显减少了辐射后的ROS水平，并保护了辐射引起的免疫功能障碍(79)，而第三个表明，在电离辐射前用富氢盐水(0.6mM)处理可以对精子生成和造血功能提供部分保护(80)。由于氢气能够迅速清除肺部辐照产生的自由基，氢气已被提议作为一种可能的辐射性肺炎的预防治疗手段(81)。
在一项针对接受肝脏肿瘤放射治疗的病人的随机、安慰剂对照研究中，调查了饮用富氢水的效果(82)。在放射治疗的第一天开始用1.5~2L富氢水(0.55~0.65mM)或安慰剂水治疗，并持续6周。饮用富氢水可以防止与放疗有关的血清总过氧化氢的明显增加，减弱了与辐射有关的血清抗氧化活性的降低。与接受安慰剂的病人相比，富氢水组的病人报告食欲不振和味觉障碍明显减少。重要的是，富氢水对放疗的疗效没有影响(82)。
Side effects of cisplatin
Based on the results of an in vivo study, hydrogen also has the potential to alleviate chemotherapy-associated toxicity. Two administration routes (oral hydrogen-enriched drinking water [0.8 mM] and inhaled hydrogen [1%]) were assessed in mice receiving cisplatin (83). Both forms of hydrogen improved survival, reduced body weight loss and ameliorated cisplatin-induced nephrotoxicity compared with control, although the effects of drinking hydrogen-enriched water appeared to be less than those of inhaled hydrogen with respect to prevention of severe nephrotoxicity. The anti-tumor efficacy of cisplatin was unaffected by concomitant administration of hydrogen by either route (83).
抑制化疗药物——顺铂的副作用
根据一项体内研究的结果，氢气也有可能减轻化疗相关的毒性。在接受顺铂的小鼠中评估了两种给药途径(口服富含氢气的饮用水[0.8mM]和吸入氢气[1%])(83)。与对照组相比，两种形式的氢气摄入都提高了病人生存率，减少了体重损失，并改善了顺铂诱导的肾毒性，尽管在预防严重肾毒性方面，饮用富氢水的效果似乎不如吸入氢气的效果。顺铂的抗肿瘤疗效不受同时通过两种途径给予氢气的影响(83)。
Based on the results of an in vivo study, hydrogen also has the potential to alleviate chemotherapy-associated toxicity. Two administration routes (oral hydrogen-enriched drinking water [0.8 mM] and inhaled hydrogen [1%]) were assessed in mice receiving cisplatin (83). Both forms of hydrogen improved survival, reduced body weight loss and ameliorated cisplatin-induced nephrotoxicity compared with control, although the effects of drinking hydrogen-enriched water appeared to be less than those of inhaled hydrogen with respect to prevention of severe nephrotoxicity. The anti-tumor efficacy of cisplatin was unaffected by concomitant administration of hydrogen by either route (83).
抑制化疗药物——顺铂的副作用
根据一项体内研究的结果，氢气也有可能减轻化疗相关的毒性。在接受顺铂的小鼠中评估了两种给药途径(口服富含氢气的饮用水[0.8mM]和吸入氢气[1%])(83)。与对照组相比，两种形式的氢气摄入都提高了病人生存率，减少了体重损失，并改善了顺铂诱导的肾毒性，尽管在预防严重肾毒性方面，饮用富氢水的效果似乎不如吸入氢气的效果。顺铂的抗肿瘤疗效不受同时通过两种途径给予氢气的影响(83)。
Other medical applications
Dermatomyositis and mitochondrial disease
The effects of drinking hydrogen-enriched water (0.5 ppm) were assessed in patients with muscle diseases (84). An open-label study was conducted in 14 patients who drank 1 L/day of hydrogen-enriched water for 12 weeks. Patients with mitochondrial myopathies (MM) and patients with progressive muscular dystrophy showed decreases in the lactate-to-pyruvate ratio (p<0.05), and those with polymyositis/dermatomyositis had a decrease in serum matrix metalloproteinase-3 and triglyceride levels (84). Subsequently, a randomized, double-blind, placebo-controlled, crossover study in 22 patients with dermatomyositis (n=10) or MM (n=12) investigated the effects of drinking 0.5 L/day of hydrogen-enriched water for 8 weeks. Treatment was associated with significant improvement in serum lactate in MM patients, but there were no obxtive changes in clinical symptoms in this or the open-label study (84). Some patients did report subjective improvements in fatigue, diarrhea and myalgia, but these were not consistent or statistically significant suggesting that the hydrogen dosage used may have been insufficient. It was suggested that >1 L/day of hydrogen-enriched water may be required to achieve beneficial effects (84).
其他医疗应用
皮肤炎和线粒体疾病
对肌肉疾病患者饮用富氢水(0.5ppm)的效果进行了评估(84)。在14名患者中进行了一项开放标签研究，他们每天喝1升富氢水，持续12周。患有线粒体肌病(MM)的病人和进行性肌营养不良症的病人显示乳酸-丙酮酸比率下降(P<0.05)，患有多发性肌炎/皮肌炎的病人的血清基质金属蛋白酶-3和甘油三酯水平下降(84)。随后，在22名皮肌炎(n=10)或线粒体肌病(n=12)患者中进行了一项随机、双盲、安慰剂对照的交叉研究，调查了饮用0.5升/天富氢水8周的效果。这一治疗与MM患者血清乳酸的显著改善有关，但在这项开放标签研究中，临床症状没有明显客观变化(84)。一些病人确实报告了疲劳、腹泻和肌痛方面的主观改善，但这些情况并不一致，也没有统计学意义。说明使用的氢气剂量可能不足。有人建议，可能需要>1升/天的富氢水才能达到有益的效果(84)。
Dermatomyositis and mitochondrial disease
The effects of drinking hydrogen-enriched water (0.5 ppm) were assessed in patients with muscle diseases (84). An open-label study was conducted in 14 patients who drank 1 L/day of hydrogen-enriched water for 12 weeks. Patients with mitochondrial myopathies (MM) and patients with progressive muscular dystrophy showed decreases in the lactate-to-pyruvate ratio (p<0.05), and those with polymyositis/dermatomyositis had a decrease in serum matrix metalloproteinase-3 and triglyceride levels (84). Subsequently, a randomized, double-blind, placebo-controlled, crossover study in 22 patients with dermatomyositis (n=10) or MM (n=12) investigated the effects of drinking 0.5 L/day of hydrogen-enriched water for 8 weeks. Treatment was associated with significant improvement in serum lactate in MM patients, but there were no obxtive changes in clinical symptoms in this or the open-label study (84). Some patients did report subjective improvements in fatigue, diarrhea and myalgia, but these were not consistent or statistically significant suggesting that the hydrogen dosage used may have been insufficient. It was suggested that >1 L/day of hydrogen-enriched water may be required to achieve beneficial effects (84).
其他医疗应用
皮肤炎和线粒体疾病
对肌肉疾病患者饮用富氢水(0.5ppm)的效果进行了评估(84)。在14名患者中进行了一项开放标签研究，他们每天喝1升富氢水，持续12周。患有线粒体肌病(MM)的病人和进行性肌营养不良症的病人显示乳酸-丙酮酸比率下降(P<0.05)，患有多发性肌炎/皮肌炎的病人的血清基质金属蛋白酶-3和甘油三酯水平下降(84)。随后，在22名皮肌炎(n=10)或线粒体肌病(n=12)患者中进行了一项随机、双盲、安慰剂对照的交叉研究，调查了饮用0.5升/天富氢水8周的效果。这一治疗与MM患者血清乳酸的显著改善有关，但在这项开放标签研究中，临床症状没有明显客观变化(84)。一些病人确实报告了疲劳、腹泻和肌痛方面的主观改善，但这些情况并不一致，也没有统计学意义。说明使用的氢气剂量可能不足。有人建议，可能需要>1升/天的富氢水才能达到有益的效果(84)。
Hemodialysis
The effects of using hydrogen-enriched water as a hemodialysis solution have been investigated in two clinical trials. In the first, regular hemodialysis patients received one month of treatment using a standard solution followed by another month of treatment using hydrogen-enriched water (99 parts per billion [ppb]) as the dialysis solution (85). Hemodialysis with both the standard and hydrogen-enriched water solutions was effective at reducing blood pressure. Compared with standard solution, hydrogen-enriched water was associated with preserved cellular viability of polymorphonuclear leukocytes, resulting in better ability to generate superoxide anions. Use of hydrogen-enriched water during hemodialysis was feasible and well tolerated, with no symptomatic adverse events observed during the study period (85). The second clinical trial included a larger number of patients (n=21) dialyzed with hydrogen-enriched solution (average H2 levels ranged from 48 ppb to 210 ppb) over a longer period of time (6 months) (24). Once again, hemodialysis with hydrogen water had a good tolerability profile and was feasible, and significant reductions in blood pressure were achieved after each hemodialysis session; these were greater when hemodialysis was performed with hydrogen versus standard solution. Significant decreases were also observed in the oxidant markers plasma myeloperoxidase and monocyte chemoattractant protein-1 (24). These results suggest that use of hydrogen-enriched solutions during hemodialysis has the potential to ameliorate inflammatory reactions and improve blood pressure control.
血液透析
在两项临床试验中，对使用富氢水作为血液透析液的效果进行了调查。在第一项试验中，普通血液透析患者接受了使用标准溶液的一个月的治疗，然后又接受了使用富氢水(十亿分之99[ppb])作为透析溶液的一个月的治疗(85)。使用标准和富氢水溶液进行血液透析都能有效降低血压。与标准溶液相比，富氢水与保存多形核白细胞的细胞活力有关，从而产生超氧阴离子的能力更强。在血液透析期间使用富氢水是可行的，而且耐受性良好，在研究期间没有观察到任何症状性的不良事件(85)。第二项临床试验包括更多的病人(n=21)在更长的时间内(6个月)用富氢水透析(平均H2水平在48 ppb到210 ppb之间)(24)。再一次证明用氢水进行血液透析具有良好的耐受性，而且是可行的，每次血液透析后血压都有明显的下降；用氢水进行血液透析时比用标准溶液进行血液透析时降幅更大。还观察到氧化剂标记物血浆骨髓过氧化物酶和单核细胞螯合蛋白-1含量也有明显的下降(24)。这些结果表明，在血液透析过程中使用富含氢气的溶液有可能改善炎症反应并改善血压控制。
The effects of using hydrogen-enriched water as a hemodialysis solution have been investigated in two clinical trials. In the first, regular hemodialysis patients received one month of treatment using a standard solution followed by another month of treatment using hydrogen-enriched water (99 parts per billion [ppb]) as the dialysis solution (85). Hemodialysis with both the standard and hydrogen-enriched water solutions was effective at reducing blood pressure. Compared with standard solution, hydrogen-enriched water was associated with preserved cellular viability of polymorphonuclear leukocytes, resulting in better ability to generate superoxide anions. Use of hydrogen-enriched water during hemodialysis was feasible and well tolerated, with no symptomatic adverse events observed during the study period (85). The second clinical trial included a larger number of patients (n=21) dialyzed with hydrogen-enriched solution (average H2 levels ranged from 48 ppb to 210 ppb) over a longer period of time (6 months) (24). Once again, hemodialysis with hydrogen water had a good tolerability profile and was feasible, and significant reductions in blood pressure were achieved after each hemodialysis session; these were greater when hemodialysis was performed with hydrogen versus standard solution. Significant decreases were also observed in the oxidant markers plasma myeloperoxidase and monocyte chemoattractant protein-1 (24). These results suggest that use of hydrogen-enriched solutions during hemodialysis has the potential to ameliorate inflammatory reactions and improve blood pressure control.
血液透析
在两项临床试验中，对使用富氢水作为血液透析液的效果进行了调查。在第一项试验中，普通血液透析患者接受了使用标准溶液的一个月的治疗，然后又接受了使用富氢水(十亿分之99[ppb])作为透析溶液的一个月的治疗(85)。使用标准和富氢水溶液进行血液透析都能有效降低血压。与标准溶液相比，富氢水与保存多形核白细胞的细胞活力有关，从而产生超氧阴离子的能力更强。在血液透析期间使用富氢水是可行的，而且耐受性良好，在研究期间没有观察到任何症状性的不良事件(85)。第二项临床试验包括更多的病人(n=21)在更长的时间内(6个月)用富氢水透析(平均H2水平在48 ppb到210 ppb之间)(24)。再一次证明用氢水进行血液透析具有良好的耐受性，而且是可行的，每次血液透析后血压都有明显的下降；用氢水进行血液透析时比用标准溶液进行血液透析时降幅更大。还观察到氧化剂标记物血浆骨髓过氧化物酶和单核细胞螯合蛋白-1含量也有明显的下降(24)。这些结果表明，在血液透析过程中使用富含氢气的溶液有可能改善炎症反应并改善血压控制。
Liver disease
Lipid peroxidation plays an important role in the pathology of viral hepatitis and has been suggested as a major cause of liver injury (86). The addition of hydrogen-enriched water (0.55–0.65 mM; three times daily) to standard treatment for 6 weeks in patients with chronic hepatitis B was associated with significant improvements in a number of oxidative stress parameters, including superoxide dismutase, glutathione S transferase, xanthine oxidase and malondialdehyde compared with both baseline (p<0.05) and the standard treatment only group (p<0.01) (87). There were trends towards improvements in liver function and reductions in hepatitis B virus DNA load in the hydrogen treatment versus routine treatment group, but these did not reach statistical significance (87).
肝病
脂质过氧化在病毒性肝炎的病理过程中起着重要作用，并被认为是肝脏损伤的一个主要原因(86)。在慢性乙型肝炎患者的标准治疗中加入富氢水(0.55~0.65mM；每天三次)，为期6周，与基线(p<0.05)和仅标准治疗组(p<0.01)相比，一些氧化应激参数有明显改善，包括超氧化物歧化酶、谷胱甘肽S转移酶、黄嘌呤氧化酶和丙二醛(87)。氢气治疗组与常规治疗组相比，肝功能有改善的趋势，乙肝病毒DNA载量也有减少，但这些都没有达到统计学意义(87)。
Lipid peroxidation plays an important role in the pathology of viral hepatitis and has been suggested as a major cause of liver injury (86). The addition of hydrogen-enriched water (0.55–0.65 mM; three times daily) to standard treatment for 6 weeks in patients with chronic hepatitis B was associated with significant improvements in a number of oxidative stress parameters, including superoxide dismutase, glutathione S transferase, xanthine oxidase and malondialdehyde compared with both baseline (p<0.05) and the standard treatment only group (p<0.01) (87). There were trends towards improvements in liver function and reductions in hepatitis B virus DNA load in the hydrogen treatment versus routine treatment group, but these did not reach statistical significance (87).
肝病
脂质过氧化在病毒性肝炎的病理过程中起着重要作用，并被认为是肝脏损伤的一个主要原因(86)。在慢性乙型肝炎患者的标准治疗中加入富氢水(0.55~0.65mM；每天三次)，为期6周，与基线(p<0.05)和仅标准治疗组(p<0.01)相比，一些氧化应激参数有明显改善，包括超氧化物歧化酶、谷胱甘肽S转移酶、黄嘌呤氧化酶和丙二醛(87)。氢气治疗组与常规治疗组相比，肝功能有改善的趋势，乙肝病毒DNA载量也有减少，但这些都没有达到统计学意义(87)。
Respiratory system
The role of oxidative stress in the development of acute lung injury is well established (33). In animal models, hydrogen-enriched saline and inhaled hydrogen (2%) reduced apoptosis, neutrophil infiltration, lipid membrane peroxidation, nuclear factor kappa B activation and proinflammatory cytokine levels (88-90).
呼吸系统
氧化应激在急性肺损伤发展中的作用已确立(33)。在动物模型中，富氢盐水和吸入氢(2%)可减少凋亡、嗜中性粒细胞渗透、脂膜过氧化、核因子卡帕B活化和宣告细胞因子水平(88-90)。
The role of oxidative stress in the development of acute lung injury is well established (33). In animal models, hydrogen-enriched saline and inhaled hydrogen (2%) reduced apoptosis, neutrophil infiltration, lipid membrane peroxidation, nuclear factor kappa B activation and proinflammatory cytokine levels (88-90).
呼吸系统
氧化应激在急性肺损伤发展中的作用已确立(33)。在动物模型中，富氢盐水和吸入氢(2%)可减少凋亡、嗜中性粒细胞渗透、脂膜过氧化、核因子卡帕B活化和宣告细胞因子水平(88-90)。
Ocular effects
There are a number of ocular diseases that have been shown to benefit from hydrogen treatment in preclinical studies. Hydrogen-enriched saline has been shown to have antioxidant effects and to protect against blue light-induced retinal damage (91) and retinopathy associated with hyperoxia or diabetes (92, 93), and to prevent selenite-induced cataract (94).
眼部效果
在临床前研究中，有许多眼部疾病已被证明可从氢气治疗中获益。富氢盐水已被证明具有抗氧化作用，并能防止蓝光引起的视网膜损伤(91)和与高氧或糖尿病有关的视网膜病变(92，93)，并能防止硒酸盐引起的白内障(94)。
There are a number of ocular diseases that have been shown to benefit from hydrogen treatment in preclinical studies. Hydrogen-enriched saline has been shown to have antioxidant effects and to protect against blue light-induced retinal damage (91) and retinopathy associated with hyperoxia or diabetes (92, 93), and to prevent selenite-induced cataract (94).
眼部效果
在临床前研究中，有许多眼部疾病已被证明可从氢气治疗中获益。富氢盐水已被证明具有抗氧化作用，并能防止蓝光引起的视网膜损伤(91)和与高氧或糖尿病有关的视网膜病变(92，93)，并能防止硒酸盐引起的白内障(94)。
Conclusion
Hydrogen is an effective antioxidant, anti-inflammatory and cytoprotective agent that sextively scavenges potent oxidants such as ·OH and peroxynitrite in cells without affecting redox homeostasis. Key features of hydrogen as a therapeutic agent include sextive reaction with highly reactive ROS, rapid diffusion into cells and onset of action, inert characteristics at body temperature in mammalian cells, an almost adverse event-free tolerability profile, the ability to administer therapy in a variety of ways to best suit the patient or indication being treated, and low cost. The non-specific nature of the effects of hydrogen mean that it has therapeutic potential across a wide range of medical applications, as has been shown by a good volume of preclinical data and a growing body of clinical evidence.
Accumulating data also show the potential for hydrogen as an anti-ageing solution and in wellness applications, particularly sports and injury. It is possible that drinking hydrogen-enriched water may become a novel and beneficial new rehydration strategy for athletes. Data from future clinical studies will help to better define the role of hydrogen in medical applications, exercise physiology and wellness strategies. Hydrogen has the potential to become a hugely important agent in many aspects of human health, particularly in reducing the effects of ageing.
结论
氢气是一种有效的抗氧化剂、抗炎剂和细胞保护剂，可以选择性地清除细胞中的强效氧化剂，如·OH和过氧亚硝酸盐，而不影响氧化还原的稳态。氢气作为治疗剂的主要特点包括：与高活性的ROS发生选择性反应，迅速扩散到细胞中并开始发挥作用，在哺乳动物细胞的体温下具有惰性特征，几乎没有不良事件的强大耐受性，能够以各种方式进行治疗以最适合被治疗的病人或适应症，而且成本低。氢气作用的非特异性意味着它在广泛医疗应用中具有治疗潜力，大量的临床前数据和越来越多的临床证据已经证明了这一点。
积累数据也显示了氢气作为抗衰老解决方案和健康应用的潜力，特别是在运动和受伤方面。饮用富含氢气的水有可能成为运动员的一种新颖和有益的新补水策略。未来临床研究的数据将有助于更好地确定氢气在医疗应用、运动生理学和健康战略中的作用。氢气有可能在人类健康的许多方面成为一种极为重要的药剂，特别是在减少衰老的影响方面。
Hydrogen is an effective antioxidant, anti-inflammatory and cytoprotective agent that sextively scavenges potent oxidants such as ·OH and peroxynitrite in cells without affecting redox homeostasis. Key features of hydrogen as a therapeutic agent include sextive reaction with highly reactive ROS, rapid diffusion into cells and onset of action, inert characteristics at body temperature in mammalian cells, an almost adverse event-free tolerability profile, the ability to administer therapy in a variety of ways to best suit the patient or indication being treated, and low cost. The non-specific nature of the effects of hydrogen mean that it has therapeutic potential across a wide range of medical applications, as has been shown by a good volume of preclinical data and a growing body of clinical evidence.
Accumulating data also show the potential for hydrogen as an anti-ageing solution and in wellness applications, particularly sports and injury. It is possible that drinking hydrogen-enriched water may become a novel and beneficial new rehydration strategy for athletes. Data from future clinical studies will help to better define the role of hydrogen in medical applications, exercise physiology and wellness strategies. Hydrogen has the potential to become a hugely important agent in many aspects of human health, particularly in reducing the effects of ageing.
结论
氢气是一种有效的抗氧化剂、抗炎剂和细胞保护剂，可以选择性地清除细胞中的强效氧化剂，如·OH和过氧亚硝酸盐，而不影响氧化还原的稳态。氢气作为治疗剂的主要特点包括：与高活性的ROS发生选择性反应，迅速扩散到细胞中并开始发挥作用，在哺乳动物细胞的体温下具有惰性特征，几乎没有不良事件的强大耐受性，能够以各种方式进行治疗以最适合被治疗的病人或适应症，而且成本低。氢气作用的非特异性意味着它在广泛医疗应用中具有治疗潜力，大量的临床前数据和越来越多的临床证据已经证明了这一点。
积累数据也显示了氢气作为抗衰老解决方案和健康应用的潜力，特别是在运动和受伤方面。饮用富含氢气的水有可能成为运动员的一种新颖和有益的新补水策略。未来临床研究的数据将有助于更好地确定氢气在医疗应用、运动生理学和健康战略中的作用。氢气有可能在人类健康的许多方面成为一种极为重要的药剂，特别是在减少衰老的影响方面。
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