Hydrogen as a Stress for Resilience
Hydrogen as a Stress for Resilience
Typically, when stress is mentioned, it is in the context of psychological stress. Traumatic events can lead to acute psychological stress, while daily life can lead to chronic psychological stress, both of which can take a toll on our mental and physical health. Less frequently discussed, but important, is physiological stress. Like psychological stress, physiological stress can arise from an acute traumatic event or from chronic exposure to biological stressors. Physiological stressors, like psychological stressors, can be beneficial when the "dose" is low enough for us to overcome, manage and grow from. However, they can be problematic when we are unable to effectively recover. For both psychological and physiological stress, development of one can lead to the other.
Many pseudoscientific cures promoted by quacks and con men alike claim miraculous benefits for a wide range of ailments, even all ailments, by mechanisms either not defined, impossible, or fabricated with scientific sounding explanations not rooted in reality. Many skeptics decry H₂ therapy as quackery because many marketers are quick to give preposterous explanations of how hydrogen therapy works, particularly in relation to hydrogen water, while simultaneously dramatically over stating the benefits.
Hydrogen therapy has shown potential in numerous different models ranging across every organ. This is a red flag. However, upon literature review and understanding the mechanisms by which it works, it is fully explainable. As I discuss in Part7 of my series on hormesis, molecular hydrogen seems to function as a hormetic agen (a beneficial stress), while having a very high safety profile. By altering our gene expression, also known as epigenetics, molecular hydrogen is able to positively impact many biological functions and protect against in which adolescent mice were exposed to chronic, mild, and unpredictable stressors for 28 days, demonstrated that hydrogen gas was able to increase stress resilience, protecting against the development of both chronic psychological and physiological stress.¹
We tend to associate some forms of hormesis, such as exercise, as unequivocally "good for us," but the truth is with the wrong "dose" or "duration," this beneficial stress can become just plain old stress. Acute, strenuous exercise in obese individuals can lead to a pro-inflammatory outcome.² Even in those with a high level of fitness, such as elite athletes, overtraining can lead to a myriad of issues, such as tears, fatigue, sleep issues,³ and even hormonal issues, such as chronically low testosterone levels in men⁴ and menstrual disorders in women.⁵ Hydrogen gas has shown to potentiate the results of exercise, acutely raising exercise-induced reactive oxygen species (ROS) yet regulating a faster antioxidant response, while blunting inflammation in a rat model using exhaustive exercise in sedentary rodents.⁶ In humans, hydrogen water has shown to protect against free radical injury in athletes after high intensity exercise,⁷ improve redox status of athletes after three consecutive days of exhaustive training⁸, and improve antioxidant status and oxidative stress markers after strenuous exercise⁹¹⁰
Other potentially beneficial forms, such as fasting and cold exposure, have tipping points towards damage much more abruptly. Hydrogen water has shown to improve the survival rate of Dropsophila (the common fruit fly) when fasting¹¹ and potentiate the benefits of cold exposure following ischemia-reperfusion injury in rats.¹²
One of, if not the most, greatest stress many of us endure is consuming a diet with a caloric surplus. There is no magic pill for weight loss, the closest thing to it being a potentially lethal toxic substance of its own commonly abbreviated as "DNP." As I previously wrote in regards to why activities to increase thermogenesis, while potentially beneficial, are not magical:
"A 'magic pill' to cure obesity is really attractive and exciting, the closest we have come to is a now banned illegal good called 2.4-Dinitrophenol or 'DNP'. DNP works. You will drop loads of weight. Life will be hard, your energy expenditure will become very inefficient. Getting out of bed will be a task, and when you do you will find you possible ruined your mattress from sweat. This is just the tip of the iceberg.
As Wikipedia bluntly puts it "Chronic oral exposure to DNP can lead to the formation of cataracts and skin lesions and has caused effects on the bone marrow, central nervous system, and cardiovascular system." That isn't even the worst of it. DNP will lead to death in even low doses, and it is not from the toxicity. It is from the rise in body temperature created by the very uncoupling and thermogenesis that allows it to be so effective. "The factor that limits ever-increasing doses of DNP is not a lack of ATP energy production, but rather an excessive rise in body temperature due to the heat produced during uncoupling.
"Accordingly, DNP overdose will cause fatal hyperthermia, with body temperature rising to as high as 43.1 °C (109.6 °F)²⁴ shortly before death. In light of this, when it was used clinically, the dose was slowly titrated according to personal tolerance, which varies greatly."
There is no healthy option to combat a caloric surplus, the best we can do is mitigate the damage if this occurs. Molecular hydrogen, particularly hydrogen water, as shown to do just this. Hydrogen water has shown to significantly decrease obesity and energy expenditure in mice by activation of FGF21,¹³ a hormone excreted from the liver which plays a role in fatty acid and glucose expenditure and protects us from diet induced obesity, resistance to it being linked to obesity itself.¹⁴ Molecular hydrogen has also shown to activate PGC1a, a protein which is the master regulator of mitochondrial biogenesis, further increasing fatty acid metabolism, ¹⁵ a process leading to increased energy production.
In humans, molecular hydrogen has shown to improve body composition,¹⁶ improve insulin sensitivity in a model utilizing our tablets, and protects against obesity driven non-alcoholic fatty liver disease. Some of the best evidence for the usage of hydrogen is on the date regarding metabolic issues, such as metabolic syndrome, to which a fully dedicated article will be out in the coming months.
Demonization over all pesticides has reached hysterical levels throughout many communities, driving sales towards "organic" due to the common misconception that organic crops do not use pesticides (they do), and/or organic approved pesticides are less toxic (they're not). That being sad, and I will expand greatly on this in the future, many pesticides used throughout history, and in some cases still today, are known to be quite toxic to mammals.
Paraquat is a toxic herbicide restricted in the USA for specific uses and banned in many countries that has been linked to "Parkinson's Disease¹⁷ and disruption of mammalian redox status via the generation of superoxide radicals. ¹⁸ In one model, paraquat was utilized to induce lung injury in rats, an outcome which hydrogen water significantly ameliorated.¹⁹
In another study, where a cell culture model was incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin, a herbicide which is a persistent organic pollutant and carcinogen present in "Agent Orange" a now infamous due to its weaponized use in a chemical warfare program during the Vietnam War, and its role in the Seveso Disaster, molecular hydrogen showed to balance and protect both NAD+/NADH levels while alleviating cellular senescence. NAD+/NADH levels are important for energy metabolism and tend to change during the aging process, with a decrease in NAD+ increase in NADH. Cellular senescence, a phenomenon sometimes described as "zombie cells" occurs when cells stop dividing. The accumulation of these senescent calls can contribute to chronic inflammation and act as a causative factor in aging itself.
Many of us deal with physiological stresses from the consumption of drugs, both prescription and illegal narcotics. As any long-time reader of mine will know by now, I am not against pharmaceutical drugs. Often, they are not only, and best, option. That said, many come with side effects along with beneficial outcomes. H2 has shown to have protective effects in a rodent study against aspirin-induced gastric damage, ²¹ acetaminophen-induced hepatotoxicity in two rodent studies, ²²²³ has increased effectiveness and decrease the toxic side effects of chemotherapy in rodent studies leading to longer survival rates, including a pair of rodent studies using fluorouracil (5FU), ²⁴²⁵ a pair of rodent studies utilizing the chemotherapy drugs cisplatin ²⁶²⁷ and a significant human study following 152 patients in a controlled, randomized single blind clinical trial of patients undergoing mFOLFOX6 chemotherapy²⁸.
For recreational drugs, many of us have partaken in our lives, particularly during our youth. Some do throughout their entire life. One of the most common testimonials we hear is what hydrogen water does for self-induced hangovers. There is only a small amount of research on this, however, hydrogen water has shown to be potentially beneficial for ethanol-induced hangovers ²⁹, and methamphetamine-induced neurotoxicity³⁰.
Radiation damage is a topic discussed less frequent in terms of aging, however very ³¹³²³³ Some have even suggested low dose radiation could extend lifespan by acting as a form of hormesis³⁴. As is true for overexposure to other forms of hormesis, such as exercise and alcohol, molecular hydrogen has shown to protect against radiation-damaging effects. ³⁵³⁶³⁷ For example, this was observed in rodent models with full body damage ³⁸³⁹⁴⁰⁴¹ and another study where it aided in healing post-radiation burns in rats, ⁴²⁴³ as well as one model studying chickens to determine relevance for those exposed to radiation during Fukushima.⁴⁴ Furthermore, NASA scientists have hypothesized that hydrogen water, hydrogen gas inhalation - or both - could serve as tools to protects astronauts from radiation exposure. ⁴⁵⁴⁶ The precise mechanism in which H₂ assists in these models, with particular emphasis on the mitigation of oxidative stress, have been described in great detail in two review papers, one confirming results with a rodent model of their own design where elevated levels of superoxide dismutase (SOD), a naturally occurring enzyme capable of breaking down the antioxidant system and phosphorylated-AKT, a cell growth and survival signaling protein, were observed⁴⁷⁴⁸.
With one human study using hydrogen water to mitigate the side effects of radiation therapy in cancer patients,⁴⁹ research on hydrogen water and its protection against radiation is under way with positive results, but more research is needed. As of the time of this writing, there is another single ongoing trial actively recruiting published on clinicaltrials.gov in which StonyBrook Medicine will follow 15 patients with high grade gliomas receiving radiation therapy, chemotherapy, and hydrogen therapy for 1 year and measure quality of life.
Molecular hydrogen is less studied for the abatement of psychological stresses, however, there is some early research which has been promising. In a pair of mouse model studies, hydrogen water showed to positively impact depressive like behaviour⁵⁰ and hydrogen gas inhalation similarly showed a benefit in mitigating social deficits and depressive-like behaviours.⁵¹ In another model the epileptic drugs valproic acid was used in high levels to induce autistic-like behaviour, which hydrogen water significantly reduced. ⁵² Remember, the dose makes the poison (or medication), and even water is toxic and lethal in high doses. This study further demonstrates molecular hydrogen's rescuing capacity against physiological assault, and may not necessarily translate directly to autism itself, which is a combination of genetic and environmental factors. A single human study with only 26 participants is published suggesting hydrogen water may positively impact mood and anxiety,⁵³ so more research in humans is needed to further explore this potential benefit.
Stress, both psychological and physiological, accumulates every day from almost every angle. Molecular hydrogen is not a magic cure, but it does show significant potential in assisting your ability to handle these stresses and overcome them. It is not a standalone, and cannot be relied on as a magic pill, but with the proper utilization along with other healthy lifestyle practices it can be a tremendous ally.
9 Effects of Hydrogen-rich Water on Antioxidant Capacity in Female Judo Athletes in Training
Chin J Sports Med，Jan. 2017 Minghao et al *IN CHINESE, ENGLISH ABSTRACT AVAILABLE
10 Koyama et al., 2008. Effect of hydrogen saturated alkaline electrolyzed water on urinary oxidative stress markers after an acute exercise: A randomized controlled trial. Anti-aging Med.