The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 16 No. 11 • December 2013

Hydrogen Therapy NEW RESULTS

Hydrogen-enriched Water Treatment Protects Mice From LPS-induced Neuroinflammation and Sickness Behavior

We continue here our ongoing review of new papers on hydrogen therapy. As this newer paper shows, more recent papers are providing additional details of the mechanisms underlying hydrogen’s protective effects which, in this recent paper1 include protection against neuroinflammation induced by LPS (lipopolysaccharide, a component of the wall of Gram-negative bacteria that activates the mammalian immune system) via changes in gene expression.

The authors of the new paper note that molecular hydrogen can be delivered via inhalation or as dissolved in water or produced by intestinal bacteria. We have written extensively on how hydrogen is produced by certain bacteria in the human gastrointestinal tract and how this production can be increased by ingesting particular prebiotics (such as long chain inulin). (See “Hydrogen Therapy” in the June 2012 issue of Life Enhancement.)

Protective effects of hydrogen that we have reported earlier include reduction of damage due to ischemia-reperfusion (reduced blood flow followed by restoration of flow) in organs such as liver, intestine, kidney, and tissues including nervous system and vascular system. In this new paper, scientists induced neuroinflammation and “sickness behavior” (decreased activity and social interactions,, depression-like symptoms, and cognitive deficits) associated with it in mice by administering LPS and tested the protective effects of hydrogen by giving the LPS-treated mice either chronic ad lib hydrogen-enriched water or vehicle (no hydrogen). The results showed that “molecular hydrogen limits the development and facilitates the resolution of sickness behavior. In addition, it enhances the induction, and promotes the resolution of neuroinflammation, thereby presumably promoting the efficiency of the defense response.”1

Neuroinflammation occurs as a result of LPS activation of microglia (immune system cells resident in the brain) that causes microglia to release proinflammatory cytokines.

Changes in Gene Expression As a Result of Hydrogen Treatment

The researchers assessed the changed expression of several genes in the hippocampus following neuroinflammation induced by LPS. After two hours, the controls (given LPS but no hydrogen), had significantly increased expression of genes for IL-1beta, IL-6, IL-10, iNOS, catalase, Nrf2, and HO-1, indicative of a proinflammatory state. At 48 hours, iNOS was downregulated in the controls. In the hydrogen-treated mice, iNOS was downregulated 4 hours after exposure to LPS and was significantly different from controls at 2 and 48 hours after exposure. Nrf2, a master regulator of antioxidant defenses, was upregulated at 2 hours in the LPS-treated but no hydrogen (control) mice, and was upregulated at 48 hours in the hydrogen and LPS treated mice. At 48 hours, Nrf2 expression was higher in the hydrogen-LPS mice as compared to the LPS mice.

In summary, the authors state: “… molecular hydrogen induces a more robust induction of proinflammatory cytokines ITNF-alpha, IL-1beta, IL-6) and antiinflammatory (IL-10) cytokines in the acute phase (2–4 h), followed by a faster decay in expression at later timepoints (24 h). Recovery from “sickness behavior” was associated with an upregulation of BDNF (brain-derived neurotrophic factor), a neurotrophin that is involved in neurogenesis; this upregulation was significantly greater in the hydrogen-treated LPS mice.

These inflammation-protective effects were quite impressive, with no adverse effects noted. Just another good reason to take supplemental prebiotics (such as long chain inulin) that provides fuel for resident GI tract microbiota to produce hydrogen, which diffuses into all tissues including the brain plus passing through cellular membranes to reach intracellular organelles such as mitochondria.


  1. Spulber et al. Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLoS One. 7(7):e42078 (July 2012).


Hydrogen Prevents Bone Loss in Ovariectomized Rats

A new paper1 reports in the British Journal of Pharmacology that ovariectomized rats (which are susceptible to developing osteoporosis like postmenopausal women after their ovaries stop producing estrogen or, as in the rat study, the ovaries are removed) are protected against bone loss by HW (hydrogen dissolved in water). The possible mechanisms for this protection were also investigated in the study.

Oxidative stress results from either the formation of excessive ROS (reactive oxygen species) or a deficiency of some aspects of the system of antioxidative protection. The poor efficacy of vitamins C and E in some clinical trials for osteoporosis have led some to conclude that these antioxidants are not targeted adequately to the sources of the oxidative stress. Hydrogen gas, on the other hand, is selective for protecting against hydroxyl radicals, while not interfering excessively with other radicals that are important physiological signaling entities. And, importantly, molecular hydrogen is small and electrically neutral, allowing it to diffuse throughout the body even into areas such as organelles (including mitochondria and the nucleus) not usually reachable by ordinary antioxidants.1

The researchers observed that the ovariectomized rats had decreased vertebral bone mass and lowered vertebral mechanical strength. Ovariectomy in the rats resulted in oxidative stress, with increased levels of MDA (malondialdehyde, a breakdown product of lipid peroxidation), as well as reduced expression of antioxidant defense enzymes including SOD1, SOD3, and catalase, with increased expression of oxidative enzymes including NOX4 and p22phox in the rats’ femurs. In addition, ovariectomy increased the pro-inflammatory cytokine TNF-alpha mRNA and NF-kappaB p65 (a subunit of NF-kappaB). All these effects (except for the increase in expression of p22phox) were reduced in the rats treated with HW (hydrogen water). Since HW had no effect on estrogen levels, however, its protective actions against bone loss were independent of estrogen. The authors conclude that the most likely source of its protection is to reduce oxidative stress.

The researchers explain how the various observed changes could be important in protecting against bone loss. For example, they note that “TNF-alpha has been shown to decrease osteoblastic bone formation through the suppression of osteoblast [bone forming cells] proliferation, induction of osteoblast apoptosis [programmed cell death] and inhibition of osteoblast differentiation.”

The authors conclude: “HW [hydrogen water] consumption prevents osteopenia [deficiency of bone-making cells] in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.”1


  1. Guo et al. Hydrogen water consumption prevents osteopenia in ovariectomized rats. Br J Pharmacol. 168:1412-20 (2013).

Hydrogen Therapy Reduces Bone Loss In Rat Model of Microgravity Hindlimb Suspension is Also Used to Model Bone Loss From Extended Bedrest or Inactivity

Loss of bone from inactivity or extended bed rest can be a serious adverse result of enforced inactivity. You can have recovered from an accident or illness that kept you in bed, then finally recovered, get on your feet and fall, breaking a bone while you’re at it due to the bone loss resulting from the enforced bedrest. Oooops.

A new way to reduce the loss of bone during enforced bedrest is reported in a new paper,1 in which rats were subjected to hindlimb suspension (a way to prevent loading of bones and, thus, a model for enforced inactivity). While rats were hindlimb suspended, they either received hydrogen water therapy or no hydrogen. The effects of incubation with hydrogen-rich medium on MC3T3-E1 and RAW264.7 cells exposed to this model of microgravity were measured.

Hindlimb suspension in the absence of hydrogen treatment resulted in reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Differentiation of osteoblasts (bone forming cells) was reduced while osteoclasts (bone resorbing cells) were increased. There was augmentation of malondialdehyde (a measure of lipid peroxidation) and peroxynitrite (a potent oxidant resulting from the interaction between superoxide radicals and nitric oxide, generally considered to be due to increased production of iNOS) content and reduction of total sulfhydryl content (thiol antioxidants such as glutathione) in femur and lumbar vertebra.

Hydrogen treatment significantly alleviated these effects. “Treatment with molecular hydrogen alleviates microgravity-induced bone loss in rats. Molecular hydrogen could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.”1 Of more practical benefit to Earth-bound humans, hydrogen treatment may be a useful therapy for reducing bone loss resulting from inactivity as a result of enforced bedrest, for example.

The researchers report that exposure to the hindlimb suspension model of microgravity resulted in aggravated oxidative stress not only in the circulation, but also in the brain, liver, and muscle in animals or humans. “… microgravity exposure enhanced bone resorption through inducing oxidative stress.”1 Consumption of hydrogen water alleviated the bone loss due to oxidative stress during hindlimb suspension.

If you want to be a space traveling human (or rat), you will certainly want to receive hydrogen therapy (or an equivalent) to protect your bones. We envision the use of selective prebiotics to be fermented by your gut microbiota, releasing hydrogen that diffuses into your body tissues, including your bones, to provide protection by an alternative method of administering hydrogen, simpler to prepare than hydrogen water and released over a longer period of time.


  1. Sun et al. Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. 24:969-78 (2013).

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