Bone Health, Explained: What the Research Says About Oxidative Stress — and How Hydrogen Water May Help
Most people picture the skeleton as finished work. It isn't. Bone is living tissue, and it is being torn down and rebuilt right now, in you, today. Roughly a tenth of your skeleton is replaced every year. By your mid-fifties you are walking around on bone that did not exist a decade ago.
That constant renewal is what keeps bone strong. It is also where bone loss begins, because the rebuilding depends on a balance between two crews of cells — and that balance is sensitive to oxidative stress.
This article covers what that balance is, why it shifts with age, and what the peer-reviewed research on molecular hydrogen and bone shows so far. Every claim is tied to a numbered study from the Bone Studies section of our site, so you can read the source yourself.
The two crews
Bone remodeling runs on two cell types with opposite jobs.
They lay down new bone matrix and mineralize it. They are the construction crew.
They dissolve old bone and clear it away so new bone can replace it. They are the demolition crew.
For most of adult life the two keep pace. Demolition clears out micro-damaged bone, construction replaces it, and net bone mass holds steady. The problem is not that osteoclasts exist — without them, bone would accumulate old micro-fractures and become brittle. The problem is when demolition starts outpacing construction.
That is what happens with age. In women it accelerates sharply after menopause, when estrogen withdrawal removes a brake on osteoclast activity. Bone mineral density falls, the internal lattice of the bone (the trabecular structure) thins and loses connections, and the bone becomes mechanically weaker. Enough of that and the clinical labels follow: osteopenia, then osteoporosis.
Where oxidative stress comes in
Free radicals are unstable molecules produced as a byproduct of normal metabolism. When production outruns the body's ability to neutralize them, the result is oxidative stress — a state that damages DNA, proteins and cell membranes, and that rises with age.
In bone, oxidative stress does not act as a neutral background irritant. It tilts the remodeling balance. Reactive oxygen species promote the formation and activity of osteoclasts, and they make conditions harder for osteoblasts. Inflammatory signaling molecules such as TNF-α and IL-6 are part of the same picture, pushing in the same direction.
This is why researchers studying bone loss keep arriving at the same question: if oxidative stress is one of the levers, can reducing it protect bone? That question is what sent researchers to molecular hydrogen.
Why molecular hydrogen
Molecular hydrogen (H₂) is two hydrogen atoms bonded together — the smallest molecule in existence. It is electrically neutral, which lets it pass through cell membranes easily and reach places larger antioxidants cannot, including the mitochondria where free radicals are generated.
The modern research era began with a 2007 paper in Nature Medicine showing that hydrogen selectively neutralizes the hydroxyl radical, the most destructive reactive oxygen species, while leaving the useful radicals the body uses for signaling alone. That selectivity is what made researchers in other fields — including bone — take an interest.
Hydrogen-rich water is produced by electrolysis. Passing a current through water splits it, and at the cathode the water becomes alkaline and saturated with dissolved molecular hydrogen. That is what a water ionizer does, and it is what the drinking-water studies below used.
What the bone research shows
Thirteen studies on our Bone Studies list bear on skeletal tissue. Here is what they found, grouped by what was measured. All of this work was done in cells and animals. None of it has been repeated in human trials, which matters and is addressed below.
Bone density and strength in an osteoporosis model
The most relevant study is Guo and colleagues, published in the British Journal of Pharmacology in 2013 [24]. The researchers used ovariectomized rats — the standard laboratory model for post-menopausal bone loss, since removing the ovaries removes estrogen the way menopause does. Rats drank hydrogen water at about 1.3 mg per liter for three months. Hydrogen water did not affect estrogen production. What it did do was prevent the loss of bone mineral content and bone mineral density in both the femur and the vertebrae; preserve mechanical strength, measured as ultimate load, stiffness and energy; and preserve the internal bone structure, including trabecular bone volume fraction, trabecular number and trabecular thickness. The treated animals also showed less oxidative stress and lower expression of the inflammatory signals IL-6 and TNF-α in the femur. The authors attributed the effect to blunting the oxidative stress caused by estrogen withdrawal.
Bone loss under a different kind of stress
Sun and colleagues, writing in Osteoporosis International in 2013, tested hydrogen in rats under modeled microgravity — a well-established way to induce rapid bone loss [31]. Hydrogen treatment reduced oxidative stress and alleviated the bone loss. Two different mechanisms of bone loss, two studies, the same direction of effect.
The demolition crew
Li and colleagues, in the Journal of Bone and Mineral Metabolism in 2013, looked at how osteoclasts are formed [30]. RANKL is the signal that drives precursor cells to become mature, bone-dissolving osteoclasts. Treatment with hydrogen prevented RANKL-induced osteoclast differentiation in cultured cells, and did so alongside reduced reactive oxygen species and the inactivation of several signaling pathways involved in that process. In plain terms: fewer demolition workers got hired.
The construction crew
Cai and colleagues, in Molecular and Cellular Biochemistry in 2013, treated osteoblasts with TNF-α — the inflammatory signal that injures bone-building cells — and found that hydrogen alleviated that injury [22]. Kawasaki and colleagues reported that hydrogen gas extended the replicative lifespan of bone marrow multipotential stromal cells in culture while preserving their ability to differentiate, meaning the precursor cells that become osteoblasts stayed viable longer [27].
Cartilage and joints
Hanaoka and colleagues found that molecular hydrogen protected chondrocytes — the cells that maintain cartilage — from oxidative stress, apparently by reducing peroxynitrite derived from nitric oxide [25]. Yamada and colleagues found that adding hydrogen to a preservation solution improved the viability of osteochondral grafts [84].
Inflammation, the common thread
Several studies on the list address the inflammatory side of the same process rather than bone directly: hydrogen inhibited nitric oxide production in activated macrophages [26], and hydrogen-rich saline showed anti-inflammatory effects in two standard inflammation models [33]. Fujita and colleagues looked next door to bone, at disuse muscle atrophy, using hydrogen-saturated alkaline electrolyzed water [23].
What this does and does not mean
The pattern across these studies is coherent. Hydrogen appears to act on both sides of the remodeling balance — fewer osteoclasts forming, better-protected osteoblasts — and the whole-animal studies found that this translated into preserved bone density, structure and strength in two different models of bone loss.
But the honest summary has to include the limit: this is laboratory and animal research. Hydrogen water has not been shown to prevent osteoporosis or bone fractures in people. Rats are not women, three months is not three decades, and a promising animal result is the beginning of a research story rather than the end of one. Anyone managing bone density should be doing it with their doctor, with the tools that do have human evidence behind them — weight-bearing exercise, adequate calcium and vitamin D, bone density screening, and prescription treatment where it is warranted.
What the research supports is a reason to be interested, not a reason to substitute. Hydrogen-rich water is water. It is something you were going to drink anyway, and the safety studies on our list have not turned up a problem with it.
Reading further
Every study referenced here is listed with a link to the original paper on our Studies page. The bone section is studies 22 through 34. Read them yourself — the abstracts are short, and the findings are stated plainly.
Questions about hydrogen water or Life Ionizers systems? Talk with a hydrogen water expert, or request a free report on your local water supply.
Call (800) 323-3137Educational information only. Not intended to diagnose, treat, cure, or prevent any disease. Consult your doctor.
References
Numbers match the Bone Studies section at lifeionizers.com/pages/studies. Studies 28, 29, 32 and 34 appear in that section but concern cornea, neonatal brain hemorrhage, platelet aggregation and stem-cell transplantation; they are not cited in the article. Study 84 is listed in the Brain section but tagged as bone on the page.
| # | Study | Journal, year | Model |
|---|---|---|---|
| 22 | Cai WW et al. Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast | Mol Cell Biochem, 2013 | Osteoblasts (in vitro) |
| 23 | Fujita R et al. Effect of molecular hydrogen saturated alkaline electrolyzed water on disuse muscle atrophy in gastrocnemius muscle | J Physiol Anthropol, 2011 | Animal (muscle) |
| 24 | Guo JD et al. Hydrogen water consumption prevents osteopenia in ovariectomized rats | Br J Pharmacol, 2013 | Rat, drinking water, 3 months |
| 25 | Hanaoka T et al. Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide | Med Gas Res, 2011 | Chondrocytes (in vitro) |
| 26 | Itoh T et al. Molecular hydrogen inhibits lipopolysaccharide/interferon gamma-induced nitric oxide production through modulation of signal transduction in macrophages | Biochem Biophys Res Commun, 2011 | Macrophages (in vitro) |
| 27 | Kawasaki H, Guan JJ, Tamama K. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials | Biochem Biophys Res Commun, 2010 | Bone marrow stromal cells (in vitro) |
| 30 | Li DZ et al. Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-κB pathways in murine RAW264.7 cells | J Bone Miner Metab, 2013 | Osteoclast precursors (in vitro) |
| 31 | Sun Y et al. Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats | Osteoporos Int, 2013 | Rat |
| 33 | Xu Z et al. Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema | J Inflamm (Lond), 2012 | Cells + animal |
| 84 | Yamada T et al. Hydrogen supplementation of preservation solution improves viability of osteochondral grafts | ScientificWorldJournal, 2014 | Osteochondral grafts |
Background reference cited in the article for mechanism, from the Antioxidant section: Ohsawa I et al., Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, Nature Medicine, 2007 (Study 9).
Reference Links
Studies indicate that hydrogen water can protect against bone density loss, the key factor in osteoporosis, by reducing oxidative damage in bone tissue.
22.Cai, W.W., et al., Treatment with hydrogen molecule alleviates TNFalpha-induced cell injury in osteoblast. Mol Cell Biochem, 2013. 373(1-2): p. 1-9.
23.Fujita, R., et al., Effect of molecular hydrogen saturated alkaline electrolyzed water on disuse muscle atrophy in gastrocnemius muscle. Journal of Physiological Anthropology, 2011. 30(5): p. 195-201.
24.Guo, J.D., et al., Hydrogen water consumption prevents osteopenia in ovariectomized rats. Br J Pharmacol, 2013. 168(6): p. 1412-20.
25.Hanaoka, T., et al., Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide. Medical Gas Research, 2011. 1(1): p. 18.
26.Itoh, T., et al., Molecular hydrogen inhibits lipopolysaccharide/interferon gamma-induced nitric oxide production through modulation of signal transduction in macrophages. Biochemical and Biophysical Research Communications, 2011. 411(1): p. 143-9.
27.Kawasaki, H., J.J. Guan, and K. Tamama, Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials. Biochemical and Biophysical Research Communications, 2010. 397(3): p. 608-613.
28.Kubota, M., et al., Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model. Investigative Ophthalmology and Visual Science, 2011. 52(1): p. 427-33.
29.Lekic, T., et al., Protective effect of hydrogen gas therapy after germinal matrix hemorrhage in neonatal rats. Acta Neurochir Suppl, 2011. 111: p. 237-41.
30.Li, D.Z., et al., Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells. J Bone Miner Metab, 2013.
31.Sun, Y., et al., Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporos Int, 2013. 24(3): p. 969-78.
32.Takeuchi, S., et al., Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study. Internal Medicine, 2012. 51(11): p. 1309-13.
33.Xu, Z., et al., Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema. J Inflamm (Lond), 2012. 9: p. 2.
34.Yuan, L., et al., Administration of hydrogen-rich saline in mice with allogeneic hematopoietic stem-cell transplantation. Med Sci Monit, 2015. 21: p. 749-54.
