Should molecular hydrogen therapy be included in a musculoskeletal medicine routine?

Molecular hydrogen (H 2) has recently been recognized as a potential novel therapeutic agent in biomedicine. Initially proposed to be a possible treatment for certain types of neuromuscular disorders, cardio-metabolic diseases and cancer,molecular hydrogen  H 2 improved clinical end-points and surrogate markers in several clinical trials, mainly acting as an anti-inflammatory agent and powerful antioxidant. In this paper, the medicinal properties of molecular hydrogen H 2 in musculoskeletal medicine are discussed with the aim to provide an updated and practical overview for health professionals working in this field.

Background

As the oldest and the most abundant molecule in the universe, molecular hydrogen (H 2) has been traditionally recognized as a biologically inert gas. However, several trials in the past 10 years reported beneficial effects of molecular hydrogen H 2 in the clinical environment, revealing its possible role as a novel therapeutic agent in medicine – . Usually administered orally or via inhalation, molecular hydrogen H 2 improves both patient- and clinician-reported outcomes, and biomarkers of different pathologies and disorders, from metabolic diseases to chronic systemic inflammatory disorders to cancer [for detailed review see Ref. ].

Its clinical relevance seems to be particularly notable in the musculoskeletal medicine, with several small-scale short-term studies –  reporting that molecular H 2 was able to restore the health and functional abilities of patients after acute injuries or chronic illnesses affecting the muscles and bones. Since musculoskeletal conditions account for a large proportion of a general practitioner’s workload , one might consider molecular hydrogen  H 2 as a promising medication or adjuvant that could alleviate these prevalent conditions. In this opinion paper, the medicinal properties of molecular hydrogen H 2 in musculoskeletal medicine are discussed to provide an updated and practical overview for health professionals working in this field.

Promising results from preliminary studies

Being prompted by the prominent effects of molecular hydrogen H 2 on disuse muscle atrophy, cartilage trauma, and osteopenia in animal studies – , a number of clinical investigators from 2010 onwards evaluated the effectiveness of molecular hydrogen H 2 in patients suffering from different muscle and bone ailments – from sprains and strains to chronic joint disorders to myopathies – . Typically, these studies were designed as single-blind pilot trials, with small sample sizes (< 40 participants) and of short duration (≤ 12 weeks). Although limited in size and scope, those studies can provide early support for specific therapeutic claims about molecular hydrogen H 2 in musculoskeletal medicine. In a first trial, a combination of oral and topical molecular hydrogen H 2 resulted in a faster return to normal joint flexibility in 36 young men who had suffered sports-related soft tissue injuries, when administered for 14 days as a complementary treatment to a traditional medical protocol for soft tissue injuries 7.molecular  hydrogen  H 2intervention (hydrogen-rich packs 6 times per day for 20 min and 2 g of oral molecular hydrogen H 2 daily) was found to augment plasma viscosity decrease after an injury, while other biomarkers of inflammation (C-reactive protein, interleukin-6) and clinical outcomes (pain scores at rest and at walking, degree of limb swelling) were not affected by the intervention 7.

Another study in Japan reported that drinking 530 ml of a liquid containing 4 to 5 ppm of molecular hydrogen H  (dissolved in water) every day for 4 weeks significantly reduced disease activity in 20 patients with rheumatoid arthritis, as evaluated by changes in the degree of tenderness and swelling in 28 joints and C-reactive protein levels 8.  Molecular hydrogen H 2 was administered as an adjuvant to regular disease-modifying anti-rheumatic drugs and biological drugs, with the efficacy of molecular hydrogen H 2 found to be not inferior comparing to abatacept, methotrexate or a combination of two. In total, 47.4% of patients went into remission, with anti-citrullinated protein antibody (ACPA)-positive patients (ACPA levels above 300 U/mL; patients with worse prognosis and higher rates of erosive damage) responding best to the treatment.

Finally, the consumption of water containing a high concentration of moleuculr hydrogen H 2 (31% saturation) for up to 12 weeks improved surrogate markers of muscle pain and fatigability in 22 patients with inherited and acquired myopathies treated with low-dose prednisone . Taken together, the above studies seem to pave the way for a future use of molecular hydrogen H 2 therapy in musculoskeletal medicine.

please note that although the article above adds  little salt regarding molecular hydrogen safety due to it’s novelty ,one of the best parts about molecular hydrogen water is that it has been shown to have a tremendous safety profile. This has been demonstrated in a few ways:

  • Out of 600-plus scientific studies, molecular hydrogen  H2 has shown no cytotoxic effects or cytotoxic by-products in the human body. 22
  • We have a basal level of molecular hydrogen  H2 in our blood stream at all times, around 1~5 micromolar or less. 23
  • Humans can produce up to 10 liters of molecular hydrogen  H2 a day with a good diet containing fruits, vegetables, and fiber-rich foods. This is due to the production of molecular hydrogen  H2 by our gut flora (gut bacteria). 24
  • Another reason we know molecular hydrogen H2 is safe is because it has been used to ameliorate decompression sickness in deep sea diving since 1945. 25 The molecular hydrogen H2 concentration has been as high 98.87 percent molecular hydrogen  H2 and 1.26 percent of O2, at 19.1 atm with minimal to no adverse or cytotoxic effects. 26 The United States military also has been using molecular hydrogen H2 for deep sea diving since the 60s. 27 Molecular hydrogen has been demonstrated to be extremely safe for the human body. 28

 

This information tells us that molecular hydrogen-rich water is safe for consumption in all age groups, from children to adults, as a preventive beverage that has the potential to reduce oxidative stress and so much more. Everyone, including children, is exposed to oxidative stress, which has been linked to the pathogenesis of nearly all disease conditions, including cancer. 29 Consuming water infused with molecular hydrogen is exactly what our society needs to aid in the battle against degenerative diseases.

Please note that most studies and research with molecular hydrogen gas were performed using molecular hydrogen rich water

References

1. Kajiyama S, Hasegawa G, Asano M, et al. : Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res.2008;28(3):137–43. 10.1016/j.nutres.2008.01.008 [PubMed] [Cross Ref]
2. Nakao A, Toyoda Y, Sharma P, et al. : Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr.2010;46(2):140–9. 10.3164/jcbn.09-100 [PMC free article] [PubMed] [Cross Ref]
3. Nakayama M, Nakano H, Hamada H, et al. : A novel bioactive haemodialysis system using dissolved dihydrogen (H 2) produced by water electrolysis: a clinical trial. Nephrol Dial Transplant.2010;25(9):3026–33. 10.1093/ndt/gfq196 [PubMed] [Cross Ref]
4. Yoritaka A, Takanashi M, Hirayama M, et al. : Pilot study of H 2 therapy in Parkinson’s disease: a randomized double-blind placebo-controlled trial. Mov Disord. 2013;28(6):836–9. 10.1002/mds.25375[PubMed] [Cross Ref]
5. Xia C, Liu W, Zeng D, et al. : Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin Transl Sci. 2013;6(5):372–5. 10.1111/cts.12076[PMC free article] [PubMed] [Cross Ref]
6. Ostojic SM: Molecular hydrogen: An inert gas turns clinically effective. Ann Med. 2015;47(4):301–4. 10.3109/07853890.2015.1034765 [PubMed] [Cross Ref]
7. Ostojic SM, Vukomanovic B, Calleja-Gonzalez J, et al. : Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries. Postgrad Med. 2014;126(5):187–95. 10.3810/pgm.2014.09.2813[PubMed] [Cross Ref]
8. Ishibashi T, Sato B, Rikitake M, et al. : Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Med Gas Res. 2012;2(1):27. 10.1186/2045-9912-2-27 [PMC free article] [PubMed][Cross Ref]
9. Ito M, Ibi T, Sahashi K, et al. : Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med Gas Res.2011;1(1):24. 10.1186/2045-9912-1-24 [PMC free article] [PubMed] [Cross Ref]
10. Hunter DJ, Reddy KS: Noncommunicable diseases. N Engl J Med. 2013;369(14):1336–43. 10.1056/NEJMra1109345 [PubMed] [Cross Ref]
11. Fujita R, Tanaka Y, Saihara Y, et al. : Effect of molecular hydrogen saturated alkaline electrolyzed water on disuse muscle atrophy in gastrocnemius muscle. J Physiol Anthropol. 2011;30(5):195–201. 10.2114/jpa2.30.195 [PubMed] [Cross Ref]
12. Guo JD, Li L, Shi YM, et al. : Hydrogen water consumption prevents osteopenia in ovariectomized rats. Br J Pharmacol. 2013;168(6):1412–20. 10.1111/bph.12036 [PMC free article] [PubMed] [Cross Ref]
13. Hanaoka T, Kamimura N, Yokota 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;1(1):18. 10.1186/2045-9912-1-18 [PMC free article] [PubMed] [Cross Ref]
14. Derry S, Wiffen P, Moore A: Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain. JAMA. 2016;315(8):813–4. 10.1001/jama.2016.0249 [PubMed] [Cross Ref]
15. Strehl C, Bijlsma JW, de Wit M, et al. : Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis. 2016;75(6):952–7. 10.1136/annrheumdis-2015-208916[PubMed] [Cross Ref]
16. The Food and Drug Administration (FDA): Agency Response Letter GRAS Notice No. 520. (Assessed at October 28, 2016). Reference Source
17. The Food and Drug Administration (FDA): Inspections, Compliance, Enforcement, and Criminal Investigations. (Assessed at October 28, 2016). Reference Source

Approved

1Department of Neurology and Psychiatry, Saint Louis University School of Medicine, Saint Louis, MO, USA
Competing interests: No competing interests were disclosed.
Review date: 2016 Dec 8. Status: Approved

The title is appropriate with reference to the content of the article.

The article is a review of the literature with reference to utilizing molecular hydrogen to enhance sports related injuries.

After a detailed review of the literature, the conclusion is there is not enough information to make any solid recommendation concerning utilizing molecular hydrogen to treat sports related injuries, so the implication is probably molecular hydrogen doesn’t improve recovery from sports related injuries enough to make any difference.

This appears to be a good review of the related literature.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Approved

Xiaoli SunReferee1 and Ning ZhangCo-referee2
1Department of Diving Medicine, Second Military Medical University, Shanghai, China
2Department of Naval Aeromedicine, Second Military Medical University, Shanghai, China
Competing interests: No competing interests were disclosed.
Review date: 2016 Dec 8. Status: Approved

This opinion paper provides an undated and practical overview on the properties of molecular hydrogen in musculoskeletal medicine. The paper focuses on the preliminary studies of H2 on musculoskeletal medicine, and the concerns over the general use of products containing H2. I sympathize the author’s prudent attitudes, which toward the hydrogen should be regarded as an experimental agent and not recommended to general use provisionally. However, I think this paper should also mention the long-term diving practices which high pressure hydrogen inhalation involved to prove the possible safe use of H2 gas.

We have read this submission. We believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Articles from F1000Research are provided here courtesy of F1000 Research Ltd
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Version 1. . 2016; 5: 2659.
Published online 2016 Nov 10. doi:  10.12688/f1000research.9758.1
PMCID: PMC5147523
Should hydrogen therapy be included in a musculoskeletal medicine routine?
1Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia
2University of Belgrade School of Medicine, Belgrade, Serbia
Competing interests: No competing interests were disclosed.

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