Molecular Hydrogen and Autoimmune Disease

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Multiple clinical studies report improvements in autoimmune disease with hydrogen treatment

Although hydrogen (H₂) is well known as an alternative fuel, recognized as such in the Energy Policy Act of 1992, only in 2007 did it begin to really make the scene in medicine. Although used for the purpose of preventing decompression sickness in divers since the 1940s,^[1],[2] it wasn’t practically useful as a therapy due to its high flammability, being easily ignited at a concentration of approximately 4% in air. In 2007, the first research using H₂ in a format that is practical clinically (dissolved in air at a concentration of less than 4% or in a cellular nutrient medium) was published in Nature Medicine,^[3] and the research exploded.

Since then, H₂ has been administered in clinical studies as an inhaled gas,^[4] dissolved in water for oral delivery or topical application,^[5],[6] and delivered in saline intravenously.^[7] From human research we have seen that molecular H₂ has potential benefits for metabolic health,^[8] fatty liver disease,^[9] exercise performance,^[10] autonomic nervous system balance,^[11] acute cerebral infarction,⁴ Parkinson’s disease,^[12] and in patients receiving radiation treatment for liver cancer,^[13] among many other things.^[14],[15]

H₂ has been demonstrated to be a selective antioxidant,^[16] an anti-inflammatory,^[17],[18] and an activator of the body’s endogenous antioxidant production via the Nrf2 cell-signaling pathway.^[19] Given each of these things, should we find it surprising that it also has been investigated as a treatment for autoimmune disease?

Clinical application of hydrogen in autoimmune disease

Multiple clinical studies have shown that treatment with H₂-rich water may be of benefit to individuals with autoimmune disease. The first publication of this nature was an open-label pilot study that investigated the impact of consumption of supersaturated H₂ water on patients with rheumatoid arthritis (RA).^[20] In this study, participants consumed 530 mL of H₂-rich water (containing 4 to 5 ppm of H₂) daily for four weeks, then had a four-week washout, followed by another four weeks of H₂ water consumption. Of the 20 patients in the study, five of them had early RA (duration of less than 12 months), and four of these individuals were not on any medication. The other participants were either on methotrexate or abatacept, a combination of these, or no medications (abandoned due to side effects). No one in the study was being treated with steroid hormones.

During each period of treatment with the H₂-rich water, RA disease activity scores improved.

During each period of treatment with the H₂-rich water, RA disease activity scores, based on assessment of 28 joints (DAS28), improved. In the first four weeks, scores decreased in 18 of the 20 patients. By the end of the study, the average DAS28 score for all participants had decreased from the baseline of 3.83 to 2.26, and the five patients having early RA all achieved remission (defined for the purpose of this study as a DAS28 < 2.3, although a cutoff value of 2.6 is often used^[21]), with four of them becoming symptom-free.

One particularly interesting finding in this study was that the DAS28 score continued to improve during the four-week washout period, suggesting that the H₂ treatment continued to have residual effects. Urinary 8-hydroxy-deoxyguanosine (8-OHdG) levels, a marker of DNA oxidative damage,^[22] also improved not only during treatment but during the washout phase as well, remaining below the baseline through the end of the study. It has been suggested that some of the longer term effects seen with H₂ as a therapy are due to its impact on cellular signal transduction, protein activity, and genetic transcription, as its direct antioxidant effects would be limited roughly to its time in circulation which is 45 to 90 minutes, as evidenced by its level in expired air.^[23]

Prolonged benefits with hydrogen treatment were also seen in a follow-on randomized, double-blind, placebo-controlled study of rheumatoid arthritis patients that looked at the impact of treatment for five days with 500 mL of intravenous, H₂-enhanced saline.⁷ In this study, the DAS28 score in the H₂-treated group decreased from the baseline of 5.18 to 4.02 immediately after infusions and to 3.74 by four weeks while there was no change in the score of the placebo group. Additionally, the level of interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3), markers of inflammation and joint damage,^[24] decreased significantly in the H₂-treated group while they increased in the placebo group.

Bathing in H₂-rich water also has been studied as a treatment for psoriasis and resulted in an improvement of 75% or more in the Psoriasis Area Severity Index score in 10 of 41 of patients after eight weeks.

A publication of three psoriasis case studies using a variety of different H₂ administration techniques (inhalation, intravenous, and taken orally in water) reported improvements in skin lesions and psoriatic arthritis symptoms regardless of the route of intervention.^[25] Bathing in H₂-rich water also has been studied as a treatment for psoriasis and resulted in an improvement of 75% or more in the Psoriasis Area Severity Index (PASI) score in 10 of 41 of patients after eight weeks, while only 1 of 34 patients in the control group had the same level of improvement.⁶ Although a whole body bath may not be practical for most, soaking a portion of the body that is affected with psoriasis lesions in H₂-rich water is not tremendously difficult and worthy of consideration.

The positive outcomes of these studies, and other findings from numerous animal models of autoimmune disease,^{[26],[27],[28]} make it evident that we will continue to see research surrounding the use of H₂ in autoimmune disease. The improvements or sustained benefits seen post-intervention for a prolonged period also are particularly exciting, as this would minimize cost and the burden of taking a daily supplement. Clearly, many exciting applications for H₂ as a therapy will be seen in years to come.

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