Molecular Hydrogen as a Potential Adjunctive Therapy to Improve Renal Function and Reduce Fatigue in an Elderly Patient With Chronic Comorbidities: A Case Report

Abstract

Background/Aim

Hydrogen therapy has demon-strated potential as an antioxidant and anti-inflammatory intervention, particularly in the management of chronic diseases such as chronic kidney disease (CKD) and autoimmune conditions. This case report presents the possible therapeutic benefits of molecular hydrogen capsule treatment in enhancing renal function and alleviating chronic fatigue in an elderly female with coronary artery disease (CAD), type 2 diabetes mellitus (DM) complicated by nephropathy, and systemic lupus erythematosus (SLE). The aim of this study was to investigate the efficacy of adjunctive hydrogen therapy in an elderly patient with multiple chronic comorbidities.

Case Report

An 89-year-old female with a history of CAD s/p who had undergone coronary artery bypass grafting (CABG) over 40 years ago, type 2 DM complicated by nephropathy, and SLE was admitted with recurrent cellulitis at the saphenous vein donor site from her previous CABG. Despite antibiotic treatment, wound healing remained limited. In January 2023, the patient initiated adjuvant treatment with molecular hydrogen capsules. Following the introduction of hydrogen therapy, her renal function improved, evidenced by a reduction in serum creatinine levels. Chronic fatigue, assessed using the Taiwan Brief Fatigue Inventory (BFI-T), showed significant improvement. Immuno-logical evaluation revealed a series of changes, suggesting that immune modulation may be the mechanism underlying the observed clinical benefits.

Conclusion

Hydrogen therapy was associated with improved renal function and a reduced chronic fatigue in this elderly patient with multiple comorbidities, including CAD, DM, and SLE. The case underscores the potential therapeutic role of hydrogen therapy in immune modulation and the management of chronic conditions, suggesting the need for further investigation in clinical settings.

Hydrogen therapy has emerged as a novel antioxidant and anti-inflammatory treatment in various medical fields (1), including chronic kidney disease (CKD), Parkinson’s disease, systemic lupus erythematosus (SLE), chronic obstructive pulmonary disease (COPD), and immune modulation (2-5). Additionally, chronic fatigue is a prevalent symptom among elderly patients with complex comorbidities (6). The Taiwan Brief Fatigue Inventory (BFI-T) is a fatigue scale specifically designed for Taiwanese patients with cancer, chronic diseases or prolonged fatigue symptoms. This inventory assesses the severity of a patient’s fatigue based on the various aspects of daily life, including general activities, mood, work capacity, mobility, social interactions, and overall enjoyment of life, using a 0 to 10 point scale, where 0 indicates no fatigue and 10 represents the most severe fatigue (7). Hydrogen has demonstrated potential in scavenging free radicals and improving mitochondrial function (1).

We present a case report of the 89-year-old female diagnosed with CAD, SLE, and type 2 diabetes mellitus complicated by nephropathy. Despite receiving standard treatments, her renal function deteriorated, and she frequently exhibited pitting edema, which prompted the initiation of molecular hydrogen therapy as an adjuvant treatment. This study was approved by the Institutional Review Board (IRB) of Tri-Service General Hospital, National Defense Medical Center, Taiwan, and complied with relevant guidelines (IRB: B202105106, approval date: 18 July 2023). Written informed consent was obtained from the patient for the publication of this case report. The study adhered to the ethical standards of the institution and the 1964 Helsinki Declaration, along with its later amendments or comparable ethical standards.

Case Report

The patient is an 89-year-old female with a complex medical history, including systemic lupus erythematosus (SLE), type 2 diabetes mellitus (DM) complicated by nephropathy, and coronary artery disease (CAD) status post coronary artery bypass grafting (CABG) performed over 40 years ago. Due to these chronic conditions, the patient frequently experienced significant fatigue, which was systematically assessed using the Taiwan Brief Fatigue Inventory (BFI-T). Prior to the initiation of molecular hydrogen therapy, the BFI-T scores indicated severe fatigue across all domains, substantially affecting her quality of life.

Recently, the patient was readmitted due to persistent cellulitis at the saphenous vein donor site from her previous CABG surgery. This cellulitis was characterized by the formation of bulla and swelling, accompanied by pitting edema in the left lower limb (Figure 1). Despite receiving standard antibiotic treatment, her symptoms persisted, underscoring the necessity for additional therapeutic approaches to enhance her overall condition. In January 2023, the patient commenced treatment with molecular hydrogen capsules as an adjuvant therapy. Following this intervention, significant improvements were observed in both her renal function and fatigue levels. Assessments using the BFI-T conducted after the initiation of hydrogen therapy revealed notable reductions in fatigue severity, with scores indicating mild to moderate levels of fatigue and no reports of severe fatigue across all domains. This represents a marked improvement compared to her condition prior to therapy.

Figure 1.

Clinical progression and response to molecular hydrogen capsule therapy in a post-coronary artery bypass grafting (CABG) patient with recurrent cellulitis. (A) Recurrent cellulitis at the saphenous vein donor site from the patient’s previous CABG procedure. (B) Formation of bullae at the saphenous vein donor site (indicated by the green circle). (C) Prior to the initiation of molecular hydrogen capsule therapy, the patient reported frequent edema in the lower limbs. (D) Following the administration of molecular hydrogen capsule therapy, renal function improved, and the patient denied experiencing frequent lower limb edema.

Renal function, as assessed by serum creatinine levels, demonstrated progressive improvement over the course of the year (Figure 2). Prior to hydrogen therapy, her creatinine levels were consistently elevated, indicative of compromised renal function likely attributable to her underlying nephropathy. However, following the initiation of molecular hydrogen capsule therapy, a steady decline in serum creatinine levels was observed. Additionally, myositis-specific antibodies, particularly PM-Scl-100 and PL-7, showed stabilization after hydrogen therapy, suggesting a broader immunomodulatory effect that may benefit patients with autoimmune conditions such as SLE (Figure 2). Immunophenotypic analysis further corroborated these observations, revealing significant alterations in immune cell populations. Specifically, there was an increase in Naïve regulatory T cells (Tregs) and CD39-Helios⁺ regulatory T cells. In contrast, a decrease in CD127⁺ regulatory T cells was observed, along with reductions in marginal cell Fas⁺, plasma cells, and plasmablasts (Figure 3).

Figure 2.

Changes in serum creatinine levels (left panel) and myositis-specific antibodies, specifically PM-Scl-100 and PL-7 (right panel), before and after molecular hydrogen therapy. Whole blood analysis was conducted twenty-three times for serum creatinine: prior to molecular hydrogen therapy (up to December 21, 2022) and post-therapy (from January 18, 2023, to August 28, 2024). In contrast, analysis for myositis-specific antibodies was performed six times: prior to molecular hydrogen therapy (up to October 20, 2022) and post-therapy (from January 18, 2023, to March 7, 2024). Serum creatinine levels demonstrated a decreasing trend following molecular hydrogen therapy, while myositis-specific antibodies (PM-Scl-100 and PL-7) showed stabilization post-therapy.

Figure 3.

Immunophenotypic changes following molecular hydrogen therapy. Whole blood analysis was conducted four times, from March 1, 2023, to March 8, 2024. (A) The percentage change in naïve regulatory T cells (Tregs) shows an increasing trend following molecular hydrogen therapy. (B) The percentage change in CD39-Helios⁺ Tregs also exhibits an increasing trend post-therapy. (C) The percentage change in CD127⁺ Tregs demonstrates a decreasing trend after molecular hydrogen therapy. (D) The percentage change in Fas⁺ marginal cells reveals a decreasing trend post-therapy. (E) The percentage change in plasma cells shows a decreasing trend following molecular hydrogen therapy. (F) The percentage change in plasmablasts indicates a decreasing trend after molecular hydrogen therapy. Treg: regulatory T cell.

Discussion

Hydrogen therapy has demonstrated potential in reducing oxidative stress and inflammation, both of which are critical factors in the progression of CKD (1). In this case, the patient exhibited significant improvement in renal function and life quality following the administration of hydrogen capsules. The observed decrease in serum creatinine levels suggests that hydrogen may exert a protective effect on renal function, consistent with recent studies that highlight its role in mitigating kidney damage by scavenging free radicals and reducing oxidative stress (1,5).

Hydrogen’s capacity to protect against oxidative injury is particularly relevant in CKD, where excessive oxidative stress can accelerate kidney damage. By reducing inflammation and oxidative burden, hydrogen therapy may decelerate the progression of kidney disease and enhance overall renal outcomes, as demonstrated by the patient’s improvement in kidney function over time (5). This case further supports the consideration of hydrogen therapy as a potential adjunct treatment for renal protection, especially in patients with complex comorbidities, such as SLE and diabetes, which are known to exacerbate CKD.

Additionally, the immunomodulatory effects of hydrogen, include an increase in Naïve regulatory T cells and CD39-Helios⁺ regulatory T cells, both of which play crucial roles in maintaining immune tolerance and suppressing excessive inflammatory responses (8). These changes suggest that hydrogen therapy may help modulate the immune system, enhancing regulatory pathways that are often disrupted in autoimmune diseases such as SLE. Conversely, there was a decrease in CD127⁺ regulatory T cells, which are associated with inflammatory responses (9), as well as in marginal cell Fas⁺, plasma cells and plasmablasts. The reduction in plasma cells and plasmablasts, which are key players in antibody production (10), could be particularly beneficial for controlling the overactive immune responses characteristic of autoimmune conditions, potentially reducing disease activity and flares.

Overall, these immunological shifts suggest that hydrogen therapy may exert a dual effect—reducing inflammation while enhancing immune regulation. This modulation could represent a key mechanism underlying the observed clinical benefits, including the improvement in renal function and reduction in fatigue. Furthermore, the improvement in her lower limb edema (Figure 1) may also reflect the systemic anti-inflammatory and antioxidant effects of hydrogen (11), which could contribute to reducing vascular inflammation and improving microcirculation. Collectively, these findings underscore the multifaceted impact of molecular hydrogen therapy, particularly its potential role in renal protection, fatigue reduction, and immune modulation.

Conclusion

This case highlights the potential therapeutic benefits of molecular hydrogen capsule treatment in an elderly patient with complex comorbidities, including coronary artery disease, systemic lupus erythematosus, and type 2 diabetes mellitus complicated by nephropathy. The observed improvements in renal function, reduction in chronic fatigue, and favorable immunological changes suggest that hydrogen therapy may offer a multifaceted therapeutic approach by addressing oxidative stress, inflammation, and immune dysregulation. While these findings are encouraging, further studies are needed to elucidate the underlying mechanisms and to assess hydrogen’s potential as a mainstream therapeutic option for similar patient populations.

Conflicts of Interest

The Authors declare that there are no conflicts of interest or competing interests related to this study.

Authors’ Contributions

YTL: Conceptualization, methodology, writing – original draft, writing review and editing. JWL: Conceptualization, methodology, writing original draft, writing review and editing. YJH: Conceptualization, methodology, project administration, writing original draft, writing, review and editing. SWL: Conceptualization, methodology, writing original draft, writing, review and editing. TYH: Conceptualization, methodology, writing original draft, writing, review and editing. FCL: Conceptualization, investigation, supervision, writing, review and editing.

Acknowledgements

This study was supported by the Ministry of Science and Technology (MOST 109-2314-B-016-052, MOST 111-2314-B-016-026), the National Science and Technology Council (NSTC 112-2314-B-016-033, NSTC 113-2314-B-016-052), and Tri-Service General Hospital (TSGH-E-111215, TSGH-E-112218) in Taiwan.