Molecular Hydrogen as an Adjuvant Therapy in Severe Lupus Serositis With Heart Failure: A Case Report on Immune Modulation and Fatigue Reduction

Abstract

Background/Aim

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-organ inflammation and damage across multiple organs, typically managed with steroids and immunomodulators. However, prolonged use of these treatments is often associated with significant side effects, underscoring the need for adjunctive therapies that improve disease outcomes while minimizing adverse effects. Molecular hydrogen (H₂) has demonstrated potential as an antioxidant and anti-inflammatory agent. This report discusses a case of SLE with cardiac complications, evaluating the therapeutic impact of molecular hydrogen therapy on fatigue, immune modulation, and cardiac function.

Case Report

A 51-year-old female with SLE and acute decompensated heart failure initially received steroids and immunomodulators for disease management. Subsequently, molecular hydrogen therapy was introduced as an adjuvant treatment. Over several months, her cardiac function showed notable improvement, evidenced by reductions in anti-dsDNA and anti-Ro52 antibody levels, and Pro-BNP levels, as well as favorable shifts in T and B cell subsets. Additionally, the patient experienced a significant reduction in fatigue. She successfully tapered off steroids while maintaining disease stability with ongoing molecular hydrogen therapy.

Conclusion

This case highlights the potential of molecular hydrogen therapy as an adjuvant treatment in SLE, with observed benefits in immune modulation and fatigue reduction. Further studies are warranted to elucidate its therapeutic role and applicability in autoimmune diseases.

Introduction

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by systemic inflammation and multi-organ damage, most commonly impacting the kidneys, heart, skin, and lungs (1,2). Treatment usually involves steroids, though prolonged steroid use increases the risk of infections, osteoporosis, and cardiovascular complications (3,4). Additionally, the chronic nature of SLE often leads to persistent fatigue and diminished quality of life (5-7). To measure chronic fatigue, the Taiwan Brief Fatigue Inventory (BFI-T) evaluates fatigue intensity across daily life activities on a 0-10 scale, where 0 indicates no fatigue and 10 signifies the most severe fatigue. The BFI-T has been used with Taiwanese patients experiencing cancer, chronic illnesses, or long-standing fatigue (8). Given the chronic course and multifaceted complications of SLE, novel therapeutic approaches are being actively investigated to improve patient outcomes, minimize steroid dependency, and better modulate the immune system.

Molecular hydrogen (H₂) has demonstrated potential as an adjuvant therapy for various autoimmune and inflammatory conditions, including cardiovascular and respiratory diseases, central nervous system disorders, and chronic kidney disease (9-12), primarily due to its antioxidant properties and potential for immune modulation (13). Research suggests that H₂ may mitigate oxidative stress and inflammation by selectively neutralizing hydroxyl radicals, thereby protecting tissue and reducing inflammatory responses (14,15). In this case, H₂ was using hydrogen capsules (PURE HYDROGEN) obtained from HoHo Biotech Co., Ltd. (Taipei, Taiwan, ROC). Each capsule contained 170 mg of hydrogen-enriched calcium, delivering approximately 1.7×1,021 molecules of hydrogen-equivalent to the hydrogen concentration in 24 cups of water with 1,200 ppb (0.6 mM in 200 ml).

In this case report, we present a 51-year-old female newly diagnosed with SLE complicated by acute decompensated heart failure, highlighting the use of H₂ therapy as part of her treatment. Emphasis is placed on H₂ therapy’s potential roles in immune modulation, reduction of fatigue, and stabilization of cardiac function. This study was approved by the Institutional Review Board (IRB) of Tri-Service General Hospital, National Defense Medical Center, Taiwan (IRB approval number: B202105106; approval date: July 18, 2023) and adhered to all relevant ethical guidelines. Written informed consent was obtained from the patient for publication of this case report. The study complied with the ethical standards of the institution and the 1964 Declaration of Helsinki and its subsequent amendments or comparable ethical standards.

Case Report

The patient, a 51-year-old female, was diagnosed with SLE in February 2020 at a district hospital. She initially presented with shortness of breath and bilateral lower limbs swelling. Laboratory tests revealed elevated serum troponin-I and pro-BNP levels, while imaging studies identified bilateral pleural effusion and cardiomegaly. Cardiac sonography indicated generalized left ventricle hypokinesia, with a reduced left ventricular ejection fraction (LVEF) of 20-25%, severe mitral regurgitation (MR) and moderate tricuspid regurgitation (TR), with a tricuspid annular plane systolic excursion (TAPSE) of 1.7 cm, consistent with heart failure with reduced ejection fraction (HFrEF). She was subsequently transferred to a medical center for further care.

The patient was initially treated with high-dose methylprednisolone (80 mg once daily), the immuno-modulators azathioprine (50 mg twice daily), and adjuvant therapy with one H₂ capsule daily. Due to bilateral pleural effusion and respiratory distress, a left-sided thoracentesis was performed, draining 550 ml of pleural fluid. To further evaluate acute decompensated heart failure, myocardial perfusion imaging with thallium-201 was conducted, revealing mild ischemia in the LAD and RCA territories, thereby ruling out significant coronary artery disease (CAD).

By March 2020, the patient’s symptoms had significantly improved, allowing for discharge in a stable condition. Over the subsequent months, her clinical condition continued to improve under treatment with steroids, an immuno-modulator, and H₂ therapy (Figure 1). By April 2020, cardiac sonography indicated a normalized LVEF of 70%, with only mild MR and TR. Steroid dosages were gradually tapered, and daily hydrogen capsule therapy was maintained. By the end of 2020, the patient successfully discontinued steroid therapy without experiencing an SLE flare-up.

Figure 1.

Clinical course of the patient. (A) Chest X-ray (CXR) images from March 4, 2020, showing patchy ground-glass opacities in both lungs, bilateral pleural effusion, prominence of bilateral hilar shadows (likely representing engorged central pulmonary vessels), and cardiomegaly, all consistent with heart failure. (B) CXR images from January 13, 2022, showing normal cardiac size, sharp costophrenic angle, and well expanded bilateral lungs. The images demonstrate notable improvements before (left) and after (right) molecular hydrogen therapy. (C) Vital signs during hospitalization, from March 2, 2020, to March 13, 2020. After the initiation of H₂ therapy on the morning of March 5, 2020, the patient’s vital signs remained stable. T: Body temperature (blue line); P: Pulse (red line); R: Respiratory rate (black line).

In addition to the stabilization of her clinical condition, immune modulation was observed. Notably, there was an increase in the expression of Fas+ T cells, regulatory T cells, and regulatory B cells (Figure 2). Furthermore, levels of pro-B-type natriuretic peptide (Pro-BNP), anti-dsDNA antibody, and anti-Ro52 antibody, which were initially elevated to 26,470 pg/ml, 506 IU/ml, and 92 IU/ml, respectively, decreased to near-normal values following discharge (Figure 3). Furthermore, the fatigue that had previously greatly impacted her quality of life also improved markedly, with her BFI-T score decreasing from 51 points to 18, indicating a substantial reduction in fatigue. The patient’s current regimen includes hydroxychloroquine (200 mg daily), mycophenolic acid (360 mg every other day), and adjuvant H₂ capsule therapy (one capsule daily). She continues regular follow-up visits at the OPD every two months, with the current treatment demonstrating effectiveness and no significant side effects.

Figure 2.

Immunophenotypic changes following molecular hydrogen therapy. Whole blood analysis was conducted nine times, from the initiation of molecular hydrogen capsule (HC) to February 22, 2024. (A) The percentage change in effector memory T helper cell expressing Fas (EM Th Fas+) shows an increasing trend following molecular hydrogen therapy. (B) The percentage change in effector memory cytotoxic T cell expressing Fas (EM Tc Fas+) also exhibits an upward trend post-therapy. (C) The percentage change in effector cytotoxic T cell expressing Fas (Effector Tc Fas+) demonstrates a similar increasing trend following molecular hydrogen therapy. (D) The percentage change in central memory cytotoxic T cell expressing Fas (CM Tc Fas+) reflects an upward trend after treatment. (E) The percentage change in regulatory B cell (Breg) shows a notable increase following molecular hydrogen therapy. (F) The percentage change in type 1 regulatory cell (Tr1 cell) also indicates an increasing trend after molecular hydrogen therapy.

Figure 3.

Changes in serum levels of anti-dsDNA, anti-Ro52 antibodies, and pro-B-type natriuretic peptide (Pro-BNP) before and after molecular hydrogen therapy. (A) Whole blood analysis for anti-dsDNA antibodies was conducted twenty-five times, with measurements taken prior to molecular hydrogen therapy (March 3, 2020) and post-therapy (from March 9, 2020, to September 28, 2024). (B) In contrast, analysis for anti-Ro52 antibodies was performed eight times, with assessments conducted prior to molecular hydrogen therapy (March 5, 2020) and post-therapy (from January 14, 2021, to September 6, 2024). Both antibodies demonstrated a decreasing trend toward near-normal levels following molecular hydrogen therapy. (C) Pro-BNP levels were analyzed twelve times, with measurements taken prior to molecular hydrogen therapy (on March 4 and 5, 2020) and post-therapy (from March 9, 2020, to April 6, 2021). The results indicated a decreasing trend following molecular hydrogen therapy, ultimately reaching the normal range.

Discussion

This case examines an alternative approach using H₂ therapy, highlighting its potential to reduce oxidative stress and inflammation in a patient with severe SLE. Notably, the patient’s cardiac function showed marked improvement, with her LVEF normalizing from 20-25% to 70% and Pro-BNP levels returning to normal range (Figure 3C). This aligns with prior studies suggesting that H₂ may exert cardioprotective effects through its antioxidant properties (16), as reactive oxygen species (ROS) and oxidative stress are known contributors to cardiac dysfunction in SLE (17). Immunologically, we observed significant changes in Fas+ T cells, regulatory T cells, and regulatory B cells (Figure 2), key mediators of immune tolerance (18,19). Additionally, reductions in anti-dsDNA and anti-Ro52 antibody levels indicated a possible stabilization of the autoimmune disease (Figure 3A and B) (20-22). This immunomodulatory effect is promising, given that SLE pathology is driven by immune dysregulation and abnormal antibody production, both of which contribute to multi-organ damage.

A particularly impactful outcome for this patient was the substantial reduction in fatigue, which significantly improved her quality of life. Prior to treatment, her BFI-T score was elevated, reflecting severe fatigue that impeded daily activities. Following H₂ therapy, her score decreased from 51 to 18 points, indicating a marked reduction in fatigue and enhanced quality of life. While the exact mechanisms by which H₂ alleviates fatigue are not yet fully understood, improved mitochondrial function and reduced oxidative stress may contribute to these effects (23,24). This improvement in fatigue supports the growing body of evidence that H₂ therapy can enhance quality of life for patients with chronic autoimmune diseases.

The case illustrates the potential of H₂ as an adjuvant therapy alongside standard SLE treatments. Its capacity to stabilize immune function, mitigate oxidative stress, and enhance cardiac function suggests that H₂ therapy may have broader applicability in autoimmune diseases. Notably, this case also indicates that H₂ therapy could reduce the need for steroids, thereby lowering the risks associated with prolonged steroid use.

Conclusion

This case report underscores the potential of H₂ therapy as a adjunctive treatment for therapy for SLE, demonstrating its promise in reducing fatigue, modulating immune responses, and enhancing cardiac function. With its antioxidant and anti-inflammatory properties, H₂ therapy may offer a complementary approach to conventional SLE management. Further research is necessary to validate these findings and develop standardized guidelines for the application of H₂ therapy in autoimmune diseases such as SLE.

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 National Science and Technology Council, Taiwan (grants NSTC 112-2314-B-016-033 and NSTC 113-2314-B-016-052), and Tri-Service General Hospital, Taiwan (grants TSGH-E-112218 and TSGH-E-113238).