1. 2025;28;E13-E22Clinical Trial of Ozonated Water Enema for the Treatment of Fibromyalgia: A Randomized, Double-Blind Trial
   Randomized Controlled Trial
   Qianhao Hou, PhD, Jinyuan Zhang, PhD, Zehua Su, PhD, Xiaomei Wang, PhD, Hongwei Fang, PhD, Shuwen Qian, PhD, Haobing Shi, PhD, Qing Wang, PhD, Yuling Li, PhD, Jiaqi Lin, PhD, Xiangrui Wang, PhD, Zetian Wang, PhD, and Lijun Liao, PhD.

BACKGROUND: The pathogenesis of fibromyalgia (FM) is currently unknown. Many patients with this condition are not effectively treated, and disorders of the intestinal dysbiosis have been identified in patients with FM. This trial aimed to investigate whether ozonated water enema could alleviate the symptoms of FM by improving intestinal dysbiosis in these patients.

OBJECTIVE: This trial aims to evaluate the therapeutic advantages of ozonated water enema therapy for patients suffering from FM.

STUDY DESIGN: A single-center, double-blind, randomized controlled trial.

SETTING: Department of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

METHODS: This is a randomized, double-blind trial conducted on FM patients (n = 66). The selected patients were randomly categorized into the O3 and control groups. The patients in the O3 and control groups received an ozonated and deionized water enema, respectively, at the same dose and frequency. After the treatment, the scores on the numerical rating scale (NRS), widespread pain index (WPI), Hamilton anxiety scale (HAMA), and the Pittsburgh sleep quality index (PSQI) were compared between the 2 groups, as were the doses of duloxetine, to evaluate the treatment effect. Furthermore, the effectiveness of the treatment was assessed by comparing fecal samples from the O3 group collected before and after treatment with 25 healthy individuals from the physical examination department of Shanghai East Hospital.

RESULTS: The patients in the O3 group indicated significant relief in pain and reduced NRS, HAMA, PSQI, and WPI scores at each follow-up time point (P < 0.001) when compared to the control group. In addition, the patients in the O3 group used lower doses of duloxetine than did those the control group (P < 0.001). Moreover, FM patients treated with ozonated water indicated improvements to their gut microbiome.

LIMITATIONS: The trial’s findings might be affected by confounding factors, including medicines, diet, and environmental circumstances. Also, this trial was limited by its sample size, and the symptom severity scores (SSS) of the patients at 3 months after treatment at the given follow-up period were not assessed.

CONCLUSION: This trial confirmed that the symptoms of pain, anxiety, and sleep disorders in FM patients were effectively relieved after treatment with an ozonated water enema. Furthermore, the ozonated water enema was associated with a significant reduction in duloxetine dosage and improved gut microbiome disorder, suggesting that the enema could target disorders related to the gut microbiome and therefore serve as a therapeutic intervention for FM.

KEY WORDS: Fibromyalgia, ozone, ozonated water enema, gut microbiome, chronic pain, dysbiosis