Effects of Curcumin-Piperine Supplementation in Fibromyalgia

Overview

The goal of this clinical trail is to evaluate the effectiveness and safety of curcumin-piperine supplementation in patients with fibromyalgia over 3 months compared to placebo. Participants will: Be randomly assigned to receive either curcumin and piperine supplements or a placebo. Attend scheduled clinic visits for clinical assessments and blood sample collection. Complete study questionnaires before and after treatment time frame. The primary question the study aim to answer is: Does Curcumin-piperine supplementation reduce pain intensity by Visual Analog Scale (VAS), compared with placebo? The secondary questions this study aims to answer are: Does supplementation improve fibromyalgia disease impact and quality of life? Does supplementation improve inflammatory biomarkers and oxidative stress? Does supplementation improve insulin resistance? Is curcumin and piperine supplementation safe and well tolerated?

Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, cognitive impairment, and mood disorders. Increasing evidence suggests that its pathogenesis is driven by a complex interaction of central sensitization, neuroinflammation, and oxidative stress. Elevated levels of pro-inflammatory cytokines and oxidative stress biomarkers have been linked to pain severity and disease progression. Although current pharmacological therapies can reduce symptoms, their effectiveness is often limited, and they do not adequately address the underlying biological mechanisms. In addition to inflammation and oxidative stress, insulin resistance (IR) has recently emerged as a potential contributor to fibromyalgia. Several clinical studies have reported higher HOMA-IR values in patients with FM than in healthy individuals, with greater insulin resistance being associated with more severe pain and poorer clinical outcomes. This relationship may be explained by chronic low-grade inflammation, increased oxidative stress, impaired glucose metabolism, and altered central pain processing. These findings suggest that metabolic dysfunction may contribute to symptom persistence and represent an additional therapeutic target in FM. Curcumin, a natural polyphenol extracted from "Curcuma longa", has attracted considerable interest because of its anti-inflammatory, antioxidant, neuroprotective, and analgesic properties. In addition to reducing inflammatory mediators, oxidative stress, and modulating pain pathways, curcumin has been shown to improve insulin sensitivity and glycemic control, suggesting that it may simultaneously target both the inflammatory and metabolic abnormalities associated with FM. These findings support the hypothesis that curcumin may improve fibromyalgia by addressing inflammation, oxidative stress, pain sensitization, and metabolic dysfunction. However, current clinical evidence remains limited by small sample sizes and short intervention periods. Furthermore, curcumin's poor oral bioavailability can be markedly enhanced by co-administration with piperine, which increases its intestinal absorption. Therefore, a well-designed randomized controlled trial is needed to evaluate the efficacy and safety of curcumin-piperine supplementation as an adjunctive therapy for patients with fibromyalgia. A total of 80 fibromyalgia patients will be enrolled in the study. Patients will be stratified according to insulin resistance status (insulin-resistant vs. non-insulin-resistant) followed by permuted block randomization to the study groups. All patients in both groups will receive standard treatment consisting of duloxetine and gabapentin, along with personalized guidance on an anti-inflammatory diet and exercise program. Participants will be educated about the study and asked to sign a written informed consent before starting the study, assuring that they can withdraw at any time if they want. The following data will be collected from patient records and by history taking from the patients upon enrollment: A. Patient demographics including age, gender, weight, height, and body mass index (BMI). B. Clinical variables including HbA1c, and HOMA-IR, complete blood picture, kidney function tests and liver function tests C. Comorbidities including but not limited to diabetes, hypertension, chronic kidney disease, cardiovascular disease, and immunosuppression. D. Medical history including previous hospitalizations, surgeries, medication history, and known drug allergies. E. Medication history including analgesic consumption (dose, frequency, and duration) The patients will be followed up by weekly phone calls to encourage adherence and to evaluate the incidence and severity of the adverse effects including GIT disturbances or any other undesirable side effects reported by the patients throughout the trial. In addition, complete blood picture, kidney function tests, and liver function tests will be assessed at baseline, after 1 month and by the end of the study (after 3 months).