Effects of Curcumin-Piperine Supplementation in Fibromyalgia

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).

Inclusion criteria

• Adult women aged ≥18 years.
• Patients with confirmed diagnosis of fibromyalgia, according to 2022 ACR Fibromyalgia criteria.

Exclusion criteria

• Diabetic patients (HbA1c ≥ 6.5).
• Patients with chronic inflammatory or autoimmune diseases other than FM.
• Patients allergic to curcumin or piperine.
• Patients receiving other anti-inflammatory medications.
• Severe hepatic or renal impairment.
• Patients receiving anticoagulant medications (e.g., clopidogrel).
• Pregnancy or lactation.
• Participation in another clinical trial