Evaluation of the Effect of Curcumin and Piperine Supplementation on Clinical Outcome in Fibromyalgia Patients.

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.