Silymarin vs Hesperidin/Diosmin in Fibromyalgia

Fibromyalgia is a chronic disease characterized by chronic widespread pain, physical exhaustion, sleep problems, and unexplained pain in joints and muscles. Although the exact causes remain unknown, several risk factors have been implicated, including genetic predisposition, physical or emotional stress, and infections. Fibromyalgia occurs predominantly in females and is associated with widespread pain in multiple body regions such as the arms, shoulders, head, and abdomen. The etiology involves alterations in sleep patterns, changes in neuroendocrine transmitters such as cortisol, growth hormone, and serotonin, along with dysfunction of the central and autonomic nervous systems. Pain is believed to result from neurochemical imbalances that lead to central amplification of pain perception, characterized by allodynia and hyperalgesia. Diagnosis of fibromyalgia is challenging, as no specific laboratory tests or imaging confirm the condition. The 1990 ACR criteria relied on tender points and widespread pain for at least three months. More recently, the ACR proposed new diagnostic criteria incorporating the Widespread Pain Index (WPI) and Symptom Severity (SS) scale, which evaluate pain in 19 body regions and rate associated symptoms such as fatigue, cognitive difficulties, headache, and dizziness. Management of fibromyalgia includes several approaches. FDA-approved medications include pregabalin, duloxetine, and milnacipran, although these may be costly and associated with side effects. Anticonvulsants, amitriptyline, and fluoxetine may also be used to improve pain and sleep. Non-pharmacological therapies include biofeedback, cognitive behavioral therapy, physiotherapy, exercise, and electromyogram-guided interventions. Alternative therapies such as acupuncture, chiropractic care, deep tissue massage, neuromuscular massage, meditation, and certain herbal supplements (e.g., echinacea purpurea, black cohosh, lavender, Silybum marianum) have shown varying degrees of benefit. Inflammatory mediators, particularly IL-6 and IL-8, are commonly elevated in fibromyalgia and correlate with functional impairment, fatigue, and sleep disturbance. Silymarin, extracted from Silybum marianum, possesses hepatoprotective, antioxidant, anti-inflammatory, immunomodulatory, and cardioprotective activities. It has demonstrated reductions in inflammatory cytokines such as TNF-α and IL-6 and showed significant reduction of IL-1α and IL-8 in clinical studies. Diosmin/hesperidin, a flavonoid combination derived from citrus fruits, also exhibits antioxidant and anti-inflammatory activity and has produced antihyperalgesic effects in neuropathic pain models through the reduction of TNF-α, IL-1β, and IL-6. Based on these findings, the current study hypothesizes that administering silymarin or diosmin/hesperidin in addition to standard fibromyalgia therapy may reduce inflammation and improve pain outcomes in patients with fibromyalgia. The study will compare the effects of silymarin versus diosmin/hesperidin on clinical symptoms, inflammatory biomarkers, and quality of life over a four-month period, as well as evaluate their safety and tolerability.