Effect of mixodin supplementation on inflammatory and oxidative stress markers, clinical symptoms, mental health, and quality of life in patients with migraine: study protocol for a randomized clinical trial.

BACKGROUND: Migraine is a highly prevalent neurological disorder related to severe, unilateral headache and symptoms such as vomiting, nausea, and photophobia. Growing evidence implicates oxidative stress and inflammation as key contributors to migraine pathophysiology, exacerbating symptoms and related mental health conditions. Mixodin is a novel bioactive formulation derived from natural compounds, including curcumin, piperine, and gingerol, which are well-established for their anti-inflammatory and antioxidant properties. While each component has shown potential in alleviating migraine-related symptoms, the combined therapeutic efficacy remains unclear. This study investigates whether the combined natural compounds in mixodin provide synergistic benefits in migraine management by targeting multiple underlying mechanisms. This study aims to examine the effects of mixodin supplementation on clinical symptoms, mental health, quality of life (QOL), inflammatory, and oxidative stress factors in patients with migraine. METHODS: This study is a randomized, double-blind, placebo-controlled clinical trial involving 60 patients diagnosed with migraine by a neurologist according to the ICHD-3 criteria. Eligible participants, aged 20 to 60 years, will be randomly assigned to one of two groups. The intervention group (n = 30) will receive two mixodin capsules daily for 8 weeks, each containing 300 mg of curcumin, 7.5 mg of gingerol, and 3.75 mg of piperine. The control group (n = 30) will receive two placebo capsules daily for the same duration. The primary outcome will be the clinical symptoms of migraine, including the frequency, severity, and duration of migraine attacks reported by patients. Secondary outcomes will include serum levels of high-sensitivity C-reactive protein (hs-CRP), calcitonin gene-related peptide (CGRP), total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and assessments of mental health status and QOL. DISCUSSION: This clinical trial aims to evaluate the effects of mixodin supplementation on inflammatory markers, oxidative stress, migraine-related symptoms, mental health, and QOL in patients with migraine. The results may suggestion insights into underlying mechanisms and support the development of evidence-based clinical guidelines that incorporate anti-inflammatory and antioxidant strategies to enhance therapeutic outcomes in migraine management. TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20241009063312N1). Registration date: 2024-12-15. TRIAL STATUS: The protocol is Version 2.0, March 01, 2025. Recruitment began November 11, 2024, and is anticipated to be completed by June 22, 2025.