The effects of Mixodin supplementation on migraine headache characteristics, oxidative stress and inflammatory biomarkers in patients with migraine: a double-blind, placebo-controlled, randomized trial

Migraine is a prevalent neurological disorder closely linked to oxidative stress and neurogenic inflammation. Curcumin, gingerol, and piperine are natural compounds with well-established anti-inflammatory and antioxidant properties; however, clinical evidence on their combined effects in migraine remains limited. This study aimed to evaluate the effects of eight weeks of Mixodin supplementation on inflammatory and oxidative stress biomarkers, and clinical migraine characteristics, in patients with migraine. This randomized, double-blind, placebo-controlled trial enrolled 60 patients with migraine, who were randomly assigned to receive two Mixodin capsules daily (each containing 300 mg curcumin, 7.5 mg gingerol, and 3.75 mg piperine) or placebo for eight weeks. Serum hs-CRP, NO, MDA, TOS, TAC, and SOD were measured before and after the intervention. Headache severity, frequency, and duration were recorded using VAS and a headache diary. Mixodin supplementation significantly reduced serum Hs-CRP (− 0.87 ± 0.19 vs. − 0.16 ± 0.09 mg/L; P = 0.001) and NO levels (− 5.53 ± 1.53 vs. + 3.51 ± 1.79 µmol/L; P = 0.042) compared with placebo. Additionally, eight weeks of Mixodin supplementation resulted in a trend toward increased SOD activity and TAC, and a trend toward decreased TOS; however, these changes did not reach statistical significance when compared with the control group (all P > 0.05). No significant change was observed in MDA levels. Mixodin supplementation significantly reduced headache severity (-1.93 ± 0.30vs. -0.36 ± 0.21; P = 0.001) compared with placebo, whereas frequency and duration did not differ significantly between groups (P = 0.737 and P = 0.873, respectively). Eight weeks of Mixodin supplementation significantly improved hs-CRP, NO levels, and headache severity among migraine patients, suggesting a promising role for this combination as an adjunctive therapeutic approach in migraine management. Further large-scale trials with longer follow-up are needed. Iranian Registry of Clinical Trials (www.irct.ir) (ID: IRCT20241009063312N1).