Migraine is a widespread incapacitating neurologic disorder with debilitating headaches which are usually throbbing due to inefficacy and several side effects, complementary therapies recommended as possible alternatives. The current randomized controlled trial was carried out to evaluate the effect of zinc gluconate supplementation on migraine-related symptoms, serum level of high sensitivity C-reactive protein (hs-CRP) and lipid profile in migraineurs. Present study was designed as randomized double-blind, placebo-controlled trial. Sixty women with migraine (mean age of 35.44 ± 7.42 years ) were randomly allocated to obtain 15 mg per day of zinc gluconate or placebo for 12 weeks. Frequency, periods of headaches and severity of migraine based on numerical rating scale questionnaire and migraine disability assessment (MIDAS) test were checked. Fasting serum level of lipid profile and hs-CRP were assessed at the beginning and the end of trial. Zinc gluconate supplementation significantly reduced the frequency (p = 0.001), periods of migraine attacks (p < 0.001) and severity of migraine and MIDAS (p < 0.001) compared with control group. The serum level of low-density lipoprotein (p < 0.001), total cholesterol (p < 0.001) and hs-CRP (p < 0.001) decreased following zinc supplementation, but no significant differences in serum level of triglycerides (p = 0.1) and high-density lipoprotein (p = 0.3) was observed. However, after adjustment for baseline values using analysis of covariance test, none of lipid profile components and hs-CRP showed a significant difference. Zinc supplementation has beneficial effect on the migraine related complications like its severity, frequency. Trial Registration Iranian Registry of Clinical Trials Identifier: IRCT20191014045100N1

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