Effects of Curcumin Supplementation on Clinical Features and Inflammation, in Migraine Patients: A Double‑Blind Controlled, Placebo Randomized Clinical Trial

Sheyda Rezaie, Gholamreza Askari, Fariborz Khorvash, Mohammad Javad Tarrahi, Reza Amani


Background: Migraine is a prevalent health condition associated with significant pain and disability. Neurogenic inflammation has a key role in migraine pathophysiology. Curcumin is a well‑known herb compound with anti‑inflammatory function. This study was aimed to evaluate the effects of curcumin supplementation on clinical features, as well as on serum levels of calcitonine gene‑related peptide (CGRP) and interleukin‑6 (IL‑6). Methods: This randomized double‑blind placebo‑controlled clinical trial was carried out on 44 women with migraine, receiving either 500 mg curcumin twice a day or placebo supplements for 8 weeks. Serum CGRP and IL-6 concentration, and clinical symptoms including headache severity, duration and frequency were measured at the baseline and end of study. Results: After 8‑week intervention, compared with placebo, curcumin supplementation led to significand reduction in CGRP (P < 0.001), IL‑6 (P = 0.041), severity (P = 0.001), and duration of headache (P = 0.007). Headache frequency showed marginal improvement in curcumin group, compared to controls (P = 0.052). Within-analysis indicated significant decrease in CGRP and severity (P < 0.001), frequency (P = 0.014) and duration (P = 0.003) and no significant decrease in IL‑6 (P = 0.454), compared to baseline in curcumin group. There were no significant changes in body mass index (BMI), weight, percent body fat (PBF), and percent body muscle (PBM) between the two groups. Conclusions: Curcumin supplementation improved the pro-inflammatory markers and clinical features of migraine headaches and that could be contributed to could be to its anti‑inflammatory properties.


Calcitonin gene‑related peptide; curcumin; inflammation; interleukin‑6; migraine disorders; randomized controlled trial

Full Text:



Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton RB,

Scher A, et al. The global burden of headache: A documentation

of headache prevalence and disability worldwide. Cephalalgia


Goadsby PJ, Holland PR, Martins‑Oliveira M, Hoffmann J,

Schankin C, Akerman S. Pathophysiology of migraine:

A disorder of sensory processing. Physiol Rev 2017;97:553‑622.

Yeh WZ, Blizzard L, Taylor BV. What is the actual prevalence of

migraine? Brain Behav 2018;8:e00950.

Pavlovic JM, Akcali D, Bolay H, Bernstein C, Maleki N. Sexrelated influences in migraine. J Neurosci Res 2017;95:587‑93.

Theoharides TC, Donelan J, Kandere‑Grzybowska K,

Konstantinidou A. The role of mast cells in migraine

pathophysiology. Brain Res Brain Res Rev 2005;49:65‑76.

Wang F, He Q, Ren Z, Li F, Chen W, Lin X, et al. Association

of serum levels of intercellular adhesion molecule‑1 and

interleukin‑6 with migraine. Neurol Sci 2015;36:535‑40.

D’Andrea G, Cevoli S, Cologno D. Herbal therapy in migraine.

Neurol Sci 2014;35:135‑40.

Razeghi Jahromi S, Ghorbani Z, Martelletti P, Lampl C,

Togha M. Association of diet and headache. J Headache Pain


Al‑Hashel JY, Ahmed SF, Alshawaf FJ, Alroughani R. Use of

traditional medicine for primary headache disorders in Kuwait.

J Headache Pain 2018;19:118.

Chandran B, Goel A. A randomized, pilot study to assess

the efficacy and safety of curcumin in patients with active

rheumatoid arthritis. Phytother Res 2012;26:1719‑25.

Shehzad A, Rehman G, Lee YS. Curcumin in inflammatory

diseases. Biofactors 2013;39:69‑77.

Shishodia S. Molecular mechanisms of curcumin action: Gene

expression. Biofactors 2013;39:37‑55.

Bulboacă AE, Bolboacă SD, Stănescu IC, Sfrângeu CA,

Bulboacă AC. Preemptive analgesic and antioxidative effect of

curcumin for experimental migraine. BioMed Res Int 2017;2017.

Bulboacă AE, Bolboacă SD, Stănescu IC, Sfrângeu CA,

Porfire A, Tefas L, et al. The effect of intravenous administration

of liposomal curcumin in addition to sumatriptan treatment in

an experimental migraine model in rats. Int J Nanomedicine


Abdolahi M, Sarraf P, Javanbakht MH, Honarvar NM, Hatami M,

Soveyd N, et al. A novel combination of ω‑3 fatty acids and

nano‑curcumin modulates interleukin‑6 gene expression and high sensitivity C‑reactive protein serum levels in patients with

migraine: A randomized clinical trial study. CNS Neurol Disord

Drug Targets 2018;17:430‑8.

Abdolahi M, Tafakhori A, Togha M, Okhovat AA, Siassi F,

Eshraghian MR, et al. The synergistic effects of ω‑3 fatty

acids and nano‑curcumin supplementation on tumor necrosis

factor (TNF)‑α gene expression and serum level in migraine

patients. Immunogenetics 2017;69:371‑8.

Abdolahi M, Honarvar NM, Tafakhori A, Sarraf P, Hatami M,

Soveyd N, et al. The combined effects of Omega3 fatty acids

and nano‑curcumin supplementation on gene expression and

serum levels of some inflammatory and endothelial factors in

migraine patients: Study protocol for a randomized controlled

trial. Int J Pharm Sci Invent 2016;5:12‑7.

Parohan M, Sarraf P, Javanbakht MH, Foroushani AR,

Ranji‑Burachaloo S, Djalali M. The synergistic effects of

nano‑curcumin and coenzyme Q10 supplementation in migraine

prophylaxis: A randomized, placebo‑controlled, double‑blind trial.

Nutr Neurosci 2019;1‑10. doi: 10.1080/1028415X.2019.1627770.

Online ahead of print.

Durham PL. Calcitonin gene-related peptide (CGRP) and

migraine. Headache 2006;46 Suppl 1(Suppl 1):S3‑8.

Olesen J. International classification of headache disorders.

Lancet Neurol 2018;17:396‑7.

Panahi Y, Sahebkar A, Parvin S, Saadat A. A randomized

controlled trial on the anti‑inflammatory effects of curcumin

in patients with chronic sulphur mustard‑induced cutaneous

complications. Ann Clin Biochem 2012;49:580‑8.

Mohammadi A, Sahebkar A, Iranshahi M, Amini M, Khojasteh R,

Ghayour-Mobarhan M, et al. Effects of supplementation with

curcuminoids on dyslipidemia in obese patients: A randomized

crossover trial. Phytother Res 2013;27:374‑9.

Panahi Y, Hosseini MS, Khalili N, Naimi E,

Simental‑Mendía LE, Majeed M, et al. Effects of curcumin

on serum cytokine concentrations in subjects with metabolic

syndrome: A post‑hoc analysis of a randomized controlled trial.

Biomed Pharmacother 2016;82:578‑82.

Panahi Y, Sahebkar A, Amiri M, Davoudi SM, Beiraghdar F,

Hoseininejad SL, et al. Improvement of sulphur mustard‑induced

chronic pruritus, quality of life and antioxidant status

by curcumin: Results of a randomised, double‑blind,

placebo‑controlled trial. Br J Nutr 2012;108:1272‑9.

Jagdale SC, Phule PS, Chavan GJ. Formulation and evaluation of

modified pulsincap drug delivery system of rizatriptan benzoate.

Int J Pharm Pharm Sci 2014;6:48‑52.

Su M, Ran Y, Han X, Liu Y, Zhang X, Tan Q, et al. Rizatriptan

overuse promotes hyperalgesia induced by dural inflammatory

stimulation in rats by modulation of the serotonin system. Eur J

Neurosci 2016;44:2129‑38.

Ferrara L. Nutrition and phytotherapy: A winning combination

against headache. Int J Med Rev 2019;6:6‑13.

Parohan M, Sarraf P, Javanbakht MH, Ranji‑Burachaloo S, Djalali M.

Effect of coenzyme Q10 supplementation on clinical features of

migraine: A systematic review and dose–response meta‑analysis

of randomized controlled trials. Nutr Neurosci 2019;1‑8. doi:

1080/1028415X.2019.1572940. Online ahead of print.

Martami F, Togha M, Seifishahpar M, Ghorbani Z, Ansari H,

Karimi T, et al. The effects of a multispecies probiotic

supplement on inflammatory markers and episodic and chronic

migraine characteristics: A randomized double‑blind controlled

trial. Cephalalgia 2019;39:841‑53.

Gaul C, Diener H‑C, Danesch U. Improvement of

migraine symptoms with a proprietary supplement

containing riboflavin, magnesium and Q10: A randomized,

placebo‑controlled, double‑blind, multicenter trial.

J Headache Pain 2015;16:32.

Derosa G, Maffioli P, Simental‑Mendia LE, Bo S, Sahebkar A.

Effect of curcumin on circulating interleukin‑6 concentrations:

A systematic review and meta‑analysis of randomized controlled

trials. Pharmacol Res 2016;111:394‑404.

Dahri M, Tarighat‑Esfanjani A, Asghari‑Jafarabadi M,

Hashemilar M. Oral coenzyme Q10 supplementation in patients

with migraine: Effects on clinical features and inflammatory

markers. Nutr Neurosci 2019;22:607‑15.

Cernuda‑Morollón E, Larrosa D, Ramón C, Vega J,

Martínez‑Camblor P, Pascual J. Interictal increase of CGRP

levels in peripheral blood as a biomarker for chronic migraine.

Neurology 2013;81:1191‑6.

Panahi Y, Saadat A, Beiraghdar F, Sahebkar A. Adjuvant therapy

with bioavailability‑boosted curcuminoids suppresses systemic

inflammation and improves quality of life in patients with solid

tumors: A randomized double‑blind placebo‑controlled trial.

Phytother Res 2014;28:1461‑7.

Ho T, Mannix L, Fan X, Assaid C, Furtek C, Jones C,

et al. Randomized controlled trial of an oral CGRP receptor

antagonist, MK‑0974, in acute treatment of migraine. Neurology


Olesen J, Diener H‑C, Husstedt IW, Goadsby PJ, Hall D,

Meier U, et al. Calcitonin gene–related peptide receptor

antagonist BIBN 4096 BS for the acute treatment of migraine.

N Engl J Med 2004;350:1104‑10.

Mottaghi T, Askari G, Khorvash F, Maracy MR. Effect of

vitamin D supplementation on symptoms and C‑reactive protein

in migraine patients. J Res Med Sci 2015;20:477‑82.

Sharma S, Kulkarni SK, Agrewala JN, Chopra K. Curcumin

attenuates thermal hyperalgesia in a diabetic mouse model of

neuropathic pain. Eur J Pharmacol 2006;536:256‑61.

Hoppe U, Bergemann J, Diembeck W, Ennen J, Gohla S,

Harris I, et al. Coenzyme Q10, a cutaneous antioxidant and

energizer. Biofactors, 1999;9: pp.371-8.

Tapia E, Soto V, Ortiz‑Vega KM, Zarco‑Márquez G,

Molina‑Jijón E, Cristóbal‑García M, et al. Curcumin induces

Nrf2 nuclear translocation and prevents glomerular hypertension,

hyperfiltration, oxidant stress, and the decrease in antioxidant

enzymes in 5/6 nephrectomized rats. Oxid Med Cell Longev


Arzani M, Jahromi SR, Ghorbani Z, Vahabizad F, Martelletti P,

Ghaemi A, et al. Gut‑brain Axis and migraine headache:

A comprehensive review. J Headache Pain 2020;21:15.

Zam W. Gut microbiota as a prospective therapeutic target

for curcumin: A review of mutual influence. J Nutr Metab


Amer M, Woodward M, Appel LJ. Effects of dietary sodium and

the DASH diet on the occurrence of headaches: Results from

randomised multicentre DASH‑Sodium clinical trial. BMJ Open