Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 5/2020

01-05-2020 | Migraine | Original Article

Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial

Authors: Zeinab Ghorbani, Mansoureh Togha, Pegah Rafiee, Zeynab Sadat Ahmadi, Reyhaneh Rasekh Magham, Mahmoud Djalali, Sahar Shahemi, Fahimeh Martami, Mahnaz Zareei, Soodeh Razeghi Jahromi, Shadi Ariyanfar, Maryam Mahmoudi

Published in: Neurological Sciences | Issue 5/2020

Login to get access

Abstract

Introduction

Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs.

Methods and materials

This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 μg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method.

Results

At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055).

Conclusion

Based on the results of this study, we found that 2000 IU (50 μg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.
Literature
1.
Steiner TJ, Stovner LJ, Vos T, Jensen R, Katsarava Z (2018) Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain 19(1):17PubMedPubMedCentralCrossRef
2.
Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A et al (2007) The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 27(3):193–210PubMedCrossRef
3.
Vetvik KG, MacGregor EA (2017) Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol 16(1):76–87PubMedCrossRef
4.
Headache Classification Committee of the International Headache Society (IHS) (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia : an international journal of headache 38(1):1–211
5.
6.
Waeber C, Moskowitz MA (2005) Migraine as an inflammatory disorder. Neurology 64(10 suppl 2):S9–S15PubMedCrossRef
7.
Peroutka SJ (2005) Neurogenic inflammation and migraine: implications for the therapeutics. Mol Interv 5(5):304–311PubMedCrossRef
8.
Bruno P, Carpino F, Carpino G, Zicari A (2007) An overview on immune system and migraine. Eur Rev Med Pharmacol Sci 11(4):245–248PubMed
9.
Ramachandran R (2018) Neurogenic inflammation and its role in migraine. Semin Immunopathol 40(3):301–314PubMedCrossRef
10.
Pietrobon D (2005) Migraine: new molecular mechanisms. Neuroscientist 11(4):373–386
11.
Ceylan M, Bayraktutan OF, Becel S, Atis O, Yalcin A, Kotan D (2016) Serum levels of pentraxin-3 and other inflammatory biomarkers in migraine: association with migraine characteristics. Cephalalgia 36(6):518–525PubMedCrossRef
12.
Palm-Meinders IH, Koppen H, Terwindt GM, Launer LJ, Konishi J, Moonen JM, Bakkers JT, Hofman PA, van Lew B, Middelkoop HA, van Buchem M, Ferrari MD, Kruit MC (2012) Structural brain changes in migraine. Jama 308(18):1889–1897PubMedPubMedCentralCrossRef
13.
Sadeghi O, Nasiri M, Maghsoudi Z, Pahlavani N, Rezaie M, Askari G (2015) Effects of pyridoxine supplementation on severity, frequency and duration of migraine attacks in migraine patients with aura: a double-blind randomized clinical trial study in Iran. Iran J Neurol 14(2):74–80PubMedPubMedCentral
14.
Eren Y, Dirik E, Neselioglu S, Erel O (2015) Oxidative stress and decreased thiol level in patients with migraine: cross-sectional study. Acta Neurol Belg 115(4):643–649PubMedCrossRef
15.
Ghorbani Z, Togha M, Rafiee P, Ahmadi ZS, Rasekh Magham R, Haghighi S, et al (2019) Vitamin D in migraine headache: a comprehensive review on literature. Neurol Sci
16.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930PubMedCrossRef
17.
Anjum I, Jaffery SS, Fayyaz M, Samoo Z, Anjum S (2018) The Role of Vitamin D in Brain Health: A Mini Literature Review. Cureus 10(7):e2960-e
18.
van Harten-Gerritsen AS, Balvers MG, Witkamp RF, Kampman E, van Duijnhoven FJ (2015) Vitamin D, Inflammation, and colorectal Cancer progression: a review of mechanistic studies and future directions for epidemiological studies. Cancer Epidemiol Biomark Prev 24(12):1820–1828CrossRef
19.
20.
21.
Togha M, Razeghi Jahromi S, Ghorbani Z, Martami F, Seifishahpar M (2018) Serum vitamin D status in a Group of Migraine Patients Compared with Healthy Controls: a case-control study. Headache 58(10):1530–1540PubMedCrossRef
22.
Martami F, Razeghi Jahromi S, Togha M, Ghorbani Z, Seifishahpar M, Saidpour A (2018) The serum level of inflammatory markers in chronic and episodic migraine: a case-control study. Neurol Sci 39(10):1741–1749PubMedCrossRef
23.
Sarchielli P, Alberti A, Baldi A, Coppola F, Rossi C, Pierguidi L et al (2006) Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache: J Head Face Pain 46(2):200–207CrossRef
24.
Fidan I, Yuksel S, Ymir T, Irkec C, Aksakal FN (2006) The importance of cytokines, chemokines and nitric oxide in pathophysiology of migraine. J Neuroimmunol 171(1–2):184–188PubMedCrossRef
25.
Tietjen G, Khubchandani J, Khan A, Herial N (2010) Adiponectin and Inflammatory Cytokines in Young Women with Migraine
26.
Yücel M, Kotan D, Çiftçi GG, Çiftçi I, Cikriklar H (2016) Serum levels of endocan, claudin-5 and cytokines in migraine. Eur Rev Med Pharmacol Sci 20(5):930–936PubMed
27.
Uzar E, Evliyaoglu O, Yucel Y, Ugur Cevik M, Acar A, Guzel I et al (2011) Serum cytokine and pro-brain natriuretic peptide (BNP) levels in patients with migraine. Eur Rev Med Pharmacol Sci 15(10):1111–1116PubMed
28.
Oliveira AB, Bachi ALL, Ribeiro RT, Mello MT, Tufik S, Peres MFP (2017) Unbalanced plasma TNF-α and IL-12/IL-10 profile in women with migraine is associated with psychological and physiological outcomes. J Neuroimmunol 313:138–144PubMedCrossRef
29.
Jahromi SR, Abolhasani M, Ghorbani Z, Sadre-Jahani S, Alizadeh Z, Talebpour M et al (2017) Bariatric surgery promising in migraine control: a controlled trial on weight loss and its effect on migraine headache. Obes Surg:1–10
30.
Mottaghi T, Askari G, Khorvash F, Maracy MR (2015) Effect of vitamin D supplementation on symptoms and C-reactive protein in migraine patients. J Res Med Sci 20(5):477–482PubMedPubMedCentralCrossRef
31.
Gazerani P, Fuglsang R, Pedersen JG, Sorensen J, Kjeldsen JL, Yassin H et al (2019) A randomized, double-blinded, placebo-controlled, parallel trial of vitamin D3 supplementation in adult patients with migraine. Curr Med Res Opin 35(4):715–723PubMedCrossRef
32.
Buettner C, Nir RR, Bertisch SM, Bernstein C, Schain A, Mittleman MA et al (2015) Simvastatin and vitamin D for migraine prevention: a randomized, controlled trial. Ann Neurol 78(6):970–981PubMedPubMedCentralCrossRef
33.
Wang M (2013) Cortical spreading depression and calcitonin gene-related peptide: a brief review of current progress. Neuropeptides 47(6):463–466PubMedCrossRef
34.
Close LN, Eftekhari S, Wang M, Charles AC, Russo AFJC (2018) Cortical spreading depression as a site of origin for migraine: Role of CGRP 0333102418774299
35.
(2015) Pathophysiology of Headaches From Molecule to Man. Paolo Martelletti RJ (ed). Springer, Cham
36.
Vanmolkot F, De Hoon J (2007) Increased C-reactive protein in young adult patients with migraine. Cephalalgia 27(7):843–846PubMedCrossRef
37.
Kurth T, Ridker P, Buring J (2008) Migraine and biomarkers of cardiovascular disease in women. Cephalalgia 28(1):49–56PubMedCrossRef
38.
Hamed SA, Hamed EA, Eldin AME, Mahmoud NM (2010) Vascular risk factors, endothelial function, and carotid thickness in patients with migraine: relationship to atherosclerosis. J Stroke Cerebrovasc Dis 19(2):92–103PubMedCrossRef
39.
40.
Güzel I, Taşdemir N, Çelik Y (2013) Evaluation of serum transforming growth factor β1 and C-reactive protein levels in migraine patients. Neurol Neurochir Pol 47(4):357–362PubMedCrossRef
41.
Covelli V, Munno I, Pellegrino N, Altamura M, Decandia P, Marcuccio C, di Venere A, Jirillo E (1991) Are TNF-alpha and IL-1 beta relevant in the pathogenesis of migraine without aura? Acta Neurol 13(2):205–211
42.
Perini F, D'andrea G, Galloni E, Pignatelli F, Billo G, Alba S et al (2005) Plasma cytokine levels in migraineurs and controls. Headache: J Head Face Pain 45(7):926–931CrossRef
43.
44.
Olesen J (2008) The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. Pharmacol Ther 120(2):157–171PubMedCrossRef
45.
Al-Daghri NM, Bukhari I, Yakout SM, Sabico S, Khattak MNK, Aziz I et al (2018) Associations of serum nitric oxide with vitamin D and other metabolic factors in apparently healthy adolescents. Biomed Res Int 2018:1489132PubMedPubMedCentralCrossRef
46.
Golden TN (2016) The role of inducible nitric oxide synthase in macrophage activation following acute lung injury
47.
de Oliveira DL, Hirotsu C, Tufik S, Andersen ML (2017) The interfaces between vitamin D, sleep and pain. J Endocrinol 234(1):R23–R36PubMedCrossRef
48.
Linden J, Granasen G, Salzer J, Svenningsson A, Sundstrom P (2019) Inflammatory activity and vitamin D levels in an MS population treated with rituximab. Mult Scler J Exp Transl Clin 5(1):2055217319826598PubMedPubMedCentral
49.
Wang Y, Yang S, Zhou Q, Zhang H, Yi B (2019) Effects of vitamin D supplementation on renal function, inflammation and glycemic control in patients with diabetic nephropathy: a systematic review and meta-analysis. Kidney Blood Press Res 44(1):72–87PubMedCrossRef
50.
Filgueiras MS, Rocha NP, Novaes JF, Bressan J (2018) Vitamin D status, oxidative stress, and inflammation in children and adolescents: a systematic review. Crit Rev Food Sci Nutr 1–10
51.
Chen N, Wan Z, Han SF, Li BY, Zhang ZL, Qin LQ (2014) Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials. Nutrients 6(6):2206–2216PubMedPubMedCentralCrossRef
52.
Sepidarkish M, Farsi F, Akbari-Fakhrabadi M, Namazi N, Almasi-Hashiani A, Maleki Hagiagha A, Heshmati J (2019) The effect of vitamin D supplementation on oxidative stress parameters: a systematic review and meta-analysis of clinical trials. Pharmacol Res 139:141–152PubMedCrossRef
53.
Akbari M, Ostadmohammadi V, Lankarani KB, Tabrizi R, Kolahdooz F, Heydari ST et al (2018) The effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res 50(4):271–279PubMedCrossRef
54.
Colotta F, Jansson B, Bonelli F (2017) Modulation of inflammatory and immune responses by vitamin D. J Autoimmun 85:78–97PubMedCrossRef
55.
Sarchielli P, Floridi A, Mancini M, Rossi C, Coppola F, Baldi A, Pini LA, Calabresi P (2006) NF-κB activity and iNOS expression in monocytes from internal jugular blood of migraine without Aura patients during attacks. Cephalalgia 26(9):1071–1079PubMedCrossRef
56.
Dursun E, Gezen-Ak D, Yilmazer S (2014) The influence of vitamin D treatment on the inducible nitric oxide synthase (INOS) expression in primary hippocampal neurons. Noro Psikiyatri Arsivi 51(2):163–168PubMedPubMedCentralCrossRef
57.
Shipton EA, Shipton EE (2015) Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities. Pain Res Treat 2015:904967PubMedPubMedCentral
58.
59.
Andrukhova O, Slavic S, Zeitz U, Riesen SC, Heppelmann MS, Ambrisko TD et al (2014) Vitamin D is a regulator of endothelial nitric oxide synthase and arterial stiffness in mice. Mol Endocrinol (Baltimore, Md) 28(1):53–64CrossRef
60.
Metadata
Title
Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial
Authors
Zeinab Ghorbani
Mansoureh Togha
Pegah Rafiee
Zeynab Sadat Ahmadi
Reyhaneh Rasekh Magham
Mahmoud Djalali
Sahar Shahemi
Fahimeh Martami
Mahnaz Zareei
Soodeh Razeghi Jahromi
Shadi Ariyanfar
Maryam Mahmoudi
Publication date
01-05-2020
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 5/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-019-04220-8

Other articles of this Issue 5/2020

Neurological Sciences 5/2020 Go to the issue

Letter to the Editor

Steroid-responsive myositis in a patient with Sjögren’s syndrome and refractory peripheral neuropathy

Review Article

Clinical potential and current progress of mesenchymal stem cells for Parkinson’s disease: a systematic review

Original Article

Neuropsychological assessment in acute stroke patients

Letter to the Editor

Acute venous thrombosis of inferior cerebellar vein, case report

Original Article

The frequency of central nervous system complications in the Cypriot cohort of ATTRV30M neuropathy transplanted patients

Original Article

Charcot-Marie-Tooth disease: experience from a large Italian tertiary neuromuscular center