The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial

doi:10.1186/s40780-021-00192-0

. 2021 Mar 3;7(1):9.

doi: 10.1186/s40780-021-00192-0.

The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial

Zeinab Ghorbani^{1

2

3}, Pegah Rafiee^{3

4}, Samaneh Haghighi^{3

5}, Soodeh Razeghi Jahromi⁶, Mahmoud Djalali⁷, Hedieh Moradi-Tabriz⁸, Maryam Mahmoudi^{9

10

11}, Mansoureh Togha^{12

13}

Affiliations

¹ Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
² Department of Community Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
³ Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Student Research Committee, Department and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Headache Department, Neurology Ward, Sina University Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Department of Pathology, Sina University Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁹ Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. maryam.mahmoudi73@gmail.com.
¹⁰ Pediatric Gastroenterology and Hepatology Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. maryam.mahmoudi73@gmail.com.
¹¹ Dietitians and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN), Tehran, Iran. maryam.mahmoudi73@gmail.com.
¹² Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. toghae@sina.tums.ac.ir.
¹³ Headache Department, Neurology Ward, Sina University Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. toghae@sina.tums.ac.ir.

PMID: 33653409
PMCID: PMC7927391
DOI: 10.1186/s40780-021-00192-0

The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial

Zeinab Ghorbani et al. J Pharm Health Care Sci. 2021.

. 2021 Mar 3;7(1):9.

doi: 10.1186/s40780-021-00192-0.

Authors

Zeinab Ghorbani^{1

2

3}, Pegah Rafiee^{3

4}, Samaneh Haghighi^{3

5}, Soodeh Razeghi Jahromi⁶, Mahmoud Djalali⁷, Hedieh Moradi-Tabriz⁸, Maryam Mahmoudi^{9

10

11}, Mansoureh Togha^{12

13}

Affiliations

¹ Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
² Department of Community Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
³ Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Student Research Committee, Department and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Headache Department, Neurology Ward, Sina University Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Department of Pathology, Sina University Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁹ Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. maryam.mahmoudi73@gmail.com.
¹⁰ Pediatric Gastroenterology and Hepatology Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. maryam.mahmoudi73@gmail.com.
¹¹ Dietitians and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN), Tehran, Iran. maryam.mahmoudi73@gmail.com.
¹² Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. toghae@sina.tums.ac.ir.
¹³ Headache Department, Neurology Ward, Sina University Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. toghae@sina.tums.ac.ir.

PMID: 33653409
PMCID: PMC7927391
DOI: 10.1186/s40780-021-00192-0

Abstract

Background: Although the exact mechanism involved in migraine pathogenesis remained uncertain, and different researches have been developed to address the role of neuroinflammation and immune dysfunction. Therefore, considering the immune protective functions of vitamin D3, we aimed to investigate the effects of daily administration of 2000 IU D3 supplements on serum status of immune markers in migraine patients.

Methods and materials: Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000 IU/d or placebo for 12-week were enrolled in this placebo-controlled double-blind trial included. Serum concentrations of transforming growth factor-beta (TGF-β) and interleukin (IL)-17 were evaluated at baseline and after the trial via the ELISA method.

Results: Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that the serum level of TGF-β was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P-value = 0.012); on the other hand, vitamin D prevented the increment in IL-17 serum level in the intervention group after the trial (adjusted mean:37.84 ng/L) comparing to the controls (adjusted mean:70.09 ng/L; P-value = 0.039). The Pearson correlation analysis revealed a significant positive correlation between changes in serum 25-hydroxy-vitamin D (25(OH)D) and TGF-β (r = - 0.306, P-value = 0.008). In contrast, no significant correlations were noted between serum 25(OH) D and IL-17 changes throughout the study.

Conclusion: Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance the Th17/Treg related cytokines balance in episodic migraineurs. Although these findings are promising, it is needed to be extended.

Trial registration: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6 ( https://www.irct.ir/trial/31246 ).

Keywords: Cholecalciferol; Headache; Immune cells; Th17/Treg cytokines; Vitamin D3.

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Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

**Fig. 1**
The correlation between changes in serum 25(OH) D and serum levels of Treg/Th17 related cytokines throughout the 12-week trial. a The correlation between changes in serum 25(OH) D and serum levels of TGF-β throughout the 12-week trial. b. The correlation between changes in serum 25(OH)D and serum levels of IL-17 throughout the 12-week trial

**Fig. 2**
The correlation between changes in the number of headache days per month and serum levels of Treg/Th17 related cytokines throughout the 12-week trial. a The correlation between changes in the number of headache days per month and serum levels of TGF-β throughout the 12-week trial. b. The correlation between changes in the number of headache days per month and serum levels of IL-17 throughout the 12-week trial

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References

1. Steiner TJ, Stovner LJ, Vos T, Jensen R, Katsarava Z. Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain. 2018;19(1):17. doi: 10.1186/s10194-018-0846-2. - DOI - PMC - PubMed
1. Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, Steiner T, Zwart JA. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193–210. doi: 10.1111/j.1468-2982.2007.01288.x. - DOI - PubMed
1. Steiner TJ, Stovner LJ, Vos T (2016) GBD 2015: migraine is the third cause of disability in under 50s. - PMC - PubMed
1. Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol. 2017;16(1):76–87. doi: 10.1016/S1474-4422(16)30293-9. - DOI - PubMed
1. Chang C-C, Wu C-H, Liu L-K, Chou R-H, Kuo C-S, Huang P-H, Chen L-K, Lin S-J. Association between serum uric acid and cardiovascular risk in nonhypertensive and nondiabetic individuals: the Taiwan I-Lan longitudinal aging study. Sci Rep. 2018;8(1):5234. doi: 10.1038/s41598-018-22997-0. - DOI - PMC - PubMed

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[1] Steiner TJ, Stovner LJ, Vos T, Jensen R, Katsarava Z. Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain. 2018;19(1):17. doi: 10.1186/s10194-018-0846-2. - DOI - PMC - PubMed

[2] Steiner TJ, Stovner LJ, Vos T, Jensen R, Katsarava Z. Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain. 2018;19(1):17. doi: 10.1186/s10194-018-0846-2. - DOI - PMC - PubMed

[3] Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, Steiner T, Zwart JA. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193–210. doi: 10.1111/j.1468-2982.2007.01288.x. - DOI - PubMed

[4] Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, Steiner T, Zwart JA. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193–210. doi: 10.1111/j.1468-2982.2007.01288.x. - DOI - PubMed

[5] Steiner TJ, Stovner LJ, Vos T (2016) GBD 2015: migraine is the third cause of disability in under 50s. - PMC - PubMed

[6] Steiner TJ, Stovner LJ, Vos T (2016) GBD 2015: migraine is the third cause of disability in under 50s. - PMC - PubMed

[7] Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol. 2017;16(1):76–87. doi: 10.1016/S1474-4422(16)30293-9. - DOI - PubMed

[8] Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol. 2017;16(1):76–87. doi: 10.1016/S1474-4422(16)30293-9. - DOI - PubMed

[9] Chang C-C, Wu C-H, Liu L-K, Chou R-H, Kuo C-S, Huang P-H, Chen L-K, Lin S-J. Association between serum uric acid and cardiovascular risk in nonhypertensive and nondiabetic individuals: the Taiwan I-Lan longitudinal aging study. Sci Rep. 2018;8(1):5234. doi: 10.1038/s41598-018-22997-0. - DOI - PMC - PubMed

[10] Chang C-C, Wu C-H, Liu L-K, Chou R-H, Kuo C-S, Huang P-H, Chen L-K, Lin S-J. Association between serum uric acid and cardiovascular risk in nonhypertensive and nondiabetic individuals: the Taiwan I-Lan longitudinal aging study. Sci Rep. 2018;8(1):5234. doi: 10.1038/s41598-018-22997-0. - DOI - PMC - PubMed

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The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial

Affiliations

The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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