Vitamin D Deficiency Linked to Migraine Prevalence with Negative Correlation

Credit: Adobe Stock/ Viacheslav Yakobchuk

A recent study found that migraine prevalence rises as serum vitamin D levels lower, providing evidence for the association between vitamin D deficiency and migraine.¹

“The link between vitamin D and migraine is underpinned by intricate and diverse processes,” wrote investigators, led by Shunfa Hao, from the department of encephalopathy at The First Affiliated Hospital of Henan University of Traditional Chinese Medicine in China.

Previous studies have shown the association between vitamin D deficiency and migraine.^2,3 Vitamin D regulates the immune system and inflammatory response by blocking pro-inflammatory cytokines like IL-2, IL-12, interferon-γ, and TNF-α. Elevated levels of these markers have been linked to neurovascular inflammation associated with migraine episodes. However, some studies examining the association between vitamin D deficiency and migraine reached inconclusive results, highlighting the need for further research.^4,5

Hao and colleagues conducted a population-based analysis to examine the relationship between vitamin D and migraine headaches, leveraging 9142 participants from the 2001 – 2004 National Health and Nutrition Examination Survey (NHANES).¹ In the study, “serum vitamin D” referred to the concentration of 25OHD2 + 25OHD3 (nmol/L) in the blood. A migraine diagnosis was based on self-reports in the miscellaneous pain section of the NHANES questionnaires.

Covariates collected included gender, age, race (Mexican American, other Hispanic, non-Hispanic white, non-Hispanic black, or other), education level (not in high school, high school, or >high school), poverty-to-income ratio, body mass index (BMI), smoking status (daily, occasionally, never), alcohol consumption (≥ 12 drinks annually), hypertension status, hyperlipidemia status, diabetes status, and stroke status. Participants self-reported their diagnosis of hypertension, hyperlipidemia, diabetes mellitus, and stroke.

The sample included 20.53% of participants with migraine. Participants were stratified into 4 serum vitamin D quartiles: 9.1–40.9 (quartile 1), 40.9–55.7 (quartile 2), 55.7–70.6 (quartile 3), and 70.6–198.0 (quartile 4).

The top quartile of serum D levels (70.6 – 198.0) had greater poverty-to-income ratio (2.96 ± 1.60), Mexican Americans (78.46%), high school graduates (27.43%), highly educated individuals (51.54%), males (46.29%), and drinkers (74.23%) compared with the bottom quartile (P < .05). Conversely, participants in the top quartile had a lower BMI (26.65 ± 5.09) and a prevalence in hypertension, (28.07%), hyperlipidemia (36.09%), diabetes (7.25%), stroke (3.28%), and smokers (P < .05).

Investigators observed that the migraine prevalence was greater in those with lower serum vitamin D levels. Participants in the highest quartile of serum vitamin D levels had a 16% lower prevalence than participants in the lowest quartile, as seen in the analysis adjusted for all covariates (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.71 – 0.99; P < .05).

Subgroup analyses on age, gender, race, BMI, poverty-to-income ratio, and stroke demonstrated that the relationship between serum vitamin D and migraine was not statistically different between strata (P > .05).

“Future studies should focus on exploring the causal relationship between vitamin D and migraine, especially considering individuals’ baseline vitamin D levels and migraine severity,” investigators concluded. “Long-term randomized controlled trials are recommended to assess the efficacy of vitamin D supplementation as an intervention for migraine symptoms. Meanwhile, in-depth analyses of vitamin D metabolic pathways and how genetic factors influence its relationship with migraine will help to reveal underlying mechanisms and provide personalized preventive or therapeutic strategies.”

References

1. ^{Hao S, Qian R, Chen Y, Liu J, Xu X, Guan Y. Association between serum vitamin D and severe headache or migraine: A population-based analysis. PLoS One. 2025 Jan 3;20(1):e0313082. doi: 10.1371/journal.pone.0313082. PMID: 39752405; PMCID: PMC11698344.}
2. ^{Celikbilek A, Gocmen AY, Zararsiz G, Tanik N, Ak H, Borekci E, Delibas N. Serum levels of vitamin D, vitamin D-binding protein and vitamin D receptor in migraine patients from central Anatolia region. Int J Clin Pract. 2014 Oct;68(10):1272-7. doi: 10.1111/ijcp.12456. Epub 2014 May 18. PMID: 24837712.}
3. ^{Ioannidou E, Tsakiris C, Goulis DG, Christoforidis A, Zafeiriou D. The association of serum vitamin D concentrations in paediatric migraine. Eur J Paediatr Neuro. 2023;47:60–6. pmid:37738749}
4. ^{Kjaergaard M, Eggen AE, Mathiesen EB, Jorde R. Association between headache and serum 25-hydroxyvitamin D: the Tromsø Study: Tromsø 6. Headache. 2012;52(10):1499–505. http://doi.org/10.1111/j.1526-4610.2012.02250.x.}
5. ^{Zandifar A, Masjedi SS, Banihashemi M, Asgari F, Manouchehri N, Ebrahimi H, et al. Vitamin D status in migraine patients: a case-control study. Biomed Res Int. 2014;2014:514782. pmid:24524078}