Serum Vitamin D Levels Negatively Correlated With Prevalence of Migraine, Study Suggests

Author(s):

Key Takeaways

Higher serum vitamin D levels are associated with a reduced risk of migraine, with significant findings across multiple adjusted models.
Future research should explore the causal relationship between vitamin D and migraine, including long-term randomized controlled trials.
Subgroup analyses revealed no significant differences in the vitamin D-migraine relationship across demographic and health-related factors.
The study's cross-sectional design and reliance on self-reported data are notable limitations, warranting cautious interpretation of results.

Adjusted models confirmed a consistent negative correlation between serum vitamin D and migraine prevalence, with statistical significance (P < 0.05) across all analyses.

A population-based analysis of more than 9000 participants from the National Health and Nutrition Examination Survey (NHANES) showed that the prevalence of migraine was higher among individuals with lower serum vitamin D levels, suggesting a negative correlation between the two.

In the study, investigators defined “serum vitamin D” as the blood level of 25-hydoxyvitamin D2 (25OHD2) plus 25-hydoxyvitamin D3 (25OHD3) measured in nanograms per milliliter. Serum vitamin D was categorized into quartiles, with ranges of 9.1-40.9 (quartile 1), 40.9-55.7, 55.7-70.6, and 70.6-198.0 (quartile 4). Using an unadjusted model, serum vitamin D was significantly associated with migraine in quartile 4 compared with quartile 1, with an odds ratio (OR) of 0.77 (95% CI, 0.67-0.89).

In model 2, which adjusted for gender, age, and race, results showed that serum vitamin D levels were negatively associated with migraine, indicated by an OR of 0.74 (95% CI, 0.63-0.87). Using a third model that adjusted for all covariates, including additional factors such as the ratio of family income to poverty, education, body mass index, hypertension, hyperlipidemia, diabetes, smoking, stroke, and drinking, serum vitamin D in quartile 4 was significantly associated with migraine, shown by an OR of 0.84 (95% CI, 0.71-0.99). In all 3 models, the P value trend was less than 0.05.

"Future studies should focus on exploring the causal relationship between vitamin D and migraine, especially considering individuals’ baseline vitamin D levels and migraine severity. Long-term randomized controlled trials are recommended to assess the efficacy of vitamin D supplementation as an intervention for migraine symptoms," lead author Shunfa Hao of Henan University, China, concluded. "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."

Subgroup analyses by age, gender, race, BMI, PIR, and stroke revealed that the relationship between serum vitamin D and migraine was not statistically different between strata (interaction test, P >.05). There were a few limitations to the subgroup analyses and study, including the cross-sectional design of the study, the reliance on self-reports from the NHANES Pain Questionnaire, and the lack of accounting for other nutrients that may have had an impact on migraine.

Coming into the study, the top quartile showed significantly higher PIR (2.96 [±1.60]), a greater proportion of Mexican Americans (78.46%), more high school graduates (27.43%), and highly educated individuals (51.54%), along with a higher percentage of males (46.29%) and drinkers (74.23%) compared to the bottom quartile. Conversely, they had lower BMI (26.65 [±5.09]), and lower prevalence rates of hypertension (28.07%), hyperlipidemia (36.09%), diabetes (7.25%), stroke (3.28%), and smoking. All differences between quartiles were statistically significant (P < 0.05).

The literature on the relationship between vitamin D and migraine has been mixed to date. A 2020 meta-analysis found that migraine sufferers have lower blood vitamin D levels than the general population, suggesting the use of vitamin D supplements, while Ioannidou et al. linked vitamin D to migraines in children, and Niu et al. showed elevated vitamin D levels reduce migraine risk through Mendelian randomization.^2-4 However, contrasting evidence from Kjaergaard et al. found no significant association between migraines and serum 25(OH)D in a cross-sectional study, and another study comparing plasma 25(OH)D levels in migraine patients and controls also showed no significant differences.⁵

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. Published January 3, 2025. doi:10.1371/journal.pone.0313082
2. Nowaczewska M, Wiciński M, Osiński S, Kaźmierczak H. The Role of Vitamin D in Primary Headache-from Potential Mechanism to Treatment. Nutrients. 2020;12(1). pmid:31963460
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. Niu PP, Wang X, Xu YM. Higher Circulating Vitamin D Levels Are Associated With Decreased Migraine Risk: A Mendelian Randomization Study. Front Nutr. 2022;9:907789. pmid:36159496
5. 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. doi:10.1111/j.1526-4610.2012.02250.x.