Association between serum folate levels and migraine or severe headaches: A nationwide cross-sectional study

Abstract

Migraine and severe headaches are common neurological disorders with significant societal impact. Previous research indicates a potential link between serum folate levels and migraine occurrence, yet there is a lack of sufficient relevant studies and more are required. This study aimed to determine the association between a severe headache or migraine and serum folate levels in large populations. Using data from the National Health and Nutrition Examination Survey, we conducted a cross-sectional study. Using multivariable logistic regression models, we investigated the association between serum folate and severe headache or migraine. In a subsequent subgroup analysis, several confounding factors were also explored to investigate the association between migraine and serum folate. A total of 13,351 individuals participated in the study, with 2742 reporting severe headache or migraine in the previous 3 months. Serum folate was negatively associated with severe headache or migraine (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.28-0.89, P = .018). The stratified analysis revealed this association persisted among female (OR = 0.38, 95% CI = 0.18-0.82, P < .001), individuals aged 20 to 50 years (OR = 0.53, 95% CI = 0.28-0.99, P < .001), and non-Hispanic White participants (OR = 0.38, 95% CI = 0.17-0.87, P < .001). We found that greater levels of serum folate were significantly related to a decreased likelihood of migraine onset, especially among women, young and middle-aged populations, and non-Hispanic White participants. Further research is required to validate and expand upon our results.

Figure 1.

Detailed information about subject recruitment.

Figure 2.

Association between serum folate level and severe headache or migraine in RCS. The model was adjusted for sex, age, race, marital status, poverty, education, hyperlipidemia, drinking, smoking, BMI, Hcy, CRP, serum folate acid supplement, and serum vitamin B12. Solid line, OR; shade, 95% CI. BMI = body mass index, CI = confidence interval, CRP = C-reactive protein, Hcy = homocysteine, OR = odds ratio, RCS = restricted cubic spline.

Figure 3.

The forest plot shows ORs for subgroup analysis for the associations of serum folate and severe headache or migraine. The model was adjusted for sex, age, race, marital status, poverty, education, hyperlipidemia, drinking, smoking, BMI, Hcy, CRP, serum folate acid supplement, and serum vitamin B12. BMI = body mass index, CRP = C-reactive protein, Hcy = homocysteine, OR = odds ratio.

Figure 4.

Forest plot shows ORs of serum folate level in severe headache or migraine using propensity score analysis. The model was adjusted for sex, age, race, marital status, poverty, education, hyperlipidemia, drinking, smoking, BMI, Hcy, CRP, serum folate acid supplement, and serum vitamin B12. BMI = body mass index, CRP = C-reactive protein, Hcy = homocysteine, OR = odds ratio.