Increasing the levels of serum B12 by more than 643 pg/mL is accompanied by roughly an 80% decrease in the adjusted odds of having a migraine, according to a study published in the journal Headache.

In this case-control study that was a preplanned secondary analysis of a previous study on the association between levels of vitamin D and migraine, researchers recruited patients with migraine (n=70) and migraine-free healthy volunteers to serve as controls (n=70) between April and September 2017. Inclusion criteria for the case group were chronic or episodic migraine having occurred for ≥6 months preceding the study. Exclusion criteria included neurologist-diagnosed medication-overuse headache, vitamin B12 supplement use over the prior 3 months, metformin use, and several other criteria assigned according to the associations between the conditions and B12 and/or migraine status.

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Participants in the case group completed 30-day headache diaries, which included the number of headache days, severity of headaches on the scale of 0 to 10, and the duration of headache attacks in hours. To assess serum B12 and methylmalonic acid (MMA) levels, fasting blood samples (5 mL) were obtained from each group.

Mean values for serum B12 was lower in the case group than in the healthy control group (512 [300] pg/mL vs 667 [351] pg/mL; P =.007). Participants in the case group had higher levels of MMA than the controls (1.39 [0.59, 4.01] µg/dL vs 1.01 [0.49, 1.45] µg/dL; P =.027). There was no significant correlation between the frequency of headache days per month with serum B12 levels (Pearson correlation: 0.05; 95% CI, -0.18 to 0.29; P =.629) or serum MMA levels (Pearson correlation: -0.21; 95% CI, -0.43 to 0.02; P =.080). There was a significant negative association between serum levels of B12 and odds of having migraine in a multiple regression model.

Limitations of this study may include the effects of confounding factors that could affect B12 status — its function in relation to risk for migraine could not be fully eliminated, despite attempts to control for possible and potential confounders using a multiple regression model. The exact dosages of prescribed drugs could also affect the results. The present findings failed to determine the direction of the association between levels of B12 and migraine.

The researchers suggested that individuals with an increasing level of serum B12 had a roughly 80% decrease in the odds of having a migraine and that higher MMA levels were associated with an approximate 4- to 5-fold increase in the odds of having a migraine. These results need to be validated by long-term cohort studies and well-designed clinical trials that examine the link between the functional role of vitamin B12 levels in migraine.


Togha M, Razeghi Jahromi S, Ghorbani Z, Martami F, Seifishahpar M. Serum vitamin B12 and methylmalonic acid status in migraineurs: a case-control study [published online August 31, 2019]. Headache. doi: 10.1111/head.13618