Sphingolipid Metabolism in Women With Episodic Migraine

Sphingolipid Metabolism in Women With Episodic Migraine

Results from a case-control study suggest that women with episodic migraine have alterations in sphingolipid metabolism.1 If these results are confirmed in larger studies, sphingolipid panels may become useful for diagnosing migraine.

Study Design

The study included 52 women with episodic migraine and 36 controls.1 The women with migraine had a mean of 5.6 headache days per month. The mean score on the Headache Impact Test-6 (HIT-6) questionnaire, a measure of headache-related disability, was 62.9. Nearly half (48%) of participants reported aura.

Each participant was weighed and measured. In addition to routine lab work, sphingolipidomic analysis was performed. These results were analyzed to identify associations between sphingolipid levels and episodic migraine. Additionally, the data were used to develop a model that correctly classified individuals with episodic migraine.


Sphingolipid concentrations associated with migraine. The authors found that episodic migraine was associated with lower levels of total ceramide and total dihydroceramide (DHC), as well as lower levels of specific very long chain ceramides.1 Mean crude levels (ng/mL) for controls and cases, respectively, were:

  • Total ceramides (10,518.5 vs. 6,052.9, p < 0.0001)
  • Total DHC (63.1 vs. 39.3, p < 0.0001)
  • Ceramide C24:0 (8,354.4 vs. 4,090.1, p < 0.0001)
  • DHC C24:0 (42.6 vs. 20.8, p < 0.0001)
  • Monohexosylceramide C26:0 (17.0 vs. 9.6, p < 0.0001)

The fully adjusted multivariate analysis showed that each standard deviation increase in total ceramide or total DHC was associated with more than 92% decreased odds of having episodic migraine.1

  • Total ceramides (OR 0.07; 95% CI, 0.02-0.22; p < 0.001)
  • Total DHC (OR 0.05; 95% CI, 0.01-0.21; p < 0.001)

The women with episodic migraine had increased levels of the sphingomyelin (SM) species C18:0 and C18:1.1 The fully adjusted multivariate analysis showed that each standard deviation increase in these lipids was associated with significantly increased odds of having episodic migraine.

  • SM C18:0 (OR 4.28; 95% CI, 1.87-9.81; p = 0.001)
  • SM C:18:1 (OR 2.93; 95% CI, 1.55-5.54; p = 0.001)

Differentiating migraine presence and absence. The authors tested the idea that sphingolipid levels could separate women with and without episodic migraine with two statistical models. Orthogonal partial least squares discriminant analysis showed that these groups could be clearly separated. Then, using hierarchical clustering analysis, the study authors identified the specific sphingolipid species that separated women with and without episodic migraine. These findings were consistent with the results of the logistic regression analyses.1

Developing a decision tree. Finally, the authors used recursive partitioning to create a decision tree that classified the women with episodic migraine based on their sphingolipid levels. This model was validated using an out-of-sample group of 14 participants (6 control and 8 cases). The model correctly classified each of the 14 participants as case or control.


According to the authors, these results suggest that migraineurs may have decreased de novo synthesis of ceramides and increased downstream production of ceramide metabolic products such as sphingomyelin. While acknowledging that the decision tree needs to be tested in a larger sample, the authors also state that a sphingolipid panel has potential to be useful in migraine diagnosis. They conclude that additional research is needed to understand the role of sphingolipid metabolism in migraine.

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