TY - JOUR
T1 - Association between liver enzyme levels and prevalence of migraine
T2 - the atherosclerosis risk in communities study
AU - Ruban, Angela
AU - Schneider, Andrea L.C.
AU - Liang, Menglu
AU - Gottesman, Rebecca F.
AU - Selvin, Elizabeth
AU - Coresh, Josef
AU - Lazo, Mariana
AU - Koton, Silvia
N1 - Publisher Copyright:
© The Author(s), 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
PY - 2025/1/1
Y1 - 2025/1/1
N2 - Background: Cumulative research data indicate that migraine is characterized by a glutamatergic imbalance, particularly an excessive glutamatergic signal. Increases in glutamate levels in the brain and plasma of migraine patients have been reported, but less is known about the association between liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT) that regulate blood glutamate levels and migraine. Objectives: We evaluated associations between AST, ALT, and GGT levels across the quartiles and a history of probable/defined migraine in the Atherosclerosis Risk in Communities Study cohort. Design: We included 11,718 participants with measured liver enzyme levels and self-reported data on migraine with and without aura. Multiple logistic regression models were used to assess associations of sex-specific quartiles of liver enzymes with probable/definite migraine. Results: A total of 1626 probable/definite migraine events were reported in 1993–1995. After adjustment for age, race-center, and sex, higher levels of AST, ALT, and GGT were associated with a lower prevalence of migraine. The adjusted odds ratios (95% CIs) for migraine for Q1 versus Q4 levels of AST, ALT, and GGT were 1.24 (1.06–1.45), 1.17 (1.00–1.37) and 1.21 (1.03–1.41), respectively. Analysis by yes/no aura showed higher odds of migraine without aura for lower (Q1) compared with higher (Q4) levels of ALT (adjusted OR 1.38, 95% CI 1.05–1.82), while no significant association was observed between enzyme levels and prevalence of migraine with aura. Conclusion: Our findings suggest that higher AST, ALT, and GGT levels are associated with a lower prevalence of migraine. Although the exact mechanisms linking lower blood levels of AST, ALT, and GGT to migraines remain unclear, their association may be explained by inefficient plasma glutamate regulation, which could play a role in migraine pathology. This finding is important for patients as it sheds light on potential metabolic contributions to migraines, supporting the hypothesis that factors beyond traditional neurovascular theories are involved.
AB - Background: Cumulative research data indicate that migraine is characterized by a glutamatergic imbalance, particularly an excessive glutamatergic signal. Increases in glutamate levels in the brain and plasma of migraine patients have been reported, but less is known about the association between liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT) that regulate blood glutamate levels and migraine. Objectives: We evaluated associations between AST, ALT, and GGT levels across the quartiles and a history of probable/defined migraine in the Atherosclerosis Risk in Communities Study cohort. Design: We included 11,718 participants with measured liver enzyme levels and self-reported data on migraine with and without aura. Multiple logistic regression models were used to assess associations of sex-specific quartiles of liver enzymes with probable/definite migraine. Results: A total of 1626 probable/definite migraine events were reported in 1993–1995. After adjustment for age, race-center, and sex, higher levels of AST, ALT, and GGT were associated with a lower prevalence of migraine. The adjusted odds ratios (95% CIs) for migraine for Q1 versus Q4 levels of AST, ALT, and GGT were 1.24 (1.06–1.45), 1.17 (1.00–1.37) and 1.21 (1.03–1.41), respectively. Analysis by yes/no aura showed higher odds of migraine without aura for lower (Q1) compared with higher (Q4) levels of ALT (adjusted OR 1.38, 95% CI 1.05–1.82), while no significant association was observed between enzyme levels and prevalence of migraine with aura. Conclusion: Our findings suggest that higher AST, ALT, and GGT levels are associated with a lower prevalence of migraine. Although the exact mechanisms linking lower blood levels of AST, ALT, and GGT to migraines remain unclear, their association may be explained by inefficient plasma glutamate regulation, which could play a role in migraine pathology. This finding is important for patients as it sheds light on potential metabolic contributions to migraines, supporting the hypothesis that factors beyond traditional neurovascular theories are involved.
KW - excitotoxicity
KW - glutamate
KW - liver enzymes
KW - migraine
KW - treatment
UR - https://www.scopus.com/pages/publications/105015843310
U2 - 10.1177/17562864251370097
DO - 10.1177/17562864251370097
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C2 - 40955422
AN - SCOPUS:105015843310
SN - 1756-2856
VL - 18
JO - Therapeutic Advances in Neurological Disorders
JF - Therapeutic Advances in Neurological Disorders
M1 - 17562864251370097
ER -