Ruban Angela, Schneider Andrea L C, Liang Menglu, Gottesman Rebecca F, Selvin Elizabeth, Coresh Josef, Lazo Mariana, Koton Silvia
Department of Nursing, Grey Faculty of Medical and Health Sciences, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, P.O. Box 39040.
Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Ther Adv Neurol Disord. 2025 Sep 13;18:17562864251370097. doi: 10.1177/17562864251370097. eCollection 2025.
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.
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.
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.
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.
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.
累积的研究数据表明，偏头痛的特征是谷氨酸能失衡，尤其是谷氨酸能信号过度。已有报道称偏头痛患者大脑和血浆中的谷氨酸水平升高，但对于调节血液谷氨酸水平的肝酶，如天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和γ-谷氨酰转肽酶（GGT）与偏头痛之间的关联了解较少。
我们在社区动脉粥样硬化风险研究队列中评估了四分位数范围内的AST、ALT和GGT水平与可能/确诊偏头痛病史之间的关联。
我们纳入了11718名有肝酶水平测量值以及偏头痛有无先兆的自我报告数据的参与者。使用多元逻辑回归模型来评估肝酶的性别特异性四分位数与可能/确诊偏头痛之间的关联。
在1993 - 1995年期间共报告了1626例可能/确诊偏头痛事件。在对年龄、种族中心和性别进行调整后，较高水平的AST、ALT和GGT与较低的偏头痛患病率相关。AST、ALT和GGT的Q1水平与Q4水平相比，偏头痛的调整优势比（95%置信区间）分别为1.24（1.06 - 1.45）、1.17（1.00 - 1.37）和1.21（1.03 - 1.41）。按有无先兆分析显示，与较高（Q4）水平的ALT相比，较低（Q1）水平的ALT使无先兆偏头痛的几率更高（调整后的OR为1.38，95%置信区间为1.05 - 1.82），而酶水平与有先兆偏头痛的患病率之间未观察到显著关联。
我们的研究结果表明，较高的AST、ALT和GGT水平与较低的偏头痛患病率相关。尽管较低的血液AST、ALT和GGT水平与偏头痛之间的确切机制尚不清楚，但其关联可能可以通过血浆谷氨酸调节效率低下来解释，这可能在偏头痛病理过程中起作用。这一发现对患者很重要，因为它揭示了偏头痛潜在的代谢影响因素，支持了除传统神经血管理论之外的因素也参与其中的假设。
