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The relationship between one-carbon metabolism and nitric oxide metabolism in pediatric patients with migraine and tension-type headache Cover

The relationship between one-carbon metabolism and nitric oxide metabolism in pediatric patients with migraine and tension-type headache

Open Access
|Feb 2026

Abstract

Background

Pediatric headache is a common neurological condition that adversely affects quality of life. Vitamin B12 is involved in homocysteine (Hcy) and methylmalonic acid (MMA) metabolism, and nitric oxide (NO) plays a role in neurovascular signaling. This study evaluated vitamin B12–related biomarkers and NO in pediatric migraine and tension-type headache (TTH).

Methods

The study included 39 migraine, 42 TTH and 29 control. Vitamin B12 and folic acid were measured using the Roche Cobas e601, Hcy were measured with the Shimadzu LC-20 HPLC, MMA were measured by a modified LC-MS/MS method, NO were measured using the Griess method.

Results

Hcy levels differed significantly between the migraine and control, as well as between the TTH and control (p<0.05). For MMA, a significant difference was observed between the TTH and control groups (p<0.05). Total nitrite and nitrate concentrations were significantly higher in patients than in controls(p<0.05).

Conclusions

Although serum vitamin B12 concentrations did not show a significant difference, median MMA values were elevated in the patient groups. MMA is recognized as a biomarker of subclinical vitamin B12 deficiency, and because oxidative stress may impair the cellular function of vitamin B12, MMA measurement provides valuable information even when serum B12 levels remain within the normal range. Furthermore, endothelial damage induced by Hcy, together with chronic oxidative stress associated with the Hcy–NO pathway, may contribute to the pathogenesis of pediatric migraine and TTH. Consistent with this, the significantly higher levels of NO metabolites in patients compared with controls suggest that NO may play a role in the development of migraine and TTH in the pediatric population.

DOI: https://doi.org/10.2478/rrlm-2026-0006 | Journal eISSN: 2284-5623 | Journal ISSN: 1841-6624
Language: English
Page range: 71 - 80
Submitted on: Oct 6, 2025
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Accepted on: Jan 9, 2026
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Published on: Feb 5, 2026
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2026 Ayşenur Macun Ayan, Mehmet Şeneş, Arzu Yılmaz, Sedat Abuşoğlu, Ali Ünlü, Doğan Yücel, published by Romanian Association of Laboratory Medicine
This work is licensed under the Creative Commons Attribution 4.0 License.