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Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis.
Headache. 2020 Jul 02 [Online ahead of print]H

Abstract

BACKGROUND

Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies.

OBJECTIVE

The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO).

METHODS

Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias.

RESULTS

Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I2 = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I2 = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I2 = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I2 = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I2 = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I2 = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I2 = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I2 = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I2 = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I2 = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I2 = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I2 = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I2 = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I2 = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO.

CONCLUSIONS

Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.

Authors+Show Affiliations

Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.Department of Microbiology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece. Public Health Laboratories, Hellenic Pasteur Institute, Athens, Greece.Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.Department of Neurosurgery, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32615014

Citation

Liampas, Ioannis, et al. "Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis." Headache, 2020.
Liampas I, Siokas V, Mentis AA, et al. Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis. Headache. 2020.
Liampas, I., Siokas, V., Mentis, A. A., Aloizou, A. M., Dastamani, M., Tsouris, Z., Aslanidou, P., Brotis, A., & Dardiotis, E. (2020). Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis. Headache. https://doi.org/10.1111/head.13892
Liampas I, et al. Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis. Headache. 2020 Jul 2; PubMed PMID: 32615014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis. AU - Liampas,Ioannis, AU - Siokas,Vasileios, AU - Mentis,Alexios-Fotios A, AU - Aloizou,Athina-Maria, AU - Dastamani,Metaxia, AU - Tsouris,Zisis, AU - Aslanidou,Paraskevi, AU - Brotis,Alexandros, AU - Dardiotis,Efthimios, Y1 - 2020/07/02/ PY - 2020/03/24/received PY - 2020/05/10/revised PY - 2020/05/11/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - cobalamin KW - homocysteine KW - methylmalonic acid KW - migraine KW - vitamin B9 JF - Headache JO - Headache N2 - BACKGROUND: Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies. OBJECTIVE: The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO). METHODS: Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias. RESULTS: Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I2 = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I2 = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I2 = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I2 = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I2 = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I2 = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I2 = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I2 = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I2 = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I2 = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I2 = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I2 = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I2 = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I2 = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO. CONCLUSIONS: Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy. SN - 1526-4610 UR - https://www.unboundmedicine.com/medline/citation/32615014/Serum_Homocysteine,_Pyridoxine,_Folate,_and_Vitamin_B12_Levels_in_Migraine:_Systematic_Review_and_Meta-Analysis L2 - https://doi.org/10.1111/head.13892 DB - PRIME DP - Unbound Medicine ER -
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