Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta‐Analysis

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.

Serum lipid abnormalities in migraine: A meta‐analysis of observational studies

“…The accumulation of further evidence may, additionally, feature the presence of relatively elevated LDL‐C levels in migraine patients. It is, therefore, likely that the lipid component consists one of several contributors that confer to the increased vascular risk of migraine 75,76 . It is important that future studies investigating the presence of lipid abnormalities in migraine individuals report obtained results for MWA and MWoA individuals separately, in view of the possibly stronger association of MWA with greater vascular risk 77 .…”

“…It is, therefore, likely that the lipid component consists one of several contributors that confer to the increased vascular risk of migraine. 75,76 It is important that future studies investigating the presence of lipid abnormalities in migraine individuals report obtained results for MWA and MWoA individuals separately, in view of the possibly stronger association of MWA with greater vascular risk. 77 Moreover, future research should address the confounding of increased body weight and lifestyle in order to better capture serum lipid abnormalities in migraine individuals, while the relative contribution of prophylactic medications should be determined.…”

Changes and Associations between Cervical Range of Motion, Pain, Temporomandibular Joint Range of Motion and Quality of Life in Individuals with Migraine Applying Physiotherapy: A Pilot Study

“…Homocysteine catalyzes vitamins B6, B12, and folic acid, which can reduce the severity of migraines with aura. Therefore, these vitamins may be useful prophylactic drugs for the treatment of migraines with aura [36].…”

Truths and Myths in Pediatric Migraine and Nutrition

“…Limited data are available for the prophylaxis of migraine in children with melatonin [ 125 ], pyridoxine, vitamin B12, folate [ 126 ], and vitamin D [ 127 ].…”