Nutritional supplements for migraine prevention: evaluating evidence sufficiency and effect modifiers through network meta-analysis, trial sequential analysis, and meta-regression
Abstract
Background: This network meta-analysis (NMA) integrated trial sequential analysis (TSA) limited to eligible direct pairwise comparisons and network meta-regression to compare efficacy and safety of nutritional supplements for migraine prevention, assess evidence maturity and identify potential effect modifiers.
Methods: We retrieved randomized controlled trials (RCTs) of nutritional supplements for adult migraineurs from four databases up to January 2025. Primary outcomes were migraine frequency, duration and severity; adverse events were the secondary outcome. Frequentist random-effects NMA calculated mean differences (MD) for continuous indicators and odds ratios (OR) for adverse events with 95% confidence intervals (CIs). Treatment rankings were assessed using rank probabilities and the surface under the cumulative ranking curve but were interpreted as exploratory. Inconsistency was tested where network structure allowed valid evaluation. Network meta-regression detected between-study heterogeneity, TSA was restricted to eligible direct pairwise comparisons and the CINeMA framework evaluated overall evidence certainty.
Results: Fourteen RCTs (791 participants) formed a six-node network: vitamins, magnesium, coenzyme Q10, probiotics, vitamin-probiotic combinations and placebo. For migraine frequency, probiotics produced the largest frequency reduction vs. placebo (MD = -2.60 attacks/month, 95% CI - 3.96 to -1.20; 72% top-rank probability), followed by vitamin-probiotics…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 791 participants or records.
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