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Head-to-head evidence comparison — which supplement is right for you?
Methylfolate vs Riboflavin: Riboflavin has the stronger overall evidence (6.5 vs 6/10); they're alternatives for prenatal support — the best pick depends on your goals. Take the 60-second quiz for a pick tailored to your goals.
Riboflavin wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Likely helps
6 of 6 studies with measurable effects showed benefit.
Top outcomes
Verdict
Likely helps
5 of 5 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (2)
Outcomes where both Methylfolate and Riboflavin have evidence — compare verdict strength side-by-side.
400-800mcg daily
Morning with or without food, Consistent daily timing
L-Methylfolate (5-MTHF)
25-50mg for general health; 400mg for migraine prevention (the one cited trial used 400 mg, none used 25 to 50 mg)
With food for better absorption, Morning with other B vitamins
Riboflavin or Riboflavin-5-Phosphate (R-5-P)
2-4 weeks
1-3 weeks
4-8 weeks
Days to weeks
3 months
2-4 weeks
Immediate
Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials
Nutritional neuroscience (2023) · Systematic review · n=2256
20 RCTs with 2,256 subjects with depression or anxiety, covering several B vitamins and vitamin D, not methylfolate alone.
Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders
Pharmacopsychiatry (2022) · Meta analysis · n=6707
Nine articles (N=6,707 patients) were assessed qualitatively. The pooled analyses were smaller: three studies (N=483) and four studies (N=507).
Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis
Psychopharmacology (2018) · Meta analysis · n=925
Ten RCTs with 925 patients were reviewed, of which two tested methylfolate (n = 96). Seven RCTs entered the meta-analysis.
Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis
Nutritional neuroscience (2022) · Meta analysis · n=673
Eight randomized controlled trials and one controlled clinical trial with 673 subjects were analyzed using meta-analysis.
Effects of selected dietary supplements on migraine prophylaxis: A systematic review and dose-response meta-analysis of randomized controlled trials
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (2025) · Meta analysis
Twenty-two trials were included in the systematic review and meta-analysis.
Riboflavin supplements for blood pressure lowering in adults
The Cochrane database of systematic reviews (2025) · Meta analysis · n=374
We included four RCTs, which contributed 374 total participants for quantitative synthesis, although the number of participants included for each outcome varied.
Two randomised trials in people whose depression had not responded to an SSRI (PMID 23212058). In the first (148 patients), L-methylfolate at 7.5 mg a day for 30 days, then 15 mg, did no better than placebo. In the second (75 patients), 15 mg a day throughout beat placebo on response and symptom scores, with side effects no different from placebo. A meta-analysis found benefit only for methylfolate at 15 mg once daily added to an SSRI, with all evidence rated low or very low quality (PMID 29442609). The 800 mcg point comes from an open-label, non-randomised trial of 44 patients where adding methylfolate to an antidepressant improved PHQ-9 scores more by day 28 (40% vs 26%), but remission did not differ (PMID 39844190). No trial compared doses head to head, so no minimum or optimal dose is set.
AI-estimated from published studies. Interpret as directional guidance.
Riboflavin has a higher evidence score (6.5/10 vs 6/10) and wins in 2 of 3 categories.
For prenatal support, Riboflavin has a higher relevance score (78 vs 70).
No documented interaction was found in the data searched. This does not establish that this exact combination is safe.
CoQ10, zinc, selenium, carnitine modestly help sperm parameters — but live-birth evidence is weak.
Saffron, EPA omega-3, SAMe have real adjunct evidence — but these aren’t a substitute for care, and some interact dangerously.
Magnesium, riboflavin, CoQ10 — the supplements with real migraine-prevention evidence (and doses).
The right pick depends on your goals. Answer a few quick questions for a personalised recommendation — or dig into the full evidence on each.