Head-to-head evidence comparison — which supplement is right for you?
Methylfolate wins 1 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
400-800mcg daily
Morning with or without food, Consistent daily timing
L-Methylfolate (5-MTHF)
50-100mg daily; 150-600mg benfotiamine for neuropathy
With food, Morning with other B vitamins
Benfotiamine (fat-soluble, higher bioavailability)
2-4 weeks
1-3 weeks
4-8 weeks
Days to weeks
2-4 weeks
4-8 weeks
4-12 weeks
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
Systematic review examining Methylfolate efficacy
Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders
Pharmacopsychiatry (2022) · Meta analysis · n=6707
In the meta-analysis of categorical Hamilton Rating Scale for Depression-17 response, (three studies, N=483) adjunctive L-methylfolate was associated with a small effect versus antidepressant monotherapy (relative risk: 1.25, 95% confidence interval [CI]=1.08 to 1.46, p=0.004).
Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis
Psychopharmacology (2018) · Meta analysis · n=925
Pooled FA + AP treatments were more effective than placebo + AP for negative symptoms (N = 5, n = 281; SMD = -0.25, 95% CI = -0.49, -0.01, p = 0.04, I2 = 0%).
Dietary supplements for dysmenorrhoea
The Cochrane database of systematic reviews (2016) · Meta analysis · n=3101
Supplements versus other supplementsThere was no evidence of a difference in effectiveness between ginger and zinc sulphate (MD 0.02 points, 95% CI -0.58 to 0.62; one RCT, 101 women).
Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial
The Lancet. Haematology (2024) · Rct · n=316
Clinical trial examining Thiamine efficacy
Effect of intravenous thiamine administration on critically ill patients: A systematic review and meta-analysis of randomized controlled trials
Clinical nutrition (Edinburgh, Scotland) (2024) · Meta analysis · n=3494
Conversely, thiamine administration resulted in a slight increase in the length of ICU stay (MD, 0.40 days; 95% CI, 0.01-0.79 days; High CoE).
Methylfolate has a higher evidence score (9/10 vs 9/10) and wins in 1 of 3 categories.
For fertility support, Methylfolate has a higher relevance score (95 vs 70).
No known interactions between Methylfolate and Thiamine have been documented in our database. However, always consult a healthcare provider before combining supplements.