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)
2-4g daily for PCOS; up to 12-18g for anxiety
Divided doses with meals, Morning and evening
Myo-inositol powder
2-4 weeks
1-3 weeks
4-8 weeks
Days to weeks
3-6 months
4-6 weeks
2-3 months
Initial use or high doses
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%).
Antenatal dietary supplementation with myo-inositol for preventing gestational diabetes
The Cochrane database of systematic reviews (2023) · Meta analysis · n=1319
For the primary neonatal outcomes, only one study measured the risk of a large-for-gestational-age infant and found myo-inositol was associated with both appreciable benefit and harm (RR 1.40, 95% CI 0.65 to 3.02; 1 study, 234 infants; low-certainty evidence).
Inositol Nutritional Supplementation for the Prevention of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Nutrients (2022) · Meta analysis · n=1321
Pooled results were expressed as relative risk (RR) or mean difference (MD) with a 95% confidence interval (95% CI).
Short period-administration of myo-inositol and metformin on hormonal and glycolipid profiles in patients with polycystic ovary syndrome: a systematic review and updated meta-analysis of randomized controlled trials
European review for medical and pharmacological sciences (2022) · Meta analysis · n=612
Compared with metformin, the suitable supplemental dosage of myo-ins may be helpful in lowering levels of TG and avoiding adverse events (AEs).
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 92).
No known interactions between Methylfolate and Myo-Inositol have been documented in our database. However, always consult a healthcare provider before combining supplements.