Loading…
We use essential cookies (authentication, your saved goals/stack) by default. With your permission we'll also enable privacy-respecting analytics (Vercel Web Analytics, anonymous load-time metrics) and error-replay diagnostics (Sentry — DOM snapshots only when an error fires) so we can fix bugs faster. Learn more
Head-to-head evidence comparison — which supplement is right for you?
Methylfolate and Vitamin D3 are closely matched across evidence, studies, and safety.
Verdict
Likely helps
13 of 15 studies with measurable effects showed benefit.
Top outcomes
Verdict
Probably helps
15 of 26 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (1)
Outcomes where both Methylfolate and Vitamin D3 have evidence — compare verdict strength side-by-side.
400-800mcg daily
Morning with or without food, Consistent daily timing
L-Methylfolate (5-MTHF)
2000-4000 IU daily
Morning with breakfast
D3 (cholecalciferol) softgel or liquid
2-4 weeks
1-3 weeks
4-8 weeks
Days to weeks
4-8 weeks
4-8 weeks
2-4 weeks
4-8 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%).
Vitamin D supplementation vs. placebo and incident type 2 diabetes in an ancillary study of the randomized Vitamin D and Omega-3 Trial
Nature communications (2025) · Meta analysis · n=5205
Mean body mass index (BMI) was 27.5 kg/m2 (SD = 5.3), with 51% female and 17% Black race/ethnicity.
Vitamin D Supplementation for Patients with Dysmenorrhoea: A Meta-Analysis with Trial Sequential Analysis of Randomised Controlled Trials
Nutrients (2024) · Meta analysis · n=687
TSA revealed that the current RCTs provide sufficient information.
Vitamin D and respiratory tract infections
BMJ (2017) · Meta analysis · n=11321
12% reduction in respiratory infections overall
Based on meta-analysis showing small effect size for adjunctive L-methylfolate. RCT showed efficacy at high doses but effectiveness appears modest. Risk increases with higher doses due to overmethylation symptoms.
Meta-analysis showed 12% overall reduction in respiratory infections, with greater benefits in severely deficient individuals. Daily dosing more effective than bolus. Conservative estimate assumes most users not severely deficient.
AI-estimated from published studies. Interpret as directional guidance.
Both Methylfolate and Vitamin D3 are closely matched — the best choice depends on your specific health goals.
For fertility support, Methylfolate has a higher relevance score (95 vs 85).
No known interactions between Methylfolate and Vitamin D3 have been documented in our database. However, always consult a healthcare provider before combining supplements.