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Head-to-head evidence comparison — which supplement is right for you?
Methylfolate vs Tribulus: Methylfolate has the stronger overall evidence (6 vs 5.5/10); they're alternatives for fertility support — the best pick depends on your goals. Take the 60-second quiz for a pick tailored to your goals.
Methylfolate wins 3 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
3 of 3 studies with measurable effects showed benefit.
Top outcomes
400-800mcg daily
Morning with or without food, Consistent daily timing
L-Methylfolate (5-MTHF)
250-750mg daily (standardized to 45-60% saponins)
With meals, Morning or divided doses
Extract standardized to 45-60% saponins (protodioscin)
2-4 weeks
1-3 weeks
4-8 weeks
Days to weeks
2-4 weeks
4-8 weeks
N/A
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.
Effects of Tribulus (Tribulus terrestris L.) Supplementation on Erectile Dysfunction and Testosterone Levels in Men-A Systematic Review of Clinical Trials
Nutrients (2025) · Systematic review · n=483
10 studies (9 clinical trials and 1 study without a control) with 483 men in total, aged 16 to 70.
Dietary Supplements for Erectile Dysfunction: Analysis of Marketed Products, Systematic Review, Meta-Analysis and Rational Use
Nutrients (2023) · Meta analysis
Based on the scoring system, 2 (8%) supplements matched with the cluster of higher expected efficacy, 3 (12%) with the lower efficacy cluster and 20 (80%) matched with the criterion of no expected efficacy.
Beneficial effects of natural products on female sexual dysfunction: A systematic review and meta-analysis
Phytomedicine : international journal of phytotherapy and phytopharmacology (2021) · Meta analysis
536 studies were identified and 20 met the criteria. The abstract gives no participant total.
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.
Methylfolate has a higher evidence score (6/10 vs 5.5/10) and wins in 3 of 3 categories.
For fertility support, Methylfolate has a higher relevance score (95 vs 80).
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.
Mostly hype unless you’re deficient — what has modest evidence vs what doesn’t, and when to see a doctor.
The right pick depends on your goals. Answer a few quick questions for a personalised recommendation — or dig into the full evidence on each.