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Head-to-head evidence comparison — which supplement is right for you?
Methylfolate wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Likely helps
14 of 16 studies with measurable effects showed benefit.
Top outcomes
Verdict
Mostly mechanism / observational
Top outcomes
400-800mcg daily
Morning with or without food, Consistent daily timing
L-Methylfolate (5-MTHF)
100-200mg daily
Morning or early afternoon, 30-60 minutes before focus work, Pre-workout
TeaCrine (branded theacrine)
2-4 weeks
1-3 weeks
4-8 weeks
Days to weeks
30-60 minutes, lasts 4-6 hours
30-60 minutes
30-60 minutes
30-60 minutes
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%).
A caffeine and theacrine combination improves cognitive performance in tactical personnel under physically fatiguing conditions
Journal of the International Society of Sports Nutrition (2025) · Rct · n=20
In the Object Hit & Avoid task, CAF and CTC significantly improved task accuracy (p < 0.01) while reducing omission (p < 0.01) and commission errors (p < 0.01) compared to PLA.
Theacrine as a novel ergogenic aid: impact on canoe sprint performance
Journal of the International Society of Sports Nutrition (2025) · Rct · n=20
Caffeine significantly improved the 500-meter time trial (-1.872 s vs.
Uncovering the effects and mechanisms of tea and its components on depression, anxiety, and sleep disorders: A comprehensive review
Food research international (Ottawa, Ont.) (2024) · Systematic review
The underlying molecular mechanisms involve the regulation of neurotransmitters, including monoamines, GABA, and brain-derived neurotrophic factor (BDNF), as well as the suppression of oxidative stress and inflammation.
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.
Effects are modest and inconsistent across studies. Several RCTs showed no significant cognitive improvements. Benefits appear primarily in subjective energy/focus rather than objective cognitive tasks. Studies show mixed results with some finding no statistical significance.
AI-estimated from published studies. Interpret as directional guidance.
Methylfolate has a higher evidence score (6/10 vs 5.5/10) and wins in 2 of 3 categories.
For support mood, Methylfolate has a higher relevance score (85 vs 60).
No known interactions between Methylfolate and Theacrine have been documented in our database. However, always consult a healthcare provider before combining supplements.