Folate for Depression
For depression, folate (especially L-methylfolate) shows a small-to-modest benefit only as an add-on to antidepressant medication, not as a standalone treatment. Everyday 400-600 mcg supplements are far below the doses tested and should not be viewed as a depression therapy.
Why this grade7-layer evidence engine
This earns a Preliminary (B) grade because multiple meta-analyses converge on a real but modest add-on effect. Pooled trials found adjunctive L-methylfolate raised antidepressant response rates (RR 1.25 and RR 1.36) and lowered symptom scores (SMD roughly -0.38 to -0.42) versus medication alone (PMID 34794190, 34450256, 38873435). A pivotal double-blind RCT (PMID 23212058) found 15 mg/day effective but 7.5 mg/day non-significant, showing a real yet dose-dependent effect.
It is held at B rather than higher because the quantitative evidence base is small (pooled N around 483-507), confidence intervals for remission sit near unity, several pivotal trials are manufacturer-sponsored, and one major meta-analysis carries a disclosed industry-linked conflict of interest (PMID 34794190). Benefit also concentrates in subgroups such as people with low folate status, MTHFR variants, obesity, or elevated inflammation, limiting how broadly it applies.
Regulators (FDA, WHO, UK NHS) strongly endorse folate, but only for preventing neural-tube defects in pregnancy, not for depression. Clinical sources match the modest tone: the Mayo Clinic notes low folate is associated with depression and suggests discussing folic acid with your doctor, while Cleveland Clinic, Harvard Health, and the specialty consensus all treat it as a recognized but cautious adjunctive option, never a first-line therapy.
Scoring transparency
All scores computed by a 7-layer evidence engine — fully auditable▸View the full decision path (audit trail)
- compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.577
- tier_from_score — 依分數區間映射至 tier letter
- apply_hec_rules — 高品質 SR/MA 顯示 positive (1 篇 > 0 negative)
- tier_strict_requirement_check — Tier 條件達標，未降階
- detect_disputes — 偵測到 0 個 hard + 1 個 soft dispute
- decide_status — 依 tier + dispute 結果決定 status