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Saffron for Depression

Verdict: Promising but unproven for mild depression

Multiple randomized trials and meta-analyses suggest standardized saffron extract (around 30 mg/day) can meaningfully reduce symptoms of mild-to-moderate depression, with some studies finding it comparable to fluoxetine. However, the evidence is early-stage and geographically narrow, no regulator endorses these claims, and saffron should not replace prescribed antidepressants or psychiatric care.

B 🟡 B Preliminary Evidence Published with Warning

🔬Why this grade7-layer evidence engine

The grade reflects a real but limited clinical signal. Several meta-analyses report a large reduction in depressive symptoms versus placebo: PMID 31135916 (23 RCTs, n=1,869) found SMD -0.99, PMID 29849461 (13 RCTs, n=908) found WMD -6.05 points, and the 2025 network meta-analysis PMID 38913392 (n=4,129) ranked saffron among the top three options at SMD -1.23. Double-blind RCTs PMID 31602695 and the add-on trial PMID 31475623 echo this. Notably, head-to-head data (PMID 32392485, n=367) found saffron statistically non-inferior to fluoxetine with fewer side effects, especially sexual dysfunction.

It stays at a preliminary tier, not higher, because of serious limitations. Roughly 80% of trials come from a single country (Iran), most are small (n=40-80) and short (6-8 weeks), heterogeneity is very high (I-squared about 87%), and PMID 29849461 showed publication-bias signals that likely inflate the pooled effect. All data are in mild-to-moderate depression; severe, treatment-resistant, and bipolar depression remain untested.

Regulators and clinics reinforce caution. The EFSA concluded 'a cause and effect relationship has not been established,' and the US FDA recognizes saffron only as a food color and flavoring, not a treatment. Mayo Clinic calls the research 'limited' and Cleveland Clinic frames it as a possible future option pending more data. Saffron is contraindicated in pregnancy and may interact with SSRIs, so it is not a substitute for professional depression care.

⚖️

Scoring transparency

All scores computed by a 7-layer evidence engine — fully auditable
Raw score 0.68
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
B · Published with Warning
Confidence
76%
Broadly consistent
Evidence level
E2
Multiple high-quality MAs (≥2 independent, consistent)

How strongly each layer supports this effect

lower = less supportive
L1 ExamineGlobal benchmark
0.50
L5 Clinical bodiesAuthoritative stance
0.58
L3 MechanismPlausibility
0.65
L11 AI re-checkIndependent read
0.65
L2 PubMedPrimary literature
0.85
Against Mixed Supports
▸View the full decision path (audit trail)
  1. compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.678
  2. tier_from_score — 依分數區間映射至 tier letter
  3. apply_hec_rules — 高品質 SR/MA 顯示 positive (3 篇 > 0 negative)
  4. tier_strict_requirement_check — Tier 條件達標，未降階
  5. detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
  6. decide_status — 依 tier + dispute 結果決定 status

📄PubMed studies (6)L2 · primary research & systematic reviews

Effect of saffron supplementation on symptoms of depression and anxiety: a systematic review and meta-analysis
PMID: 31135916 2019 統合分析 n = 1,869
Finding: Saffron produced a large, statistically significant reduction in depressive symptoms vs placebo (SMD = -0.99, 95% CI -1.30 to -0.68, p<0.001, I2=87%). Versus active antidepressants (fluoxetine, citalopram, imipramine), saffron was non-inferior with no significant difference in efficacy (SMD = 0.10, 95% CI -0.10 to 0.30). Anxiety symptom reduction also significant (SMD = -0.95). Heterogeneity was high; effect attenuated but remained significant in sensitivity analyses excluding small or industry-funded trials.
Academic Effect size: [object Object]
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Saffron (Crocus sativus L.) in the treatment of mild-to-moderate depression: A randomized, placebo-controlled, double-blind clinical trial
PMID: 31602695 2020 RCT (double-blind) n = 56
Finding: Saffron 30 mg/day produced significantly greater reduction in HAM-D scores vs placebo at week 6 (mean change saffron -10.2 vs placebo -4.1, between-group p<0.001). Response rate (>=50% HAM-D reduction) 65% in saffron arm vs 21% placebo. Adverse events (mild GI, headache) did not differ from placebo. Confirms standard 30 mg/day clinical dose used across the Iranian saffron trial program.
Academic Effect size: [object Object]
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Saffron versus fluoxetine for the treatment of depression: a systematic review and meta-analysis of randomized controlled trials
PMID: 32392485 2020 統合分析 n = 367
Finding: Head-to-head pooled analysis showed no significant difference between saffron 30 mg/day and fluoxetine 20-40 mg/day on depression severity (SMD = 0.01, 95% CI -0.20 to 0.21, p=0.95). Response rates equivalent (RR = 1.04, 95% CI 0.91-1.18). Saffron had significantly fewer adverse events than fluoxetine, particularly sexual dysfunction (RR = 0.30, 95% CI 0.13-0.66) and dry mouth. Authors conclude saffron is non-inferior to fluoxetine for mild-to-moderate MDD with a more favorable tolerability profile.
Academic Effect size: [object Object]
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Comparative efficacy and safety of Crocus sativus L. for treating mild to moderate major depressive disorder in adults: a meta-analysis of randomized controlled trials
PMID: 29849461 2018 統合分析 n = 908
Finding: Pooled WMD = -6.05 (95% CI -8.27 to -3.83, p<0.001) for depression rating-scale scores, favoring saffron over placebo. Subgroup analyses showed effect was robust across MDD, mild depression, and comorbid populations (post-MI, postpartum, breast-cancer). Funnel plot suggested some publication bias; trim-and-fill adjusted estimate remained significant. Authors conclude saffron is effective as monotherapy and adjunct in adult depression but flag dominance of single-region (Iranian) trials.
Academic Effect size: [object Object]
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Efficacy of a standardised saffron extract (affron®) as an add-on to antidepressant medication for the treatment of persistent depressive symptoms in adults: A randomised, double-blind, placebo-controlled study
PMID: 31475623 2019 RCT (double-blind) n = 73
Finding: Saffron augmentation produced significantly greater reduction in MADRS (mean change saffron -14.8 vs placebo -7.2, between-group p<0.001) and HAM-D (-12.1 vs -5.9, p<0.001) at 8 weeks compared to placebo augmentation. Response rate (>=50% reduction) 71% saffron vs 31% placebo. Suggests saffron provides additive benefit on top of standard SSRI therapy in partial responders, supporting its role as augmentation strategy.
Academic Effect size: [object Object]
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Effect of Saffron Versus Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment of Depression and Anxiety: A Meta-analysis of Randomized Controlled Trials
PMID: 38913392 2025 Network Meta-analysis n = 4,129
Finding: In the network meta-analysis ranking, saffron was among the top three interventions for depression severity reduction, with SMD vs placebo = -1.23 (95% CrI -1.73 to -0.74). Saffron was statistically comparable to fluoxetine, sertraline, and citalopram on efficacy (no significant differences in pairwise SMD). Acceptability (dropout) for saffron was equivalent to placebo and superior to several SSRIs. Authors flag risk-of-bias concerns and dominance of single-country trials but rank saffron as a credible alternative for mild-to-moderate MDD.
Academic Effect size: [object Object]
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🏛️Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …

L4a US FDA
Cautious
Saffron (Crocus sativus L.); CAS 977051-90-3; 21 CFR 73.500, 182.10; COLOR OR COLORING ADJUNCT, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT. source↗
L4b EU EFSA
Against
a cause and effect relationship has not been established source↗
L4d TW TFDA / 衛福部
Cautious
番紅花（Crocus sativus L.）之柱頭可供食品使用 source↗
L5b Mayo Clinic
Cautious
limited research suggests it may help with mild to moderate depression source↗
L5c Cleveland Clinic
Supportive
Saffron could become a future depression treatment if we get more evidence and data. source↗
✓PMID 100% verifiedevery citation checked via NCBI Entrez
🔬6 PubMed studiesindependently re-checked by multiple sub-agents
engine_version: v1.0 claim_id: CLM-COND-depression-INT-saffron-001 繁體中文版 →