Depression
Supplements studied for depression.
Overview
St. John's Wort has the strongest evidence (WA 88, 28 studies): standardized extracts at 600–1800 mg daily appear effective for mild to moderate depression versus placebo and comparable to some SSRIs in short-term trials. Vitamin B9 (Folate) (WA 68; medium effect size, very high evidence, medium trust) may modestly augment antidepressants, especially when folate is low, but is not a substitute for medication.
Curcumin (~1 g daily), SAMe, and Zinc (WA 72; medium effect size, high evidence, very high trust) show medium-strength but mixed results. Curcumin may work best with antidepressants; SAMe alone matches some drugs in short trials but add-on benefits are unclear; zinc 7–25 mg daily with antidepressants modestly improved symptoms in some studies. See the heatmap and evidence reviews below for all 42 supplements.
Effect graph
Relevant supplements
Relevant supplements sorted by DEX Score.
| St. John's Wort | ★★★★★ | High |
| Zinc | ★★★★★ | Medium |
| SAMe | ★★★★★ | Medium |
| Acetyl-L-Carnitine | ★★★★★ | Medium |
| Vitamin B9 (Folate) | ★★★★★ | Medium |
| Curcumin | ★★★★★ | Medium |
| L-Carnitine | ★★★★★ | Medium |
| Ayahuasca | ★★★★★ | Low |
| Vitamin D | ★★★★★ | Low |
| Rhodiola | ★★★★★ | Low |
| Green Tea | ★★★★★ | Low |
| Vitamin K | ★★★★★ | Low |
| Vitamin A | ★★★★★ | Low |
| Selenium | ★★★★★ | Low |
| L-Tryptophan | ★★★★★ | Low |
| Caffeine | ★★★★★ | Low |
| Blueberry | ★★★★★ | Low |
| Vitamin B2 (Riboflavin) | ★★★★★ | Low |
| Theanine | ★★★★★ | Low |
| Olive Oil | ★★★★★ | Low |
| N-Acetyl Cysteine (NAC) | ★★★★★ | Low |
| Lion's Mane Mushroom | ★★★★★ | Low |
| Inositol | ★★★★★ | Very Low / None |
| Chromium | ★★★★★ | Low |
| Bacopa | ★★★★★ | Low |
| Ashwagandha | ★★★★★ | Low |
| Vitamin C | ★★★★★ | Very Low / None |
| Vitamin B12 | ★★★★★ | Very Low / None |
| Valerian | ★★★★★ | Low |
| Phosphatidylserine | ★★★★★ | Low |
| Panax Ginseng | ★★★★★ | Low |
| Melatonin | ★★★★★ | Very Low / None |
| Lycopene | ★★★★★ | Low |
| Lutein | ★★★★★ | Low |
| Black Tea | ★★★★★ | Low |
| Probiotics | ★★★★★ | Very Low / None |
| Yohimbe | ★★★★★ | Very Low / None |
| Tyrosine | ★★★★★ | Very Low / None |
| Sulforaphane | ★★★★★ | Very Low / None |
| Quercetin | ★★★★★ | Very Low / None |
| Alpha-Linolenic Acid | ★★★★★ | Very Low / None |
| Oleic Acid | ★★★★★ | Very Low / None |
Studies
Find individual evidence reviews for supplements sorted by DEX Score.
42 supplements for , , and rated at least stars. All purchase bands. No minimum star filter.
St. John's WortView supplement →
Proven purchase·★★★★★
How we scored this▸
- St. John's wort can be an effective option for mild to moderate depression, helping to lift mood, reduce anxiety, and improve sleep.
- Studies have shown that it works better than a placebo and can be as effective as some prescription antidepressants, like low-dose SSRIs, with fewer side effects such as stomach upset, neurological issues, or sexual problems.
- Most research uses specific extracts standardized to contain about 0.2-0.3% hypericin and 5-6% hyperforin, taken in doses from 600 to 1800 mg daily.
- It’s important to choose a high-quality product and discuss use with a healthcare provider, especially if you’re taking other medications, because St. John’s wort can interact with many drugs.
- While it’s generally safe for adults, its benefits are most clear for mild to moderate depression, and it might not be enough for severe cases.
- Pediatric use has been studied but is less conclusive.
- In some people with bipolar disorder, SJW can cause mania.
- Always check with your doctor or pharmacist before starting St. John’s wort to ensure it’s appropriate for your situation.
Browse 28 studies·7 meta-analyses
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
MetaClinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis2017n=3,808
A 2016 meta-analysis of 27 St John's wort trials (3808 patients) found extracts more effective than placebo and comparable to standard antidepressants for mild-to-moderate depression.
- Effect
- Benefit
- Duration
- 4–12 weeks
- Population
- Depression patients
- Participants
- 3,808
MetaComparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis2017
A systematic review and meta-analysis found several CAM therapies including St John's wort had modest benefits for initial major depression versus second-generation antidepressants, with varying effect sizes.
- Effect
- Benefit
- Population
- Adults
- Avg age
- ~18
MetaA meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults2016n=3,126
A meta-analysis comparing St John's wort with SSRIs found similar efficacy for depression with fewer adverse events than standard antidepressants in included trials.
- Effect
- Benefit
- Population
- Adults
- Participants
- 3,126
MetaA systematic review of St. John's wort for major depressive disorder2016n=2,922
A systematic review of St John's wort for major depression found it more effective than placebo and generally comparable to antidepressants, with fewer side effects in many trials.
- Effect
- Benefit
- Population
- Adults
- Participants
- 2,922
GuideNonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians2016
ACP guidelines concluded nonpharmacologic therapies including St John's wort may benefit some adults with major depressive disorder, though evidence quality varied by intervention.
- Effect
- Benefit
- Population
- Adults
RCTEvaluation of Pharmaceutical Products of St. John's Wort Efficacy Added on Tricyclic Antidepressants in treating Major Depressive Disorder: A Double Blind Randomized Control Trial2012n=40
An Iranian RCT in major depression found Hypericum perforatum added to tricyclic antidepressants improved depressive symptoms versus antidepressants alone.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 75–100 mg/day
- Population
- Patients with major depressive disorder
- Participants
- 40
- Ages
- 18–54
MetaEfficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis2009
A meta-analysis found Hypericum perforatum comparably effective to SSRIs for major depression with better tolerability on several side-effect measures.
- Effect
- Benefit
- Population
- Patients with major depressive disorder
RCTContinuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression--a double-blind, randomized, placebo controlled long-term trial2008n=5,570
A long-term randomized trial showing that Hypericum extract WS 5570 effectively maintained remission and reduced relapse risk in moderate depression. A 26-week study (+ 12 month extension) of 426 patients with recurrent moderate major depression found that St. John’s wort (3 x 300 mg WS 5570 /day for 26-weeks) improved depressive symptoms and increased time to relapse in acute and chronic depression. Treatment was then maintained for 12-months and had a pronounced prophylactic effect in patients with early onset depression and those with a high degree of chronicity. WS 5570 was similarly safe to placebo.
- Effect
- Benefit
- Duration
- 26 weeks
- Dose
- 300 mg/day
- Population
- Adults
- Participants
- 5,570
Systematic reviewSt John's wort for major depression2008n=5,489
A Cochrane review found St John's wort extracts more effective than placebo for major depression and similarly effective to standard antidepressants, with fewer dropouts due to adverse effects.
- Effect
- Benefit
- Population
- Depression patients
- Participants
- 5,489
RCTAcute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine2005n=251
A 6-week study including 251 patients with acute major depression (>=22 on HAMD) taking St. John’s wort (900 mg /day WS 5570) or paroxetine (20 mg/day) found a baseline reduction in depression scores of 56.6% in those taking SJW and 44.8% in the paroxetine group. Dosages were safely increased to 1800 mg/day SJW or 40 mg paroxetine in participants who did not respond to treatment after 2 weeks. SJW was at least as effective as paroxetine and was better tolerated. Incidence of adverse events was lower in SJW (0.035 events per day of exposure) compared to paroxetine (0.060).
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 900 mg/day
- Population
- Adults
- Participants
- 251
Systematic reviewLarge-scale observational studies of hypericum extracts in patients with depressive disorders--a systematic review2005n=100
A systematic review of large observational St John's wort studies found clinically relevant improvement in depressive symptoms in most treated patients over at least 4 weeks.
- Effect
- Benefit
- Duration
- 4–6 weeks
- Population
- Patients with depressive disorders
- Participants
- 100
MetaSt John's wort for depression2005
A Cochrane review concluded Hypericum extracts outperform placebo for depression and match standard antidepressants, with fewer side effects than older antidepressants.
- Effect
- Benefit
- Population
- Adults
MetaSt John's wort for depression: meta-analysis of randomised controlled trials2005
An updated Cochrane meta-analysis of 37 RCTs found St John's wort more effective than placebo for depression, with efficacy similar to standard antidepressants in severe depression trials.
- Effect
- Benefit
- Population
- Adults
Open-labelAn open-label pilot study of St. John's wort in juvenile depression2003
An open-label pilot in youths aged 6–16 with major depression found St John's wort safe and associated with symptomatic improvement, though uncontrolled design limits inference.
- Effect
- Benefit
- Duration
- 8 weeks
- Dose
- 900 mg/day
- Population
- Children/adolescents
- Ages
- 6–16
RCTEffect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial2002n=340
In 388 adults with major depression over 6 weeks, LI-160 St John's wort did not significantly outperform placebo on primary depression outcomes in this large RCT.
- Effect
- No Benefit
- Duration
- 8 weeks
- Dose
- 900–1500 mg/day St John's wort (LI-160)
- Population
- Adults
- Participants
- 340
MetaA systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review2001
A comprehensive meta-analysis found St John's wort more effective than placebo for depression and generally comparable to standard antidepressants in efficacy.
- Effect
- Benefit
RCTEffectiveness of St John's wort in major depression: a randomized controlled trial2001n=102
In 200 adults with major depression over 8 weeks, standardized St John's wort did not significantly beat placebo on HAM-D response rates in this rigorous trial.
- Effect
- No Benefit
- Duration
- 8 weeks
- Dose
- 900 mg/day
- Population
- Adults
- Participants
- 102
- Avg age
- ~42
RCTEfficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial2001n=72
A multicenter randomized double-blind trial showing that WS 5572 extract was more effective than placebo for mild to moderate depression with good tolerability. A 6-week study including 72 patients with mild-to-moderate major depressive disorder found that 3 x 300 mg/day St. John’s wort (WS 5572) led to significant benefits after four (P = 0.011) and six weeks (P < 0.001) . After six weeks, the SJW group experienced a greater reduction in Hamilton Depression Scale score (19.7 +/- 3.4 to 8.9 +/- 4.3, -10.8 points) compared to the placebo group (20.1 +/- 2.6 to 14.4 +/- 6.8, -5.7 points).
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 300 mg/day
- Population
- Depression patients
- Participants
- 72
ObservationalExperience with St John's Wort (Hypericum perforatum) in children under 12 years with symptoms of depression and psychovegetative disturbances2001n=101
In 101 children under 12 with depressive symptoms over at least 4 weeks, St John's wort extract was associated with marked symptom improvement in this post-marketing surveillance study.
- Effect
- Benefit
- Duration
- 4–6 weeks
- Dose
- 1800 mg/day
- Population
- Children/adolescents
- Participants
- 101
RCTComparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study2000n=30
A pilot randomized trial showing similar antidepressant effects between Hypericum extract LI 160 and sertraline in mild to moderate depression. A 7-week manufacturer-funded study was performed in 30 patients with mild to moderate depression. Participants were given St. John’s wort (600 mg/day) or sertraline (50 mg/day) for one week. Then, they were given an increased dose of SJW (900 mg/day) and sertraline (75 mg/day) for 6 weeks. Whilst similar improvements were found for SJW and sertraline, the differences were not statistically significant. SJW clinical response rates (defined as >= 50% reduction in HAM-D scores) were 47% compared to 40% in patients receiving sertraline. This study was funded by Lichtwer Pharma AG, a German herbal supplement company.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 600 mg/day
- Population
- Adults
- Participants
- 30
- Avg age
- ~46
RCTComparison of St John's wort and imipramine for treating depression: randomised controlled trial2000n=324
In 324 outpatients with mild to moderate depression, Hypericum extract ZE 117 250 mg twice daily for 6 weeks matched imipramine 75 mg twice daily on Hamilton depression scores, with fewer adverse events (39% vs 63%) and withdrawals.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 150 mg/day
- Population
- Patients with mild to moderate depression
- Participants
- 324
RCTEquivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression2000n=240
In mild-to-moderate depression, Hypericum Ze 117 was equivalent to fluoxetine on HAM-D improvement over 6 weeks in this randomized double-blind trial.
- Effect
- Benefit
- Duration
- 6 weeks
- Population
- Patients with mild to moderate depression
- Participants
- 240
RCTComparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine1999n=77
A randomized comparison showing that St. John’s wort extract LoHyp-57 demonstrated antidepressant effects similar to fluoxetine in mild to moderate depression. A 6-week study of 149 elderly patients (129 females) found that St. John’s wort (800 mg/day, LoHyp-57) was as effective as 20 mg fluoxetine for mild to moderate depression. Hamilton Depression Scale scores fell in those taking SJW from 16.6 to 7.91 and in those taking fluoxetine from 17.18 to 8.11. SJW resulted in fewer side effects and greater adherence compared to fluoxetine.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 800 mg/day
- Population
- Older adults
- Participants
- 77
RCTClinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities1998
In 147 outpatients with mild or moderate depression, two St John's wort extracts improved HAM-D scores similarly over 6 weeks, with hyperforin content correlating with response.
- Effect
- Benefit
- Duration
- 42 days
- Dose
- 3×1 tablet Hypericum extract/day
- Population
- Adults
RCTHypericum treatment of mild–moderate depression in a placebo–controlled study. A prospective, double–blind, randomized, placebo–controlled, multicentre study1998
A prospective double-blind trial evaluated Hypericum for mild-to-moderate depression; published abstract details on participants, dose, and outcomes were not available.
- Effect
- Benefit
RCTSt. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy1998
In 147 outpatients with mild or moderate depression, St John's wort extract was more effective than placebo on HAM-D scores over 6 weeks in this multicenter RCT.
- Effect
- Benefit
- Duration
- 42 days
- Dose
- 3×1 tablet Hypericum extract/day
- Population
- Adults
RCTEffectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study1994n=102
In 102 depressed patients over 6 weeks, standardized hypericum LI 160 matched maprotiline for antidepressant efficacy with better tolerability.
- Effect
- Benefit
- Duration
- 4 weeks
- Dose
- 900 mg/day Hypericum
- Population
- Depression patients
- Participants
- 102
Acetyl-L-CarnitineView supplement →
Consider purchase·★★★★★
How we scored this▸
- Taking acetyl-L-carnitine by mouth may help reduce symptoms of depression and dysthymia, with effects similar to common antidepressant medications.
- Studies done mainly in Europe show that taking 1 to 4 grams daily for 3 to 24 weeks can moderately improve depression symptoms, especially in older adults.
- Higher doses seem to work better.
- How long the treatment lasts and how severe symptoms are at the start do not seem to change the results.
Browse 4 studies·1 meta-analysis
MetaAcetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis2018n=791
A meta-analysis of ALC trials (791 participants) found acetyl-L-carnitine supplementation reduced depressive symptoms versus control with moderate effect sizes.
- Effect
- Benefit
- Population
- Older adults
- Participants
- 791
- Avg age
- 54±0
RCTEffect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders1990n=60
Sixty patients aged 60–80 years with dysthymic disorders (DSM III) were randomized to acetyl-L-carnitine 3 g/day orally or placebo. After a 1-week washout, participants were assessed with the Hamilton Rating Scale for Depression, Beck Depression Inventory, and Sandoz Clinical Assessment–Geriatric at baseline and after 30 and 60 days. Acetyl-L-carnitine significantly reduced depressive symptom severity versus placebo (p<0.002) and significantly improved quality-of-life items (p<0.0027).
- Effect
- Benefit
- Dose
- 3 g/day
- Population
- Older adults
- Participants
- 60
- Ages
- 60–80
RCTEvaluation of the effects of L-acetylcarnitine on senile patients suffering from depression1990n=28
Twenty-eight patients aged 70–80 years with depression (DSM III R, cat. 300.40) were randomized to two groups of 14: L-acetylcarnitine 500 mg three times daily or placebo. Outcomes were assessed with the Hamilton Rating Scale for Depression, Beck Depression Inventory, Sandoz Clinical Assessment–Geriatric, and clinical global impression. L-acetylcarnitine was effective in reducing depressive symptoms, with decreased Hamilton and Beck scores and beneficial effects on behavioural aspects.
- Effect
- Benefit
- Dose
- 500 mg 3×/day
- Population
- Older adults
- Participants
- 28
- Ages
- 70–80
Controlled trialL-acetylcarnitine in depressed elderly subjects. A cross-over study vs placebo1987
An open crossover trial in 24 hospitalized geriatric patients with depression found acetylcarnitine for 1 month significantly reduced depressive symptoms, especially in patients with more severe baseline scores.
- Effect
- Benefit
- Duration
- 1 month
- Population
- Older adults
SAMeView supplement →
Consider purchase·★★★★★
How we scored this▸
- Short-term studies suggest that SAMe supplements may help improve symptoms of depression in adults, but the evidence is mixed.
- Some research shows benefits, while others do not.
- SAMe does not seem to boost the effects of prescription antidepressants when taken together.
- It works about as well as some antidepressants when used alone.
- Doctors generally do not recommend SAMe as the only treatment but may suggest it as an add-on.
- More long-term research is needed to understand how well SAMe works over time.
Browse 8 studies·3 meta-analyses
MetaEfficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis2024n=2,183
A meta-analysis of 23 trials (2,183 patients) found SAMe reduced depression scores and had similar acceptability to placebo or antidepressants.
- Effect
- Benefit
- Population
- Depression patients
- Participants
- 2,183
MetaS-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis2024n=1,522
A meta-analysis found SAMe as adjunct or monotherapy reduced depressive symptoms versus placebo, with combination antidepressant therapy showing added benefit.
- Effect
- No Benefit
- Dose
- 200–3200 mg/day SAMe
- Population
- Depression patients
- Participants
- 1,522
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
MetaS-adenosyl methionine (SAMe) for depression in adults2016n=619
A Cochrane review found SAMe may reduce depressive symptoms versus placebo and be similar to some antidepressants, though evidence quality was moderate.
- Effect
- No Benefit
- Population
- Adults
- Participants
- 619
RCTS-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response2014n=144
In 144 adults with major depression, SAMe 1600–3200 mg/day did not significantly outperform escitalopram or placebo on primary depression outcomes in this substudy.
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 1600 mg/day
- Population
- Adults
- Participants
- 144
RCTEffects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder2011
A secondary analysis of 46 SSRI non-responders with major depression in a 6-week adjunctive SAMe RCT found greater improvement in recall (p=0.04) and a trend for word-finding vs placebo.
- Effect
- Benefit
- Population
- Depression patients
RCTS-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial2010
A 6-week double-blind RCT in 73 SSRI non-responders with major depression found adjunctive SAMe 1600 mg/day raised HAM-D response (36.1% vs 17.6%) and remission (25.8% vs 11.7%) vs placebo.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 1600 mg/day
- Population
- Patients with depression
S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease2003
A review concluded SAMe has evidence for depression, osteoarthritis, and liver disease, though indication-specific trial quality varies.
ZincView supplement →
Consider purchase·★★★★★
How we scored this▸
- Taking zinc by mouth along with antidepressant medicine may help improve mood and reduce depression symptoms.
- Studies have found that people who eat more zinc or have higher blood zinc levels have about a 28% lower risk of developing depression.
- Research combining zinc with antidepressants shows that adding 7 to 25 mg of zinc daily for up to 12 weeks can modestly improve symptoms compared with antidepressants alone.
- In one study, adding zinc to imipramine helped people whose depression hadn’t improved with medicine alone.
- Some experts suggest 25 mg of zinc daily, preferably in chelated or picolinate form.
Browse 8 studies·5 meta-analyses
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
MetaZinc supplementation combined with antidepressant drugs for treatment of patients with depression: a systematic review and meta-analysis2021n=60
A meta-analysis of five RCTs found zinc supplementation with antidepressants reduced depressive symptoms by a mean SMD of −0.36 versus placebo, with larger effects (SMD −0.61) in participants aged 40 years or older.
- Effect
- Benefit
- Population
- Adults
- Participants
- 60
- Ages
- 18+
MetaZinc in depression: From development to treatment: A comparative/ dose response meta-analysis of observational studies and randomized controlled trials2020
A meta-analysis of observational and RCT data found higher dietary zinc linked to lower depression risk and that zinc supplementation significantly lowered depressive symptom scores in depressed patients (WMD −4.15 points).
- Effect
- Benefit
- Population
- Depression patients
MetaDietary zinc and iron intake and risk of depression: A meta-analysis2017
A meta-analysis of nine zinc and three iron intake studies found highest versus lowest dietary zinc associated with 33% lower depression risk (RR 0.67) and dietary iron with 43% lower risk.
- Effect
- Benefit
RCTEffects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression2014n=20
In 44 adults with major depression, 25 mg/day elemental zinc added to SSRI antidepressants for 12 weeks significantly reduced Hamilton Depression Rating Scale scores versus placebo without changing IL-6, TNF-α, or BDNF levels.
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 25 mg/day
- Population
- Depression patients
- Participants
- 20
- Ages
- 18–55
MetaZinc in depression: a meta-analysis2013n=2,447
A meta-analysis of 17 studies in 1,643 depressed versus 804 control subjects found serum zinc approximately 1.85 µmol/L lower in depression, with greater deficits linked to higher symptom severity.
- Population
- Depression patients
- Participants
- 2,447
RCTZinc supplementation augments efficacy of imipramine in treatment resistant patients: a double blind, placebo-controlled study2009n=30
In 60 depressed adults on imipramine (~140 mg/day), 25 mg/day zinc for 12 weeks significantly improved outcomes in treatment-resistant but not treatment-naive patients versus placebo.
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 140 mg/day
- Population
- Depression patients
- Participants
- 30
- Ages
- 18–55
RCTEffect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study2003n=14
A pilot RCT in unipolar depression found 25 mg/day zinc plus standard antidepressants significantly reduced Hamilton and Beck depression scores at 6 and 12 weeks versus placebo.
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 25 mg/day
- Population
- Depression patients
- Participants
- 14
CurcuminView supplement →
Consider purchase·★★★★★
How we scored this▸
- Curcumin may help treat depression, especially in middle-aged adults, when taken at doses of about 1 gram daily for at least 6 weeks.
- Studies show it works best when used with regular antidepressants and may be less helpful alone in mild depression.
- One study found that curcumin alone was about as effective as fluoxetine at 1 gram daily, and taking both together worked even better.
- A long-term study found that taking 750 mg twice daily for a year modestly lowered depression symptoms.
- Some experts support using curcumin for mild to moderate depression, either by itself or with other treatments.
Browse 10 studies·3 meta-analyses
RCTCurcumin Reduces Depression in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial2024n=227
A 12-month study including 227 obese adults with type 2 diabetes found that 1.5 g/day curcumin significantly reduced depression severity (-20.4%) compared to placebo (-2.63%). The curcumin group experienced higher levels of serotonin and reduced markers of insulin resistance (HOMA-IR), malondialdehyde and levels of pro-inflammatory biomarkers IL-1B, IL-6 and TNF-alpha. The group taking curcumin had improved total antioxidant status, measured through increases in superoxide dismutase and glutathione peroxidase activity. [10176]
- Effect
- Benefit
- Duration
- 12 months
- Dose
- 1.5 g/day
- Population
- Adults
- Participants
- 227
- Ages
- 35+
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
MetaThe efficacy and acceptability of curcumin for the treatment of depression or depressive symptoms: A systematic review and meta-analysis2021n=594
A meta-analysis of 10 depression trials in 594 patients found curcumin reduced depressive symptoms (SMD −0.32) and improved response rates (OR 3.20) versus control.
- Effect
- Benefit
- Population
- Patients with depression
- Participants
- 594
RCTAdd-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study2018n=61
A study including 61 patients (aged 18 to 63 yrs) with major depression found that curcumin (500 to 1500 mg/day, increasing by 250 mg/week then maintained at 1500 mg/day) may improve symptoms of major depression in those already taking a stable dose of a traditional antidepressant (fluoxetine, SSRIs, sertraline, mianserine and trazodone), and/or mood stabliser (sodium valproate or lamotrigine) for at least 8 weeks prior to the initiation of the study. Higher doses of 1500 mg/day and longer treatment durations appeared to confer greater benefits and were well-tolerated. Curcumin was more effective in men compared to women. At both dosage completion at 12 weeks and 16 weeks follow up, curcumin was more effective than placebo in improving depressive symptoms. [10177]
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 1500 mg/day
- Population
- Depression patients
- Participants
- 61
- Ages
- 18–63
RCTEfficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study2017n=123
A 12-week study of 123 patients with major depressive disorder found that doses of 500 and 1000 mg/day curcumin or 500 mg/day curcumin + saffron reduced anxiety and depression compared to placebo. [10178]
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 1000 mg/day
- Population
- Adults
- Participants
- 123
MetaThe Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials2016
A mini meta-analysis of major depression trials found curcumin reduced depression scores (SMD −0.34), with larger effects at higher doses and longer durations.
- Effect
- Benefit
- Population
- Depression patients
RCTAn investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial2015n=30
A study of 30 obese participants found that 1 g/day curcumin reduced anxiety but had no effect on depressive symptoms. [10180]
- Effect
- No Benefit
- Duration
- 30 days
- Dose
- 1 g/day
- Population
- Overweight adults
- Participants
- 30
RCTChronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study2015n=108
A study of 108 male adults aged between 31 and 59 in China found that 2 g/day curcumin taken for 6 weeks reduced inflammatory cytokines IL-1β and tumor necrosis factor α, increased brain plasma BDNF and reduced cortisol. This presented as reductions in Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores. [10179]
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 2 g/day
- Population
- Adults
- Participants
- 108
- Ages
- 31–59
RCTCurcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study2014n=56
A study found that curcumin improved symptoms of major depressive disorder after 8 weeks but not 4 weeks. [10181]
- Effect
- Benefit
- Duration
- 8 weeks
- Dose
- 500 mg 2×/day
- Population
- Adults
- Participants
- 56
RCTEfficacy and safety of curcumin in major depressive disorder: a randomized controlled trial2014n=60
In 60 major depression patients, 1000 mg/day curcumin for 6 weeks was as effective as fluoxetine 20 mg on HAM-D17 scores, with comparable response rates across groups.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 1000 mg/day
- Population
- Healthy adults
- Participants
- 60
Vitamin B9 (Folate)View supplement →
Consider purchase·★★★★★
How we scored this▸
- Taking folic acid along with usual antidepressants may help reduce depression symptoms a little.
- People with low folate levels, especially women, are more likely to be depressed.
- Studies show that folic acid supplements with antidepressant medicine help more people improve and get better than antidepressants alone.
- Taking folic acid by itself does not work as a replacement for antidepressants.
- In young people at risk for mood problems, folic acid did not stop depression but may delay it.
- Some research suggests folic acid use may lower the chance of suicide, but this is unclear.
Browse 12 studies·3 meta-analyses
RCTAssociation Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults2022n=586
A randomized trial of 586 women found that the same analysis for the negative control, cyanocobalamin, found no association with suicide attempt (HR, 1.01; 95% CI, 0.80-1.27).
- Effect
- Benefit
- Duration
- 24 months
- Dose
- 1 mg/day
- Population
- Women
- Participants
- 586
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
MetaFolate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis2021
A meta-analysis of 5 studies found that adjunct therapy with l-Methylfolate or folic acid improves depression scale scores, patient response, and remission rates.
- Effect
- Benefit
- Population
- Adults
RCTFolic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial2014n=112
A randomized trial of 112 (ages 14–24) found that 2.5 mg/day for 14–24 years although long term folic acid supplementation was well tolerated, with high levels of adherence, there was no evidence that it reduced the incidence of mood disorder compared to those taking placebo.
- Effect
- No Benefit
- Dose
- 2.5 mg/day
- Participants
- 112
- Ages
- 14–24
MetaIs low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity2007n=315
A meta-analysis of 315 studies found that this relationship remained after adjustment for potential confounding (OR)(pooled adjusted) = 1.42; 95% CI 1.10 to 1.83).
- Effect
- No Benefit
- Participants
- 315
ObservationalRelationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample2005
An observational study in older adults found that being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level.
- Effect
- Benefit
- Population
- Older adults
- Ages
- 60–64
ObservationalPlasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification2004n=627
An observational study of 627 older adults found that the adjusted OR for high CES-D score in women in the lowest tertile of folate was 2.04 (95% CI: 1.38, 3.02), which was significantly different from that in women in the highest tertile of folate (P < 0.001).
- Population
- Older adults
- Participants
- 627
- Ages
- ≥60
Systematic reviewFolate for depressive disorders2003n=247
A systematic review of 247 studies found that fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at ten weeks (relative risk (RR) 0.47, 95% CI 0.24 to 0.92) The number needed to treat with folate for one additional person to experience a 50% reduction on this scale was 5 (95%.
- Effect
- Benefit
- Population
- Adults
- Participants
- 247
RCTEnhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial2000n=127
A randomized trial of 127 patients with major depressive disorder found that 500 µg folic acid/day plasma homocysteine was significantly decreased in women by 20.6%, but there was no significant change in men.
- Effect
- Benefit
- Dose
- 500 µg folic acid/day
- Population
- Patients with major depressive disorder
- Participants
- 127
RCTOral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study1993n=49
A randomized trial of 49 older adults found that 50 mg/day for 4 weeks 5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic.
- Effect
- Benefit
- Duration
- 4 weeks
- Dose
- 50 mg/day
- Population
- Older adults
- Participants
- 49
RCTEnhancement of recovery from psychiatric illness by methylfolate1990n=123
A randomized trial of 123 patients with major depressive disorder found that 15 mg/day for 6 months among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery.
- Effect
- Benefit
- Duration
- 6 months
- Dose
- 15 mg/day
- Population
- Patients with major depressive disorder
- Participants
- 123
Controlled trialFolic acid enhances lithium prophylaxis1986n=75
A study of 75 patients with mood disorders found that patients who had their plasma folate increased to 13 ng/ml or above had a 40% reduction in their affective morbidity.
- Effect
- Benefit
- Population
- Patients With Mood Disorders
- Participants
- 75
L-CarnitineView supplement →
Consider purchase·★★★★★
How we scored this▸
- There is not enough evidence to determine if L-carnitine has any benefit for depression.
Browse 2 studies·1 meta-analysis
MetaAcetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis2018n=791
A meta-analysis of ALC trials (791 participants) found acetyl-L-carnitine supplementation reduced depressive symptoms versus control with moderate effect sizes.
- Effect
- Benefit
- Population
- Older adults
- Participants
- 791
- Avg age
- 54±0
Acetyl-L-Carnitine in Aged Subjects with Major Depression: Clinical Efficacy and Effects on the Circadian Rhythm of Cortisol2010
In older adults with major depression, acetyl-L-carnitine improved depressive symptoms and normalized disrupted cortisol circadian rhythms versus baseline.
- Effect
- Benefit
- Population
- Older adults
AyahuascaView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Most experts currently say the evidence for ayahuasca in treating difficult depression is limited.
- Small studies suggest that ayahuasca taken by mouth might help people with moderate to severe depression that doesn’t respond to usual treatments.
- One controlled study found that a single dose improved depression symptoms after one week, with more people responding compared to a placebo.
- Other small studies showed improvement starting within 80 minutes and lasting up to three weeks.
- Some evidence also suggests ayahuasca might reduce suicidal thoughts.
- However, most studies are small and lack comparison groups, so more research is needed.
Browse 13 studies·3 meta-analyses
MetaEfficacy and safety of four psychedelic-assisted therapies for adults with symptoms of depression, anxiety, and posttraumatic stress disorder: A systematic review and meta-analysis2025
A meta-analysis of 18 psychedelic trials found psilocybin and MDMA showed large depression symptom reductions and were well tolerated, though evidence certainty was low to very low.
- Population
- Adults
ObservationalEffects of psychedelics in older adults: A prospective cohort study2024
A prospective cohort of 62 older and 62 matched younger adults found guided psychedelic sessions improved well-being similarly across age groups, with relational factors more predictive in older adults.
- Effect
- Benefit
- Population
- Older adults
- Ages
- 60+
Systematic reviewThe Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder2023
A CANMAT task force review rated psilocybin and ayahuasca as level 3 evidence for major depression, concluding psychedelics remain experimental and should mainly be used in clinical trials.
- Effect
- Benefit
MetaAssessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis2022
A meta-analysis of 9 psychedelic clinical trials found large effect sizes for anxiety (d=1.26) and depression (d=1.38), with greater benefit from multiple-dose versus single-dose protocols.
- Effect
- Benefit
- Population
- Anxiety and depression patients
MetaClassic serotonergic psychedelics for mood and depressive symptoms: A meta-analysis of mood disorder patients and healthy participants2021n=8
A meta-analysis of 12 psychedelic RCTs (257 participants) found moderate to large mood and depression improvements with psilocybin, LSD, and ayahuasca versus placebo across acute and longer-term follow-up.
- Effect
- Benefit
- Duration
- 16–60 days
- Population
- Healthy adults
- Participants
- 8
MetaLysergic acid diethylamide, psilocybin and dimethyltryptamine in depression treatment: A systematic review2021
A systematic review of 10 studies concluded psilocybin and DMT show significant associations with reduced depression symptoms, but further controlled trials are needed.
- Effect
- Benefit
Open-labelRapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: Results from an open-label trial2021n=17
A secondary analysis of an open-label trial in 17 recurrent MDD patients found a single ayahuasca dose produced large acute and sustained suicidality reductions over 21 days in 15 patients with baseline suicidality.
- Effect
- Benefit
- Duration
- 21 days
- Population
- Patients with depression
- Participants
- 17
ObservationalEffects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination2020n=40
In 40 first-time ayahuasca users, depression and psychopathology scores fell at 1 and 6 months, and 23 long-term users had lower depression and higher quality of life than naïve peers.
- Effect
- Benefit
- Population
- Women
- Participants
- 40
RCTRapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: A randomized placebo-controlled trial2019n=29
A double-blind RCT of 29 treatment-resistant depression patients found single-dose ayahuasca lowered MADRS scores versus placebo at days 1, 2, and 7, with 64% response at day 7 versus 27% on placebo.
- Effect
- Benefit
- Population
- Patients with depression
- Participants
- 29
- Ages
- 18–60
RCTThe impact of ayahuasca on suicidality: Results from a randomized controlled trial2019n=15
Secondary analyses of an ayahuasca RCT in 29 treatment-resistant depression patients found medium between-group and large within-group effect sizes for suicidality reductions over 7 days.
- Effect
- Benefit
- Duration
- 7 days
- Dose
- 1 ml/kg
- Population
- Depression patients
- Participants
- 15
- Ages
- 18–60
ObservationalSub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution2018n=57
In 57 ayahuasca ceremony attendants, depression and stress fell after the ceremony and remained lower at 4 weeks, with improvements linked to ego-dissolution intensity rather than prior experience.
- Effect
- Benefit
- Duration
- 4 weeks
- Participants
- 57
Open-labelAntidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A SPECT study2016n=17
An open-label trial of 17 recurrent depression patients given 2.2 mL/kg ayahuasca found rapid antidepressant effects through 21 days and increased perfusion in mood-related brain regions on SPECT.
- Effect
- Benefit
- Dose
- 2.2 mL/kg ayahuasca
- Population
- Patients with depression
- Participants
- 17
Open-labelAntidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A preliminary report2015
A preliminary open-label study of six depression patients found a single ayahuasca dose reduced depressive scores up to 82% over 21 days without inducing mania.
- Effect
- Benefit
- Duration
- 21 days
- Population
- Patients with depression
Green TeaView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Research suggests drinking a lot of green tea each day is linked to a lower chance of feeling depressed.
- In Japan, people who drink 4 or more cups daily have about half the risk of depression compared to those who drink only 1 cup or less.
- Studies in China show even drinking 1 cup daily lowers depression risk over time.
- Drinking less than 1 cup daily does not seem to help.
- More research is needed to confirm these benefits and understand how green tea affects mood.
Browse 4 studies·1 meta-analysis
MetaGreen Tea Consumption and Risk of Depression Symptoms: A Systematic Review and Meta-Analysis of Observational Studies2022
A meta-analysis found higher green tea consumption associated with lower depression risk in observational studies, with stronger associations in Asian cohorts.
- Effect
- Benefit
- Population
- Adults
ObservationalGreen tea consumption and risk of depressive symptoms: Results from the TCLSIH Cohort Study2022n=7,524
In a prospective cohort of 7524 adults followed up to 5 years, higher green tea consumption was associated with lower depressive symptoms versus lower intake.
- Effect
- Benefit
- Population
- Adults
- Participants
- 7,524
- Ages
- 25–90
ObservationalGreen tea and coffee consumption is inversely associated with depressive symptoms in a Japanese working population2014n=537
In a cross-sectional study of 537 Japanese workers (ages 20–68), higher green tea and coffee consumption were inversely associated with depressive symptoms.
- Effect
- Benefit
- Population
- Adults
- Participants
- 537
- Ages
- 20–68
ObservationalGreen tea consumption is associated with depressive symptoms in the elderly2009
In a cross-sectional study of 1058 elderly Japanese, higher green tea consumption was associated with lower prevalence of depressive symptoms.
- Effect
- Benefit
- Population
- Older adults
- Ages
- ≥70
RhodiolaView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Medical guidelines say rhodiola is not currently recommended either on its own or with other medicines for major depression because research results are inconsistent.
- In one study, taking a specific rhodiola extract (340 mg once or twice a day) for six weeks helped improve symptoms of mild-to-moderate depression compared with a placebo, especially mood, emotional stability, sleep, and physical complaints, but it didn’t boost self-esteem.
- Another small study showed that taking a higher dose (600 mg daily) of rhodiola alongside the antidepressant sertraline for 12 weeks worked better than sertraline alone or sertraline with a lower dose of rhodiola (300 mg).
Browse 5 studies·2 meta-analyses
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
RCTAntidepressants effects of Rhodiola capsule combined with sertraline for major depressive disorder: A randomized double-blind placebo-controlled clinical trial2020n=100
A meta-analysis found probiotics reduced C. difficile-associated diarrhea in adults and children, including S. boulardii-containing regimens.
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 0.6 g/day
- Population
- Depression patients
- Participants
- 100
RCTRhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial2015n=57
Removing routine S. boulardii order sets in hospitalized patients was followed by increased hospital-onset C. difficile rates in this before-after analysis.
- Effect
- No Benefit
- Duration
- 12 weeks
- Participants
- 57
RCTRhodiola rosea (SHR-5), Part 2: A standardized extract of Rhodiola rosea is shown to be effective in the treatment of mild to moderate depression2014
Part 2 of the SHR-5 program reported that standardized Rhodiola rosea extract improved mild-to-moderate depression symptoms versus placebo in a clinical trial.
- Effect
- Benefit
RCTClinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression2007n=31
In 57 adults with mild-to-moderate depression, SHR-5 Rhodiola rosea extract reduced HAMD and Beck scores versus placebo over 6 weeks.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 340 mg/day
- Population
- Patients with initial HAMD scores between 21 and 31 were randomi
- Participants
- 31
- Ages
- 18–70
Vitamin DView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is unclear if vitamin D helps treat depression, but some research suggests have modest benefits.
- People with moderate to severe depression or low vitamin D levels may feel some improvement when they take vitamin D for a long time (over a year).
- Studies found that taking vitamin D daily in moderate doses (about 1500 to 4000 IU) can reduce symptoms somewhat.
- However, vitamin D does not seem to prevent depression in healthy people.
- Experts suggest vitamin D supplements for depression mainly in people with low vitamin D or limited sunlight exposure.
Browse 9 studies·6 meta-analyses
MetaThe effect of vitamin D supplementation on primary depression: A meta-analysis2024
A meta-analysis of 18 depression RCTs found vitamin D reduced depressive symptoms overall (SMD −0.15), with significant benefit only when baseline 25(OH)D exceeded 50 nmol/L.
- Effect
- Benefit
- Population
- Adults
RCTEffects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL)2023
In 720 VITAL-DEP participants aged ≥50 given 2000 IU/day vitamin D for 2 years, neither vitamin D nor omega-3 reduced incident depression or mood score change.
- Effect
- No Benefit
- Duration
- 2 years
- Dose
- 2000 IU/day
- Population
- Older adults
MetaEfficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials2023n=1,980
A meta-analysis of 18 depression RCTs (1,980 participants) found vitamin D supplements superior to placebo for reducing depression (SMD −0.49), especially in adults versus adolescents.
- Effect
- Benefit
- Population
- Adults
- Participants
- 1,980
- Avg age
- ~39
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
MetaThe Effect of Vitamin D Supplementation on Symptoms of Depression in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials2022n=161
A meta-analysis of 3 RCTs in 161 type 2 diabetic patients with depression found vitamin D significantly improved depressive symptoms versus placebo (SMD −0.39).
- Effect
- Benefit
- Population
- Diabetic patients
- Participants
- 161
RCTVitamin D Supplementation for the Treatment of Depressive Symptoms in Women with Type 2 Diabetes: A Randomized Clinical Trial2022n=129
In 119 women with type 2 diabetes and depression given 5000 or 50,000 IU/week vitamin D for 6 months, both doses similarly improved CES-D scores over time.
- Effect
- No Benefit
- Duration
- 6 months
- Dose
- 50000 IU/day
- Population
- Women
- Participants
- 129
- Avg age
- ~50
RCTEffect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial2020n=871
In VITAL-DEP (18,353 adults, 2000 IU/day for median 5.3 years), vitamin D did not reduce risk of depression or clinically relevant depressive symptoms versus placebo.
- Effect
- No Benefit
- Dose
- 2000 IU/day
- Population
- Adults
- Participants
- 871
- Avg age
- ~50
MetaVitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws2014
A meta-analysis of 15 depression RCTs without biological flaws found vitamin D improved depression (SMD +0.78); flawed trials showed opposite results.
- Effect
- Benefit
- Dose
- 800 IU/day
MetaVitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials2014n=3,191
A meta-analysis of 7 depression RCTs (3,191 participants) found no overall benefit, though clinically depressed subgroups showed moderate significant improvement (SMD −0.60).
- Effect
- Benefit
- Population
- Depression patients
- Participants
- 3,191
BlueberryView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Research on using blueberry supplements or juice for depression has produced mixed results.
- Some small studies show that blueberries may help reduce depression symptoms in certain groups, including people with specific health conditions or young people with low fruit intake.
- However, one well-conducted study found that blueberries were less effective than a placebo in lowering depression symptoms over several weeks, though they did improve mood and thinking shortly after a single dose.
- Blueberries have natural antioxidants that may protect the brain, but it’s unclear if they are truly helpful for treating depression over time.
- More research is needed.
Browse 4 studies
RCTA biphasic response to blueberry supplementation on depressive symptoms in emerging adults: a double-blind randomized controlled trial2024n=60
In 60 emerging adults with moderate-to-severe depressive symptoms, 6 weeks of wild blueberry supplementation increased depression scores by 5.8 BDI points more than placebo, though a single dose improved positive affect and executive function acutely.
- Effect
- No Benefit
- Duration
- 6 weeks
- Population
- Young adults
- Participants
- 60
- Avg age
- ~20
RCTEffects of Montmorency Tart Cherry and Blueberry Juice on Cardiometabolic and Other Health-Related Outcomes: A Three-Arm Placebo Randomized Controlled Trial2022n=45
In 45 adults over 20 days, 60 mL/day blueberry juice lowered total cholesterol (4.36 to 3.79 mmol/L) and LDL (2.71 to 2.23 mmol/L) versus placebo and improved Beck Depression and anxiety inventory scores.
- Effect
- Benefit
- Duration
- 20 days
- Dose
- 60 mL/day
- Population
- Adults
- Participants
- 45
RCTEffect of 4 weeks daily wild blueberry supplementation on symptoms of depression in adolescents2020
In adolescents with depressive symptoms, 4 weeks of wild blueberry (253 mg anthocyanins/day) significantly reduced self-reported depression versus placebo, without changing anxiety or anhedonia scores.
- Effect
- Benefit
- Duration
- 4 weeks
- Dose
- 253 mg/day
- Population
- Young adults
- Ages
- 12–17
RCTBlueberry Phenolics Reduce Gastrointestinal Infection of Patients with Cerebral Venous Thrombosis by Improving Depressant-Induced Autoimmune Disorder via miR-155-Mediated Brain-Derived Neurotrophic Factor2017n=124
In 124 cerebral venous thrombosis patients with depression, 3 months of blueberry phenolics (10 mg/day) improved depressive symptoms and lipid profiles versus placebo, associated with increased BDNF and miR-155.
- Effect
- Benefit
- Duration
- 3 months
- Dose
- 10 mg/day
- Population
- Patients with depression
- Participants
- 124
CaffeineView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Caffeine consumption is linked to a lower risk of depression, according to multiple studies.
- One large analysis of over 330,000 people found that drinking an extra cup of coffee each day reduced the risk of depression by about 8%.
- Another study confirmed that people with higher depression scores generally consumed less caffeine.
- Interestingly, the strongest protective effect seemed to occur with moderate caffeine intake—around 0 to 90 mg per day.
- This suggests that moderate caffeine consumption may help support mental well-being.
Browse 2 studies·1 meta-analysis
ObservationalCaffeine is negatively associated with depression in patients aged 20 and older2022n=3,263
In 3,263 U.S. adults (ages 20+), higher caffeine intake correlated with lower depression scores on PHQ-9, but the association disappeared above ~90 mg/day in curve-fitting analysis.
- Effect
- Benefit
- Dose
- 90 mg/day
- Population
- Adults
- Participants
- 3,263
- Ages
- 20+
MetaCoffee and caffeine consumption and depression: A meta-analysis of observational studies2016n=330,677
A meta-analysis of 11 observational studies (330,677 participants) found coffee and caffeine intake associated with lower depression risk (pooled RR 0.76 for coffee, 0.72 for caffeine).
- Effect
- Benefit
- Dose
- 68 mg/day
- Participants
- 330,677
L-TryptophanView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- L-tryptophan is not recommended for treating depression because there is little solid evidence that it works, and it may rarely cause serious side effects like serotonin syndrome.
- Some older studies suggest it could help when taken with certain older antidepressants, but it's not clear if it helps with newer medications.
- Taking it together with antidepressants that affect serotonin can be dangerous and result in serotonin syndrome.
Browse 2 studies·1 meta-analysis
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
RCTPotentiation of the antidepressant action of clomipramine by tryptophan1976n=24
In 24 patients with endogenous depression, clomipramine plus tryptophan showed faster mood improvement than clomipramine plus placebo after 12 days.
- Effect
- Benefit
- Duration
- 3 weeks
- Population
- Patients with depressive disorders
- Participants
- 24
SeleniumView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Research shows that people with and without depression have similar selenium levels in their blood.
- Some studies suggest that taking selenium supplements might help reduce symptoms of depression a little, but the research is limited and more studies are needed.
Browse 1 study·1 meta-analysis
MetaThe role of selenium in depression: a systematic review and meta-analysis of human observational and interventional studies2022
A meta-analysis of 15 studies found selenium supplementation reduced depressive symptoms, while observational serum selenium differences between depressed and healthy subjects were inconsistent.
- Effect
- Benefit
- Population
- Healthy adults
Vitamin AView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Population studies show that people who eat more vitamin A tend to have a lower risk of depression.
- Those with depression often have lower vitamin A levels.
- It is not yet clear if taking vitamin A supplements helps with depression.
Browse 1 study·1 meta-analysis
Systematic reviewAssociations of Dietary Vitamin A and Beta-Carotene Intake With Depression. A Meta-Analysis of Observational Studies2022n=100,955
A meta-analysis of 25 observational studies (100,955 participants) found higher dietary vitamin A (RR 0.83) and beta-carotene (RR 0.63) intake were inversely associated with depression.
- Effect
- Benefit
- Participants
- 100,955
Vitamin KView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Research shows that older adults who eat more than 232 micrograms of vitamin K daily have lower chances of feeling symptoms of depression compared to those eating less than 83 micrograms—if they are not taking vitamin D supplements.
- The study found that for every 100 microgram more vitamin K eaten per day, the risk of depressive symptoms dropped by 18%.
- There was no link found in people who take vitamin D. Vitamin K’s effect on clinical depression has not been studied.
Browse 2 studies
Systematic reviewExploring the Link Between Vitamin K and Depression: A Systematic Review2025n=17
In a systematic review of 17 participants, mechanisms including inflammation reduction, oxidative stress modulation, sphingolipid regulation, and vitamin K-dependent protein signaling (e.g., GAS6 and osteocalcin) were discussed based on indirect evidence and require further investigation in depression-specific contexts.
- Population
- Women
- Participants
- 17
ObservationalThe Relationship between Dietary Vitamin K and Depressive Symptoms in Late Adulthood: A Cross-Sectional Analysis from a Large Cohort Study2019n=4,375
In an observational study of 4,375 participants, for 30 days, in conclusion, higher dietary vitamin K intake was significantly associated with a lower presence of depressive symptoms, also after accounting for potential confounders.
- Effect
- Benefit
- Duration
- 30 days
- Population
- Older adults
- Participants
- 4,375
- Ages
- 45–79
AshwagandhaView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is uncertain if ashwagandha helps depression.
- One small study found that taking a specific ashwagandha extract with piperine daily for 3 months reduced depression symptoms, improved sleep and quality of life, and increased serotonin levels compared to placebo.
Browse 1 study
RCTA Standardized Withania somnifera (Linn.) Root Extract with Piperine Alleviates the Symptoms of Anxiety and Depression by Increasing Serotonin Levels: A Double-Blind, Randomized, Placebo-Controlled Study2023n=36
In adults with depression and anxiety, ashwagandha 500 mg plus piperine 5 mg daily for 90 days improved HAM-A, HDRS, sleep, and quality-of-life scores and raised serum serotonin versus placebo.
- Effect
- Benefit
- Duration
- 90 days
- Dose
- 5 mg/day
- Population
- Adults
- Participants
- 36
BacopaView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is unclear whether taking bacopa helps with depression.
- Early research in adults who did not improve after taking citalopram (an antidepressant) found that adding bacopa extract 300 mg twice a day for 4 weeks helped improve depression symptoms more than taking citalopram alone.
Browse 1 study
RCTBacopa monnieri as augmentation therapy in the treatment of anhedonia, preclinical and clinical evaluation2020n=42
Preclinical and clinical work in 42 anhedonic depression patients found 300 mg bacopa twice daily plus citalopram improved depression, pleasure, and behavioral scores more than citalopram alone over 4 weeks.
- Effect
- Benefit
- Duration
- 4 weeks
- Dose
- 300 mg 2×/day
- Population
- Patients with depression
- Participants
- 42
ChromiumView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Chromium supplements might help with certain symptoms of atypical depression, especially by reducing cravings for carbohydrates and improving appetite, mood swings, and sexual drive.
Browse 2 studies
RCTA double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving2005n=41
In 113 adults with atypical depression, 600 µg/day chromium picolinate for 8 weeks did not improve overall depression scores, but reduced carbohydrate craving and appetite in high-craving subgroups.
- Effect
- No Benefit
- Duration
- 8 weeks
- Dose
- 600 mcg/day
- Population
- Adults
- Participants
- 41
- Avg age
- ~46
RCTEffectiveness of chromium in atypical depression: a placebo-controlled trial2003n=15
In 15 adults with atypical depression, 600 µg/day chromium picolinate for 8 weeks improved depressive symptoms in 70% versus 0% on placebo.
- Effect
- Benefit
- Duration
- 8 weeks
- Dose
- 600 mcg/day
- Population
- Patients with atypical depression
- Participants
- 15
InositolView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Clinical guidelines and recent research say there isn’t enough evidence to recommend inositol supplements to treat depression, including bipolar and major depressive disorders, or premenstrual mood symptoms.
- Most studies show that inositol does not improve depression symptoms, whether used alone or along with antidepressants like SSRIs, and some people who feel better while taking it tend to relapse quickly after stopping.
Browse 10 studies·2 meta-analyses
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
- Effect
- No Benefit
MetaA meta-analysis of inositol for depression and anxiety disorders2014n=242
A meta-analysis of 242 participants found inositol may help panic disorder but showed limited evidence for depression and other anxiety disorders.
- Effect
- Benefit
- Population
- Depression patients
- Participants
- 242
RCTTreatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone2006n=66
In 66 patients with treatment-resistant bipolar depression over 8 weeks, inositol, lamotrigine, and risperidone augmentation each produced limited and comparable benefits.
- Effect
- Benefit
- Duration
- 8 weeks
- Population
- Bipolar depression patients
- Participants
- 66
Systematic reviewInositol for depressive disorders2004n=141
A Cochrane review of inositol for depressive disorders (141 participants across trials) found mixed and generally limited evidence for antidepressant efficacy.
- Effect
- No Benefit
- Population
- Patients with depressive disorders
- Participants
- 141
RCTCombination of inositol and serotonin reuptake inhibitors in the treatment of depression1999
In 27 depressed patients over 4 weeks, adding inositol to SSRIs did not improve depression scores versus SSRI plus placebo.
- Effect
- No Benefit
- Duration
- 4 weeks
- Population
- Depression patients
RCTInositol addition does not improve depression in SSRI treatment failures1999
In SSRI non-responders, inositol augmentation did not improve depression versus placebo in a controlled trial.
- Effect
- No Benefit
- Population
- Depression patients
RCTDouble-blind, controlled trial of inositol treatment of depression1995n=15
In 28 depressed patients over 4 weeks, inositol (12 g/day) significantly improved Hamilton Depression scores versus placebo.
- Effect
- Benefit
- Duration
- 4 weeks
- Dose
- 12 g/day
- Population
- Depression patients
- Participants
- 15
RCTFollow-up and relapse analysis of an inositol study of depression1995n=28
Follow-up of 28 depressed patients 10–12 months after inositol treatment found rapid relapse after discontinuation in responders, unlike placebo responders.
- Duration
- 10–12 months
- Dose
- 12 g/day
- Population
- Depression patients
- Participants
- 28
Inositol 6 g daily may be effective in depression but not in schizophrenia1993
Clinical reports suggested 6 g/day inositol may improve depression but showed no benefit in schizophrenia.
- Effect
- Benefit
- Dose
- 6 g/day
RCTThe effects of lithium discontinuation and the non-effect of oral inositol upon thyroid hormones and cortisol in patients with bipolar affective disorder1991
In euthymic bipolar patients, oral inositol did not significantly change thyroid hormones or cortisol during an 11-day trial after lithium discontinuation.
- Effect
- No Benefit
- Duration
- 11 days
- Population
- Bipolar patients
Lion's Mane MushroomView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Lion's mane mushroom (Hericium erinaceus) has natural compounds that may help the brain.
- In a small study, 30 menopausal women ate either lion's mane cookies or placebo cookies for 4 weeks.
- Those who ate lion's mane reported less depression and fewer general complaints like palpitations, poor concentration, irritability, and anxiety compared to the placebo group.
- This suggests lion's mane might support mood and mental well-being, though more research is still needed.
Browse 1 study
RCTReduction of depression and anxiety by 4 weeks Hericium erinaceus intake2010
In adults taking Hericium erinaceus for 4 weeks, depression, anxiety, and sleep quality improved on validated scales versus placebo.
- Effect
- Benefit
- Duration
- 4 weeks
- Population
- Adults
N-Acetyl Cysteine (NAC)View supplement →
Reconsider purchase·★★★★★
How we scored this▸
- A study tested taking N-acetylcysteine (NAC) daily for 12 weeks as an add-on treatment for major depression.
- The main results at 12 weeks showed no clear benefit, but some improvements were seen 4 weeks after stopping NAC.
- Reports from doctors showed people taking NAC felt less depressed, more optimistic, had better relationships, and were less impaired in daily life.
- This suggests NAC might help with depression in ways that are not always measured in regular tests.
Browse 2 studies
RCTEffects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis2023n=21
An 8-week RCT of 21 adults found NAC (600 mg twice daily) reduced oxidative stress markers and improved depression and anxiety scores.
- Effect
- No Benefit
- Duration
- 8 weeks
- Dose
- 600 mg 2×/day
- Population
- Pregnant women
- Participants
- 21
- Ages
- 18–60
RCTThe Impact of N-acetylcysteine on Major Depression: Qualitative Observation and Mixed Methods Analysis of Participant Change during a 12-week Randomised Controlled Trial2023n=2,000
An RCT of 2,000 adults found NAC (2000 mg/day for 12 weeks) significantly reduced depressive symptoms versus placebo.
- Effect
- Benefit
- Duration
- 12 weeks
- Dose
- 2000 mg/day
- Population
- Children
- Participants
- 2,000
- Ages
- 18+
Olive OilView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It’s uncertain if taking olive oil helps with depression.
- In a small study, people with severe depression who took about 2 tablespoons of extra virgin olive oil daily for nearly two months had a modest improvement in symptoms, but there was no benefit for those with milder depression.
Browse 1 study
RCTExtra-Virgin Olive Oil Improves Depression Symptoms Without Affecting Salivary Cortisol and Brain-Derived Neurotrophic Factor in Patients With Major Depression: A Double-Blind Randomized Controlled Trial2022n=73
An RCT of 73 adults with major depression found 25 mL/day extra-virgin olive oil for 52 days reduced depression scores versus sunflower oil, especially in severe depression, without changing cortisol or BDNF.
- Effect
- Benefit
- Duration
- 52 days
- Dose
- 25 mL/day extra-virgin olive oil
- Population
- Adults
- Participants
- 73
TheanineView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- L-theanine, a compound sometimes used to help with stress and sleep, has limited evidence for depression.
- Small studies suggest it might reduce symptoms and improve sleep when taken at night in doses around 200-250 mg, either alone or with an antidepressant.
- But these studies were small and short, and it’s not clear how much benefit you might really get.
- More research is needed.
Browse 3 studies
RCTl-theanine adjunct to sertraline for major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial2023n=50
An RCT of 50 MDD patients found that L-theanine (200 mg/day) adjunct to sertraline significantly improved HDRS scores, with 100% response and higher remission rates at 6 weeks versus placebo.
- Effect
- Benefit
- Dose
- 200 mg/day
- Population
- Patients with major depressive disorder
- Participants
- 50
Open-labelEffects of chronic l-theanine administration in patients with major depressive disorder: an open-label study2017n=20
An open-label study of 20 MDD patients found that 250 mg/day L-theanine for 8 weeks significantly reduced HAMD-21, anxiety, and sleep disturbance scores and improved cognitive function.
- Effect
- Benefit
- Duration
- 8 weeks
- Dose
- 250 mg/day
- Population
- Patients with major depressive disorder
- Participants
- 20
- Avg age
- 41±14.1
Open-labelEffects of chronic l-theanine administration in patients with major depressive disorder: an open-label study2017n=20
An open-label study of 20 MDD patients found that 250 mg/day L-theanine for 8 weeks significantly reduced HAMD-21, anxiety, and sleep disturbance scores and improved cognitive function.
- Effect
- Benefit
- Duration
- 8 weeks
- Dose
- 250 mg/day
- Population
- Patients with major depressive disorder
- Participants
- 20
- Avg age
- 41±14.1
Vitamin B2 (Riboflavin)View supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is uncertain if taking riboflavin (vitamin B2) by mouth helps with depression.
- A large study showed that middle-aged adults who consumed more riboflavin in their diet (over 2.1 mg per day) were slightly less likely to have depression than those who ate less (less than 1.6 mg per day).
- The connection was stronger in men.
- More studies are needed.
Browse 1 study
RCTEffect of White Potatoes on Subjective Appetite, Food Intake, and Glycemic Response in Healthy Older Adults2020n=20
A randomized trial of 20 older adults found that 13.7 g subjective appetite and glycemic response were measured for 120 min using visual analogue scales and capillary blood samples, respectively.
- Dose
- 13.7 g
- Population
- Older adults
- Participants
- 20
- Avg age
- 70.4±0.6
Black TeaView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Some studies suggest that drinking black tea regularly may help lower the risk of depression.
- People who drink more black tea, more often, and for many years tend to have fewer depressive symptoms.
- Socializing while drinking tea might also play a role, but benefits are seen even without social factors.
- These findings mainly come from research in China, so more studies are needed to see if they apply elsewhere.
Browse 2 studies
ObservationalHabitual tea consumption was associated with lower levels of depressive symptoms among older Chinese: Guangzhou Biobank Cohort Study2022n=10,014
In 10,014 older Chinese adults, regular tea consumption was associated with lower Geriatric Depression Scale scores and 49% lower odds of depressive symptoms (GDS ≥8) versus never-drinkers, across green, black, and oolong tea.
- Effect
- Benefit
- Population
- Adults
- Participants
- 10,014
Effects of black tea consumption and caffeine intake on depression risk in black tea consumers2021n=491
In 491 Turkish adults (30.1% depressed by BDI), black tea consumption up to 4 cups/day and caffeine intake of 450–600 mg/day were associated with lower depression risk versus lower intake levels.
- Effect
- Benefit
- Dose
- 600 mg/day
- Population
- Adults
- Participants
- 491
LuteinView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- In adults with heart and metabolic diseases, eating more lutein and zeaxanthin-rich foods was linked to about a 30% lower chance of depression.
- People with depression generally ate less of these nutrients.
- The relationship seems complex, with the lowest depression risk at moderate intakes and possibly higher risk at very high intakes.
- More studies are needed to know if eating more lutein and zeaxanthin prevents depression.
Browse 1 study
ObservationalThe Association between Dietary Carotenoid Intake and Risk of Depression among Patients with Cardiometabolic Disease2023n=8,655
In 8,655 US adults with cardiometabolic disease, higher dietary lutein/zeaxanthin intake was associated with lower depression odds (OR 0.69 for highest vs lowest tertile), with a U-shaped relation for total carotenoids.
- Effect
- Benefit
- Population
- Adults
- Participants
- 8,655
- Ages
- 20+
LycopeneView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- In a study of more than 8,600 people with heart and metabolic conditions, those who ate more lycopene-rich foods, like tomatoes, were less likely to have depression.
- When looking at all carotenoids together, the benefit followed a U-shape—moderate intake was linked with lower risk, but very high amounts were tied to higher risk.
- More research is needed.
Browse 1 study
ObservationalThe Association between Dietary Carotenoid Intake and Risk of Depression among Patients with Cardiometabolic Disease2023n=8,655
In 8,655 US adults with cardiometabolic disease, higher dietary lutein/zeaxanthin intake was associated with lower depression odds (OR 0.69 for highest vs lowest tertile), with a U-shaped relation for total carotenoids.
- Effect
- Benefit
- Population
- Adults
- Participants
- 8,655
- Ages
- 20+
MelatoninView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Most research shows that taking melatonin does not help reduce depression symptoms or prevent depression. Taking 5 to 10 mg before bed for up to 3 months usually does not improve depression in people with bipolar disorder or major depression. Some studies suggest melatonin combined with another medication called buspirone might help a bit, but buspirone is not commonly used to treat depression. There is also some concern melatonin could make depression worse in some people.
- Melatonin’s effects on sleep and body rhythms might help mood in some cases, but overall, the evidence is mixed and not strong. People with depression should talk to their doctor before using melatonin for this purpose.
Browse 7 studies·3 meta-analyses
MetaEffects of melatonin intake on depression and anxiety in postmenopausal women: a systematic review and meta-analysis of randomised controlled trials2024
A meta-analysis of RCTs in postmenopausal women found melatonin supplementation significantly reduced depression and anxiety scores compared with placebo.
- Effect
- Benefit
- Population
- Postmenopausal women
MetaEffects of melatonin supplementation on BDNF concentrations and depression: A systematic review and meta-analysis of randomized controlled trials2022
A meta-analysis of adult RCTs found melatonin did not significantly raise serum BDNF (WMD −5.61) despite some trials reporting lower depression scores.
- Effect
- Benefit
- Dose
- 10 mg/day
- Population
- Adults
MetaThe therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis2014n=486
A meta-analysis of 10 RCTs (n=486) found melatonin had modest antidepressant effects, particularly when depressive symptoms were linked to sleep disturbance.
- Effect
- No Benefit
- Duration
- 2 weeks to 3.5 years
- Dose
- 6 mg/day
- Population
- Adults
- Participants
- 486
RCTAn exploratory study of combination buspirone and melatonin SR in major depressive disorder (MDD): a possible role for neurogenesis in drug discovery2012
An exploratory RCT of buspirone 15 mg plus sustained-release melatonin 3 mg suggested antidepressant activity in major depressive disorder, building on preclinical neurogenesis findings.
- Effect
- Benefit
- Dose
- 3 mg/day
RCTA randomized double-blind placebo-controlled trial of treatment as usual plus exogenous slow-release melatonin (6 mg) or placebo for sleep disturbance and depressed mood2010n=33
In 33 adults with MDD and early-morning waking, 6 mg slow-release melatonin for 4 weeks improved sleep but did not significantly reduce depressive symptoms versus placebo.
- Effect
- No Benefit
- Duration
- 4 weeks
- Dose
- 6 mg
- Population
- Adults
- Participants
- 33
RCTMelatonin for the treatment of sleep disturbances in major depressive disorder1998n=10
In 19 outpatients with MDD on fluoxetine, adding slow-release melatonin for 4 weeks improved Pittsburgh Sleep Quality Index scores but did not accelerate mood improvement versus placebo.
- Effect
- No Benefit
- Duration
- 4 weeks
- Population
- Patients with MDD
- Participants
- 10
Controlled trialNegative effects of melatonin on depression1976
An early study of 6 depressed patients and 2 with Huntington's chorea found melatonin exacerbated dysphoric symptoms, caused weight loss, sleep disruption, and lowered oral temperature.
- Effect
- No Benefit
- Population
- Depression patients
Panax GinsengView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is not known if Panax ginseng helps with depression.
- In a small study of adults whose depression did not improve with usual medicines, taking 2 grams of Panax ginseng daily for 6 weeks helped 39% of people feel better and lowered depression scores by nearly half.
- However, the study had no control group and had other weaknesses, making the results less reliable.
Browse 1 study
ObservationalEffectiveness and Tolerability of Korean Red Ginseng Augmentation in Major Depressive Disorder Patients with Difficult-to-treat in Routine Practice2020n=36
In 36 difficult-to-treat major depression patients, Korean red ginseng augmentation for 6 weeks achieved 39.3% remission by MADRS and reduced MADRS scores 44.4% from baseline.
- Effect
- Benefit
- Duration
- 6 weeks
- Dose
- 2 g/day
- Population
- Patients with depression
- Participants
- 36
PhosphatidylserineView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is not clear if taking phosphatidylserine helps with depression.
- A small study in older adults with depression found that 300 mg daily for 30 days led to small improvements in mood compared with before taking the supplement.
- More research is needed to know if phosphatidylserine is useful for treating depression.
Browse 1 study
Clinical trialEffects of phosphatidylserine therapy in geriatric patients with depressive disorders1990
In 10 elderly women with depression, phosphatidylserine 300 mg/day for 30 days after placebo run-in improved depression, memory, and behavior ratings without changing amine metabolites.
- Effect
- Benefit
- Duration
- 15 days
- Dose
- 300 mg/day
- Population
- Women
ValerianView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It’s unclear if valerian helps with depression.
- One study suggested that taking higher doses of valerian along with St. John’s wort may improve depression symptoms faster, but it’s not clear if valerian alone was responsible.
- Another small study found valerian might improve depression for people on dialysis, but not everyone had depression at the beginning of the study.
Browse 2 studies
RCTThe Effects of Valerian on Sleep Quality, Depression, and State Anxiety in Hemodialysis Patients: A Randomized, Double-blind, Crossover Clinical Trial2021n=20
A crossover RCT of 39 hemodialysis patients found that valerian significantly improved sleep quality, state anxiety, and depression scores versus placebo over two 1-month treatment periods.
- Effect
- Benefit
- Duration
- 1 month
- Population
- Hemodialysis patients
- Participants
- 20
Open-labelTreating depression comorbid with anxiety--results of an open, practice-oriented study with St John's wort WS 5572 and valerian extract in high doses2003
An open-label study found that high-dose St John's wort combined with valerian extract improved depression with comorbid anxiety more quickly than St John's wort alone.
- Effect
- Benefit
- Population
- Patients with depression and anxiety
Vitamin B12View supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is not clear if taking vitamin B12 helps reduce the risk of depression.
- Some studies suggest eating more vitamin B12 might lower depression risk by about 14%, but this may not apply to men.
- One study found older men who ate more vitamin B12 had a much lower risk, while this was not seen in women.
- Low vitamin B12 levels during pregnancy have been linked to higher depression risk.
- However, studies giving elderly people vitamin B12 supplements usually with folic acid did not show they felt less depressed, and most people in these studies were not diagnosed with depression.
Browse 7 studies·4 meta-analyses
MetaAssociations of dietary vitamin B1, vitamin B2, vitamin B6, and vitamin B12 with the risk of depression: a systematic review and meta-analysis2021
A meta-analysis of 18 studies found that the pooled RR (95% CI) of depression for the highest vs the lowest category of dietary vitamin B2 was 0.80 (0.64-0.99) in females and 0.83 (0.67-1.02) in males, for dietary vitamin B6 was 0.71 (0.59-0.86) in females and 0.92 (0.76-1.12) in males, and for dietary vitamin B12.
- Effect
- Benefit
MetaEffects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression2021n=6,276
A meta-analysis of 6276 participants found that in most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain.
- Effect
- No Benefit
- Population
- Adults
- Participants
- 6,276
Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression2020
A study in women found that numerous studies were reviewed, and based on these studies, it was concluded that supplementation of Vitamin B12 early enough can delay the onset of depression and improve the effect of anti-depressants when used in conjunction with Vitamin B12.
- Effect
- Benefit
- Population
- Women
- Ages
- 18–25
MetaA Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and 'At-Risk' Individuals2019n=958
A meta-analysis of 958 participants found that a benefit to depressive symptoms did not reach significance ( n = 568, SMD = 0.15, 95% CI = -0.01, 0.32, p = 0.07), and there was no effect on anxiety ( n = 562, SMD = 0.03, 95% CI = -0.13, 0.20, p = 0.71).
- Effect
- No Benefit
- Population
- Adults
- Participants
- 958
ObservationalRisk of depression in pregnant women with low-normal serum Vitamin B122019n=174
An observational study of 174 women found that in multivariate logistic regression models, pregnant women with low-normal serum Vitamin B12 levels (OR = 3.82, 95% CI [1.10-13.31], p < 0.04) were 3.82 times more likely to experience depression, controlling for sociodemographic characteristics, pre-pregnancy BMI, and the.
- Effect
- Benefit
- Population
- Women
- Participants
- 174
ObservationalIntakes of folate, vitamin B6 and B12 and risk of depression in community-dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging2016n=1,368
An observational study of 1368 adults found that women in the highest tertile of B6 intake from food were 43% less likely to become depressed when adjusting for demographic and health factors (multivariate odds ratio (OR) 0.57, 95% confidence interval (CI) 0.39-0.96), but adjustment for energy intake attenuated the effect.
- Effect
- Benefit
- Duration
- 3 years
- Population
- Adults
- Participants
- 1,368
- Avg age
- 74±4
MetaSystematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression2015
A meta-analysis of 5 studies found that this systematic review aimed to clarify if, compared with placebo, treatment with folate and/or vitamin B12 reduces depression scale scores, increases remission, and prevents the onset of clinically significant symptoms of depression in people at risk.
- Effect
- No Benefit
- Population
- Adults
Vitamin CView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is not clear if taking vitamin C helps treat or prevent depression.
- One small study in children and teens found that taking vitamin C twice a day with an antidepressant (fluoxetine) helped reduce depression symptoms better than the antidepressant alone.
- But another small study in adults found that vitamin C did not improve depression when taken with a different antidepressant (citalopram).
- Some research suggests that women going through menopause who eat more vitamin C have fewer symptoms of depression, but more research is needed.
Browse 7 studies·1 meta-analysis
ObservationalAscorbic acid intake is inversely associated with prevalence of depressive symptoms in US midlife women: A cross-sectional study2022n=3,088
A study of 3,088 midlife women found higher dietary ascorbic acid intake inversely associated with depressive symptoms (OR 0.70, highest vs lowest quartile).
- Effect
- Benefit
- Population
- Women
- Participants
- 3,088
- Ages
- 42–52
MetaClinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
RCTVitamin C supplementation promotes mental vitality in healthy young adults: results from a cross-sectional analysis and a randomized, double-blind, placebo-controlled trial2022n=24
A manufacturer-funded study including 46 healthy subjects with low serum vitamin C levels found that 1000 mg/day vitamin C did not have a significant effect on depression or mood but did improve work absorption (P=0.03) and attention (P=0.03) after 4 weeks. Vitamin C showed a trend towards improving fatigue (P = 0.06). The earlier cross-sectional analysis (n =214, 20-39 yrs) performed in this study found no significant association between serum vitamin C levels and anxiety, depression and mood.
- Effect
- No Benefit
- Duration
- 4 weeks
- Dose
- 1000 mg/day
- Population
- Healthy adults
- Participants
- 24
- Ages
- 20–39
ObservationalDietary Vitamin C and Vitamin C Derived from Vegetables Are Inversely Associated with the Risk of Depressive Symptoms among the General Population2021n=25,895
Cross-sectional analysis of NHANES data (2007-2018) including 25,895 adults showing higher dietary vitamin C intake and vitamin C derived from vegetables were associated with lower odds of depressive symptoms (OR ≈ 0.73 for highest vs lowest intake). Depression was least likely at 126 mg/day intake of vitamin C (U shaped response).
- Effect
- Benefit
- Dose
- 126 mg/day
- Population
- Adults
- Participants
- 25,895
- Ages
- 18–39
RCTKiwiC for Vitality: Results of a Randomized Placebo-Controlled Trial Testing the Effects of Kiwifruit or Vitamin C Tablets on Vitality in Adults with Low Vitamin C Levels2020n=167
A manufacturer-funded (Zespri) study of healthy adults who were not deficient in vitamin C found that 250 mg/day vitamin C did not improve anger, depressive symptoms or anxiety after 4 weeks. However it did lead to a small increase in energy levels. Participants given kiwifruit (2 SunGold kiwifruit/day) had similar but greater improvements in well-being and vitality.
- Effect
- No Benefit
- Dose
- 250 mg/day
- Population
- Healthy adults
- Participants
- 167
- Ages
- 18–35
RCTVitamin C as an adjuvant for treating major depressive disorder and suicidal behavior: a randomized placebo-controlled clinical trial2015n=22
An RCT in 43 adults with major depression found adding vitamin C to citalopram did not improve depression scores versus citalopram plus placebo.
- Effect
- No Benefit
- Duration
- 7 days
- Dose
- 60 mg/day
- Population
- Adults
- Participants
- 22
- Ages
- 18–65
RCTEfficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study2013n=12
A pilot RCT in 24 pediatric depression patients found fluoxetine plus 1,000 mg/day vitamin C improved depression ratings more than fluoxetine alone.
- Effect
- Benefit
- Dose
- 20 mg/day
- Population
- Children
- Participants
- 12
- Ages
- <18
ProbioticsView supplement →
Do not purchase·★★★★★
How we scored this▸
- Probiotics have insufficient evidence for Depression.
Browse 1 study·1 meta-analysis
MetaThe Effect of Probiotics on Obesity with Comorbid Depression: A Systematic Review and Meta-Analysis2024n=488
A meta-analysis of 5 RCTs (n=488) found probiotics did not significantly improve depression scores in obese adults versus placebo (MD 0.08, p=0.82).
- Effect
- No Benefit
- Duration
- 12 weeks
- Population
- Adults
- Participants
- 488
Alpha-Linolenic AcidView supplement →
Do not purchase·★★★★★
How we scored this▸
- Taking alpha-linolenic acid (about 2 grams daily) for over 3 years did not lessen depression symptoms in older people who had a heart attack, based on one study.
- It is uncertain if alpha-linolenic acid helps with depression.
Browse 1 study
RCTEffects of n-3 fatty acids on depressive symptoms and dispositional optimism after myocardial infarction2011n=1,030
40-month RCT in post-MI patients given 2 g/day ALA found neither ALA nor EPA-DHA changed depressive symptoms or dispositional optimism versus placebo.
- Effect
- No Benefit
- Duration
- 40 months
- Dose
- 2 g/day
- Population
- Patients with depression
- Participants
- 1,030
- Ages
- 60–80
QuercetinView supplement →
Do not purchase·★★★★★
How we scored this▸
- It is unclear whether taking quercetin helps with depression after a heart attack.
- A study in people 6 to 8 weeks after a heart attack found that taking 500 mg of quercetin daily for 8 weeks did not improve depression scores compared to placebo.
- Most participants had only mild depression at the start, which may have made it harder to see any benefit.
Browse 1 study
RCTEffects of quercetin supplementation on endothelial dysfunction biomarkers and depression in post-myocardial infarction patients: A double-blind, placebo-controlled, randomized clinical trial2023n=44
In 88 post-MI patients, quercetin 500 mg/day for 8 weeks did not significantly change ICAM-1, VCAM-1, or depression scores versus placebo.
- Effect
- No Benefit
- Duration
- 8 weeks
- Dose
- 500 mg/day
- Population
- Post-myocardial infarction patients
- Participants
- 44
- Ages
- 30–65
SulforaphaneView supplement →
Do not purchase·★★★★★
How we scored this▸
- It is uncertain if taking sulforaphane helps with depression.
- In a small study of people with mild to moderate depression after heart procedures, 30 mg of sulforaphane daily for 6 weeks helped reduce depression scores by half in some people more than placebo.
- But there was no clear difference in the number of people who fully recovered from depression.
Browse 1 study
RCTEfficacy and safety of sulforaphane for treatment of mild to moderate depression in patients with history of cardiac interventions: A randomized, double-blind, placebo-controlled clinical trial2021n=33
In post-PCI or CABG patients with depression, sulforaphane did not significantly improve depressive symptoms versus placebo in this randomized trial.
- Effect
- No Benefit
- Population
- Patients with depression
- Participants
- 33
TyrosineView supplement →
Do not purchase·★★★★★
How we scored this▸
- It is not clear if tyrosine helps depression.
- A small study giving tyrosine for four weeks found no improvement in depression symptoms compared to a placebo.
Browse 1 study
RCTTyrosine for depression: a double-blind trial1990
An RCT of 65 outpatients with major depression found that 100 mg/kg/day L-tyrosine for 4 weeks did not show antidepressant activity versus imipramine or placebo.
- Effect
- No Benefit
- Duration
- 4 weeks
- Dose
- 100 mg/kg
YohimbeView supplement →
Do not purchase·★★★★★
How we scored this▸
- It is not clear if taking yohimbine helps with depression.
- In a small study, taking yohimbine with an antidepressant did not improve depression compared to the antidepressant alone.
- Another small study found that a single dose of yohimbine did not change behaviors related to depression.
Browse 2 studies
RCTApproach-avoidance tendencies in depression and childhood trauma: No effect of noradrenergic stimulation2021n=131
In 131 adults with or without depression and childhood trauma, a single yohimbine dose did not change approach-avoidance tendencies; emotional valence modulated responses but group and treatment effects were absent.
- Effect
- No Benefit
- Dose
- 10 mg/day
- Population
- Women
- Participants
- 131
RCTDesipramine-yohimbine combination treatment of refractory depression. Implications for the beta-adrenergic receptor hypothesis of antidepressant action1986n=11
In 21 treatment-resistant major depression patients, combined desipramine plus yohimbine was not more effective than desipramine alone, providing evidence against the beta-adrenergic receptor hypothesis of antidepressant action.
- Effect
- No Benefit
- Population
- Depression patients
- Participants
- 11
Oleic AcidView supplement →
Do not purchase·★★★★★
How we scored this▸
- It is unclear if taking oleic acid helps with depression.
- One study in women around menopause found that those who ate the most oleic acid had about twice the risk of depression symptoms compared to those who ate the least.
- The effects of oleic acid supplements on depression are unknown.
Browse 1 study
ObservationalAssociations between dietary oleic acid and linoleic acid and depressive symptoms in perimenopausal women: The Study of Women's Health Across the Nation2020n=2,793
In 2793 SWAN perimenopausal women, higher dietary oleic and linoleic acid intake was associated with higher depression scores and greater odds of CES-D ≥16 in adjusted models.
- Effect
- No Benefit
- Population
- Women
- Participants
- 2,793
Evidence visualised
Same ratings as above, aggregated so you can see coverage and imbalance.
| Supplement | DEX | Studies | Meta-analyses | Share |
|---|---|---|---|---|
| St. John's Wort | ★★★★★88% | 28 | 7 | 16% |
| Ayahuasca | ★★★★★56% | 13 | 3 | 7% |
| Vitamin B9 (Folate) | ★★★★★68% | 12 | 3 | 7% |
| Curcumin | ★★★★★68% | 10 | 3 | 6% |
| Inositol | ★★★★★44% | 10 | 2 | 6% |
| Vitamin D | ★★★★★52% | 9 | 6 | 5% |
| SAMe | ★★★★★72% | 8 | 3 | 5% |
| Zinc | ★★★★★72% | 8 | 5 | 5% |
| Melatonin | ★★★★★40% | 7 | 3 | 4% |
| Vitamin B12 | ★★★★★40% | 7 | 4 | 4% |
| Vitamin C | ★★★★★40% | 7 | 1 | 4% |
| Rhodiola | ★★★★★52% | 5 | 2 | 3% |
| Acetyl-L-Carnitine | ★★★★★72% | 4 | 1 | 2% |
| Blueberry | ★★★★★48% | 4 | 0 | 2% |
| Green Tea | ★★★★★52% | 4 | 1 | 2% |
| Theanine | ★★★★★44% | 3 | 0 | 2% |
| Black Tea | ★★★★★40% | 2 | 0 | 1% |
| Caffeine | ★★★★★48% | 2 | 1 | 1% |
| Chromium | ★★★★★44% | 2 | 0 | 1% |
| L-Carnitine | ★★★★★64% | 2 | 1 | 1% |
| L-Tryptophan | ★★★★★48% | 2 | 1 | 1% |
| N-Acetyl Cysteine (NAC) | ★★★★★44% | 2 | 0 | 1% |
| Valerian | ★★★★★40% | 2 | 0 | 1% |
| Vitamin K | ★★★★★48% | 2 | 0 | 1% |
| Yohimbe | ★★★★★32% | 2 | 0 | 1% |
| Alpha-Linolenic Acid | ★★★★★32% | 1 | 0 | <1% |
| Ashwagandha | ★★★★★44% | 1 | 0 | <1% |
| Bacopa | ★★★★★44% | 1 | 0 | <1% |
| Lion's Mane Mushroom | ★★★★★44% | 1 | 0 | <1% |
| Lutein | ★★★★★40% | 1 | 0 | <1% |
| Lycopene | ★★★★★40% | 1 | 0 | <1% |
| Oleic Acid | ★★★★★28% | 1 | 0 | <1% |
| Olive Oil | ★★★★★44% | 1 | 0 | <1% |
| Panax Ginseng | ★★★★★40% | 1 | 0 | <1% |
| Phosphatidylserine | ★★★★★40% | 1 | 0 | <1% |
| Probiotics | ★★★★★36% | 1 | 1 | <1% |
| Quercetin | ★★★★★32% | 1 | 0 | <1% |
| Selenium | ★★★★★48% | 1 | 1 | <1% |
| Sulforaphane | ★★★★★32% | 1 | 0 | <1% |
| Tyrosine | ★★★★★32% | 1 | 0 | <1% |
| Vitamin A | ★★★★★48% | 1 | 1 | <1% |
| Vitamin B2 (Riboflavin) | ★★★★★44% | 1 | 0 | <1% |