Herbs and Supplements for Depression and Low Mood, Ranked by Trial Evidence
The herbs with the best evidence for depression are St John's wort, saffron and EPA-rich omega-3, followed by SAM-e and curcumin. St John's wort matched standard antidepressants for mild to moderate depression across 29 trials in a Cochrane review, saffron at 30 mg/day beat placebo and matched fluoxetine in several small trials, and EPA at 1 to 2 g/day helps as an add-on in diagnosed depression. Rhodiola, vitamin D, L-methylfolate, lavender and probiotics each have narrower or weaker data.
This guide is for adults with mild to moderate low mood, seasonal dips, or diagnosed depression who want an evidence-based addition alongside therapy or medication with their prescriber's knowledge. It is not for severe depression, which these herbs have not been shown to treat, and it is not a reason to stop an antidepressant. If you have thoughts of harming yourself, cannot look after yourself, have stopped eating or sleeping, or hear or see things others do not, get help today: in the US call or text 988, in the UK call 111 or Samaritans on 116 123, or go to the nearest emergency department.
St John's wort interacts with more prescription drugs than almost any other supplement, so read its cautions before you buy. And for all of them: track your mood with a validated scale such as the PHQ-9 and stop what does not move it.
Quick answer
- St John's wort — as effective as standard antidepressants for mild to moderate depression in a 29-trial Cochrane review
- Saffron — 30 mg/day beat placebo and matched fluoxetine in meta-analyses of 8 to 12 small trials
- Omega-3 (EPA-rich) — 1 to 2 g/day of EPA improves diagnosed depression as an add-on across 26 trials
- SAM-e — 800 mg twice daily doubled response rates as an add-on to SSRIs in a 6-week trial
- Curcumin — reduced depression scores versus placebo in meta-analyses of 6 to 10 trials
- L-methylfolate — 15 mg/day doubled response in SSRI non-responders over 60 days
The 10 best herbs and supplements for depression and mood
Ranked by the strength of human evidence. Strong = multiple trials or a meta-analysis. Moderate = a few small trials. Preliminary = early or animal data.
The 2008 Cochrane review of 29 trials (5,489 people) found St John's wort extracts were superior to placebo for mild to moderate major depression and as effective as standard antidepressants, with fewer dropouts from side effects; a 2016 review of 35 trials agreed. The effect was smaller in trials from outside German-speaking countries, and there is no good evidence for severe depression. Trials used 900 mg/day of a standardised extract for 4 to 12 weeks.
- Key evidence
- 2008 Cochrane review of 29 RCTs, n=5,489
- Studied dose
- 300 mg three times daily (900 mg/day) of extract standardised to 0.3% hypericin or 3–5% hyperforin, 6–12 weeks
- Best for
- Mild to moderate depression in someone taking no other regular medication
- Cautions
- Induces CYP3A4 and P-glycoprotein, lowering levels of oral contraceptives (unplanned pregnancies reported), warfarin, digoxin, ciclosporin and tacrolimus (transplant rejection reported), HIV antiretrovirals, some chemotherapy and many other drugs; combined with SSRIs, SNRIs, tramadol or triptans it risks serotonin syndrome. Can trigger mania in bipolar disorder, causes photosensitivity, and must be stopped 2 weeks before anaesthesia.
Meta-analyses pooling 8 to 12 randomised trials find saffron at 30 mg/day reduced depression scores by a large margin versus placebo over 6 to 8 weeks, and matched fluoxetine 20 mg or imipramine 100 mg in head-to-head trials. The trials are small (20 to 60 people), mostly from Iran, and short, so the real effect is probably smaller than the pooled numbers suggest. Still, it is the best-supported herb after St John's wort and has far fewer interactions.
- Key evidence
- 2019 meta-analysis of 11 RCTs (Tóth et al.); 2013 meta-analysis of 5 RCTs
- Studied dose
- 30 mg/day of standardised stigma or petal extract (often 15 mg twice daily), 6–8 weeks
- Best for
- Mild to moderate depression in people who take other medication and cannot use St John's wort
- Cautions
- Safe at 30 mg/day; doses above 1.5 g cause vomiting and dizziness and above 5 g can be fatal. Avoid medicinal doses in pregnancy (uterine stimulant), expect a mild antiplatelet effect, and buy a product that names the extract and dose because adulteration is common.
Omega-3 fish oil (EPA-rich)
Moderate evidenceA 2019 meta-analysis of 26 RCTs (2,160 people) found omega-3 improved depression, but only formulations with at least 60% EPA at 1 to 2 g/day of EPA worked; DHA-dominant products did nothing. The effect was strongest as an add-on to antidepressants in diagnosed major depression, and absent in healthy people taking it to prevent low mood. It is also one of the few options with a clean safety record in pregnancy at these doses.
- Key evidence
- 2019 meta-analysis of 26 RCTs (Liao et al.), n=2,160
- Studied dose
- 1–2 g/day of EPA from a product that is at least 60% EPA, 8–12 weeks
- Best for
- Diagnosed depression alongside an antidepressant, or depression with inflammation or heart risk
- Cautions
- Bleeding risk with anticoagulants above 1 g/day and an atrial fibrillation signal at 4 g/day; stop before surgery. Choose products tested for oxidation, since rancid oil is a common cause of stomach upset.
A 6-week RCT of 73 SSRI non-responders found adding 800 mg SAM-e twice daily doubled the response rate (36% versus 18%) and remission (26% versus 12%). A 2002 US Agency for Healthcare Research and Quality review found SAM-e outperformed placebo and matched tricyclics in older trials, many using injections. A larger 2014 trial found no difference from placebo as a standalone treatment, so the add-on role is better supported than solo use.
- Key evidence
- 2010 RCT of SAM-e augmentation (Papakostas et al.), n=73
- Studied dose
- 400–800 mg twice daily of enteric-coated tablets on an empty stomach, 6–12 weeks
- Best for
- Partial response to an SSRI, under prescriber supervision
- Cautions
- Can precipitate mania in bipolar disorder and has caused serotonin syndrome with antidepressants, so combine only under supervision. Causes anxiety, insomnia and nausea in some people and may worsen Parkinson's symptoms with levodopa.
Meta-analyses of 6 to 10 RCTs (around 400 to 500 people) found curcumin reduced depression scores versus placebo with moderate effect sizes over 6 to 12 weeks. The best single trial gave 500 mg twice daily of a bioavailable form for 8 weeks and found separation from placebo from week 4, mainly in atypical depression. The trials are short and small, but it is low-risk and may suit people whose depression comes with inflammation or pain.
- Key evidence
- 2020 meta-analysis of 10 RCTs (Fusar-Poli et al.)
- Studied dose
- 500–1,000 mg/day of an enhanced-absorption curcumin, 8–12 weeks
- Best for
- Low mood with pain, obesity or raised inflammatory markers
- Cautions
- Antiplatelet effect with anticoagulants; stop before surgery and avoid with gallstones. Rare liver injury has been reported with high-dose enhanced-absorption products; stop if urine darkens or skin itches.
A 12-week RCT of 57 adults with mild to moderate depression compared rhodiola (340 to 680 mg/day) with sertraline and placebo: rhodiola produced a smaller improvement than sertraline but with half the rate of side effects. An earlier 6-week trial of 89 people found 340 to 680 mg/day reduced depression and insomnia scores versus placebo. It is best thought of as a fatigue-and-stress herb that lifts mood rather than an antidepressant.
- Key evidence
- 2015 RCT vs sertraline and placebo (Mao et al.), n=57, 12 weeks
- Studied dose
- 340–680 mg/day of extract standardised to 3% rosavins and 1% salidroside, taken before noon, 6–12 weeks
- Best for
- Low mood with fatigue, burnout or low energy; people who feel sedated by antidepressants
- Cautions
- Stimulating, so it can cause insomnia or jitteriness and may trigger agitation or mania in bipolar disorder. Possible interactions with CYP2C9 and P-glycoprotein substrates; use care with blood-pressure and diabetes drugs.
Low vitamin D is associated with depression, but correcting it only helps when it is actually low. Meta-analyses of trials in depressed people with low levels show a moderate benefit; the 18,353-person VITAL-DEP trial found 2,000 IU/day did nothing to prevent depression in adults with normal levels over 5 years. Test, and if you are under 20 ng/mL (50 nmol/L), supplement; if not, choose something else from this list.
- Key evidence
- VITAL-DEP RCT (JAMA 2020), n=18,353, negative in non-deficient adults; positive meta-analyses in deficient people
- Studied dose
- 1,000–4,000 IU/day of vitamin D3 if deficient, retest after 3 months
- Best for
- Winter low mood with a low blood level, dark skin or little sun exposure
- Cautions
- Do not exceed 4,000 IU/day without monitoring; toxicity causes high calcium, nausea, confusion and kidney stones. Check with your doctor if you have sarcoidosis, hyperparathyroidism or kidney disease, or take thiazide diuretics or digoxin.
Two parallel RCTs in 148 adults with SSRI-resistant depression found adding 15 mg/day of L-methylfolate for 60 days doubled the response rate versus placebo (32% versus 15%). Folic acid itself does not do this: the 475-person FolATED trial of 5 mg/day folic acid added to antidepressants was negative. The benefit is largest in people who are overweight or have raised inflammatory markers or MTHFR variants.
- Key evidence
- 2012 paired RCTs of L-methylfolate augmentation (Papakostas et al.), n=148
- Studied dose
- 15 mg/day of L-methylfolate as an add-on (prescription-strength); 400–800 mcg/day of methylfolate for general support
- Best for
- Partial response to an SSRI, especially with obesity or a known MTHFR variant
- Cautions
- High-dose folate can mask vitamin B12 deficiency and worsen nerve damage, so check B12 first. Interacts with methotrexate, phenytoin and other antifolate drugs; at 15 mg/day use only with a prescriber.
Silexan, a standardised oral lavender oil, has several RCTs in anxiety disorders, and a 10-week trial of 318 people with mixed anxiety and depression found 80 mg/day reduced both anxiety (HAM-A) and depression (MADRS) scores versus placebo. It is not an antidepressant for depression without anxiety, and the evidence is tied to this one preparation rather than lavender tea or aromatherapy.
- Key evidence
- 2016 RCT in mixed anxiety-depression (Kasper et al.), n=318, 10 weeks
- Studied dose
- 80 mg/day of oral Silexan capsule, 6–10 weeks
- Best for
- Low mood tangled up with anxiety, restlessness and poor sleep
- Cautions
- Causes lavender-flavoured burping and nausea in about 1 in 10 people and may add to sedatives and benzodiazepines. Not studied in pregnancy; never swallow essential oil, which is toxic neat.
Probiotics (Lactobacillus and Bifidobacterium strains)
Preliminary evidenceA 2019 meta-analysis of 34 controlled trials found probiotics produced a small reduction in depressive symptoms in people with diagnosed depression and no effect in healthy volunteers. An 8-week RCT of 110 people with major depression found a Lactobacillus helveticus plus Bifidobacterium longum combination lowered Beck Depression Inventory scores versus placebo. Strains, doses and outcomes vary so much between trials that any single product is a bet.
- Key evidence
- 2019 meta-analysis of 34 trials (Liu et al.); 2019 RCT in MDD (Kazemi et al.), n=110
- Studied dose
- A multi-strain product with at least 10 billion CFU/day of named Lactobacillus and Bifidobacterium strains, 8 weeks
- Best for
- Depression with IBS or antibiotic-disrupted gut, as a low-risk add-on
- Cautions
- Avoid in severe immunosuppression, central lines or acute pancreatitis, where bloodstream infections have occurred. Bloating in the first 2 weeks is common; no meaningful drug interactions.
How to choose
- If you take no regular medication and have mild to moderate depression, St John's wort at 900 mg/day has the strongest evidence; confirm with a pharmacist that nothing else you take is affected, including the pill.
- If you take any prescription medication, skip St John's wort and start with saffron at 30 mg/day; it has the next-best data and almost no interactions.
- If you are already on an antidepressant and only partly better, EPA-rich omega-3, SAM-e or L-methylfolate are the add-ons with trial support; discuss them with your prescriber rather than adding them quietly.
- If low energy or burnout dominates, rhodiola in the morning fits better than the sedating options; if anxiety and restlessness dominate, lavender (Silexan) fits better.
- Get vitamin D tested in autumn. If it is low, correcting it is the simplest step; if it is normal, more will not lift mood.
- Rate your mood with the PHQ-9 before you start and every 2 weeks. If a studied dose has not moved the score by 5 points in 8 weeks, stop it and try the next option or talk to your doctor.
What to skip
5-HTP
The Cochrane review found only 2 of 108 trials were good enough to analyse, and they were tiny. 5-HTP raises serotonin directly, so combining it with an antidepressant, tramadol or St John's wort risks serotonin syndrome, and past batches were contaminated with a compound linked to eosinophilia-myalgia syndrome. Weak evidence and real risk is a poor trade.
Zinc as a standalone antidepressant
Small trials of 25 mg/day zinc added to antidepressants showed modest extra benefit, but there is no evidence it treats depression on its own, and more than 40 mg/day long-term causes copper deficiency and anaemia. Fix a deficiency if you have one; do not expect it to replace treatment.
Kava for depression
Kava has trial support for anxiety, not depression, and several countries restricted it after cases of liver failure. Depression with anxiety is better served by lavender or saffron, which have mood data without the liver signal.
Mood gummies and 'happy' blends
Blends typically contain token doses of a dozen ingredients, well below trial amounts, and often include St John's wort without the interaction warnings. Buy single ingredients at studied doses.
Safety and when to see a clinician
- Get help now, not a supplement, if you have thoughts of suicide or self-harm, feel unable to keep yourself safe, cannot eat, sleep or get out of bed, or have symptoms of psychosis. In the US call or text 988 (Suicide and Crisis Lifeline); in the UK call Samaritans on 116 123 or NHS 111; elsewhere go to the nearest emergency department. Severe depression is treatable and none of these herbs is the treatment.
- St John's wort reduces the effect of oral contraceptives, warfarin, digoxin, ciclosporin and tacrolimus, HIV antiretrovirals, some antiepileptics and some cancer drugs by speeding up their clearance; transplant rejections and unplanned pregnancies are documented. Tell every prescriber and pharmacist you take it, and stop it 2 weeks before surgery.
- Serotonin syndrome: combining St John's wort, SAM-e or 5-HTP with an SSRI, SNRI, tramadol, triptans, lithium or MAOIs can cause agitation, racing heart, high temperature, sweating, tremor, muscle twitching and diarrhoea within hours. This is an emergency; do not combine them without a prescriber's agreement.
- Bipolar disorder: St John's wort, SAM-e and rhodiola have all triggered manic episodes. If you have ever had a manic or hypomanic episode, or a family history of bipolar disorder, avoid these three.
- Never stop an antidepressant to switch to a herb without a plan from your prescriber. Abrupt SSRI withdrawal causes symptoms and relapse, and the herb may take 4 to 6 weeks to work, if it works at all.
- Pregnancy and breastfeeding: EPA omega-3 and vitamin D (at tested levels) are the only picks with reassuring safety data. Avoid St John's wort, medicinal-dose saffron, SAM-e and rhodiola, and talk to your midwife or doctor; perinatal depression has specific, effective treatments.
What matters as much as any herb
- Exercise: a Cochrane review and a 2023 meta-analysis of over 200 trials found aerobic exercise and strength training reduce depression about as much as medication for mild to moderate cases. Three 30- to 45-minute sessions a week is the dose; walking counts.
- Psychological therapy: CBT, behavioural activation and interpersonal therapy have effect sizes larger than any herb here and lower relapse rates than medication alone. Online CBT is free through the NHS and inexpensive elsewhere.
- Sleep regularity: insomnia doubles the risk of a depressive episode and treating it with CBT-I improves depression directly. A fixed wake time and morning daylight come before any herb.
- Morning bright light: for seasonal and non-seasonal depression, 10,000 lux for 30 minutes on waking matched fluoxetine in an 8-week trial, at almost no cost and with few side effects.
- Alcohol: it is a depressant, disrupts sleep and blunts every treatment. Cutting back for 4 weeks is often the single biggest mood lift people report.
Frequently asked questions
What is the best natural antidepressant?
St John's wort has the most evidence: as effective as standard antidepressants for mild to moderate depression across 29 trials in a Cochrane review. Its problem is drug interactions, not effectiveness. If you take any other medication, saffron at 30 mg/day is the best-supported alternative. Neither is proven for severe depression.
Can I take St John's wort with antidepressants?
No, not without a prescriber's explicit agreement. Combining it with SSRIs, SNRIs or similar drugs risks serotonin syndrome, which can be life-threatening. It is sometimes used in a supervised cross-taper, but that is the prescriber's decision, not a shelf purchase.
How long do herbs for depression take to work?
Most trials saw separation from placebo at 4 to 6 weeks and ran 6 to 12 weeks; saffron and rhodiola trials often reported improvement by week 2 to 4. If you have felt no change after 8 weeks at a studied dose, switch or talk to your doctor about other options.
Does saffron really work for depression?
In 11 small randomised trials, 30 mg/day of saffron beat placebo and matched fluoxetine. The trials were small, short and mostly from one country, so the true effect is probably smaller than the pooled figures, but it is consistent, cheap at this dose and safe. Make sure the product states 30 mg of actual extract.
Is omega-3 good for depression?
Yes, with conditions: it needs to be EPA-rich (at least 60% EPA), at 1 to 2 g/day of EPA, and it works best added to an antidepressant in diagnosed depression. DHA-heavy products and low doses have not helped, and fish oil does not prevent depression in healthy people.
Which vitamin deficiency causes depression?
Low vitamin D, B12 and folate are each associated with depression, and correcting a true deficiency can lift mood. The key word is deficiency: in people with normal levels, adding more does nothing, as the 18,000-person VITAL-DEP trial showed for vitamin D. Ask for a blood test rather than guessing.
References
- Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database of Systematic Reviews (2008)
- Apaydin EA, Maher AR, Shanman R, et al.. A systematic review of St. John's wort for major depressive disorder. Systematic Reviews (2016)
- Tóth B, Hegyi P, Lantos T, et al.. The efficacy of saffron in the treatment of mild to moderate depression: a meta-analysis. Planta Medica (2019)
- Liao Y, Xie B, Zhang H, et al.. Efficacy of omega-3 PUFAs in depression: a meta-analysis. Translational Psychiatry (2019)
- Papakostas GI, Mischoulon D, Shyu I, et al.. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. American Journal of Psychiatry (2010)
- Papakostas GI, Shelton RC, Zajecka JM, et al.. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. American Journal of Psychiatry (2012)
- Fusar-Poli L, Vozza L, Gabbiadini A, et al.. Curcumin for depression: a meta-analysis. Critical Reviews in Food Science and Nutrition (2020)
- Mao JJ, Xie SX, Zee J, et al.. Rhodiola rosea versus sertraline for major depressive disorder: a randomized placebo-controlled trial. Phytomedicine (2015)
- Okereke OI, Reynolds CF, Mischoulon D, et al.. Effect 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 trial (VITAL-DEP). JAMA (2020)
- Kasper S, Volz HP, Dienel A, Schläfke S. Efficacy of Silexan in mixed anxiety-depression: a randomized, placebo-controlled trial. European Neuropsychopharmacology (2016)
- Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neuroscience and Biobehavioral Reviews (2019)
- National Center for Complementary and Integrative Health. St. John's Wort: Usefulness and SafetyView source
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Ask about depression and moodThis guide is educational and is not medical advice. Herbs and supplements can interact with prescription medicines and are not regulated like drugs. Talk with a clinician or pharmacist before starting anything new, especially if you are pregnant, breastfeeding, have a chronic condition, or take medication.