Condition

Depression

Depression is a mood condition tied to changes in brain chemistry, inflammation, and the brain's ability to form and adjust connections. Among supplements, St. John's wort and omega-3 fish oil have the strongest evidence, and trials found depression symptoms eased with both, to a moderate degree. The fish oil studies were small, and several focused on depression around pregnancy, while severe depression calls for professional care.

Sources: PMID 15684231; PMID 27468236; PMID 18247194

Supplements studied: 34
Graded outcomes: 37
Trials: 67
People studied: 81,835

Evidence by supplement

Strong
Moderate
Limited
Very limited

34 supplements

Fish Oil

Fish Oil: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Depression Symptoms Moderate Improvement	Improves (the measure goes down)	Moderate effect	14 studies	204 people
Studies that measured depression symptoms The effect of omega 3 fatty acid supplementation on premenstrual syndrome and health-related quality of life: a randomized clinical trialJ Psychosom Obstet Gynaecol · PMID 28707491 Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processingAm J Obstet Gynecol · PMID 12748510 Omega-3 fatty acids for a better mental state in working populations - Happy Nurse Project: A 52-week randomized controlled trialJ Psychiatr Res · PMID 29627596 and 11 more on the Fish Oil page
	Postpartum Depression Symptoms	Improves (the measure goes down)		2 studies	93 people
Studies that measured postpartum depression symptoms Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trialBMC Pregnancy Childbirth · PMID 28599630 Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation for prevention and treatment of perinatal depression: a systematic review and meta-analysis of randomized-controlled trials.Nord J Psychiatry · PMID 33190574

St. John's Wort

St. John's Wort: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms Moderate Improvement	Improves (the measure goes down)	Moderate effect	3 studies	3,064 people
Studies that measured depression symptoms St John's wort for major depression.Cochrane Database Syst Rev · PMID 18843608 St John's wort for depression: meta-analysis of randomised controlled trials.Br J Psychiatry · PMID 15684231 A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults.Neuropsychiatr Dis Treat · PMID 27468236

Curcumin

Anxiety Symptoms: improves
Depression Symptoms: improves
Interleukin 1-beta: improves

Curcumin: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Anxiety Symptoms Large Improvement	Improves (the measure goes down)	Large effect		284 people
	Depression Symptoms	Improves (the measure goes down)		9 studies	531 people
Studies that measured depression symptoms Curcumin for depression: a meta-analysisCrit Rev Food Sci Nutr · PMID 31423805 Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled studyJ Affect Disord · PMID 27723543 Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled studyJ Affect Disord · PMID 25046624 and 6 more on the Curcumin page
	Interleukin 1-beta	Improves (the measure goes down)		1 study	108 people
Studies that measured interleukin 1-beta Effects of curcumin on serum inflammatory biomarkers in patients with knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.BMC Complement Med Ther · PMID 40615851
	Cortisol	Improves (the measure goes down)			108 people
	Serum BDNF	Improves (the measure goes up)			108 people
	TNF-Alpha	Improves (the measure goes down)			108 people

Saffron

Anxiety Symptoms: improves
Appetite
Depression Symptoms: improves

Saffron: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Anxiety Symptoms Small Improvement	Improves (the measure goes down)	Small effect	6 studies	656 people
Studies that measured anxiety symptoms Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical TrialPharmacopsychiatry · PMID 27701683 The effects of alcoholic extract of saffron (Crocus satious L.) on mild to moderate comorbid depression-anxiety, sleep quality, and life satisfaction in type 2 diabetes mellitus: A double-blind, randomized and placebo-controlled clinical trialComplement Ther Med · PMID 30477839 A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depressionJ Complement Integr Med · PMID 27101556 and 3 more on the Saffron page
	Appetite No effect		NoneNo effect		74 people
	Depression Symptoms	Improves (the measure goes down)		18 studies	656 people
Studies that measured depression symptoms Crocus Sativus L. (saffron) versus sertraline on symptoms of depression among older people with major depressive disorders-a double-blind, randomized intervention studyPsychiatry Res · PMID 31669837 Saffron improved depression and reduced homocysteine level in patients with major depression: A Randomized, double-blind studyAvicenna J Phytomed · PMID 29387573 Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trialPhytomedicine · PMID 16979327 and 15 more on the Saffron page
	Weight	Improves (the measure goes down)		3 studies	74 people
Studies that measured weight Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy womenNutr Res · PMID 20579522 A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depressionJ Clin Pharm Ther · PMID 31602695 Effects of saffron (Crocus sativus L.) on anthropometric and cardiometabolic indices in overweight and obese patients: A systematic review and meta-analysis of randomized controlled trials.Phytother Res · PMID 35866520
	Sexual Function	Improves (the measure goes up)		2 studies	34 people
Studies that measured sexual function Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled studyHum Psychopharmacol · PMID 23280545 Effects of saffron (Crocus sativus) on sexual dysfunction among men and women: A systematic review and meta-analysis.Avicenna J Phytomed · PMID 31516855
	Sleep Quality	Improves (the measure goes up)		1 study	231 people
	Homocysteine	Improves (the measure goes down)			40 people
	Hot Flash Symptoms	Improves (the measure goes down)			60 people
	Subjective Well-Being	Improves (the measure goes up)			177 people

S-adenosylmethionine

Depression Symptoms: improves
Attention
Osteoarthritis Symptoms: improves

S-adenosylmethionine: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Depression Symptoms Small Improvement	Improves (the measure goes down)	Small effect	6 studies	1,558 people
Studies that measured depression symptoms S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trialMov Disord · PMID 11104210 S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trialAm J Psychiatry · PMID 20595412 S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of responseJ Affect Disord · PMID 24856557 and 3 more on the S-adenosylmethionine page
	Attention No effect		NoneNo effect	1 study	46 people
Studies that measured attention Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorderJ Affect Disord · PMID 21911258
	Osteoarthritis Symptoms	Improves (the measure goes down)		6 studies	1,558 people
Studies that measured osteoarthritis symptoms Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritisJ Fam Pract · PMID 12019049 Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patientsClin Ther · PMID 20110025 Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint diseaseAm J Med · PMID 3318442 and 3 more on the S-adenosylmethionine page
	Itching	Improves (the measure goes up)			1,558 people
	Memory	Improves (the measure goes up)			46 people
	Motivation	Improves (the measure goes up)			46 people

5-HTP

Depression Symptoms: improves

5-HTP: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms Moderate improvement in depression symptoms	Improves (the measure goes down)	Moderate effect	4 studies	133 people
Studies that measured depression symptoms Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis.Nutr Rev · PMID 31504850 Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode.Asian J Psychiatr · PMID 23380314 A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine.Psychopathology · PMID 1909444 and 1 more on the 5-HTP page

Rhodiola Rosea

Depression Symptoms: improves
Insomnia Signs and Symptoms: improves
Subjective Well-Being: improves

Rhodiola Rosea: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Depression Symptoms Small Improvement	Improves (the measure goes down)	Small effect	4 studies	235 people
Studies that measured depression symptoms The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood SymptomsPhytother Res · PMID 26502953 Rhodiola rosea (SHR-5), Part I: a proprietary root extract of Rhodiola rosea is found to be effective in the treatment of stress-related fatigueHolist Nurs Pract · PMID 24503750 Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trialPhytomedicine · PMID 25837277 and 1 more on the Rhodiola Rosea page
	Insomnia Signs and Symptoms	Improves (the measure goes down)		1 study	89 people
Studies that measured insomnia signs and symptoms Rhodiola rosea (SHR-5), Part 2: A standardized extract of Rhodiola rosea is shown to be effective in the treatment of mild to moderate depressionHolist Nurs Pract · PMID 24722617
	Subjective Well-Being	Improves (the measure goes up)			89 people

Coenzyme Q10

Depression Symptoms: improves
Fatigue Symptoms: improves

Coenzyme Q10: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Depression Symptoms Moderate Improvement	Improves (the measure goes down)	Moderate effect	2 studies	137 people
Studies that measured depression symptoms Effects of Coenzyme Q10 Supplementation on Depressive Symptoms and Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.J Clin Psychopharmacol · 2026 · PMID 41294251 Evaluating the Effect of Coenzyme Q10 Augmentation on Treatment of Bipolar Depression: A Double-Blind Controlled Clinical TrialJ Clin Psychopharmacol · PMID 30106880
	Fatigue Symptoms	Improves (the measure goes down)		3 studies	48 people
Studies that measured fatigue symptoms The effects of coenzyme Q10 supplementation on performance during repeated bouts of supramaximal exercise in sedentary menJ Strength Cond Res · PMID 19644406 Antifatigue effects of coenzyme Q10 during physical fatigueNutrition · PMID 18272335 Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trialNutr Neurosci · PMID 25603363

Folic Acid (Vitamin B9)

Depression Symptoms: improves
Schizophrenia symptoms: improves

Folic Acid (Vitamin B9): outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Depression Symptoms Small Improvement	Improves (the measure goes down)	Small effect	2 studies	247 people
Studies that measured depression symptoms Folate for depressive disordersCochrane Database Syst Rev · PMID 12804463 Enhancement of recovery from psychiatric illness by methylfolateLancet · PMID 1974941
	Schizophrenia symptoms	Improves (the measure goes down)		2 studies	123 people
Studies that measured schizophrenia symptoms Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis.Psychopharmacology · PMID 29785555 Folate and vitamin B12 supplementation in patients with schizophrenia and low serum folate level: A 24-week randomized, double-blind, placebo-controlled study.J Formos Med Assoc · PMID 39645464

Vitamin D

Combined Anxiety & Depression: improves
Depression Symptoms: improves

Vitamin D: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Combined Anxiety & Depression Small Improvement	Improves (the measure goes down)	Small effect	1 study	7,534 people
Studies that measured combined anxiety & depression The Effect of Vitamin D Supplement on Negative Emotions: A Systematic Review and Meta-AnalysisDepress Anxiety · PMID 32365423
	Depression Symptoms	Improves (the measure goes down)		5 studies	24,510 people
Studies that measured depression symptoms Efficacy of vitamin D supplementation on depressive symptoms in older patients: a meta-analysis of randomized controlled trials.Front Med · PMID 39450108 Evaluating the effects of vitamin D and vitamin E supplement on premenstrual syndrome: A randomized, double-blind, controlled trialIran J Nurs Midwifery Res · PMID 27095989 Effects of cholecalciferol supplementation on depressive symptoms, C-peptide, serotonin, and neurotrophin-3 in type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial.Narra J · PMID 39816051 and 2 more on the Vitamin D page

Melatonin

Depression Symptoms: improves
Serum BDNF: improves

Melatonin: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Depression Symptoms Small Improvement	Improves (the measure goes down)	Small effect		2,070 people
	Serum BDNF	Improves (the measure goes up)		1 study	2,070 people
Studies that measured serum bdnf Effects of melatonin supplementation on BDNF concentrations and depression: A systematic review and meta-analysis of randomized controlled trials.Behav Brain Res · PMID 36049659

Omega-3 Fatty Acids

Depression Symptoms: improves
Anxiety Symptoms: improves
Quality of Life: improves

Omega-3 Fatty Acids: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People
	Depression Symptoms Small Improvement	Improves (the measure goes down)	Small effect	5 studies	1,373 people
Studies that measured depression symptoms Omega-3 fatty acids for depression in adultsCochrane Database Syst Rev · PMID 26537796 Effects of long-chain omega-3 polyunsaturated fatty acids on reducing anxiety and/or depression in adults; A systematic review and meta-analysis of randomised controlled trialsProstaglandins Leukot Essent Fatty Acids · PMID 37028202 Exploration of the optimized portrait of omega-3 polyunsaturated fatty acids in treating depression: A meta-analysis of randomized-controlled trials.J Affect Disord · PMID 40049535 and 2 more on the Omega-3 Fatty Acids page
	Anxiety Symptoms Small Improvement	Improves (the measure goes down)	Small effect	2 studies	2,189 people
Studies that measured anxiety symptoms Efficacy and safety of omega-3 fatty acids supplementation for anxiety symptoms: a systematic review and dose-response meta-analysis of randomized controlled trials.BMC Psychiatry · PMID 38890670 Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders - Results from a double-blind, randomized and placebo-controlled clinical trialJ Psychiatr Res · PMID 30317101
	Quality of Life	Improves (the measure goes up)		1 study	383 people
Studies that measured quality of life Effect of Omega-3 Fatty Acids on Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Int J Chron Obstruct Pulmon Dis · PMID 34588776

Magnesium

C-Reactive Protein (CRP): improves
Serum Magnesium: improves
Depression Symptoms: improves

Magnesium: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
C-Reactive Protein (CRP) Small Decrease	Improves (the measure goes down)	Small effect	3 studies	108 people
Serum Magnesium	Improves (the measure goes up)		6 studies	154 people
Depression Symptoms	Improves (the measure goes down)		3 studies	177 people
Interleukin 6	Improves (the measure goes down)			108 people
Serum BDNF	Improves (the measure goes up)			154 people
TNF-Alpha	Improves (the measure goes down)			108 people

Theanine

Anxiety Symptoms: improves
Attention: improves
Executive Function: improves

Theanine: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
Anxiety Symptoms Small Improvement	Improves (the measure goes down)	Small effect	2 studies	20 people
Attention	Improves (the measure goes up)		4 studies	20 people
Executive Function	Improves (the measure goes up)		3 studies	20 people
Sleep Quality	Improves (the measure goes up)		2 studies	20 people
Depression Symptoms	Improves (the measure goes down)			20 people
Motor Speed	Improves (the measure goes up)			20 people
Verbal Fluency	Improves (the measure goes up)			20 people
Verbal Memory	Improves (the measure goes up)			20 people
Working Memory	Improves (the measure goes up)			20 people

Probiotics

Depression Symptoms: improves
Sleep Quality: improves
Sleep Duration: improves

Probiotics: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
Depression Symptoms Small Improvement	Improves (the measure goes down)	Small effect	1 study	140 people
Sleep Quality	Improves (the measure goes up)		1 study	424 people
Sleep Duration	Improves (the measure goes up)			226 people
Sleep Efficiency	Improves (the measure goes up)			166 people
Sleep Latency	Improves (the measure goes down)			226 people

Red Clover Extract

Anxiety Symptoms: improves
Depression Symptoms: improves

Red Clover Extract: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Anxiety Symptoms Moderate Improvement	Improves (the measure goes down)	Moderate effect	1 study	109 people
	Depression Symptoms	Improves (the measure goes down)			109 people

Nefiracetam

Apathy: improves
Depression Symptoms

Nefiracetam: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Apathy Small Improvement	Improves (the measure goes down)	Small effect	1 study	137 people
	Depression Symptoms No effect		NoneNo effect		137 people

Zinc

Aggression: improves
Depression Symptoms: improves
Serum BDNF: improves

Zinc: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
Aggression Small Improvement	Improves (the measure goes up)	Small effect		30 people
Depression Symptoms	Improves (the measure goes down)		3 studies	162 people
Serum BDNF	Improves (the measure goes up)		2 studies	90 people
Subjective Well-Being	Improves (the measure goes up)		1 study	30 people
Interleukin 6	Improves (the measure goes down)			44 people
TNF-Alpha	Improves (the measure goes down)			44 people

Chromium

Appetite: improves
Depression Symptoms: improves
Libido: improves

Chromium: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
Appetite Small Decrease	Improves (the measure goes down)	Small effect		75 people
Depression Symptoms	Improves (the measure goes down)		4 studies	90 people
Libido	Improves (the measure goes up)			75 people

Apigenin

Depression Symptoms: improves

Apigenin: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms Moderate Decrease in Hamilton Depression Rating Scale	Improves (the measure goes down)	Moderate effect		57 people

GABA

Depression Symptoms: improves

GABA: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms Improvement in depression scores (90-day trial with exercise)	Improves (the measure goes down)	Moderate effect		30 people

Tryptophan

Depression Symptoms (Mild-Moderate): improves
Severe Depression: improves

Tryptophan: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms (Mild-Moderate) Better than placebo for mild-moderate depression (Cochrane review)	Improves (the measure goes down)	Moderate effect		300 people
	Severe Depression Not effective for severe depressive symptoms	Improves (the measure goes down)	Small effect		150 people

Ginkgo Biloba

Libido
Sleep Quality: improves

Ginkgo Biloba: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Libido No effect		NoneNo effect	4 studies	63 people
	Sleep Quality	Improves (the measure goes up)		2 studies	16 people

Vitamin B12

Depression Symptoms
Cognition
Fatigue Symptoms: improves

Vitamin B12: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
Depression Symptoms No effect		NoneNo effect	2 studies	2,912 people
Cognition No effect		NoneNo effect		2,912 people
Fatigue Symptoms	Improves (the measure goes down)		1 study	2,912 people

Baikal Skullcap

Depression Symptoms
Anxiety Symptoms
Sleep Quality: improves

Baikal Skullcap: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
Depression Symptoms No effect		NoneNo effect	1 study	177 people
Anxiety Symptoms No effect		NoneNo effect		177 people
Sleep Quality	Improves (the measure goes up)			177 people
Subjective Well-Being	Improves (the measure goes up)			177 people

Inositol

Bipolar Disorder Symptoms
Depression Symptoms: improves
Schizophrenia symptoms: improves

Inositol: outcomes studied for Depression
Outcome	Effect	Size	Studies	People
Bipolar Disorder Symptoms No effect		NoneNo effect	1 study	66 people
Depression Symptoms	Improves (the measure goes down)		5 studies	113 people
Schizophrenia symptoms	Improves (the measure goes down)		2 studies	21 people

Docosahexaenoic Acid

Depression Symptoms
Postpartum Depression Symptoms

Docosahexaenoic Acid: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms No effect		NoneNo effect	1 study	36 people
	Postpartum Depression Symptoms No effect		NoneNo effect	1 study	2,320 people

B Vitamins

Depressive Symptoms

B Vitamins: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depressive Symptoms Meta-analysis: SMD 0.15 (-0.01-0.32, p=0.07) - trend but not significant		NoneNo effect		568 people

N-Acetylcysteine

Anxiety Symptoms
Depression Symptoms: improves

N-Acetylcysteine: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Anxiety Symptoms No effect		NoneNo effect		319 people
	Depression Symptoms	Improves (the measure goes down)		4 studies	574 people

Maca

Sexual Function: improves

Maca: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Sexual Function	Improves (the measure goes up)		2 studies	45 people

L-Carnitine

Depression Symptoms: improves

L-Carnitine: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms	Improves (the measure goes down)		2 studies	447 people

Creatine

Depression Symptoms: improves

Creatine: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms	Improves (the measure goes down)		2 studies	60 people

L-Tyrosine

Depression Symptoms: improves

L-Tyrosine: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms	Improves (the measure goes down)		1 study	65 people

Lactobacillus reuteri

Depression Symptoms: improves

Lactobacillus reuteri: outcomes studied for Depression
Grade	Outcome	Effect	Size	Studies	People	Studies list
	Depression Symptoms	Improves (the measure goes down)		1 study	509 people

Key findings

Depression SymptomsFish OilImproves (the measure goes down)
Anxiety SymptomsCurcuminImproves (the measure goes down)
Combined Anxiety & DepressionVitamin DImproves (the measure goes down)

The Depression (Major Depressive Disorder) protocol

2 primary supplements · 4 supporting supplements

Omega-3 Fatty Acids (EPA)1–2 g EPA daily (EPA-dominant formula, EPA:DHA ratio >2:1)
St. John's Wort300 mg 3× daily (standardized to 0.3% hypericin)

See the full protocol

Shop the evidence-backed picks

Fullscript collectionStress and mood: evidence-graded picksOpen on Fullscript

The collection holds the supplements we grade A or B for its theme, in third-party tested products where the catalog has them. It opens in our Fullscript store. You can look through it without signing in; Fullscript asks for a free account to order.

Or shop one supplement

The supplements graded A or B for Depression. Each opens third-party tested products for that supplement.

Grade A
Grade A
Grade A
Grade B
Grade B
Grade B

We earn from purchases made in our Fullscript store, and links to Fullscript, iHerb or Thorne carry our referral, so we may earn a commission at no extra cost to you. Grades come from the research and never change based on what we earn. Full disclosure

Studies cited

7 studies from PubMed

Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis.J Affect Disord · PMID 36209780
Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorderAm J Psychiatry · PMID 11870016
Repeated thermal therapy diminishes appetite loss and subjective complaints in mildly depressed patients.Psychosom Med · PMID 16046381
Optimal dose and type of exercise to improve depressive symptoms in older adults: a systematic review and network meta-analysis.BMC Geriatr · PMID 38849780
Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial.Nutrients · PMID 39064748
Effect of Different Dietary Patterns on Patients with Depressive Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Nutrients · PMID 39940421
Violet light photobiomodulation therapy for depression: A double-blind randomized crossover trial.J Affect Disord · PMID 39961441

Evidence by supplement

Key findings

The Depression (Major Depressive Disorder) protocol

Shop the evidence-backed picks

Studies cited

Related conditions

Supplement stack for Depression