Condition
Major Depressive Disorder (MDD)
Major depression involves shifting brain chemistry, inflammation, oxidative stress and weaker connections between neurons, not simply low serotonin. Among supplements, the evidence is strongest for curcumin, where anxiety symptoms improved in people with depression, followed by vitamin D, where depression symptoms improved, and omega-3s, which also eased anxiety. Most of these studies were small, and only curcumin's evidence reaches moderate.
Sources: PMID 23832433; PMID 39450108; PMID 30317101
- Supplements studied
- 9
- Graded outcomes
- 8
- Trials
- 9
- People studied
- 1,084
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
Omega-3 Fatty Acids
- Anxiety Symptoms: improves
- Depression Symptoms: improves
- Sleep Quality: improves
Bacopa Monnieri
- Anhedonia: improves
- Depression Symptoms: changes; see studies
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anhedonia Small Improvement | Improves (the measure goes down) | Small effect | 1 study | 42 people | ||
Studies that measured anhedonia | ||||||
| Depression Symptoms | Changes; see studies | 42 people | ||||
L-Carnitine
- Cortisol: improves
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cortisol Small Decrease | Improves (the measure goes down) | Small effect | 30 people | |||
| Depression Symptoms | Improves (the measure goes down) | 2 studies | 30 people | |||
Curcumin
- Anxiety Symptoms: improves
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anxiety Symptoms Large Improvement | Improves (the measure goes down) | Large effect | 111 people | |||
| Depression Symptoms | Improves (the measure goes down) | 9 studies | 156 people | |||
Studies that measured depression symptoms | ||||||
Agmatine
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Depression Symptoms Case series only (n=3) - very preliminary | Improves (the measure goes down) | Moderate effect | 3 people |
N-Acetylcysteine
- Anxiety Symptoms
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anxiety Symptoms No effect | NoneNo effect | 315 people | ||||
| Depression Symptoms | Improves (the measure goes down) | 4 studies | 579 people | |||
Studies that measured depression symptoms
| ||||||
Chromium
- Depression Symptoms: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Depression Symptoms | Improves (the measure goes down) | 4 studies | 15 people | |||
Studies that measured depression symptoms
| ||||||
Key findings
- Blood glucoseImproves (the measure goes down)
- Depression SymptomsImproves (the measure goes down)
- Anxiety SymptomsImproves (the measure goes down)
The Major Depressive Disorder protocol
2 primary supplements · 4 supporting supplements
- Omega-3 Fatty Acids (EPA-dominant)2–4 g daily (minimum 60% EPA)
- S-Adenosyl-L-Methionine (SAMe)800–1,600 mg daily
Shop the evidence-backed picks
Support alongside medical care. These supplements are not a treatment for Major Depressive Disorder (MDD). If you are being treated for it, talk to your clinician before adding one: supplements can interact with medicines.
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.
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
100 studies from PubMed
- Effect of curcumin on inflammatory markers and disease activity in patients with rheumatoid arthritis: A meta-analysis.
- Effects of omega-3 fatty acids on chronic pain: a systematic review and meta-analysis.
- Effect of vitamin D supplementation for major adverse cardiovascular events: a meta-analysis based on randomised controlled trials.
- The Effect of Antioxidant Polyphenol Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.
- The Effectiveness of Curcumin, Resveratrol, and Silymarin on MASLD: A Systematic Review and Meta-Analysis.
- Safety Profile of Bacopa monnieri in Clinical Trials
- Chromium in PCOS: A Systematic Review and Meta-Analysis
- Optimal Vitamin D Status: Evidence and Guidelines
- Vitamin D and Cancer Prevention: A Comprehensive Review
- Effects of Bacopa monnieri on Memory: A Review of Clinical Evidence
- Bacopa monnieri and Attention: A Systematic Review
- Bacopa monnieri and Pediatric Cognitive Function: A Review
- Chromium Supplementation and Metabolic Diseases: Evidence from Clinical Trials
- Effects of Chromium Supplementation on Body Composition: A Systematic Review
- Safety of Chromium Supplementation: Evidence from Clinical Studies
- Curcumin alleviates postprandial glycaemic response in healthy subjects: A cross-over, randomized controlled study
- Substantial Variability Across Individuals in the Vascular and Nutrigenomic Response to an Acute Intake of Curcumin: A Randomized Controlled Trial
- Effects of Vitamin D Supplementation on Musculoskeletal Health: A Systematic Review and Meta-Analysis
- Vitamin D and Prevention of Respiratory Tract Infections: A Systematic Review and Meta-Analysis
- Effects of Vitamin D Supplementation on Depression: A Systematic Review and Meta-Analysis
- Vitamin D and Immune Function: A Review
- Vitamin D Supplementation for Prevention of Mortality: A Meta-Analysis
- Vitamin D Supplementation During Pregnancy: Safety and Efficacy Review
- Bacopa monnieri and Cognitive Enhancement: A Systematic Review
- Neuroprotective Effects of Bacopa monnieri: A Review
- Anxiolytic Effects of Bacopa monnieri: Mechanisms and Clinical Evidence
- Bacopa monnieri and Neuroprotection: Mechanisms of Action
- Effects of Chromium Supplementation on Glucose Metabolism and Lipids: A Systematic Review and Meta-Analysis
- Chromium and Insulin Sensitivity: A Review of Mechanisms
- Chromium Supplementation in Depression and Mood Disorders: A Review
- Chromium Supplementation and Glycemic Control in Diabetes: An Updated Review
- Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress
- Vitamin D Supplementation: A Comprehensive Review of Efficacy for Various Health Outcomes
- Vitamin D Deficiency: Global Health Perspective
- Vitamin D and Cardiovascular Disease: A Review of Evidence
- Vitamin D and Bone Health in Adults: A Systematic Review
- Meta-Analysis of Bacopa monnieri on Cognitive Function and Anxiety
- Bacopa monnieri in Older Adults: Clinical Evidence Review
- Chromium Picolinate in Type 2 Diabetes: A Meta-Analysis of Randomized Trials
- Chromium Effects on Blood Pressure: A Meta-Analysis
- Novel Form of Curcumin Improves Endothelial Function in Young, Healthy Individuals: A Double-Blind Placebo Controlled Study
- Vitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status
- Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects
- Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects
- Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen
- Association of A1C levels with vitamin D status in U.S. adults: data from the National Health and Nutrition Examination Survey
- Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus: a randomized, parallel-group, placebo-controlled, 8-week study
- Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey
- Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal
- Effects of acute chromium supplementation on postprandial metabolism in healthy young men
- The effects of inorganic chromium and brewer's yeast on glucose tolerance, plasma lipids, and plasma chromium in elderly subjects
- Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men
- Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial
- Bacopa monnieri as augmentation therapy in the treatment of anhedonia, preclinical and clinical evaluation
- Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial
- Randomized controlled trial of standardized Bacopa monniera extract in age-associated memory impairment
- An acute, double-blind, placebo-controlled crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance
- Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial
- Brahmi for the better? New findings challenging cognition and anti-anxiety effects of Brahmi (Bacopa monniera) in healthy adults
- The Neurocognitive Effects of Bacopa monnieri and Cognitive Training on Markers of Brain Microstructure in Healthy Older Adults
- Efficacy of Standardized Extract of Bacopa monnieri (Bacognize®) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial
- The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects
- The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects
- Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers
- Chronic effects of Brahmi (Bacopa monnieri) on human memory
- Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial
- Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study
- The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data
- An acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood
- L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study
- L-Carnitine's Effect on the Biomarkers of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy
- Comparative study to evaluate the effect of l-carnitine plus glimepiride versus glimepiride alone on insulin resistance in type 2 diabetic patients
- Effects of simvastatin and carnitine versus simvastatin on lipoprotein(a) and apoprotein(a) in type 2 diabetes mellitus
- Comparison between orlistat plus l-carnitine and orlistat alone on inflammation parameters in obese diabetic patients
- Effects of combination of sibutramine and L-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients
- L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes
- Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with type II diabetes mellitus
- Effect of carnitine-orotate complex on glucose metabolism and fatty liver: a double-blind, placebo-controlled study
- Efficacy and tolerability of combined treatment with L-carnitine and simvastatin in lowering lipoprotein(a) serum levels in patients with type 2 diabetes mellitus
- Blood Pressure and Metabolic Effects of Acetyl-l-Carnitine in Type 2 Diabetes: DIABASI Randomized Controlled Trial
- The effects of oral L-carnitine treatment on blood lipid metabolism and the body fat content in the diabetic patient
- The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus
- The effects of L-carnitine supplementation on cardiovascular risk factors in participants with impaired glucose tolerance and diabetes: a systematic review and dose-response meta-analysis.
- Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial
- Effect of oral L-carnitine administration on insulin sensitivity and lipid profile in type 2 diabetes mellitus patients
- The effects of L-carnitine supplementation on glycemic markers in adults: A systematic review and dose-response meta-analysis.
- L-carnitine improves glucose disposal in type 2 diabetic patients
- Caloric restriction and L-carnitine administration improves insulin sensitivity in patients with impaired glucose metabolism
- Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes
- Acetyl-l-carnitine versus placebo for migraine prophylaxis: A randomized, triple-blind, crossover study
- The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis
- Effects of carnitine on glucose and lipid metabolic profiles and fertility outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis.
- Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial
- Effects of Carnitine Administration on Carotid Intima-media Thickness and Inflammatory Factors in Patients with Polycystic Ovary Syndrome: A Randomized, Double-blind, Placebo-controlled Trial
- Effects of L-carnitine supplementation for women with polycystic ovary syndrome: a systematic review and meta-analysis
- Effect of glycine propionyl-L-carnitine on aerobic and anaerobic exercise performance
- Influence of L-carnitine administration on maximal physical exercise
- Effects of nine weeks L-Carnitine supplementation on exercise performance, anaerobic power, and exercise-induced oxidative stress in resistance-trained males
- l-Carnitine l-tartrate supplementation favorably affects biochemical markers of recovery from physical exertion in middle-aged men and women