By goal
Evidence-Backed Supplements for Mood and Depression
Some supplements have randomized-trial support for low mood and depressive symptoms, saffron, St. John's Wort, and omega-3s (EPA-dominant) are among the most studied, while many popular options rest on thin or preliminary evidence. This guide grades each one and flags interactions. Supplements are not a substitute for professional care, and St. John's Wort in particular interacts dangerously with antidepressants and many other drugs.
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Best-supported here: Creatine Monohydrate (Strong), Folate / Folic Acid (Strong), Vitamin B12 (Strong), Ashwagandha (Moderate) — each graded below by the weight of human evidence.
| Supplement | Evidence for this goal | Typical dose | Key caution | Studies |
|---|---|---|---|---|
| Creatine Monohydrate | Strong | 3–5 g/day. Optional loading: 20 g/day (split) for 5–7 days. | Very safe. | 19 |
| Folate / Folic Acid | Strong | 400-800 mcg/day for anyone who could become pregnant (start >=1 month b… | Folic acid is generally very safe at recommended doses; the tolerable upper intake level fo… | 13 |
| Vitamin B12 | Strong | 2.4 µg/day RDA; deficiency corrected with high oral (500–1,000 µg) or i… | Very safe; excess excreted. | 23 |
| Ashwagandha | Moderate | 300–600 mg/day of root extract (standardized to 5% withanolides), often… | Avoid in pregnancy (traditionally abortifacient) and while breastfeeding. | 18 |
| Kiwifruit | Moderate | Two green kiwifruit daily (about 140-180 g) is the dose used in most co… | Kiwifruit is a recognised allergen and can cause oral allergy syndrome or, rarely, anaphyla… | 8 |
| L-Theanine | Moderate | 100–200 mg; often paired 1:2 with caffeine (e.g. 100mg theanine + 50mg… | Very safe, no known serious side effects. | 16 |
| Magnesium | Moderate | 200–400 mg elemental/day. Glycinate & citrate absorb best; oxide is poo… | Safe. | 20 |
| N-Acetylcysteine (NAC) | Moderate for this goal | 600–1,800 mg/day; psychiatric trials often use 2,400 mg/day. | Generally safe. | 21 |
| Omega-3 (EPA/DHA) | Moderate for this goal | 1–2 g combined EPA+DHA/day; up to 4 g (Rx) for high triglycerides. | Safe at typical doses. | 20 |
| Saffron | Moderate for this goal | 30 mg/day standardized extract. | Safe at supplement doses. | 20 |
| St. John's Wort | Moderate for this goal | Standardized extract (e.g., 0.3% hypericin / ~3-5% hyperforin) 300 mg t… | DANGER: This is a pharmacologically active herb, not a benign supplement. | 16 |
| Vitamin D3 | Moderate for this goal | 1,000–2,000 IU/day maintenance; higher to correct deficiency under test… | Tolerable upper limit ~4,000 IU/day for most adults; toxicity (hypercalcemia) occurs with c… | 16 |
| Curcumin (Turmeric) | Preliminary for this goal | 500–1,000 mg curcuminoids/day; bioavailability-enhanced forms preferred. | Generally safe. | 23 |
| Glycine | Preliminary | 3 g before bed for sleep. | Very safe. | 16 |
| Inositol (Myo-Inositol) | Preliminary for this goal | PCOS: typically 2 g myo-inositol twice daily (4 g/day), often with 400… | Generally well tolerated; the most common side effects are mild, dose-related gastrointesti… | 14 |
| Maca | Preliminary for this goal | 1.5–3 g/day of dried root powder (as used in trials). | Generally well tolerated as a food. | 15 |
| Panax Ginseng | Preliminary | 200–400 mg/day standardized extract. | Generally safe short-term. | 16 |
| Probiotics | Preliminary for this goal | Strain-specific; commonly 1–10 billion CFU/day. Match strain to the stu… | Safe for most. | 19 |
| Rhodiola Rosea | Preliminary for this goal | 200–600 mg/day standardized to 3% rosavins / 1% salidroside. | Well tolerated. | 17 |
| Zinc | Preliminary for this goal | 8–11 mg/day RDA; up to 40 mg upper limit. Lozenges (75mg+/day) only sho… | Safe within limits (adult upper limit ~40 mg/day). | 21 |
| 5-HTP | Mixed for this goal | 50–300 mg/day; start low. Do NOT combine with antidepressants. | GI upset common. | 15 |