Ranked by evidence
Best supplements for low mood
For mild-to-moderate depression a few supplements have real trial support, with St John's wort the strongest. Everything below is ranked by the evidence for mood specifically, and none of it treats severe depression or replaces care if you have thoughts of self-harm. Several of these interact seriously with antidepressants, so check before combining.
Picks are ranked by the strength of published evidence for this goal in otherwise healthy adults. A persistent symptom needs a clinician's evaluation, and no supplement on this list replaces treatment.
Evidence last reviewed: September 2026
Top picks
| Option | Evidence | Best for | The honest note | |
|---|---|---|---|---|
| St John's Wort | Strong evidence | mild-to-moderate depression | A Cochrane review of 29 trials found it comparable to standard antidepressants and better tolerated. It is also the herb most often implicated in dangerous drug interactions, including contraceptive failure. | View |
Solid options
| Option | Evidence | Best for | The honest note | |
|---|---|---|---|---|
| Saffron Extract | Moderate evidence | an alternative to St John's wort | Trials at 30 mg/day beat placebo and matched fluoxetine in mild-to-moderate depression, but they were small and nearly all from Iran. Doses far above that are toxic. | View |
| Acetyl-L-Carnitine | Moderate evidence | low mood in older adults | A meta-analysis of 12 studies found it reduced depressive symptoms with markedly fewer adverse events than antidepressants. The trials were mostly small, short and in older adults. | View |
| SAM-e | Moderate evidence | a cautious second-line option | It has more trial support than most mood supplements, but Cochrane rated the evidence low quality and inconclusive. It can trigger mania in people with bipolar disorder. | View |
Situational
| Option | Evidence | Best for | The honest note | |
|---|---|---|---|---|
| Bifidobacterium Longum | Moderate evidence | low mood alongside IBS | Only strain NCC3001 has the data: in 44 IBS patients it improved depression scores in 64% versus 32% on placebo. Generic B. longum products have not been shown to do this. | View |
| Stress B-Complex | Moderate evidence | stress rather than depression | A meta-analysis of 18 trials found a small reduction in perceived stress in healthy adults, with no clear benefit for depressive symptoms. Check that the vitamin B6 dose is not high enough to risk neuropathy. | View |
Popular for this goal — but the evidence says skip
- 5-HTP Limited evidence
Of 108 trials reviewed, only 2 with 64 participants met basic quality criteria, and combining it with antidepressants risks serotonin syndrome.
- Rhodiola Rosea Limited evidence
In the one rigorous depression trial it did no better than placebo.
- L-Tryptophan Moderate evidence
The antidepressant evidence is old and low quality, and it risks serotonin syndrome when combined with antidepressants.
- Lithium Orotate Limited evidence
No randomised trial has tested it for mood, and it is an unmonitored psychoactive metal with a narrow therapeutic index.
- Psychobiotics Limited evidence
In clinically diagnosed patients the effects are small and inconsistent, and generic blends labelled for mood have no strain-specific data.
- Mood Support Formulas Limited evidence
The finished formulas are almost never tested and often underdose the ingredients that work, while hiding St John's wort's interaction risks.
Our verdict
St John's wort has the strongest evidence, but check every medication you take before starting it; saffron is a reasonable alternative with a thinner evidence base. Skip 5-HTP, rhodiola, lithium orotate and mood blends.