Natural Antidepressants: What the Evidence Shows

1 December 2023, by SANUSq Research team
13 min reading time

Man sitting on a bench by a window with his head in his hands, with zinc, magnesium, vitamin C and D icons

When your mood has hit the floor, looking for natural antidepressants is an understandable first instinct. Some options have been studied seriously, others barely at all, and one of the best known carries a real risk of drug interactions. Here is what the evidence can tell you, and what it can't.

Written by SANUSq Research Team | Medically reviewed by Dr Ajay Kumar, MD
Published: 1 December 2023 | Updated: 1 December 2023

First things first: low mood or depression?

A rough patch and a depressive episode are different in kind. Clinical depression means a low mood or a marked loss of interest and pleasure, lasting at least two weeks and present most of the time, together with changes in sleep, appetite, concentration and energy.

Depression is common, and it responds to care. The approaches with the strongest evidence are talking therapies, antidepressant medication when it is appropriate, and physical activity, often in combination and chosen with a health professional.

If that description sounds familiar, the most useful step is not finding the right supplement. It is talking to your GP or another health professional. If you are having dark thoughts, that conversation should not wait.

One more point before going further. If you already take a prescribed antidepressant, don't stop it or reduce it because you have read about a natural alternative. Stopping suddenly can bring on withdrawal symptoms and raises the risk of relapse, so any change should be planned with your doctor.

St John's wort: it has real effects, and that is the problem

St John's wort (Hypericum perforatum) is the most thoroughly studied herb in mild to moderate depression, and the plant most people have in mind when they talk about natural antidepressants.

A Cochrane review by Linde et al. (2008) pooled 29 trials with 5,489 people with major depression. The extracts tested did better than placebo, appeared similar to standard antidepressants and led to fewer drop-outs because of side effects. But results varied widely between trials, and studies from German-speaking countries reported more favourable findings than those from elsewhere, which the authors said complicates interpretation.

Shop products also vary in what they contain. The decisive point, though, is safety. Precisely because St John's wort is pharmacologically active, it speeds up the liver enzymes and transport proteins that clear many medicines from the body, lowering their levels and their effect.

In a review of clinical reports, Borrelli and Izzo (2009) list well-documented interactions including lower blood levels of the transplant drug ciclosporin, serotonin syndrome when St John's wort was combined with serotonin reuptake inhibitor antidepressants, unplanned pregnancies in women taking the contraceptive pill, and reduced levels of some HIV and cancer drugs. They describe some of these interactions as potentially life-threatening.

The list of medicines affected is long. It includes:

Antidepressants such as SSRIs, where the combination can lead to serotonin syndrome (agitation, sweating, tremor, a racing heart and, in severe cases, a medical emergency).
Hormonal contraception, including the pill, which may become less reliable.
Blood thinners such as warfarin.
Heart medicines such as digoxin, and some statins.
Anti-rejection drugs after an organ transplant, HIV medicines, some epilepsy drugs and some cancer treatments.

A plant origin does not make it harmless. Don't take it without speaking to a doctor or pharmacist first, especially if you take anything else, and never combine it with a prescribed antidepressant.

Supplements for depression: what the research shows

Beyond St John's wort, the evidence for other supplements for depression is more modest than marketing suggests.

Omega-3 fatty acids

A Cochrane review by Appleton et al. (2021) gathered 35 trials of omega-3 supplements in adults with major depression. Compared with placebo, there was a small to modest reduction in symptoms, but the authors judged it unlikely to be clinically meaningful, rated the evidence as low to very low certainty and found no difference in rates of remission or response. They concluded that there is not enough high-certainty evidence to judge omega-3 as a treatment for depression.

That is neither nothing nor much, and it does not justify replacing proper care with capsules.

Vitamin D

Vitamin D is often low in people with depression, but going out less and spending less time in daylight can be consequences of depression as much as causes.

In the large VITAL-DEP trial, Okereke et al. (2020) gave 18,353 adults aged 50 and over either 2,000 IU (50 µg) of vitamin D3 a day or a placebo for a median of 5.3 years. There was no significant difference in the risk of depression or in mood scores between the two groups. Most participants were not depressed at the start, so the trial speaks to prevention in the general population rather than to people who are already unwell.

Vitamin D contributes to the normal function of the immune system and to the maintenance of normal bones and muscle function. Correcting a deficiency confirmed by a blood test is worthwhile for those reasons. Expecting it to lift depression is not supported by strong evidence.

Magnesium

Magnesium contributes to the normal functioning of the nervous system and to normal psychological function. Research on mood itself is thin, and most of it looks at anxiety rather than depression.

A systematic review by Boyle et al. (2017) examined 18 studies of magnesium supplements and subjective anxiety. The findings suggested a possible benefit in groups already prone to anxiety, such as people with mild anxiety or premenstrual symptoms, but the authors rated the quality of the evidence as poor and called for well-designed trials.

Saffron

Saffron extract has attracted growing interest. Most trials are small and many come from a single country.

A meta-analysis by Mahmoudi et al. (2026), covering 34 placebo-controlled trials with 1,769 adults, found lower scores on self-reported depression and anxiety questionnaires with saffron. However, there was no significant effect on the depression scale rated by clinicians, results varied a great deal between trials, and the authors stressed the need for high-quality studies.

Promising, then, but not settled, and not a reason to delay seeing a doctor.

Natural remedies for depression with the strongest evidence

If you are looking for natural remedies for depression with solid research behind them, the best candidate isn't in a bottle. It is physical activity.

The latest Cochrane review of exercise for depression, by Clegg et al. (2026), included 73 randomised trials. Exercise may be moderately more effective than no treatment or a control activity in reducing symptoms of depression, although the evidence was rated low certainty. In a small number of trials it appeared no more or less effective than talking therapy or antidepressant medication. Long-term follow-up was rare and many trials had design weaknesses.

Brisk walking, cycling, swimming or a group class can all count. What matters is regularity, and when energy is very low the starting point should be deliberately small: ten minutes out of the house is a real start.

A regular daily structure, daylight, a steady sleep routine and staying in touch with people also help. They don't replace treatment when it is needed, but they support it.

Food and mood, in proportion

Many studies link a Mediterranean-style diet with a lower risk of depression, and the findings are fairly consistent.

A meta-analysis of observational studies by Lassale et al. (2019) found that people who followed a Mediterranean diet most closely had about a third lower risk of developing depression over time than those who followed it least, based on four longitudinal studies. Less inflammatory diets showed a similar association.

These studies show association, not cause and effect: depression also changes appetite and food choices.

A diet rich in vegetables, pulses, wholegrains, fish and olive oil is good for the heart, metabolism and sleep, all of which weigh on mood. It is a support, not a treatment, and one simple, sustainable change beats an ambitious plan abandoned within a week.

What the phrase "natural antidepressants" hides

The phrase suggests a comforting trade: the same effect, with less risk. Both halves are open to question.

Same effect? No product available without a prescription has been shown to match established treatment for clinical depression in well-designed, consistent trials.
Less risk? "Natural" does not mean risk-free, and St John's wort is the clearest example.

The most serious risk, though, isn't pharmacological. It is lost time. Untreated depression tends to last longer, deepen and become harder to shift, and months spent trying one product after another are months in which effective care could have been working. Supplements are not a substitute for medical care.

When to get help

Talk to your GP or a mental health professional if your mood has been low for more than two weeks, if your sleep or appetite have changed and stayed changed, if work or relationships are suffering, or if you are having dark thoughts.

If you are thinking about suicide or harming yourself, get help now. Call your local emergency number, go to the nearest emergency department, or contact a crisis line in your country. In the UK and Ireland, Samaritans are available free, day and night, on 116 123. You don't have to deal with this alone, and asking for help is not a sign of weakness.

The bottom line

St John's wort has the most research behind it, but it interacts with many common medicines and should only be used with medical advice. Omega-3, vitamin D, magnesium and saffron have weak, mixed or still-emerging evidence. Regular physical activity, daily structure and good food habits are worthwhile supports. The step that matters most is a conversation with a health professional.

Frequently asked questions

Is there a natural antidepressant that works?

No over-the-counter product has been shown to match established treatment for clinical depression. St John's wort has the most trial data in mild to moderate depression, but results vary between studies and it carries serious interaction risks.

Is St John's wort safe?

Not for everyone, and not on your own initiative. It can make the contraceptive pill, blood thinners such as warfarin, transplant drugs and some HIV and cancer medicines less effective, and combined with an antidepressant it can cause serotonin syndrome. Speak to a doctor or pharmacist before taking it.

Do omega-3 supplements help with depression?

A Cochrane review found a small effect on symptoms that was unlikely to be clinically meaningful, based on low-certainty evidence, and no difference in remission rates. Omega-3 is not a replacement for proper care.

Can vitamin D improve mood?

Low vitamin D is common in people with depression, but a large five-year trial found no effect of supplements on depression risk or mood scores in older adults. Correcting a confirmed deficiency is sensible for other reasons.

Can I stop my antidepressants and switch to supplements?

Don't stop or change prescribed antidepressants without medical advice. Stopping abruptly can cause withdrawal symptoms and raises the chance of relapse, and some supplements, St John's wort in particular, interact dangerously with antidepressants.

When should I see a doctor about low mood?

If low mood lasts more than two weeks, if sleep, appetite or daily life are affected, or if you have dark thoughts. If you are thinking of suicide, call your local emergency number or a crisis line straight away; in the UK and Ireland, Samaritans answer 24 hours a day on 116 123.

References

Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database of Systematic Reviews. 2008;(4):CD000448. PMID 18843608
Borrelli F, Izzo AA. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS Journal. 2009;11(4):710–727. PMID 19859815
Appleton KM, Voyias PD, Sallis HM, et al. Omega-3 fatty acids for depression in adults. Cochrane Database of Systematic Reviews. 2021;11(11):CD004692. PMID 34817851
Okereke OI, Reynolds CF 3rd, 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. JAMA. 2020;324(5):471–480. PMID 32749491
Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress — a systematic review. Nutrients. 2017;9(5):429. PMID 28445426
Mahmoudi R, Mohammadi-Sartang M, Servatyari K, Rafieipour N. Effect of saffron on depression, anxiety and mood disorder: a GRADE assessed systematic review and meta-analysis of 34 randomized controlled trials. Nutritional Neuroscience. 2026;29(7):816–837. PMID 41693488
Clegg AJ, Hill JE, Mullin DS, et al. Exercise for depression. Cochrane Database of Systematic Reviews. 2026;1(1):CD004366. PMID 41500513
Lassale C, Batty GD, Baghdadli A, et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Molecular Psychiatry. 2019;24(7):965–986. PMID 30254236

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The health information in this article is provided for educational purposes only. Consult your healthcare professional before making any medical decisions.

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