Health Check: five supplements that may help with depression

While there’s evidence for the efficacy of some supplements as potential treatments for depression, there’s none for others, and some have been found to be ineffective. Михал Орела/Flickr, CC BY-SA

Over two-thirds of Australians are thought to use complementary medicines ranging from vitamin and mineral supplements to herbal to aromatherapy and homeopathic products. Mental health concerns are one of the reasons why people use supplements, but are they really useful?

While there’s evidence for the efficacy of some supplements as potential treatments for depression, there’s none for others, and some have been found to be ineffective. But effectiveness is not the only concern – the quality and cost of unregulated products can also be problematic.

And then there’s the issue of discerning between bone fide evidence from double-blind randomised controlled trials and slick company marketing campaigns.

Of the supplements that have been studied for improving general mood or treating clinical depression, omega-3 fatty acids, St John’s wort, S-adenosyl-methionine (SAMe), N-acetyl cysteine (NAC) and zinc are the most researched and commonly used.

Omega-3 fatty acids

There are three types of omega-3 fatty involved in human physiology. They are important for normal metabolism.

Epidemiological studies show that low dietary intake of omega-3 oils from fish may be related to increased risk of depressive symptoms. A review of dozens of clinical trials on major depression that assessed the efficacy of these fatty acids alone or in combination with antidepressants, supported their use in depression.

And a meta-analysis combining the results of five similar studies found a significant effect in favour of omega-3 fatty acids for reducing bipolar depression.


S-adenosyl-methionine (SAMe) is a naturally occurring compound found in almost every tissue and fluid in the body that’s involved in processes, such as producing and breaking down brain chemicals including serotonin, melatonin, and dopamine.

Double-blind studies show injected and oral preparations (between 800 milligrams to 1600 milligrams) of SAMe are as effective as antidepressants, and tend to produce relatively fewer adverse effects. SAMe also improves the response to antidepressant medication.

It’s a little expensive but SAMe appears well tolerated with only mild adverse effects such as headaches, restlessness, insomnia and gastrointestinal upsets.

St John’s wort

St John’s wort (Hypericum perforatum) is a flowering plant that has a long history of medicinal use. It’s been studied for treating depression in over 40 clinical trials of varying methodological quality.

A 2008 Cochrane review of 29 trials involving 5,489 patients analysed comparisons of St John’s wort with placebo or dummy pills and with antidepressants. It showed people were significantly more likely to respond to St John’s wort than to placebo. In the same analysis, St John’s wort had an equivalent effect to antidepressants.

Because of the risk of drug interactions, people taking other medicines should only use St John’s wort with low amounts of the plant chemical hyperforin, which has effects on drug levels in the body (see an appropriate health professional for advice on this).

The supplement should not be taken with antidepressants as it can cause serotonin syndrome, a potentially fatal nervous system event.


N-acetyl cysteine (NAC) is an amino acid with strong antioxidant properties that has a history of use in the management of paracetamol overdose. It’s been found to significantly reduce depression in bipolar disorder.

In a 24-week placebo-controlled trial of 75 people with bipolar disorder, one gram of NAC twice a day significantly reduced depression. The supplement appears to have no significant adverse reactions but is currently only available from compounding pharmacies or from overseas.


Zinc is a mineral found in some food, and there’s emerging evidence that it improves depressed mood.

A 2012 review of randomised controlled trials found two 12-week trials, with sample sizes of 60 and 20 people, showed zinc as an adjunct to antidepressants significantly lowered depression.

Zinc can be safely prescribed in doses up to 30 milligrams a day, although it should have amino acid another aid to improve absorption. While zinc is a fairly safe supplement, it may cause nausea on an empty stomach.

A cautionary note

This is a very basic overview of the evidence for these five supplements, and people considering their use should get health professional advice before starting to take them.

The studies mentioned here tend to support that “add-on” prescription of a range of nutrients, such as omega-3 fatty acids, SAMe, folic acid, N-acetyl cysteine and zinc, with various medicines, such as antidepressants, have a beneficial effect in improving treatment beyond that of placebo. But again, be sure to seek medical advice before combining any supplements with medications.

Clinical trials have demonstrated little or no effect for valerian in insomnia, St John’s wort in anxiety disorders or attention deficit hyperactivity disorder, n-acetyl cysteine or docosahexaenoic acid (DHA) fatty acids for unipolar depression, and omega-3 for bipolar mania, among others.

The majority of Australians, especially women, already take a range of nutrient and herbal-based supplements for a number of mental health problems. But, consumers should be mindful of the evidence for their effectiveness and differences between the quality and standardisation of supplements, as well as potential drug interactions.

Click here for information on participating in a clinical trial, running in Brisbane and Melbourne, assessing the use of nutraceuticals for people who are depressed.