The Four Supplements to Consider for Help With Depression

This article does not replace the advice of a medical professional and is only intended for informational and educational purposes.

Research has shown that depression is influenced by a number of processes inside the body, including inflammation, oxidative stress, and more. Because of this, certain supplements have been used to help treat depression symptoms for decades, either taken together with antidepressant medication or used alone. 

While there is no substitute for professional medical treatment by psychologists, psychiatrists, and professional medical treatment by licensed providers, there is evidence that natural remedies such as vitamins or dietary supplements may help relieve symptoms of depression. Before we take a thorough look at four specific supplements for depression that you may want to try, let’s briefly examine depression in general.

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What is depression?

Depression is a mood disorder that affects millions of people worldwide. Technically, depression is a term that is used to define several similar, sometimes related, but clinically different, mood disorders. According to the National Institute of Health, and The American Psychiatric Association’s Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), depression is generally categorized into one (or more) of these classifications:

  • major depressive disorder (MDD)
  • disruptive mood dysregulation disorder
  • persistent depressive disorder
  • premenstrual dysphoric disorder
  • depressive disorder due to another medical condition

The National Institute of Health goes on to explain that all of these classifications share common symptoms, including:

  • Sadness
  • Emptiness 
  • Irritable mood

Which are “accompanied by somatic and cognitive changes that significantly affect the individual’s capacity to function.” It is this range of diagnoses and symptoms that make it challenging to explore natural remedies for depression, as we’ll discuss below.

Depression is profoundly widespread. The National Institute of Health, indicates that in the United States alone, depression impacts 17 million adults, but they caution that that number is artificially low. They say:

Because of false perceptions, nearly 60% of people with depression do not seek medical help. 

For those who do seek medical help, there are a number of treatment options available for depression, with the most effective generally including a combination of therapy, medication, and lifestyle changes (including the use of supplements or vitamins for depression).

Which supplements are best for depression?

Numerous studies have evaluated the role of supplements in treating depression. Nonetheless, not all studies are of equal quality and it’s important to consider findings from rigorous studies published in high quality journals. A Harvard affiliated analysis published in the American Journal of Psychiatry completed a comprehensive evaluation of existing studies (called a meta-analysis), offering a condensed and reliable way to review what works. They analyzed existing study results across 16 different depression-related supplements to determine which ones had sufficient evidence to suggest they help reduce symptoms of depression when taken with antidepressant medication. 

Here are the depression supplements they found to be successful:

  • Fish oil (high EPA)

Fish oil is high in omega-3 fatty acids, which are key to certain brain functions and may help reduce inflammation associated with depression. There are two types of omega-3s in fish oil: EPA and DHA. Researchers found that EPA is the one that helps the most when it comes to depression.

  • L-methylfolate (a specific type of folic acid)

Certain people have a genetic makeup that actually impairs their use of folic acid in cellular processes, which may be associated with depression. Supplementing with L-methylfolate can help bridge this gap and keep the cellular processes moving. In fact, there is already an FDA-approved form of L-methylfolate that doctors prescribe to individuals who don’t initially respond to antidepressant treatment.

  • SAM-e (S-adenosylmethionine)

For people not taking antidepressants, a Harvard panel identified the above depression supplements, as well as St. John’s Wort, as “safe – and often effective – natural therapies” for depression. It’s also worth noting that supplementing fish oil is believed to have broader health benefits beyond depression treatment, including maintaining healthy bones, cells, and cardiovascular function. 


Natural antidepressants: best vitamins for energy and depression

  • B Vitamins

Ample evidence suggests that B vitamins can help with depression. B vitamins control and produce important chemicals in your brain that impact depression and mood regulation. As Healthline explains: “folate [B9], B12, and B6, are needed for the production and regulation of neurotransmitters like serotonin, gamma-aminobutyric acid (GABA), and dopamine.” Further, research suggests that deficiencies in these vitamins may increase the risk of depression, and that “treatment with folate and/or vitamin B12 reduces depression scale scores, increases remission, and prevents the onset of clinically significant symptoms of depression in people at risk.”

So when you’re looking for vitamins that help with depression, B vitamins are well worth discussing with your provider.

  • Zinc

Zinc is a naturally occurring mineral that, in the words of Healthline, “is critical to brain health and the regulation of neurotransmitter pathways. It also boasts antioxidant and anti-inflammatory properties.” More importantly, it is a mineral that has been closely linked to depression. 

Dr. Emily Deans, in Psychology Today, has tracked research on the relationship between Zinc and depression. Some key findings include:

“The more depressed someone is, the lower the zinc level.”

“Zinc supplementation has been shown to have antidepressant effects in humans.”

“Successful treatment with antidepressants will increase serum zinc levels.”

While the research of zinc as a natural supplement for depression is still emerging, and more is needed to know its full impact, it stands to reason that it’s a good idea to talk with your treatment team about adding zinc supplements to your depression treatment plan.

  • Magnesium

Another vital mineral that may be one of many natural depression supplements, is magnesium. Like zinc, the research is a bit sparse, but several major studies have demonstrated that magnesium supplements can reduce depression symptoms. Like zinc, the same studies have concluded that magnesium deficiency is a common trait in people who have depression. 

  • Vitamin D

Our bodies produce vitamin D naturally with adequate exposure to the sun; however, studies have found that most people actually have insufficient levels, especially those living in northern latitudes with less sunlight exposure, and that people with low vitamin D levels are prone to higher rates of depression. There are vitamin D receptors in parts of the brain associated with depression and it may be involved in the creation of certain neurotransmitters Healthline explains three key points:

  • Research shows that people with depression are more likely to be low or deficient in vitamin D. Those with the condition tend to have lower vitamin D levels than the general population, and people with the lowest levels tend to have the most significant depressive symptoms.
  • Vitamin D may fight depression through several mechanisms, including reducing inflammation, regulating mood, and protecting against neurocognitive dysfunction.
  • A 2019 review of four randomized controlled trials found that vitamin D supplements led to clinical benefits in people with major depression.

Evidence is mounting to suggest that vitamin D supplements for depression may be a big help in battling both causes and symptoms. 



Research has shown that supplements can be a natural and effective tool for managing symptoms of depression. “Supplements can be a proven and natural part of an effective depression treatment plan,” says Jacob Behrens, MD, a Brightside doctor and Clinical Advisor.

While the positive research around these supplements for depression is encouraging, it’s important to keep in mind that these results aren’t perfect or definitive.  Experts have concluded that they appear to tell us enough about the potential safety and efficacy of these supplements as a part of a depression treatment plan, but that more studies are necessary to be conclusive. We should think of the research conducted so far as a solid starting point. It’s also important to note that each of the supplements was studied in isolation and combining them could create different results.

If you are considering supplements to help combat depression, it’s important to talk to a licensed provider about what is right for you. Nutritional supplements are not FDA regulated and tests have consistently shown variable quality and purity across manufacturers. If you’re going to use supplements to help your depression, be sure you’re purchasing them from a high-quality brand. Finally, remember that supplements are not a replacement for a healthy diet, but instead may be a helpful boost for our bodies to work against the symptoms of depression.

The best way to know which of these vitamins or supplements may help with your depression is to talk to a licensed mental health expert. Brightside can help.

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