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The Four Supplements to Consider for Help With Depression

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. 

Unfortunately the supplement market today is full of mixed messages and exaggerated claims about which supplements are the best for treating depression, so it can be hard to know what actually works. By taking a closer look at what the research says and which specific supplements experts recommend, you can determine which supplements may be right for you.

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 supplements to determine which ones had sufficient evidence to suggest they help reduce symptoms of depression when taken with antidepressant medication. 

Here are the supplements they found to be successful:

  1. 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.
  2. 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
  3. 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. 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 patients who don’t initially respond to antidepressant treatment.
  4. SAM-e (S-adenosylmethionine)
    SAM-e is a prescription drug in Europe but is available over the counter in the U.S. It’s a natural substance present in every cell in the body and brain that plays a role in numerous cellular processes. SAM-e is believed to work by increasing levels of serotonin in the brain, creating a similar effect to antidepressant medication.

For people not taking antidepressants, a Harvard panel identified the above 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 and vitamin D is believed to have broader health benefits beyond depression treatment, including maintaining healthy bones, cells, and cardiovascular function. 


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 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, 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 doctor 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, 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.



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