Supplements for Depression—What Options Are Available?

You might be surprised about which supplements are most effective.

The multibillion-dollar market for dietary supplements is filled with products that claim to boost mood or improve depression. Some products are even billed as an alternative to prescription antidepressants.

Don't believe everything you read on a label, however. Often the claims made by supplement manufacturers aren't backed up by solid scientific evidence, and the potency and contents of supplements can vary widely. Serious depression generally requires professional help, whether or not that includes antidepressant medication.

That said, if you experience mild depression or related conditions like seasonal affective disorder, some supplements have been tested fairly extensively and may improve your symptoms. These supplements include things such as vitamins, compounds, and neurotransmitters, which are chemical messengers for neurons in the body that help the brain carry out different functions according to the National Library of Medicine (NLM).

Below, we break down the evidence (or lack thereof) supporting popular supplements used to treat depression and mood.

Folic Acid

Folic acid is the synthetic form of folate, a B vitamin (B9) found in fruits, leafy vegetables, and other foods, that affects the neurotransmitters known as monoamines, according to the American Psychological Association. Folic acid is sold in stores as a capsule or tablet.

Folate deficiency has been linked to depression, according to a January 2018 Egyptian Journal of Hospital Medicine study. However, the level of folate does not always correlate to the presentation of depression or symptoms of the condition. For example, researchers for a December 2021 study published in the British Journal of Nutrition conducted a four-year longitudinal study to explore the connection between folate and vitamin B12 and the occurrence of depressive symptoms. They found that the level of vitamin B12 mattered more than the level of folate: Low levels of vitamin B12 were associated with depressive symptoms but not folate.

Consequently, the evidence for the effectiveness of folic acid on its own is still under consideration. Regardless, it appears that folic acid could offer some benefits in conjunction with antidepressants, according to researchers of a May 2021 study in Frontiers in Nutrition. Additionally, 5-MTHF and a related form of folate called L-methylfolate might be helpful as an addition to antidepressants. You should still be wary of nonprescription products that list 5-MTHF, L-methylfolate, or "optimized folate" as the main ingredient.

GABA

Gamma-aminobutyric acid (GABA) is a neurotransmitter involved in inhibition and stress relief and sold as a capsule, pill, or powder. Notably, low GABA levels have been linked to depression and anxiety, per the NLM. A November 2020 study in Heliyon noted that "GABA functions as an antidepressant…"—but in reference to how GABA plays a role in depression in rats. Therefore, it appears that evidence of commercial GABA supplements' impact on mood is still to be determined.

Omega-3s

The polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential to brain function and cardiovascular health, are considered to be omega-3s. Combined in roughly equal amounts, EPA and DHA are the main ingredients in fish oil, but they are also sold in formulas that include more of one than the other.

Researchers who conducted a July 2015 study published in Integrative Medicine Research found that the efficacy of omega-3s was mixed: Some studies found that they were helpful, while others were inconclusive. Another May 2021 Journal of Food Bioactives review noted that studies had not yet determined "a causal relationship between omega-3 fatty acids and depression."

Thus, it remains unclear just how effective omega-3s are, and what formulation and combination of treatments are most beneficial. But omega-3s have few side effects and have cardiovascular and other health benefits, so they may be worth a try (after consulting your healthcare provider first).

Saffron

A spice, made from the dried stigmas of crocus plants, saffron is used in cooking and also in traditional Persian medicine to treat symptoms of depression (among other conditions). Although they can be found online, saffron supplements are not widely available.

Researchers conducted a meta-analysis, published in January 2019 in Planta Medica. They found that the studies investigated showed saffron to be more effective than placebos for mild to moderated depression. However, they were not found to be superior to selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and citalopram. (According to the NLM, SSRIs are antidepressants that generally work by increasing serotonin levels to decrease depressive symptoms.)

Additionally, a May 2021 Bioactive Compounds in Health and Disease article noted that saffron was also helpful for adults dealing with premenstrual syndrome (PMS) and menopause or menopausal symptoms along with depression.

For saffron, more research is needed to confirm the exact level of effectiveness for treating depression—though it appears to be a promising treatment for milder cases of depression.

SAMe

S-adenosylmethionine (SAMe, pronounced "sammy") is a naturally occurring compound that affects neurotransmitters, including serotonin and dopamine.

As with most of the substances on this list, lower levels of SAMe have been associated with depression. Specifically, SAMe can be helpful when used in conjunction with other natural treatments for depression. For example, one June 2020 The Primary Care Companion for CNS Disorders study explored the use of SAMe with L. plantarum HEAL9 (a probiotic) compared to a placebo. The researchers discovered that the combined supplementation was beneficial for improving depressive symptoms in participants after only two weeks.

SAMe has proven to be useful for the treatment of depression, but questions about its overall effectiveness and delivery methods remain. SAMe does have some side effects: It can exacerbate mania or hypomania in people with bipolar disorder. Thus, you should not take SAMe without consulting a physician.

Tryptophan

Tryptophan is an amino acid—most famous for being found in Thanksgiving turkey—that helps produce serotonin, the neurotransmitter targeted by drugs such as Prozac (SSRIs). It is sold over-the-counter in capsule form as L-tryptophan and 5-HTP, which represent different stages in the serotonin production process.

Studies have shown a connection between tryptophan depletion and depressive symptoms. Researchers of a January 2016 Nutrients study concluded that "emotional processing…is inhibited in subjects with depression…after tryptophan depletion." Another study, published in February 2021 in Translational Psychiatry, noted that individuals with depression have negative affect with acute tryptophan depletion. However, the overall evidence is inconclusive regarding tryptophan's effectiveness.

As early as 1990, the U.S. Food and Drug Administration (FDA) temporarily pulled all L-tryptophan products off the market after more than 1,500 people who took L-tryptophan supplements developed a blood disorder called eosinophilia myalgia syndrome—which may have occurred due to contamination, according to MedlinePlus. More than two dozen people died as a result. Furthermore, safety concerns exist if a person takes L-tryptophan for more than three weeks. Thus, it might be worth looking into other options that may be more beneficial for treating depressive symptoms.

Vitamin D

Vitamin D is a versatile nutrient in that it is naturally made by your body but can also be consumed through foods and supplements, according to the National Institutes of Health (NIH). It is the primary vitamin responsible for bone growth through calcium absorption.

Research is growing in regard to vitamin D's efficacy and depression. A January-February 2020 study published in the Indian Journal of Psychological Medicine indicated that a connection between depression and vitamin D exists. The researchers noted that this may be due to vitamin D receptors playing a part in the regulation of emotions and vitamin D as part of the link between depression and inflammation, for example. However, they also mentioned that vitamin D might be more helpful for people diagnosed with depression compared to people who only exhibit a few depressive symptoms—just not enough for an official diagnosis.

Zinc

The NIH has noted zinc as a nutrient that plays a role in immunity, protein and DNA production, and wound healing. An individual's age determines the amount of zinc they need on a daily basis—but this might vary if depression is a factor in your life.

According to a May 2018 Nutrients article, zinc and depression have been known to be linked since the 1980s. The researchers also stated that "psychological and biological changes may act in concert to influence the development of depression, which itself could further reduce serum zinc levels." In other words, a deficiency in zinc could make a person more susceptible to depression, making zinc supplements a possible remedy for alleviating depression.

Ultimately, if you are interested in using any of the options above, your healthcare provider will know which supplements—if any—could help you best manage your depressive symptoms.

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