Can you blueberry your way out of depression? The evidence on dietary supplements

Can you blueberry your way out of depression? The evidence on dietary supplements
There has been increased interest in nutritional supplements as an adjunct or alternative to medications in the treatment of depression.

Depression is a common mental health complaint. Although there are effective treatments available, many patients fail to experience satisfactory improvement. There has been increased interest in nutritional supplements as an adjunct or alternative to medications in the treatment of depression. This has contributed to the growth of the dietary supplement industry (projected to reach 230 billion by 2026). Let’s examine the evidence for the dietary supplements that have generated interest in recent years.

Omega-3 fatty acids (EPA/DHA)

A systematic review shows mild-moderate improvement in depressive symptoms, with the best outcomes in studies where omega-3 supplementation is concomitant to standard antidepressant therapy. There is a great deal of heterogeneity in dosing, duration of treatment and EPA/DHA content. Products with a high EPA content appear to be more efficacious than other omega-3 supplements. However, quality of evidence is low due to methodological flaws. Differences in study design and methodology makes it difficult to analyze data across studies. Omega-3 supplements have a favorable safety profile and are well tolerated.

B group vitamins

Folate- Possible dose dependent response in depression but level of evidence is low. Although folate is well tolerated, it has been associated with risk for proliferation of carcinogenic cells in the colon.

L-methylfolate-Available as pharmaceutical product FDA approved for depression. Data shows efficacy at 15mg/d. Some studies show efficacy as augmentation strategy for depression as comparable to lithium and atypical antipsychotics. Usually well tolerated with lower risk for proliferation of cancerous cells than folate.

Vitamin D

A 2019 systematic review of clinical trials showed improvement in depression ratings associated with supplementation. Findings remain tentative due to paucity of studies and methodologic bias. Vitamin D is a fat-soluble vitamin commonly found in multivitamins and other commercially available products. In the absence of a deficiency, the recommended dose is not to exceed 600IU/day.

SAM-E (S-Adenosyl methionine)

Clinical trials show mixed results. A 2016 systematic review suggested SAM-E was no better than placebo. The low quality of evidence makes it difficult to draw conclusions about efficacy. There is a need for randomized clinical trials with antidepressant comparators. SAM-E usually well tolerated but there is a possible risk for inducing mania in patients with bipolar depression.

Tryptophan/5-HTP (5-Hydroxytryptophan)

There are few high quality studies of 5-HTP. Two depression studies suggest 5-HTP is superior to placebo. Overall, level of evidence is low. Possible risk for serotonin syndrome when administered concurrently with SSRI antidepressants. Maximum recommended dose is 50mg/kg/day.

Magnesium and Zinc

There is some positive data from animal studies but evidence for efficacy in humans is low quality. There is no conclusive data on the efficacy of magnesium and zinc as coadjutant therapy in depression. Zinc and magnesium are common micronutrients and usually well tolerated.


Depression has been associated with poor diet and altered intestinal flora. Research has shown a relationship between gut health and mental health. A 2016 metaanalysis of probiotics showed an effect in reducing risk of depression in normal subjects and reduced symptoms in subjects with depression. The effect was limited to subjects under age 60. Clinical studies vary greatly in terms of bacterial species, dose, duration of treatment as well as the method of measuring of depressive symptoms. Probiotic supplements are vastly heterogeneous in terms of species composition and dosage.

There is a need for further research to determine optimal composition, dosage, duration of treatment for efficacy. Furthermore, it is important to remember that quality of diet is a major determinant in the composition of gut flora.

In conclusion, evidence for the efficacy of dietary supplements in depression remains limited. Commercially available dietary supplements vary significantly in terms of composition and bioavailability. Although supplements are well tolerated, it is important to be aware of increased risks for adverse events in some patients. Supplementation with omega-3 fatty acids as an adjunct to standard antidepressant therapy seems to hold the most promise. Further research in the area of dietary supplements is needed to determine their role in the management of depression.

For more information about Depression research studies at the Lindner Center of HOPE

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Press release above provided by Lindner Center of HOPE