Are Your Depression Patients Not Getting Better? Check For These Nutrient Deficiencies!

IV Therapy Academy

Jason A. Duprat, MBA, CRNA

Jason A. Duprat, MBA, CRNA

January 21, 2023

Nutrient Deficiencies and Depression

Depressive disorders such as major depression, persistent depressive disorder, and premenstrual dysphoric disorder negatively affect our patients’ moods and can cause changes to their physical activity levels, appetites, sleep habits, and weight. In other words, they can seriously disrupt their lives. Fortunately, we have quite a few pharmaceutical tools in our toolbox that we can utilize in order to address these concerns, but what happens when these tools fail to restore optimal wellness? According to a study funded by the National Institute of Mental Health, 1 in 3 people with depressive disorders don’t experience remission, even after trying up to 4 different antidepressant therapies.[1] That’s 33%! Given the fact that such a large portion of our patients will not experience remission even after trying multiple drugs, it’s past time that we explore additional potential causes (such as micronutrient deficiency) and potential solutions to this depression crisis that our nation is currently facing. Although they aren’t the only contributing factors to depressed mood, we absolutely need to be on the lookout for micronutrient deficiency in our patients and to know how to address them when we do identify them, because insufficient amounts of vitamins and minerals such as B vitamins, zinc, and chromium have been shown to lead to depressive symptoms.

How Does Not Having Enough B Vitamins Affect Mood?

Sufficient B vitamins are essential in helping to maintain a balanced mood. As examples, vitamin B6 plays a crucial role in metabolizing tryptophan to serotonin, while folate and vitamin B12 are crucial for one-carbon metabolism (methylation) and therefore the formation of S-adenosyl methionine.

Here’s a more specific example: Low levels of vitamin B6 are associated with symptoms of premenstrual depression as well as depression due to other causes, and increasing the body’s stores of this vitamin has been shown to result in a reduction in associated symptoms.[2-3] As another example, depressed individuals tend to have lower levels of folate and B12 than non-depressed individuals, and increasing the body’s stores of these vitamins has been demonstrated to result in significant improvements in mood. Additionally, individuals taking SSRIs who have low folate levels tend to not respond as well to the medication as those who have sufficient levels of folate.[4] Research demonstrates that folate has beneficial effects on mood, both in individuals who are taking antidepressant medication and in medication-naïve, depressed individuals.[5]

Can Low Zinc Levels Lead to Depression?

Zinc is another micronutrient that plays a significant role when it comes to mood. A subtype of unipolar depression, typically characterized by altered behavior and cognition, reduced ability to learn, and depressed mood, has been associated with low blood zinc levels.[6] Interestingly, when effectively treated with antidepressant therapies, zinc levels tend to rise in these individuals.[7]

Furthermore, double-blind, randomized, placebo-controlled clinical trials demonstrate that zinc augments the effects of SSRI medication. At the end of one trial, individuals who were given both their SSRI and zinc showed significant improvement in their depression scores compared to those who took their SSRI alone.[8] Similar results were seen when zinc was combined with antidepressants of other drug classes as well.[7]

We believe the connection between zinc status and mood can be attributed to the fact that alterations in zinc homeostasis affects neurotransmission as well as the immune system, contributing to mood disorders.[6] Preclinical studies support this mechanism, because they demonstrate alterations in brain zinc concentrations in response to pharmaceutical antidepressant therapy and other treatments such as electroconvulsive therapy.

How Does Chromium Insufficiency Contribute to Depression?

Chromium is another mineral that can significantly affect mood. We believe this is because chromium plays a crucial role in neurotransmitter synthesis. It also increases brain levels of serotonin and norepinephrine.[9]

Presumably because of chromium’s effect on neurotransmitter synthesis and on blood sugar, more specifically, insulin sensitivity, individuals enrolled in a randomized controlled trial whose depression was characterized by carbohydrate craving and depressed mood showed significant improvements in both their cravings and their mood after supplementing with chromium.[10] Chromium has also been demonstrated to improve persistent depressive disorder (formerly known as dysthymic disorder) in some individuals, even after failure of conventional medical treatments.[11]

How Can We Use This Information To Help Our Patients?

B vitamins, zinc, and chromium are only three of the many micronutrients that can significantly impact mood. The fact of the matter is that when our depressed patients don’t respond to our typical treatment options (and I would actually argue that we should do this even before starting our patients on pharmaceutical medication), we need to evaluate for deficiency and insufficiency of crucial micronutrients. After evaluation, we need to address areas of suboptimal nutrient status and we can do this in multiple ways.

Oral supplementation has been shown to be beneficial, but its success depends heavily upon the individual’s ability to absorb and/or transport said nutrients. Intravenous (IV) administration of micronutrients, on the other hand, is beneficial because it bypasses the gut and therefore eliminates this concern. Furthermore, because depression recurs in 70% of affected individuals,[9] as a part of our overarching investigation to identify the underlying cause(s) of our patients’ health concerns, it would be beneficial for us to evaluate all patients with a current diagnosis or a history of depression for micronutrient insufficiency and we should consider IV nutrient therapy as an effective means of replenishing their micronutrient stores.

Rush, A. J. et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry 163, 1905–1917 (2006).

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Wyatt KM, Dimmock PW, Jones PW, Shaughn O’Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. Bmj May 22;1999 318(7195):1375–1381. [PubMed: 10334745]

Papakostas GI, Petersen T, Denninger JW, et al. Psychosocial functioning during the treatment of major depressive disorder with fluoxetine. J Clin Psychopharmacol Oct;2004 24(5):507–511. [PubMed: 15349006]

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Petrilli, M. A., Kranz, T. M., Kleinhaus, K., Joe, P., Getz, M., Johnson, P., … Malaspina, D. (2017). The Emerging Role for Zinc in Depression and Psychosis. Frontiers in pharmacology, 8, 414. doi:10.3389/fphar.2017.00414

Nowak, G., Siwek, M.S., Dudek, D., Zięba, A.A., & Pilc, A. (2003). Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Polish journal of pharmacology, 55 6, 1143-7 .

Ranjbar, E., Kasaei, M. S., Mohammad-Shirazi, M., Nasrollahzadeh, J., Rashidkhani, B., Shams, J., … Mohammadi, M. R. (2013). Effects of zinc supplementation in patients with major depression: a randomized clinical trial. Iranian journal of psychiatry, 8(2), 73–79.

Kemper, K. J., & Shannon, S. (2007). Complementary and alternative medicine therapies to promote healthy moods. Pediatric clinics of North America, 54(6), 901–x. doi:10.1016/j.pcl.2007.09.002

Docherty JP, Sack DA, Roffman M, Finch M, Komorowski JR. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract Sep;2005 11(5):302–314. [PubMed: 16184071]

McLeod MN, Gaynes BN, Golden RN. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psychiatry Apr;1999 60(4):237–240. [PubMed: 10221284]

Jason A. Duprat, MBA, CRNA

Jason A. Duprat, MBA, CRNA


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