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SUBSCRIBE: eNewsletter

Evidence-Based Research on the Role of Zinc and Magnesium Deficiencies in Depression

  • James M. Greenblatt, MD
  • Winnie To, BS
  • Jennifer Dimino, MS
Dec 30, 2016
Volume: 
33
Issue: 
12
  • Special Reports, Depression, Psychopharmacology
© shutterstock.com
© shutterstock.com
SIGNIFICANCE FOR THE PRACTICING PSYCHIATRIST
SIGNIFICANCE FOR THE PRACTICING PSYCHIATRIST

Minerals are critical in supporting several key functions related to mood disorders, including neuro­ transmitter synthesis, cellular metabolism, and immunocompetence. While micronutrient deficiencies were presumably thought to occur in lower-income countries, micronutrient depletion has emerged as a form of “type B” malnutrition in industrialized countries despite food surpluses. Modern-day malnutrition has been attributed to poor dietary patterns, marked by excess intake of refined sugars and the absence of nutrient-dense foods.

The significance of various nutrients for mental health status has been established, but whether poor nutritional status is a causative agent or an effect of poor mental health continues to be debated. However, the prevalence of poor nutrition among depressed persons is indisputable—nutritional deficiencies have frequently been associated with the incidence and increased risk of depressive symptoms.

Related content: Micronutrients and Depression

In a population study that included 13,486 children and adolescents, excess consumption of low nutritional content foods was correlated with increased aggression, violent behaviors, and psychiatric distress.1 Earlier clinical studies also indicated a positive correlation between rates of depression and poor nutrition. In a study that comprised 184 elderly participants, researchers found that up to 50% had identified nutritional inadequacies and comorbid depression.2

The role of micronutrients in the pathophysiology of depression

Current research illustrates the vast array of mental health complications that may arise because of micronutrient deficiencies, including impairments in cognitive function and neuromotor performance, effects on brain morphology, and disruption of neurochemical pathways. Micronutrients are vital in enzymatic reactions responsible for neurotransmitter synthesis and preservation, and mineral deficits have been identified in the pathophysiology of depressive symptoms.3

Minerals are essential in the enzymatic activation of brain-derived neurotrophic factor (BDNF), a protein that regulates neuronal plasticity and promotes the maturation and differentiation of new neurons within the CNS and the peripheral nervous system. Animal studies have shown that stress can reduce BDNF expression and activity in the hippocampus, and clinical studies have echoed similar findings in which serum BDNF levels are reported to be lower in depressed patients than in controls.4,5 Augmentation strategies that can facilitate BDNF expression have been emerging as an area of interest among researchers.

Augmentation strategies with zinc

As one of the most abundant trace minerals in the brain, zinc supports several physiological functions and possesses immuno-modulation properties. Zinc also activates hippocampal neurogenesis through the upregulation of BDNF, while inhibiting glutamate and N-methyl-D-aspartate (NMDA) activity.

The bioavailability of zinc can influence CNS function through a variety of mechanisms, and diets scarce in zinc have been known to result in behavioral disturbances and diminished brain function. In a meta-analysis that evaluated 17 studies with 1643 depressed and 804 control participants, peripheral serum zinc concentrations were approximately -1.85 µmol/L lower in depressed participants.6 Moreover, low serum plasma zinc levels have been associated with impairments in information processing and impulsivity in humans.7

Disclosures: 

Dr. Greenblatt is Chief Medical Officer and Vice President of Medical Services, Walden Behavioral Care, Waltham, MA; Assistant Clinical Professor, Tufts University School of Medicine, Boston, MA; and Assistant Clinical Professor, Dartmouth College Geisel School of Medicine, Hanover, NH. Ms. To is a research assistant for Psychiatry Redefined, Manchester, NH, and a BSN/MSN candidate at Regis College, Weston, MA. Ms. Dimino is a research assistant at Psychiatry Redefined. The authors report no conflicts of interest concerning the subject matter of this article.

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References: 

1. Zahedi H, Kelishadi R, Hesmat R, et al. Association between junk food consumption and mental health in a national sample of Iranian children and adolescents: the CASPIAN-IV study. Nutrition. 2014;30: 1391-1397.

2. Payahoo L, Khaje-Bishak Y, Pourghassem B, et al. Assessment of nutritional and depression status in free-living elderly in Tabriz, Northwest Iran. Health Promot Perspect. 2013;3:288-293.

3. Rao TS, Asha R, Ramesh BN, Jagannatha KS. Understanding nutrition, depression and mental illnesses. Indian J Psychiatry. 2008;50:77-82.

4. Lee BH, Kim Y. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investig. 2010;7:231-235.

5. Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008;11:1169-1180.

6. Swardfager W, Herrmann N, McIntyre RS, et al. Potential roles of zinc in the pathophysiology and treatment of major depressive disorder. Neurosci Biobehav Rev. 2013;37:911-929.

7. Arnold LE, DiSilvestro RA. Zinc in attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2005;15:619-627.

8. Sowa-Kucma M, Kowalska M, Szlosarczyk M, et al. Chronic treatment with zinc and antidepressants induces enhancement of presynaptic/extracellular zinc concentration in the rat prefrontal cortex. Amino Acids. 2011;40:249-258.

9. Ranjbar E, Kasaei MS, Mohammad-Shirazi M, et al. Effects of zinc supplementation in patients with major depression: a randomized clinical trial. Iran J Psychiatry. 2013;8:73-79.

10. Swardfager W, Herrmann N, Mazereeuw G, et al. Zinc in depression: a meta-analysis. Biol Psychiatry. 2013;74:872-878.

11. Weston PG. Magnesium as a sedative. Am J Psychiatry. 1921;78:637-638.

12. Jacka FN, Overland S, Stewart R, et al. Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study. Aust N Z J Psychiatry. 2009;43:45-52.

13. Nechifor M. Magnesium in major depression. Magnes Res. 2009;22:163S-166S.

14. Carlson N. Foundations of Behavioral Neuroscience. 9th ed. Upper Saddle River, NJ: Pearson Education Inc; 2014.

15. Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnes Res. 2008;21:218-223.

16. Teymoor Y, Sanaz A, Kourosh S. Dietary intake of magnesium may modulate depression. Biol Trace Elem Res. 2013;151:324-329.

17. Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991;337:757-760.

18. Poleszak E. Modulation of antidepressant-like activity of magnesium by serotonergic system. J Neural Trans. 2007;114:1129-1134.

19. Heiden A, Frey R, Presslich O, et al. Treatment of severe mania with intravenous magnesium sulphate as a supplementary therapy. Psychiatry Res. 1999;89:239-246.

20. Rosanoff A, Weaver CM, Rude RK. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr Rev. 2012;70:153-164.

21. Belmaker RH, Agam G. Major depressive disorder. N Engl J Med. 2008;458:55-68.

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