Matthew Messer

Matthew Messer


Depression is a serious mood disorder that unfortunately affects millions of people worldwide. It is not an occasional foul mood, but a condition that lasts months, or even years, and makes life tremendously difficult. There are several types of depression, which are usually treated with medication, unfortunately often without success. (1) Given the serious consequences of depression for individuals and society, research regarding its risk factors and potential solutions is ongoing. The fact that deficiencies of certain micronutrients may be linked to the development of mental illness has long been known, although unfortunately this is still rarely considered in treatment today. In addition to vitamin D, B vitamins, and long-chain omega-3 fatty acids, magnesium is known to have numerous properties that make a deficiency worsen depression symptoms, while achieving adequate levels may be part of effective therapy. (2)

The link between magnesium deficiency and depression 

Magnesium is one of those vital micronutrients that most people consume far less of than they need. (3) Traditional magnesium-rich foods have been largely replaced by processed foods, and natural foods, too are steadily declining in magnesium content. Unfortunately, as a study published in 2009 points out, the decline in magnesium intake has been accompanied by an increase in the consumption of various stimulants, not to mention the constant availability of exciting input provided by modern technology. (2) Magnesium deficiency can therefore lead to various neurological disorders, according to researchers, producing symptoms similar to depression.  

This explains why magnesium supplementation id effective in some people who do not experience improvement from various antidepressant medications. Some antidepressants work by, among other things, increasing cellular magnesium levels. (4) Observational studies and research in animal models clearly demonstrate that a reduction in magnesium intake is associated with depressive symptoms, but let's look at the results of human clinical trials. (5,6) 

The effect of magnesium on depression 

In a study of people with depression, participants in one group were given 450 mg of elemental magnesium daily, while participants in the other group were given a known antidepressant for 12 weeks. (7) Magnesium supplementation was as effective as the antidepressant in reducing depressive symptoms.  

In a study of adults with mild depression published in 2017, participants were given magnesium chloride (a moderately well-absorbed form) containing 250 mg of elemental magnesium per day for 6 weeks, followed by a placebo for another 6 weeks. (8) Magnesium supplementation significantly reduced their depressive symptoms, the magnesium was fast-acting and well tolerated by participants. Most reported that they would continue supplementation after the trial.   

In another randomized controlled trial in the same year on depressed and magnesium-deficient individuals, the participants were divided into two groups. One group received two 250 mg magnesium oxide capsules per day, while the other group received a placebo. (9) Although the least absorbable form of magnesium was employed, the participants who received magnesium still showed significant improvement, with a remarkable reduction in symptoms. 

Also in 2017, magnesium supplementation was tested in people with depression who did not respond to conventional medication. (10) By the end of the 8-week trial, two-thirds of the participants had experienced significant improvement, but their condition rapidly declined again when the magnesium was stopped. 

In 2020, the results of a recent clinical trial testing the stress and anxiety-reducing effects of magnesium and the popular magnesium+B6 supplement were published. (11) Stress and anxiety are closely linked to depression, so it is encouraging that both types of supplementation were effective in reducing unpleasant symptoms compared to the placebo group. The difference between the two groups supplementing with magnesium was minimal: those who also received vitamin B6 did slightly better, but this benefit was negligible, so the main effect could be attributed to magnesium. In this study, magnesium lactate was used, which is well utilized,  in an amount equivalent to 300 mg of elemental magnesium, so both dosage and chemical formulation were well-chosen this time. 

Worth a try 

In conclusion, magnesium supplementation can be effective in treating depression, especially in the case of magnesium deficiency. Its mechanism of action is similar to that of certain drugs also used as antidepressants. Magnesium deficiency is very common, but supplementation in the right dose and form is safe and does not cause serious side effects. 

  1. Voineskos D, Daskalakis ZJ, Blumberger DM. Management of Treatment-Resistant Depression: Challenges and Strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. Published 2020 Jan 21. doi:10.2147/NDT.S198774 

  2. Eby GA 3rd, Eby KL. Magnesium for treatment-resistant depression: a review and hypothesis. Med Hypotheses. 2010 Apr;74(4):649-60. doi: 10.1016/j.mehy.2009.10.051. Epub 2009 Nov 27. PMID: 19944540. 

  3. Rosanoff A. Perspective: US Adult Magnesium Requirements Need Updating: Impacts of Rising Body Weights and Data-Derived Variance. Adv Nutr. 2021 Mar 31;12(2):298-304. doi: 10.1093/advances/nmaa140. PMID: 33179034; PMCID: PMC8009744. 

  4. Nechifor M. Magnesium in major depression. Magnes Res. 2009 Sep;22(3):163S-166S. PMID: 19780403. 

  5. Cheungpasitporn W, Thongprayoon C, Mao MA, Srivali N, Ungprasert P, Varothai N, Sanguankeo A, Kittanamongkolchai W, Erickson SB. Hypomagnesaemia linked to depression: a systematic review and meta-analysis. Intern Med J. 2015 Apr;45(4):436-40. doi: 10.1111/imj.12682. PMID: 25827510. 

  6. Spasov AA, Iezhitsa IN, Kharitonova MV, Kravchenko MS. [Depression-like and anxiety-related behaviour of rats fed with magnesium-deficient diet]. Zh Vyssh Nerv Deiat Im I P Pavlova. 2008 Jul-Aug;58(4):476-85. Russian. PMID: 18825946. 

  7. 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 Dec;21(4):218-23. PMID: 19271419. 

  8. Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLoS One. 2017 Jun 27;12(6):e0180067. doi: 10.1371/journal.pone.0180067. PMID: 28654669; PMCID: PMC5487054. 

  9. Rajizadeh A, Mozaffari-Khosravi H, Yassini-Ardakani M, Dehghani A. Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial. Nutrition. 2017 Mar;35:56-60. doi: 10.1016/j.nut.2016.10.014. Epub 2016 Nov 9. PMID: 28241991. 

  10. Bambling M, Edwards SC, Hall S, Vitetta L. A combination of probiotics and magnesium orotate attenuate depression in a small SSRI resistant cohort: an intestinal anti-inflammatory response is suggested. Inflammopharmacology. 2017 Apr;25(2):271-274. doi: 10.1007/s10787-017-0311-x. Epub 2017 Feb 2. PMID: 28155119. 

  11. Hitier S, Dualé C, Pouteau E. Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial. Magnes Res. 2020 Aug 1;33(3):45-57. doi: 10.1684/mrh.2020.0468. PMID: 33210604. 

  12. Lewitzka U, Severus E, Bauer R, Ritter P, Müller-Oerlinghausen B, Bauer M. The suicide prevention effect of lithium: more than 20 years of evidence-a narrative review. Int J Bipolar Disord. 2015;3(1):32. doi:10.1186/s40345-015-0032-2 

  13. Corriger A, Pickering G. Ketamine and depression: a narrative review. Drug Des Devel Ther. 2019 Aug 27;13:3051-3067. doi: 10.2147/DDDT.S221437. PMID: 31695324; PMCID: PMC6717708. 

Related contents: