Depression, Stress, and Anxiety - Does Magnesium Play a Role?

Magnesium and the Brain

As part of magnesium’s role as an activator of 600+ enzyme systems within our body, it has several actions in the regulation of brain and nervous system function.

Magnesium regulates the excitability of NMDA (N-methyl-D-aspartate) receptors, which play a role in learning and memory, development, and anxiety and fear conditioning.(1) When we become deficient in magnesium, these receptors become easily excitable and work less efficiently. Dysfunction of these NMDA receptors is considered by scientists to be a “major causative factor in depression.”(2)

In addition, magnesium helps regulate GABA receptors. GABA receptors are estimated to be present in almost 40% of the synapses in the human brain. (3)

Magnesium also acts as a cofactor in the synthesis of neurotransmitters. (4)

It has also been proposed that magnesium may influence the ability of corticosteroids (stress hormones) to enter the brain through the blood/brain barrier in its role regulating the function of transport proteins. In a state of low magnesium, this can create “a vicious cycle of reduced resistance to stress and further magnesium depletion.”(5)

Lastly, we know that low levels of magnesium in our neurons cause excess intracellular calcium to accumulate, which can lead to production of reactive oxidative species, and eventually neuronal cell death. (6)

Magnesium and Depression

Dietary magnesium intake and depression

• A large study found that magnesium intake <184 mg per day was significantly associated with depression. In this study, those (under age 65) with the highest magnesium intake had 20% lower odds of having depression, as compared with those with the lowest magnesium intake (highest vs lowest quartile). (7)
• Another large-scale study with more than 17,000 participants found an inverse relationship between magnesium intake and depression.(8) Those with the highest magnesium intake had 53% lower odds of depression, compared with those with the lowest magnesium intake (highest vs lowest quintile).

Magnesium supplementation and depression

• In depressed patients with low serum magnesium, supplementing with 500 mg of magnesium for 8 weeks resulted in improvement of depression, as measured by the Beck Depression Inventory scores. (9)

Magnesium and Anxiety

• A 2017 systematic review of 18 studies concluded that magnesium had a positive impact on subjective anxiety. (10)
• A placebo-controlled trial found that supplementation with a multivitamin with large amounts of magnesium, zinc, and calcium for 28 days dramatically decreased psychological distress and anxiety in participants. (11)

Magnesium and Stress

Magnesium is known to modulate activity of the HPAA axis, which is a central component of our stress response. (12)

• A German study found that supplementing with 400 mg of magnesium daily for 90 days decreased stress index scores, and increased heart rate variability (a measure of your heart’s responsiveness to nervous system signals). (13)
• Male students who supplemented with 500 mg magnesium daily for 4 weeks saw a significant decrease in serum cortisol (a biomarker for stress), and interleukin-6 (a marker of inflammation). (14)
• Another study looked at healthy adults with low serum magnesium concentrations (0.45-0.85 mmol/L), and high stress levels as measured by the DASS-42 stress subscale (Depression Anxiety Stress Scales). Participants were given either 300 mg elemental magnesium alone, or 300 mg magnesium plus 30 mg of vitamin B6 daily. After 8 weeks of supplementation the overall percent of subjects with severe or extremely severe stress decreased from 60% to 12% following supplementation. Those who supplemented with magnesium alone saw a 42.4% improvement in stress scores. The magnesium + B6 group had a 44.9% improvement in stress scores. (15)

Magnesium and Mood

• In women experiencing PMS-related mood changes, supplementation with 360 mg of magnesium, 3x per day saw significant reductions in negative affect (poor mood). (16)

References

1. Barkus, C., et al. 2010. Hippocampal NMDA receptors and anxiety: At the interface between cognition and emotion. European Journal of Pharmacology 626(1):49–56. doi:10.1016/j.ejphar.2009.10.014.
2. Paoletti, P., et al. 2013. NMDA receptor subunit diversity: Impact on receptor properties, synaptic plasticity and disease. Nature Reviews. Neuroscience 14(6):383–400. doi:10.1038/nrn3504.
3. Canadian Institutes of Health Research, Institute of Neurosciences, Mental Health and Addiction. Anxiety neurotransmitters in The Brain from Top to Bottom website https://thebrain.mcgill.ca/flash/d/d_04/d_04_m/d_04_m_peu/d_04_m_peu.html. Accessed 11 Aug. 2020.
4. Gendle, M. H., et al. 2015. Oral magnesium supplementation and test anxiety in university undergraduates. Journal of Articles in Support of the Null Hypothesis 11(2):21–31.
5. Murck, H. 2002. Magnesium and affective disorders. Nutritional Neuroscience 5(6):375–389. doi:10.1080/1028415021000039194.
6. de Baaij, J. H. F., et al. 2015. Magnesium in man: Implications for health and disease. Physiological Reviews 95(1):1–46. doi:10.1152/physrev.00012.2014.
7. Tarleton, E. K., and B. Littenberg. 2015. Magnesium intake and depression in adults. Journal of the American Board of Family Medicine: JABFM 28(2):249–256. doi:10.3122/jabfm.2015.02.140176.
8. Sun, C., et al. 2019. Dietary magnesium intake and risk of depression. Journal of Affective Disorders 246:627–632. doi:10.1016/j.jad.2018.12.114.
9. Rajizadeh, A., et al. 2017. Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial. Nutrition 35:56–60. doi:10.1016/j.nut.2016.10.014.
10. Boyle, N. B., et al. 2017. The effects of magnesium supplementation on subjective anxiety and stress—A systematic review. Nutrients 9(5):429. doi:10.3390/nu9050429.
11. Carroll, D., et al. 2000. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological well-being in healthy young male volunteers: A double-blind placebo-controlled trial. Psychopharmacology 150(2):220–225. doi:10.1007/s002130000406.
12. Boyle, N. B., et al. 2017. The effects of magnesium supplementation on subjective anxiety and stress—A systematic review. Nutrients 9(5):429. doi:10.3390/nu9050429.
13. Wienecke, E., and C. Nolden. 2016. [Long-term HRV analysis shows stress reduction by magnesium intake]. Article in German. MMW Fortschritte der Medizin 158(Suppl 6):12–16. doi:10.1007/s15006-016-9054-7.
14. Zogović, D., et al. 2014. Pituitary-gonadal, pituitary-adrenocortical hormones and IL-6 levels following long-term magnesium supplementation in male students. Journal of Medical Biochemistry 33(3):291–298. doi:10.2478/jomb-2014-0016.
15. Pouteau, E., et al. 2018. Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PLoS ONE 13(12). doi:10.1371/journal.pone.0208454.
16. Facchinetti, F., et al. 1991. Oral magnesium successfully relieves premenstrual mood changes. Obstetrics and Gynecology 78(2):177–181.