Magnesium and Depression
Not having enough magnesium can cause nerve issues. When wheat is refined, only 16% of its magnesium remains. Magnesium is often removed from drinking water, leading to deficiency. Magnesium helps control the flow of calcium in the brain, which affects nitric oxide production. If there is not enough magnesium, it can harm the nerves and possibly cause depression. Some believe magnesium supplements could treat depression (1).
In one study, depressed people with magnesium deficiency took magnesium oxide tablets daily for over 8 weeks, showing improvements in depression and magnesium levels. In this study, 60 depressed people suffering from magnesium deficiency were randomized into two groups of 30 members; one receiving two 250-mg tablets of magnesium oxide daily and the other receiving placebo for 8 weeks. The Beck Depression Inventory-II was conducted and the concentration of serum magnesium was measured (2).
At the end of the intervention, 88.5% of the magnesium group and 48.1% of the placebo group (p = 0.002) had a normal level of magnesium. The mean changes in serum magnesium were significantly different across the two groups. After the intervention, the mean Beck score significantly declined. However, in the magnesium group, this reduction was more significant than in the placebo group (p = 0.02), the mean changes in the treatment group experienced a 15.65 ± 8.9 reduction, while in the placebo group, it declined by 10.40 ± 7.9 (2). This study showed that daily consumption of 500 mg magnesium oxide tablets for more than 8 weeks by depressed patients suffering from magnesium deficiency could lead to improvements in depression status and magnesium levels (2).
Another study tested magnesium chloride supplementation for mild-to-moderate depression, resulting in a significant improvement within two weeks. 126 adults (mean age 52; 38% male) diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19 received 6 weeks of treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment). Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future (3).
Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; p<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; p<0.001). Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium supplementation was shown to be effective for mild-to-moderate depression treatment in adults. It worked quickly and was well tolerated without the need for close monitoring for toxicity (3).
A trial with a magnesium-vitamin B6 combination showed a reduction in stress levels, especially in those with severe stress. Adding vitamin B6 didn't show superiority over magnesium alone. Healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L–0.85 mmol/L, were randomized 1:1 to magnesium–vitamin B6 combination (Magne B6 [Mg–vitamin B6]; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl [Mg]; daily dose 300 mg). Outcomes included a change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (4).
Both treatments substantially reduced the DASS-42 stress subscale score from baseline to Week 8 (Mg–vitamin B6, 44.9%; Mg 42.4%); no statistical difference between treatments was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; n = 162) had a 24% greater improvement with Mg–vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). These findings suggested that oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6 (4).
The relationship between magnesium status and vitamin B6 to mental health and/or quality of life (QoL: Short Form-36 Health Survey) of this study (4) was further examined in a secondary analysis (5). Both magnesium alone and magnesium-vitamin B6 combination showed improvements in anxiety, depression, and quality of life (5).
DASS-42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks. Improvement in QoL continued over 8 weeks. Participants perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than with magnesium alone (Week 4). This study concluded that magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesium status (5).
Anxiety-related conditions are the most common affective disorders present in the general population with a lifetime prevalence of over 15%. Magnesium status is associated with subjective anxiety, leading to the proposition that Mg supplementation may attenuate anxiety symptoms. Supplementation of magnesium can be helpful to reduce stress and depression (6).
References:
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Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70. doi: 10.1016/j.mehy.2006.01.047. Epub 2006 Mar 20. PMID: 16542786.
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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.
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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.
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Pouteau E, Kabir-Ahmadi M, Noah L, Mazur A, Dye L, Hellhammer J, Pickering G, Dubray C. 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. 2018 Dec 18;13(12):e0208454. doi: 10.1371/journal.pone.0208454. PMID: 30562392; PMCID: PMC6298677.
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Noah L, Dye L, Bois De Fer B, Mazur A, Pickering G, Pouteau E. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial. Stress Health. 2021 Dec;37(5):1000-1009. doi: 10.1002/smi.3051. Epub 2021 May 6. PMID: 33864354; PMCID: PMC9292249.
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Boyle NB, Lawton C, Dye L. The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients. 2017 Apr 26;9(5):429. doi: 10.3390/nu9050429. PMID: 28445426; PMCID: PMC5452159.
Related blog: Magnesium and Sleep
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