It is time to be happy, be glad, be (Mg)nificient?
The ongoing COVID-19 pandemic has significantly increased stress and anxiety levels among college students who are simultaneously worrying about their academic success and the well-being of family and friends. While in isolation, many students are troubled with the challenge of coping with symptoms of depression and may feel limited in their resources to maintain a healthy lifestyle. Loss of appetite is one of the symptoms associated with depression that is often overlooked but can worsen a student's condition if essential minerals, such as magnesium, are not adequately consumed (1). Magnesium (Mg2+), in particular, is credited with antidepressant properties that may improve an individual's emotional state. What is the evidence for this? Let's take a closer look.
Does stress and anxiety affect magnesium levels?
A low magnesium serum concentration is reported in about 45% of Americans (2) and is commonly attributed to diets poor in magnesium; however, prolonged stress and anxiety can also contribute to the depletion of magnesium levels (3). There is an interrelationship between magnesium concentrations and the amount of stress a person is experiencing. To upkeep a “normal” level of magnesium serum of 0.75 mmol/L to 0.955 mmol/L (4), a balance of magnesium intake and renal excretion needs to be maintained (2). The stress hormones, such as cortisol and adrenaline, increase the transport and diffusion of magnesium from inside the cells to the bloodstream. The magnesium in the bloodstream is filtered and excreted by the kidney (3). In turn, higher or more frequent ingestion of magnesium is necessary to counteract the mental and physical stress causing magnesium depletion.
How does magnesium help mediate anxiety, stress, and depression?
Magnesium is pivotal in enzymatic reactions and the regulation of serotonin and dopamine transmission, and therefore, necessary in maintaining normal brain functions. Deficient magnesium levels in rodents cause anxiety, stress, and depression (5). At the molecular level, magnesium appears to have the same effects as the antidepressant ketamine in rats, playing a role in blocking the glutamatergic N-methyl-D-aspartate (NMDA) receptor, a type of neuronal receptor. When NMDA receptors are blocked in the prefrontal cortex and hippocampus areas of the brain, it has been shown to decrease an individual's depressive symptoms (6). The obstruction of the NMDA receptor by magnesium primes the central nervous system to upregulate serotonin in the synaptic cleft. This persistence of serotonin in the synaptic cleft has been theorized to be important in treating depression symptoms. A study using a serotonin synthesis inhibitor in mice while supplementing with magnesium suggests that the effects of magnesium require the serotonin system (7).
An eight-week study conducted in Iran evaluated the change in magnesium concentrations and the status of depression in 60 human individuals either receiving two 250 mg magnesium oxide tablets or placebo (control) tablets daily (8). The serum magnesium concentration was measured with a photometric method, while the depression status was assessed with the Beck Depression Inventory-II self-report (21 questions, 0-3 score per question). This study found that the mean depression scores of patients in the magnesium group improved significantly more than in the control group (8). Despite these findings, further studies have to be conducted due to the limited number of participants and the short duration of the study.
Is Magnesium testing accurate and readily available?
Currently, there is no accurate test to measure a person's magnesium levels which makes it difficult to determine a precise magnesium concentration range. Most studies measure the levels of magnesium in serum or urine collected after 24 hours, but neither analyses capture the status of magnesium in the entire body. This may be important because magnesium is low in the blood (0.8%) compared to 27% stored in muscle and 19% in soft tissue (2). As a result, health care workers rarely submit an order for magnesium testing unless the patient is displaying a more pressing health issue like chronic low calcium levels or diabetes. This often makes it more difficult for patients seeking medical assistance for magnesium deficiency-related diseases and mental health-related symptoms. However, since blood magnesium levels can show if a person has low levels of the magnesium electrolyte in serum or urine, magnesium should be tested if low magnesium levels are suspected. It should be noted that some individuals can also have high magnesium levels, which can lead to other problems, including vomiting, low blood pressure, and neurological impairment.
Lifestyle changes and nutrition
Hypomagnesemia, or low magnesium levels, is often the result of poor dietary consumption and insufficient absorption in the body and is linked to causing stress, depression, and anxiety. Changes in dietary habits and a decrease in nutritional values of many natural products over the last few decades have decreased the amount of magnesium consumption over time. Some of these changes are due to soil depletion and changes in farming methods, including the use of substantial amounts of fertilizers and processing (2). The FDA recommends a dietary allowance of magnesium per day of approximately 310 mg for adult women and 420 mg for adult men. This can be obtained by consuming greens, nuts, seeds, beans, whole grains, or dietary supplements. Intake of higher amounts of magnesium should not be done by taking magnesium citrate as the citrate form is a laxative that is used to help with occasional constipation.
Vitamin D is now recommended to be taken with magnesium since magnesium is needed to activate vitamin D (9). It is also suggested that individuals reduce the consumption of diuretics such as coffee and tea, which increases the removal of magnesium from the body. Before buying magnesium supplements and taking them, it should be noted that, like all other supplements, magnesium supplements should be consumed in moderation (unless you are being treated for a specific condition). High magnesium concentrations in the blood are associated with digestive side effects such as diarrhea, kidney failure, and hypothyroidism.
Overall, magnesium, being the fourth most abundant mineral in the body, maybe a valuable addition to pharmacological and natural remedies for managing mild-to-moderate depression. Since more than 40% of Americans may have a magnesium deficiency, it is recommended that you get your magnesium levels checked. If it is low, increase your consumption of foods containing high magnesium levels or use a magnesium supplement.
You deserve to be happy; make sure lack of magnesium is not taking that away from you.
Written by Deana Villagomes, BS and Ismael Bousso, BS. Edited by Stephanie Palacio, PhD and Aldrin V. Gomes, PhD
References
1. Ramón-Arbués, E., Martínez Abadía, B., Granada López, J. M., Echániz Serrano, E., Pellicer García, B., Juárez Vela, R., Guerrero Portillo, S., & Saéz Guinoa, M. (2019). Conducta alimentaria y su relación con el estrés, la ansiedad, la depresión y el insomnio en estudiantes universitarios [Eating behavior and relationships with stress, anxiety, depression and insomnia in university students]. Nutricion Hospitalaria, 36(6), 1339–1345.
2. Workinger, J. L., Doyle, R. P., & Bortz, J. (2018). Challenges in the Diagnosis of Magnesium Status. Nutrients, 10(9), 1202.
3. Noah, L., Pickering, G., Mazur, A., Dubray, C., Hitier, S., Duale, C., & Pouteau, E. (2020). In combination with vitamin B6, magnesium supplementation on stress and magnesium status: Secondary data from a randomized controlled trial. Magnesium Research, 33(3), 45-57.
4. Elin, R.J. (2010)Assessment of magnesium status for diagnosis and therapy. Magnesium Research 23(4): S194-8.
5. Singewald, N., Sinner, C., Hetzenauer, A., Sartori, S. B., & Murck, H. (2004). Magnesium deficient diet alters depression- and anxiety-related behavior in mice--influence of desipramine and Hypericum perforatum extract. Neuropharmacology, 47(8), 1189–1197.
6. Pochwat, B., Szewczyk, B., Sowa-Kucma, M., Siwek, A., Doboszeska, U., Piekoszewski, W., Gruca, P., Papp, M., & Nowak, G. (2014). Antidepressant-like activity of magnesium in the chronic mild stress model in rats: alterations in the NMDA receptor subunits. International Journal of Neuropsychopharmacology, 17(3), 393-405.
7. Poleszak E (2007). Modulation of antidepressant-like activity of magnesium by serotonergic system. J Neural Transm (Vienna). 114(9):1129-34.
8. Rajizadeh, A., Mozaffari-Khosravi, H., Yassini-Ardakani, M., & Dehghani, A. (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.
9. Uwitonze, A. M., & Razzaque, M. S. (2018). Role of Magnesium in Vitamin D Activation and Function. The Journal of the American Osteopathic Association, 118(3), 181–189.
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