Magnesium: The Mighty Mineral with Multifaceted Benefits

Oct 25, 2017
Volume: 
20
Issue: 
8

The human body requires a steady and adequate supply of essential nutrients in order to maintain balance—or homeostasis—to continue operating as a finely tuned machine. Of these required nutrients, vitamins and minerals are foundational. They are the sparkplugs that make our metabolic engines run, working as cofactors for enzymes and participating in the process of energy production. One mineral, magnesium, holds a special place within the group of absolutely essential nutrients. As an indispensable mineral that acts as a cofactor for hundreds of enzymes in the body, magnesium is required by every cell in the body. Unfortunately, it’s also a mineral that many of us don’t get enough of. Studies indicate that nearly 50% of the U.S. population consumes an inadequate amount of magnesium from the diet, not meeting the estimated average requirement (EAR) for this mineral.1 For adults over the age of 30, the EAR for magnesium is 350 mg/day for men and 265 mg/day for women, while the recommended dietary allowance (RDA) is 420 mg/day for men and 320 mg/day for women.

As the incidence of chronic diseases—including cardiovascular disorders, diabetes, and osteoporosis—continues to rise, one can’t help but wonder how much of a contributory factor the population’s insufficient intake of magnesium has played. After all, low levels of magnesium have been linked to all of these aforementioned conditions1, and some feel that even the RDA levels of magnesium are not high enough given that certain disease states, stress, and medications often further deplete bodily stores of magnesium.2 In such cases, they would argue, ensuring an adequate magnesium intake is even more critical.

Research continues to highlight the benefits of this magnificent mineral. Recent studies summarized here indicate magnesium’s growing importance for mental health, arterial flexibility, and metabolic function.

 

Mental Health 

Mood disorders are now highly prevalent globally, with depression alone affecting 350 million people worldwide.3 One of magnesium’s key benefits seems to be supporting healthy neurological function and mental health. Research points to magnesium insufficiency as a potential causative factor in mood disorders, anxiety, and stress-related conditions. Fortunately, recent clinical evidence suggests that magnesium supplementation can be beneficial for these conditions.

A randomized, controlled, crossover clinical trial was conducted by Emily Tarleton and colleagues from the University of Vermont (Burlington, VT) to assess the effect of magnesium supplements in the treatment of depression.3 The study included 126 adults with an average age of 52 diagnosed with mild to moderate depression. Participants were assigned to six weeks of magnesium chloride supplementation (248 mg of elemental magnesium/day) or control, and the treatments were then crossed over. Assessments of depressive symptoms were performed over the phone every two weeks and improvement was evaluated via Patient Health Questionnaire-9 scores. Anxiety symptoms were also evaluated using Generalized Anxiety Disorders-7 scores. 

According to researchers, six weeks of magnesium supplementation led to clinically significant improvements in depression symptoms as well as statistically significant improvements in anxiety. Moreover, the authors noted that improvements became evident within two weeks of the onset of supplementation. The supplements were well tolerated, with no significant adverse events noted.

A second trial led by researchers from Shahid Sadoughi University of Medical Sciences (Yazd, Iran) included 60 adults with diagnosed depression and magnesium deficiency.4 In the double-blind, placebo-controlled, eight-week trial, participants received 500 mg of magnesium oxide or placebo daily. The Beck Depression Inventory-2 assessment was used, and serum magnesium levels were followed from baseline to the end of the study. 

Beck scores declined in both groups over the eight-week period, indicating less-severe depression symptoms; however, this decline was significantly greater in the magnesium group. Concurrently, serum magnesium levels also significantly improved over the study period in the magnesium group, with 88.5% of participants reaching normal levels at the end of the study. These results support the positive benefits of magnesium supplementation in depressed individuals.

In fact, a recently published review article authored by Anna Serefko and colleagues from the Medical University of Lublin (Lublin, Poland) highlights clinical studies indicating that magnesium administration helps with major depression as well as depression and anxiety-related symptoms secondary to premenstrual syndrome, chronic fatigue syndrome, epilepsy, and type 2 diabetes.5

The authors cite possible mechanisms, including balancing and counteracting elevated levels of calcium and glutamate in the hippocampus, which leads to altered function of synapses in the brain, resulting in mood disorders and depression. A sufficient supply of magnesium would, by contrast, support the normal function of these neuronal synapses. Magnesium is also involved in both the noradrenaline and dopamine systems, which are important neurotransmitters. It further plays significant roles in modulating the stress response by controlling the access of corticosteroids to brain tissue, and it has documented anti-inflammatory activity. Both of these factors otherwise potentially contribute to mood disorders and depression.

Additionally, two recent preliminary studies in mice conducted by researchers in Denmark point to a novel mechanism of magnesium’s impact on depression and anxiety. Comparing mice fed a standard diet or a diet deficient in magnesium for six weeks, researchers noted that magnesium-deficient mice exhibited depressive behavior6 as well as anxiety symptoms7. The investigations revealed that magnesium deficiency impacted the gut microbiota in these animals, leading the researchers to hypothesize that magnesium deficiency possibly contributes to depression and anxiety via an impact on the gut-brain axis and by influencing immune function. While further research is required to investigate the influence of magnesium on the gut microbiota, it is clear that magnesium influences several aspects of healthy neurological function and contributes greatly to the maintenance of mental health.

 

Arterial Flexibility and Preventing Vascular Calcification

Magnesium intake is linked to improved cardiovascular health. For example, a meta-analysis published in 2013 including 16 studies with over 313,000 individuals found that for every 200 mg/day increment in magnesium intake, there was a 22% reduced risk of ischemic heart disease; moreover, higher circulating levels of magnesium were associated with a 30% reduced risk of overall cardiovascular disease.8

Given that dietary magnesium intake has been associated with a significant risk reduction in ischemic heart disease, Peter Joris and colleagues from the Maastricht University Medical Center (Maastricht, The Netherlands) sought to investigate the ability of supplemental magnesium to maintain arterial flexibility.9 In this double-blind, placebo-controlled, 24-week study, 52 healthy obese and overweight adults with an average age of 62 were assigned to either supplement with magnesium (350 mg/day elemental magnesium as magnesium citrate) or placebo. Measurements were taken at baseline, at week 12, and upon study completion, and included serum magnesium concentrations, 24-hour blood pressure readings, as well as carotid-to-femoral pulse wave velocity (PWV) assessments, which is considered the gold-standard measure of arterial stiffness. 

While the study results did not show a significant effect of magnesium supplementation on blood pressure (average blood pressure in both groups was already within normal limits at baseline), at the end of the study, the group supplementing with magnesium had a significant change in carotid-to-femoral PWV measurements, showing a reduction of 1.0 meter/second (m/s) and indicating an important reduction in arterial stiffness. Previous epidemiological research has shown that a decrease in carotid-to-femoral PWV of 1.0 m/s is associated with a 14% decrease in risk of cardiovascular events10, highlighting the significance of the findings in the current study and demonstrating the benefits of daily magnesium supplementation.

One possible explanation for the ability of magnesium to help support arterial flexibility is that magnesium helps prevent vascular calcification. In a recent review, Anique ter Braake and colleagues from Radboud University Medical Center (Nijmegen, The Netherlands) summarize experimental evidence suggesting that magnesium prevents vascular calcification through multiple mechanisms.11 Magnesium’s effects can be divided into two unique pathways. 

The first pathway is passive interference, suggesting that the presence of magnesium in circulation favorably alters the environment to prevent vascular calcification processes. Research points to the fact that dietary magnesium reduces the absorption of inorganic phosphate molecules by binding to them in the intestines. These phosphate molecules would otherwise be necessary to stimulate the calcification process in vascular smooth muscle cells. Additionally, magnesium passively interferes with hydroxyapatite maturation and formation in the blood vessel itself. Hydroxyapatite crystals (containing calcium and phosphorus) are otherwise linked to calcification in blood vessels.

A second pathway by which magnesium prevents vascular calcification is through direct cell-mediated mechanisms.11 Magnesium appears to prevent transcriptional changes in vascular smooth muscle cells that favor calcification, thereby halting this process. Specifically, magnesium prevents the expression of factors associated with matrix mineralization and supports against the loss of calcification inhibitors, which serve to protect smooth muscle cells. 

By acting via these two distinct pathways, magnesium plays an essential role in supporting the normal function and morphology of vascular smooth muscle cells and thereby promoting arterial flexibility.

 

References: 
  1. Rosanoff A et al., “Suboptimal magnesium status in the United States: are the health consequences underestimated?” Nutrition Reviews, vol. 70, no. 3 (March 2012): 153-164
  2. Volpe SL, “Magnesium in disease prevention and overall health,” Advances in Nutrition, vol. 4, no. 3 (May 1, 2013): 378S–383S 
  3. Tarleton EK et al., “Role of magnesium supplementation in the treatment of depression: a randomized clinical trial,” PLoS One. Published online June 27, 2017.
  4. Rajizadeh A et al., “Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: a randomized, double-blind, placebo-controlled trial,” Nutrition. Published online November 9, 2016.
  5. Serefko A et al., “Magnesium and depression,” Magnesium Research, vol. 29, no. 3 (March 1, 2016): 112-119
  6. Winther G et al., “Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour,” Acta Neuropsychiatrica, vol. 27, no. 3 (June 2015): 168-176
  7. Jørgensen BP et al., “Dietary magnesium deficiency affects gut microbiota and anxiety-like behaviour in C57BL/6N mice,” Acta Neuropsychiatrica, vol. 27, no. 5 (October 2015): 307–311 
  8. Del Gobbo LC et al., “Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies,” American Journal of Clinical Nutrition, vol. 98, no. 1 (July 2013): 160–173
  9. Joris PJ et al., “Long-term magnesium supplementation improves arterial stiffness in overweight and obese adults: results of a randomized, double-blind, placebo-controlled intervention trial,” American Journal of Clinical Nutrition, vol. 103, no. 5 (May 2016): 1260–1266
  10. Vlachopoulos C et al., “Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis,” Journal of the American College of Cardiology, vol. 55, no. 13 (March 30, 2010): 1318–1327
  11. Ter Braake AD et al., “Magnesium counteracts vascular calcification: passive interference or active modulation?” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 37, no. 8 (August 2017): 1431-1445
  12. Kieboom BCT et al., “Serum magnesium and the risk of prediabetes: a population-based cohort study,” Diabetologia, vol. 60, no. 5 (May 2017): 843-853
  13. La SA et al., “Low magnesium levels in adults with metabolic syndrome: a meta-analysis,” Biological Trace Element Research, vol. 170, no. 1 (March 2016): 33-42
  14. Saproo N et al., “Emerging role of serum magnesium in diabetes mellitus,” World Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 3 (2017): 861-866 
  15. Simental-Mendía LE et al., “A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control,” Pharmacological Research. Published online June 18, 2016.
  16. Guerrero-Romero F et al., “Magnesium in metabolic syndrome: a review based on randomized, double-blind clinical trials,” Magnesium Research, vol. 29, no. 4 (April 1, 2016): 146-153
  17. Verma H et al., “Effect of magnesium supplementation on type 2 diabetes associated cardiovascular risk factors: a systematic review and meta-analysis,” Journal of Human Nutrition and Dietetics. Published online February 2, 2017.