Magnesium’s Potential in Cardiometabolic Health

Magnesium is an essential mineral that plays a role in more than 300 metabolic reactions in the human body. The need for magnesium is crucial, in areas as diverse as bone tissue, muscles, DNA, RNA and protein synthesis, energy production, and structural support for cell membranes and chromosomes. Now, clear effort is being made to explore the benefits of magnesium in cardiovascular and metabolic-or cardiometabolic-health. The need for cardiometabolic support is clear, given the ever-increasing prevalence of cardiovascular and metabolic disorders in the population and the increasing economic burden of these disorders to society.

Much is already known about magnesium and cardiometabolic function from a mechanistic perspective. In terms of some of the mechanisms associated with its benefit, magnesium acts as a calcium channel blocker, increases nitric oxide production, improves endothelial function, enhances the efficiency of insulin, reduces inflammation, and improves the ability of blood vessels to dilate.

But what has further emerged from recent research is nothing short of amazing. Emerging science points to magnesium as a prudently simple nutritional intervention for the prevention and treatment of a variety of cardiometabolic disorders-disorders that affect large percentages of the global population. In fact, magnesium’s broad reach has now been shown to extend to promoting insulin sensitivity, blood sugar control, cardiac function, healthy cholesterol and lipid levels, and endothelial health (the health of the layer of cells lining our blood vessels).

These effects suggest a clinical benefit of optimal magnesium status in the prevention of conditions including metabolic syndrome, diabetes, heart disease, stroke, atherosclerosis, and hypertension.

Metabolic Syndrome, Diabetes, and Insulin Resistance

Magnesium deficiency has been found to be a significant independent risk factor for the development of type 2 diabetes. Multiple studies indicate that as many as half of type 2 diabetics are low in magnesium, with research further showing that low magnesium levels are a significant contributing factor in many complications of the disease. Additional clinical studies, however, have shown that oral supplementation of magnesium to non-diabetic individuals with low magnesium status improved insulin sensitivity.

In a December 2010 study published in Diabetes Care following 4,497 American young adults between ages 18 and 30 with no diabetes at baseline, Dr. Dae Jung Kim and colleagues from the UNC Gillings School of Global Public Health and School of Medicine investigated the relationship between magnesium intake and incidence of diabetes and insulin resistance. Participants were divided into quintiles based on dietary magnesium intake, and followed for 20 years.

During this period, 330 individuals developed diabetes. The research team found magnesium intake to be inversely associated with the incidence of diabetes, to the point that those in the highest quintile of dietary magnesium intake were only about half as likely to develop diabetes as those in the lowest quintile. Furthermore, serum levels of magnesium were significantly inversely correlated with insulin resistance (as indicated by HOMA-IR) and measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP).

To further highlight the role of magnesium for optimal insulin sensitivity, in a study published in Diabetes, Obesity, and Metabolism in 2011, Dr. Frank Christoph Mooren and colleagues from the Institute of Sport Sciences at Justus-Liebig University in Germany assessed the benefits of oral magnesium supplementation in non-diabetic but overweight metabolic syndrome patients (30 to 70 years of age) who had normal magnesium levels at baseline. Patients were randomized to receive magnesium (365 mg/day, in the form of magnesium aspartate hydrochloride), or placebo, daily for six months.

In the group supplemented with magnesium, significant improvements were noted compared to the placebo group, in fasting blood sugar and measures of insulin sensitivity. This study indicated the importance of optimizing magnesium status even in those insulin-resistant individuals with normal magnesium levels.

In another study published in 2011 in the European Journal of Clinical Investigation, magnesium supplementation was associated with a significantly improved ability of pancreatic beta-cells to compensate for decreases in insulin sensitivity. The randomized, double-blind clinical study by Fernando Guerrero-Romero and Martha Rodrıguez-Moran, both of whom are affiliated with The Research Group on Diabetes and Chronic Illnesses in Durango, Mexico, involved non-diabetic individuals with normal blood pressure and low serum magnesium levels who were supplemented with 2.5 g/day of magnesium chloride for three months, or allocated to the placebo group. Baseline measurements of beta-cell function were the same in both groups. No lifestyle modifications or other treatments were given during the study.

At the end of the three-month study period, the group supplemented with magnesium had a significantly improved ability of their pancreatic beta-cells to compensate for decreases in insulin sensitivity. The individuals supplemented with magnesium also had significantly reduced systolic and diastolic blood pressure, fasting plasma glucose, and fasting insulin levels compared with those in the placebo group.

This study is significant because it found that even in apparently healthy individuals with low magnesium status, oral magnesium supplementation was able to induce improvements in beta-cell function and enhance insulin efficiency.

Cardiovascular Disease and Atherosclerosis

Magnesium intake also plays a key role in cardiovascular conditions. For instance, in regards to blood pressure, epidemiological studies assessing dietary intake of magnesium generally show an inverse relationship between magnesium intake and blood pressure. Several clinical trials also have found dose-dependent decreases in blood pressure with oral magnesium supplementation. This effect may be mediated at least in part by magnesium’s ability to reduce intracellular calcium and sodium levels. Further studies highlight the correlation between magnesium intake and reduced incidence of cerebrovascular events (such as stroke), cardiovascular disease, arrhythmias, and left ventricular hypertrophy, which is a thickening of the heart muscle in the left ventricle often as a result of cardiovascular disease or hypertension. And regarding cholesterol, magnesium deficiency has been found to induce adverse changes in cholesterol metabolism.

Wen Zhang and colleagues from Osaka University and other academic institutions in Japan recently published a paper in Atherosclerosis in 2012 about an investigation of an association between magnesium intake and mortality from cardiovascular disease, in 58,615 healthy Japanese patients ages 40 to 79 (the Japan Collaborative Cohort, or JACC). Researchers assessed magnesium intake using a validated food frequency questionnaire, and followed participants for a median period of 14.7 years.

Of the participants, 2,690 died as a result of cardiovascular disease. The researchers’ analysis revealed that dietary magnesium intake was inversely correlated with mortality from conditions including hemorrhagic stroke in men and ischemic strokes, coronary heart disease, congestive heart failure, and overall cardiovascular disease in women. Based on the results, the authors concluded that higher dietary intakes of magnesium may be beneficial for reducing the risk of cardiovascular mortality in the Japanese population, especially in women. In terms of explaining magnesium’s benefits, the authors point to the mineral’s ability to regulate blood pressure, reduce serum triglyceride levels, promote normal heart rhythms, support endothelial function, and inhibit inflammation and platelet aggregation.

Several studies have evaluated the risk of stroke associated with varied dietary intakes of magnesium. Susanna Larsson and her group of researchers from the National Institute of Environmental Medicine in Stockholm, Sweden, conducted a meta-analysis of several prospective studies published in the American Journal of Clinical Nutrition in 2012 to determine the association between the intake of magnesium and stroke risk.

From the seven prospective studies included in their analysis (the studies included 241,378 participants and 6,477 cases of stroke), the researchers concluded that there exists a modest but statistically significant inverse association between magnesium intake and stroke risk. Overall, an incremental increase of 100 mg/day of magnesium was associated with an 8% reduction in overall stroke risk.

Investigating the importance of magnesium for optimal endothelial function has been the focus of Jeanette Maier’s research at the University of Milan in Italy. In a study published in Clinical Science in 2012, Maier and colleagues evaluated whether low magnesium concentrations directly affect endothelial behavior, with the purpose of determining the implications of magnesium insufficiency for the development of atherosclerosis.

By conducting experiments on human vascular endothelial cells, the group determined that magnesium deficiency directly alters endothelial cell behavior and promotes endothelial dysfunction. Magnesium deficiency was found to induce a pro-inflammatory state and initiated pro-thrombotic and pro-atherogenic pathways, leading to an environment that enhances the development of atherosclerosis and cardiovascular disease.

Previous research has also demonstrated that low magnesium status impairs the synthesis of nitric oxide, affects the release of intracellular calcium, and impacts the metabolism of low-density lipoproteins, while inhibiting the normal proliferation of endothelial cells. These effects, along with the dramatic findings of Maier’s research team, highlight the significant potential role of magnesium in protecting against poor cardiovascular outcomes.

Magnesium: Do We Get Enough?

Promoting and maintaining optimal cardiometabolic health is a multifactorial endeavor. It is clear that several genetic, dietary, and lifestyle factors coalesce to determine our overall risk of poor cardiometabolic health. Keeping the multifactorial nature of health and disease in mind, it is useful to view any single potential intervention with the correct perspective. However, given the broad range of potential benefits associated with optimizing magnesium intake, and the inexpensive nature of such a simple and ubiquitous intervention, it certainly makes sense to ensure that our overall intake of this essential mineral is adequate.

Based on information from the USDA, adequate intake is clearly not the case for the majority of the U.S. population. In fact, more than 57% of the U.S. population is likely falling short of the RDA for magnesium. It’s also likely that the RDA is less than what the majority of Americans require, as evidenced by research studies showing benefits of magnesium supplementation even in individuals with normal magnesium status.

A prudent course of action based on the evidence to date would be to ensure adequate magnesium intake through diet and supplementation. Such a simple intervention with such a profound potential impact on health status deserves a serious assessment and continued research as an initiative to enhance public health.