Magnesium’s Potential in Cardiometabolic Health

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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.

http://www.nutritionaloutlook.com/article/magnesium%E2%80%99s-potential-cardiometabolic-health-2-10228