Magnesium deficiency is so common that it’s hard to find individuals with optimal levels. A study just published in the American Heart Journal adds to the growing body if evidence for the great importance of magnesium in cardiovascular disease. The authors state:

“We hypothesized that serum magnesium (Mg) is associated with increased risk of sudden cardiac death (SCD).”

They assessed risk factors and levels of serum Mg in 14,232 45- to 64-year-old subjects and followed them for an average of 12 years. During that time there were 264 cases of SCD that they used to evaluate the association of serum Mg with risk of SCD. The data made a clear statement:

“Individuals in the highest quartile of serum Mg were at significantly lower risk of SCD in all models. This association persisted after adjustment for potential confounding variables, with an almost 40% reduced risk of SCD in quartile 4 versus 1 of serum Mg observed in the fully adjusted model.”

This is a potent result, summed by the authors’ conclusion:

“This study suggests that low levels of serum Mg may be an important predictor of SCD.”

A whole body of emerging research is illuminating the mechanisms by which suboptimal magnesium levels can have this effect. In a study just published in the journal Diabetes Care the authors set out…

“To investigate the long-term associations of magnesium intake with incidence of diabetes, systemic inflammation and insulin resistance among young American adults.”

The authors followed 4,497 Americans aged 18-30 (who had no diabetes at the beginning) for 20 years. During that time they identified 330 cases of diabetes which they correlated with quintiles of magnesium intake. They also investigated the associations between magnesium intake and inflammatory markers including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and fibrinogen, and the homeostasis model assessment of insulin resistance (HOMA-IR). What did the data show?

“Magnesium intake was inversely associated with incidence of diabetes after adjustment for potential confounders…Consistently, magnesium intake was significantly inversely associated with hs-CRP, IL-6, fibrinogen, and HOMA-IR; and serum magnesium levels were inversely correlated with hs-CRP and HOMA-IR.”

As you know, these are powerful markers for cardiovascular disease risk. As the authors state in their conclusion:

“This inverse association may be explained, at least in part, by the inverse correlations of magnesium intake with systemic inflammation and insulin resistance.”

An earlier paper published in the journal Magnesium Research documents how low magnesium in conjunction with high fructose consumption promotes inflammation associated with metabolic syndrome. The authors begin by observing:

“The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. This syndrome is occurring at epidemic rates, with dramatic consequences for human health worldwide, and appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in fructose intake, which appears to be an important causative factor in the metabolic syndrome. There is also experimental and clinical evidence that the amount of magnesium in the western diet is insufficient to meet individual needs and that magnesium deficiency may contribute to insulin resistance.”

They present present experimental evidence showing that metabolic syndrome, high fructose intake and low magnesium diet may all be linked to the inflammatory response. The data they gathered showed that:

“…a few days of experimental magnesium deficiency produces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines, appearance of the acute phase proteins and excessive production of free radicals. Because magnesium acts as a natural calcium antagonist, the molecular basis for the inflammatory response is probably the result of a modulation of the intracellular calcium concentration.”

These findings remind of the recent research linking calcium supplementation to increased heart attacks.  The authors conclude:

“Since magnesium deficiency has a pro-inflammatory effect, the expected consequence would be an increased risk of developing insulin resistance when magnesium deficiency is combined with a high-fructose diet. Accordingly, magnesium deficiency combined with a high-fructose diet induces insulin resistance, hypertension, dyslipidemia, endothelial activation and prothrombic changes in combination with the upregulation of markers of inflammation and oxidative stress.”

It goes without saying that these are primary inducers of cardiovascular disease. Another paper published last year in the same journal note the association of magnesium deficiency and C-reactive protein:

“Recent findings from epidemiologic studies support that magnesium intake is inversely associated with C-reactive protein concentration, an important marker of inflammation strongly associated with cardiovascular disease risk.”

A fascinating study published in the American Journal of the Medical Sciences investigates magnesium deficiency promotes inflammation and cardiovascular disease through neurogenic pathways:

“This review highlights some key observations that helped formulate the hypothesis that release of substance P (SP) [an inflammatory signalling molecule] during experimental dietary Mg deficiency (MgD) may initiate a cascade of deleterious inflammatory, oxidative, and nitrosative events, which ultimately promote cardiomyopathy, in situ cardiac dysfunction, and myocardial intolerance to secondary stresses.”

The authors further state:

“…SP-mediated events may…facilitate development of in situ cardiac dysfunction, especially with prolonged dietary Mg restriction.”

Additional intriguing research published in the British Journal of Anaesthesia adds even more evidence to the assertion that magnesium helps reduce cardiovascular disease by opposing calcium.  The authors begin by stating:

“Magnesium sulphate (MgSO4) has potent anti-inflammatory capacity. It is a natural calcium antagonist and a potent L-type calcium channel inhibitor. We sought to elucidate the possible role of calcium, the L-type calcium channels, or both in mediating the anti-inflammatory effects of MgSO4.”

And magnesium sulphate is not the most bioavailable form of magnesium supplementation. When the authors induced inflammation by exposure to lipopolysaccharide (LPS) as evidenced by macrophage inflammatory protein-2, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, nitric oxide/inducible nitric oxide synthase, prostaglandin E2/cyclo-oxygenase-2, and NF-κB activation.

“MgSO4…significantly inhibited the LPS-induced inflammatory molecules production and NF-κB activation. Moreover, the effects of MgSO4 on inflammatory molecules and NF-κB were reversed by extra-cellular calcium supplement with CaCl2 and L-type calcium channel activator BAY-K8644.”

In other words, in addition to opposing inflammation, magnesium is nature’s calcium channel blocker. The authors conclude:

“MgSO4 significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation… The effects of MgSO4 on inflammatory molecules and NF-κB may involve antagonizing calcium, inhibiting the L-type calcium channels, or both.”