Magnesium plays a critical role in heart disease

The symposium proceedings on Oxidative Stress and Cardiovascular Injury of the Southern Society for Clinical Investigation presented during this year's scientific session of the Southern Society for Clinical Investigation included an important paper on critical role of magnesium (Mg2+) deficiency in oxidative stress-induced cardiomyopathy.

"As emphasized by Weglicki and coworkers, Mg2+ deficiency is all too common and carries with it an increased risk of associated adverse cardiovascular events, including oxidative stress. Hypomagnesemia appears when dietary Mg2+ intake is restricted. It may also be the result of drug-induced Mg2+ wasting, such as occurs with loop diuretics and chemotherapeutics, or the neurohormonal activation that accompanies acute and chronic stressor states (ie, CHF, diabetes and the metabolic syndrome)."

The authors demonstrated that magnesium deficiency results in a rise in neurotransmitter substance P (SP) which in turn triggers a systemic inflammatory effect that includes cardiac and intestinal tissues. Elevations in substance P are sustained when the enzyme neutral endopeptidase (NEP) that is supposed to degrade it is impaired by reactive oxygen and nitrogen species. Importantly...

"An associated increase in intestinal permeability with evidence of mucosal invasion by inflammatory cells and accompanying fall in mucosal barrier function with endotoxemia are seen with Mg2+ deficiency. Endotoxin can stimulate the secretion of tumor necrosis factor-α from diverse cellular sources, including macrophages and cardiomyocytes, and can be attenuated by SP receptor blockade. Thus, this neurogenic signal-transduction pathway involving SP, endotoxemia and elevated tumor necrosis factor-α can contribute to the progressive nature of heart failure, including a decline in myocardial contractility."

In other words, magnesium deficiency is a potent promoter of inflammatory damage to the heart (and the intestinal lining). This further explains why antagonizing magnesium with calcium supplementation can contribute to cardiovascular disease. Clinicians should bear in mind the concluding statement:

"The importance of careful monitoring of serum Mg2+ in the prevention and prompt correction of hypomagnesemia cannot be overemphasized."

Readers may wish to read the previous posts on antacids and magnesium deficiency and increase in heart attack risk with calcium supplements.A paper published only a couple months earlier in the journal Magnesium Research adds further emphasis. The authors state:

"Hypomagnesemia continues to cause difficult clinical problems, such as significant cardiac arrhythmias where intravenous magnesium therapy can be lifesaving. Nutritional deficiency of magnesium may present with some subtle symptoms such as leg cramps and occasional palpitation...We found that neuronal sources of the neuropeptide, substance P (SP), contributed to very early prooxidant/proinflammatory changes during Mg deficiency. This neurogenic inflammation is systemic in nature, affecting blood cells, cardiovascular, intestinal, and other tissues, leading to impaired cardiac contractility similar to that seen in patients with heart failure...Our findings emphasize the essential role of this cation in preventing cardiomyopathic changes and intestinal inflammation in a well-studied animal model, and also implicate the need for more appreciation of the potential clinical relevance of optimal magnesium nutrition and therapy."

Clinical Pearl: serum and even erythrocyte membrane levels of magnesium reflect tissue levels poorly. Results of the intracellular x-ray fluorescence test (performed on cells scraped from the floor of the mouth) reliably correlate with heart, muscle and deep organ tissue mineral content.