Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation.
Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg. Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The effect of Mg deficiency in the development of insulin resistance in the rat model is well documented. Inflammation occurring during experimental Mg deficiency is the mechanism that induces hypertriglyceridemia and pro-atherogenic changes in lipoprotein metabolism. The presence of endothelial dysfunction and dyslipidemia triggers platelet aggregability, thus increasing the risk of thrombotic events. Oxidative stress contributes to the elevation of blood pressure. The inflammatory syndrome induces activation of several factors, which are dependent on cytosolic Ca activation. Recent findings support the hypothesis that the Mg effect on intracellular Ca2+ homeostasis may be a common link between stress, inflammation and a possible relationship to metabolic syndrome.
Studies in rats, supported by human studies, have demonstrated that magnesium deficiency promotes an inflammatory response. White blood cells are activated to release hormones called cytokines, which along with other proteins lead to free radical damage. Triglyceride levels rise, along with proinflammatory cholesterol products. Endothelial cells lining blood vessels are injured and lose their ability to regulate blood flow. Blood clots form, causing more damage to tissues throughout the body. Blood pressure rises along with blood sugar, further aggravating vascular damage. When magnesium is added, these adverse reactions are suppressed. The stress effect of magnesium deficiency correlates with aberrations in hormonal systems. The renin-angiotensin-aldosterone system, an interaction of the kidneys with the adrenal glands, leads to arterial spasm, hypertension and insulin resistance. Excitatory amino acids support the release of NFkappaB, a molecule that instigates inflammation and cell death.
Magnesium is intimately connected with many bodily functions that keep inflammation and illness in check. Of all minerals, it is the one most likely to be deficient in humans. It is the one most important in preventing the crescendo of cellular inflammation that terminates in the downward spiral of obesity, diabetes, hypertension, heart attack and stroke.
Magnesium is easily measured in the lab, well-tolerated as a supplement, and inexpensive. Excess occurs only in advanced kidney disease. Magnesium supplementation is a certain way to avoid the deficiency that causes illness.
Allan E. Sosin, MD
Founder and Medical Director
Institute for Progressive Medicine
Rayssiguier Y, Libako P, Nowacki W, Rock E. Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation. Magnes Res. 2010 Jun;23(2):73-80. doi: 10.1684/mrh.2010.0208.