PMC

Dietary Mg²⁺ deficiency is accompanied by hypomagnesaemia and release of substance P and cytokines, with ROS and RNS generation leading to oxidative stress, subsequent tissue injury, and inflammatory cell activation.

In aldosteronism (ALDOST), where plasma aldosterone levels are inappropriately elevated relative to dietary Na⁺ intake, marked excretory losses of Ca²⁺ and Mg²⁺ lead to a fall in their plasma ionized concentrations. Reduced [Ca²⁺]_o and [Mg²⁺]_o are, respectively, major and minor stimuli to the parathyroid glands’ secretion of parathyroid hormone (PTH), with secondary hyperparathyroidism (SHPT) accounting for bone resorption in an attempt to restore the homeostasis of these divalent cations. In what is coined as a calcium paradox, elevations in plasma PTH promote intracellular Ca²⁺ overloading and induction of oxidative stress. Reactive oxygen species (ROS) and peroxynitrite (OONO⁻) contribute to intracellular signalling that, in a concentration-dependent manner, eventuates in cell activation (e.g. peripheral blood mononuclear cells, PBMC) and the expression of apoptotic and necrotic cell death pathways in cardiomyocytes. Urinary and faecal losses of Zn are likewise increased during ALDOST (data not shown). A high (8%) Na⁺ diet, which suppresses plasma aldosterone levels, also leads to SHPT because of increased excretory losses of Ca²⁺.