Genotoxic Effects of Magnesium Deficiency in the Cardiovascular System and their Relationships to Cardiovascular Diseases and Atherogenesis

Abstract

The authors present evidence for a novel, new hypothesis whereby magnesium deficiency (MgD) acts as a genotoxic agent which probably causes numerous, hertofore, unrecognized consequences, even over a short-term, on the physiological, molecular and biochemical machinery of cardiovascular tissues and cells. The end result of these genotoxic effects of MgD probably plays important roles in the etiology and generation of diverse cardiovascular diseases, atherosclerosis, inflammation, and strokes via alterations in the epigenome of cardiovascular tissues and cells. The importance of adequate water-borne and dietary levels of Mg is emphasized.

Regulated RIPK3 Necroptosis is Produced in Cardiovascular Tissues and Cells in Dietary Magnesium Deficiency: Roles of Cytokines and Their Potential Importance in Inflammation and Atherogenesis

“…Our results, also encourages the idea that, water intake (e.g., from tap waters, well waters, bottled waters, beverages using tap/well/spring waters, or desalinated waters) should contain at least 25-40 mg/liter/day of Mg 2+ [58][59][60]76,77,81]. In this context, our group has performed several conclusive experiments and highlighted most of the detrimental pathophysiological implications of Mg deficiency, which includes decreased cardiac output, decreased myocardial contractility, decreased coronary blood flows, mitochondrial release of cytochrome C, lipid peroxidation of cardiac and vascular muscle membranes, increased cellular levels of NO and p53, release of cytokines and chemokines, increased cellular entry of calcium ions and overload, increases in membrane permeability, myocardial acidification, loss of cellular ATP, DNA damage, shortening of telomeres, apoptosis, and necroptosis [11,41,42,57-61,72-79-83].…”

“…Employing transmission electron microscopy (TEM), in our Mg-deficient rabbit experimentation suggested to us that, both the vascular smooth muscle cells and macrophages of the lipid-laden arterial vessels exhibited necrosis and apoptosis [16,65,66, unpublished findings of Stempak, BT Altura, M Brust and BM Altura]. Further, investigation using TEM on cardiac and arterial muscle cells of Mg-deficient rats also showed clear signs of necrosis as well as apoptosis [66][67][68][69][70][71][72][73][74][75][76][77][78]; N Shah, BT Altura and BM Altura, unpublished findings]. Experimentation with high-power TEM revealed that, these Mg-deficient muscle cells exhibited what is now termed "necroptosis".…”

“…Our studies have clearly shown that, rat cardiac and vascular smooth muscle cells exposed to short-term Mg deficiency, exhibit an early and profound elevation in cellular and plasma lelels of TNF-alpha (i.e., 5-10 fold), IL-beta and interferongamma as well [11,18,42,[58][59][60][72][73][74][75][76][77][78]. Interestingly, our experimentation with necrostatin-1, an inhibitor of RIPK1 and RIPK3 activation, reduces activation and formation of NF-kB in Mg-deficient peripheral and cerebral vascular smooth muscle cells [78].…”

Why typos in DNA may help to fuel atherogenesis and inflammation prior to heart attacks, ischemic heart disease, and sudden-death ischemic heart disease: roles of unrecognized ionized hypomagnesemia and epigenetics

“…We have provided putative evidence that magnesium (Mg) deficient environments can behave like genotoxins on cardiovascular tissues and cells. [3][4][5] We continue this line of thought, below, for believing Mgdeficient environments can result in inflammatory lesions which can result in atherogenesis, thus leading to heart attacks, ischemic heart disease (IHD), cardiac failure (CF), sudden-death ischemic heart disease (SDIHD), and strokes.…”

“…Both animal and human studies have demonstrated an inverse relationship between dietary intake of Mg and atherosclerosis. [3][4][5]17,19,[22][23][24][25][26][27][28][29][30][31] The myocardial level of Mg has consistently been observed to be lower in subjects dying from IHD and SDIHD in soft-water areas than those in hard-water areas. 17,[19][20][21][22][23][24][25]32 Mg plays critical roles in more that 500 enzymatic reactions in the body, 33 and is required for all energygenerating reactions and oxidative phosphorylation.…”