Comparison of Mechanism and Functional Effects of Magnesium and Statin Pharmaceuticals

Abstract

Since Mg(2+)-ATP is the controlling factor for the rate-limiting enzyme in the cholesterol biosynthesis sequence that is targeted by the statin pharmaceutical drugs, comparison of the effects of Mg(2+) on lipoproteins with those of the statin drugs is warranted. Formation of cholesterol in blood, as well as of cholesterol required in hormone synthesis, and membrane maintenance, is achieved in a series of enzymatic reactions that convert HMG-CoA to cholesterol. The rate-limiting reaction of this pathway is the enzymatic conversion of HMG CoA to mevalonate via HMG CoA. The statins and Mg inhibit that enzyme. Large trials have consistently shown that statins, taken by subjects with high LDL-cholesterol (LDL-C) values, lower its blood levels 35 to 65%. They also reduce the incidence of heart attacks, angina and other nonfatal cardiac events, as well as cardiac, stroke, and total mortality. These effects of statins derive less from their lowering of LDL-C than from their reduction of mevalonate formation which improves endothelial function, inhibits proliferation and migration of vascular smooth muscle cells and macrophages, promotes plaque stabilization and regression, and reduces inflammation, Mg has effects that parallel those of statins. For example, the enzyme that deactivates HMG-CoA Reductase requires Mg, making Mg a Reductase controller rather than inhibitor. Mg is also necessary for the activity of lecithin cholesterol acyl transferase (LCAT), which lowers LDL-C and triglyceride levels and raises HDL-C levels. Desaturase is another Mg-dependent enzyme involved in lipid metabolism which statins do not directly affect. Desaturase catalyzes the first step in conversion of essential fatty acids (omega-3 linoleic acid and omega-6 linolenic acid) into prostaglandins, important in cardiovascular and overall health. Mg at optimal cellular concentration is well accepted as a natural calcium channel blocker. More recent work shows that Mg also acts as a statin.

Hypomagnesemia and atherogenic dyslipidemia in chronic kidney disease: surrogate markers for increased cardiovascular risk

“…It also inhibits HMG CoA reductase, decreasing cholesterol synthesis [36] and is considered necessary for the action of lecithin cholesterol acyl transferase activity, lowering low-density lipoprotein, triglycerides and increasing HDL levels [8]. Thus magnesium deficit leads to a dyslipidemic state.…”

“…Magnesium modulates calcium uptake and distribution in the vascular smooth muscle cells and also directly affects the vascular tone, reducing peripheral resistance [7]. The cardio-protective role of magnesium is not only due to its effect on the vascular system, recent studies show that magnesium is found to reduce triglycerides and low-density lipoprotein cholesterol and increase high-density lipoprotein cholesterol levels [8]. Magnesium depletion has thus been attributed to have an important role in the pathogenesis of cardiovascular disease.…”

Dietary intake of calcium and magnesium and the metabolic syndrome in the National Health and Nutrition Examination (NHANES) 2001–2010 data

“…In skeletal muscle and fat tissue, low Mg levels have been observed to decrease glucose utilisation, resulting in insulin resistance (16) . Mg is also involved in enzymatic reactions that remove TAG from the blood and increase the production of HDL (17,18) . Few epidemiological studies have reported an association between Ca and MetSyn.…”

Role of dipeptidyl peptidase IV (DPP4) in the development of dyslipidemia: DPP4 contributes to the steroid metabolism pathway

“…3, triglyceride synthesis is initiated by the acylation of glycerol-3-phosphate with acyl-CoA substrate to form lysophosphatidic acid (LPA) (Gonzalez-Baró et al, 2007). The cholesterol biosynthesis pathway first converts acetyl coenzyme A to hydroxymethylglutaryl-CoA (HMG-CoA), and then after a series of intermediate steps, to cholesterol (Rosanoff and Seelig, 2004). From cholesterol, steroids such as testosterone are synthesized via a series of enzymatic reactions mediated by P450 and other enzymes (Liu et al, 2005).…”