Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management

Abstract

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.

Vitamin D deficiency is associated with COVID‐19 positivity and severity of the disease

“…This could lead to dysfunction of endothelial cells, resulting in excessive thrombin formation 19 . Pulmonary thrombin could even be responsible for oxygen desaturation and acute respiratory distress commonly observed in COVID‐19 patients 20‐22 . Elevated D‐dimer levels were reported to represent a hypercoagulable state in COVID‐19 patients 23 .…”

Magnesium Treatment on Methylation Changes of Transmembrane Serine Protease 2 (TMPRSS2)

“…Although no significant effect on TMPRSS2 methylation was observed among those aged 65 years or older, it is likely Mg treatment may exert benefits through other mechanisms. First, our and other studies found Mg optimized body vitamin D status and substantially reduced the doses requirement for vitamin D [9,18,66]. Vitamin D has been proposed to generate beneficial effects in ARDS through activation of the vitamin D receptor (VDR) signaling pathway by reducing the cytokine storm, regulating the renin-angiotensin system, maintaining the integrity of the pulmonary epithelial barrier, and tapering down the increased coagulability [16].…”

Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity

“…Dysregulation of the ACE2 pathway in the pancreas causes β-cell dysfunction and induces hyperglycemia [ 69 ]. The latter [ 28 ] and hyperinsulinemia [ 70 ] play a crucial role in thrombo-inflammation during COVID-19 infection. Countries with higher and lower death rates for COVID-19 appear to have high consumptions of fats and cereal, respectively [ 71 ].…”