Excessive insulin decreases vitamin D in 4 ways – problems for diabetic COVID-19 – Dec 2020

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

BMJ Open Heart 2020;7:e001356. doi: 10.1136/openhrt-2020-001356
Isabella D Cooper 1, Catherine A P Crofts 2, James J DiNicolantonio 3, Aseem Malhotra 4, Bradley Elliott1, Yvoni Kyriakidou1 and Kenneth H Brookler 5

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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.