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Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management
  1. Isabella D Cooper1,
  2. Catherine A P Crofts2,
  3. James J DiNicolantonio3,
  4. Aseem Malhotra4,
  5. Bradley Elliott1,
  6. Yvoni Kyriakidou1 and
  7. Kenneth H Brookler5
  1. 1School of Life Sciences, University of Westminster – Cavendish Campus, London, UK
  2. 2School of Public Health and Interdisciplinary Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
  3. 3Department of Preventive Cardiology, Mid America Heart Institute, Kansas, Missouri, USA
  4. 4Visiting professor of Evidence Based Medicine, Bahiana School of Medicine and Public Health, Salvador, Brazil
  5. 5Aerospace Medicine and Vestibular Research Laboratory, Mayo Clinic Arizona, Scottsdale, Arizona, USA
  1. Correspondence to Isabella D Cooper; bellamitochondria{at}


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.

  • deep vein thrombosis
  • venous thromboembol
  • cytokines
  • inflammation
  • oxidative stress

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  • Twitter @I_mitochondria, @PharmacistCath, @DrAseemMalhotra,, @Yvoni_Kyr, @kenbrookler

  • Contributors IDC performed the literature search, wrote the original draft and designed the images and reviewed and edited the final manuscript. KHB contributed to writing and developing the clinical management and reviewed and edited the final manuscript. CC guided the diagnostic and drug management and reviewed and edited the final manuscript. JJD contributed to writing and editing and reviewed and edited the final manuscript. AM, BE and YK reviewed and edited the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests JJD is Director of Scientific Affairs at Analyze. Invest. Develop. Partner.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement There are no data in this work.

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