Copper deficiency may be a leading cause of ischaemic heart disease

• Published in: Open heart 2018-10, Vol.5 (2), p.e000784-e000784
• Main Authors: DiNicolantonio, James J, Mangan, Dennis, O’Keefe, James H
• Format: Article
• Language: English
• Subjects: Animals; Atherosclerosis; Cardiovascular disease; Cholesterol; Enzymes; Gastrointestinal surgery; Health risk assessment; Heart; Hypertension; Hypotheses; Iron; Lipoproteins; Nutrition; Oxidation; Population; Trace elements; Triglycerides; Viewpoint
• ISSN: 2053-3624; 2398-595X; 2053-3624
• DOI: 10.1136/openhrt-2018-000784

[...]in copper-deficient animals, the level of dietary iron determines hyperlipidemia, not the type of dietary fat.17 The group of copper-deficient animals that were fed high-iron diets either died of ruptured hearts or developed severe anaemia, enlarged hearts and livers, hypercholesterolemia and elevated triglycerides. [...]copper deficiency ties in with the iron hypothesis of heart disease, in which excess levels of stored body iron promote IHD.18 Normally benign levels of body iron may increase heart disease risk factors in the face of dietary copper deficiency. Copper deficiency, by reducing levels of SOD, can lead to reductions in NO, which in turn leads to reduced endothelial function, lower vasodilation and increased oxidative stress, all of these being hallmarks of atherosclerosis.28 Copper deficiency also reduces liver and plasma selenoglutathione peroxidase.29 Humans with diabetic nephropathy show significantly lower plasma levels of SOD, as well as an increased urinary copper excretion.28 Both of these factors may play a role in the increased incidence of IHD seen in diabetics. [...]in individuals with diabetes and microalbuminuria, lower SOD and lower copper levels could promote IHD. Copper deficiency in experimental animals can be used as a model for studying the place of mitochondrial function in the ageing heart.41 Mitochondria of copper-deficient rats consume oxygen at a significantly lower rate than those of copper-sufficient rats; they have a lower membrane potential and an altered ATP synthase complex, indicating lower rates of energy production.42 Copper deficiency and inflammation Rats fed low amounts of copper have increased inflammation whereas copper supplementation reduces inflammation.43 Copper deficiency leads to proinflammatory effects in neutrophils and in microvascular endothelial cells, promoting interactions between neutrophils and endothelium.44 As neutrophils may enter atherosclerotic lesions and contribute causally to atherosclerosis, copper deficiency may facilitate this process.45 Copper deficiency in rats also results in upregulation of the proinflammatory enzyme COX-2, suggesting that copper may increase inflammation independently of SOD activity.46 Copper deficiency in animals leads to increased hepatic expression of genes involved in inflammation and fibrinogenesis47 and also increases nuclear factor kappa beta-1.48 Copper supplementation in rats fed a copper-deficient, high-sucrose diet restores beta-cell function