Research Blog

Optimal DX FYI: Copper Deficiency can Cause Ischemic Heart Disease

Key Points

The heart is one of the main organs affected by copper deficiency, causing a reduction in metabolism and energy supply in the heart.

Insufficient dietary copper can produce almost every risk factor for ischemic heart disease (IHD).

There are many important similarities between copper deficiency in animals and IHD in humans, including glucose intolerance, hypercholesterolemia, abnormal ECG, hyperuricemia, and hypertension, all of which are risk factors for IHD. Much of the lipid hypothesis of heart disease can be seen in the light of copper deficiency.

Copper deficiency can increase total cholesterol and increase the susceptibility of lipoproteins to oxidation, two key features that increase IHD risk.

Copper deficiency can also cause hypercholesterolemia, one mechanism for this being increased levels of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a key enzyme in the cholesterol synthesis pathway.

The oxidation of low-density lipoproteins (LDLs) is thought to play a significant role in atherosclerosis.

Copper deficiency increases the susceptibility of both LDL and other lipoproteins (high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL)) to oxidation.

Superoxide dismutase (SOD) is an antioxidant enzyme and is copper-dependent. It catalyzes the dismutation of the damaging superoxide radical.

Of importance to IHD, superoxide radicals react with nitric oxide (NO) to produce the highly toxic molecule peroxynitrite, which contributes to oxidative and nitrosative damage. Nitric oxide acts to regulate endothelial function and is, therefore, important to vascular integrity.

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.

Copper deficiency also reduces liver and plasma selenoglutathione peroxidase.

The harms of copper deficiency

Increased cholesterol, decreased glucose tolerance and abnormal ECGs.
Increased LDL and triglycerides and decreased HDL.
Increased susceptibility of lipoproteins and tissues to oxidation.
Increased apolipoprotein B.
Increased blood pressure.
Increased plasminogen activator inhibitor type 1
Increased early and advanced glycation end-products.
Increased inflammation and increase in the expression of genes involved in inflammation and fibrinogenesis.
Ultrastructural irregularities of elastin and abnormal endothelial cells, subendothelial space, collagen fibers and smooth muscle cells.
Increased atherosclerosis.
Myelodysplastic syndrome.
Hepatic iron overload.
Fatty liver disease.
Cardiac hypertrophy, cardiomyopathy.
Optic neuropathy, myelopathy, anemia and neutropenia.
Atrial thrombosis, abnormal ECGs and sudden death.

Sources of copper

Foods that are high in copper include beef liver and shellfish, both of which are not commonly eaten in the typical Western diet.

Other important sources of dietary copper include nuts, seeds, legumes, and chocolate.

Muscle meats typically contain a high ratio of zinc to copper, up to 50:1, and consumption of large amounts could result in copper imbalance. Organ meat, in contrast, has a zinc:copper ratio of about 2:1.

Alan Gaby, MD, stated that the “average copper content of fruits and vegetables declined by 81% between the years 1940 and 2000, presumably because of changes in farming methods that decreased the availability of copper in the soil”.

The reductions of copper in meat, cheese, and other dairy products are also substantial (−55%, −91% and −97%, respectively).

Thus, our current dietary pattern as well as copper depletion in the food supply is undoubtedly contributing to the problem of copper deficiency.

Reference

DiNicolantonio, James J et al. “Copper deficiency may be a leading cause of ischaemic heart disease.” Open heart vol. 5,2 e000784. 8 Oct. 2018, doi:10.1136/openhrt-2018-000784 This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0)