IHD from copper deficiency: a unified theory

Klevay, Leslie M.

doi:10.1017/s0954422416000093

Cited by 36 publications

(30 citation statements)

References 84 publications

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“…It has been suggested that iron can interfere with copper utilization (148). An experiment in rats showed that higher dietary iron can increase the dietary requirement for copper (149).…”

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

“…An experiment in rats showed that higher dietary iron can increase the dietary requirement for copper (149). Moreover, high iron consumption has been reported to interfere with copper absorption in infants and adults (148). It has been further suggested that iron overload can perturb copper utilization (295, 296).…”

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

“…In mice, high iron intake was suggested to interfere with copper absorption and tissue distribution (110). Collectively, these observations may be of particular physiological relevance since: (i) many Americans may have marginal copper intakes (148, 150); (ii) refined grain products are fortified with iron in the United States, increasing dietary iron consumption; and (iii) many individuals also consume iron supplements. This then leads to concern that higher iron consumption may disrupt copper homeostasis in some individuals, with possible pathological consequences.…”

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

“…Most importantly, iron supplementation is widely recommended for pregnant women (34, 96, 256, 274). It has in fact, been suggested that iron supplements should contain extra copper (148), which is a reasonable recommendation since the upper tolerable intake limit (UL) for copper is > 10-fold above the RDA for copper, so a slight increase in copper intake should be harmless in the majority of the U.S. population. Overall, this is an important area of scientific pursuit that has been largely unexplored in recent years, and additional future experimentation is clearly warranted.…”

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

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Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Doguer

Collins

2018

Comprehensive Physiology

112

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Iron and copper have similar physiochemical properties; thus, physiologically relevant interactions seem likely. Indeed, points of intersection between these two essential trace minerals have been recognized for many decades, but mechanistic details have been lacking. Investigations in recent years have revealed that copper may positively influence iron homeostasis, and also that iron may antagonize copper metabolism. For example, when body iron stores are low, copper is apparently redistributed to tissues important for regulating iron balance, including enterocytes of upper small bowel, the liver, and blood. Copper in enterocytes may positively influence iron transport, and hepatic copper may enhance biosynthesis of a circulating ferroxidase, ceruloplasmin, which potentiates iron release from stores. Moreover, many intestinal genes related to iron absorption are transactivated by a hypoxia-inducible transcription factor, hypoxia-inducible factor-2α (HIF2α), during iron deficiency. Interestingly, copper influences the DNA-binding activity of the HIF factors, thus further exemplifying how copper may modulate intestinal iron homeostasis. Copper may also alter the activity of the iron-regulatory hormone hepcidin. Furthermore, copper depletion has been noted in iron-loading disorders, such as hereditary hemochromatosis. Copper depletion may also be caused by high-dose iron supplementation, raising concerns particularly in pregnancy when iron supplementation is widely recommended. This review will cover the basic physiology of intestinal iron and copper absorption as well as the metabolism of these minerals in the liver. Also considered in detail will be current experimental work in this field, with a focus on molecular aspects of intestinal and hepatic iron-copper interplay and how this relates to various disease states. © 2018 American Physiological Society. Compr Physiol 8:1433-1461, 2018.

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“…It has been suggested that iron can interfere with copper utilization (148). An experiment in rats showed that higher dietary iron can increase the dietary requirement for copper (149).…”

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

Section: Intersection Of Iron and Copper Metabolism In The Intestinementioning

confidence: 99%

See 2 more Smart Citations

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Doguer

Collins

2018

Comprehensive Physiology

112

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“…What is less widely appreciated is that the adverse effects of high fructose intakes may also increase alcohol-associated liver damage [44] . Importantly, it has been known for many years that there is an interaction through which high fructose intake can exacerbate poor copper status and together these may present as disordered lipid metabolism and increased risk of cardiovascular abnormalities [45] . Copper itself has complex metabolic interactions with other divalent cations, such as iron and zinc, which are especially evident during inflammatory states [24,25] .…”

Section: Responding To Stressmentioning

confidence: 99%

Nutrition and Liver Health

Jackson

2017

Dig Dis

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Good clinical practice is based on a secure and accurate diagnosis. Poor nutrition is frequently associated with disorders of the liver, and a specific nutrition diagnosis is needed for providing best care and experiencing successful outcome. There is opportunity for better-structured approaches to making secure and consistent nutritional diagnoses in patients with liver disease. Nutrition is the set of integrated processes by which cells, tissues, organs and the whole body acquire the energy and nutrients to retain normal structure and perform the required functions. At the level of the whole body, this is achieved through dietary supply and the capacity of the body to transform the substrates and cofactors necessary for metabolism. All of these domains (diet, metabolic capacity, activity of the microbiome, body composition and the level of demand for energy and nutrients) are influenced by levels of physical activity and can vary according to physiological and pathological disease states. The liver plays a central role in establishing and maintaining these regulated processes. Its capacity to achieve and maintain these functional capabilities is established during one's early life. When these capabilities are exceeded and the ability to maintain the milieu interieur is compromised, ill-health supervenes. Stress tests that assess flow through gateway pathways can be used to determine the maximal capacity and functional reserve for critical functions. The inability of the liver to reliably integrate body lipid metabolism and the accumulation of abnormal lipid are obvious manifestations of impaired regulation both in situations of weight loss, for example, the fatty liver of severe malnutrition, and in situations of energy excess, as in non-alcoholic fatty liver disease. The use of stable isotopic probes and the more recent definition of the variability in the metabolome in different nutritional and pathological states indicate the great potential for clinical tools that would enable a more precise nutritional diagnosis, but these require systematic investigation and application. For the present, approaches that place emphasis on being able to control the metabolic state without exposing the liver to unnecessary metabolic stress remain the basis for successful nutritional support.

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The role of insufficient copper in lipid synthesis and fatty‐liver disease

et al. 2017

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Summary The essential transition metal copper is important in lipid metabolism, redox balance, iron mobilization and many other critical processes in eukaryotic organisms. Genetic diseases where copper homeostasis is disrupted, including Menkes Disease and Wilson Disease, indicate the importance of copper balance to human health. The severe consequences of insufficient copper supply are illustrated by Menkes Disease, caused by mutation in the X-linked ATP7A gene encoding a protein that transports copper from intestinal epithelia into the bloodstream and across the blood-brain barrier. Inadequate copper supply to the body due to poor diet quality or malabsorption can disrupt several molecular level pathways and processes. Though much of the copper distribution machinery has been described and consequences of disrupted copper handling have been characterized in human disease as well as animal models, physiological consequences of sub-optimal copper due to poor nutrition or malabsorption have not been extensively studied. Recent work indicates that insufficient copper may be important in a number of common diseases including obesity, ischemic heart disease, and metabolic syndrome. Specifically, marginal copper deficiency (CuD) in has been reported as a potential etiologic factor in diseases characterized by disrupted lipid metabolism such as non-alcoholic fatty-liver disease (NAFLD). In this review, we discuss the available data suggesting that a significant portion of the North American population may consume insufficient copper, the potential mechanisms by which CuD may promote lipid biosynthesis, and the interaction between CuD and dietary fructose in the etiology of NAFLD.

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IHD from copper deficiency: a unified theory

Cited by 36 publications

References 84 publications

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Nutrition and Liver Health

The role of insufficient copper in lipid synthesis and fatty‐liver disease

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