The tight regulation of copper within the body may be important in preventing the progression of the disease, hypothesise the researchers from the Francesco Balsano Foundation in Rome.
NAFLD is characterised by the accumulation of fat in the liver, primarily as a result of excess dietary carbohydrate and fat intake. NAFLD can progress to a more serious condition known as non-alcoholic steato-hepatitis (NASH), and potentially to cirrhosis and liver cancer.
“Oxidative stress plays a major role in the progression of NAFLD, which seems to be the most important mechanism leading to hepatic injury,” wrote lead researcher Barbara Barbaro.
“Among others, copper is one of the main bio-metals required for the preponderance of the enzymes involved in physiological redox reactions. Thus, copper homeostasis could be considered a target point for counteracting the progression of NAFLD.
“Fittingly, antioxidant food agents recognized to improve NAFLD and its complications have been described in the literature to bind copper,” she added.
The review examines the involvement of copper dysregulation in the progression of NAFLD and the copper binding properties of antioxidant compounds.
Copper in NAFLD and NASH
Previous studies have shown that copper restriction in rats induces altered fat metabolism, hepatic steatosis and insulin resistance. Additionally, rats fed a high-fructose, low-copper diet suffered steatosis and liver damage. Human NAFLD subjects have also displayed lower liver and blood copper levels than subjects with other liver diseases.
One study comparing copper levels in NASH and NAFLD patients showed that liver copper levels were lower in the former group, but no difference in serum levels was seen. More recent evidence has suggested serum copper levels increase as the disease progresses from NAFLD to NASH and from cirrhosis to liver cancer.
Furthermore, Wilson’s disease, characterised by excess copper, is a known risk factor for liver cancer.
Although the researchers emphasise that mechanisms underlying copper’s role in NAFLD progression are not well understood, they suggest “this evidence implies that the deregulation of copper in NAFLD and the consequent oxidative stress, if not counteracted, could lead to serious [liver] damage.”
Nutrients for NAFLD
The researchers identified a number of compounds which have shown benefits in aspects of preventing NAFLD progression. These nutrients also displayed the ability to bind copper.
Curcumin, the active ingredient in turmeric, has demonstrated an ability to bind and chelate copper and in animal studies has helped in the prevention of diet-induced liver steatosis.
Epigallocatechin-3-Gallate (EGCG), found in green tea, is also a potent copper chelator and has improved insulin sensitivity in mice.
Luteolin and Luteolin-7-Glucoside (found in oregano, parsley, olives and cacao) were shown to increase lipid beta-oxidation and downregulate sterol regulatory element-binding protein-1 (SREBP-1) in rats, thereby reducing lipogenesis. The compounds are also able to bind copper.
Coffee intake has been associated with lower risk of liver fibrosis in NAFLD patients, while caffeic acid reduced lipogenesis and improved fat oxidation in animal liver cells.
Oleuropein, a constituent of olives and olive leaves is a copper binding compound, which slowed the progression of NASH to fibrosis in mice.
Quercetin and rutin, abundant in capers, radishes and citrus fruit, reduced triglycerides and oxidative damage in animal liver cells. Their copper binding properties have also been demonstrated.
Resveratrol, described as a binder of copper, has shown benefits in animal studies in the prevention and treatment of liver steatosis.
“The Western diet is associated with high intake of fats and carbohydrates. Furthermore, it is poor in polyphenols, with devastating health consequences, such as promoting NAFLD. Many antioxidant compounds recognized as being effective against NAFLD and its progression have been demonstrated to bind copper,” explained the researchers
“Since there is a gap between the knowledge of the chemical properties of these compounds and their therapeutic applications, this review also paves the way to broaden the research on natural antioxidant compounds against NAFLD, which considers their ability to bind copper,” they concluded.
Volume 9, issue 10, 1137, doi: 10.3390/nu9101137
“Non-Alcoholic Fatty Liver Disease and Nutritional Implications: Special Focus on Copper”
Authors: Laura Antonucci, Cristiana Porcu, Gino Iannucci, Clara Balsano and Barbara Barbaro