From early inflammation to advanced fibrosis, researchers detail the liver damage caused by copper overload and the role of treatment.
A new study described the progression of liver disease in Wilson's disease (WD) by using a mouse model to examine the histological impact of copper overload.
Published in the Journal of Clinical Pathology, the study examined the stages of liver injury caused by copper accumulation, highlighting the role of inflammation, fibrosis, and atypia—and outlined potential benefits of chelation therapy.
WD is a rare genetic disorder caused by mutations in the ATP7B gene, disrupting copper transport and leading to toxic accumulation in the liver, brain, and other tissues. While WD is phenotypically diverse, liver involvement—ranging from asymptomatic changes to cirrhosis or acute liver failure—is common. However, early liver disease progression in WD remains poorly understood due to limited access to pre-symptomatic human samples, the authors noted.
This gap in knowledge prompted researchers to turn to animal models. Among them, the Atp7b−/− knockout mouse—a genetically engineered model—has emerged as a robust tool for studying WD-related liver pathology.
The study examined 138 Atp7b−/− mice across five age groups: 6, 20, 39, and 50 weeks, with and without copper chelation therapy. These groups were compared with 101 wild-type (WT) mice. The researchers performed comprehensive histological analyses to track liver injury progression.
Copper deposits in hepatocytes were detected as early as 6 weeks in Atp7b−/− mice but did not significantly increase over time. WT mice showed no copper deposition. Inflammation appeared by 6 weeks and progressively worsened, correlating with fibrosis, which became evident by 20 weeks. By 50 weeks, untreated Atp7b−/− mice displayed precirrhotic changes, while treated mice showed significantly reduced inflammation and fibrosis scores.
Significant cellular atypia, including nuclear enlargement and hepatocyte dysmorphia, emerged at 20 weeks and peaked at 39 weeks. Chelation therapy mitigated these changes but did not eliminate them. Nodular areas of regenerating liver tissue appeared in Atp7b−/− mice at 39 weeks. These nodules lacked copper deposits and were free of inflammation or fibrosis.
Unlike in human WD livers, steatosis was negligible, and no dysplastic or malignant changes were observed, aligning with the low malignancy risk typically seen in WD patients.
The study highlighted the efficacy of D-penicillamine, a copper-chelating agent, in reducing inflammation and fibrosis. However, the treatment did not reverse established nodular changes, underscoring the importance of early intervention.
Despite its strengths, the model has limitations. Unlike human WD, the mice do not exhibit neurological symptoms due to compensatory mechanisms in their brains, the authors wrote. Additionally, the absence of significant steatosis and malignancy in mice highlights differences in disease manifestation.
Moving forward, researchers aim to extend the study duration to observe whether full cirrhosis or malignancy develops and to test novel therapeutic agents.
8 Foods That Are High in Copper
Written By Helen West Edited By John Bassham
Liver Organ meats — such as liver — are extremely nutritious.
They provide good amounts of many nutrients, including vitamin B12, vitamin A, riboflavin (B2), folate (B9), iron and choline
Liver is also an excellent source of copper.
In fact, one slice (67 grams) of calf liver gives you 10.3 mg of copper — a whopping 1,144% of the Reference Daily Intake (RDI)
To add flavor and zest to liver, try pan-frying it with onions or mixing it into burger patties and stews.
However, the high amounts of vitamin A in liver can harm unborn babies. Therefore, pregnant women should avoid foods extremely high in vitamin A, including liver
Summary
Liver is an extremely nutritious meat. Just one slice of calf liver boasts over 11 times the RDI for copper, as well as good amounts of other important nutrients.
Oysters Oysters are a type of shellfish often considered a delicacy. They can be served cooked or raw, depending on your preference. This seafood is low in calories and high in many essential nutrients like zinc, selenium and vitamin B12.
In addition, oysters are a good source of copper, providing 7.6 mg per 3.5 ounces (100 grams) — or 844% of the RDI
You may be concerned about eating oysters and other shellfish due to their high cholesterol content.
However, unless you have a certain, rare genetic condition, dietary cholesterol found in foods like oysters is unlikely to significantly raise your blood levels of cholesterol (6Trusted Source).
It should be noted that high dietary intake of zinc can interfere with copper absorption, and because oysters are also very high in zinc, 154mg per 100g, this may interfere with the amount of copper absorbed Keep in mind also that raw oysters do carry a risk of food poisoning, so are not recommended for pregnant women or people with compromised immune systems
Summary
Per 3.5 ounces (100 grams), oysters contain 8.5 times the RDI for copper. This low-calorie shellfish is also high in zinc, selenium and vitamin B12.
Spirulina
Spirulina is a powdered food supplement made from cyanobacteria, or blue-green algae.
Once consumed by the ancient Aztecs, it reemerged as a health food after NASA successfully used it as a dietary supplement for astronauts on space missions. Gram for gram, spirulina is extremely nutritious. A single tablespoon (7 grams) contains just 20 calories but packs 4 grams of protein, 25% of the RDI for vitamin B2 (riboflavin), 17% of the RDI for vitamin B1 (thiamine) and around 11% of the RDI for iron (11).
The same amount provides 44% of the RDI for copper.
Spirulina is often mixed with water to make a greenish beverage. However, if you don’t like its unusual taste, you can add it to stock, smoothies or cereal to disguise the flavor.
Summary
Spirulina, is a dried supplement made from blue-green algae, is extremely nutritious — a single tablespoon (7 grams) gives nearly half of your daily copper needs.
Shiitake Mushrooms
Shiitake mushrooms are a type of edible mushroom, native to East Asia, that have a strong umami flavor. Four dried shiitake mushrooms (15 grams) offer 44 calories, 2 grams of fiber and a host of nutrients, including selenium, manganese, zinc, folate and vitamins B1, B5, B6 and D
This portion also knocks out an impressive 89% of the RDI for copper.
Summary
A handful of dried shiitake mushrooms packs nearly all of your daily needs for copper. They’re also rich in other important nutrients.
Nuts and Seeds
Nuts and seeds are tiny powerhouses of nutrition.
They’re high in fiber, protein and healthy fats, as well as a wide range of other nutrients. Although different nuts and seeds contain different nutrients, many hold substantial amounts of copper. For example, 1 ounce (28 grams) of almonds or cashews boasts 33% and 67% of the RDI, respectively
Additionally, a tablespoon (9 grams) of sesame seeds packs 44% of the RDI
You can enjoy nuts and seeds as a standalone snack, atop a salad or baked into a bread or casserole.
Summary
Nuts and seeds — particularly almonds, cashews and sesame seeds — are good sources of copper. What’s more, they’re high in fiber, protein and healthy fats.
Lobster
Lobsters are large, muscular shellfish which live on the seabed.
Their succulent flesh makes them a popular addition to soups and bisques, though they can also simply be served on their own.
Lobster meat is low in fat, high in protein and loaded with vitamins and minerals, including selenium and vitamin B12.
It’s also an excellent source of copper.
In fact, a 3-ounce (85-gram) serving of lobster contains a phenomenal 178% of the RDI
Interestingly, though low in fat, lobster is also quite high in cholesterol. However, dietary cholesterol has little effect on blood cholesterol levels in most people, so the amount in lobster shouldn’t be a concern
Summary
Lobster is a delicious seafood which is low in fat, high in protein and an excellent source of copper, providing 178% of the RDI in a 3-ounce (85-gram) serving.
Leafy Greens Leafy greens like spinach, kale and Swiss chard are extremely healthy, boasting nutrients like fiber, vitamin K, calcium, magnesium and folate in a minimal number of calories. Many leafy greens contain sizeable amounts of copper.
For example, cooked Swiss chard provides 33% of the RDI for copper in a single cup (173 grams)
Other greens have similar amounts, with a cup (180 grams) of cooked spinach also holding 33% of the RDI
These greens can be enjoyed raw in a salad, cooked into a stew or added as a side to most meals to boost both their nutrient and copper content.
Summary
Leafy greens like Swiss chard and spinach are extremely nutritious, copper-boosting additions to your diet.
Dark Chocolate
Dark chocolate contains higher amounts of cocoa solids — as well as less milk and sugar — than regular chocolate. Dark chocolate boasts antioxidants, fiber and several nutrients.
For example, a 3.5-ounce (100-gram) bar of dark chocolate — with 70–85% cocoa solids — provides 11 grams of fiber, 98% of the RDI for manganese and 67% of the RDI for iron
The same bar also packs a massive 200% of the RDI for copper. What’s more, consuming dark chocolate as part of a balanced diet is linked to improvements in several heart disease risk factors (21Trusted Source, 22Trusted Source, 23Trusted Source).
However, take care not to overeat dark chocolate. It’s still a high-calorie food loaded with fat and potentially sugar.
Summary
Dark chocolate is a sweet treat that bestows a mix of beneficial nutrients, including copper. One bar alone may give you double your daily copper needs.
The Bottom Line
Copper — which is vital to your health — is found in a wide range of foods, from meat to vegetables. Particularly good sources include oysters, nuts, seeds, shitake mushrooms, lobster, liver, leafy greens and dark chocolate. To avoid a deficiency, be sure to include a variety of these sources in your diet.
As always Stay Safe, Stay Healthy and Be Careful out there
James A Vito, D.M.D.