Lower risk for liver copper accumulation in dogs fed copper-restricted diets versus those fed copper-replete diets

Abstract

Objective: Estimate tolerable dietary copper (Cu) intake in senior dogs from a primary care hospital population representing typical pet dog demographics. Methods: Liver samples from 104 dogs euthanized for geriatric health concerns were collected from April 7, 2023, to April 22, 2024. Medical records, dietary history, and regional water analyses were acquired. Dietary Cu (manufacturer typical analyses or inductively coupled plasma atomic emission spectroscopy [USDA micronutrient laboratory]) was normalized as mg of Cu/100 kcal (energy calculations used modified Atwater factorials). Liver samples underwent histological evaluation (H&E, rhodanine), rhodanine Cu scoring, and Cu quantification (µg/g of dry weight liver [dwl]). Categorical dietary Cu intakes were Cu-restricted (0.15 to 0.24 mg of Cu/100 kcal) versus Cu-replete (0.31 to 0.39 and ≥ 0.40 mg of Cu/100 kcal). Nonparametric statistics defined significant differences and associations. Results: 51 male, 53 female, 32 breeds and 29 mixed breeds had median (95% CI) age, weight, and diet duration of 11.6 years (10.6 to 12.1 years), 23.0 kg (20.1 to 25.4 kg), and 8.0 years (7.0 to 8.7 years). No dog fed Cu-restricted diets displayed evidence of Cu insufficiency. Water Cu concentration was 0.12 mg/L (0.08 to 0.17 mg/L). Common histological features (glycogen-type vacuolation [n = 61], reactive-hepatitis [20], neoplasia [18]) did not associate with liver Cu concentration. Thirteen dogs fed Cu-restricted diets had significantly lower liver Cu than 91 dogs fed Cu-replete diets. Liver Cu in Cu-restricted-diet dogs did not exceed 355 µg of Cu/g of dwl or stain with rhodanine. Among dogs consuming Cu-replete diets were 35 of 91 (38%) with rhodanine positivity, 20 of 91 (22%) with liver Cu ≥ 400 µg of Cu/g of dwl (upper reference range), and 14 of 91 (15%) with liver Cu ≥ 600 µg of Cu/g of dwl. Conclusions: Findings demonstrated significantly higher liver Cu concentration with dietary intake ≥ 0.31 mg of Cu/100 kcal than with dietary intake of 0.15 to 0.24 mg of Cu/100 kcal. Water was exonerated as a critical Cu source. Clinical Relevance: Details indicated a tolerable upper Cu intake of 0.24 mg of Cu/100 kcal in studied dogs.