<p>Disturbances in the one-carbon metabolic pathways are linked with several diseases, and an elevated homocysteine concentration is correlated with increased risk for developing cardiovascular diseases. Fish intake reduces homocysteine concentration in some studies, whereas little is known whether other metabolites in the one-carbon pathways are affected. Most pre-clinical studies utilise rodents, but domestic dogs may be a superior alternative model for research on human nutrition. The aim of this study was to compare the effects of diets containing proteins from herring or poultry on serum concentrations of homocysteine and related one-carbon metabolites in domestic dogs. Forty home-living golden Retrievers and Labrador Retrievers were included and received each of the two experimental diets for eight weeks in this cross-over trial. Thirty-five dogs were included in the biochemical and statistical analyses. Within-group changes were compared using the Mann-Whitney U Test. The serum concentrations of homocysteine, sarcosine, cystathionine and serine were reduced after intake of either herring or poultry protein diets, with no differences between the groups. The serum betaine concentration was increased by both diets, with a more pronounced increase after poultry protein intake, whereas choline concentration was not affected by either diet. Methionine and cysteine concentrations were not affected by herring protein, but were decreased and increased, respectively, after poultry protein intake. The glycine concentration was reduced by both diets. Both herring and poultry proteins affected the one-carbon metabolism, with only marginal differences between the diets.</p>