Metabolic and Short-term Health Impacts of a 2% Dietary Betaine Intake in Lean, Healthy Adult Cats.

This study assessed dietary betaine’s impact on the metabolism and short-term health of healthy, lean adult cats. Twelve cats [4.3±0.01 yr; 4.70±0.56 kg] were enrolled in a crossover study with two 28-d periods, including a 10-d wash-in period, separated by a 30-d washout period. Cats were fed a basal diet top-dressed with a lickable treat (CTRL) or a lickable treat mixed with betaine (2% of food intake; BET). Blood samples were collected at baseline and on d-28 for complete blood count (CBC) and biochemistry profile analyses. Plasma samples were subjected to untargeted plasma metabolome analysis using an ionic metabolite assay and high-performance chemical isotope labeling LC-MS. Data were analyzed using the GLIMMIX procedure (SAS 9.4) with treatment and sex as fixed effects, cat, block and study period as random effects, and baseline measurements as a covariate. Betaine was well-accepted with no refusals (0.223±0.021 g/kg BW). No differences (P > 0.05) in food intake were observed among groups, though BET cats were 1% heavier (P < 0.05) than CTRL at d-28. CBC and biochemistry profile parameters remained within reference ranges; however, BET cats had 15.0% greater (P < 0.05) cholesterol concentrations and 13.7% lower (P < 0.05) alanine transaminase than CTRL, suggesting that betaine enhanced hepatic lipid export. Of the 598 identified metabolites, 92 had a treatment effect (P < 0.05). Plasma betaine and its downstream metabolites, N,N-dimethylglycine, sarcosine and serine, were greater (P < 0.05) in BET cats. Choline was also greater (P < 0.05) in BET than in CTRL, suggesting a potential sparing effect. Although methionine, L-cysteine, and homocysteine were similar (P > 0.05) between groups, methionine S-oxide tended to be greater (0.69 log2 fold change [log2FC]; 0.10 >P< 0.05) and trimethylamine N-oxide were greater (1.55 log2FC; P < 0.05) in BET cats. Consistent with enhanced methyl donor availability, BET cats exhibited greater (P < 0.05) guanidoacetate (0.72 log2FC) and carnitine (0.91 log2FC) than CTRL. Lysine (0.80 log2FC) and 5-aminopentanoic acid (1.74 log2FC) were also greater (P < 0.05) in the BET group, indicating greater lysine flux for carnitine synthesis. Additionally, pantothenic acid, a precursor for coenzyme A required for fatty acid oxidation, was greater (P < 0.05) in the BET group (0.61 log2FC). Greater (P < 0.05) levels of 4-imidazolylpropanoic acid and homocarnosine were observed in BET compared to CTRL, suggesting that betaine impacted histidine pathways by sparing tetrahydrofolate (THF). The purine catabolite 5-hydroxy-2-oxo4-ureido-2,5-dihydro-1H-imidaxole-5-carboxylic acid was lower (P < 0.05) in the BET cats, suggesting improved purine salvage and reduced waste flux due to higher THF. The findings of this study suggest that betaine intake (0.223 g/kg BW) in healthy cats may improve hepatic lipid mobilization, resulting in a hepato-protective effect, while acting as a metabolic modulator of one-carbon flux and methyl status, with indications of potential impacts on protein and energy metabolism.