The metabolic fate of deuterium-labeled choline in gestating and lactating Holstein dairy cows

Our objective was to evaluate changes in choline metabolism including bacterial degradation to trimethylamine (TMA), methyl group transfer, and bioavailability in pregnant and lactating cows. Six multiparous, rumen-cannulated Holstein cows were enrolled in a study design where they were abomasally infused 18 g/d choline chloride (CC; dissolved in water; 170 mL/h) for a 5-d experimental period at −3 wk from expected due date and again at 2 wk postpartum. The stable-isotope trimethyldeuterium (d9)-CC replaced 20% of daily unlabeled CC to study methyl group transfer. Cows were fed a Met deficient diet. Plasma, milk, liver, urine, and fecal samples collected on d 4 and 5 of each period (gestation and lactation) were analyzed for choline and choline metabolite concentrations and isotope enrichment using mass spectrometry. Data were analyzed using a general linear model including the fixed effect of period. Plasma betaine (P < 0.01), liver choline and betaine concentrations were lower during lactation (P < 0.01). Lactating cows had greater circulating enrichment of d3-choline, d3-betaine, d9-betaine, and d9-phosphatidylcholine (PC; P ≤ 0.05), and greater liver enrichment of d3-glycerophosphorylcholine and d9-sphingomyelin (P ≤ 0.02). Liver d3-PC was detected but not modified by period. Greater urinary and fecal losses of d3- and d9-TMA, and d3- and d9-TMA N-oxide (TMAO) were observed during pregnancy (P ≤ 0.05). Total choline metabolites detected in urine from infused CC were greater during pregnancy, relative to lactation (17 vs. 9%; P < 0.01). Total fecal choline metabolites from infused CC were greater during lactation, relative to pregnancy (5 vs. 1%; P = 0.03). We estimate that 25% of infused CC was used for milk choline metabolite enrichment. We conclude that choline is a methyl donor in the cow (e.g., detected d3-choline), and choline is utilized by the cytidine diphosphate-choline and phosphatidylethanolamine N-methyl transferase pathways. We also provide evidence for endogenous recycling of absorbed choline via bile (i.e., presence of d3-TMA). Degradation of choline to TMA and TMAO must be considered when evaluating choline bioavailability.

Key Words: choline, methyl donor, transition period