Suckling rat pups accumulate creatine primarily via de novo synthesis rather than from dam milk

During lactation, there may be a higher need for creatine replacement due to the provision of creatine to the milk. Our objectives were to: 1) quantify the creatine concentration in rat milk; 2) determine the origin of milk creatine; 3) determine the activities of the enzymes of creatine synthesis in lactating rats and pups; and 4) quantify the origin of the creatine that accumulates in rat pups. The origin of milk creatine was determined in 4 dams following the administration of (14)C-creatine by measuring the isotopic enrichment of creatine in the milk and plasma. The activities of the 2 enzymes involved in creatine synthesis were compared in lactating and virgin females (n = 7). For all experiments, the litter size was standardized to 8 pups. The data indicated that the mammary gland extracts creatine from the circulation rather than synthesizing it. This was confirmed by our failure to find substantial activities of the enzymes of creatine synthesis in mammary glands. The provision of milk creatine requires an additional 35-55% of creatine above the daily requirement by lactating rat dams. However, there was no increased creatine synthesis by these dams; the additional creatine was largely provided by hyperphagia, because creatine is present in commercial rat diet. There was a substantial accumulation of creatine in the growing pups, but only approximately 12% was obtained from milk. The great bulk of creatine accretion was via de novo synthesis by the pups, which imposed a substantial metabolic burden on them.