Medium-Chain Triglycerides in Infant Formulas and their Relation to Plasma Ketone Body Concentrations

Abstract

A B S T R A a . A mild ketosis is known to prevail in the mother, fetus, and newborn infant during the 3rd trimester and in the early neonatal period. It has been shown that during an equivalent period in the rat ketone bodies are readily oxidized and serve a s key substrates for lipogenesis in brain. Since medium-chain triglycerides are known to be ketogenic, preterm infants may benefit from dietary medium-chain triglycerides beyond the point of enhanced fat absorption. Our objective was to determine the ketogenic response in preterm infants (gestational age: 33 + 0.8 wk)fed three different isocaloric formulas by measuring the concentrations of 3-hydroxybutyrate and acetoacetate in the plasma of these infants. At the time of entrance to the study the infants were receiving 110 kcallkg124 h. Study I (1 1 infants): the infants were fed sequentially in the order; P M 60140 (PM), Special Care Formula (SCF), and Similac 20 (SIM). In S C F greater than 50% of the fat consists of medium-chain length fatty acids while P M and S I M contain about 25%. The concentration of 3-hydroxybutyrate in plasma was significantly higher when infants were fed S C F than P M and S I M [0.14 2 0.03, 0.06 f 0.01, and 0.05 f: 0.01 mM, respectively ( p < 0.01)j. Study I1 (12 infants); the infants were fed SCF, then SIM, or the reverse. The concentration of acetoacetate in plasma was 0.05 f 0.01 and 0.03 f 0.01 m M when infants were fed S C F and SIM, respectively (0.1 > p > 0.05). The concentrations of 3-hydroxybutyrate in plasma were similar to those measured in study I for the respective formulas. The increased plasma levels of 3-hydroxybutyrate and total ketone bodies when S C F was fed indicate that S C F promotes a mild ketosis in preterm infants similar to that reported in breast-fed term infants. The past decade has witnessed a major change in our concept of ketone bodies from a limited role as alternative oxidative substrates in muscle and brain to a role as key substrates for tissue respiration and lipid synthesis. Recent studies with animal models (1-4) and in human infants (5-9) suggest that the ketone bodies, AcAc and 3HB, may be particularly important in the developing infant. Several investigators have demonstrated that AcAc and 3HB, in addition to serving as general oxidative substrates, are preferentially incorporated into sterols and fatty acids in the neonatal rat brain (1, 2, 10). This occurs during the "brain growth spurt" when cell proliferation and myelination are major developmental events. In the human myelination is most active during the 3rd trimester and throughout the 1st yr of life (1 1, 12). It has also been demonstrated in both the rat (1 3-1 5) and human (6,8,16) that the uptake of ketone bodies into brain is linearly related to the arterial concentration.The concentrations of the ketone bodies in blood are elevated above typical adult levels both in the fetus during the later half of gestation (8,17) and in the breast-fed term infant (18). These data warrant considering that metabolically stable preterm in...

Quantisation of Oxidation of Medium-Chain Triglycerides in Preterm Infants1

“…When there is excess acetyl-CoA, a major pathway is formation of ketone bodies; in fact, MCFA are known to be ketogenic (26). Feeding of an MCT-containing formula for 4 d promotes a mild ketosis in preterm infants (27). These ketone bodies will be quickly utilized peripherally, especially after a period of adaptation (28).…”

Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester

“…Early studies on polyols such as 1,2-, 1,4-, and 2,3-butanediols revealed that they and monounsaturated FAs ( 61 ). Also, incorporation of MCTG into the KD may be helpful in formulating more tolerable ketogenic regimens for the long-term treatment of drug-resistant epilepsy (62)(63)(64)(65).…”

Plasma fatty acids and [13C]linoleic acid metabolism in preterm infants fed a formula with medium-chain triglycerides

“…In comparison to long-chain triacylglycerols (LCT), MCT are more efficiently absorbed in the digestive tract, and the liberated medium chain fatty acids (MCFA) are extensively and rapidly oxidized, whereas long chain fatty acids (LCFA) are largely stored in tissues (5). The intense lipid oxidation is associated with a ketogenic effect of dietary MCT, which provides an alternative energy source and is considered harmless for the infant as long as ketone body concentrations do not exceed values observed in breast fed infants (5,6).…”