Limited information is available on the metabolic fate of medium-chain triacylglycerols (triglycerides) after intestinal absorption and on their influence on essential fatty acid metabolism. We studied in preterm infants the effect of two infant formulas, one with a high (HMCT) and one with a low (LMCT) medium-chain triacylglycerol content, on plasma fatty acids. The HMCT formula contained 46 mol% 8:0 + 10:0 and the LMCT formula (4.8 mol% 8:0 + 10:0) had approximately twice the amount of long-chain saturated and monounsaturated fatty acids as the HMCT. Both formulas had similar contents of linoleic and linolenic acids. Plasma lipids and fatty acids were determined at birth and on day 24 of life in 20 infants fed the LMCT (n = 12) or HMCT (n = 8) formula. Significant amounts of medium-chain fatty acids were found in the systemic circulation of the infants fed the HMCT formula, mainly in plasma fatty acids and triacylglycerols. Despite striking dietary differences, palmitic and stearic acids were not different between groups, indicating de novo synthesis of long-chain fatty acids with the HMCT formula. Plasma phospholipid docosahexaenoic acid was significantly lower in the HMCT group than in the LMCT infants (1.38 +/- 0.07 compared with 1.73 +/- 0.07 mol%, P = 0.002). Our data indicate that a high MCT intake in preterm infants increases lipogenesis, and dietary nonessential fatty acids interfere with the metabolism of docosahexaenoic acid.