Although medium-chain triacylglycerols (MCTs, composed of medium-chain fatty acids 8:0 and 10:0) have long been described as having neutral effects on serum cholesterol concentrations, experimental evidence supporting this claim is limited. In a randomized, crossover, metabolic-ward study, we compared the lipid effects of a natural food diet supplemented with either MCTs, palm oil, or high oleic acid sunflower oil in nine middle-aged men with mild hypercholesterolemia. Rather than having a neutral effect, MCT oil produced total cholesterol concentrations that were not significantly different from those produced by palm oil (MCT oil: 5.87 +/- 0.75 mmol/L; palm oil: 5.79 +/- 0.72 mmol/L) but significantly higher than that produced by high oleic acid sunflower oil (5.22 +/- 0.52 mmol/L). Low-density-lipoprotein (LDL)-cholesterol concentrations paralleled those of total cholesterol. MCT oil tended to result in higher triacylglycerol concentrations than either palm oil or high oleic acid sunflower oil, but this difference was not significant. There were no differences in high-density-lipoprotein cholesterol concentrations. The palmitic acid and total saturated fatty acid content of plasma triacylglycerols in the MCT-oil diet was not significantly different from that in the palm oil diet. On the basis of percentage of energy, this study suggests that medium-chain fatty acids have one-half the potency that palmitic acid has at raising total and LDL-cholesterol concentrations.