Background: This study aimed to examine the changes in serum lipids in children with mild hypercholesterolemia after the use of skim milk or olive-oil-enriched skim milk in their diet and the modulation of lipid levels by the Taq 1B polymorphism in the cholesteryl-ester transfer protein gene. Methods: Thirty-six prepubertal children with mild hypercholesterolemia were randomly assigned in a crossover design into 2 groups of 16 and 20 individuals. Both groups received, in sequential inverse order, the 2 types of milk for 2 periods of 6 weeks. Results: Carriers of at least 1 B2 allele had an adjusted basal HDL cholesterol level significantly higher than children with the B1B1 genotype (1.291 mmol/l, 95% CI: 1.184–1.397, vs. 1.082 mmol/l, 95% CI: 0.931–1.233; p = 0.027). In contrast, there were no significant differences in the adjusted basal levels of apolipoprotein A-I (B2 carriers: 1.292 g/l, 95% CI: 1.218–1.367; B1B1 genotype: 1.215 g/l, 95% CI: 1.109–1.320; p = 0.223). The intake of olive-oil-enriched skim milk caused significant increases in HDL cholesterol and apolipoprotein A-I, both in B2 (0.089 mmol/l, 95% CI: 0.032–0.146, p = 0.005; 0.55 g/l, 95% CI: 0.012–0.098; p = 0.018) and in B1B1 carriers (0.179 mmol/l, 95% CI: 0.096–0.262; p < 0.001; and 0.095 g/l, 95% CI: 0.032–0.157; p = 0.003). This increase in HDL cholesterol was significantly higher in the B1B1 group (p = 0.049). Conclusion: The consumption of skim milk enriched with olive oil increases the HDL cholesterol and apolipoprotein A-I levels in children with hypercholesterolemia, this effect being more intense in carriers of the B1B1 genotype.

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