Cholesterol improves the utilization of parenteral lipid emulsions

Lipid emulsions have become an indispensable component of parenteral nutrition. Commercially available emulsions mostly have an identical composition of triglycerides (from plant oils) and egg-yolk phospholipids as emulsifier. Previous attempts to improve the composition of lipid emulsions have focused mainly on the triglyceride moiety. In the first fundamental modification of a lipid emulsion since their broader introduction into clinical medicine, we included free cholesterol in a lipid emulsion. We evaluated elimination and hydrolysis of triglycerides and lipid oxidation (by indirect calorimetry) in 10 healthy male normolipemic volunteers, comparing a conventional lipid emulsion (20% triglycerides) with an otherwise identical emulsion with the addition of 4 g/l free cholesterol. The rise in plasma triglycerides was mitigated during infusion of the cholesterol-enriched solution (323.8 +/- 27.5 vs. 202.0 +/- 18.9 mg.dL-1, p < 0.001), plasma half-life was reduced (41.6 +/- 5.4 vs. 29.3 +/- 5.1 min, p < 0.05), and total-body clearance was enhanced (0.96 +/- 0.1 vs. 1.52 +/- 0.2 ml.b.w.(.)min-1, p < 0.02). The rise in plasma free fatty acids (400.7 +/- 39.0 vs. 532.2 +/- 64.0 mumol.L-1; p < 0.02) and ketone bodies (beta-hydroxybutyrate) (151.6 +/- 37.0 vs. 226.3 +/- 33.01 mumol.L-1; p < 0.02) was augmented. Increases in plasma insulin and glucagon were less pronounced (p < 0.05). The fall in respiratory quotient was greater and the fraction of lipid oxidation as a percentage of total energy expenditure was increased (66.2% +/- 6.0 vs. 70.9% +/- 6.3, p < 0.05) during infusion of the modified solution. No impairment of gas exchange or other side effects were observed. Taken together these results indicate that the elimination of a cholesterol-supplemented lipid emulsion is accelerated, triglyceride hydrolysis is enhanced, and lipid oxidation is augmented. Thus, addition of cholesterol to a lipid emulsion might not only present a means of providing cholesterol in parenteral nutrition but also help to reshape artificial lipid particles to a more chylomicron-resembling composition and improve lipid utilization.