Displacement of Bilirubin From Albumin by Omegaven and Intralipid

Intralipid, a soybean oil-based fat emulsion, is the only FDA-approved lipid source for neonatal parenteral nutrition, but it increases unbound free fatty acids (FFAu), which can displace bilirubin from albumin and elevate the risk of bilirubin-induced neurologic dysfunction (BIND). Omegaven, a fish oil-based alternative, exhibits hepatoprotective properties; however, its effect on bilirubin displacement is less well understood.

To compare the bilirubin-displacing effects of the major FFAu components in Intralipid (oleic acid (OA), linoleic acid (LA)) and Omegaven (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) in vitro.

Utilizing ADIFAB2 fluorescence to quantify FFAu and a near-infrared probe for unbound bilirubin (Bf), we measured binding affinities and the displacement of bilirubin by OA, LA, EPA, and DHA. Titrations were conducted on human serum albumin (HSA) with and without bilirubin across FFA:HSA molar ratios ranging from 1:1 to 6:1.

Dissociation constants (Kd) were OA 5 nM, LA 15 nM, EPA 20 nM, and DHA 22 nM. Bf increased with rising FFAu, especially at FFA: HSA ratios greater than 4:1. At 5.5:1, Bf levels peaked for OA (96 nM) and LA (90 nM), while remaining lower for EPA and DHA (both 55 nM).

Omegaven-derived FFAu displaced less bilirubin from albumin than Intralipid-derived FFAu, indicating its potential neuroprotective as well as hepatoprotective advantages.