Parenteral Nutrition With the Novel Lipid Emulsion Vegaven® Containing C-18n3 Fatty Acids Is Safe in Piglets and Confirms Superior Biological Actions Compared to SMOFlipid®

Objectives: Despite newer mixed-oil parenteral lipid emulsions that contain added C-20/22n3 fatty acids derived from fish oil, inflammation and its complications remain a concern for patients dependent on parenteral nutrition (PN). We developed a novel C-18n3 fatty acid containing mixed-oil lipid emulsion (Vegaven®, VV) [1]. In PN-fed mice, we compared VV to current lipid emulsions, including Intralipid®, Omegaven®, and the mixed-oil lipid emulsion SMOFLipid® (SL). VV had superior liver protection, metabolic and immune-enhancing effects. We have now evaluated the efficacy and safety of VV in PN-fed neonatal piglets, a highly relevant preclinical model. Methods: 5-6-day-old piglets were given isocaloric isonitrogenous PN solutions that varied only by lipid emulsion (VV, n=8; SL, n=8) for 14 days. The administered lipid dose (10g/kg/day) translates to 2g/kg/d in PN-fed infants. Sow-reared piglets served as controls (CTL). Total body and organ weights, liver bile flow, blood chemistry, plasma insulin levels (day 14), and liver tissue Interleukin-10 (IL10) levels (day 14) were measured. Data is presented as mean±SEM, comparisons used ANOVA. Results: Piglet daily health evaluations, total weight gain on trial, organ weights, bile flow and blood chemistry were not different comparing VV with SL (p >0.05). Plasma insulin levels (mU/L) were increased for SL (hyperinsulinemia, insulin resistance) compared with VV (3.77±0.35 vs 2.31±0.15, p=0.04), and higher than CTL (1.58±0.04, p< 0.001), with no difference between VV and CTL (2.31±0.15 vs 1.58±0.04, p=0.27). IL10 levels in liver tissue (pg/mg) were highest in CTL (733±52, p< 0.001) and higher for VV compared with SL (466±23 vs 318±26, p=0.004). Conclusions: Consistent with our prior findings in mice, VV demonstrated superior biological actions to SL in piglets, reversing insulin resistance and reducing liver inflammation. In this piglet model, VV was proven to be safe and effective, equivalent to the currently FDA approved mixed-oil lipid emulsion SL. Disclosure: EP 21/204659.3 (patent application) References: [1] Lucchinetti et al. Am J Clin Nutr. 2022;116(6):1805-1819. doi: 10.1093/ajcn/nqac272. PMID: 36166844. Funding Sources: Canadian Institutes of Health Research (CIHR).