It has been recommended to supplement formulas for preterm infants with n-3 and n-6 long-chain polyunsaturated fatty acids (LCP) to improve growth, visual acuity, and neurodevelopmental performance. However, large amounts of LCP may increase lipid peroxidation and oxidative stress in preterm infants. We investigated if, under high supplementation of natural tocopherols, LCP addition to formula can be performed safely without causing tocopherol depletion in cell membranes. Thirty-one healthy preterm infants with gestational ages from 28 to 32 weeks were evaluated in a prospective, randomized study from birth to day 42. Nine infants received an n-3 and n-6 LCP-enriched formula (A), eleven infants a standard formula (B), and eleven infants breast milk (control group). Alpha- and gamma-tocopherol extracts were added to both formulas, amounting to five times the value in breast milk (2.3 mg/dL in both formulas versus 0.45 mg/dL in breast milk). Erythrocyte arachidonic acid (AA) and docosahexaenoic acid (DHA) in the phosphatidylethanolamine fraction were similar in the three groups over the study period, whereas a significant reduction of erythrocyte AA and DHA could be detected in the phosphatidylcholine fraction in all three groups from day 14 onwards, when compared to respective cord blood values, with lowest values in the standard formula group. Amazingly, levels of alpha- and gamma-tocopherol were higher in plasma, erythrocytes, platelets, monocytes, and polymorphonuclear leukocytes with LCP supplementation as compared to standard formula and breast milk from day 7 onwards, whereas in buccal mucosal cells, this was not the case until day 42. Gamma-tocopherol uptake in the LCP-supplemented group was also significantly higher in all cell fractions studied from day 7 onwards. We therefore hypothesize that the LCP supplementation used in formula A improves tocopherol solubility and stability in biological membranes. Under high-dose vitamin E addition to n-3 and n-6 LCP-supplemented formula, no evidence for tocopherol depletion and furthermore, high accumulation of tocopherols, can be detected in healthy preterm infants.
Protein hydrolysate versus standard formula for preterm infants