Human milk enhances antioxidant defenses against hydroxyl radical aggression in preterm infants

Background: Preterm infants endowed with an immature antioxidant defense system are prone to oxidative stress. Hydroxyl radicals are very aggressive reactive oxygen species that lack specific antioxidants. These radicals cannot be measured directly, but oxidation byproducts of DNA or phenylalanine in urine are reliable markers of their activity. Human milk has a higher antioxidant capacity than formula. Objective: We hypothesized that oxidative stress associated with prematurity could be diminished by feeding human milk. Design: We recruited a cohort of stable preterm infants who lacked perinatal conditions associated with oxidative stress; were not receiving prooxidant or antioxidant drugs, vitamins, or minerals before recruitment; and were fed exclusively human milk (HM group) or preterm formula (PTF group). Collected urine was analyzed for oxidative bases of DNA [8-hydroxy-2'-deoxyguanosine (8-oxodG)/2'-deoxyguanosine (2dG) ratio] and oxidative derivatives of phenylalanine [ortho-tyrosine (o-Tyr)/Phe ratio] by HPLC coupled to tandem mass spectrometry. Healthy term newborn infants served as control subjects. Results: Both preterm groups eliminated greater amounts of metabolites than did the control group. However, the PTF group eliminated significantly (P < 0.02) higher amounts of 8-oxodG (8-oxodG/2dG ratio: 10.46 +/- 3.26) than did the HM group (8-oxodG/2dG ratio: 9.05 +/- 2.19) and significantly (P < 0.01) higher amounts of o-Tyr (o-Tyr/Phe ratio: 14.90 +/- 3.75) than did the HM group (o-Tyr/Phe ratio: 12.53 +/- 3.49). When data were lumped together independently of the type of feeding received, a significant correlation was established between the 8-oxodG/2dG and o-Tyr/Phe ratios in urine, dependent on gestational age and birth weight. Conclusion: Prematurity is associated with protracted oxidative stress, and human milk is partially protective. Am J Clin Nutr 2009; 89: 210-5.