Maillard reaction products and lysinoalanine: urinary excretion and the effects on kidney function of preterm infants fed heat-processed milk formula.

Heat processing is essential for the preservation of milk-based infant formulas. Heating, however, induces a number of chemical changes during which lysine in the milk proteins reacts with reducing sugars to form Maillard reaction products (MRPs) and also reacts with the dehydroalanine resulting from cystine degradation to form lysinoalanine (LAL). Both products have been reported to induce histological changes in the straight portion of the proximal tubule in the rat kidney. This pilot study was made to investigate the urinary excretion by healthy preterm babies of MRPs and LAL contained in infant formula and to determine their influence on kidney function. Twelve healthy male preterm babies were first fed for 10 days with pooled human milk and then for 5 days with each of two experimental premature infant formulas in a cross-over design. The infant formulas were sterilized either by ultra-high temperature (UHT) treatment or by a conventional retort process to give products with low and high levels of MRPs and LAL, respectively. In total, some 15.6% of the initial lysine had been modified in the in-can-sterilized product, compared to 6.2% in the UHT product. Urinary excretion of MRP lactulosyllysine ranged from 1.3 to 3.9% of the ingested amount, whereas that of LAL ranged from 6.2 to 9.3%. The higher level of MRPs and LAL in the formulas compared to breast milk had no influence on creatinine clearance or electrolyte excretion. There was no evidence of tubular damage as determined by the urinary excretion of four kidney-derived enzymes. Feeding of formula, however, did result in a general increase in urinary microprotein levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Excretion and tissue distribution of radioactive lysinoalanine, N epsilon-DL-(2-amino-2-carboxyethyl)-U-14C-L-lysine (LAL) in Sprague-Dawley rats.

Rats were fed either a control soybean protein diet or a diet containing 3,000 ppm soybean protein-bound lysinoalanine (LAL) for 4 or 6 weeks, at which time all rats were dosed by stomach tube with 14C-LAL labeled in the lysine moiety. Urinary and fecal excretion and tissue distribution were followed in one experiment at 6, 12, 18, 24, 48 and 72 hours. Excretion in urine, feces and expired air was followed in the other metabolic experiment at 2-hour intervals for 48 hours, and at 24-hour intervals for the next 7 days. Tissue samples were counted and LAL determination was made by amino acid analysis in both experiments. The group of rats fed LAL excreted slightly more LAL than the group fed the control diet. Very little LAL remained in the rat tissues after either experiment, and the largest remaining quantity of radioactivity was found as lysine. Quantitation of 14C-lysine in the original material and in the material from rat organs showed that the rat has some capacity for converting LAL to lysine. Less than 0.5% of the original 14C remained in any organ examined 9 days after dosing in the either control or LAL-fed rats. Autoradiographs of the kidneys 24 hours after dosing showed that the radioactive material had accumulated in the proximal convoluted tubules of the corticomedullary junction.