Metabolic responses in lactose-free vs regular infant formula fed infants

This summary is adapted from ‘Postprandial metabolic response of breast-fed infants and infants fed lactose-free vs regular infant formula: A randomized controlled trial’ by Slupsky et al. 2017

Lactose is the major carbohydrate in human breast milk, with a 50% higher concentration than is found in cow’s milk1. Infant formulas aim to match the composition of human milk with high levels of lactose, however lactose-free formulas are growing in use due to concerns around lactose intolerance in infants. There are widely and increasingly available infant formulas which replace lactose with corn syrup solids. There is still further evidence needed that reduced lactose formulas are beneficial and provide an equivalent alternative to cow’s milk-based formulas and breast milk. There have been results indicating that the growth of infants fed reduced lactose formulas is normal, but there may be other effects on the body that differ from cow’s milk formula and breast milk. In this study, researchers aimed to investigate the effects of corn syrup solids-based formula on the infant’s metabolism, meaning how substances are broken down and processed in the body. This is important, as alterations in metabolism can predispose infants to disorders such as insulin resistance and obesity. In addition, they can indicate deficiencies in the infant’s diet.

Read more about the role of lactose in infant formula 

23 formula-fed infants and 11 breast-fed infants were included in this study at 3 months of age. Half of the formula-fed infants received cow’s milk-based infant formula and the other half received corn syrup solid-based infant formula. Parents or guardians of infants in the formula groups were given their experimental formulas to acclimatise their infants to the taste prior to the test day. Blood samples were taken before and after the infants were fed with breast milk or the experimental formula to compare levels of markers of the infant’s metabolism across the different feeding groups.

At baseline (pre-feeding) there were differences in the metabolic profiles between the breast-fed and formula-fed infants, indicating there was a difference in how these infants are processing substances. There were no differences pre-feeding in infants fed cow’s milk-based formula or corn syrup solids-based formula. These differences between breast and formula-fed infants were maintained in the analysis of blood taken after feeding, and in this analysis, there were also some differences between the two formula-fed groups. Both formula-fed groups had elevated insulin compared to breast-fed infants and interestingly, infants fed the cow’s milk-based formula had higher insulin than those fed corn syrup solids-based formula along with significantly higher glucose. Levels of ketone bodies were measured, which are produced when the body breaks down fat for energy instead of its predominant source of energy, glucose. When insulin levels are low, such as in diabetes, the body’s ability to use glucose for energy is impaired and fat can be used instead, producing higher levels of these ketone bodies. In this analysis, it was found that ketone bodies were significantly higher in infants fed the cow’s milk-based formula in comparison to the corn syrup solids-based formula after feeding. These values were similar to those found in breast-fed infants. Furthermore, there were more rapid and higher increases in amino acids (the building blocks of protein), creatinine and urea (indicative of kidney function) in formula-fed infants compared to breast-fed infants.

These results indicated that there were distinct differences in metabolic analysis of infants fed breast milk, cow’s milk-based formula, and corn syrup solids-based formula. This leads us to believe that the metabolic state in infants, or how the infant is processing chemicals in the body, is shaped by the infant’s diet. The specific differences noted in this study are difficult to interpret, as they could be caused by a wide variety of factors and may or may not have an effect on the infant’s health status. The number of infants included in this study was also too small to make any concrete conclusions. The increase in protein degradation pathways seen in formula-fed infants, for example urea, creatine, and amino acids, in formula-fed infants are likely caused by the higher protein content in the formula compared to breast milk. In this study, the formulas used had around twice as much protein as breast milk, which could explain these differences seen. Another factor which could be influencing the concentrations of these markers is stomach emptying rates. Formulas and breast milk are emptied from the stomach at different rates, which can lead to concentrations of substances reaching the blood faster or slower after feeding. Again, what effect this may have on the infant is not investigated in this study.

Of note, differences in insulin levels were noted across the groups of infants here. Formula-fed infants had increased blood insulin compared to breast-fed infants, with cow’s milk formula producing the highest concentration. Other markers associated with insulin resistance and impaired glucose regulation, early signs of diabetes development, were also higher in the formula-fed groups. There has been no evidence of increased risk associated with infant formula compared with breastfeeding, however there has been an association with higher fat mass2. Further studies may investigate the effects of the alterations of this aspect of metabolism on infant health and health later on in life.

Overall, the differences seen in this study highlight that changes in infant metabolism can be associated with infant formula compared to breast milk, and cow’s milk-based formula and corn syrup solids-based formula. This study shows that analysis of these markers should be carried out in further studies to investigate potential areas which are impacting infant health. This will improve the quality of infant formulas available.

Read full study here


  1. Schaafsma G. Lactose and lactose derivatives as bioactive ingredients in human nutrition. International Dairy Journal. 2008 May 1;18(5):458-65.
  2. Gale C, Logan KM, Santhakumaran S, Parkinson JR, Hyde MJ, Modi N. Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis. The American journal of clinical nutrition. 2012 Mar 1;95(3):656-69.
Metabolic responses in lactose-free vs regular infant formula fed infants

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