Human milk has a higher concentration of
nucleotides than bovine milk which is the source of most infant formulas. As the composition of human milk is considered the 'gold standard,' an increasing number of infant formulas are supplemented with
nucleotides. This review summarises the biology of human milk
nucleotides and evaluates the studies which investigated the clinical benefits of feeding infants with
nucleotide-supplemented formulas. Although dietary
nucleotides have been suggested to have beneficial gastrointestinal and immunological effects,
nucleotide-supplemented formula feeding has not been shown to confer the same benefits as breast feeding, and randomised controlled trials have yet to prove that healthy term infants fed
nucleotide-supplemented formulas compared to those fed nonsupplemented formulas, have accelerated physical growth and neurological development, better growth and development of their gastrointestinal tract resulting in improved digestive and absorptive functions, enhanced development of their immune system resulting in increased resistance to
infection and lower bacterial and
viral infection rates during infancy, and a more favourable intestinal microflora associated with a lower rate of infectious diarrhoea. However, a randomised controlled trial has reported that term infants with severe
intrauterine growth retardation do have better catch-up growth with
nucleotide supplementation. The hypothesis that
nucleotides are semi-essential nutrients needs to be further studied, in particular in the presence of prematurity,
fetal growth retardation, intestinal injury and limited nutrient intake. As no deleterious effects have been reported with the use of
nucleotide-supplemented formulas, the first of which was introduced over 30 years ago, such products are considered safe when
nucleotides are supplemented to an amount equivalent to the free
nucleotide concentration of human milk. More basic and clinical research studies are awaited to further define the biology and role of human milk
nucleotides, and to critically assess the potential benefits and appropriate level of
nucleotide supplementation of infant formula.