Taurine (2-aminoethanesulphonic acid) was isolated from ox (Bos taurus) bile in 1827¹ but, until the mid to late 1970s, it was thought to be merely a byproduct of sulphur amino acid metabolism. In 1975, it was noted that taurine deficiency in cats was associated with retinal degeneration, which was reversed by taurine supplementation.² This observation coupled with the high concentration of taurine in the developing brain³ and mature retina⁴ raised suspicion that taurine may play an important role in brain development. This was supported by observations that brain taurine concentration of several species decreased during the weaning period³ and that taurine was the primary free amino acid in the milk of most mammals, including humans.⁵ Moreover, labelled taurine injected intraperitoneally into lactating rats was found in the milk of the dam as well as the brain of the suckling pups,⁶ suggesting that adequate intake of taurine was important for maintaining brain taurine content.

Shortly after the observation that taurine deficiency in cats resulted in retinal degeneration, evidence that taurine may be a conditionally essential nutrient for the human infant began appearing. The first such evidence came from a study in Scandinavia showing that plasma and urinary taurine concentrations of formula fed infants were lower than those of infants fed human milk,⁷ whereas the plasma and urinary concentrations of all other amino acids were higher in formula fed infants.^8,9 This was attributed to the presence of taurine in human milk but not formulas. Subsequently, it was shown that prolonged taurine-free parenteral nutrition resulted in retinal degeneration that was reversed with taurine supplementation.¹⁰ Retinal abnormalities were also found in primates fed a taurine-free infant formula.¹¹

On the basis of these findings, taurine was added to most infant formulas by the early to mid 1980s. The only randomised controlled trial of taurine supplementation was started before its routine addition to formulas but terminated for ethical reasons after 37 rather than the planned 50 infants were enrolled. Nonetheless, preterm infants assigned to the taurine supplemented formula had a more mature auditory brain stem evoked response than those assigned to the taurine-free formula.¹² However, no differences in electroretinograms or Brazelton scores were detected. Infants fed taurine supplemented formulas also have a bile salt conjugation pattern more like that of breast fed infants as well as a larger bile salt pool, but reported effects on fat absorption have been mixed.^13–15

Owing to the relative lack of evidence that taurine supplementation of infant formulas has beneficial clinical effects, recent recommendations for the nutrient contents of term infant formulas do not include a minimum content of taurine.¹⁶ However, as formulas have contained taurine for almost two decades and these seem to be well tolerated, a maximum amount (12 mg/100 kcal) is specified. This is near the maximum content observed in human milk and about 25% more than the content of modern formulas. A minimum content of taurine (5 mg/100 kcal) is specified for preterm infant formulas but without much enthusiasm.¹⁷

The findings of Wharton et al,¹⁸ reported in this issue, suggest that the recommendations for taurine content of infant formulas should be reconsidered. These findings suggest that low plasma taurine concentration during the hospital stay may explain the paradox of higher developmental scores at 18 months¹⁹ and 7 years of age²⁰ in preterm infants assigned to a nutrient enriched compared with a term formula during initial hospital admission but similar scores in infants assigned to banked human milk compared with the nutrient enriched formula despite the fact that the nutrient density of the banked human milk was even lower than that of the term formula.²¹ Although the possibility that the paradoxical neurodevelopmental outcomes were related to taurine intake during infancy was suggested in reviews by Sturman and Chesney in 1995²² and Chesney et al in 1998,²³ Wharton et al¹⁸ provide the first indication that this explanation may be valid. They show that the Bayley mental developmental index at 18 months of age and the WISC-R arithmetic subtest score at 7 years of age are correlated with plasma taurine concentrations during infancy. They also report that the positive association of neurodevelopment with own mother’ milk²⁴ was not significant after plasma taurine concentration had been allowed for. These findings are attributed to the presence of taurine in the preterm formula and human milk but not in the term formula.

As the authors emphasise, these findings are far from robust. Firstly, they are not derived from a randomised, controlled trial but, rather, from a retrospective analysis of existing data. Secondly, the strength of the reported relations is modest (r  =  0.28 and 0.22). Nonetheless, they support the hypothesis that low neonatal taurine status adversely affects later neurodevelopment of preterm infants and that the neurodevelopmental advantage of human milk may be related to its taurine content. Thus the new data provide further support for the view that taurine is a conditionally essential nutrient for the preterm infant. They also provide an additional example of apparent long term effects of short term early differences in nutrient intake.

The findings of Wharton et al also present a quandary. Randomised, controlled trials of taurine supplementation for both preterm and term infants should clearly be the next step, but would either trial now be ethical? Like so many other issues in neonatal nutrition and, indeed, all of clinical medicine, it is unlikely that the role of taurine in infant nutrition will ever be evaluated in a randomised controlled trial.