{'fraction_non_alphanumeric': 0.02418054809242343, 'fraction_numerical': 0.015045674368619023, 'mean_word_length': 5.352673492605233, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Modelling human infant requirements for long-chain polyunsaturated fatty acids

Linoleate (18 : 2n-6) anda-linolenate (18 : 3n-3) are generally recognized as essential nutrients in the mammalian diet. However, whether linoleate and a-linolenate are able to meet the requirement for long-chain polyunsaturated fatty acids during early postnatal development is currently under debate. Regulatory agencies in different countries have different views on whether the major long-chain polyunsaturates, arachidonate (20 : 4 n-6) and docosahexaenoate (22 : 6n-3), should be included in milk formulas. Low tissue levels of docosahexaenoate are well recognized as impairing visual and neurological development. Low tissue levels of arachidonate are associated with retarded somatic development. A growing body of evidence indicates that, in particular, a-linolenate alone cannot adequately meet the requirement of human infants for docosahexaenoate. Two general models have predominated in the development of the evidence concerning possible inclusion of longchain polyunsaturates in infant formulas. One such general model employs human blood, milk or tissue samples while the other employs samples from various sub-human species; fewer samples, especially tissues, are available from humans but sub-human species do not always reliably model human development. Both general models have relied heavily on correctly interpreting fatty acid profiles as a measure of the adequacy of accumulation of arachidonate and docosahexaenoate in organs such as the human brain. The aim of this commentary is briefly to put these two models into perspective relative to the challenge of demonstrating adequacy or inadequacy of tissue accumulation of long-chain polyunsaturates as it relates to early human somatic and neurological development. Quite a number of studies have reported plasma and/or erythrocyte fatty acid profiles obtained from human infants consuming breast milk or different formulas. In general, plasma or erythrocyte arachidonate and docosahexaenoate levels fall postnatally regardless of feeding type but they fall less on breast milk or on formulas containing arachidonate and docosahexaenoate than on formulas only providing linoleate anda-linolenate (Innis, 1992; Hamosh & Salem, 1998). By themselves, these differences and trends in blood fatty acid profiles do not necessarily prove that the tissue status of long-chain polyunsaturates is impaired when arachidonate and docosahexaenoate are not provided in the milk formula. Rather, this depends on demonstrating that tissue levels of these fatty acids are also proportionately low when docosahexaenoate and arachidonate are not provided in the diet. In fact, brain, liver and adipose tissue fatty acid profiles have been described for infants consuming breast milk or formulas providing only linoleate anda-linolenate (Farquharson et al. 1992; Makrideset al. 1994). From this work, it seems clear that brain levels of docosahexaenoate found in breast-fed infants cannot be sustained in formula-fed infants under 6–12 months old unless pre-formed docosahexaenoate is provided. Interestingly, brain arachidonate levels are not as susceptible to depletion in the absence of dietary arachidonate. Despite this unique and valuable information from infant autopsy specimens, these were still two small studies that urgently need confirmation by other researchers. Until more human tissue data are published, animal models will still provide important data regarding the link between dietary intake of long-chain polyunsaturates, tissue levels and behavioural and developmental measures. Recent studies, including the one by Rooke et al. (1999) in this issue of the Journal, indicate that plasma, umbilical cord and erythrocyte values for arachidonate and docosahexaenoate in newborn piglets and in more mature miniature swine are poorly correlated to those in the brain (Rioux et al. 1997; Berlin et al. 1998). The study by Rooke t al. (1999) compared the effects of tuna and soyabean oil given during late pregnancy on fatty acid profiles of piglet organs at birth. Tuna oil increased brain weight at birth but did not affect body or other organ weights. In comparison with soyabean oil, tuna oil also increased long-chain-3 polyunsaturates in various organs including brain. Nevertheless, the arachidonate and docosahexaenoate content of the brain was poorly correlated to umbilical cord or umbilical plasma values. However, erythrocyte levels of docosahexaenoate have been positively correlated to brain docosahexaenoate in human infants (Makrideset al. 1994). This lack of agreement between data from the human infant and the piglet model is disappointing from a modelling perspective. However, perhaps it is partly explained by the fact that docosahexaenoate accumulation in the brains of the formula-fed infants was impaired by 21 % over 40 weeks postnatally, whereas the piglets in the study by Rookeet al. (1999) were studied at birth. One potential confounder in the piglet model is that piglet brain growth is relatively slow near term and in the first 2 weeks of postnatal life (Sweasey et al. 1976), a factor that probably influences the rate of brain fatty acid accumulation and, thus, the relationship to dietary or blood fatty acid profiles. Hence, it is not clear that studying the piglet very early postnatally actually gives useful information about the adequacy of brain levels of long-chain polyunsaturates in human infants on different intakes of polyunsaturates. British Journal of Nutrition(1999),82, 163–164 163