The Journal of Nutritionjn.nutrition.org
1. J. Nutr. February 1, 1998 vol. 128 no. 2 401S-406S
* © 1998 American Society for Nutritional Services
Programming by Early Nutrition: An Experimental Approach1
1. Alan Lucas
1. 1MRC Childhood Nutrition Research Centre, Institute of Child Health, London WC1N 1EH, United Kingdom
That events during critical or sensitive periods of development may “program” long-term or life-time structure or function of the organism is well recognized. Evidence for programming by nutritionis established in animals, in whom brief pre- or postnatal nutritional manipulations may program adult size, metabolism, blood lipids, diabetes, blood pressure, obesity, atherosclerosis, learning, behavior and life span. Human epidemiological data link potential markers of early nutrition (size at birth or in infancy) to cardiovascular disease and its risk factors in adulthood. However, these retrospective data cannot prove nutritional cause or underpin health policies. After 16 y, however, of ethical, randomized intervention studies of early nutrition in humans with long-term follow-up to test experimentallythe nutritional programming hypothesis, we find that humans, like other species, have sensitive windows for nutrition in terms of later outcomes; for instance, perinatal diet influences neurodevelopment and bone mineralization into mid-childhood. Possible biological mechanisms for storing throughout life the “memory” of early nutritional experience and its expression in adulthood include adaptive changes in gene expression, preferential clonal selection of adapted cells in programmed tissues and programmed differential proliferation of tissue cell types. Animal and human evidence supporting nutritional programming has major potential biological and medical significance. * -------------------------------------------------
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CLINICAL AND HISTORICAL CONTEXT
Over the past three centuries there has probably been more research on infant nutrition than on any other area of pediatrics. By 1953, Macy et al. were able to collate over 1,500 publications on the biochemistry of breast milk—just one small area of infant nutrition research. Yet, despite the massive scientific effort, fundamental issues in infant nutrition practice remain unresolved, resulting in confusion among health professionals and in inconsistent, inadequately supported public health recommendations and standards of practice. When such uncertainty exists in the presence of such a large body of research and knowledge, it is reasonable to challenge whether the right questions have been addressed. To throw more light on this uncertainty, it is instructive to examine how other fields of health intervention have generally evolved. Usually this has been a three-stage process (Lucas 1987). In stage I, anecdotal observations raise the question, “is this worth pursing?” In stage II, epidemiological and physiological research provide descriptive and mechanistic data that raise testable hypotheses concerning the potential effect of intervention. Finally, in stage III, formal intervention experiments test the efficacy and safety of clinical or public health practice. Thus, taking the analogy of research into high blood pressure, stage III research shows whether intervention with antihypertensive drugs mattersin terms of improving long-term health (e.g., reduced risk of stroke, improved survival). The ability of antihypertensive drugs simply to lower blood pressure (stage II research) has real value only if it improves outcome (stage III research). Twenty years ago, the field of early nutrition had largely become...
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