12. The effects of early feeding practices on the programming of metabolism

The impact of specific nutrients, rather than of energy on long-term health, needs to be recognized because otherwise an intake of energy may be incorrectly identified as undesirable; it is difficult at present to exclude the possibility that the inadequate or excessive intake of some nutrients may be far more important than energy per se in programming facets of metabolism which are of key importance to long-term health. One very interesting example is the recent evidence that an adequate supply of absorbable dietary iron is crucial to tissue-dependent changes in brain development which determine the long-term ability to learn (HAAS and FAIRCHILD, 1989).

Crucial phases of brain development may depend on the adequate provision of specific nutrients at that time; when these nutrients are supplied later, functional recovery may not occur. One must therefore consider the concept of critical periods for specific nutrient supply as not just hypothetical but plausible. Crawford has recently emphasized this point in relation to the need for an appropriate supply and balance of w-3 and w-6 essential fatty acids in the processes of brain growth and myelination (CRAWFORD et al., 1989), but the quantitative aspects of this hypothesis have not been set out.

The ideal intake of a nutrient may also vary at different times of life. Thus, for example, a plentiful intake of absorbable iron is regarded universally as essential to health, whether one is considering children or adults (FAO, 1988). Yet, recently we have suggested that a crucial component of the atherosclerotic process is free radical damage to lipids promoted by intracellular iron and that intracellular iron stores, whilst useful as reserves in the bone marrow to cope with increased demands, may, when present in other tissues such as the endothelium, serve as activators of the atherosclerotic process, unless there is a plentiful supply of free radical scavengers such as vitamins C and E (JAMES, DUTHIE and WAHLE, 1989; DUTHIE, WAHLE and JAMES, 1989). Age-specific needs for nutrients could thus emerge.

Evidence for long-term programming of cholesterol metabolism comes from both human and primate research. Thus, MARMOT et al. (1980) have analysed the relationship between breast-feeding and subsequent serum cholesterol levels in the two longitudinal British studies, the 1946 Birth Cohort Study and the Whitehall Study of British Civil Servants. At the age of 32, men showed little difference in their serum cholesterol when those who had been breast-fed or bottle-fed from birth were distinguished, but in women who had been breast-fed, serum cholesterol was almost 0.5 mm lower than in those who had been bottle-fed despite consuming the same type of diet and amounts of fat. Adjusting for possible social class or body weight differences failed to eliminate the apparent effect of breast-feeding.

Cogent physiological evidence on the potential for the long-term programming of cholesterol metabolism again comes from primate studies by MOTT (1986). Infant baboons were breast-fed or provided with formulae containing specified and graded concentrations of cholesterol. After 14 weeks the baboons were weaned on to specified diets containing 40% energy as fat and either enriched with saturated fatty acids (P/S ratio 0.37) or unsaturated fatty acids (P/S ratio 2.1). The cholesterol content was also either 0.01 mg or 1.0 mg cholesterol/kcal so that four types of weaning diet could be tested with the effects of saturated fat and dietary cholesterol being distinguished. Three to six years later, cholesterol metabolism was assessed in detail.

The breast-fed baboons proved to have a higher concentration of total, VLDL and LDL cholesterol than those originally formula-fed, i.e., the effect was the opposite of that found by MARMOT et al. (1980) in adult women. Breast-feeding followed by a high saturated fatty acid intake also led to a lower HDL cholesterol concentration than in formula-fed animals, but the impact of polyunsaturated fatty acids on HDL cholesterol concentrations was very different in the breast-fed and bottle-fed baboons. Whereas a prolonged diet rich in unsaturated fatty acids increased HDL cholesterol levels, the same diet in animals initially formula-fed decreased cholesterol concentrations. Thus, the delayed effects of breast-feeding involve profound changes in the regulatory responses in cholesterol and/or lipoprotein metabolism to adult diets.

Table 2 shows data on cholesterol turnover from MOTT's (1986) review. Formerly breast-fed animals had a lower synthesis rate of cholesterol in association with the higher VLDL and LDL cholesterol concentrations. Cholesterol turnover was lower and the size of the cholesterol pool (presumably in tissues) was substantially lower in the breast-fed baboons. Despite these changes the fractional absorption of dietary cholesterol was increased by 15%. Again sex differences were observed with female baboons having a higher production rate of cholesterol. All the deferred effects of breast-feeding may well have reflected primary changes in lipoprotein synthesis, exchange or receptor uptake, but these facets of lipoprotein turnover were not studied.

Table 2. Deferred effects of breast-feeding in baboons: 4-¹⁴C cholesterol feeding at 3.5 years of age

All differences significant p < 0.05.
MOTT (1986).

It seems reasonable to conclude that the early overfeeding of babies could be harmful in that it increases the probability of a high rate of weight gain, of early obesity persisting into adult life with all its attendant sequelae of increased morbidity and premature mortality. On this basis, it might seem self-evident that the return to breast-feeding alone for the first 4-6 months of life with the increased likelihood of reasonable and not excessive growth rates should be welcome. Current data suggest that modern breast-fed children in affluent societies grow more slowly in length and weight, but that the divergence from the NCHS growth pattern is particularly evident in the second half of infancy, i.e., when they are being substantially supplemented with ordinary foods.

Whatever the link between modern breast-feeding and supplementary feeding practices, the net effect is a lower nutrient intake than that needed to achieve the NCHS standards. We thus might specify that the upper desirable intakes of energy are either above those usually consumed by the breast-fed child or that we need to revise the NCHS charts if they are to continue to be a standard rather than a reference set of measurements. Before doing so, however, one needs to examine evidence linking growth rates in infancy to adult morbidity and mortality since at present we have only been concerned with links inferred from studies on adiposity and those adult insurance data presenting evidence that early obesity is particularly hazardous.