Plausible mechanisms for effects of long-chain polyunsaturated fatty acids on growth.

A few studies conducted over the past decade suggest that formulas supplemented with long-chain polyunsaturated n-3 fatty acids may adversely affect growth of preterm infants. Others suggest that a high intake of alpha-linolenic acid (ALA; 18:3 n-3), the precursor of the long-chain polyunsaturated n-3 fatty acids, also may limit growth. The majority of studies, however, have not shown an effect of either long-chain polyunsaturated n-3 fatty acids or their precursor on growth. Nonetheless, the importance of growth during infancy and the possibility that these fatty acids may inhibit growth under some circumstances makes the issue worthy of further consideration. At the very least, plausible mechanisms for such an effect of n-3 PUFA on growth should be considered. These include (1) altered nutrient intake, absorption, and/or utilization; (2) low plasma and tissue contents of arachidonic acid (ARA;20:4 n-6); (3) an imbalance between n-6 and n-3 LCPUFA eicosanoid precursors and, hence, the eicosanoids produced from each; (4) altered membrane characteristics; and (5) effects on gene expression. Each of these is discussed. It is concluded that any or all are feasible but that none can be specifically implicated. Moreover, since few studies were designed specifically to assess growth, the reported effects of n-3 PUFA on growth could represent chance findings secondary to the suboptimal design. Furthermore, although additional data are needed for a definitive conclusion, the observed effects on growth, regardless of mechanism, does not appear to be biologically significant.