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LETTER TO THE EDITOR |
Martek Biosciences Corporation
6480 Dobbin Road
Columbia, MD 21045
E-mail: ckuratko{at}martekbio.com
Dear Sir:
Research into the role of individual long-chain polyunsaturated fatty acids (LCPUFAs) is providing exciting data on infant development. The recent meta-analysis, "Supplementation of infant formula with long-chain polyunsaturated fatty acids does not influence the growth of term infants" by Makrides et al (1) in the May issue of the Journal supports the safety of adding these LCPUFAs to infant formula. In their meta-analysis, Makrides et al showed that formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (AA) support growth equal to that from control infant formula without added LCPUFAs. We are concerned, however, that readers may draw an additional, unsupported conclusion that omission of AA from LCPUFA-supplemented infant formula is acceptable.
Confusion may result from the meta-analysis tool itself. This type of statistical analysis is currently used in some settings as a way to define "best practice" approaches for a desired clinical outcome or to conclude the "evidence-based" effectiveness of a drug or a treatment on a clinical outcome. The meta-analysis by Makrides et al simply defines the results of AA on growth at 4 and 12 mo. The review does not, in this case, imply that omitting AA from infant formula is either desirable or to be considered a best practice for supplementing infant formula.
In their article, Makrides et al state that "growth is the main [criterion] used to assess nutritional health and well-being of infants." We agree that growth failure is a well-recognized result of poor nutrition, but, in fact, it is a late indicator of a nutrient deficiency. As in adults, nutrient status indicates a continuum of sufficiency, spanning from overt clinical deficiency (ie, growth) to overt clinical toxicity. Before a state of overt deficiency occurs, tissue and blood concentrations of a nutrient decrease and begin limiting the physiologic processes with which it is involved. In the case of AA and infant formula, growth failure would be an overt clinical sign of a gross deficiency.
In their meta-analysis, Makrides et al report that the trials they reviewed showed a mean reduction in plasma AA of 
25% compared with the control treatment. This may represent an earlier, and perhaps more sensitive, indication of deficiency. More important, during this early stage of reduced AA concentrations, eicosanoid metabolism may be altered and the development and maturation of immune function may be limited or altered (2, 3).
Many studies have shown that the endogenous synthesis of AA in the neonate is insufficient and that blood and tissue concentrations decrease rapidly after birth unless either human milk (which always contains AA) or an AA-supplemented infant formula is provided. Plasma and red blood cell concentrations of AA are significantly lower in infants fed unsupplemented formula than in those who are breastfed (4, 5). Supplementation of formula with preformed AA is required to achieve plasma and red blood cell concentrations that are equivalent to those of the breastfed infant (6, 7).
Makrides et al credit the contributions of DHA in visual and mental performance. However, the effect of AA and DHA on neural development needs consideration. In one of the studies reviewed, formula supplemented with a combination of DHA and AA proved to be of benefit in mental development (8). In that study, DHA plus AA improved mental function compared with unsupplemented controls, whereas DHA alone did not perform better than did the unsupplemented controls. Most important, no research has been conducted that has shown long-term advantages of formula containing DHA without AA. The combination of DHA and AA, on the other hand, has shown benefits to visual function, cognitive development, and blood pressure well beyond the period of supplementation and into early childhood (9–11). Formulas supplemented with preformed DHA and AA are now widely available to provide these nutritional benefits to infants who cannot or will not be breastfed.
In summary, the analysis presented by Makrides et al shows that LCPUFA supplementation has no detrimental effect on growth. The importance of AA as a structural and metabolically active lipid, however, was not addressed. In addition, supplementation of infant formula with a combination of DHA and AA has long-term nutritional benefits compared with unsupplemented formula. Therefore, the addition of both DHA and AA to infant formulas is important for optimal health and development in formula-fed infants.
ACKNOWLEDGMENTS
All authors are employees of Martek Biosciences, a nutritional products company that supplies long-chain polyunsaturated fatty acids from single-cell sources to companies for use in infant formulas.
REFERENCES
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