Several studies have examined the relationships between supplemented infant formula, omega-3 and omega-6-fatty acid status, and infant development, pre-term infant growth, and visual acuity. However, most of these studies have been conducted in a clinical trial setting where infants are randomly assigned to receive a certain type of formula. Under these circumstances, the setting is controlled and may not represent what would happen in subjects in a community who are not selected for clinical trials. The DAISY study has the advantage of being an observational study, where mothers are given no advice on their diet or on what to feed their infants. From the time that DHA and ARA supplemented formulas became available on the market, we have been able to observe the choices in feeding patterns that DAISY mother’s made. Use of supplemented formulas has increased in DAISY from 3% of infants in 2001 to 36% in 2002 to 70% of infants in 2005 (unpublished data). In the beginning, mothers likely chose to use ARA and DHA supplemented formulas because they believed them to be healthier. Later on, use of supplemented formulas became less of a parental choice and more of an availability issue, as supplemented formulas became a larger and larger proportion of formulas on the market in the United States.
The efficacy of DHA and ARA supplemented formulas has been a controversial issue for many years. While the formulas are considered to be safe and are generally well-tolerated (Birch et al. 1998
, Lucas et al. 1999
, Hoffman et al. 2006
, Hoffman et al. 2008
), studies show mixed results as far as increases in development or visual acuity (reviewed in Wright et al. 2006
, Rosenfeld et al. 2008
, Simmer et al. 2008a
, Simmer et al. 2008b
). Our study shows that infants who are fed supplemented formula have higher levels of DHA and omega-3 fatty acids in erythrocyte membranes than infants fed non-supplemented formulas. Omega-3 fatty acid content of erythrocyte membranes is relevant because it is a marker of bioavailability of fatty acid supplements (Innis & Hansen 1996
, Vidgren et al. 1997
, Clandinin et al. 2005
), and has been associated with risk of diabetes-related autoimmunity (Norris et al. 2007
), cardiovascular disease, chronic inflammatory diseases and mental health illnesses (reviewed in (Assisi et al. 2006
, Breslow 2006
, Calder 2006
We also found that even though supplemented formulas have higher amounts of both DHA and ARA, the erythrocyte membrane ARA content was not increased in children drinking supplemented formulas. In addition, levels of omega-6 fatty acids were actually lower in infants that were fed supplemented formula compared with those fed non-supplemented formula. This may be explained by the competitive nature of these two fatty acids, where, when both are available, DHA is preferentially incorporated into the membrane over ARA. Therefore, diets where the omega-3 to omega-6 ratio is high result in increased omega-3 and DHA erythrocyte fatty acid content (Wander & Patton 1991
, Romon et al. 1995
). In our study, the infants fed supplemented formula were likely consuming higher levels of DHA from the formula, which was preferentially incorporated, leading to the lower levels of omega-6 fatty acids.
In our population, the levels of DHA and omega-3 fatty acids in erythrocyte membranes of the infants fed supplemented formula were higher than that of children who received breast-milk as their sole source of milk. This is interesting because one of the purposes of supplementing infant formulas with DHA and ARA was to make formulas more similar to breast-milk in their fatty acid composition. As this specific comparison was not the main focus of our study, our findings are difficult to interpret, because we did not measure the levels of ARA and DHA in breast-milk given to the child, nor did we obtain maternal diet data, which is an important determinant of the levels ARA and DHA in breast-milk. Additional work in this area may be important in assessing the need for and benefits of increasing the intake of DHA (either via supplements or dietary change) of lactating women.
As this was an observational study, we did not control or limit the other non-milk sources of omega-3 and omega-6 fatty acids in the diets of our study population. While we confirmed via parental report that none of the children in our study were taking dietary fatty acid supplements, the children may have been eating foods that had varying levels of omega-3 or omega-6 fatty acids. We do not believe that this is a serious limitation, as most 9 month old infants would be unlikely to eat large quantities of any of the common foods high in omega-3 and omega-6 fatty acids, such as fish, oils and meats. We also did not collect information on the cost of supplemented versus non-supplemented formula, or the receipt of WIC (Women, Infants, and Children) supplements by mothers. Both of these variables might have influenced which type of formula parents chose to purchase. In addition to the cost of formula, there is the issue of availability of supplemented versus non-supplemented formula, which may have changed over the course of the study. When DHA/ARA supplemented formulas were first introduced, they were fairly rare (only one or two brands were available, initially). As time passed, these formulas became more common-place, and non-supplemented formulas became more rare (for example, it is currently very difficult to find non-supplemented formulas in stores). The availability may also have influenced cost, with the supplemented formulas being more expensive when they were initially released, but decreasing in price as they became more commonplace. Due to the observational nature of this study, we also did not measure any functional outcomes, such as development or visual acuity. However, other than an increased risk for development of T1D, the infants in this study were generally healthy, and we found it more feasible to measure the intermediate outcome of fatty acid status, rather than less frequent poor outcomes.
In conclusion, in healthy infants whose mothers did not receiving any dietary advice, those who were fed DHA and ARA supplemented formulas had higher erythrocyte membrane levels of DHA and total omega-3 fatty acids than infants who drank non-supplemented formula or breast-milk alone. The results of this study may provide potentially useful data on a population or community basis; and may support survey studies that are trying to infer the benefit of DHA and ARA supplementation of formula, without having to test a biomarker. Additionally, this study may provide important surrogate for fatty acid status in studies for which only data on infant diet are available. Studies such as these are important, as they are similar to the need to translate excellent randomized clinical trial results to effects that can be observed in the community.
- This study compares erythrocyte membrane fatty acids in infants consuming formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) with those consuming other types of milks.
- Infants consuming supplemented formula had significantly higher levels of DHA, omega-3, and lower levels of omega-6 fatty acids than infants consuming non-supplemented formula.
- There was no significant difference between levels of ARA in infants consuming supplemented formula versus non-supplemented formula.
- Infants consuming supplemented formula had significantly higher levels of DHA and omega-3 fatty acids than infants consuming breast-milk.
- In this observational study, infants fed supplemented formula had higher omega-3 and lower omega-6 fatty acid levels.