EVALUATION OF MINERAL ABSORPTION IN INFANTS FED HUMAN MILK OR FORMULA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。Enfamil和Enfamil Lifestyle富含棕榈油精，脂肪混合物由40%棕榈酸和43%油酸组成。然而，与人乳不同，植物油中的棕榈酸主要在sn-1和sn-3位酯化，而不是在sn-2位酯化（1），人乳中的棕榈酸也是如此（2，3）。在sn-1和sn-3位酯化的棕榈酸倾向于在消化过程中水解，并可形成不溶性钙皂，导致脂肪和钙吸收比在sn- 1和sn-3位具有较少棕榈酸的配方更差（4-6）。在Enfamil配方中加入酯交换棕榈油精（sn-2位含有更多棕榈酸）是否会比目前的配方更好地吸收脂肪和钙，目前尚不清楚。此外，目前的安婴儿配方中的钙吸收是否与母乳中的钙吸收相似，尚未直接研究。 现在市场上的配方食品，像许多婴儿配方食品一样，棕榈酸主要在sn-1和sn-3位酯化，而不是在sn-2位酯化，就像在人乳中发现的棕榈酸一样。第二种配方在sn-2位有更多的棕榈酸（sn-1和sn-3位较少），使其更接近母乳。由于它的成分更接近母乳，我们认为它是一种安全的产品，只是评估对钙吸收的影响。从FDA的角度来看，这一变更被认为是次要变更，例如，不需要进行一整套研究来允许重大变更所需的变更。最后，先前的耐受性研究已经完成，以证明该公式的安全性。 由于配方的修改和改进是以母乳的营养成分和功能性营养成分为指导的，因此美赞臣约翰逊营养品公司（美赞臣）必须确认安婴儿奶粉与母乳相比的功能性充足性。母乳中钙的平均吸收率为58 +/- 17%，平均钙含量为41 mg/100 kcal，每日钙吸收率为24.6 +/- 15（SD）mg/100 kcal。美赞臣较高的钙含量（78 mg/100 kcal）实际上弥补了较低的钙吸收分数（38 +/- 16%）。因此，每日钙吸收量为29.6 +/- 12.5 mg/100 kcal。所有这些值都反映了使用经典平衡技术而不是双稳定同位素产生的值。先前的研究表明，通过使用双同位素吸收法，我们可以预期Enfamil Lifecycle的SD为8，而不是12.5，Enfamil Lifecycle与酯交换棕榈油脂肪混合物（IPO-EL）的SD值约为40 +/- 10。与配方奶粉相比，母乳中的钙含量在母亲之间也有显著差异，除了测量的吸收分数的差异外，预计各组之间更相似。因此，将母乳中绝对钙吸收的更广泛经典平衡与公式中估计的双同位素方法方差（标准差为15、8和10）合并，以估计群体方差为11.4，从而计算本研究所需的n，以提供80%把握度，α水平为0.05。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Enfamil and Enfamil Lipil are rich in palm olein, with a fat blend comprised on 40% palmitic acid and 43% oleic acid. However, in contrast to human milk, the palmitic acid in vegetable oils is predominantly esterified in the sn-1 and sn-3 position rather than the sn-2 position (1), as is the case for palmitic acid found in human milk (2,3). Palmitic acid that is esterified in the sn-1 and sn-3 position tends to be hydrolyzed during digestion and made available to form insoluble calcium soaps, resulting in poorer fat and calcium absorption than is seen with formulas with less palmitic in the sn- 1 and sn-3 position (4-6). Whether the inclusion of interesterified palm olein (with greater palmitic acid in the sn-2 position) in an Enfamil formulation would results in better fat and calcium absorption than the current formulation is not known. Moreover, whether calcium absorption in the current Enfamil formulation is similar to that provided by human milk has not been studied directly. The formula on the market now, like many infant formulas, has the palmitic acid predominantly esterified in the sn-1 and sn-3 position rather than the sn-2 position, as is the case for palmitic acid found in human milk. The second formula has more palmitic acid in the sn-2 position (less in the sn-1 and sn-3 positions), making it more comparable to human milk. As it is even closer in composition to human milk, we consider it to be a safe product and are merely assessing the effect on calcium absorption. From an FDA level, this change is considered minor and does not, for example, require the full set of research studies to allow the change as would be needed for a major change. Finally, previous tolerance studies have been done to demonstrate the safety of the formula. Since modifications and improvements of formulations have been guided by the nutrient content and functional nutrient composition of human milk, it is important that Mead Johnson Nutritionals (MJN) confirm the functional adequacy of Enfamil Lipil compared to human milk. The mean published absorption of calcium from breast milk is 58 +/- 17% with a mean calcium content of 41 mg/100 kcal, yielding a daily calcium absorption of 24.6 +/- 15 (SD) mg/100 kcal. The higher calcium content of Enfamil (78 mg/100 kcal) actually compensates for less fractional calcium absorption (38 +/- 16%). Therefore daily calcium absorption is 29.6 +/- 12.5 mg/100 kcal. All of these values reflect values generated using classic balance techniques rather than dual stables isotopes. Previous studies have shown that by using dual isotope absorption methods we can expect SD for Enfamil Lipil of 8 rather than 12.5 and SD values for Enfamil Lipil with interesterified palm olein fat blend (IPO-EL) of about 40 +/- 10. In contrast to formula, human milk calcium content also varies significantly between mothers in addition to variation in measured fractional absorption, which would be expected to be more similar between groups. Thus, the wider classical balance for absolute calcium absorption from human milk was pooled with the estimated double isotope method variance from the formulas (standard deviations of 15, 8, and 10) to estimate the population variance of 11.4 to calculate the n needed for this study to provide 80% power with an alpha level of 0.05.