Docosahexaenoic Acid and Arachidonic Acid Nutrition in Early Development.

Docosahexaenoic acid (DHA; 22:6–3) is an omega-3 fatty acid with 22 carbons and 6 double bonds (22:6n-3). Arachidonic acid (ARA; 20:4–6) is an omega-6 fatty acid with 20 carbons and 4 double bonds. These two fatty acids are the predominant long-chain (20 and 22 carbons) polyunsaturated fatty acids (LCPUFAs) in human brain [1,2]. Brain DHA begins to accumulate around 22 weeks’ gestation and the absolute amount per gram of brain as well as the weight percent of total fatty acids increases progressively from 22 weeks until at least 2 years of age [3–6]. The absolute amount of ARA per gram of brain also increases in brain but decreases in weight percent of total fatty acids after birth [1]. All human milk contains ARA and DHA to support DHA and ARA requirements for the growing and developing brain as well as other organs and tissue after birth. In human milk, the amount of ARA typically exceeds that of DHA. Milk ARA content is also less varied than DHA and, unlike DHA, does not seem to be linked to maternal intake. Because worldwide DHA intake is variable, milk DHA content is variable across cultures. Reports of milk DHA concentration range from 0.05% of total fatty acids in vegan vegetarians [7] to 2.8% in the marine region of China, where a diet high in seafood is consumed [8]; the median value of DHA in human milk worldwide is ~0.3% [9]. Women in the United States have low milk DHA levels (levels around 0.1% DHA are typical [10]) unless they regularly consume DHA or a supplement during and/or after their pregnancy. Jensen and colleagues [11] found that a supplement of 200 mg of DHA per day in US women could increase milk DHA to ~0.3% of total fatty acids, which is the amount that the European Food Safety Authority (EFSA) requires in infant formula in order to make a claim for support of infant visual development [12]. Red blood cell DHA and ARA levels are lower in infants fed formula without DHA and ARA, compared with infants fed human milk [10,13,14]; this is evidence of lower status. However, autopsy studies find lower brain DHA levels and higher omega-6 LCPUFA levels in infants fed formula without LCPUFA [14–16]. In term infants, frontal cortex DHA level is about 20% [14] lower if fed formulas without DHA and ARA. In preterm infants, who do not have the same opportunity to accumulate DHA from placental transfer, the amount of DHA that accumulates is ~50% less if formula is lacking in DHA and ARA [15]. DHA, ARA, and docosatetraenoic acid (DTA; 22:4–6) are the major LCPUFAs in brain phosphoglycerides [6,14,15,17]; however, the amount of omega-6 LCPUFAs (ARA, DTA, and docosapentaenoic acid [omega 6 DPA; 22:5–6]) exceeds the amount of DHA in the brains of humans and nonhuman primates. It is not known what happens to brain composition if human infants are fed only omega-3 LCPUFA (DHA or DHA plus EPA); however, some studies suggest that diets feeding only omega-3 result in major reductions in the omega-6 to omega-3 LCPUFA ratio. Baboon infants fed a formula with a higher proportion of DHA than ARA (0.96% and 0.64%, respectively) were shown to have reduced cortical and hypothalamic omega-6 LCPUFA levels, and omega-3 LCPUFA level exceeded that of omega-6 LCPUFA in the frontal lobe [18]. A recent trial conducted in our laboratory (the DHA Intake and Measurement of Neural Development [DIAMOND] trial, discussed later) included a formula in which omega-3 LCPUFA intake was substantially higher than omega-6 LCPUFA intake, and in which outcomes were somewhat consistent with these animal studies. It seems advisable and prudent to follow human milk as a model for adding LCPUFA in infant formula given that the optimal balance of these two families of fatty acids in the developing brain is unknown. Infant formulas in the United States have contained both DHA and ARA since 2002, typically in a ratio of ~2:1 of ARA to DHA, although the amounts of DHA and ARA fed vary. Before 2002, all formula-fed preterm and term infants in the United States received formula without DHA and ARA. Long-chain polyunsaturated fatty acid intake as a source of docosahexaenoic acid and arachidonic acid As noted previously, human newborns obtain both DHA and ARA from human milk and infant formulas currently contain these fatty acids. However, other foods provide little DHA and ARA in the diet of US infants. Using validated assessments of food intake in 207 infants, the authors estimated DHA intake at 9 and 12 months of age to be on average 4.0 mg (median = 0 mg) and 13 mg (median = 4 mg), respectively. ARA intake from foods other than human milk or formula in the same 207 infants at the same ages was estimated respectively to average 15 mg (median = 4 mg) and 41 mg (median = 20 mg) at 9 and 12 months of age. Fish, chicken, and egg yolk are good food sources of DHA and ARA, but only 3 of 207 children were reported to have consumed these foods on the day of their 12-month, 24-hour dietary recall (Carlson SE, unpublished data, 2016). US infants may depend on human milk or formulas with DHA and ARA for their primary intake of these nutrients in infancy. After infancy, DHA intake in US children is not appreciably higher than is found at 12 months of age [19].