Arachidonic acid, formula

Figure 14.8 Incorporation ofdeuterated arachidonic acid in Ectocarpus siliculosus (the framed part of the arachidonic acid formula is incorporated by the alga).

Another commercially available product containing naturally occurring marine products is Formulaid , produced by Martek Biosciences as a nutritional supplement for infant formulas. Formulaid contains two fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), extracted from a variety of marine microalgae. ARA and DHA are the most abundant polyunsaturated fatty acids found in breast milk, and they are the most important fatty acids used in the development of brain gray matter. They are especially desirable for use in infant formulas because they come from nonmeat sources and can be advertised as vegetarian additives to the product. 

It is becoming more popular in the US for infant formula manufactures to add fish oils to fortify infant formulae with long-chain polyunsaturated fatty acids, which are critical in early child development because they are necessary for the formation of neural tissues and cells of vascular tissue, but are produced de novo at very low levels from the dietary essential fatty acids Ci8 2, m-3 and Cis 3, co-3. Typically, the long-chain fatty acids, doco-sahexaenoic acid (DHA C22 6) and arachidonic acid (AA C2o 4), were not added to infant formulae available in the US until recently. Many commercial infant formulae manufactures, including Wyeth, Ross and Mead Johnson, now produce infant formulae that are supplemented with DHA and AA. The level of DHA is approximately 0.32%, w/w of fat, and the level of AA is approximately 0.64% w/w of fat. Breast-milk naturally contains small amounts of these long-chain polyunsaturated fatty acids. 

Mackerel, menhaden, herring, cod liver, and salmon are rich in EPA and DHA. However, the content of n-3 FA can vary appreciably among fish of different types. Many reports state that EPA and especially DHA are important for human development, particularly of the brain and eye (Connor et al 1992 Uauy et al., 1992). Supplementation of infant formula with EPA and DHA clearly improves visual acuity supplementation with both arachidonic acid and DHA produces right balance. 

The answer is d. (Murray, pp 258-297. Scriver, pp 2705-2716. Sack, pp 121-138. Wilson, pp 362-367.) Infants placed on chronic low-fat formula diets olten develop skin problems, impaired lipid transport, and eventually poor growth. This can be overcome by including linoleic acid to make up 1 to 2% ol the total caloric requirement. Essential fatty acids are required because humans have only A", A , A , and A fatty acid desaturase. Only plants have desaturase greater than A . Consequently, certain fatty acids such as arachidonic acid cannot be made from scratch (de novo) in humans and other mammals. However, linoleic acid, which plants make, can be converted to arachidonic. acid. Arachidonate and eicosapentaenoate are 20-carbon prostanoic acids that are the starting point of the synthesis of prostaglandins, thromboxanes, and leukotrienes. 

Owens SP, Innis SM. Docosahexaenoic acid and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in frontal cortex caused by a 1 inoleic and a-linolenic acid deficient diet in formula-fed piglets. J Nutr 1999 129 2088-2093. 

Austead N. Innis SM. de la Presa Owens S. Auditory evoked response and brain phospholipids fatty acids and monoamines in rats fed formula with out without arachidonic acid (AA) and/or docosahexaenoic acid (DHA). Brain Uptake and Utilization of Fatty Acids. Conference Organizations W atkins P, Spector A, Hamilton J. Katz. R. Applications to Peroxisomal Biogenesis Disorders. National Institutes of Health Conference, Bethesda. MD, 2000, p. 3. 

Hibbeln JR, DePetrillo P. Higley JD, Schoaf S, Lindell S. Salem N Jr. Improvement in heai t rate variability which persist into adolescence using infant formulas containing docosahexaenoic and arachidonic acids. American College of Neuropsychopharmacology Annual Meeting, 1999. 

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are two fatty acids abundant in human milk, but until recently, were not contained in commercial infant formulas. While the role of ARA supplementation is unclear, DHA is known to be important in both brain and eye development. In some studies, DHA and ARA supplementation has been shown to provide benefits to a child s visual function and/or cognitive and behavioral development. " Other studies have shown no difference with DHA and ARA supplementation. The FDA has classified the plant-based fatty acid blends of DHA and ARA (DHASCO, ARASCO Martek Biosciences Corporation) as generally recognized as safe in infant formulas. 

Ward, G.R., Huang, Y.-S., Bobik, E., Xing. H-C.. Mutsaers, L., Auestad, N., Montalto, M., and Wainwright, P.E. (1998) Long-Chain Polyunsaturated Fatty Acid Levels in Formulae Influence Deposition of Docosahexaenoic Acid and Arachidonic Acid in Brain and Red Blood Cells of Artificially Reared Neonatal Rats, J. Nutr. 128,2473 2487. 

One such factor that is in human milk, but not in conventional infant formula, is arachidonic acid (ARA 20 4n-6) (Table 1). In human milk from Western populations, ARA is usually 0.5% of total fatty acids, but on a world-wide basis, its concentration ranges from 0.1 to 0.7% of total fatty acids (3). Dietary ARA could promote tissue accumulation of this essential fatty acid and subsequent synthesis of ARA-de-rived eicosanoids in the mucosa. 

Fig. 4. Parallelism in postnatal time course of prostaglandin E2 (PGE2) production and arachidonic acid (ARA) in phosphatidylcholine (PC) fraction of pig mucosal phospholipids. Mucosal PGE2 in the naturally reared (NR) piglets was greater (P< 0.05) than in the formula-fed (EE) group at 8, 12, and 16 d phospholipid ARA in the naturally reared piglets was greater (P < 0.05) than in the formula-fed group at 4, 8, 12, and 16 d.

Fig. 5. Design of Experiment II Effect of addition of arachidonic acid (ARA) and docosa-hexaenoic acid (DHA) to neonatal formula. The standard formula contained a fat blend similar to conventional infant formula.

Fig. 6. Effect of dietary treatment on arachidonic acid (ARA) as wt% of total fatty acids in mucosal phosphatidylcholine. Values shown are means + SD, n = 6. Bars with different superscript letters differ, (P< 0.05). Baseline (BL), piglets killed at 1 d of age before initiation of dietary treatment SOW, piglets naturally reared on sow s milk FF(STD), piglets formula-fed a milk replacer formula containing a standard (STD) fat blend similar to that in conventional Infant formula FF + ARA, piglets formula-fed a milk replacer formula containing a standard fat supplemented with ARA FF + ARA/DHA, piglets formula-fed a milk replacer formula containing a standard fat blend supplemented with ARA and docosahexaenoic acid (DHA).

Fig. 1. The n-3 and n-6 polyunsaturates in the four formulas. Diet designations correspond to multiples of the long-chain docosahexaenoic acid (DHA) and arachidonic acid (AA) concentrations in Diet 1, which contains levels recommended for human infant formulas. Diet 0 is a long-chain polyunsaturated fatty acid (LC-PUFA)-free control. Diets 2 and 5 had 2- and 5-fold greater concentrations of DHA and AA than Diet 1.

Concentrations of n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids (LC-PUFA) in Liver and Heart of Piglets Fed Formulas Supplemented with Single-Cell Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) ... 

Fig.l. Docosahexaenoic acid (DHA) in forebrain phosphatidylethanolamine (PE) of 18-d-old artificially reared rat pups fed formulae supplemented with DHA and arachidonic acid (AA) from d 5. Main effects of DHA and AA, P < 0.05. Source adapted from Reference 1 7. 

Several spedes are of commercial interest for the fish feed industry and as natural sources of PUFAs for health food and infant nutrition formulas. Health food applications focus on products containing eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) while infant formulas contain arachidonic acid (ARA) and DHA as PUFA components. EPA enriched products are mainly based on purified fish oils, whereas ARA and DHA are also produced microbially in an industrial scale. ... 

Fish protein isolate Magnesium lactate Psyllium Vitamin Ki Yeast supplement, infant formulas Arachidonic acid Docosahexaenoic acid supplement, mineral Cobalt diacetate supplement, vitamin (+)-y-Tocopherol supporter, storage batteries 2-Chloronaphthalene suppressant, appetite Guar (Cyanopsis tetragonoloba) gum suppressant, smoke paints Zinc hydroxystannate suppressant, smoke plastics Zinc hydroxystannate Zinc stannate suppressant, smoke rubber Zinc hydroxystannate suppressant, sulfide Ferrous sulfate anhydrous suractant mfg. 

Historically one approach to match human-milk composition is to add new ingredients (see Appendix B for the composition of formulas and human milk). This turns out to be a quixotic quest since human milk is a complex body fluid that is variable not only among individuals, but within an individual over time. In addition, it contains components, such as live cells and bioactive compounds, that either cannot be added to formulas or cannot survive a shelf life. Finally, not all human-milk constituents are essential some, like LC-PUFAs, docosahexaenoic acid (DHA), and arachidonic acid (ARA), can be synthesized by term and preterm infants born at 33 weeks gestation (Uauy et al., 2000). 

FIGURE 1.8 Chemical structure of arachidonic acid. The formula of arachidonic acid is C20 4(o6, indicating this fatty acid has 20 carbon atoms and 4 double bonds. According to this formula, the first double bond is in (o6, which, following the co + 3 rule, gives the exact position of all other double bonds (thus, co9, col2, and (ol5). 

As a result of the action of lipoxygenases [3], hydroxyfatty acids and hydroperoxyfatty acids are formed from arachidonate, from which elimination of water and various conversion reactions give rise to the leukotrienes. The formulae only show one representative from each of the various groups of eicosanoids. 

Capaldi RA., ed. Membrane Proteins and Their Interactions with Lipids. Marcel Dekker, New York, 1977, p. 1. Carlson SE, Ford AJ, Workman SH, Peeples JM, Koo WWK, Visual acuity and fatty acid status of term infants fed human milk and formula with and without docosahexaenoate and arachidonate from egg yolk... 

Clandinin MT, Van Aerde IE, Parrott A, Field CJ, Euler A. R, Lien EL. Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas fatty acid composition of erythrocyte membrane lipids. Pediatr Res 1997 42 819-825. 

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