Arachidonic acid infants

Knupfer H, Knupfer MM, Hotfilder M, Preiss R. 1999. P450-expression in brain tumors. Oncol Res 11 523-528. Koletzko B, Decs T, Demmelmair H. 1996. Arachidonic acid supply and metabolism in human infants born at full term. 

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. 

Polyunsaturated fatty acids (PUFAs) have various physiological functions and are widely used as pharmaceuticals, neutraceuticals, and as food additives. The ethyl ester of eicosapentaenoic acid (EPA) has been used for the treatment of arteriosclerosis and hyperlipemia since 1991 in Japan (Hara, 1993). DHA possesses not only similar physiological activities to those of EPA, but also an important function in the brain and retina (Hung, 2007). In addition, DHA accelerates the growth of preterm infants as does arachidonic acid (Carlson et al., 1993 Lanting et al., 1994). From these reasons, DHA ethyl ester (DHAEE) is currently expected to be used as a medicine, and the development of the purification methods is desired. 

Carlson, S. E., Werkman, S. H., Peeples, J. M., Cooke, R. I, and Tolley, E. A. 1993. Arachidonic acid status correlates with first year growth in preterm infants. Proc. Natl. Acad. Sci. USA, 90,1073-1077. 

More than 100 difTerent faUy acids hav. been identified about 4( of them occur widely. Palmitic acid stearic acid (C, ) are the most abundant saturated fatty acids oleic and linoletc acids cC,m) are the most abundant unsaturated ones. Oleic acid is monoiuisaturated since it hastmly one double bond, whereas lineleic, linolenic, and arachidonic acids are polyunsaturated fatty acids, or Pt PA s, because they have more than one double bond. Linoleic and tinolenic acids occur in cream and ore essen tial in fhs b arn an diet infants grow poorly and develop akin lesions if fed a diet of notuCat iniVk for prolonged periods. 

Ltd., located in Wuhan City, has been producing arachidonic acid using Mort. alpi-na since 2001 (see www.aUdng.com.cn). Production appears to be at the 50,000-L level although larger fermenters may be under commission. The oil is thought to be used in infant milk powder but also may be exported to unknown destinations. 

FAs liberated from food during absorption are metabolized more easily if they are short or medium chain, i.e., C10 or below. The sn-2 monoacylglycerols can be absorbed directly. Therefore, essential or desired FAs are most efficiently utilized from the sn-2 position in acylglycerols. In accordance with this, TAGs with short-chain FAs (SCFAs) or MCFAs at the sn-1 and sn-3 positions and PEFAs at the sn-2 position are rapidly hydrolyzed with pancreatic lipase (sn-1,3-specific lipase) and absorbed efficiently into mucosal cells. SCFAs or MCFAs are used as a source of rapid energy for infants and patients with fat malabsorption-related diseases. LCFAs, especially DHA and arachidonic acid, are important in both the growth and development of an infant, while n-3 PEFAs have been associated with reduced risk of cardiovascular disease in adults (Christensen et al., 1995 Jensen et al., 1995). 

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. 

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. 

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. 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.

Birch, E.E., Hoffman, D.R., Uauy, R., Birch, D.G., and Prestidge, C. (1998) Visual Acuity and the Essentiality of Docosahexaenoic Acid and Arachidonic Acid in the Diet of Term Infants, Pediatr. Res. 44,201-209. 

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). 

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