Ординатура / Офтальмология / Английские материалы / Handbook of Nutrition and Ophthalmology_Semba_2007

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infants usually contained linoleic acid and α-linolenic acid but not arachadonic acid or DHA. Most research has focused on the question whether preterm and term infant formula should be supplemented with arachadonic acid and/or DHA, in addition to linoleic acid and α-linolenic acid. Recent technological advances in chemical and physical separation of fatty acids has allowed the use of concentrated AA and DHA for clinical use, and many preterm and term infant formulas in developed countries now contain AA and/or DHA (3). In 2002 and 2003, infant formulas with added LC-PUFAs became commercially available for term and preterm infants in the United States (4).

3. HISTORICAL BACKGROUND

Early pioneering work on the chemistry of fatty acids was conducted by Michel-Eugène Chevreul (1786–1889), professor of chemistry at the Manufactures Royales des Gobelins, the French national tapestry workshop, and director of the Muséum d’Histoire Naturelle in Paris. Chevreul showed that lard contained a solid and a liquid fat that he named stearin and elain, respectively. His work on the chemistry of natural fats and oils was reported in his influential monograph Recherches chimiques sur les corps gras (1823) (5). In 1822, Edmund Davy (1785–1851) reported that iodine could interact with fats, and this observation eventually led the enumeration of the number of unsaturated bonds in fatty acids by the “iodine number” of fats. The first phospholipid to be described was lecithin, a substance isolated from egg yolk and found to contain both phosphorus and nitrogen by Nicolas Théodore Gobley (1811–1876) in 1846. Further investigations led to the description of kephalin by Johann Ludwig Thudichum (1829–1901) in 1884.

In the late 1920s, Herbert McLean Evans (1882–1971) and George Oswald Burr (b. 1896) described a deficiency disease among rats raised on a diet low in fat (6–8). Lafayette Mendel (1872–1935) and his colleagues found that growth was improved when rats received peanut oil in addition to vitamin A, but the investigators considered it inconclusive whether the difference was due to fat alone (9). In 1929, Burr and his wife, Mildred M. Burr, announced the essentiality of dietary fat in their research with rats. A syndrome consisting of growth failure, scaly skin, kidney lesions, and necrosis of the tail was found when rats were raised on a diet low in fat, and the syndrome was prevented or cured by the addition of 2% fatty acids to the diet (10). Burr and Burr coined the term “essential fatty acids,” and although the idea was initially received with controversy, further work established the essentiality of some fatty acids (11).

In 1933, the pediatrician Arild Edstein Hansen (b. 1899) showed that infantile eczema was associated with alterations in serum lipids, and the condition could be treated successfully with corn oil or other unsaturated fatty acids (12,13). Further clinical investigations helped to establish that deficiency of essential fatty acids could occur among infants (14,15). More definitive evidence for the importance of essential fatty acids came with reports of essential fatty acid deficiency among infants and adults on total parenteral nutrition without fats (16–19). By the mid-1970s, intravenous fat emulsions became generally available, and linoleic acid was considered to be an important component of total parenteral nutrition (20). In 1982, a syndrome of neurological disturbances and blurred vision was described in a young girl who was receiving total parenteral nutrition in which safflower oil was the only source of lipid (21). The patient improved after soybean oil, high in α-linolenic acid, was substituted for safflower oil. A more detailed history of fatty acids can be found elsewhere (22).

4. BIOCHEMISTRY OF FATTY ACIDS

Fatty acids are nonpolar hydrocarbon chains that vary in length from 2 to 30 carbon atoms and have a terminal carboxylic group, with the overall formula: CH3-(CH2)n-COOH. Fatty acids can be classified on the basis of chain length (short, 4-6 carbon atoms; medium, 8-12 carbon atoms; long, 14+ carbon atoms), or on the degree of unsaturation. Saturated fatty acids have a chain of carbon atoms in which there are no C=C double bonds and each carbon in the chain is bonded to hydrogen atoms except the carbon of the terminal carboxylic group. Monounsaturated fatty acids contain one C=C double bond in the chain. Polyunsaturated fatty acids (PUFAs) contain more than one C=C double bond. LC-PUFAs are fatty acids of 14 or greater carbon atoms with more than one C=C double bond. Most PUFAs exist in the cis configuration in which the double bonds are interrupted by a methylene group.

Fatty acids may be described using common or trivial names, systematic chemical names, shorthand notation, or chemical formulae. Shorthand notation, or code, is a useful way to describe fatty acids. The first number indicates the number of carbon atoms, followed by a colon. The number following the colon is the number of unsaturated bonds. The n or omega (ω) indicates the position of the first double bond, counting carbon atoms from the methyl end of the fatty acid. The cis or trans configuration of each double bond can be indicated at the end of the code. Most PUFAs are of the n-3, n-6, and n-9 families, and are known alternatively as omega-3, omega-6, and omega-9 fatty acids. The common names, systematic names, codes, and formulae of some PUFAs covered in this chapter are shown in Table 1.

Linoleic acid and linolenic acid are “parent essential fatty acids” necessary for the synthesis of long-chain fatty acids. LC-PUFAs of the n-6 family are synthesized from linoleic acid through a process of desaturation and elongation (Fig. 1). In the n-3 family, the same processes are involved, with a terminal step of β-oxidation in the formation of DHA (Fig. 1). The n-6 and n-3 families of fatty acids compete for the same enzymes involved in desaturation, and there can be relative inhibition of the enzyme system by fatty acid products from either of the n-3 or n-6 families. Thus, an imbalance in the dietary intake of n-6 and n-3 precursor fatty acids can influence the resulting amount of LC-PUFAs of each family. The derived essential fatty acids that contain 20 or more carbon atoms and 4 or more double bonds are known as the long-chain polyenes, of which AA (20:4, n-6) and DHA (22:6, n-3) have received special attention in studies of visual development because of their high concentrations in the retina and brain.

5. ABSORPTION AND METABOLISM OF ESSENTIAL FATTY ACIDS

During fetal development, linoleic acid, α-linolenic acid, and long-chain polyenes, such as AA and DHA, are accreted after placental transfer. Unesterified fatty acids, triacylglycerols of very low-density lipoprotein (VLDL), fatty acids of low-density lipoprotein (LDL), glycerolipids, and sterol esters are the most important sources of fatty acids for placental transfer (23). AA and DHA appear to have different uptake and transport modes from the placenta to the fetus (24). An estimated 31 mg of n-6 fatty acids and 15 mg of n-3 fatty acids accumulate in fetal brain each week from 26 wk until delivery (25). An accretion of essential fatty acids also occurs in the fetal liver (26). The precise role of the fetal liver and brain in the synthesis of LC-PUFAs is not clear, and during fetal development, the accretion