Linoleic acid infants

Hansen, A. E., Haggard, M. E., Borlsche, A. N., Adam, D.J.D. and Wiese, H. F. 1958. Essential fatty acid in infant nutrition. III. Clinical manifestations of linoleic acid deficiency. J. Nutr. 66, 565-576. 

Burr and Burr reported in 1929 a new deficiency disease produced by the rigid exclusion of fat from the diet. 1 Rodents fed a fat-free diet showed reduced growth and reproductive failure, accompanied by two prominent changes in the skin, that is, increased scaliness and impaired barrier function.1,2 Reversal of the features of deficiency by administration of linoleic acid (LA), led to the concept of essential fatty acids (EFA) that cannot be synthesized by the higher animals.2 Similarities between the clinical features of EFA deficiency and atopic dermatitis led Hansen in 1937 to discover low blood levels of unsaturated fat in atopic children,3 and he later reported that EFA-deficient infants developed an eczematous rash, which responded to LA supplements.4 Several studies had previously examined a range of dietary oil supplements in atopic dermatitis,5-8 with generally reported benefit. 

In humans, the conversion of ALA to EPA and DHA is extremely slow, with only about 15% and 5% of ALA converted to EPA and DHA, respectively (Cunnane, 1995). This conversion appears to be affected by a number of dietary factors. For example, a diet rich in linoleic acid has been found to reduce this conversion by as much as 40% (Emken, 1995). In addition, saturated and lruns fatty acids also interfere with ALA desaturation and elongation steps (Ackman and Cunnane, 1992 HouwelingenandHornstra, 1994). DHA can be reconverted back to EPA, although in humans it appears to be a very minor pathway (Brossard et al., 1996). DHA appears to play an important in the brain and retina and was found to be incorporated during the last trimester of pregnancy and the first year of life. Visual acuity was shown to develop much faster in preterm infants fed formulas rich in DHA compared with standard infant formulas low in long chain n-3 fatty acids (Jorgensen et al., 1996). 

It is noteworthy that virtually all of the naturally occurring polyunsaturated fatty acids contain 18-22 carbon atoms. Linoleic acid is the predominant polyunsaturated fatty acid. It is of considerable interest that most animals cannot synthesize linoleic acid and must take it in the diet. If insufficient amounts of this acid are present in the diet of animals, severe symptoms, such as skin lesions, kidney damage, cataracts, increased permeability to water, and so on, can occur. Thus, the term essential fatty acids has been applied to these compounds. It is not certain, however, that dietary unsaturated fatty acids are needed by the human adult, but there is evidence of such a requirement by the human infant. 

Vitamin K is a fat-soluble vitamin. The RDA for the adult man is 10 mg of a-loeophenol, or its biological equivalent. The RDA for infants should also be mentioned, as vitamin E deficiency, when it occurs, tends to strike this population. The RDA for the newborn is 5 mg of a-tocopherol, or its equivalent. The vitamin needs of the infant have been expressed in terms of the amount of polyunsaturated faltj acids (as fats and oils) in the diet, for example, 0,7 mg of a-tocopherol per gram of linoleic acid. A common level of dietary intake is about 10 mg per day. A deficiency iit the vitamin is quite rare. 

More than 100 different fatty acids have been identified about 40 of them occur widely. Palmitic acid (Cje) and stearic acid (Cis) are the most abundant saturated fatty acids oleic and linoleic acids (Cik) are the most abundant unsaturated ones. Oleic acid is monounsaturated since it has only one double bond, whereas linoleic, linolenic, and arachidonic acids are polyunsaturated fatty acids, or PUFA s, because they have more than one double bond. Linoleic and linolenic acids occur in cream and are essential in the human diet infants grow poorly and develop skin lesions if fed a diet of nonfat milk for prolonged periods. 

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. 

Hrboticky N, Mackinnon MJ, Innis SM. Effect of a vegetable oil formula rich in linoleic-acid on tissue fatty-acid accretion in the brain, liver, plasma, and erythrocytes of infant piglets. Am J Clin Nutr 1990 51(2) 173-182. 

Hansen AE, Wiese HE, Boelsche AN, Haggard ME, Adam DJD, Davis H. Role of linoleic acid in infant nutrition. Clinical and chemical study of 428 infants fed on milk mixtures varying in kind and amount of fat. Pediatrics 1963 31 171-192. 

The mammary gland produces milk, which is the major source of nutrients for the breastfed human infant. The fatty acid composition of human milk varies, depending on the diet of the mother. However, long-chain fatty acids predominate, particularly palmitic, oleic, and linoleic acids. Although the amount of fat contained in human milk and cow s milk is similar, cow s milk contains more short- and medium-chain fatty acids and does not contain the long-chain, polyunsaturated fatty acids found in human milk that are important in brain development. 

This first generation n-3 deficiency may be considered a model of the human case in which the mother has a diet containing a-linolenic acid but low in long-chain n-3 polyunsaturates such as DHA. The infant is then given a formula with its EFA content derived from corn oil or some other linoleic acid-rich seed oil and devoid of any long-chain n-3 pol3ninsat-urate source, as has been a common p ractice in North America... 

The. animal work will be described only sufficiently to allow the reader to appreciate lietter the discussion of the human studies. When it became apparent in 19.55 that the peroxide hemolysis test was dependent not only on the tocopherol level of the blood but also upon the level of linoleic acid (and other autoxidizable components) in the stroma of the erythrocyte, animal experiments were designed to obtain more exact correlations between tocopherol needs and linoleic acid intake. This relationship between linoleic acid content of the diet and the incidence of chick encephalomalacia (Century and Horwitt, 19.58) was not recorded until later (Century et al., 19.59 Century and Horwitt, 19.59) when observation of cerebellar encephalomalacia in an infant that had been fed a commercial cottonseed oil preparation intravenously came to our attention (Horwitt and Bailey, 1959). In the meantime, there had been a number of reports to certify the relationship between linoleic acid consumption and chick encephalomalacia (Dam et al, 19.58 Machlin and Gordon, 1960). With the advent of better gas chromatographic techniques, it was soon possible to show that the linoleic acid content of the cerebellum was diet dependent (Horwitt et al., 1959 Witting et al., 1961). The marked effects of diet on the fatty acids of the mitochondria of chick brains has also been reported (Horwitt, 1981a). The levels of linoleic acid are much lower in brain tissues than in any tissue analyzed to date and this relatively low linoleic acid level may be considered a characteristic of brain tissue. The significance of this difference is not known. It is of interest to note that the current interpretations of the effect of more unsaturated fats on the production of chick encephalomalacia were anticipated by Dam in 1944. 

Some experiments suggest that high doses of a-linolenic acid exert untoward effects, possibly inhibiting prostaglandin synthesis of the 1- and 2-series. The ratio between linoleic and a-linolenic acid in relevant experiments is such that only excessive use of hnseed oil could produce them under conventional dietary conditions [22]. Still it may be considered prudent to keep the a-linolenic acid content of diet well below that of linoleic acid. On the other hand, possible adverse effects of high doses of linoleic acid on the tissue levels of long chain poljmnsaturated fatty adds, espedally DHA, in developing liver and brain of newborn infants are under discussion [17]. 

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