Arachidonic acid conditional essential fatty acids

A functional method for detection depends upon competition for the activity of the and desaturases between a non-essential fatty acid (e.g. oleic acid) and an essential fatty acid (see above). If the latter is deficient, oleic acid is readily converted, via the desaturases, to Mead acid, since there is little competition (Figure 11.14). Hence the amount of the latter can be used as a marker for deficiency of essential fatty acids, although it is better to use the ratio of double bonds only three are present in Mead acid (i.e. a triene) but four are present in arachidonic acid (i.e. a tetraene). A ratio in plasma, triene/tetraene >4.0 is an indication of a deficiency of essential fatty acids. This method has shown that a deficiency can occur in a number of conditions which can lead to disease (Table 11.5). 

Very soon after the discovery of essential fatty acid phenomena in rats, medical researchers at the University of Minnesota began investigations on humans. The first medical phenomenon related to essential fatty acids was a dermatitis associated with intractable eczema. Hansen and his co-workers chose cases which did not respond to the usual treatments for eczema and gave these patients supplements of lard which contains approximately 10% of linoleic acid and a few percent of arachidonic acid (Hansen, 1937). They found that in the cases of intractable eczema the serum iodine number was low, and that when the diets were supplemented with lard, the iodine value rose to normal and the skin cleared up in 75% of the cases. An example of this disease which responded to essential fatty acids is shown in Figure 4 (Azerad Crupper, 1949). A study of the histological features of normal and essential fatty acid deficient human skin shown in Figure 5 indicates that in the deficient condition... 

The measurements of the total amount of various essential fatty acids as co-3 fatty acids in plasma, serum, or erythrocyte membrane phospholipids have been indicated as useful markers of essential polyunsaturated fatty adds. Essential fatty acid deficiency is a clinical condition that derives from inadequate status of co-3 and co-6 fatty acids however, the symptoms are nonspecific and may not present prior to marginal essential fatty acid status. Widely used biomarkers for bicx hemi( essai-tial fatty acid deficiency are mead acid and the triene/tetraene ratio. Howcvct, the total plasma triene/tetraene ratio has been considered the gold standard for essential fatty acid deficiency. Mead acid, or 5,8,11-eicosatrienoic acid (5,8,11-20 3 co-9) is synthesized from endogenous oleic acid and is increased when there is insufficient concentrations of linoleic and a-linolenic acid to meet the needs of polyunsaturated fatty acids. Under normal conditions only trace amounts of mead acid are found in plasma. EPA and DHA inhibit mead acid synthesis. Mead acid measurement is an indicator of essential fatty acid deficiency state, while essential fatty add depletion is associated with a decrease in plasma hnoleate and arachidonate percentages. Assessment of long-term essential fatty acid intake is measured in adipose tissue, and it is considered the best indicator because of its slow tumover. - Cutoff values for the assessment of essential fatty adds and to-3 fatty acid status in erythrocytes have been reported. Proposed cutoff values for children older than 0.2 years are 0.46 mol% 20 3 co-9 (mead acid) for early suspicion of essential fatty acid defidency, 0.068 mol/mol docosapentaenoic/arachidonic acid... 

Fatty acids, such as linoleic, hnolenic, and arachidonic acids, contain two or more cis carbon-carbon double bonds and are referred to as polyunsaturated fatty acids. Several of these fatty acids, including linoleic and linolenic acids, are required nutrients for humans and must be part of a healthy diet. They are termed essential fatty acids, of which there are eight. These fatty acids cannot be synthesized by human beings but are essential to human health. Therefore, they must be consumed in adequate amounts in a healthy diet, specifically in the form of ingested plant-derived foods. A diet devoid of the essential fatty acids eventually results in a fatal condition characterized by inflammation of the skin (dermatitis), failure of wounds to heal, and poor growth. The essential fatty acids serve as precursors for complex molecules termed eicosanoids, to which we return below. 

A common chemical property of polyunsatured fatty acids, which are needed to maintain animals in healthy condition, seems to be cis double bonds at the w6 and w9 positions [14]. Important essential fatty acids in the diet are linoleic (18 2w6) and a-linoleic (18 3w3) acids, which both occur in plants. In the mammalian organism, these fatty acids can be desaturated and elongated to form the derived essential fatty acids, dihomo-y-linolenic acid (20 3w6), arachidonic acid (20 4 6) and timnodonic acid (20 5to3), the three precursor acids of prostaglandins (Fig. 2, see also Fig. 11). The derived essential fatty acids can also be obtained in the diet. Arachidonic and dihomo-y-linolenic acids occur in animal tissues timnodonic acid in fish. The mammalian organism cannot introduce double bonds at the co3 and <06 positions of long-chain fatty acids, which partly explains why fatty acids of the w3 and w6 series must be provided in the diet (see refs. 15-18 for reviews). These fatty acids are also essential to man, however, deficiency states can only be induced by... 

The perturbation of the incorporation of linoleic add metabolites into mammary gland lipids by CLA metabolism may lead to the hypothesis that CLA is able to create a mild arachidonic acid deficiency condition, in particular in the mammary tissue which is composed mainly of neutral lipids. In fact, because CLA and some of its metabolites are preferentially incorporated into neutral lipids (15), unlike linoleic acid, which is instead incorporated mainly into phospholipids, the preponderance of neutral lipids in the mammary tissue renders the competition between these two fatty acids more favorable toward CLA. It has been demonstrated that mammary tumorigenesis requires essential fatty acids, and eicosanoid inhibitors are able to reduce tumor incidence in experimental models (22). CLA, likely by decreasing the supply of arachidonic acid and inhibiting eicosanoid formation through its metabolites, may counteract arachidonic acid-derived eicosanoid action. Because the decrease of arachidonic acid, CLA metabolite incorporation, TEB density, and tumor incidence correlated with the (XA dietary intake, we can speculate that TEB density could also be modulated by eicosanoids. More data are required, however, to substantiate this hypothesis and to identify which eicosanoid(s) may be responsible for such effects. 

The first proof that fats comprise a necessary component in the diet was adduced in 1926 by Evans and Burr. Shortly thereafter, McAmis et al. (1929) also reported that rats grew better on fat-containing diets than on regimens deficient in this foodstuff in fact, the latter workers reported deficiency symptoms in rats which received the fat-free diets. It remained for Burr and Burr (1929) to demonstrate in a clear-cut manner that the beneficial effect of fat on growth was due to the fact that it prevented a dietary disease. This deficiency condition was not to be ascribed to the lack of vitamins A and D, but rather to the absence of components present in the saponifiable fraction. The latter active compounds were shown to be polyunsaturated fatty acids, which are usually referred to as essential fatty adds (EFA). The fat eficiency symptoms produced by a fat-free diet were found to disappear in a dramatic fashion when certain unsaturated fats, or linoleic, linolenic, or arachidonic acids, were fed (Burr and Burr, 1930). Earlier reviews of the nutritional significance of the EFA included that of Burr (1942), and of... 

---