A.G. Hassam

ESSENTIAL FATTY ACIDS AND FETAL BRAIN GROWTH

The fetal brain accumulates long-chain (C20 and 22) polyunsaturated fatty acids--arachidonic and docosahexaenoic--during cell division. De-novo synthesis of these acids does not occur and they are thought to be either directly derived from food or by metabolism from linoleic and linolenic acids, respectively. Administration of isotopically labelled linoleic and linolenic acids to pregnant guineapigs showed that only a small proportion of the label was converted to their respective long-chain polyunsaturated derivatives in the maternal liver. The proportion was increased within the phospholipids (structural lipids) by what appeared to be amultiple processing system which increased chain length and degree of polyunsaturation from maternal liver to placenta, fetal liver, and to fetal brain. Observations in man suggest a similar trend. The porportion of long-chain polyunsaturated acids increased in the phospholipids from maternal blood, cord blood, fetal liver, and fetal brain. These data show that the placenta and fetus are radically modifying the maternal phospholipids so as to achieve the high proportions of the C20 and C22 polyunsaturated fatty acids in the structural lipids of the developing brain.

Essential fatty acid requirements in pregnancy and lactation with special reference to brain development.

Abstract In the human pregnancy, the additional energy requirements appear to be guaranteed by a substantial deposition of lipid stores (40,500 kcal) during the early part of pregnancy which can then provide both for the foetal growth spurt of late pregnancy and meet part of the energy cost of lactation. The foetal accumulation of protein is quantitavely small (1600 kcal). In human milk, lipid provides 60% of the infants dietary energy and 10–12% of that is the essential fatty acid component. Protein only accounts for about 6% of the dietary energy. Lipids are involved in a major way in the development of the brain and vascular systems. Because these systems are developed to an outstanding degree in the human species, the suggestion will be made that dietary consideration of lipids, both quantitatively and qualitatively, may be of greater significance to early human development than consideration of protein. Lipid is quantitatively the most important component of the nervous system. The extent of brain development during foetal and early postnatal growth in the human is remarkable by comparison with other animal species. In the human, much of the brain cell division occurs during foetal growth. Brain cells and synapses have a high content of essential fatty acids. These are present as 20 and 22 carbon chain length polyunsaturated derivatives of linoleic and α-linolenic acids. Experimental depletion of these long-chain PUFA is associated with functional distortions and high perinatal mortality. The rate of synthesis of the long-chain PUFA is limited by the desaturase reactions and the high concentrations achieved by other foetus are the result of sequential metabolism of reprocessing the maternal liver, placenta, foetal liver and foetal brain. The thesis is presented that foetal and infant development is normally protected by deposition of fat and other nutrient stores in the mother and the infant, in advance of requirements. If this theory is correct, it implies that measures for the prevention of low birth weight and malnutrition need to be implemented early in pregnancy, if not before.

The incorporation of orally fed radioactive γ-linolenic acid and linoleic acid into the liver and brain lipids of suckling rats.

The incorporation of radioactivity from orally administered γ-linolenic acid-1-14C and linoleic acid-3H into the liver, plasma, and brain lipids of suckling rats was studied. Significantly more radioactivity from the former compound was incorporated into the liver and brain lipids 22 hr after dosing. The distribution of the radioactivity in the fatty acids of the liver and brain lipids was different for each isotope. Most of the3H was still associated with linoleic acid, whereas most of the14C was in the 20∶3 and 20∶4ω6 fractions. These results suggest that the desaturation of linoleic to γ-linolenic acid in vivo is a rate-limiting step in the conversion of linoleic to arachidonic acid.

DEFECTIVE ESSENTIAL-FATTY-ACID METABOLISM IN CYSTIC FIBROSIS

Cystic fibrosis (C.F.) is characterised by low serum levels of essential fatty acids (E.F.A.). However, the fatty-acid pattern does not totally resemble that of dietary E.F.A. deficiency. The differences suggest a reduction in the desaturation of E.F.S. It is not known whether this defect is the primary lesion in C.F. or is the result of tissue damage in the disease. It is proposed that C.F. patients might have increased linoleic-acid requirements, and possibly specific requirements for its desaturation products.

The failure of the cat to desaturate linoleic acid; its nutritional implications.

In vivo administration of 1-14C-linoleic acid to domestic cats demonstrated that these animals are unable to convert this essential fatty acid to its physiologically active metabolities. This experiment confirms the absence of both the delta6 and delta8 desaturases in the cat, and suggests that this species has a dietary requirement for polyunsaturated fatty acids of animal origin.

The inability of the lion, Panthera leo L. To desaturate linoleic acid

Most studies of the metabolism of polyunsaturated fatty acids have been conducted on laboratory rodents. These animals have relatively high A6 desaturase activity and are therefore able to convert linoleic acid (18:2606) to the prostaglandin precursors dihomogamma-linolenic acid (20:3606) and arachidonic acid (20:4606). It has been assumed without much evidence that other species can desaturate polyunsaturated fatty acids equally well. However, recent work on the domestic cat, Felis catus L. [1] and the turbot, Scopthalamus maximus, L. [2] has shown that these obligate carnivores are unable to desaturate linoleic acid (18:2606) or linolenic acid (18:3603). It has been suggested that these species, have, therefore, a dietary requirement for the long-chain polyenoic acids (LCP), particularly 20:3606 and 20:4606, and hence for polyunsaturated lipid of animal origin. Because of the wider implications of the lack of desaturase activity we have begun a comparative study of fatty acid desaturation in animals of different dietary habits. We wish here to make a preliminary report of studies on the African lion, Panthera leo, which demonstrate the absence of A6 and A8 desaturase activity in this animal.

Essential fatty acid restriction inhibits vitamin D-dependent calcium absorption.

Essential fatty acid (EFA) restriction has been found to inhibit the action of vitamin D on the active transport of calcium in the intestine. This inhibition suggests EFAs are involved in facilitating the active transport of calcium across the mucosal membrane.

The effect of essential fatty acid-deficient diet on the levels of prostaglandins and their fatty acid precursors in the rabbit brain

Rabbits were maintained on an EFA-deficient diet. After eight weeks on this diet, lipid analysis showed no major alterations in the levels of brain dihomo-gamma-linolenic and arachidonic acids when compared with animals maintained on the standard laboratory diet. However, there were substantial reductions in the brain prostaglandin contents. It is suggested that the dihomo-gamma-linolenic acid and arachidonic acid utilized for prostaglandin production may be more directly related to the dietary essential fatty acid input rather than to the size of the precursor pool in the principal phospholipids.

FETAL ACCUMULATION OF LONG-CHAIN POLYUNSATURATED FATTY ACIDS

The developing brain accumulates long-chain (C20 and C22) polyenoic fatty acids, particularly during cell division (Crawford & Sinclair, 1972; Sinclair & Crawford, 1972). De novo synthesis of these acids does not occur in higher animals and they are derived either directly from food or by metabolism from the parent essential fatty acids, linoleate and α-linolenate.

Dietary management in multiple sclerosis

Zntroduct ion There are three current views on the cause of multiple sclerosis (MS): nutrition, viral infection and autoimmune reaction. Interest in nutrition arose from studies on the epidemiology which indicated a high prevalence in countries with relatively high saturated fat intakes; in addition, low levels of essential fatty acids (EFA) were recorded in the blood of MS patients (Swank, 1950; Swank et al. 1952; Sinclair, 1956; Agranoff & Goldberg, 1974). The conclusion was drawn that MS might be related to a dietary deficiency of polyunsaturated or EFA (Swank, 1950; Sinclair, 1956; Allison, 1963; Bernsohn & Stephanides, 1967; Dick, 1976). These findings led to a double-blind trial of linoleic acid supplementation in Belfast and London and later in Newcastle (Millar et al. 1973; Bates et a f . 1978), which gave encouraging results. The ‘linoleic acid effect’ is the reason for the current interest in diet and MS. The interest in EFA centred principally on linoleic acid. However, Bernsohn & Stephanides (1967) suggested that of the two EFAs, linoleic and a-linolenic acids, the evidence pointed more to dietary deficiency of a-linolenic acid. They called attention to epidemiological information which seemed to indicate that the geographical distribution of MS was inversely related to the intake of foods rich in a-linolenic acid and its derivatives ( 0 3 fatty acids), such as fish. This proposition arose because of the relatively low incidence of MS found in the Faroe Islands, compared to the Shetlands. The Islanders came from the same Danish genetic backgrounds but the Faroe Islanders remained as fishermen whilst the Shetlanders adopted a British agricultural practice. Similar contrasts were apparent in Scandinavia. The matter has not been followed up, possibly because of the lack of any supporting evidence that 0 3 fatty acids have a nutritional role. However, there is now a substantial amount of analytical information demonstrating the presence of long chain 0 3 fatty acids in the central nervous system (Crawford, Casperd et al.