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Essential fatty acids in plasma of patients with leprosy.

We have investigated the fatty-acid composition of plasma phospholipids in 61 patients with leprosy of various clinical types with either a short or long duration of treatment. All patients had significantly decreased levels of linoleic acid and alpha-linoleic acid, the parent fatty acids of the n-6 and n-3 families, respectively. Patients with a treatment duration of more than 6 months had significantly low levels of arachidonic acid and eicosapentaenoic acid compared to controls or to patients with a treatment duration of less than 6 months. There were no differences in the fatty-acid composition between multibacillary patients and paucibacillary patients. We conclude that dietary supplementation with essential fatty acids may be indicated in patients with leprosy, particularly in those with a long treatment duration.

Arachidonic Acid↗

Potential of essential fatty acid deficiency with extremely low fat diet in lipoprotein lipase deficiency during pregnancy: A case report.

BACKGROUND: Pregnancy in patients with lipoprotein lipase deficiency is associated with high risk of maternal pancreatitis and fetal death. A very low fat diet (< 10% of calories) is the primary treatment modality for the prevention of acute pancreatitis, a rare but potentially serious complication of severe hypertriglyceridemia. Since pregnancy can exacerbate hypertriglyceridemia in the genetic absence of lipoprotein lipase, a further reduction of dietary fat intake to < 1-2% of total caloric intake may be required during the pregnancy, along with the administration of a fibrate. It is uncertain if essential fatty acid deficiency will develop in the mother and fetus with this extremely low fat diet, or whether fibrates will cross the placenta and concentrate in the fetus. CASE PRESENTATION: A 23 year-old gravida 1 woman with primary lipoprotein lipase deficiency was seen at 7 weeks of gestation in the Lipid Clinic for management of severe hypertriglyceridemia that had worsened with pregnancy. While on her habitual fat intake of 10% of total calories, her pregnancy resulted in an exacerbation of the hypertriglyceridemia, which prompted further restriction of fat intake to < 2% of total calories, as well as administration of gemfibrozil at a lower than average dose. The level of gemfibrozil, as the active metabolite, in the venous and arterial fetal cord blood was within the expected therapeutic range for adults. The clinical signs and a biomarker of essential fatty acid deficiency, namely the ratio of 20:3 [n-9] to 20:4 [n-6] fatty acids, were closely monitored throughout her pregnancy. Despite her extremely low fat diet, the levels of essential fatty acids measured in the mother and in the fetal blood immediately postpartum were normal. Normal essential fatty acid levels may have been achieved by the topical application of sunflower oil. CONCLUSIONS: An extremely low fat diet in combination with topical sunflower oil and gemfibrozil administration was safely implemented in pregnancy associated with the severe hypertriglyceridemia of lipoprotein lipase deficiency.

Journal Article↗

Essential fatty acid deficiency and postresection mucosal adaptation in the rat.

The effect of short-term (biochemical) and long-term (clinical) essential fatty acid (EFA) deficiency on mucosal adaptation was studied in a surgical model of short bowel syndrome. Rats fed an EFA-deficient diet for 4 wk had biochemical evidence of EFA deficiency (hepatic and red blood cell triene to tetraene ratios greater than 0.4). Resected animals (70% proximal jejunoileal resection) receiving an EFA-deficient diet had a significantly impaired intestinal mucosal hyperplasia response in all remaining small bowel segments compared with resected controls. The effect of refeeding a control diet to clinically EFA-deficient resected rats was also evaluated. Short-term refeeding (2 wk) of a control diet resulted in a significant return toward normal tissue triene to tetraene ratios. Concomitantly, refed animals had significantly greater mucosal adaptation in the remaining duodenal/jejunal segment compared with resected animals maintained on an EFA-deficient diet postoperatively. These experiments underscore the dynamic nature of tissue EFA status and the importance of fatty acids in the normal compensatory mechanisms of mucosal adaptation after resection.

Adaptation, Physiological↗

Essential fatty acids in erythrocyte phospholipids during pregnancy and at delivery in mothers and their neonates: comparison with plasma phospholipids.

Evidence that the essential fatty acid (EFA) status during pregnancy and at birth may not be optimal is mainly based on fatty acid profiles of maternal and neonatal plasma phospholipids. However, erythrocyte phospholipids may be more reliable than plasma phospholipids to reflect the EFA status of an individual. Therefore, the present study compares the levels of EFA and of their derivatives (LCPUFA) in erythrocyte and plasma phospholipids collected during pregnancy and at delivery of 184 women and of their infants at birth. In general, the relative concentrations of erythrocyte and plasma phospholipid fatty acids (% of total fatty acids) were strongly correlated, but not at early pregnancy. The overall changes in fatty acid concentrations during pregnancy were qualitatively comparable between erythrocytes and plasma, although the comparability became less towards the end of pregnancy. The changes in absolute amounts (mg/l) of fatty acids in erythrocyte and plasma phospholipids also compare quite well till 32 weeks of gestation, but not thereafter. Most maternal-neonatal differences in relative fatty acid concentrations are qualitatively comparable for erythrocyte and plasma phospholipids. However, significant differences were observed for the absolute amounts of arachidonic and docosahexaenoic acids. No matter these differences, plasma and erythrocyte phospholipids seem equally suitable to reliably quantify the more functional EFA and LCPUFA status based on fatty acid ratios. Correlations between neonatal and maternal fatty acid values at delivery/birth are highly significant in erythrocyte as well as plasma phospholipids. Neonatal erythrocyte (but not plasma) values also correlated strongly with maternal values at early pregnancy. Therefore, the neonatal EFA and LCPUFA status might be predicted on the basis of EFA and LCPUFA concentrations of maternal erythrocyte phospholipids at early pregnancy.

Adolescent↗

Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation.

We assessed essential fatty acid (EFA) and B-vitamin status, together with their determinants, in 61 patients with schizophrenia and established whether those with poor status responded biochemically to the appropriate dietary supplements. As a group, the patients had high erythrocyte saturated fatty acids (FAs), monounsaturated FA and low polyunsaturated FA of the omega3 and omega6 series. Patients reporting not to take vitamin supplements had low vitamin B12 and high homocysteine. Homocysteine variance proved best explained by folate in both the total group and male patients, and by vitamins B12 and B6 in females. Alcohol consumption and duration of illness are risk factors for low polyunsaturated FA status (< P2.5 of reference range), while male gender and absence of fish consumption predict hyperhomocysteinemia (> P97.5 of reference range). Two patients exhibited biochemical EFA deficiency and seven showed biochemical signs of omega3/docosahexaenoic acid (DHA) marginality. Four patients exhibited moderate hyperhomocysteinemia with plasma values ranging from 57.5 to 74.8 micromol/L. None of the five patients with either moderate hyperhomocysteinemia, biochemical EFA deficiency, or both, was predicted by their clinicians to have poor diets. That diet was nevertheless at the basis of these abnormalities became confirmed after supplementing 4 of them with B vitamins and with soybean and fish oils. We conclude that a subgroup of patients with schizophrenia has biochemical EFA deficiency, omega3/DHA marginality, moderate hyperhomocysteinemia, or combinations. Correction seems indicated in view of the possible relation of poor EFA and B-vitamin status with some of their psychiatric symptoms, but notably to reduce their high risk of cardiovascular disease.

Adolescent↗

Essential fatty acid deficiency during pregnancy in the rat: influence of dietary carbohydrates.

We investigated the role of gestation in the development of essential fatty acids (EFA) deficiency by comparing four groups of nonpregnant rats and four groups of pregnant rats fed either glucose or sucrose as carbohydrate source (61.5% kJ) and either corn oil (EFA) or hydrogenated coconut oil [saturated fat (SF)] as fat source (5% kJ). Pregnancy was a crucial period for the onset of EFA deficiency in sucrose-fed rats. The arachidonic acid content of plasma lipids and liver microsomes was lower in SF-sucrose pregnant rats than in SF-sucrose nonpregnant rats. The liver microsome delta 6- and delta 5-desaturase activities were higher in sucrose pregnant rats than in sucrose nonpregnant rats. In glucose-fed rats the EFA deficiency was less severe. delta 6- and delta 5-desaturase activities were higher in SF-glucose rats than in EFA-glucose rats, except for delta 5-desaturase of the pregnant rats, in which activity was high in both glucose-fed groups. This might explain the effect of glucose in preventing the onset of EFA-deficiency in pregnant rats fed an SF diet.

Animals↗

Factors influencing essential fatty acid requirement in total parenteral nutrition (TPN).

Twenty patients, after major injuries or elective abdominal surgery, were studied with respect to essential fatty acids in total serum and lipoprotein fractions. The regimen of total parenteral nutrition was altered in its content of energy, carbohydrates or fat. In all patients the linoleic acid levels decreased and the 20:3/20:4 ratio increased. Serum low density lipoproteins developed remarkable alterations of the biochemical composition and of morphology by electronmicroscopy. The degree of these alterations depended on the kind of illness, the amount of carbohydrates infused, special hormonal situation due to surgery and linoleic acid supply. As a consequence of these results, the supply of a sufficient amount of linoleic acid should be considered in every case of total parenteral nutrition.

Adolescent↗

Essential fatty acid diet supplementation. Effects on peripheral nerve and skeletal muscle function and capillarization in streptozocin-induced diabetic rats.

Effects of essential fatty acids on nerve conduction, hypoxic resistance, skeletal muscle contractile properties, and capillary density were examined in streptozocin-induced diabetic rats. Nondiabetic and diabetic controls and three diabetic groups treated with 10% supplements of corn oil, evening primrose oil (Efamol), or a mixture of 80% evening primrose oil and 20% fish oil (Efamol Marine) for 2 mo were used. Efamol and Efamol Marine increased plasma gamma-linolenic acid levels, but arachidonic acid was elevated only with Efamol. Diabetes resulted in 15-29% reductions in sciatic motor and sensory saphenous nerve conduction velocity. Efamol prevented conduction deficits more effectively than Efamol Marine, and corn oil had no effect. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for action potential amplitude to decline by 50% with diabetes. Corn oil had no significant effect. With Efamol, hypoxic resistance was within the nondiabetic range. Efamol Marine produced intermediate results. Functional improvements may relate to enhanced vasa nervorum perfusion, because endoneurial capillary density increased by 22% with Efamol, angiogenesis perhaps resulting from eicosanoid production from arachidonic acid. Soleus muscle contractions were prolonged by diabetes. This was partially corrected by treatment, Efamol being most effective. Extensor digitorum longus muscle had reduced tetanic tension with diabetes, and this was prevented by all treatments. Soleus showed a modest increase in capillarization with Efamol, which may have contributed to reduced susceptibility to fatigue. The data suggest involvement of abnormal fatty acid metabolism in the etiology of diabetic neuropathy and myopathy.

Animals↗

Essential fatty acid deficient rats in the study of cystic fibrosis: an X-ray microanalytical and ultrastructural study in chronically reserpinized rats.

Essential fatty acid (EFA) deficiency has been proposed as a major pathogenic mechanism for cystic fibrosis (CF) and EFA-deficient animals have been proposed as an animal model for CF. In the present study, the elemental composition and ultrastructure of the acinar cells of the submandibular and parotid gland of the pancreas of EFA-deficient rats were investigated by X-ray microanalysis and electron microscopy. The effects of EFA-deficiency were compared to changes in these exocrine glands in chronically reserpine-treated rats, an established animal model for CF. EFA-deficiency did not cause any significant changes in the elemental composition of the acinar cells of the submandibular or parotid gland, or of the pancreas. The changes in elemental composition induced by reserpine treatment were only slightly modified by EFA-deficiency, mainly towards normalization. EFA-deficiency resulted in the presence of abnormal, electron translucent, zymogen granules in the parotid gland and in a reduction of the number of zymogen granules in pancreatic acinar cells. Since EFA-deficiency in rats only causes minor changes in structure and elemental composition of salivary glands and pancreas, and does not potentiate the effect of chronic reserpine treatment on these tissues, it is concluded that EFA-deficiency is likely to be of minor importance in the exocrine gland disturbances in CF.

Animals↗

Essential fatty acid deficiency inhibits the in vivo generation of leukotriene B4 and suppresses levels of resident and elicited leukocytes in acute inflammation.

Essential fatty acid (EFA) deficiency exerts an anti-inflammatory effect in several models of inflammation. In an effort to understand underlying mechanisms, the effect of EFA deficiency on the generation of eicosanoids and the elicitation of leukocytes in a model of acute inflammation was examined. Acute inflammation was induced by the i.p. injection of zymosan in mice. The injection of zymosan in normal mice was followed by a short burst of eicosanoid synthesis lasting 2 hr. Leukotriene (LT)B4, LTC4, LTD4, and LTE4, thromboxane B2, and 6-keto-prostaglandin F1 alpha were detected using high pressure liquid chromatography and specific radioimmunoassays. This initial phase of eicosanoid production was followed by a more prolonged infiltration of leukocytes (predominantly polymorphonuclear neutrophils (PMN)) lasting 48 hr with little eicosanoid synthesis. When challenged with zymosan, EFA-deficient mice exhibited a marked decrease in the production of eicosanoids during the early phase. No LTB could be detected at all. The number of resident peritoneal macrophages in EFA-deficient mice was also substantially decreased, and the influx of PMN during the inflammatory response was markedly diminished. In order to establish that the generation of eicosanoids during the early phase of this model of acute inflammation played a causal role in the later infiltration of PMN, the effect of the mixed lipoxygenase/cyclooxygenase inhibitor, BW755C, on LTB formation and PMN influx in this model of inflammation was assessed in control animals. BW755C completely blocked LTB synthesis and inhibited the subsequent influx of PMN. In conclusion, EFA deficiency inhibits eicosanoid generation, depresses levels of resident macrophages, and markedly diminishes the influx of PMN in the acute inflammatory response. The decrease in PMN influx appears to result from the inhibition of the antecedent generation of LTB.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Effects of essential fatty acid deficiency on renal papillary lipid methylation.

The relationship between lipid methylation and prostaglandin release was examined in rat renal papillae. Essential fatty acid deficiency (EFAD) was produced to deplete tissues of arachidonate precursors. The in vitro release of prostaglandin E was determined after exposure of the papillae to hypertonic sodium chloride. The EFAD animals were observed to have significantly less renal papillary lipid methylation than rats fed control diets (50%; P less than 0.05). However, stimulation of prostaglandin production in vitro was not accompanied by any detectable changes in total lipid methylation in tissues from either normal or EFAD rats.

Animals↗

Essential fatty acid deficient hairless mouse: a model of chronic epidermal hyperproliferation.

Epidermal DNA synthesis has been shown to be increased approximately three-fold in hairless mice that were fed a diet deficient in essential fatty acids (EFA deficient) for 65 days, compared with animals fed a standard diet. Autoradiographic labelling indices showed a 330% increase in the EFA deficient mice over controls. The animals developed evidence of a diffuse thickening, scalping and loss of elasticity of the skin after 40 days on the EFA deficient diet. Histologically, the epiderma of the EFA deficient animals showed acanthosis, hypergranulosis, hyperkeratosis and increased intracellular epidermal spaces. Increased mitotic indices were found with Feulgen staining. This is further evidence that deficiencies of essential fatty acids are associated with disturbance of normal epidermal cell proliferation and control of keratinization. A single application of topical 0.1% betamethasone valerate to EFA deficient mice reduced the epidermal DNA synthesis to that of normal diet mice. Ten percent linoleic acid topically over 2 weeks also returned epidermal DNA synthesis to normal levels.

Animals↗

The preferential mobilisation of C20 and C22 polyunsaturated fatty acids from the adipose tissue of the chick embryo: potential implications regarding the provision of essential fatty acids for neural development.

The aim of this study was to determine the relative mobilisation of the different fatty acyl components of the triacylglycerol (TAG) of the chick embryo's adipose tissue in the light of the specific requirements of the developing neural tissues of the embryo for C20-22 polyunsaturated fatty acids. Pieces of adipose tissue, obtained from embryos at various developmental stages, were incubated in vitro in Dulbecco's Medium containing serum albumen. The fatty acid compositions of the initial tissue TAG and of the free fatty acid (FFA) mobilised from the tissue during 1 h of incubation were determined and compared. The composition of the FFA released into the medium under conditions of basal (i.e., unstimulated) lipolysis was markedly different in several respects from that of the TAG from which it originated. The polyunsaturated fatty acids, 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n-3, were consistently found to be preferentially released into the medium, whereas the major fatty acyl constituents of the tissue, 16:0 and 18:1n-9, were selectively retained in the TAG. For example, at day 18 of development, the proportions (% w/w of fatty acids) of 20:5n-3 and 22:6n-3 released into the incubation medium were respectively 6.5 and 7.5 times higher than in the original tissue TAG. Glucagon stimulated the overall rate of mobilisation by approx. 2-fold and also partially suppressed the preferential mobilisation of C20-22 polyunsaturates. These results may be relevant to the elucidation of the means by which essential polyunsaturates are delivered from the yolk to the neural tissues of the embryo, with the implication of a mediatory role for the embryonic adipose tissue in this transfer.

Adipose Tissue↗

Essential fatty acid deficiency in the pig: effects on eicosanoid basal levels and in vitro synthesis by the small intestine.

The influence of nutritional essential fatty acid (EFA) deficiency on arachidonate metabolism by porcine small intestine has been studied. Great care was exercised in the manipulation of the jejunal wall to avoid artefactual metabolism of arachidonate. Thus, jejunal wall was frozen in liquid nitrogen after organ removal and washing, and subsequently lyophilized. This lyophilized tissue was used as starting material for all experiments, including organic solvent extractions (for basal level determinations) and reconstitution in aqueous buffer (for neosynthesis experiments). Feeding pigs with a low linoleate diet for 12 weeks resulted in a 36% diminution in the % of arachidonate in jejunal phospholipids. Basal levels of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thromboxane B2 (TXB2), PGF2 alpha, PGE2, PGD2 and leukotriene B4 (LTB4) were not altered in the EFA-deficient state. However, we observed a significant lowering of the synthesis of each of these eicosanoids (except LTB4) by the EFA-deficient jejunum during brief (15s) in vitro neosynthesis experiments. The origin of arachidonate as a substrate of PG endoperoxide synthase, also named PGH synthase or cyclooxygenase (Cox) in these neosynthesis experiments is probably a non-esterified fatty acid pool since, (1) neosynthesis was not inhibited by the phospholipase A2 (PLA2) inhibitor parabromophenacylbromide, and (2) substantial amounts of arachidonic acid were found in the jejunum, frozen or lyophilized. Cox activity of the lyophilized jejunum and Cox content of liver and intestine microsomes were not modified in the EFA-deficient state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Repeated automated assessment of abstinent male alcoholics: essential fatty acid supplementation and age effects.

A double-blind trial carried out with alcohol-dependent males randomly allocated to n-6 essential fatty acid (EFA) supplementation or placebo capsules over a 6-month period incorporated a battery of automated neuropsychological tests. Results from problem-solving and perceptual motor speed tests are used. The effect that EFA supplementation had on recovery over 6 months of abstinence is shown, as well as the tests in which younger (aged 20-39) alcohol-dependent males differ from the older (aged 40-59) subjects.

Adult↗

Proliferative epidermis of essential fatty acid deficient mice has reduced cyclic AMP content.

We have simultaneously measured epidermal DNA synthesis, epidermal thickness and cyclic nucleotide levels in essential fatty acid (EFA) deficient hairless mice skin. In vitro epidermal DNA synthesis and epidermal thickness were significantly increased in EFA deficient epidermis. Cyclic AMP levels were significantly reduced when expressed using three different data bases. Cyclic GMP levels were increased using two data bases but these increases were not statistically significant; Cyclic AMP/cyclic GMP ratios were significantly decreased in the EFA deficient skin. The results provide evidence that cyclic nucleotide levels are altered in an animal model of benign epidermal proliferation.

Animals↗

Cholesteryl ester depletion from the ovaries of superovulated female rats fed a normal or essential fatty acid deficient diet.

The cholesteryl ester content of the ovaries was determined in rats diets containing corn oil or hydrogenated coconut oil (essential fatty acid (EFA) deficient) and subjected to superovulation by injection of luteinizing hormone and follicle-stimulating hormone. Superovulation increased ovarian weight; the effect was greater in animals fed corn oil. Superovulation significantly decreased total ovarian cholesteryl ester concentration in animals fed corn oil, with disproportionately large decreases occurring in the esters of 20:1, 20:2, 22:5w6, and 22:6w3. Significant decreases were observed in these esters when the data were expressed on a unit mass of tissue basis or in relation to total ovarian mass. In superovulated, EFA-deficient rats, esters of 18:1, 20:1, 22:5w6, and 22:6w3 were significantly lower per unit mass of tissue but this was due, in all cases except that of 22:6w3, to the increased mass of ovarian tissue; there was no decrease in total esters per ovary weight during superovulation of deficient rats. The pattern and degree of selective changes in ovarian cholesteryl esters during superovulation were different from those previously reported for adrenal esters of stressed rats.

Animals↗