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Abnormalities of essential fatty acid distribution in the plasma phospholipids of patients with bladder cancer.

We have examined the composition of the essential fatty acids in the plasma phospholipid fractions of 98 patients with histologically proven bladder cancer. These patients were attending hospital for regular follow-up by check cystoscopy. Patients were divided into two groups, depending on the cystoscopic findings, of either active (tumour recurrence seen) or inactive (no evidence of tumour recurrence) disease. Compared with a normal population, the plasma levels of most of the fatty acids, including arachidonic acid, were significantly lower in the 98 cancer patients (P less than 0.001, t-test). We were unable, however, to demonstrate any significant differences (Mann-Whitney U-test) between the active and inactive disease groups. Plasma levels of the essential fatty acids are abnormal in patients with bladder cancer; they do not help, however, to distinguish those patients with active disease from those with inactive disease. This may arise because the deficit in essential fatty acids we have demonstrated is a predisposing factor for the development of bladder cancer rather than a metabolic consequence of the tumour. Further studies are needed to establish the possible clinical role of measurement of essential fatty acids in patients with bladder carcinoma.

Aged↗

Essential fatty acids as determinants of lipid requirements in infants, children and adults.

Essential fatty acids (EFA) are the indispensable component of the lipid supply beyond the provision of energy as a fuel for oxidation. They serve as dietary precursors for the formation of prostanoids and other eicosanoids thus are of great significance in health and modulation of disease conditions. Eicosanoids are powerful autocrine and paracrine regulators of cell and tissue functions: thrombocyte aggregation, inflammatory reactions and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, and uterine contraction. Recent attention has focused on the effect of n-3 and n-6 long chain EFAs in normal fetal development. Results from human infant studies suggest that n-3 fatty acids are needed for optimal development of visual and brain function. Human milk is the best and only time proven source of fat and dietary essential fatty acids for infant feeding. International recommendations for n-3 and n-6 EFA dietary intake are reviewed and suggested intakes for long chain EFAs are provided.

Adult↗

Essential fatty acids and their role in conditions characterised by impulsivity.

There is a biological basis for anticipating a role for the essential fatty acids (EFAs) in the therapeutics of the large number of conditions characterized by impulsivity, hostility and aggression. Abnormalities in these constructs have been linked to dysfunction of several monoaminergic systems, 5-hydroxytryptamine (5-HT) in particular. The EFAs ameliorate the function of these systems and also act through a number of other mechanisms. While limited in volume, a number of EFA supplementation studies support their role in the treatment of such conditions. This paper summarises the literature in terms of epidemiology, clinical science and therapeutics in clinical and non-clinical populations.

Aggression↗

[Recent biochemical nutrition knowledge in relation to metabolism and the significance of essential fatty acids and n-3-fatty acids contained in fish].

A survey is given on some newer knowledge about metabolism and about the importance of the essential fatty acids and of the n-3 fatty acids (eicosapentaenic, docosapentaenic, docosahexaenic acids) which occur in fish oils. In the body the linoleic acid via intermediate steps can be transformed into the arachidonic acid, from which various prostaglandins and leucotriens as well as the thromboxane A2 can be formed. The transformation of the linolenic acid into the eicosapentaenic acid is slight in man. The docosahexaenic acid is necessary for the construction of phospholipids in the brain and in the retina. The uptake of fish fatty acids inhibits the formation of thromboxane A2 and of leukotriens from the arachidonic acid. The fish fatty acids further in the liver in the peroxisomas the activity of the enzymes for the beta-oxidation; the formation of lipoproteins of high density increases under their influence: the triacylglyceride content, the cholesterol as well as the lipoprotein content of very low and low density decreases, when there is an adequate part of fish fatty acids in the nutrition.

Animals↗

The usefulness of topical application of essential fatty acids (EFA) to prevent pressure ulcers.

This study investigated whether the topical application of essential fatty acids improves hydration and elasticity and helps prevent skin breakdown in individuals with poor nutritional status. Between June 1995 and July 1996, 86 patients, equally divided into two groups, underwent double-blind research (mean age = 60; range 26-78). All patients had a Norton Scale score of 9 and were fed orally a high-protein diet and/or received parenteral nutrition (92% were severely malnourished). Pressure ulcer prevention was the same for both groups. Every 8 hours, approximately 20 ml of solution A (1.6 gr EFA with linoleic acid extracted from sunflower oil, 112 UI vitamin A, and 5 UI Vitamin E) or B (1.6 gr mineral oil, 112 UI Vitamin A, and 5 UI Vitamin E) was applied all over the body inclusive of all potential wound sites for a mean of 21 days. In group A, two patients developed ulcers (both Stage I, one per patient); 42 (98%) had hydrated skin and 32 (76%) maintained skin elasticity. In group B, 12 (27%) developed ulcers (all Stage II, ten with 1 ulcer, two with 2 ulcers); 9 (22%) had hydrated skin while 34 (78%) showed scaly skin/deep dehydration; 10 (24%) maintained skin elasticity while 33 (76%) showed a loss of elasticity. These results lead us to believe that essential fatty acids really do make a difference in the skin.

Administration, Topical↗

Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation.

In a group of 19 normal pregnant women, plasma lipids were extracted, phospholipids were isolated, and the fatty acid (FA) compositions were measured by capillary gas chromatography. Blood samples were taken at 36 wk, at labor, and at 6 wk postpartum. The FA profiles showed deficiencies of omega 6 and omega 3 FA (omega indicating the length of the terminal saturated chain), the latter more severe, at all three times. Mean melting point (MMP) was calculated for each sample as an index of "fluidity" based upon all FA present. MMP varied linearly with total polyunsaturated FA and with double bond index, current measures of "fluidity" and essential FA status. MMP was elevated 9-11 degrees C in plasma phospholipids of women during pregnancy and labor and postpartum. Lactating mothers showed less recovery from the deficiencies than did the nonlactating mothers, but neither approached normal at 6 wk. The changes seen in phospholipid profiles suggest a significant transfer of omega 3 and omega 6 polyunsaturated FA from the mother to the fetus. These FA are essential for normal fetal growth and development; their relative deficiency in maternal circulation suggests that dietary supplementation may be indicated.

Adult↗

Schizophrenia, tardive dyskinesia and essential fatty acids.

Several reports have indicated that people suffering from schizophrenia show an associated abnormality in levels of certain essential fatty acids (EFAs) in blood cells. Similar abnormalities have also been noted in association with the presence of tardive dyskinesia (TD). In order to study this further, 72 patients with the diagnosis of schizophrenia or schizoaffective disorder were examined to assess the relationship between psychiatric status, movement disorder (TD) and relative levels of the n-3 and n-6 essential fatty acids in red blood cell membranes and plasma. Patients were followed up over the next 4.5 years to determine whether or not changes in clinical state showed any systematic relationship to changes in essential fatty acid levels. We hypothesised that patients with schizophrenia would show persistently lowered levels of n-6 and n-3 series essential fatty acids, compared with normal controls. We further hypothesised that this abnormality would be greater in the presence versus absence of TD and the dominance of negative rather than positive symptoms. The only consistent findings were that lower levels of linoleic acid and higher levels of dihomogamma-linolenic acid characterised the patient population compared with control subjects but there was considerable variability in patients' EFA profile.

Adolescent↗

Retention of linoleic acid in carcass lipids of rats fed different levels of essential fatty acids.

Rats of an inbred Sprague-Dawley strain were fed purified diets with low (0.3% of total energy), normal (3%) or high (10%) content of essential fatty acids (EFA) for at least three generations. Two 30-day-old rats with similar weights were chosen from one litter. One was killed; weight increase and food consumption of the other rat was measured for 15 days. Total lipid content and fatty acid composition in total lipid and lipid classes were determined in both rats. Seven pairs of rats from each group were treated in the same way. Calculations based on amount of linoleic acid ingested and retained in the carcass lipids showed that 50% of the ingested linoleic acid was retained in the low EFA rats compared to 10-15% in the normal and high EFA rats.

Animals↗

Essential fatty acid deficiency: a new look at an old problem.

Essential fatty acid (EFA) deficiency is a useful tool to study the role of arachidonate and its metabolites in various physiologic and pathologic states. Recent studies have clarified the effects of EFA deficiency on membrane arachidonate and its metabolites, and have demonstrated that 20:3(n-9) (which accumulates in EFA deficiency) can be metabolized to a variety of eicosanoids. EFA deficiency has been shown to exert an anti-inflammatory effect. The mechanism of this effect may in part be mediated through a decrease in leukocyte leukotriene formation. In contrast, studies using the novel fatty acid, columbinic acid, have shown that the epidermal dysfunction seen in EFA deficiency may be a function of linoleate and its lipoxygenase metabolites rather than of arachidonate and the prostaglandins. Finally, it has recently been shown that EFA deficiency potentiates the effects of volatile anesthetics. EFA deficiency may thus provide a useful tool to investigate the molecular mechanism of these drugs.

Anesthetics↗

Schizophrenia: the role of abnormal essential fatty acid and prostaglandin metabolism.

There are two series of essential fatty acids (EFAs), the n6 series starting with linoleic acid and the n3 series starting with alpha-linolenic acid. Members of both series are important in brain structure and can act as precursors for prostaglandin formation. Normally the desaturase enzymes which metabolize EFAs have a higher affinity for the n3 series. It is proposed that in schizophrenia mutant desaturases are present which prefer the n6 series. This change would account for the low levels of linoleic acid, dihomogammalinolenic acid and 1 series prostaglandins which have been reported in schizophrenia. It would also explain the high levels of arachidonic and alpha-linolenic acids and the recently described therapeutic response to alpha-linolenic acid. The abnormal pattern in n6 series EFAs in schizophrenics can almost exactly be imitated in rats by depriving them of n3 EFAs. This is the nearest experimental equivalent to an inability to metabolize EFAs because of an enzyme defect. Heterozygotes carrying such a mutant gene would have an advantage over either form of homozygote since they would be better able to cope with variations in dietary intake of n3 and n6 EFAs.

Animals↗

Prostaglandin E2 production in submandibular salivary glands of rats in essential fatty acid deficiency.

Three groups of rats were fed an essential fatty acid (EFA)-deficient diet (EFAD), marginally EFA-deficient diet (MEFAD) or a control diet. Arachidonic acid levels in total phospholipids and the ex-vivo production of prostaglandin E2 (PGE2) in the presence of calcium ionophore were measured at 5 and 9 weeks in the submandibular salivary glands (SMSG). The arachidonic acid levels were significantly different among the 3 groups of rats fed the respective diets for 9 weeks. Ex-vivo PGE2 production was significantly decreased in the EFAD group but not in the MEFAD group as compared to the control group. The changes in fatty acid composition, arachidonic acid levels and ex-vivo production of PGE2 were reversed after 5 weeks of feeding the control diet to the EFAD or the MEFAD rats. Since arachidonic acid and PGE2 are involved in signal transduction pathways in the SMSG, an EFA deficiency is likely to modify these pathways.

Animals↗

Effect of essential fatty acids on natural cytotoxicity in patients with colorectal cancer.

Essential fatty acids (EFAs), have been shown to modulate lymphocyte reactivity and destroy various tumour cells in vitro. Natural cytotoxicity, mediated by NK and LAK cells, is believed to play an important anti-cancer role in vivo. The effect of EFAs, given orally as dietary supplementation, on NK and LAK cell cytotoxic activity in patients with localized (n = 10) and advanced (n = 20) colorectal cancer has been studied, using in-vitro 51Cr release cytotoxicity assays with K562 (NK) and DAUDI (LAK) cells. The activity of effector cells was expressed as lytic units. NK cell activity showed no significant change following 15 days ingestion of EFAs in the group with localized cancer, but was significantly reduced in the group with advanced disease and continued to decline, reaching minimal levels following 6 months supplementation (P = 0.017). LAK cell activity showed no overall alteration after 15 days ingestion of EFAs in patients with localized cancer, but in the group with advanced disease, the reduction in the activity occurred at day 15 and steadily declined on prolonged intake, reaching significant minimal levels after 6 months of supplementation (P = 0.05). Cell surface marker analysis (FACS-CD MABs) revealed reduced absolute numbers of CD16+, CD56+ and CD57+ lymphocytes (P < 0.05) in the patients with advanced colorectal cancer. More importantly, the cytotoxicity of NK and LAK cells returned to the pre-supplementation values, 3 months after cessation of EFA intake. Furthermore, there was no alteration in the cytotoxic activity of NK and LAK cells in the control group (advanced colorectal cancer without EFA supplementation) during the 6 months period of evaluation. These results suggest that prolonged EFA supplementation, in the doses used in this study, may have detrimental effects on natural anti-cancer cytotoxic mechanisms in patients with malignant disease.

Aged↗

Essential fatty acids in the nutrition of severely neurologically disabled children.

Essential fatty acids (EFA) are important for the normal development and functioning of the brain, retina and immune competent cells. Severely neurologically handicapped children often have feeding difficulties, and the composition of the diet may be critical with respect to an optimal nutrient content. The aim of the present investigation was to evaluate if the dietary intakes and serum phospholipid concentrations of EFA were adequate in a group of severely neurologically impaired children in an institution. To achieve this, a prospective study was done. The investigation showed low dietary intakes of both n-6 fatty acids (FA) and n-3 FA. The serum concentrations of total n-6 FA, linoleic acid and 22:6n-3 (docosahexaenoic acid) as proportions of the total serum phospholipid FA concentration were initially low. The serum concentrations of 20:3n-9 and 22:5n-6 cholesterol, triacylglycerol, total saturated FA, total monounsaturated FA and apolipoproteins A-I and B were high compared with levels in a reference group of healthy children. Following supplementation with fish oil and soyabean oil, the serum lipid profile approached normal. We conclude that the study children had suboptimal intakes of EFA and that elevated serum concentrations of 20:3n-9 and 22:5n6 were useful serological markers of suboptimal EFA status. Recommended dietary allowances for EFA given as a percentage of energy underestimate EFA requirements in children with a low energy intake. Severely disabled children with feeding difficulties should probably be monitored with serum phospholipid FA measurements or calculation of dietary absolute intakes of EFA.

Adolescent↗

Fat intake of women during normal pregnancy: relationship with maternal and neonatal essential fatty acid status.

OBJECTIVE: To study the relationships between the essential fatty acid (EFA) composition of maternal diet, maternal EFA status and the EFA status of healthy newborn infants. METHODS: A prospective longitudinal study was performed in which 176 pregnant women completed a food frequency questionnaire (FFQ) before 13, at 22, and at 32 weeks of gestation, so that changes in nutrient intake throughout pregnancy could be recorded. Around 22 weeks, a dietary history was performed and a maternal blood sample was collected. Immediately after delivery, a blood sample from the umbilical vein and a piece of the umbilical cord were collected. Fatty acid compositions were determined for phospholipids (PLs) isolated from maternal and umbilical plasma and from umbilical vein and artery vessel walls. RESULTS: No significant differences in the mean daily intake of total fat, saturated fat, mono-unsaturated fat, polyunsaturated fat and linoleic acid (18:2(n-6), LA) were observed between the three trimesters. Maternal LA intake was positively associated with LA levels in maternal and umbilical plasma and negatively associated with 20:3(n-9), 18:3(n-3), 20:4(n-3) and 22:5(n-3) levels in maternal plasma, with 20:5(n-3) levels in umbilical plasma and with 22:6(n-3) levels in umbilical vein vessel walls. Significant positive correlations for almost all (n-6) and (n-3) fatty acids were observed between maternal and umbilical plasma levels. CONCLUSIONS: The maternal dietary fat composition appears to be consistent during pregnancy. A high maternal LA intake may have a lowering effect on the maternal as well as on the neonatal (n-3) fatty acid status. Finally, neonatal EFA status is strongly related to maternal EFA status.

Adult↗

Dependence of human milk essential fatty acids on adipose stores during lactation.

The relationships between essential fatty acid (EFA) composition of colostrum, mature milk, and white adipose tissue (WAT) were examined on days 5 and 30 postpartum in 24 healthy French mothers. Fatty acid composition was assessed by capillary gas chromatography. In WAT, the proportion of individual polyunsaturated fatty acids (PUFAs) did not change during lactation and was greater (18:2n-6) or lower (18:3n-3, long-chain PUFAs) than values found in colostrum or mature milk (P < 0.04). The 18:2n-6 content and the ratio of 18:3n-3 to 18:2n-6 correlated between WAT and colostrum (r = 0.52 and r = 0.57, respectively) or mature milk (r = 0.64 and r = 0.65, respectively). These relationships agree with an expected qualitative effect of WAT fatty acid composition on interindividual variability of milk parent EFA content. The decrease in the long-chain PUFA content observed from colostrum to mature milk and the concomitant occurrence of a precursor-product relationship between the linoleate and its long-chain PUFA are consistent with the mobilization of a preformed long-chain PUFA pool during early lactation.

Adipose Tissue↗

Maternal and infant essential fatty acid status in Havana, Cuba.

BACKGROUND: Adequate intake of essential fatty acids (EFAs) is required for optimal development of the central nervous system and visual acuity in infants. Little information exists regarding the EFA status of vulnerable populations living in Southern regions. OBJECTIVE: We examined the adequacy of EFA status in Cuban breast-feeding mothers and their infants. DESIGN: Blood and breast-milk samples were obtained from a cross-sectional sample of mothers and term infants in Havana at 2 mo postpartum. We determined the fatty acid profiles of total lipids in breast milk, plasma, and erythrocytes and assessed infant visual acuity by using Teller acuity cards. RESULTS: Of the 56 mothers and infants examined, none showed biochemical signs of poor EFA status. Compared with values reported in the literature, mothers had an adequate EFA profile in their breast milk, plasma, and erythrocytes. The docosahexaenoic acid (DHA) concentration in breast milk was 0.43 +/- 0.26% of total fatty acids. It appeared that these breast-fed infants had an adequate dietary supply of DHA, as reflected by the mean plasma and erythrocyte DHA concentrations (2.82 +/- 0.84% and 7.41 +/- 1.16% of total fatty acids, respectively). Infant visual acuity testing showed a mean of 2.00 +/- 0.68 cycles/degree, which is within the normal range of mean binocular acuities for 2-mo-old term infants. The data did not show any relation between EFA concentrations and visual acuity. CONCLUSION: The results suggest that n-3 fatty acid deficiency and potential related deficits in early visual neural development are rare, if they exist at all, in breast-feeding women and their infants in Havana.

Adult↗

Structural and biochemical effects of essential fatty acid deficiency on peripheral nerve.

The effect of postweaning essential fatty acid (EFA) deficiency on the peripheral nerve was studied in groups of rats. At 325 days, the characteristic biochemical changes of EFA deficiency were present in isolated peripheral myelin, although to a lesser degree than reported in non-neural tissues. There was no significant difference between control and deficient groups in number or size distributions of myelinated fibers (MFs) in muscle and sensory nerves, in the incidence of teased fiber abnormalities, in rates of axonal transport of dopamine-beta-hydroxylase and acetylcholinesterase, or in conduction velocity and compound action potentials of peripheral nerve in vivo or in vitro. Four weeks after a standard sciatic crush injury, the median MF diameter in regenerated peroneal nerves was significantly smaller in EFA-deficient rats than in control rats, but this difference was no longer significant at 18 weeks. At 18 weeks, EFA-deficient and control regenerated nerves showed similar myelin periodicity and relationship of axonal area to number of myelin lamellae. We conclude that acquired EFA deficiency in the rat leads to biochemically abnormal peripheral myelin, but that this state is unaccompanied by clinical, physiological, or morphological evidence of neuropathy.

Acetylcholinesterase↗