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PubMed1980

Effect of chronic ingestion of DDT on physiological and biochemical aspects of essential fatty acid deficiency.

Male weanling rats were fed semipurified diets with and without essential fatty acid (EFA) and DDT (150 ppm) for 14 weeks to determine the effects of the pesticide on physiological and biochemical aspects of EFA deficiency (EFAD). DDT did not affect EFAD-induced reduction in growth rate of final body weight, nor did the pesticide affect EFAD-induced changes in feed efficiency or skin dermatitis. The pesticide did increase liver/body mass ratios, but did not interact with EFAD, which also increased this ratio. The pesticide produced complex changes in total fatty acid composition of liver and tail skin; liver levels of 18:0, 18:2 and 20:3 omega 9 were increased, whereas levels of 12:0, 14:0 and 16:0 were decreased. In both tissues, DDT interacted with EFA to increase 18:2 levels. DDT did not change the total fatty acid 20:3 omega 9/20:4 omega 6 ratio in either tissue. In this study, although DDT did not exacerbate the physiological aspects of EFAD, DDT-induced changes in fatty acid composition of liver and tail skin indicated that 150 ppm DDT in the diets did alter lipid metabolism of the rats in an unexplained manner.

Animals↗
PubMed1987

Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent, and impulsive offenders.

Plasma phospholipid essential fatty acids and some of their main metabolites, prostaglandins, were measured among habitually violent and impulsive male offenders, who all had alcohol abuse problems, and nonviolent control persons. Linoleic acid (18:2n-6), the precursor of the n-6 fatty acids, was below normal in intermittent explosive disorder, but the dihomogammalinolenic acid (DGLA) (20:3n-6) and some subsequent n-6 acids were at the same time elevated among all offenders. Also, a monounsaturate, oleic acid (18:1n-9) was elevated. The high DGLA correlated with low cholesterol level in intermittent explosive disorder. The arachidonic acid metabolites PGE2 and TxB2 were elevated in violent antisocial personality. The PGE1/DGLA ratio was low in intermittent explosive disorder. The number of registered violent crimes and violent suicidal attempts correlated with high phospholipid DGLA values. The possibility that the high phospholipid DGLA is connected with low free DGLA pool, and therefore low PGE1 formation, among these offenders is discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1994

Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome.

Abnormalities of Essential Fatty Acid (EFA) incorporation into phospholipid are found in chronic diseases. More recently changes in circulating EFA metabolites (EFAM) together with EFAM hypo-responsiveness of immune cells and EFAM production from cells have been found associated with disease. We hypothesize that changes in ratio of EFAMs are the normal physiological responses to stressors, but when stressors are excessive or prolonged, EFAM systems may become unpredictably hypo-responsive owing to factors such as receptor down regulation and substrate depletion. In time, many homeostatic system become deranged and held in that state by minor stressors. Literature review of chronic fatigue syndrome (CFS) shows hyper and hypo-responsiveness in immune function, several Hypothalamo-Pituitary (HP) axes and sympathetic nervous system, all relatable to dysfunctional changes in EFA metabolism. For the first time, we explain chronic immune system activation and hypo-responsive immune function in CFS; through EFAMs. Dietary EFA modulation (DEFA) can alter ratios of both membrane EFAs and produced EFAMs, and if maintained can restore hypo-responsive function. We discuss dietary strategies and relevance in CFS, and a case series of CFS patients applying DEFA with other titrated published managements which saw 90% gaining improvement within 3 months and more than 2/3 fit for full time duties. This hypothesis and DEFA may have relevance in other chronic conditions.

Chronic Disease↗
PubMed2005

Essential fatty acids and the brain: from infancy to aging.

The major effects of essential fatty acids (EFA) on brain structure and functions are reviewed. EFA determine the fluidity of neuronal membrane and control the physiological functions of the brain. EFA is also involved in synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Since they must be supplied from the diet, a decreased bioavailability is bound to induce major disturbances. While the brain needs a continuous supply during the life span, there are two particularly sensitive periods-infancy and aging. EFA deficiency during infancy delays brain development, and in aging will accelerate deterioration of brain functions. In discussing the role of EFA two issues must be considered-the blood-brain barrier, which determines the bioavailability, and the myelination process, which determines the efficiency of brain and retinal functions.

Aging↗
PubMed2000

Effects of protein-energy malnutrition and human immunodeficiency virus-1 infection on essential fatty acid metabolism in children.

This report summarizes data on the availability of essential fatty acids (EFAs) and their long-chain polyunsaturated fatty acid (LCPUFA) metabolites in protein-energy malnutrition (PEM), in human immunodeficiency virus-1 (HIV-1) infection for which less information is available, and the combination of both PEM and HIV-1. The contribution of different EFAs and LCPUFAs to the fatty-acid composition of plasma and erythrocyte membrane lipids was found to be reduced in children with PEM in comparison with well-nourished children. In addition to limited dietary EFA supply, reduced bioconversion of EFAs to their respective LCPUFA metabolites and/or peroxidative degradation of LCPUFAs may contribute to the reduction of LCPUFA status in malnourished children. Restoration of normal energy, protein, and EFA intakes does not appear to readily correct abnormalities of plasma and erythrocyte membrane LCPUFA values. Enhanced dietary supply of LCPUFAs and/or improved supply of antioxidant vitamins may represent novel therapeutic modalities in severe PEM. With and without PEM, HIV infection was related to altered availability of various EFAs and LCPUFAs in HIV-seropositive children. The plasma total lipid fatty-acid profiles seen in well-nourished children with HIV infection were compatible with an HIV infection-related enhancement of the metabolic activity of the conversion of EFAs to their respective LCPUFA metabolites. However, the plasma phospholipid EFA and LCPUFA profiles seen in severely malnourished children with HIV infection more closely resembled those seen in children with PEM but without HIV infection than in those in children with HIV infection but no PEM. Metabolic studies using stable isotope-labeled fatty acids may contribute to better understanding of the HIV-related changes in EFA metabolism and clearly are needed before therapeutic conclusions can be drawn.

Acquired Immunodeficiency Syndrome↗
PubMed1966

The proportions of different lecithins in the livers of rats deficient in essential fatty acids.

1. Lecithin was prepared from the livers of rats deficient in essential fatty acids and analysed by means of countercurrent distribution. Thin-layer chromatography showed that only lecithin was present. 2. The distributions of phosphorus and the fatty acids at the 3 and 2 positions were determined. 3. It has been shown that 26% of the fatty acids in the 3 position were unsaturated and that most of the Delta(5,8,11)-eicosatrienoic acid and the arachidonic acids occur as the stearoyl or oleoyl lecithins.

Animals↗
PubMed1979

Effect of pre- and postnatal essential fatty acid deficiency on brain development and myelination.

Pregnant mice were fed an essential fatty acid (EFA) deficient diet from day 1 of gestation. Several biochemical parameters of postnatal brain growth and myelination were measured on their progeny and compared with controls fed a normal diet containing 4% corn oil or a commercial breeder diet. Measurements of brain DNA, RNA and protein content of the EFA deficient mice suggested a retardation of brain growth and development of about 1 week compared to controls, with the most striking differences noted at ages below 15 days. DNA content of both control and experimental mice became comparable at 20 to 22 days but brain protein and RNA content remained lower in deficient mice at all ages studied. The levels of several myelin specific constituents were also measured in experimental and control brains. The brain galactolipid content was severely depressed at levels 21% of controls at 40 days of age. Proteolipid protein was also significantly reduced (23% of controls at 40 days of age). In contrast, the activity of the myelin marker enzyme, 2',3'-cyclic nucleotide-3'-phosphodiesterase, appeared to be totally unaffected by EFA deficiency. The results indicate that pre-and postnatal EFA deficiency results in a retardation of brain development and a profound reduction of some but not all myelin specific components.

Aging↗
PubMed1990

Essential fatty acid deficiency mimicking porphyria cutanea tarda in a patient with chronic cholestasis.

Essential fatty acid deficiency was documented in a 3-year-old boy with chronic cholestasis secondary to paucity of intrahepatic bile ducts (Alagille's syndrome). Dietary management had consisted almost exclusively of a proprietary formula with over 80% of the fat as medium-chain triglycerides. The bullous lesions involved mostly sun-exposed areas and were diagnosed initially as being compatible with acquired porphyria cutanea tarda. Improvement followed correction of the fatty acid abnormalities with a polyunsaturated fat supplement administered orally. We postulate that the association of fatty acid deficiency and abnormal vitamin E status contributed to skin damage, possibly involving photosensitizing compounds poorly cleared by the markedly cholestatic liver.

Child, Preschool↗
PubMed1977

Essential fatty acid deficient hairless mouse: the effects of topical agents on the epidermis.

Essential fatty acid deficient (EFA deficient) hairless mice were used to test the ability of topical agents to reduce the high epidermal DNA synthesis and acanthosis present in EFA deficiency. An established therapeutic agent known to be effective in psoriasis (betamethasone 17-valerate) significantly reduced the epidermal DNA synthesis, mitotic count and epidermal cell thickness. Linoleic acid reduced DNA synthesis and returned epidermal histology towards that of normal skin. Prostaglandin E2 analogue (15 (S)-15-methyl PGE2 methyl ester) reduced epidermal DNA synthesis both in treated and distant skin sites. Prostaglandin E2 was less effective than the analogue but slightly reduced epidermal DNA synthesis and thickness. Prostaglandin F2alpha had no obvious effect on the epidermis. Chlorambucil reduced epidermal DNA synthesis and thickness. Vitamin A acid increased DNA synthesis and epidermal cell thickness but reduced the hyperkeratosis of EFA deficiency. A rapid epidermal cell transit was found in EFA deficient mice, approximately three times faster than in normal mouse epidermis.

Administration, Topical↗
PubMed2004

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis.

A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF phenotype. To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects LCPUFA synthesis, we quantified EFA metabolism in cftr-/-CAM and cftr+/+CAM mice. Effects of intestinal phenotype, diet, age, and genetic background on EFA status were evaluated in cftr-/-CAM mice, DeltaF508/DeltaF508 mice, and littermate controls. EFA metabolism was measured by 13C stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr-/-CAM mice, DeltaF508/DeltaF508 mice, littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After enteral administration of [13C]EFA, arachidonic acid (AA) and docosahexaenoic acid (DHA) were equally 13C-enriched in cftr-/-CAM and cftr+/+CAM mice, indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr-/-CAM and DeltaF508/DeltaF508 mice and controls. LCPUFA levels were also equal in liquid diet-weaned cftr-/-CAM mice and littermate controls, but consistently higher than in age- and diet-matched C57Bl/6 wild types. We conclude that cftr-/-CAM mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably linked to the CF genotype. EFA status in murine CF models is strongly determined by genetic background.

Animals↗
PubMed2002

Maternal dietary intake of essential fatty acids affects adipose tissue growth and leptin mRNA expression in suckling rat pups.

We have previously shown that maternal intake of essential fatty acids during late gestation and lactation affects the level of serum leptin in pups. The aim of the present study was to investigate the effect of dietary essential fatty acids on leptin content in the milk of rat dams and leptin expression in white adipose tissue of pups during the suckling period. During late gestation and throughout lactation, rats were fed a control or an essential fatty acid-deficient (EFAD) diet. Milk of the EFAD dams contained more saturated and less polyunsaturated fatty acids compared with the control dams. Milk leptin levels were higher in the EFAD dams than in the control dams at 3 wk of lactation. The weight of inguinal white adipose tissue depots and the serum leptin levels of the EFAD pups were significantly lower than in the control pups during the whole suckling period. In addition, semiquantitative reverse transcriptase-PCR analysis of leptin mRNA levels in inguinal white adipose tissue showed a reduction in the EFAD pups compared with the control pups at 3 wk of age. We conclude that maternal dietary essential fatty acid intake affects serum leptin levels in pups by regulating both the amount of adipose tissue and the leptin mRNA expression.

Adipose Tissue↗
PubMed2006

Do essential fatty acids have a role in the treatment of depression?

BACKGROUND: Complementary and alternative medicine (CAM) therapies are used more than conventional therapies by people with self-defined anxiety and depression. Preliminary evidence supports a hypothesis that low plasma concentration of essential fatty acids is associated with depression. Reported here is the result of a systematic review examining the therapeutic efficacy of essential fatty acids for depression. METHODS: Data sources included Medline, Psychinfo, AMED (Allied and Complementary Medicine), and Cochrane Controlled Trials Register databases searched from inception through September 2001. English language randomized controlled trials, controlled clinical trials, intervention studies, case control studies, reviews, and case reports of humans were selected, without limits for demographics or co-morbidities. Two abstractors independently evaluated each study, then reconciled findings. When possible, between group treatment effect size was noted or calculated. RESULTS: Six articles met inclusion criteria: one RCT, two reviews, and three case control trials. A common outcome measure among the case control trials allowed for direct comparison of effect sizes. CONCLUSIONS: The evidence implies promise of a treatment effect of omega-3 fatty acids for depression in adults; although a statement of definitive clinical efficacy is premature. Further study of essential fatty acids as independent and adjuvant therapy for adult depression is indicated, including more sophisticated investigation of dose-response in particular populations.

Boron Compounds↗
PubMed1997

Does chronic essential fatty acid deficiency constitute a pro-tumorigenic condition?

Many experimental, clinical and epidemiological data indicate that n-3 and n-6 essential fatty acids are therapeutic nutrients which may delay the development as well as improve the course of cancer. The present hypothesis correlates well with these data and it is proposed that chronic essential fatty acid deficiency, when coexisting with chronic hyperproliferative states (hyperplasias) and de-differentiation (dysplasias) both acting synergistically, may constitute a pro-tumorigenic situation. Evidence showing that, indeed, these hyperproliferative states are consistently reported in essential fatty acid deficiency in many species, including humans, in malpighian layers of skin and the upper alimentary and urinary tracts, among others, is discussed.

Animals↗
PubMed2004

Oral essential fatty acid supplementation in atopic dermatitis-a meta-analysis of placebo-controlled trials.

BACKGROUND: Essential fatty acids are components of cell membranes and precursors of immunomodulating factors that may play a role in the inflammatory and immunological pathogenesis of atopic dermatitis. Trials of supplementation with essential fatty acids (EFA) to alleviate atopic dermatitis (AD) have given inconsistent results. OBJECTIVES: To summarize and quantify the results of placebo-controlled trials with EFA for AD. DESIGN: Publications of clinical trials were searched in a systematic way and the study characteristics assessed independently by three assessors. Trials were selected for inclusion in the meta-analysis when they had included a placebo group and when the outcome measure included the severity of AD. The pooled effect sizes of improvement of the overall severity of AD were calculated by random effects meta-analysis. The dependence of the results on study characteristics was studied using meta-regression analysis. RESULTS: We identified 34 publications of controlled trials in AD up to April 2002. Nineteen trials of gamma-linolenic acid (GLA) and five trials of fish oil matched our inclusion criterion of placebo-controlled trial. The effect size of GLA supplementation on the improvement of the overall severity of AD could be calculated from 11 of these trials. The pooled effect size was 0.15 [95% confidence limits (CL) - 0.02, 0.32]. The effect size of fish oil supplementation, calculated from three trials was - 0.01 (95% CL - 0.37, 0.30). For component subscales such as itch, scaling and lichenification, EFA supplementation showed no benefit. The study characteristics showed no detectable influence on the overall result. CONCLUSIONS: Supplementation with EFA has no clinically relevant effect on the severity of AD.

Administration, Oral↗
PubMed1993

[The modulation of the function of the immunocompetent system and of nonspecific body resistance in rats with different ratios of essential fatty acids in the diet].

The influence of dietary essential fatty acids on the immune functions and nonspecific resistance of male Wistar rats weighing 135.0 +/- 3.2 g was investigated after 3 months feeding. Rats were fed isocaloric purified diets containing 24% of fat (combinations of lard, sunflower oil and fish oil, eiconol, this providing the ratios of omega 6/omega 3 fatty acids equal to 1.1; 2.1; 6.1; and 49.0. An increase of immune responsiveness and nonspecific resistance in the groups fed diets with the minimal ratios of omega 6/omega 3 fatty acids as compared to that in rats fed a diet with ratio 49.0 was noted. Fatty acid analysis of peripheral lymphoid organs tissue lipids showed an increase in percentage of eicosenic omega 3 fatty acids in rats fed diets with increased content of polyunsaturated fatty acids omega 3.

Animals↗
PubMed1976

Effect of essential fatty acid deficiency on the lipid composition of the Yoshida ascites hepatoma (AH 130) and of the liver and blood plasma from host and normal rats.

In order to study the response of a poorly differentiated tumor to nutritional manipulation, the Yoshida ascites hepatoma (AH 130) was grown in rats fed an essential fatty acid (EFA)-deficient diet and in rats fed a control diet. Hepatomas, livers, and blood plasma from host rats and normal rats were studied as to the effects of EFA deficiency on the lipid composition. Normal rats fed an EFA-deficient diet showed an increased concentration of triglycerides and cholesteryl esters in the liver and a reduced level of total phospholipids in plasma. Host rats fed the EFA-deficient diet showed a lower concentration of triglycerides in the liver when compared with the host rats fed a control diet. In addition, EFA-deficient host rats had reduced levels of plasma free fatty acids and triglycerides. These latter were markedly high in host rats under normal dietetic conditions. As compared to the livers of either host rats or normal rats fed the control diet, the Yoshida hepatoma cells had a lower content of total phospholipids and free fatty acids as well as a higher level of free cholesterol; they also showed a typical fatty acid pattern in their phospholipids. The main characteristics of this pattern were a high content of oleic and palmitoleic acids and a low level of C20 and C22 polyunsaturated fatty acids. Exposure of Yoshida hepatoma cells to an EFA-deficient environment resulted in a decrease in the concentration of total phospholipids and free fatty acids and in changes in the fatty acid composition similar to those observed in the livers of normal and host rats. These changes suggest that, under the experimental conditions used, the Yoshida hepatoma cells are responsive to EFA deficiency.

Animals↗
PubMed1995

Effect of essential fatty acid deficiency on forskolin binding sites, adenylate cyclase and cyclic AMP-dependent protein kinase activity, the levels of G proteins and ventricular function in rat heart.

Three groups of rats were fed semi-purified diets. Diet I was deficient in essential fatty acids (EFAD), diet II was marginally deficient in essential fatty acids (MEFAD), and diet III contained adequate levels of essential fatty acids (control). After 9 weeks, some rats within each group were killed and cardiac membranes were prepared. Adenylate cyclase activity, [3H]forskolin binding sites, the levels of G proteins (Gi and Gs) and fatty acid composition of the membrane phospholipids were measured. Typical changes of EFA deficiency were observed in fatty acid composition of the membrane phospholipids. Adenylate cyclase activity was significantly lower in membranes of EFA-deficient rats than those of the controls. The MEFAD group gave intermediate values. Similar results were obtained with forskolin-stimulated activity with different concentrations of forskolin. Concentrations of the forskolin binding sites were also lower in the EFAD, but not in the MEFAD rats compared with the controls. There was no significant difference in forskolin binding affinities among the three groups. The decrease in adenylate cyclase activity in EFA-deficient rat heart was partially restored by feeding the control diet for 5 weeks to the EFAD or the MEFAD rats. The levels of Gi alpha and Gs alpha were not significantly different in cardiac membranes of rats fed the EFAD or the MEFAD diets from those of the control group. Lower adenylate cyclase activity in hearts of EFAD rats was also reflected in correspondingly lower activity of cAMP-dependent protein kinase. The results suggest an impairment of the cellular signalling pathway for the production of cAMP in rat heart during EFA deficiency. The beta-adrenergic response of isolated heart preparations obtained from rats fed the three diets was, however, not significantly altered.

Adenylyl Cyclases↗
PubMed1978

Essential fatty acid deficiency in total parenteral nutrition: time course of development and suggestions for therapy.

Thirty-two patients receiving total intravenous nutrition were studied prospectively for biochemical and clinical signs of essential fatty acid deficiency. Individual constituents of the phospholipid fraction were examined consecutively and the triene:tetraene ratio was determined. All patients nourished parenterally for 4 weeks had triene:tetraene ratios of greater than 0.4. Levels of eicosatrienoic and linoleic acid were abnormal after 1 week, and arachidonic acid levels became abnormal after 2 weeks of fat-free parenteral nutrition. Skin lesions suggestive of essential fatty acid deficiency developed in two patients studied. Biochemical abnormalities responded rapidly to the intravenous administration of Intralipid.

8,11,14-Eicosatrienoic Acid↗