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The effect of fat emulsion (Intralipid) on essential fatty acid deficiency in infants receiving intravenous alimentation.

Thirteen infants who received IVA in four different ways were studied. The serum fatty acid composition of the infants who received fat-free IVA showed EFA deficiency within 1 wk. This deficiency was cured by administering fat emulsion which accounted for 4% of the total caloric content of the infusate. Fat emulsion which accounted for 2% of the total calories neither improved nor prevented EFA deficiency. This means that intravenous fat emulsion, Intralipid, which accounted for 2% of the total calories as linoleic acid, still satisfies the essential fatty acid requirement.

Child, Preschool↗

Problems with essential fatty acids: time for a new paradigm?

The term 'essential fatty acid' is ambiguous and inappropriately inclusive or exclusive of many polyunsaturated fatty acids. When applied most rigidly to linoleate and alpha-linolenate, this term excludes the now well accepted but conditional dietary need for two long chain polyunsaturates (arachidonate and docosahexaenoate) during infancy. In addition, because of the concomitant absence of dietary alpha-linolenate, essential fatty acid deficiency is a seriously flawed model that has probably led to significantly overestimating linoleate requirements. Linoleate and alpha-linolenate are more rapidly beta-oxidized and less easily replaced in tissue lipids than the common 'non-essential' fatty acids (palmitate, stearate, oleate). Carbon from linoleate and alpha-linolenate is recycled into palmitate and cholesterol in amounts frequently exceeding that used to make long chain polyunsaturates. These observations represent several problems with the concept of 'essential fatty acid', a term that connotes a more protected and important fatty acid than those which can be made endogenously. The metabolism of essential and non-essential fatty acids is clearly much more interconnected than previously understood. Replacing the term 'essential fatty acid' by existing but less biased terminology, i.e. polyunsaturates, omega3 or omega6 polyunsaturates, or naming the individual fatty acid(s) in question, would improve clarity and would potentially promote broader exploration of the functional and health attributes of polyunsaturated fatty acids.

Animals↗

Effect of methyl linoleate administration on phospholipid fatty acid composition and osmotic fragility of erythrocytes in essential fatty acid deficient rats.

Methyl linoleate (18:2 omega 6) was administered to rats deficient in essential fatty acids (EFA) and the effects on osmotic fragility and lipid composition of their red blood cells were studied. Even if they remained deficient in omega-3 fatty acids, the fragile red cells of EFA-deficient rats were remarkably strengthened by the linoleate treatment. It is concluded that omega-3 fatty acids are not essential for the maintenance of cell membrane integrity in rats. Since the cholesterol/phospholipid ratio in red cells was lower in untreated than in treated rats, it is suggested that this factor might be responsible in part for the higher fragility of red cells in EFA-deficient rats. Despite the prolonged administration of overload quantities of methyl linoleate, the proportion of 18:2 omega 6 in the red blood cell phospholipids of treated rats was actually lower than that in rats fed a regular stock diet, while the relative content of other omega-6 fatty acids (20:4 omega 6, 22:4 omega 6, and 22:5 omega 6) increased. These results indicate that the metabolic processes of omega-6 fatty acids in treated rats were stimulated, probably as a result of the lack of competition from omega-3 fatty acids for the same enzyme systems.

Animals↗

Effect of dietary protected lipids on the essential fatty acid status of the newborn kid.

Pregnant goats were fed either a control diet or one in which part of the concentrate ration was replaced, for either the last 2 mo or the last month of gestation, with a polyunsaturated fatty acid supplement protected from biohydrogenation in the rumen. On the day of parturition, goats fed a supplemented diet, during either 1 or 2 mo before parturition, exhibited markedly higher concentrations of linoleic acid in the major plasma lipid fractions, i.e., phospholipids, cholesteryl esters, triacylglycerols and nonesterified fatty acids, than did goats not fed the supplement. At birth, the four main lipid fractions in the plasma of the kids from goats fed the supplemented diet, during either 1 or 2 mo before parturition, exhibited considerably higher proportions of linoleic and arachidonic acids and lower proportions of eicosatrienoic acid than did those of newborn kids from unsupplemented mothers. These findings show appreciable transfer of lipids across the placenta and demonstrate that the low essential fatty acids status of kids at birth can be raised by this particular manipulation of the maternal diet.

Animals↗

Development of an in vitro model of essential fatty acid deficiency in fish cells.

Levels of eicosapentaenoic acid (EPA; 20:5, n-3) greatly exceed those of arachidonic acid (AA; 20:4, n-6) in the tissue phospholipids of most fish species. Despite this, it is 20:4, n-6-derived eicosanoids that are produced predominantly in fish cells. The development of an essential fatty acid (EFA)-deficient fish cell line would greatly assist the study of this selectivity and so several fish cell lines were cultured in EFA-deficient (EFAD) media. All n-3 and n-6 polyunsaturated fatty acids (PUFA) and total PUFA were considerably reduced in all lines, except turbot fin (TF) in which total n-9 PUFA doubled from 13.8% to 27.5% of total fatty acids. In the topminnow hepatocarcinoma cell line (PLHC-1), there was almost complete depletion of both n-3 and n-6 PUFA and in TF cells, no n-3 PUFA were detected. In the carp epithelial papilloma cell line (EPC), both n-6 and n-3 PUFA were reduced by approximately 70%. The reduced PUFA in cells cultured in EFAD media was compensated to a large extent in most cell lines by significantly increased percentages of monounsaturated fatty acids, particularly 18:1, n-9. Total n-9 PUFA were significantly increased in all cell lines by culture in EFAD media, with 20:2, n-9 significantly increased in all cell lines. There were relatively small increases, but often significant, in 20:3, n-9 in all cell lines. Of the cell lines investigated, only EPC and PLHC-1 showed proliferation after four passages in EFAD medium, although the growth rates were reduced in comparison with media supplemented with serum, but EPC was the only cell line able to survive and proliferate in long-term culture on EFAD medium. The EFAD-EPC line is a potentially useful model system for the study of the effects of EFA deficiency on cell structure and function and eicosanoid metabolism in fish.

Animals↗

Energy supplements rich in linoleic acid improve body weight and essential fatty acid status of cystic fibrosis patients.

BACKGROUND: Patients with cystic fibrosis who have steatorrhea frequently are underweight and have essential fatty acid (EFA) depletion, which is associated with a poor clinical course. It has been stated that poor EFA status is difficult to correct in patients with cystic fibrosis, and an impaired EFA metabolism with reduced synthesis of long-chain polyunsaturated fatty acids has been proposed. In this study, the effects of an oral energy supplement rich in linoleic acid were investigated in patients with cystic fibrosis who had a body weight below 95% of normal for height. METHODS: Thirty-six patients (16 girls) more than 4 years of age were randomized either to a control group (n = 20, age 13.3 +/- 3.8 years, mean +/- SD) receiving intensive dietary counseling only, or an intervention group (n = 16, age, 10.4 +/- 4.3 years) treated for 3 months with dietary counseling plus 628 +/- 254 mL (= kcal) per day of an energy supplement rich in fat (31% of energy) and linoleic acid (16% of energy). RESULTS: In contrast to the control group, the patients with supplemented diets achieved significant increases of energy intake (2189 +/- 731 kcal/day vs. 2733 +/- 762 kcal/day), weight for height (82.8% +/- 8.6% vs. 84.8% +/- 9.6% of normal), and body fat (5.1 +/- 1.7 kg vs. 5.8 +/- 2.2 kg) as well as the initially low values of plasma phospholipid linoleic acid (11.8% +/- 1.1% vs. 17.6% +/- 1.6% of total phospholipid fatty acids) and its main metabolite arachidonic acid (4.4% +/- 0.4% vs. 5.9% +/- 0.3%). CONCLUSIONS: Patients with cystic fibrosis with low body weight and poor EFA status benefit from EFA-rich energy supplements and can synthesize arachidonic acid from the precursor linoleic acid.

Adolescent↗

Some effects of the essential fatty acids linoleic acid and alpha-linolenic acid and of their metabolites gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and of prostaglandins A1 and E1 on the proliferation of human osteogenic sarcoma cells in culture.

Gamma-linolenic acid has been shown to suppress the rate of proliferation of a number of malignant cell lines in culture. To test the proposal that this was a specific prostaglandin 1- or 2-series effect, 379 batches of MG63 human osteogenic sarcoma cells were seeded in Greiner flasks and cultured in media supplemented with a range of unsaturated fatty acids and prostaglandins. The monounsaturated fatty acid oleic acid enhanced the rate of cancer cell proliferation. The polyunsaturated fatty acids linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as prostaglandins E1 and A1 suppressed the rate of cell proliferation. Total suppression of colony forming and cell proliferation occurred at high levels of polyunsaturated fatty acid supplementation. In addition gamma-linolenic in the form of evening primrose seed oil and vitamin C has been given to 6 patients with histologically diagnosed primary liver cell cancer. Some clinical improvement and reduction in tumor size occurred in 3 cases. One patient has shown remarkable improvement in reduction of liver and tumor size on the CAT scan and reduction of the serum alkaline phosphatase from 2830 to 295 units and gamma-glutamyl transaminase from 274 to 82 units. Thus preliminary clinical results suggest that gamma-linolenic acid may be effective in the management of human cancer patients and further trials should be conducted. However, the cell culture results suggest that although the essential fatty acids suppress proliferation, eicosanoids of all 3 series may be involved. The proliferation suppressive effect of docosahexaenoic acid suggests that other aspects than only eicosanoid activity may also be important in the suppression of cancer cell proliferation.

Alprostadil↗

Supplemental calories improve essential fatty acid deficiency in cystic fibrosis patients.

Fatty acid composition of plasma lipids was analyzed in malnourished cystic fibrosis patients undergoing 6 months of nutritional rehabilitation. There were three males and five females (mean age 15.1 yr); five patients had pancreatic insufficiency. Nutritional rehabilitation in seven of eight patients was accomplished by nocturnal nasogastric infusion of a high-carbohydrate semisynthetic diet, in addition to daily meals. One patient received high-energy food supplements as snacks in addition to regular meals. All patients were moderately to severely malnourished on entry to the study and showed significant improvement over the 6 months in (means +/- SE) energy intake (96 +/- 8.0 to 126 +/- 11% recommended daily allowance) and body composition (80 +/- 4 to 90 +/- 4% ideal body weight). Daily intakes of linoleic acid were not significantly different before or during nutritional rehabilitation either as an absolute amount (383 +/- 45 to 557 +/- 124 mg/kg/day) or as a percentage of total calories (4.50 +/- 0.40 to 4.73 +/- 0.14%). In comparison to the controls, the relative percentage of plasma cholesterol ester fatty acids of the CF patients on entry into the study showed a marked decrease of linoleic acid (52.7 +/- 1.0 versus 42.3 +/- 2.7%) with elevated palmitoleic (2.34 +/- 0.2 versus 5.64 +/- 0.7%) and oleic (18.7 +/- 1.0 versus 25.2 +/- 1.4%) acids; a pattern consistent with essential fatty acid deficiency. However, this pattern is not truly characteristic of a pure linoleic acid deficiency as the metabolites of linoleic acid were not decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Normalization of essential-fatty-acid-deficient keratinocytes requires palmitic acid.

Cultured adult human keratinocytes show accelerated growth rates in medium that is essential fatty acid deficient. The cells also show decreased amounts of the essential fatty acids 18:2, 20:3, and 20:4 and contain increased amounts of the monounsaturated fatty acids 16:1 and 18:1. These lower levels of polyunsaturated fatty acids were only partially restored by supplementing the medium with 18:2 and 20:4 fatty acid. The addition of the non-essential fatty acid 16:0 (5 microM), along with the essential fatty acids, resulted in the successful normalization of the major fatty acids in the deficient keratinocytes. Normalized cells showed a constant total fatty acid/mg of protein in the phospholipid fraction, as the total cell fatty acid content per cell increased with augmenting fatty acid supplementation. Supplementation of the medium with 16:0 and essential fatty acids decreased the growth and passage potential of the cells. Use of 18:1 in lieu of 18:2 fatty acid yielded essential-fatty-acid-deficient keratinocyte growth values. Likewise the least supplemented medium (5 microM 18:2 + 5 microM 16:0) also gave the accelerated cell growth rates. This study shows that manipulation of the essential fatty acid levels, if accompanied by 5 microM 16:0 in the growth medium, alters the growth properties of adult human primary keratinocytes.

Adult↗

Monitoring the optimal infusion of intravenous lipids. Detection of essential fatty acid deficiency.

Since increased amounts of the trienoic acid C20:3w9 are produced in patients with essential fatty acid (EFA) deficiency (EFAD) of the linoleic (w6) family, the trienoic (C20:3w9)-to-tetraenoic (C20:4w6) fatty acid ratio (T/T ratio) is used as a biochemical indicator of w6 EFAD. A T/T ratio above 0.02 is suggestive of w6 EFAD. Fatty acid profiles, listing the percent of individual and families of fatty acids, are useful in evaluating the effects of intravenous lipid infusions during treatment. We evaluated the condition of a patient with fat malabsorption treated with a soybean oil-based intravenous lipid solution and found that levels of linoleic acid and its derivatives did not reach reference levels, while linolenic acid and its derivatives quickly exceeded reference levels. A persistently elevated T/T ratio suggested that altered fatty acid metabolism characteristic of linoleic acid deficiency was not corrected by the treatment. Plasma levels of the EFA, ie, linoleic and linolenic acids, cannot be predicted from the lipid treatment or from the patient's clinical course; therefore, periodic measurements of EFA are required to monitor the effects of therapy. To provide the most effective therapy, the amounts and proportions of linoleic and linolenic acids provided in the intravenous infusions should be varied, as indicated by periodic monitoring of the fatty acid profile.

Adult↗

Relationship between essential fatty acid requirements of aquatic animals and the capacity for bioconversion of linolenic acid to highly unsaturated fatty acids.

1. [1-14C]linolenic acid was injected into the rainbow trout, Salmo gairdnerii, ayu, Plecoglossus altivelis, eel, Anguilla japonica, red sea bream, Chrysophrys major, rockfish, Sebastiscus marmoratus, globefish, Fugu rubripes rubripes and prawn, Penaeus japonicus (molting stage D"1-D2), and the bioconversion of linolenic acid (18:3 omega 3) to highly unsaturated fatty acids such as eicosapentaenoic (20:5 omega 3) and docosahexaenoic (22:6 omega 3) acids was investigated. 2. Linolenic acid was converted to 20:5 omega 3 and 22:6 omega 3 intensively in the rainbow trout, moderately in the ayu, eel and prawn, but slightly in the red sea bream, rockfish and globefish. 3. These results were discussed in relation to the essential fatty acid requirements of the aquatic animals.

Animals↗