Biochemical Essential Fatty Acid Deficiency Research Articles

Characterization of Fatty Acid Profiles in Infants With Intestinal Failure-Associated Liver Disease.

The purpose of this study was to characterize fatty acid profiles (FAPs) in parenteral nutrition (PN)-dependent infants with intestinal failure-associated liver disease (IFALD) receiving soybean oil-based lipid emulsion (SO) doses of ∼3 and ∼1 g/kg/d. Prospectively collected data were retrospectively reviewed. Serum FAPs of patients <1 year old who experienced development of IFALD while receiving standard PN with SO were examined before transitioning to a fish oil-based lipid emulsion for IFALD treatment. Time on SO, dose, gestational age, and weight- and length-for-age z scores were also reviewed. Among the 49 patients analyzed, there were no differences in demographics or anthropometrics between patients who received standard SO (SO-S) (n = 14, range of dosage 2.06-3.31 g/kg/d) and reduced SO (SO-R) (n = 35, range of dosage 0.90-1.34 g/kg/d). Patients received SO for a median of 53 days (interquartile range 39, 73) before FAP measurement. Patients who received SO-R had significantly higher Mead acid and lower α-linolenic, eicosapentaenoic, linoleic, stearic, total ω-3, and total ω-6 fatty acid levels than patients who received SO-S (P < .01). Triene:tetraene ratios were higher in patients who received SO-R (P = .0009), and no patients experienced biochemical essential fatty acid deficiency (EFAD). PN-dependent infants with IFALD receiving SO-R have different FAPs than patients receiving SO-S. No patients in either group had biochemical EFAD.

Essential fatty acid deficiency during parenteral soybean oil lipid minimization.

To determine if parenteral lipid minimization in infants results in essential fatty acid (EFA) deficiency. Prospective study of infants >30 days old and >34 weeks postmenstrual age receiving parenteral lipid minimization (<1.5 g kg-1 per day) with either soybean oil or fish oil and >90% of total nutritional intake parenterally in the 14 days before a serum EFA sample. Nonparametric tests were used for statistical analyses with significance at 0.05. Fifteen samples on soybean oil and nine on fish oil were included. Energy and macronutrient intakes and weight gain were similar between groups. Biochemical EFA deficiency occurred in 60% receiving soybean oil but none receiving fish oil (P<0.01). Average daily weight gain was 49% less in EFA deficient infants than EFA sufficient infants (P=0.02). Infants on lipid minimization with parenteral soybean oil, but not fish oil, are at high risk of biochemical EFA deficiency with slower weight gain.

The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice

ObjectiveParenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. Materials/methodsSix groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. ResultsAll groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. ConclusionThese results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation.

The effect of varying ratios of docosahexaenoic acid and arachidonic acid in the prevention and reversal of biochemical essential fatty acid deficiency in a murine model

ObjectiveEssential fatty acids (EFA) are necessary for growth, development, and biological function, and must be acquired through the diet. While linoleic acid (LA) and alpha-linolenic acid (ALA) have been considered the true EFAs, we previously demonstrated that docosahexaenoic acid (DHA) and arachidonic acid (AA) taken together as the sole source of dietary fatty acids can prevent biochemical essential fatty acid deficiency (EFAD). This study evaluates the effect of varying dietary ratios of DHA:AA in the prevention and reversal of biochemical EFAD in a murine model. MethodsUsing a murine model of EFAD, we provided mice with 2.1% of daily caloric intake in varying DHA:AA ratios (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) for 19 days in association with a liquid high-carbohydrate fat-free diet to evaluate the effect on fatty acid profiles. In a second experiment, we evaluated the provision of varying DHA:AA ratios (20:1, 200:1, 100:0) on the reversal of biochemical EFAD. ResultsMice provided with DHA and AA had no evidence of biochemical EFAD, regardless of the ratio (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) administered. Biochemical EFAD was reversed with DHA:AA ratios of 20:1, 200:1, and 100:0 following 3 and 5 weeks of dietary provision, although the 20:1 ratio was most effective in the reversal and stabilization of the triene:tetraene ratio. ConclusionProvision of DHA and AA, at 2.1% of daily caloric intake in varying ratios can prevent biochemical evidence of EFAD and hepatic steatosis over the short-term, with a ratio of 20:1 DHA:AA most effectively reversing EFAD.

Comparison of 5 intravenous lipid emulsions and their effects on hepatic steatosis in a murine model

BackgroundPlant-based intravenous lipid emulsions have been shown to contribute to parenteral nutrition–associated liver disease (PNALD). There is mounting evidence that fish oil–based emulsions may prevent this liver injury. This study compares 5 emulsions with different fat compositions and their effect on hepatic steatosis, one of the first hits in PNALD. MethodsC57BL/6J mice were placed on a fat-free diet and randomized into 5 equal groups. Each group received one of the commercially available intravenous lipid emulsions (Intralipid [Baxter/Fresenius Kabi, Deerfield, Ill], Liposyn II [Hospira Inc, Lake Forest, Ill], ClinOleic [Baxter/Clintec Parenteral SA, Cedex, France], SMOFlipid [Fresenius Kabi, Bad Homburg, Germany], or Omegaven [Fresenius Kabi Deutschland GmbH]) or normal saline. Liver enzymes, degree of steatosis, and fatty acid compositions were analyzed after 19 days. ResultsIntralipid, Liposyn II, ClinOleic, and SMOFlipid groups all demonstrated moderate steatosis with hepatic fat contents of 17.4%, 21.9%, 22.5%, and 12.6%, respectively. Omegaven mice, however, had normal livers. Saline control mice developed biochemical evidence of essential fatty acid deficiency (EFAD). Lipid supplementation with Intralipid, Liposyn II, and Omegaven prevented the onset of biochemical EFAD, whereas administration of ClinOleic and SMOFlipid did not. ConclusionThe fish oil–based lipid emulsion Omegaven prevented hepatic steatosis and EFAD in this murine model. ω-3 fatty acids may be efficacious in preventing PNALD and should be explored in the development of novel lipid emulsions.

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 ω3 and ω6 series. Patients reporting not to take vitamin supplements had low vitamin B 12 and high homocysteine. Homocysteine variance proved best explained by folate in both the total group and male patients, and by vitamins B 12 and B 6 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 ω3/docosahexaenoic acid (DHA) marginality. Four patients exhibited moderate hyperhomocysteinemia with plasma values ranging from 57.5 to 74.8 μmol/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, ω3/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.

Assessment of essential fatty acid and ω3-fatty acid status by measurement of erythrocyte 20:3ω9 (Mead acid), 22:5ω6/20:4ω6 and 22:5ω6/22:6ω3

Background. Early suspicion of essential fatty acid deficiency (EFAD) or ω3-deficiency may rather focus on polyunsaturated fatty acid (PUFA) or long-chain PUFA (LCP) analyses than clinical symptoms. We determined cut-off values for biochemical EFAD, ω3-and ω3/22:6ω3 [docosahexaenoic acid (DHA)]-deficiency by measurement of erythrocyte 20:3ω9 (Mead acid), 22:5ω6/20:4ω6 and 22:5ω6/22:6ω3, respectively. Methods. Cut-off values, based on 97.5 percentiles, derived from an apparently healthy omnivorous group (six Dominica breast-fed newborns, 32 breast-fed and 27 formula+LCP-fed Dutch low-birth-weight infants, 31 Jerusalem infants, 33 Dutch 3.5-year-old infants, 69 omnivorous Dutch adults and seven Dominica mothers) and an apparently healthy group with low dietary LCP intake (81 formula-fed Dutch low-birth-weight infants, 12 Dutch vegans). Cut-off values were evaluated by their application in an EFAD suspected group of 108, mostly malnourished, Pakistani children, three pediatric patients with chronic fat-malabsorption (abetal-ipoproteinemia, congenital jejunal and biliary atresia) and one patient with a peroxisomal β-oxidation disorder. Results. Erythrocyte 20:3ω9, 22:5ω6/20:4ω6 and 22:5ω6/22:6ω3 proved age-dependent up to 0.2 years. Cut-off values for ages above 0.2 years were: 0.46mol% 20:3ω9 for EFAD, 0.068mol/mol 22:5ω6/20:4ω6 for ω3-deficiency, 0.22mol/mol 22:5ω6/22:6ω3 for ω3/DHA-marginality and 0.48mol/mol 22:5ω6/22:6ω3 for ω3/DHA-deficiency. Use of RBC 20:3ω9 and 22:5ω6/20:4ω6 cut-off values identified 20.4% of the Pakistani subjects as EFAD+ω3-deficient, 12.9% as EFAD+ω3-sufficient, 38.9% as EFA-sufficient+ω3-deficient and 27.8% as EFA-sufficient+ω3-sufficient. The patient with the peroxisomal disorder was classified as EFA-sufficient, ω3-sufficient (based on RBC 22:5ω6/20:4ω6) and ω3/DHA-deficient (based on RBC 22:5ω6/22:6ω3). The three other pediatric patients were classified as EFAD, ω3-deficient and ω3/DHA-deficient. Conclusion. Use of the combination of the present cut-off values for EFA, ω3 and ω3/DHA status assessment, as based on 97.5 percentiles, may serve for PUFA supplement intervention until better concepts have emerged.

Effect of essential fatty acid depletion on tissue phospholipid fatty acids in spontaneously hypertensive and normotensive rats.

Weanling male spontaneously hypertensive (SHR) and normotensive (WKY) rats were maintained on a fat-free semisynthetic diet and killed at various intervals. The effects of fat-depletion on the appearance of essential fatty acid (EFA) deficiency symptoms, the progressive changes of major fatty acids in plasma, liver, heart, and kidney phospholipids (PL), and in skin total lipids were compared between these two strains. After five weeks on the diet, the slower growth and the appearance of EFA deficiency symptoms became evident in SHR. In general, fat-depletion reduced the levels of n-6 fatty acids, whereas it increased those of 20:3n-9. However, the fat-depletion induced reduction of 18:2n-6 in heart PL and 20:4n-6 in kidney, while the elevation of 20:3n-9 in plasma, heart, and kidney PL were greater in WKY than in SHR. As a result, the elevation of biochemical EFA deficiency index--20:3n-9/20:4n-6 ratio--was greater in WKY than in SHR. In comparison with WKY, the concentrations of liver triacylglycerols and the weights of adipose tissues in SHR were reduced to a greater extent, indicating an active catabolism of triacylglycerols in SHR. This study suggests that the earlier appearance of morphological symptoms of EFA deficiency in SHR was not associated with the reducing n-6 EFA levels or with an elevation of triene/tetraene ratio, but possibly to a reduced supply of n-6 EFA for skin prostaglandin synthesis.

Plasma fatty acids of marrow transplant recipients on fat-supplemented parenteral nutrition

The study was conducted to determine the adequacy of fat infusion in preventing essential fatty acid deficiency during parenteral feeding. Eight adult patients receiving marrow transplantation for the treatment of leukemia were studied. Total daily intravenous and oral calorie and fat intakes were monitored. Insignificant amounts of food were consumed orally during the 30-day study period. Parenteral nutrition, initiated pretransplant, included 250 ml of 10% fat infusion daily. Plasma total fatty acids were determined by gas-liquid chromatography at specified intervals to detect biochemical essential fatty acid deficiency. The results showed a rapid and significant decline of linoleic acid, 18:2ω6, as percentage of total fatty acids. The arachidonic acid, 20:4ω6, was not significantly altered. The abnormal fatty acid, eicosatrienoic acid, 20:3ω9, was found in trace amounts in five patients. None of the patients developed a 20:3ω9/20:4ω6 ratio of 0.2 or more. The level of fat infused prevented biochemical essential fatty acid deficiency, but the plasma fatty acid profile was significantly different from normal levels.

The relationship of dietary fats to prostaglandin biosynthesis

The direct and indirect evidence that the fatty acid composition of dietary fat is involved in the regulation of prostaglandin biosynthesis was reviewed. Direct evidence included effects of essential fatty acid deficiencies and excesses on endogenous tissue levels and production rates of prostaglandins by several tissues. Indirect evidence included lipolytic, platelet aggregatory, hypertensive, inflammatory and immune responses. In general, composition of dietary fat did not affect prostaglandin biosynthesis unless a biochemical essential fatty acid deficiency was induced or the linoleate to saturated fatty acids ratio of the dietary fat was greater than 5. Most results were interpreted in light of changing fatty acid composition; however, very few direct measurements have been made.

Essential fatty acid deficiency in infants receiving parenteral nutrition

The clinical and biochemical features of essential fatty acid deficiency are described in an infant with gastroschisis who required long-term (6 mo) parenteral nutrition. The deficiency responded to therapy with Intralipid, topical sunflower oil, and breast milk. In a prospective study of three infants with gastroschisis, biochemical essential fatty acid deficiency developed in each during the first week of lipid-free parenteral nutrition; clinical signs of the deficiency were absent. The biochemical features were progressive in the one patient followed for 19 days, and were associated with a decrease in weight gain. Both the deficiency and weight gain were corrected by Intralipid. Biochemical essential fatty acid deficiency did not develop in three other gastroschisis infants who were given prophylactic Intralipid (two patients) or topical sunflower oil (one patient). We conclude that all infants on parenteral nutrition should receive a source of linoleic acid to prevent essential fatty acid deficiency.

The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally.

The hypothesis that clinical and biochemical essential fatty acid deficiency (EFA) might occur from the feeding of eucaloric, fat-free diets was tested in two experiments in healthy men. In Study I, eight men were given fat-free, eucaloric diets containing 80% of calories as glucose and 20% as amino acid hydrolysates by a constant drip over a 24-h period. The diets were fed in succession for periods of 2 wk each, either through a superior vena cava catheter or via a nasogastric tube. EFA deficiency was detected by decreases in linoleic acid and by the appearance of 5, 8, 11-eicosatrienoic acid in lipid fractions of plasma. Linoleic acid decreased significantly during 2 wk of the fat-free diet given intravenously from 48.8 to 9.8% (percent of total fatty acids) in cholesterol esters, from 21.2 to 3.2% in phospholipids, from 9.6 to 2.0% in free fatty acids, and from 14.1 to 2.6% in triglycerides. Eicosatrienoic acid, normally undetectable, appeared 0.6% in cholesterol esters, 2.5% in phospholipids, 0.2% in free fatty acids, and 2.3% in triglycerides. EFA deficiency occurred similarly during the nasogastric feeding. In Study II a subject received the same diet continuously by the nasogastric route for 10 days followed by a 24-h fast. He was then given the fat-free diet intermittently in three meals per day for 3 days. Finally, he was repleted with a diet containing 2.6% linoleic acid. By the 3rd day of the continuous nasogastric feeding, linoleic acid had fallen significantly and eicosatrienoic acid had appeared in plasma lipid fractions as in Study I. These findings were accentuated by day 10. Adipose tissue fatty acid composition did not change. Free fatty acid outflow from adipose tissue was presumably suppressed during the 10 days of continuous feeding. With increased free fatty acid outflow during fasting and intermittent feeding, linoleic acid rose and eicosatrienoic acid decreased. After 13 days of repletion with dietary linoleic acid, the EFA deficiency readily develops when fat-free diets containing glucose are given intravenously or orally as constant 24-h infusions. These diets are similar to the hyperalimentation formulas now being used clinically.