Mead Acid Research Articles

Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease.

Intravenous fish oil (FO) treats pediatric intestinal failure-associated liver disease (IFALD). There are concerns that a lipid emulsion composed of ω-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study's objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. Inclusion criteria for this prospective study were children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared with age-based norms to determine the percentage of subjects with low and high concentrations. Subjects (n=17) started receiving FO at a median of 3.6 months (interquartile range 2.4-9.6 months). Over time, α-linolenic, linoleic, arachidonic, and Mead acid decreased, whereas docosahexaenoic and eicosapentaenoic acid increased (P<0.001 for all). Triene-tetraene ratios remained unchanged (P=1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs SO (95% CI: 1.4-2.3, P<0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs SO; however, this was not significant (95% CI: 0.9-2.6, P=0.08). In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant.

Reelin deficiency leads to aberrant lipid composition in mouse brain

Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler mice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in the reeler mouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.

Effect of changing the lipid component of home parenteral nutrition in adults

The effect of different lipid emulsions (LEs) within the parenteral nutrition (PN) regimen of adult home PN (HPN) patients is not clear. This study investigated the effect of changing adult HPN patients from a soybean oil based LE (Intralipid) to either a fish oil containing LE (providing n-3 fatty acids) (SMOFLipid) or an olive oil based LE (ClinOleic). Thirty two adults receiving long-term HPN with Intralipid as the LE were transferred to receive either SMOFLipid (n=13) or ClinOleic (n=19) for 60 days. Liver function markers, cholesterol, triglycerides, a full profile of fatty acids, and several cytokines were measured at study entry and after 60 days. SMOFLipid did not affect liver function markers, blood lipids or plasma cytokines. ClinOleic lowered both gamma-glutamyltranspeptidase (P=0.044) and interleukin-8 (P=0.030) concentrations. Both LEs induced marked changes in the fatty acid profile of plasma. SMOFLipid resulted in significant decreases in the proportions of linoleic acid, several other n-6 fatty acids and the essential fatty acid (EFA) deficiency indicator mead acid and significant increases in the proportions of the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. ClinOleic resulted in significant decreases in the proportions of some saturated fatty acids, linoleic acid, several n-6 fatty acids, all n-3 fatty acids and mead acid and a significant increase in the proportion of oleic acid. The ratio of mead to arachidonic acid in plasma was not altered by either SMOFLipid or ClinOleic. No patient had a mead acid to arachidonic acid ratio of >0.2, the cut-off used to indicate EFA deficiency. Both SMOFLipid and ClinOleic significantly alter the fatty acid profile of plasma in adult HPN patients previously using Intralipid. Neither LE induces EFA deficiency in these patients. SMOFLipid did not alter liver function markers or inflammation. In contrast, ClinOleic decreased some, though not all, markers of liver function and inflammation. SMOFLipid and ClinOleic may both be considered for use in adult HPN patients.

FADS2 inhibition in essential fatty acid deficiency induces hepatic lipid accumulation via impairment of very low-density lipoprotein (VLDL) secretion

Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), and is involved in Mead acid (20:3n-9) production during essential fatty acid deficiency (EFAD). In this study, an obvious hepatic lipid accumulation was observed in EFAD mice treated with a FADS2 inhibitor. FADS2 inhibition in the EFAD state reduced secretion of very low-density lipoprotein (VLDL) and markedly diminished Mead acid in phosphatidylcholine (PC) in the liver and plasma. As the results, the amount of C20 HUFAs in hepatic and plasma PC dramatically reduced in the EFAD mice treated with a FADS2 inhibitor, whereas the decrease of C20 HUFA levels of PC in EFAD mice was not observed because of the increased Mead acid in PC. These results supposed that Mead acid in PC is important as a component of VLDL. It is possible that Mead acid plays the role of a substitute of HUFAs in VLDL secretion during EFAD.

Serum n-6 and n-9 Fatty Acids Correlate With Serum IGF-1 and Growth Up to 4 Months of Age in Healthy Infants.

The aim of this study was to study the relationship between insulin-like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in healthy full-term newborns during infancy. Prospective observational study of a population-based Swedish cohort comprising 126 healthy, term infants investigating cord blood and serum at 2 days and 4 months of age for IGF-1 and phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4 months, compared with anthropometric measurements (standard deviation scores). At all time-points arachidonic acid (AA) was negatively associated with IGF-1. IGF-1 had positive associations with linoleic acid (LA) at 2 days and 4 months and mead acid (MA) showed positive associations in cord blood. Multiple regression analyses adjusted for maternal factors (body mass index, weight gain, smoking, education), sex, birth weight and feeding modality confirmed a negative association for the ratio AA/LA to IGF-1. MA in cord blood correlated to birth size. Changes in the ratios of n-6/n-3 and AA/docosahexaenoic acid from day 2 to 4 months together with infants' weight and feeding modality determined 55% of the variability of delta-IGF-1. Breast-fed infants at 4 months had lower IGF-1 correlating with lower LA and higher AA concentrations, which in girls correlated with lower weight gain from birth to 4 months of age. Our data showed interaction of n-6 fatty acids with IGF-1 during the first 4 months of life, and an association between MA and birth size when adjusted for confounding factors. Further follow-up may indicate whether these correlations are associated with later body composition.

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.

The role of fatty acid desaturase (FADS) genes in oleic acid metabolism: FADS1 Δ7 desaturates 11-20:1 to 7,11-20:2

IntroductionIn mammals, FADS2 catalyzes “front-end” Δ4-, Δ6-, and Δ8-desaturation of fatty acyl chains, whereas FADS1 has Δ5-desaturase activity. Eighteen and 20-carbon precursors to highly unsaturated n-3 and n-6 fatty acids are the usual substrates for FADS1 and FADS2. Our main objective was to characterize the metabolic fate of oleic acid (OA) due to action of FADS gene products. MethodsMCF-7 cells were stably transformed with either FADS1 or FADS2 or empty vector. A series of dose-response experiments were conducted with albumin-bound fatty acid substrates (18:1n-9 and 20:1n-9) provided in concentrations up to 100µM. Cells were harvested after 24h, after which FAME were prepared and analyzed by GC-FID and covalent adduct chemical ionization tandem mass spectrometry (CACI-MS/MS). ResultsWhen stably transformed cells were incubated with 18:1n-9, FADS1 and control cells elongated 18:1n-9 → 20:1n-9 (11-20:1), while FADS2 cells Δ6 desaturated, elongated, and then Δ5 desaturated via FADS1 coded activity leading to Mead acid, 9-18:1 → 6,9-18:2 → 8,11-20:2 (20:2n-9) → 6,8,11-20:3 (20:3n-9). Surprisingly, FADS1 cells Δ7 desaturated 11-20:1 → 7,11-20:2, the latter detected at low levels in control and FADS2 cells. Our results imply three pathways operate on 18:1n-9: 1) 18:1n-9 → 18:2n-9 → 20:2n-9 → 20:3n-9; 2) 18:1n-9 → 20:1n-9 → 20:2n-9 → 20:3n-9 and 3) 18:1n-9 → 20:1n-9 → 7,11-20:2. ConclusionAlternative pathways for oleic acid metabolism exist depending on FADS2 or FADS1 activities, we present the first evidence of Δ7 desaturation via the FADS1 gene product

Essential fatty acids for oleaginous fungus Mortierella alpina

Abstract Oleaginous fungus Mortierella alpina 1S-4 accumulates arachidonic acid (20:4ω6) as a major polyunsaturated fatty acid. However, 20:4ω6 is not essential for the growth of M. alpina 1S-4, because various mutants that produce no 20:4ω6 were isolated. M. alpina JT-180, a Δ12 desaturation-defective mutant that was derived from M. alpina 1S-4 by treatment with a chemical mutagen, accumulates Mead acid (20:3ω9) instead of 20:4ω6. p -Anisidine was found to be a Δ6 desaturation inhibitor in this study. The concentration of 0.1 mg/ml of p -anisidine had an inhibitory effect on the growth of M. alpina JT-180. The addition of p -anisidine to the medium caused M. alpina JT-180 to produce only monoenoic acids such as oleic acid (18:1ω9) and eicosenoic acid (20:1ω9) as unsaturated fatty acids. The effects of exogenous fatty acids were investigated when M. alpina JT-180 was cultivated in medium containing p -anisidine. The addition of linoleic acid (18:2ω6) and 6 Z ,9 Z -octadecadienoic acid (18:2ω9) restored the growth of M. alpina JT-180 cultivated on the medium containing p -anisidine, but palmitic acid (16:0), 18:1ω9, and vaccenic acid (18:1ω7) had no effect. For the growth of oleaginous fungus M. alpina , 18-carbon length fatty acids with more than two double bonds are considered to be essential.

Blood fatty acids in the development and correction of metabolic syndrome

to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA). Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA. Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells. The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.

Whole Blood Levels of the n-6 Essential Fatty Acid Linoleic Acid Are Inversely Associated with Stunting in 2-to-6 Year Old Tanzanian Children: A Cross-Sectional Study

BackgroundIn Tanzania, 35% of all children below five years of age are stunted. Dietary fatty acids (FA) are critical for growth and development. However, whole blood FA levels in Tanzanian children are poorly described.ObjectiveThe objectives of this cross-sectional study were to assess 1) whole blood levels of essential fatty acids and 2) the association between whole blood FA levels and growth parameters in Tanzanian children 2–6 years of age.MethodsA drop of blood was collected on an antioxidant treated card and analyzed for FA composition. Weight and height were measured and z-scores calculated. Relationships between FAs and growth parameters were analyzed by linear regression.ResultsOf the 334 children that participated, 30.3% were stunted. The average whole blood level of Mead acid was 0.15%. The anthropometric z-score height-for-age (HAZ) was inversely associated with Mead acid, the Mead acid to arachidonic acid (T/T) ratio, and total n-9 FA. Additionally, HAZ was positively associated with linoleic acid and total n-6 FA. BMI-for-age was positively associated with oleic acid, total n-9 FA and T/T ratio but inversely associated with arachidonic acid and total n-6 FA. Weight-for-height was inversely associated with arachidonic acid and total n-6 FAs and positively associated with oleic acid and total n-9 FA. Weight-for-age was not associated with any FA tested. Total n-3 FAs were not associated with any growth parameters measured.ConclusionsThe EFA linoleic acid and the markers of FA deficiency were associated with HAZ, an indicator for stunting in 2–6 year old Tanzanian children. Total n-6, total n-9, and a number of individual FAs were associated with growth. Increasing dietary intake of EFA and n-6 FAs may be a strategy to combat stunting in this population.

Organ and phospholipid class fatty acid specificity in response to dietary depletion of essential n-3 fatty acids in Atlantic salmon (Salmo salarL.)

The cell membrane phospholipid composition is of major importance for normal cell functions. However, it is not known how complete depletion of both shorter and longer chain omega-3 fatty acids in salmon diets influences fatty acid composition of phospholipid subclasses in different organs of Atlantic salmon. We describe here the fatty acid composition in phospholipid subclasses of liver, muscle, heart and intestine in Atlantic salmon after 18 months of dietary n-3 essential fatty acids deprivation. The percentage of 22:6n-3 was markedly reduced in almost all phospholipid subclasses, and except for muscle phosphatidylcholine, phosphatidylethanolamine (PE) and phosphatidylinositol (PI), phospholipids in deficient fish were totally devoid of 20:5n-3. As compensation, we observed significant increases in 20:4n-6, and especially in 20:3n-9 (Mead acid) and 22:5n-6, varying among phospholipids and organs. High amounts of 20:3n-9 were found in liver and intestinal PE, little in PE from heart and muscle. For 22:5n-6, we saw a small incorporation in PI in liver and intestine compared to heart and muscle. Generally in PI, the preference for 20:4n-6 to 20:5n-3 differed significantly between organs. Overall, changes upon n-3 deprivation seemed to be strongest in liver and intestine, the lipid-secreting organs, and less in muscle and heart.

Anti-inflammatory Activity and Chemical Composition of Essential Oil Extracted with Supercritical CO2 from the Brown Seaweed Undaria pinnatifida

Essential oil extracted with supercritical CO2 fluid from the brown seaweed Undaria pinnatifida showed high anti-inflammatory activity. Optimal extraction with supercritical CO2 was observed at 45°C and 20 MPa. The essential oil was active against mouse ear inflammation induced by phorbol myristate acetate, with median inhibition concentration IC50 values of 87, 134, and 158 µg per ear for edema, erythema, and blood flow, respectively. The major component compounds were palmitic acid (26 %), 2-(9,12- octadecadienyloxy)-,(z,z)-ethanol (16 %), eicosa-5,8,11,14,17-pentaenoate (EPA; 13 %), and 5,7,11- eicosatrienoic acid (mead acid; 12 %). These findings are consistent with the claims that the seaweed U. pinnatifida can be used in remedies for inflammation-related symptoms.

Dietary effects of mead acid on N-methyl-N-nitrosourea-induced mammary cancers in female Sprague-Dawley rats.

The effect of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of the development and growth of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Sprague-Dawley rats was examined. The MA diet (2.4% MA) or control (CTR) diet (0% MA) was started at 6 weeks of age, MNU was injected intraperitoneally at 7 weeks of age, and the rats were maintained on the respective diets for the whole experimental period (until 19 weeks of age). All induced mammary tumors were luminal A subtype carcinomas (estrogen and progesterone receptor positive and HER2/neu negative). The MA diet significantly suppressed the initiation and promotion phases of mammary carcinogenesis; MA suppressed the development (incidence, 61.5 vs. 100%; multiplicity, 2.1 vs. 4.5) and the growth (final tumor weight, 427.1 vs. 1,796.3 mg) of mammary cancers by suppressing cell proliferation, but not by accelerating cell death. There were evident changes in the major fatty acid composition of n-3, n-6, and n-9 fatty acids in the serum of the MA diet group; there was a significant increase in MA and significant decreases in oleic acid (OA), linoleic acid, arachidonic acid and docosahexaenoic acid. In non-tumorous mammary tissue, there was a significant increase in MA and a significant decrease in OA in the MA diet group. The n-6/n-3 ratios in serum and mammary tissue of the MA diet group were significantly decreased. The MA diet suppressed MNU-induced luminal A mammary cancer by lowering cancer cell proliferation. Therefore, MA may be a chemopreventive and chemotherapeutic agent. In addition to hormone therapy, MA supplementation may be a beneficial chemotherapeutic agent for the luminal A subtype of breast cancer.

Denovo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1year of supplementation as compared with a control diet. The denovo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced denovo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected denovo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing.

Essential Fatty Acid Deficiency in 2015: The Impact of Novel Intravenous Lipid Emulsions.

The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles.

Association of blood fatty acids and growth in Tanzanian children 2‐6 years of age.

In Tanzania, 42% of all children below five years of age are stunted. Dietary essential fatty acids (EFA) are critical for growth and development. However, EFA status of Tanzanian children is poorly described. The objective of this study was to assess the association between red blood cell (RBC) fatty acid levels and growth parameters in Tanzanian children 2-6 years of age. A drop of blood was collected on an antioxidant treated card and analyzed for fatty acids by OmegaQuant (n=335). Weight, height, and head circumference were measured and z-scores were calculated using WHO Anthro/plus. Within the sample, 70% of the children were EFA deficient as demonstrated by a triene/tetraene (T/T) ratio<0.022. No significant associations were observed between Z-scores and T/T ratio or Mead acid (markers of EFA deficiency). However, height-for-age was positively associated with total polyunsaturated fatty acids and n-6 fatty acids (p<.05). Height-for-age was inversely correlated with palmitoleic acid, oleic acid, total n-9, and total monounsaturated fatty acids (p<.05). Linoelaidic acid was positively correlated with weight-for-age (p<.05). BMI-for-age inversely correlated with eicosadienoic acid, and a positively correlated with oleic acid (p<.05). Weight-for-heightwas inverselycorrelated with docosatetraenoic acid (p<.01) and lignoceric acid (p<.05). These data indicate that there is an association between essential and non-essential fatty acids and growth parameters in Tanzanian children aged 2 to 6. Funding Source: USAID/iAGRE.

Association between fatty acid status and executive function in Tanzanian children aged 2‐6

Fatty acids, particularly the essential fatty acids (EFA), arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important for brain development and cognitive function. The objective of this study was to determine the association between red blood cell fatty acids and cognitive function in Tanzanian children. A sample of 335 children between 2-6 years were given dimensional change card sort (DCCS) testing and a drop of blood was collected on anti-oxidant treated cards for fatty acid analysis (OmegaQuant). Correlations and regressions were run between the cognitive measures and various fatty acids using SPSS. Significant correlations were observed between the different DCCS analyses of cognitive function with the omega-3 index (RBC EPA+DHA), total n-3 and n-6 fatty acids. Further, we observed a significant positive correlation between the highest test passed and omega-3 index (p<0.05). An inverse correlation between myristic acid (p<0.02) and highest test passed and the overall pass, palmitic acid (p<0.02) was inversely correlated with all the measures of cognitive function. As the triene to tetraene ratio increased (indicative of EFA deficiency), there was a decrease in the overall pass in the cognitive test. No relationship was observed between Mead acid and cognitive status. EFA intervention studies should be designed to determine if EFA supplementation can improve cognitive function in Tanzanian children. Funding source USAID/iAGRI.

Mead acid (20:3n-9) and n-3 polyunsaturated fatty acids are not associated with risk of posterior longitudinal ligament ossification: Results of a case-control study

Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to be involved in the development of OPLL, its pathogenesis remains to be elucidated. Given previous findings that 5,8,11-eicosatrienoic acid [20:3n-9, Mead acid (MA)] has depressive effects on osteoblastic activity and anti-angiogenic effects, and that n-3 polyunsaturated fatty acids (PUFAs) have a preventive effect on heterotopic ossification, we hypothesized that both fatty acids would be involved in OPLL development. To examine the biological significance of these and other fatty acids in OPLL, we conducted this case-control study involving 106 patients with cervical OPLL and 109 age matched controls. Fatty acid composition was determined from plasma samples by gas chromatography. Associations between fatty acid levels and incident OPLL were evaluated by logistic regression. Contrary to our expectations, we found no significant differences between patients and controls in the levels of MA or n-3 PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid). Logistic regression analysis did not reveal any associations with OPLL risk for MA or n-3 PUFAs. In conclusion, no potential role was found for MA or n-3 PUFAs in ectopic bone formation in the spinal canal.

ESSENTIAL FATTY ACID DEFICIENCY IN VERY LONG-CHAIN ACYL-COA DEHYDROGENASE DEFICIENT PATIENTS

Introduction: Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), a long-chain fatty acid (LCFA) beta-oxidation dis order, may be treated with LCFA restriction. As Essential Fatty Acids (EFAs) are LCFAs, patients may be at risk for EFA deficiency. Objectives: Investigate whether LCFA restrictions lead to EFA deficiency in VLCADD and which markers are indicative of EFA deficiency. Methods: Thirty-nine LCFA profiles of 16 VLCADD patients were determined in erythrocytes and compared to 48 healthy controls. The predictive value of EFA deficiency markers was calculated from data of a historic cohort (n=4523, 0-39yrs). Results: Linoleic acid (LA), dihomo-γ-linolenic acid (DHLA) and eicosapentaenoic acid (EPA) were significantly decreased in VLCADD patients. Patients on docosahexaenoic acid (DHA) and arachidonic acid (AA) supplementation exhibited even lower LA. Mead acid, a presumed marker for EFA-deficiency, was not increased in patients. In the historic cohort, sensitivity of MA was low for LA deficiency (24% for levels <2.5 percentile) and for DHA+AA deficiency (12% for levels <2.5 percentile). Discussion: VLCADD patients on LCFA restriction are prone to develop LA deficiency. Furthermore, MA is a specific, but not a sensitive marker for LA or EFA deficiency, neither in VLCADD patients, nor in healthy controls, nor in a large patient cohort.

Food allergy in small children carries a risk of essential fatty acid deficiency, as detected by elevated serum mead acid proportion of total fatty acids

BackgroundElevated serum Mead acid as a proportion of total fatty acids is an indirect marker of a deficiency of essential fatty acids (EFA). The aim of the study was to evaluate the symptoms and nutrition of food-allergic children with elevated or normal serum Mead acid.MethodsSerum fatty acid compositions from 400 children were studied by clinical indications, mostly by suspicion of deficiency of EFA due to inadequate nutrition. A Mead acid level exceeding 0.21% (percentage of total fatty acids) was considered to be a specific sign of an insufficient EFA supply. From a total of 31 children with elevated Mead acid (MEADplus group), 23 (74%) had food allergy. The symptoms and dietary restrictions of this MEADplus group of food allergic children were compared to 54 age-and sex-matched controls with food allergy but normal Mead acid proportions (MEADminus group) before and 6 months after the serum fatty acid determination.ResultsAt the beginning of the 6-month follow-up, 44% of the food allergic children in both MEADplus and MEADminus groups were on an elimination diet. These diets did not differ between the two groups and we were not able to document an association between the severity of elimination diet and elevated Mead acid proportion. However, the MEADplus children were on average more symptomatic than MEADminus children. In the MEADplus group, food allergy presented with skin symptoms in 100% (vs. 70% in the MEADminus group, p < 0.001) and with vomiting or diarrhea in 70% (vs. 44% in the MEADminus group, p < 0.05). Clinical suspicion of malnutrition resulted in increase in the use of vegetable oil and milk-free margarine in both groups from <50% to 65-74% during the follow-up. After 6 months, 64% of the MEADplus children with food allergy had been sent to a control serum fatty acid analysis. Of these children, Mead acid had declined to normal level in 69%, and remained elevated in 31%.ConclusionsSevere symptoms of food allergy combined with elimination diets in children may lead to insufficient nutrition presenting with elevated serum Mead acid. Adding of supplementary polyunsaturated fat to the diet should be considered in these children.