Relative levels of dietary EPA and DHA impact gastric oxidation and essential fatty acid uptake.

Previous research showed that increasing the proportion of docosahexaenoic acid (DHA) in marine lipid supplements significantly reduces associated health benefits compared with balanced eicosapentaenoic acid (EPA):DHA supplementation Dasilva et al., 2015 [1]. It was therefore hypothesized that the EPA and DHA molecules might have differential resistance to oxidation during gastric digestion and that the oxidation level achieved could be inversely correlated with intestinal absorption and, hence, with the resultant health benefits. Accordingly, we tested this proposed mechanism of action by investigating the degree of oxidation in the stomach, and the levels of bioaccessible lipids, of varying molar proportions of DHA and EPA (2:1, 1:1 and 1:2) using the dynamic gastrointestinal tract model TIM-1. In addition, small intestine enterocyte absorption and metabolism were simulated by Caco-2 cell monolayers that were incubated with these same varying proportions of DHA and EPA, and comparing oxidized and nonoxidized polyunsaturated fatty acids (PUFAs). The results show an inverse correlation between lipid oxidation products in the stomach and the levels of bioaccessible lipids. The balanced 1:1 EPA:DHA diet resulted in lower oxidation of PUFAs during stomach digestion relative to the other ratios tested. Finally, cell-based studies showed significantly lower assimilation of oxidized EPA and DHA substrates compared to nonoxidized PUFAs, as well as significant differences between the net uptake of EPA and DHA. Overall, the present work suggests that the correct design of diets and/or supplements containing marine lipids can strongly influence the stability and bioaccessibility of PUFAs during gastrointestinal digestion and subsequent absorption. This could modulate their health benefits related with inflammation, oxidative stress and metabolic disorders.

Influence of omega-3 fatty acids from the flaxseed (Linum usitatissimum) on the brain development of newborn rats / Influencia de los ácidos grasos omega-3 de la linaza (Linum usitatissimum) en el desarrollo del cerebro de ratas recién nacidas

Objectives: The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum) is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. Material and methods: Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n = 6), FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. Results: Significant increase in brain weight (39%) and relative brain weight (37%) was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3) fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA) (38%), as well as in total of omega-3 (n-3) fatty acids (62%). Conclusion: Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats (AU)

Objetivos: La importancia de los ácidos grasos esenciales, en particular la familia omega-3, en el desarrollo del sistema nervioso central de los recién nacidos está bien documentada. La semilla de linaza (Linum usitatissimum) es considerada una de las mejores fuentes vegetales de ácidos grasos omega-3. Se evaluó la influencia de los ácidos grasos omega-3 de la linaza en el desarrollo del cerebro de ratas recién nacidas. Material y métodos: Las crías de la generación F1 se obtuvieron a partir de 18 ratas Wistar divididas en 3 grupos (n = 6), GL: alimentados con dieta a base de linaza adicionada con caseína, GC: a base de caseína, y GCM: con caseína modificada suplementada con fibras y aceite de soja. Las crías recién nacidas fueron pesadas y sometidas a eutanasia; los cerebros fueron recolectados para la evaluación del peso y el perfil lipídico mediante cromatografía gaseosa. Resultados: Se verificó aumento significativo en el peso cerebral (39%) y en el peso relativo del cerebro (37%) en las crías de madres alimentadas con la dieta de linaza. Los ácidos grasos omega-3 (n-3) de la linaza se encontraron en abundancia en la dieta elaborada con esta oleaginosa, y también hubo importante aumento en el ácido docosahexaenoico (DHA) (38%), así como en el total de ácidos grasos omega-3 (n-3) (62%). Conclusión: La dieta materna a base de linaza durante el embarazo influye en la incorporación de ácidos grasos omega-3 en la composición del tejido cerebral, asegurando un buen desarrollo de este órgano en ratas recién nacidas (AU)

Essential fatty acids in the treatment of dry eye.

Essential fatty acids (EFAs) play many important roles in human biology, affecting organ systems and cellular and intracellular function. Omega-3 and omega-6 EFAs are the precursors of eicosanoids, locally acting hormones involved in mediating inflammatory processes. It is largely via the production of these eicosanoids that the essential fatty acids influence human health and disease. In general, the omega-3 derived eicosanoids are anti-inflammatory while the n-6 pathway eicosanoids promote inflammation. To date, EFAs have been primarily studied with regard to systemic diseases, particularly cardiovascular disease. Currently, no dietary recommendations of EFAs for the prevention or treatment of eye disease exist. The majority of studies concerning EFAs and eye disease have focused on diseases of the retina. This article provides an overview of the current literature regarding EFAs and dry eye disease (DED). Eight studies were identified, including six randomized controlled trials. All the studies preliminarily confirmed that there is a relationship between EFA supplementation and improvement in DED. However, strong conclusions cannot be made yet because of limitations in the research reported. The role of essential fatty acids is an important topic that would benefit from a large, multicenter, randomized clinical trial powered to reach a conclusion regarding the efficacy of essential fatty acids in the treatment of dry eye disease.

Ácidos grasos omega-3 y enfermedades neuropsiquiátricas / Omega-3 fatty acids and neuropsychiatric disorders

Los ácidos grasos poliinsaturados omega-3 desempeñan un destacado papel en el correcto funcionamiento de la membrana neuronal. Numerosos estudios sugieren que el consumo de suplementos de estos compuestos (especialmente ácido eicosapentanoico [EPA] y ácido docosahexanoico [DHA]) podría producir una mejoría clínica en algunas enfermedades neuropsiquiátricas. En este trabajo se presenta una revisión actualizada de la evidencia disponible en relación con el uso de ácidos grasos omega-3 en el tratamiento de la esquizofrenia, la depresión, el trastorno bipolar y otras enfermedades neuropsiquiátricas

Omega-3 polyunsaturated fatty acids play a major role in the correct functioning of the neuronal membrane. Numerous studies suggest that the consumption of omega-3 fatty acid supplements (especially eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) could produce a clinical improvement in some neuropsychiatric disorders. This article presents an updated review of the evidence available on the use of these compounds in the treatment of schizophrenia, depression, bipolar disorder, and other neuropsychiatric abnormalities

Diet and asthma: has the role of dietary lipids been overlooked in the management of asthma?

OBJECTIVE: This article discusses the role of diet in the management of asthma. Readers will gain an understanding of how evolution of the western diet has contributed to increased asthma prevalence and how dietary modification that includes management of dietary lipids may reduce symptoms of asthma. DATA SOURCES: Relevant studies published in English were reviewed. STUDY SELECTION: Medline search to identify peer-reviewed abstracts and journal articles. RESULTS: Asthma and obesity, which often occur together, have increased in prevalence in recent years. Studies suggest adaption of a western diet has not only contributed to obesity, but that increased intake of specific nutrients can cause changes in the frequency and severity of asthma. Increased asthma prevalence has also been proposed to arise from increased exposure to diesel particles or lack of exposure to infectious agents or endotoxins during childhood, generating a biased Th2 immune response, and increased cytokine and leukotriene production. Antagonists directed against these pro-inflammatory mediators include anticytokines and antileukotrienes. A reduction in the levels of inflammatory mediators associated with asthma has also been seen with dietary interventions, such as the administration of oils containing gamma-linolenic acid and eicosapentaenoic acid. CONCLUSIONS: Evidence suggests elevated body mass index and dietary patterns, especially intake of dietary lipids, contribute to symptoms of asthma. Dietary modification may help patients manage their asthma as well as contribute to their overall health.

Bioavailability of omega-3 essential fatty acids from perilla seed oil.

Increased dietary intake of fish oil omega-3 fatty acids, eicosapentanoic acid and docosohexanoic acid, and their precursor, alpha-linolenic acid (ALA), is associated with various health benefits. Enteric-coating (Entrox), which improves stability of omega-3 capsules, has been shown to facilitate fish oil absorption after chronic treatment. To assess the effect of Entrox coating on the short-term bioavailability of ALA administered in the form of ALA-rich Perilla seed oil, 12 healthy subjects (6 males and 6 females) received in a random order Entrox-coated and non-coated ALA formulations, each as a single 6g dose separated by a 3-week washout period. Measurements of plasma ALA concentrations from 0 to 24h showed no difference in ALA pharmacokinetics between the two formulations. However, significantly greater increases in plasma ALA levels from baseline to 24h were observed after ingestion of Entrox vs. non-coated product, suggesting a possible benefit of Entrox with long-term treatment.

Essential polyunsaturated fatty acids and the barrier to the brain: the components of a model for transport.

Several areas of research have contributed to the establishment of a paradigm that meets the requirements for the selective uptake of essential polyunsaturated fatty acids (EPUFA) into brain. First, discrete studies have demonstrated that cholesterol and the nonessential fatty acids, (palmitic, oleic, stearic) do not enter the brain parenchyma. These studies demonstrated that the 18 carbon-monocarboxylic fatty acids, linoleic acid with two cis-double bonds entered brain, whereas oleic acid, with one cis-double bond, did not enter brain. It was concluded the entry of essential fatty acids into brain is accomplished in a highly selective and discrete manner. Further, the typical blood-borne lipoproteins do not traverse the endothelial cells of the capillary network and enter into the brain, otherwise cholesterol, palmitic, oleic, and stearic acids from blood would be located within brain. Second, several investigators have shown that the endothelial cells of the capillary network contain lipoprotein receptors, yet one conclusion is that the brain does not utilize low-density lipoprotein (LDL)-cholesterol. Third, recently, the existence and function of a significant number of distinctive trans-membrane monocarboxylic acid transporters, (MCTs) and fatty acid transport proteins (FATPs) have been described. No transporters have been described to date with the specificity necessary to transfer only EPUFA into brain. A blueprint with the minimal elements for delivery and selectivity is proposed. Lipoproteins enter the endothelial cells because the lipoprotein receptors are positioned on their luminal membrane. Essential fatty acid transporter(s) are positioned on the abluminal membrane of these endothelial cells to allow for the entry of EPUFA into brain. Within the endothelial cell there is opportunity for lipid management and transformation such that EPUFAs are selectively culled for delivery to the essential fatty acid transporter(s), which facilitates their transfer into brain.

Dietary long-chain fatty acids and visual response in malnourished nursing infants.

Polyunsaturated fatty acids (PUFAs) derived from essential fatty acids (EFAs) play an important role in prenatal visual and neural development. Protein-energy malnutrition affects PUFA supply, and hence the synthesis of structural lipids during growth. Recently, some physiological studies reported abnormalities in the visual function of formula-fed infants relative to breast-fed infants. The purpose of our study was to assess whether fatty acid composition of the malnourished infant diet modifies the visual function and erythrocyte phospholipid fatty acid composition. Three groups of full-term malnourished infants were selected. Two groups received commercial formulas. One of them supplied linoleic and alpha -linolenic acid: Formula I (FI), and the other supplied, in addition, long-chain PUFAs from n-3 and n-6 series: Formula II (FII). A reference group of breast-fed infants was also enrolled. Visual function was assessed using full-field flash electroretinography, and the erythrocyte phospholipid fatty acid composition was determined by gas-liquid chromatography. Those infants receiving the supplemented formula (FII) exhibited a similar retinal function to that of breast-fed infants. However, normal results were not achieved when infants were fed on the FI formula. In all groups, the results were correlated with the proportion of docosahexaenoic acid in erythrocyte phospholipid fatty acid composition. We conclude that in malnourished infants a nutrient formula enriched with long-chain fatty acids of n-6 and n-3 series could be helpful to achieve an erythrocyte fatty acid pattern and a visual function similar to that obtained in breast-fed infants.

Differences in essential fatty acid requirements by enteral and parenteral routes of administration in patients with fat malabsorption.

BACKGROUND: Essential fatty acid (EFA) requirements of patients receiving home parenteral nutrition (HPN) are uncertain. OBJECTIVE: The objective was to evaluate the influence of the route of administration (enteral compared with parenteral) on plasma phospholipid EFA concentrations. DESIGN: Intestinal absorption, parenteral supplement of EFAs, and plasma phospholipid EFA concentrations were investigated in balance studies in 4 groups (A, B, C, and D) of 10 patients with short-bowel syndrome and a fecal loss of >2000 kJ/d. Groups A (fat malabsorption <50%) and B (fat malabsorption >50%) did not receive HPN, whereas group C received HPN containing lipids (7.5 and 1.2 g/d linoleic and linolenic acids, respectively) and group D received fat-free HPN. RESULTS: Intestinal absorption of linoleic and linolenic acids was 8.9 and 1.3 g/d and 2. 6 and 0.4 g/d in groups A and B, respectively, whereas EFA absorption was negligible in groups C and D. Thus, intestinal absorption of EFAs in group A corresponded to parenteral EFA supplements in group C, whereas group D was almost totally deprived of EFAs. The median plasma phospholipid concentration of linoleic acid decreased by 21.9%, >16.3%, >13.8%, 11.0%, and >7.7% and linolenic acid by 0.3%, 0.2%, 0.2%, >0.2%, and 0.1%, respectively, in 10 healthy control subjects and groups A, B, C, and D (P < 0.001). CONCLUSIONS: Intestinally absorbed EFAs maintained plasma EFA status better than did an equal quantity of parenterally supplied EFAs. Intravenous requirements of EFAs in patients with negligible absorption of EFAs are probably higher than the amounts recommended to patients with preserved intestinal absorption of EFAs.

Pharmacokinetic data of gamma-linolenic acid in healthy volunteers after the administration of evening primrose oil (Epogam).

Defects in the metabolism of gamma-linolenic acid are thought to play a major role in the pathogenesis of atopic eczema, but little is known about the pharmacokinetic behavior of this fatty acid and its metabolic products. We investigated the serum level-time courses of 8 fatty acids after the administration of Epogam, a preparation of evening primrose oil which contains gamma-linolenic acid as an active ingredient. From 6 volunteers, serum concentration time curves of gamma-linolenic acid and 7 other fatty acids were profiled 24 h with and without the administration of Epogam. Six capsules of Epogam were administered to each subject in the morning at 7:00 and further 6 capsules in the evening at 19:00. On the days of investigation the volunteers had a diet of low fat meals. The serum concentrations of the fatty acids were determined as their methyl esters by means of gas chromatography mass spectrometry. Gamma-linolenic acid shows an absorption-elimination pattern after the administration of Epogam and its AUC24h and Cmax are significantly increased over the baseline values. After the evening administration, t(max) is shorter (2.7 +/- 1.2 h) than after the morning administration (4.4 +/- 1.9 h). The other fatty acids show no significant increase in their concentrations, especially dihomo-gamma-linolenic acid and arachidonic acid, which are metabolic products of gamma-linolenic acid. Conclusively, an effect of the administration of gamma-linolenic acid on the serum concentrations of dihomo-gamma-linolenic acid and arachidonic acid and, therefore, on the biosynthesis of prostaglandin PGE1 and PGE2 could not clearly be established in healthy volunteers. Further investigations will show if there is a significant effect in patients suffering from atopic eczema.

Metabolic conversion and growth effects of n-6 and n-3 polyunsaturated fatty acids in the T47D breast cancer cell line.

The incorporation and conversion of polyunsaturated fatty acids (PUFA) of n-3 and n-6 families were examined in the T47D breast cancer cell line in parallel with their effects on cell proliferation. In low serum-containing medium, PUFA exerted differential growth effects, depending both on their affiliation and unsaturation degree. The study of PUFA processing suggested that T47D cells are deficient in delta 6 and delta 4-desaturation activities whereas they can process to delta 5-desaturation. Thus, the PUFA growth effect on T47D cells appeared to be associated with a lack of desaturation.

A high-density-lipoprotein receptor appears to mediate the transfer of essential fatty acids from high-density lipoprotein to lymphocytes.

It has been shown previously that a specific high-density lipoprotein (HDL) receptor exists on human lymphocytes that recognizes apoprotein (apo) A1 as its ligand, and may be responsible for utilization of HDL lipids to respond optimally to mitogenic stimulation when cultured in serum-free medium supplemented with HDL. To clarify further the relationship between various HDL lipids used by lymphocytes and HDL receptor activity, the lipid composition of the cells and the regulation of HDL and low-density lipoprotein (LDL) receptors on freshly isolated lymphocytes and mitogen-activated T-blasts after treatment with lipoproteins, liposomes or fatty acids were investigated. Our data show that the linear increase in cell proliferation correlates with the presence of HDL in fatty-acid-free culture medium in the concentration range of HDL receptor saturation. Decreased binding/uptake of dioctadecylindocarbocyanine (DiI)-fluorescence-labelled HDL by freshly isolated lymphocytes was observed in the presence of unlabelled HDL in 4-day culture, whereas T-blast binding/uptake was down-regulated by preincubation not only with HDL but also with LDL. T-blasts pretreated with HDL showed increased cellular contents of phosphatidylcholine, oleic acid (C18:1,n-9) and linoleic acid (C18:2,n-6), which are essential for optimal proliferation of mitogen-stimulated lymphocytes. Furthermore, DiI-HDL binding on lymphocytes was down-regulated by up to 20% (resting T cells) and 50% (T-blasts) when cultured in the presence of apoA1-phosphatidylcholine liposomes (T-blasts only), oleic acid or linoleic acid, but not by stearic acid (C18:0). The results indicate that HDL provide lymphocytes with essential fatty acids, which in turn regulate HDL receptor activity.