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)

Injectable lipid emulsions-advancements, opportunities and challenges.

Injectable lipid emulsions, for decades, have been clinically used as an energy source for hospitalized patients by providing essential fatty acids and vitamins. Recent interest in utilizing lipid emulsions for delivering lipid soluble therapeutic agents, intravenously, has been continuously growing due to the biocompatible nature of the lipid-based delivery systems. Advancements in the area of novel lipids (olive oil and fish oil) have opened a new area for future clinical application of lipid-based injectable delivery systems that may provide a better safety profile over traditionally used long- and medium-chain triglycerides to critically ill patients. Formulation components and process parameters play critical role in the success of lipid injectable emulsions as drug delivery vehicles and hence need to be well integrated in the formulation development strategies. Physico-chemical properties of active therapeutic agents significantly impact pharmacokinetics and tissue disposition following intravenous administration of drug-containing lipid emulsion and hence need special attention while selecting such delivery vehicles. In summary, this review provides a broad overview of recent advancements in the field of novel lipids, opportunities for intravenous drug delivery, and challenges associated with injectable lipid emulsions.

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.

Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers.

The effects of cigarette smoking on n-3 essential FA metabolism were studied in male and female subjects by fitting the concentration-time curves of the d(5)-labeled plasma fatty acids (FAs) originating from a dose of d(5)-18:3n-3 to a compartmental model of n-3 FA metabolism. For 3 weeks, female (smokers, n = 5; nonsmokers, n = 5) and male (smokers, n = 5; nonsmokers, n = 5) subjects subsisted on a beef-based diet. Beginning in the third week, subjects received a dose of d(5)-18:3n-3 ethyl ester (1 g). Plasma FAs were analyzed using gas chromatography (GC) and GC-mass spectrometry, and the kinetic rate parameters were determined from the concentration-time curves for d(5)-18:3n-3, d(5)-20:5n-3, d(5)-22:5n-3, and d(5)-22:6n-3. Women smokers had a 2-fold greater percent of dose in plasma (5.8% vs. 2.9%; P < 0.01) and a higher fractional rate constant coefficient for formation of d(5)-22:6n-3 from d(5)-22:5n-3 (0.03 h(-1) vs. 0.01 h(-1); P < 0.01), compared with nonsmokers. Male smokers had elevated total plasma n-3 FAs, more-rapid turnover of 18:3n-3 (13.3 mg/day(-1) vs. 4.3 mg/day(-1); P < 0.001), a disappearance rate of d(5)-20:5n-3 that was both delayed and slower (0.001 h(-1) vs. 0.012 h(-1); P < 0.05), and a percentage of d(5)-20:5n-3 directed into formation of d(5)-22:5n-3 (99% vs. 61%; P < 0.03) that was greater compared with nonsmokers. Smoking increased the bioavailability of n-3 FAs from plasma, accelerated the fractional synthetic rates, and heightened the percent formation of some long-chain n-3 PUFAs in men and women.

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

Simultaneous quantitative determination of deuterium- and carbon-13-labeled essential fatty acids in rat plasma.

This study reports methods for the quantitative determination of stable isotope-labeled essential fatty acids (EFAs) as well as an experiment in which deuterium-labeled linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) were compared with those labeled with carbon-13 in rat plasma in vivo. Standard curves were constructed to compensate for concentration and plasma matrix effects. It was observed that endogenous pools of fatty acids had a greater suppressing effect on the measurements of 13C-U-labeled EFAs relative to those labeled with 2H5. Using these methods, the in vivo metabolism of orally administered deuterated-linolenate, 13C-U-labeled linolenate, deuterated-linoleate, and 13C-U-labeled linoleate was compared in adult rats (n = 11). There were no significant differences in the concentrations of the 2H versus 13C isotopomers of 18:2n-6, 18:3n-3, arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3) in rat plasma samples at 24 h after dosing. Thus, there appears to be little isotope effect for 2H5- versus 13C-U-labeled EFAs when the data are calculated using the conventional standard curves and corrected for endogenous fatty acid pool size and matrix effects.

Dietary essential fatty acids in immune function and brain development

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Regional uptake of meal fatty acids in humans.

Two protocols were performed to study meal fatty acid metabolism. In protocol 1, 14 patients scheduled for elective intra-abdominal surgery (11 undergoing bariatric surgery for severe obesity) consumed a meal containing [3H]triolein in the evening before surgery. This allowed us to measure adipose tissue lipid specific activity (SA) in mesenteric and omental, deep and superficial abdominal subcutaneous adipose tissue. Intra-abdominal adipose tissue lipid SA was greater than subcutaneous lipid SA. There were no significant differences between mesenteric and omental or between deep and superficial abdominal subcutaneous adipose tissue. In protocol 2, meal fatty acid oxidation and uptake into subcutaneous and omental adipose tissue ([3H]triolein) were measured in six normal, healthy volunteers. Meal fatty acid oxidation (3H2O generation) plus that remaining in plasma ( approximately 1%) plus uptake into upper body subcutaneous, lower body subcutaneous, and visceral fat allowed us to account for 98 +/- 6% of meal fatty acids 24 h after meal ingestion. We conclude that omental fat is a good surrogate for visceral fat and that abdominal subcutaneous fat depots are comparable with regard to meal fatty acid metabolic studies. Using [3H]triolein, we were able to account for virtually 100% of meal fatty acids 24 h after meal ingestion. These results support the meal fatty acid tracer model as a way to study the metabolic fate of dietary fat.

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.

Analysis of the intestinal absorption of essential fatty acids in vivo in the rat.

The absorption and competition kinetics of the essential fatty acids (EFAs), linoleic acid (LA), alpha-linolenic acid (alphaLnA) and arachidonic acid (AA) in vivo were studied in the perfused rat jejunum. Uptake of each EFA on its own followed saturable kinetics at low luminal concentrations, suggesting a facilitative transport process, the affinity of which increased with chain length and degree of unsaturation. Absorption of one EFA was enhanced by low, whilst competitively inhibited by high, concentrations of a second EFA. Whereas LA and alphaLnA each interfered with the absorption of one another, both had little effect on AA. There was a strong inverse correlation between the relative unsaturation of an EFA and the change in Km of its absorption observed upon inhibition with another EFA. Overall, the results indicated a specific absorptive mechanism, probably involving a transport protein, the affinity of which increased with the degree of unsaturation of the EFA.

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.

Intestinal absorption of essential fatty acids under physiological and essential fatty acid-deficient conditions.

The adequate supply of essential fatty acids (EFA) to the body depends upon sufficient dietary intake and subsequent efficient intestinal absorption. Lipid malabsorption is not only a leading cause of EFA deficiency (EFAD), but also occurs secondarily to EFAD. Understanding the relationship between EFAD and lipid malabsorption may be helpful in the development and optimization of oral treatment strategies. Sequential steps involved in EFA absorption, including lipolysis, solubilization by bile, uptake into the enterocyte, and chylomicron secretion into lymph are reviewed, both under physiological and EFAD conditions. EFAD in itself affects the deficiency state by impairment of EFA absorption due to its effects on bile formation and on chylomicron secretion. These processes may be interrelated as decreased phosphatidylcholine secretion into the bile (a consequence of EFAD) is known to result in decreased chylomicron assembly and secretion. Possible treatments of EFAD include increasing dietary amounts of triacylglycerols and/or specifically tailoring lipids (structured triacylglycerols, EFA-rich phosphatidylcholines, EFA-ethyl esters). It is forseen that insights into the relationship between lipid malabsorption and EFAD will refine rational approaches to prevent and treat EFAD in specific patient groups.