Dietary Fatty Acid Supplementation Research Articles

P92 - Psychiatric disorders and omega-3 fatty acids

Psychiatric disorders, especially mood disorders in children and adolescent are serious problem of all over the world in the field of child and adolescent psychiatry. In the recent years mood disorders occur in the earlier age. The prevalence of major depression (MD) is about 1-2% in preadolescent children and 3-8% in adolescents. When the major depression is not treated there is a big risk of worsening of symptoms, risk of suicide and development of comorbid disorders. The quality of life of the patient and its family is decreasing in the whole view.The molecular basis of major depression is not well known. The main pathomechanism of MD is in noradrenergic, serotonergic and dopaminergic pathway dysregulation, nutition factors, which can influence structure and metabolism of lipids. It was found decreased level of omega 3 fatty aids (FA), increased ratio of omega 6/omega 3 FA in the serum and in erythrocyte membrane.It is supposed that the oxidative neuronal injury can be prevented by dietary supplementation of antioxidants and that membrane phospholipids can be repaired by dietary supplementation of fatty acids. Omega-3 fatty acids may also participate in modulation of membrane fluidity, which influences the transmission of neurotransmitters. The membrane fluidity is affected by the ratio of phospholipids to free cholesterol. In addition, activation of the inflammatory response was found in depressive patients through increased production of pro-inflammatory cytokines (IL-1b, IL-6, interferon gamma, TNF-alpha) and eicosanoids (prostaglandin E2) in blood and cerebrospinal fluid. This results in increased lipid peroxidation and degradation of polyunsaturated fatty acids, which may result in increased oxidative stress. Omega-3 fatty acids also stimulate anti-inflammatory cytokines (IL-10) or inhibit the cyclooxygenase, platelet aggregation and formation of eicosanoids. The potential molecular mechanisms will be discussed.

Omega-3 fatty acids and the increased risk of bleeding

U.S. consumers spend more than $6 billion annually on omega-3 fatty acid (n-3FA) dietary supplements and fortified foods, plus another $916 million on prescription fish oil capsules.1 Many n-3FA supplements are available OTC. Two prescription formulations, omega-3-acid ethyl esters (Lovaza—GlaxoSmithKline) and icosapent ethyl (Vascepa— Amarin Pharma), also are currently available.

Childhood asthma and obesity—what is the true link?

Obesity rates have increased significantly in children in many parts of the world, especially in North America.1 According to data from the most recent National Health and Nutrition Examination Survey, approximately 17% (or 12.5 million) of US children and adolescents 2 to 9 years old are obese.2 The impact that childhood obesity has on pediatric diseases has become a major prevention initiative by the Obama administration and several public health organizations. Children with obesity are at increased risk for developing asthma, one of the most common chronic diseases in children.3 Childhood asthma accounts for more than 14 million missed school days per year and is the primary cause of school absences in the United States.4 A relation between obesity and asthma is supported by prospective studies in adults and children suggesting that being overweight and obese can precede the onset of asthma5 and studies in adults showing alleviation of asthma symptoms with weight loss.6 Despite consistent evidence linking obesity to the incidence and prevalence of asthma and several postulated hypotheses to explain this association, a definitive mechanism remains a mystery. Genetic and Environmental Factors Asthma and obesity are likely to be connected in a multifactorial fashion. Although genetic susceptibility can contribute to the development of asthma and obesity, the rapid increase in a relatively short period suggests that changes in lifestyle, such as diet, physical activity, early life exposures, and other environmental interactions, also can play a role. Epigenetic mechanisms associated with obesity and asthma have been proposed. Obesity and asthma likely have their beginnings in utero and in early childhood. Diet and nutrition, especially prenatal and early infant diet, may play a part in these diseases. Greater consumption of fruits and vegetables, antioxidants, minerals and vitamins, fish, and legumes during pregnancy seems to confer protection against childhood asthma and wheeze7 and may influence the neonatal immune system and lung development.8 However, 1 study showed that fatty acid dietary supplementation during pregnancy did not lower the overall incidence of asthma.9 To further support the idea that intrauterine nutrition is important, associations between low birth weight and resulting obesity and asthma have been shown. In 1 study, low birth weight led to the development of asthma and excess body mass increased the risk.10 Rapid growth in body mass index (BMI) during the first 2 years of life increased the risk of asthma up to 6 years of age based on published data from 8 European birth cohorts.11

Dietary Medium Chain Fatty Acid Supplementation Leads to Reduced VLDL Lipolysis and Uptake Rates in Comparison to Linoleic Acid Supplementation

Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.

Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to critically influence brain development and functions. Dietary supplementation with n-3 PUFAs has been suggested as a non-pharmacological therapy for a number of developmental disorders, e.g., autistic spectrum disorders (ASD), but human studies so far have led to conflicting results. Furthermore, it has been hypothesized that the therapeutic impact of n-3 PUFAs on these disorders might be explained by their anti-inflammatory properties and their promoting effects on synaptic function and plasticity, but no clear evidence has been produced in this direction. We evaluated the impact of n-3 PUFA dietary supplementation in a mouse model of fragile X syndrome (FXS), i.e., a major developmental disease and the most frequent monogenic cause of ASD. Fmr1-KO and wild-type mice were provided with a diet enriched or not with n-3 PUFAs from weaning until adulthood when they were tested for multiple FXS-like behaviors. The brain expression of several cytokines and of brain-derived neurotrophic factor (BDNF) was concomitantly assessed as inflammatory and synaptic markers. n-3 PUFA supplementation rescued most of the behavioral abnormalities displayed by Fmr1-KO mice, including alterations in emotionality, social interaction and non-spatial memory, although not their deficits in social recognition and spatial memory. n-3 PUFAs also rescued most of the neuroinflammatory imbalances of KOs, but had a limited impact on their BDNF deficits. These results demonstrate that n-3 PUFAs dietary supplementation, although not a panacea, has a considerable therapeutic value for FXS and potentially for ASD, suggesting a major mediating role of neuroinflammatory mechanisms.

Omega-3 Fatty Acids Could Alleviate the Risks of Traumatic Brain Injury – A Mini Review

Traumatic brain injury (TBI) is an acquired brain trauma that occurs when any sudden trauma/injury causes damage to the brain. TBI is characterized by tissue damage and imbalance in the cerebral blood flow and metabolism. It has been established through laboratory experiments that the dietary supplementation of omega-3 fatty acids (FAs) could reduce the oxidative stress developed in brain due to TBI. The inclusion of omega-3 FA in diet could normalize the levels of brain-derived neurotrophic factor (BDNF), and thus, it could restore the survival of neuronal cells. BDNF improves the synaptic transmission by regulating synapsin 1 and cyclic adenosine monophosphate (cAMP) response element binding protein. The brain tissue analysis of TBI models supplemented with omega-3 polyunsaturated fatty acids (PUFAs) showed significantly reduced lipid peroxidation, nucleic acid and protein oxidation, thereby promoting neuronal and glial cell survival. Thus, omega-3 FA intake could be considered as a therapeutic option to reduce the secondary neuronal damages initiated by TBI.

Benefits of omega-3 fatty acid dietary supplementation on health-related quality of life in patients with meibomian gland dysfunction.

BackgroundWe assessed the impact of a dietary supplement based on the combination of omega-3 essential fatty acids and antioxidants on health-related quality of life in patients with meibomian gland dysfunction (MGD).MethodsPatients of either sex (aged 18–85 years) diagnosed with MGD according to criteria identified at a 2011 International Workshop on Meibomian Gland Dysfunction participated in this randomized, double-masked, placebo-controlled study. Group A patients (controls) received an oral placebo supplement and group B patients received the oral study supplement (Brudysec® 1.5 g; Brudy Laboratories, Barcelona, Spain). At baseline and at 3-month follow-up, the patients completed the 36-Item Short Form Health Survey questionnaire using a Spanish validated version. The Physical (PCS) and Mental (MCS) Component Summary scores were the main outcome variables.ResultsA total of 61 patients completed the study (group A, n=31; group B, n=30). There were no significant differences in PCS and MCS scores at baseline between the two study groups, but after 3 months of treatment, significantly higher mean PCS and MSC scores were observed in patients treated with the active omega-3 dietary supplement as compared with controls (mean [standard deviation] PCS score 53.33±5.57 versus 47.46±7.31, P=0.008; mean MCS score 54.60±5.64 versus 47.80±8.45, P=0.0005). Moreover, mean differences between values at 3 months as compared with baseline were statistically significant for patients in group B (PCS score 7.14±5.81, 95% confidence interval 4.97–9.31, P=0.000; MCS score 5.96±7.64, 95% confidence interval 3.10–8.81, P=0.0002), whereas mean differences in patients assigned to group A were not statistically significant.ConclusionDietary supplementation with a combination of omega-3 essential fatty acids and antioxidants had a significant beneficial effect on HRQoL (health-related quality of life) in patients with MGD.

Dietary pre‐exposure of rats to fish oil does not enhance myocardial efficiency of isolated working hearts or their left ventricular trabeculae

Numerous epidemiological studies, supported by clinical and experimental findings, have suggested beneficial effects of dietary fish or fish oil supplementation on cardiovascular health. One such experimental study showed a profound (100%) increase in myocardial efficiency (i.e. the ratio of work output to metabolic energy input) of the isolated whole heart, achieved by a corresponding decrease in the rate of myocardial oxygen consumption. However, a number of other investigations have returned null results on the latter energetic index. Such conflicting findings have motivated us to undertake a re-examination. To that effect, we investigated the effects of dietary fatty acid supplementation on myocardial mechano-energetics, with our primary focus on cardiac efficiency. We used both isolated hearts and isolated left ventricular trabeculae of rats fed with one of three distinct diets: reference (REF), fish oil-supplemented (FO) or saturated fat-supplemented (SFA). For all three groups, and at both spatial levels, we supplied 10 mm glucose as the exogenous metabolic substrate. In the working heart experiments, we found no difference in the average mechanical efficiency among the three dietary groups: 14.8 ± 1.1% (REF), 13.9 ± 0.6% (FO) and 13.6 ± 0.7% (SFA). Likewise, we observed no difference in peak mechanical efficiency of left ventricular trabeculae among the REF, FO and SFA groups: 13.3 ± 1.4, 11.2 ± 2.2 and 12.5 ± 1.5%, respectively. We conclude that there is no effect of a period of pre-exposure to a diet supplemented with either fish oil or saturated fatty acids on the efficiency of the myocardium at either spatial level: tissue or whole heart.

Omega-3 fatty acids and protein metabolism

The increased age observed in most countries, with the associated higher rates of chronic illnesses and cancer, and a diffuse sedentary lifestyle, will increase the number of patients with clinically relevant anabolic resistance, sarcopenia and its complications. The need for solutions to this major health issue is, therefore, pressing. The metabolic derangements and other consequences associated with sarcopenia can be slowed or even prevented by specific nutritional interventions. New evidence is available about the efficacy of omega-3 fatty acid dietary supplementation to improve protein metabolism and counteract anabolic resistance through indirect effects. Studies show that the anabolic stimuli from substrates (e.g. amino acids or proteins), hormones (e.g. insulin) and/or physical activity in skeletal muscle can be enhanced by long-term fish oil administration. The review of data from recent studies on this topic suggests that dietary omega-3 fatty acid supplementation, in association with an anabolic stimulus, could potentially provide a safe, simple and low-cost intervention to counteract anabolic resistance and sarcopenia. This intervention may contribute to prevent cachexia and disabilities. Supplementation should be given in the earlier stages of sarcopenia (e.g. precachexia). Further research should, however, be performed to better understand the mechanisms involved and the best dosage and timing of administration.

Omega-3 PUFA supplementation differentially affects behavior and cognition in the young and aged non-human primate Grey mouse lemur (Microcebus murinus)

Data are divergent about the ability of dietary ω3 fatty acids to prevent age-associated cognitive decline. Most of the clinical trials failed to demonstrate a protective effect of ω3 fatty acids against cognitive decline and methodological issues are still under debate. Conversely to human studies, experiments performed in adult rodents clearly indicate that long chain ω3 fatty acids play a beneficial role in behavioral and cognitive functions. Inconsistent observations between human and rodent studies highlight the importance of the use of non-human primate models. We recently started a series of experiments on Grey mouse lemurs, an emerging non-human primate model of aging in order to assess the impact of ω3 fatty acids dietary supplementation on several brain functions. These experiments started with the determination of the fatty acids composition of target organs (brain, adipose tissue, liver, plasma) of animals fed under control diet. We then explored the impact of ω3 polyunsaturated fatty acids (PUFA) supplementation on cognition and behavior in young and aged grey mouse lemurs. The aim of the present review is to compare the observations made in young and aged grey mouse lemurs and to explore the possibilities of new experiments in order to bridge the gap between rodents and Humans.

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome.

To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome. A prospective, interventional, placebo controlled, double blind randomized trial was done at two referral eye centers. Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule (500mg) two times a day containing 325mg EPA and 175mg DHA for 3 months (omega-3 group). The omega-3 group was compared to a group of patients (n=254) who received a placebo (placebo group). There were 4 patient visits (at baseline, 1 month, 2 months and 3 months). On each visit, recording of corrected distance visual acuity (CDVA), slit lamp examination and questionnaire based symptom evaluation and scoring was done. A symptomatic score of 0-6 was mild, 6.1-12 moderate and 12.1-18 severe dry eye. Response to intervention was monitored by routine tear function tests like Schirmer I test, tear film break-up time (TBUT), Rose Bengal staining and most notably, conjunctival impression cytology. Sixty-five percent of patients in the omega-3 group and 33% of patients in placebo group had significant improvement in symptoms at 3 months (P=0.005). There was a significant change in both Schirmer's test value and TBUT values in the omega-3 group (P<0.001), both comparisons. However, there was a larger drift in TBUT values in omega-3 than the placebo group, in comparison to Schirmer's test values. The mean TBUT score was 2.54±2.34 in the omega-3 group and 0.13±0.16 in placebo group, respectively. The mean reduction in symptom score in omega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebo group (P<0.001). Despite a slight increase mean score, the Schirmer scores did not correlate well with symptomatic improvement. Omega-3 fatty acids have a definite role for dry eye syndrome. The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease. The role of omega fatty acids in tear production and secretion needs further evaluation.

Treatment with omega-3 fatty acid ethyl-ester alters fatty acid composition of lipoproteins in overweight or obese adults with insulin resistance

IntroductionThe effects of dietary fatty acid supplementation on lipoprotein fatty acid composition have rarely been described. Patients and methodsSixty-one overweight and obese adults with dyslipidemia and insulin resistance were randomized to placebo, 2g/day extended-release nicotinic acid (ERN), 4g/day prescription omega-3 fatty acid ethyl ester (P-OM3), or combination therapy for 16 weeks. Lipoprotein fatty acid composition was analyzed by gas chromatography pre- and post-treatment. ResultsTreatment with P-OM3 or combination, but not ERN, increased proportions of eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, and reduced those for arachidonic acid in all lipoprotein fractions, with greatest impact in the high-density lipoprotein fraction. P-OM3-induced changes in eicosapentaenoic acid within low-density lipoproteins and very low-density lipoproteins were associated with beneficial effects on mean arterial pressure and pulse pressure. ConclusionsP-OM3 supplementation, with or without ERN, was associated with differentially altered lipoprotein fatty acid composition and improved blood pressure parameters.

Maternal omega-3 fatty acid intake increases placental labyrinthine antioxidant capacity but does not protect against fetal growth restriction induced by placental ischaemia–reperfusion injury

Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders. Oxidative stress occurs when excess reactive oxygen species (ROS) damages cellular components, an outcome limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) also limits ROS production. We recently reported that maternal dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation reduced placental oxidative damage and enhanced fetal and placental growth in the rats. Here, we examined the effect of n-3 PUFAs on placental antioxidant defences and whether n-3 PUFA supplementation could prevent growth restriction induced by placental ischaemia-reperfusion (IR), a known inducer of oxidative stress. Rats were fed either standard or high-n-3 PUFA diets from day 1 of pregnancy. Placentas were collected on days 17 and 22 in untreated pregnancies (term=day 23) and at day 22 following IR treatment on day 17. Expression of several antioxidant enzyme genes (Sod1, Sod2, Sod3, Cat, Txn1 and Gpx3) and Ucp2 was measured by quantitative RT-PCR in the placental labyrinth zone (LZ) and junctional zone (JZ). Cytosolic superoxide dismutase (SOD), mitochondrial SOD and catalase (CAT) activities were also analyzed. Maternal n-3 PUFA supplementation increased LZ mRNA expression of Cat at both gestational days (2- and 1.5-fold respectively; P<0.01) and female Sod2 at day 22 (1.4-fold, P<0.01). Cytosolic SOD activity increased with n-3 PUFA supplementation at day 22 (1.3-fold, P<0.05). Sod1 and Txn1 expression decreased marginally (30 and 22%, P<0.05). JZ antioxidant defences were largely unaffected by diet. Despite increased LZ antioxidant defences, maternal n-3 PUFA supplementation did not protect against placental IR-induced growth restriction of the fetus and placental LZ.

The Eicosapentaenoic Acid Metabolite 15-Deoxy-δ12,14-Prostaglandin J3 Increases Adiponectin Secretion by Adipocytes Partly via a PPARγ-Dependent Mechanism

The intake of ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA) increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ12,14-PGJ3 (15d-PGJ3), a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ)-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s) for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation.

The omega-3 fatty acid eicosapentaenoic acid accelerates disease progression in a model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease characterised by loss of motor neurons that currently has no cure. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), have many health benefits including neuroprotective and myoprotective potential. We tested the hypothesis that a high level of dietary EPA could exert beneficial effects in ALS. The dietary exposure to EPA (300 mg/kg/day) in a well-established mouse model of ALS expressing the G93A superoxide dismutase 1 (SOD1) mutation was initiated at a pre-symptomatic or symptomatic stage, and the disease progression was monitored until the end stage. Daily dietary EPA exposure initiated at the disease onset did not significantly alter disease presentation and progression. In contrast, EPA treatment initiated at the pre-symptomatic stage induced a significantly shorter lifespan. In a separate group of animals sacrificed before the end stage, the tissue analysis showed that the vacuolisation detected in G93A-SOD1 mice was significantly increased by exposure to EPA. Although EPA did not alter motor neurone loss, EPA reversed the significant increase in activated microglia and the astrocytic activation seen in G93A-SOD1 mice. The microglia in the spinal cord of G93A-SOD1 mice treated with EPA showed a significant increase in 4-hydroxy-2-hexenal, a highly toxic aldehydic oxidation product of omega-3 fatty acids. These data show that dietary EPA supplementation in ALS has the potential to worsen the condition and accelerate the disease progression. This suggests that great caution should be exerted when considering dietary omega-3 fatty acid supplements in ALS patients.

Chemical analysis of omega‐3 (n‐3) fatty acid supplements for the Dietary Supplement Ingredient Database (DSID)

A study of a national sample of n‐3 fatty acid dietary supplement products included multiple lots of 83 fish oil, flax oil and fish/plant oil blends purchased from retail and direct channels. Products were analyzed for six n‐3 fatty acids using validated methods and certified reference materials, and data were compared to label information. Preliminary results show mean % differences from label within 10% of label claims for the major n‐3 fatty acids: alpha‐linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The minor n‐3 fatty acids, docosapentaenoic acid (DPA) and stearodonic acid (SDA) each add about 7–8% to the EPA+DHA totals for fish oil products. Some lab methods have additional fatty acids included in the total. Product labels listed a total n‐3 fatty acid amount 65% (n=54) of the time, with a variety of calculations indicated. The optimum number of n‐3 fatty acids to include in the DSID totals for comparison to labels is being investigated. National estimates for n‐3 fatty acids will be included in the next release of the DSID, which currently reports estimates of ingredients in multivitamin dietary supplements (http://dsid.usda.nih.gov). Funding: ARS/USDA &amp; ODS/NIH Y1CN501006

Nutrition and the risk of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD.

A Dietary Supplement with a High Eicosapentaenoic Acid to Docosahexaenoic Acid Ratio Reduces Triglyceride Levels in Mildly Hypertriglyceridemic Subjects

There is compelling evidence that omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) provide cardioprotective benefits. This open-label study evaluated whether an omega-3 fatty acid dietary supplement with a high EPA to DHA ratio (2.3:1) reduces triglyceride (TG) levels in mildly hypertriglyceridemic subjects. Twenty subjects, with a mean baseline TG level of 321.7 ± 108.7 mg/dL, were administered 4 g/day of Ocean BlueProfessional Omega-3 2100TM (OB) supplements. Each gram of OB contains the ethyl esters of EPA (675 mg) and DHA (300 mg). Baseline and end of study blood values were collected to assess changes in fasting levels of TG, total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). Supplementation was provided for 30 to 228 days (mean = 106 ± 50 days). Mean age at enrollment was 50.3 ± 6.3 years. Compared with baseline values, mean TG levels decreased by 48% (p = 0.001). There were no changes in TC and HDL-C levels (p = NS); however, subjects had a significant increase in LDL-C levels (16.4%, p = 0.05). Results indicated that a high ratio of EPA to DHA (>2:1) had a statistically significant TG-lowering effect in mildly hypertriglyceridemic subjects. The lipid effects of OB are compared with those published in the literature for n-3 drugs indicated for hypertriglyceridemia (very high TG levels, > 500 mg/dL).

Fish Omega-3 Fatty Acids Induce Liver Fibrosis in the Treatment of Bile Duct-Ligated Rats

Biliary atresia-induced cholestasis increases hepatic oxidative stress with eventual progression to cirrhosis and liver failure. Omega-3 fatty acids play a possible role in the regulation of oxidative stress and the improvement of cholestasis. The goal of the present study is to investigate the role of dietary supplementation of fish omega-3 fatty acids in the reduction of hepatocellular damage by using a rat common bile duct ligation model. Sprague-Dawley rats received either sham or bile duct ligation (BDL) and were divided into four study groups: Sham+saline (Sham+sal) group, Sham+Fish oil (Sham+FO) group, BDL+saline (BDL+sal) group, and BDL+Fish oil (BDL+FO) group. Rats from each group were assigned to receive, besides regular chow, once daily with either normal saline or fish omega-3 fatty acids (0.4 % of its own body weight) via gavage for 10 days. Samples of blood, liver tissue homogenates, and histological studies from different groups were analyzed at the end of the study. Rats from BDL+FO had significantly impaired liver function as compared to other study groups (p < 0.05 is of significant difference). Ishak scores and the TGF-b1 contents were significantly higher in rats that received BDL+FO, p < 0.05. Contrary to TGF-b1 liver content, rats from the BDL+FO group had the lowest glutathione levels among the study groups, p < 0.05. Fish omega-3 fatty acids supplementation, albeit increased tissue content of DHA, tended to increase liver fibrosis in BDL rats, decrease liver glutathione level, and compromise hepatic function; fish oil supplementation to subjects with biliary atresia might be of potential hazard and should be used with caution.

An ω-6 Fatty Acid, Dgla, Prevents Platelet Activation and Thrombosis in Vivo.

AbstractAbstract 2169Platelets play a pivotal role in thrombotic events leading to clot formation and clot stability in vivo. Uncontrolled signaling events in the platelet can result in unwanted thrombosis, which may eventually lead to the development of myocardial infarction or stroke. Previously, we have shown that ex vivo treatment of human platelets with the ω-6 fatty acid dihomo-γ-linolenic acid (DGLA) or its eicosanoid derived from 12-LOX oxidation, 12-hydroxyeicosatrienoic acid (12(S)-HETrE), inhibits PAR and collagen-induced platelet aggregation, clot retraction, and GPIIbIIIa activation. Since early studies have shown dietary supplementation of fatty acids increase fatty acid incorporation into the platelet lipid membrane (Barre, DE Lipids 1992; 27(5): 315–320; Marry, MJ Prostaglandins Leukot Essent Fatty Acids 1997; 56(3):223–223), we postulated that altering fatty acid composition in the platelet through dietary supplementation in vivo may be a viable approach to inhibiting platelet function. Therefore, a longitudinal study of wild-type mice on normal chow compared to mice supplemented with high (.5 g/kg) or low (.13 g/kg) DGLA diets was conducted. Each set of mice (7–8 mice) was given the designated diet for a period of 1, 2, or 3 months. At each time point, tail bleeding times and ex vivo platelet function in PRP were performed. Tail bleeding times from mice on the high DGLA diet were significantly prolonged by more than 15 minutes. Further, a smaller but statistically significant delay in clotting time was observed in mice on the low DGLA diet compared with control mice. Additionally, ex vivo aggregation response to collagen (1 μg/mL to 20 μg/mL) and PAR4-AP (50 μM to 500 μM) in platelets from mice on the high DGLA diet showed significant shifts to the right in their ability to induce platelet aggregation compared with control mice suggesting these mice were protected against thrombosis. JON/A and P-selectin binding to the PRP of high and low DGLA were also significantly attenuated in response to PAR4-AP. This study, which evaluated the in vivo and ex vivo effects of DGLA on regulation of platelet reactivity, supports DGLA as a potent, endogenous anti-thrombotic agent. Understanding the mechanistic details by which DGLA protects against thrombosis and maintains hemostasis through its COX-1 and 12-LOX-dependent bioactive metabolites will help to identify the potential viability of this target for anti-platelet intervention. Disclosures:No relevant conflicts of interest to declare.