Depression and long chain n-3 fatty acids in adipose tissue in adults from Crete

BACKGROUND: Only one study has investigated the relationship of essential fatty acids in the adipose tissue with depression in adults and suggested an inverse relationship between docosahexaenoic acid (22:6 n-3) (DHA) and depression. OBJECTIVE: To examine the relation between adipose tissue polyunsaturated fatty acids especially n-3 and n-6 fatty acids, an index of long-term or habitual fatty acid intake, and depression in adults. DESIGN: Cross-sectional study of healthy adults from the island of Crete. SETTING: The Preventive Medicine and Nutrition Clinic, University of Crete, Greece. SUBJECTS: A total of 130 healthy adults (59 males, 71 females) aged 22-58 years. The sample was a sub-sample of the Greek ApoEurope study group. METHODS: Fatty acids were determined by gas chromatography in adipose tissue. Information about depression was obtained through the Zung Self-rating Depression Scale. RESULTS: Adipose tissue DHA was inversely related with depression. Multiple linear regression analysis taking into account the possible confounding effect of age, gender, body mass index, smoking and educational level confirmed this association. CONCLUSIONS: The inverse relationship between adipose DHA and depression in adults, replicates findings of a previous study. This relationship indicates that a low long-term dietary intake of DHA is associated with an increased risk for depression in adults.     

Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition,conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men

The effect of increased dietary intakes of alpha-linolenic acid (ALNA) or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 2 months upon plasma lipid composition and capacity for conversion of ALNA to longer-chain metabolites was investigated in healthy men (52 (SD 12) years). After a 4-week baseline period when the subjects substituted a control spread, a test meal containing [U-(13)C]ALNA (700 mg) was consumed to measure conversion to EPA, docosapentaenoic acid (DPA) and DHA over 48 h. Subjects were then randomised to one of three groups for 8 weeks before repeating the tracer study: (1) continued on same intake (control, n 5); (2) increased ALNA intake (10 g/d, n 4); (3) increased EPA+DHA intake (1.5 g/d, n 5). At baseline, apparent fractional conversion of labelled ALNA was: EPA 2.80, DPA 1.20 and DHA 0.04 %. After 8 weeks on the control diet, plasma lipid composition and [(13)C]ALNA conversion remained unchanged compared with baseline. The high-ALNA diet resulted in raised plasma triacylglycerol-EPA and -DPA concentrations and phosphatidylcholine-EPA concentration, whilst [(13)C]ALNA conversion was similar to baseline. The high-(EPA+DHA) diet raised plasma phosphatidylcholine-EPA and -DHA concentrations, decreased [(13)C]ALNA conversion to EPA (2-fold) and DPA (4-fold), whilst [(13)C]ALNA conversion to DHA was unchanged. The dietary interventions did not alter partitioning of ALNA towards beta-oxidation. The present results indicate ALNA conversion was down-regulated by increased product (EPA+DHA) availability, but was not up-regulated by increased substrate (ALNA) consumption. This suggests regulation of ALNA conversion may limit the influence of variations in dietary n-3 fatty acid intake on plasma lipid compositions.     

Anti-inflammatory and anti-angiogenic effect of long chain n-3 polyunsaturated fatty acids in intestinal microvascular endothelium

Background & aims

The role of endothelial cells in inflammatory bowel disease has been recently emphasized. Endothelial activation and expression of adhesion molecules are critical for leukocytes recruitment into the inflammatory wall. Compelling evidence demonstrated anti-inflammatory effects of long chain n-3 PUFA in inflammatory models. We previously showed that long chain n-3 PUFA (EPA and DHA) inhibited inflammatory response in epithelial and dendritic cells. As long chain n-3 PUFA treatment led to a decreased expression of adhesion molecules in endothelial cells from other organs, we have now investigated their effect on intestinal endothelial cells in vitro and in colitic rats.

Methods

In vitro study: Primary culture of human intestinal microvascular endothelial cells (HIMEC) were pre-treated with DHA and then incubated with IL-1β. In vivo study: Colitis was induced in 2 groups at day0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS). Rats received by gavage either fish oil, rich in EPA and DHA (TNBS+n-3) or an isocaloric isolipidic oil formula for 14 days.

Results

DHA led to a decreased VCAM-1, TLR4, cyclooxygenase-2 and VEGFR2 expression and a decreased production of IL-6, IL-8 and GM-CSF and a reduced production of PGE₂ and LTB₄ (p < 0.001) in IL-1β-induced HIMEC. Similarly, dietary intervention with fish oil rich in EPA and DHA significantly decreased colon production of PGE₂ and LTB_4, endothelial VCAM-1 and VEGFR2 in rats with colitis.

Conclusions

Data obtained from in vitro and in vivo studies reveal a potential anti-angiogenic role of long chain n-3 PUFA in intestinal endothelial cells. This protective effect of long chain n-3 PUFA may partly explain the observed benefit of dietary intake of long chain n-3 PUFA in IBD development.     

Dietary (n-3) long chain polyunsaturated fatty acids prevent sucrose-induced insulin resistance in rats

This study was designed to determine the effect of substituting (n-3) long-chain PUFAs (LCPUFAs) for linoleic acid and hence decreasing the (n-6):(n-3) fatty acid ratio on sucrose-induced insulin resistance in rats. Weanling male Wistar rats were fed casein-based diets containing 100 g/kg fat for 12 wk. Insulin resistance was induced by replacing starch (ST) with sucrose (SU). The dietary fats were formulated with groundnut oil, palmolein, and fish oil to provide the following ratios of (n-6):(n-3) fatty acids: 210 (ST-210, SU-210), 50 (SU-50), 10 (SU-10), and 5 (SU-5). Compared with starch (ST-210), sucrose feeding (SU-210) significantly increased the plasma insulin and triglyceride concentrations and the plasma insulin area under the curve (AUC) in response to an oral glucose load. Adipocytes isolated from rats fed SU-210 had greater lipolytic rate, lower insulin stimulated glucose transport, and lower insulin-mediated antilipolysis than those from rats fed ST-210. Decreasing the dietary (n-6):(n-3) ratio in sucrose-fed rats (SU-10 and SU-5) normalized the plasma insulin concentration and the AUC of insulin after a glucose load. The sucrose-induced increase in plasma triglyceride concentration was normalized in rats fed SU-50, SU-10 and SU-5. Further, sucrose-induced alterations in adipocyte lipolysis and antilipolysis were partially reversed and glucose transport improved in rats fed diets SU-5 and SU-10. In diaphragm phospholipids, decreasing the (n-6):(n-3) ratio in the diet increased the concentration of (n-3) LCPUFAs with concomitant decreases in the concentration of (n-6) LCPUFAs. These results suggest that (n-3) LCPUFAs at a level of 2.6 g/kg diet [0.56% energy (n-3) LCPUFAs, (n-6):(n-3) ratio = 10] may prevent sucrose-induced insulin resistance by improving peripheral insulin sensitivity.     

Estimated conversion of α-linolenic acid to long chain n-3 polyunsaturated fatty acids is greater than expected in non fish-eating vegetarians and non fish-eating meat-eaters than in fish-eaters

Background: It is believed that n‐3 polyunsaturated fatty acid (PUFA) status is important for cardiovascular health. However, the major sources of the essential dietary PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are fish and fish oil supplements. Limited conversion of α‐linoleic acid (ALA), found in plant foods (flaxseeds, walnuts, soya and rape‐seed oils), to EPA, DPA (docosapentaenoic acid) and DHA occurs in men (0.2–6% for EPA and DPA, ≤0.05% for DHA) but is greater in younger women (Burdge, 2006). Therefore, n‐3 PUFA status may be compromised in individuals not eating fish or fish‐oils, compared with fish‐eaters. An investigation into n‐3 PUFA status and estimated potential conversion of ALA in middle‐aged women with different dietary habits in the EPIC‐Norfolk population was conducted. Methods: Data were collected via a nurse examination between 1993 and 1997 (Welch, 2006). Circulating plasma phospholipid n‐3 PUFA were measured using gas liquid chromatography (HP 5980 gas chromatograph) (Welch, 2006). Diet was estimated using a 7‐day food diary and data were entered using the DINER data entry program (Welch, 2001). Only participants with dietary data and plasma fatty acids, who did not consume fish oils, were included in this study (n = 2256). Ethical permission was granted by the Norfolk and Norwich Ethics Committee. Participants were divided according to dietary habit into non‐fish‐eating vegetarians, non‐fish‐eating meat‐eaters and fish‐eaters (97% meat‐eaters). The ratio of circulating long chain n‐3 PUFA (LCn‐3PUFA are the total of EPA, DPA and DHA) to intake of ALA was calculated (PLCn‐3PUFA:DALA). A larger ratio implies greater conversion of ALA. Statistics were performed with STATA 10.0 and as ALA conversion may be affected by dietary EPA, DHA and linoleic acid, age, body mass index (BMI) and smoking habit, the ratio was adjusted for these covariates. The P for the difference between groups was calculated using anova . Results: Although intakes of total n‐3 PUFA were ≈30% lower in vegetarians and meat‐eaters than fish‐eaters, circulating plasma LCn‐3 PUFA were only 12% and 9% lower, respectively. The PLCn‐3PUFA:DALA was greater in vegetarians and meat‐eaters than in fish‐eaters.

Table Table. Population characteristics, diet, n‐3 PUFA status and the ratio of circulating long chain n‐3 PUFA to intake of dietary ALA (PLCn‐3PUFA:DALA) in 2256 women aged 39–78 years

Effect of n-3 long chain polyunsaturated fatty acids during the perinatal period on later body composition

A systematic review to identify studies reporting the effects of n-3 long chain polyunsaturated fatty acids (LCPUFA) intake, during pregnancy and postnatally, on infants and young children's body composition was performed. A structured search strategy was performed in the MEDLINE (PubMed), EMBASE, and LILACS databases. Inclusion and exclusion criteria were defined according to the research question. Only those studies addressing the relationship between n-3 LCPUFA exposure during the perinatal period and later adiposity measured in terms of weight, height, body mass index (BMI), skinfold thickness and/or circumferences were included regardless of the study design. Studies quality was scored and were thereafter categorised into those reporting on maternal intake of n-3 LCPUFA during pregnancy or lactation (6 publications) or on infant's n-3 LCPUFA intake (7 publications). Two studies showed inverse associations between maternal n-3 LCPUFA intake and children's later body composition (lower adiposity, BMI or body weight), two showed direct associations and no effects were observed in the remaining two studies. Among those studies focusing on n-3 LCPUFA intake through enriched infant formulas; three observed no effect on later body composition and two showed higher weight and adiposity with increased amounts of n-3 LCPUFA. Reversely, in two studies weight and fat mass decreased. In conclusion, reported body composition differences in infants and young children were not clearly explained by perinatal n-3 LCPUFA intake via supplemented formulas, breastfeeding or maternal intakes of n-3 LCPUFA during pregnancy and lactation. Associated operational mechanisms including n-3 LCPUFA doses and sources applied are not sufficiently explained and therefore no conclusions could be made.     

Very long chain n-3 polyunsaturated fatty acids in the food chain in the UK and the potential of animal-derived foods to increase intake

Summary  The very long chain (VLC) n -3 polyunsaturated fatty acids (PUFA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are widely recognised to have beneficial effects on human health. However, recommended intakes of VLC n -3 PUFA (450 mg/day) are not being met by the diet in the majority of the population mainly because of low consumption of oil-rich fish. Current mean intake of VLC n -3 PUFA by adults is estimated to be about 282 mg/day with EPA and DHA contributing about 244 mg/day. Furthermore, the fact that only about 27% of adults eat any oil-rich fish (excluding canned tuna) and knowledge of the poor conversion of α-linolenic acid to EPA and DHA in vivo , particularly in men, leads to the need to review current dietary sources of these fatty acids. Animal-derived foods are likely to have an important function in increasing intake and studies have shown that feeding fish oils to animals can increase the EPA and DHA content of the resulting food products. This paper highlights the importance of examining current and projected consumption trends of meat and other animal products when exploring the potential impact of enriched foods by means of altering animal diets. When related to current food consumption data, potential dietary intakes of EPA+DHA from foods derived from animals fed enriched diets are calculated to be about 231 mg/day. If widely consumed, such foods could have a significant impact on progression of conditions such as cardiovascular disease. Consideration is also given to the sources of VLC n -3 PUFA in animal diets, with the sustainability of fish oil being questioned and the need to investigate the use of alternative dietary sources such as those of algal origin.     

n-3 fatty acids in psoriasis

Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the efficacy and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.     

Lack of dose response by dietary n-3 fatty acids at a constant ratio of n-3 to n-6 fatty acids in suppressing eicosanoid biosynthesis from arachidonic acid

This study evaluated whether it is the ratio of n-3 to n-6 fatty acids or the absolute amount of n-3 fatty acids in diets that determines the degree of inhibition of eicosanoid biosynthesis from arachidonic acid (AA). Rats were fed diets containing different doses of linolenic acid or menhaden oil for 3 mo. Constant ratios of n-3 to n-6 fatty acids were maintained by concomitant increases in safflower oil as the n-6 fatty acid source. Results showed that AA concentrations in liver, platelet, and lung phospholipids and concentrations of eicosanoids synthesized in tissues were significantly (P less than 0.05) suppressed both by linolenic acid and menhaden oil; however, there was a lack of a dose response within groups fed different amounts of the same dietary fat. These results indicate that the ratio of n-3 to n-6 fatty acids in the diets, rather than the absolute amount of n-3 fatty acids, is the determining factor in inhibiting eicosanoid biosynthesis from AA.     

n-3 fatty acids from vegetable oils

Principal food sources of the n-3 fatty acid alpha-linolenic acid are salad and cooking oil, salad dressing, shortening, margarine, and food-service fat and oil products made from canola oil or soybean oil. Using food production data provided by US trade associations and by Statistics Canada, I estimated the per capita availability of alpha-linolenic acid from vegetable-oil products in the United States to be approximately 1.2 g/d and in Canada, approximately 2 g/d. The higher alpha-linolenic acid availability in Canada is largely accounted for by widespread use of canola oil there. Considering also contributions to dietary alpha-linolenic acid of other foods such as nuts, dairy products, and vegetables, it would appear that total intake of alpha-linolenic acid in US and Canadian diets adequately exceeds the reported nutritional requirement. Emerging research has suggested possible health benefits associated with modest increases in dietary alpha-linolenic acid, including reduced blood-clotting tendency and reduced blood pressure.     

Blood pressure-lowering effects of long chain n-3 fatty acids from meals enriched with liquid fish oil and from microencapsulated powder

Background: Diet plays an important role in the etiology of hypertension. Blood pressure (BP)-lowering properties of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) are promising. The aim was to investigate whether different formulations of fish oil differently affect blood pressure in community-dwelling adults. The hypothesis was that fish oil formulations would improve BP in comparison with a placebo.

Methods: In this 4-week randomized, placebo-controlled, doubly-blinded dietary intervention study, participants (N?=?99,?>50 years) from the capital area of Iceland were randomized into three groups. Group 1 (n?=?38) received 6 meals/week fortified with a liquid fish oil and placebo powder. Group 2 (n?=?30) received conventional (unfortified) meals and microencapsulated powder. Group 3 (n?=?31) was the control group which received conventional meals and placebo powder. Calculated on a weekly basis, the amount of EPA?+?DHA provided was 1.5?g/d. Systolic (SBP) and diastolic BP (DBP) were measured before and after the intervention period.

Results: Seventy-seven subjects finished the study (77.8%). Drop-out rates were not different between groups. According to multivariate statistics, endpoint SBP was lower in Group 1 (?7.0?mmHg, p?=?0.037) and in Group 2 (?7.2?mmHg, p?=?0.037) as compared with Group 3. There was no significant difference in DBP between the groups.

Conclusion: Our study shows that LC n-3 PUFA from microencapsulated powder are equally effective to meaningfully reduce SBP as LC n-3 PUFA from meals enriched with liquid fish oil in comparison with a control group.     

Antiarrhythmic effects of n-3 polyunsaturated fatty acids

The n-3 or omega 3 polyunsaturated fatty acids are a promising dietary preventive therapy for cardiovascular disease. The main dietary source of n-3 polyunsaturated fatty acids comes from sea fish. During recent years, the subject of antiarrhythmic role of n-3 polyunsaturated fatty acids has been investigated extensively. A great deal of evidence has shown that the antiarrhythmic effect of n-3 polyunsaturated fatty acids is exerted by altering the electrophysiology of myocytes. This article is intended to review specifically this role of n-3 polyunsaturated fatty acids as demonstrated by both basic and clinical evidence in animal and human studies, including current concepts on the antiarrhythmic mechanism of this class of polyunsaturated fatty acids.     

Lower ratio of n-3 to n-6 fatty acids in cultured than in wild fish

Fish are the major dietary source of very-long-chain n-3 polyunsaturated fatty acids. We investigated whether cultured fish contain fewer n-3 fatty acids than do wild fish. Fifty-eight trout, 51 eel, and 5 salmon were collected from fishermen and hatcheries throughout Europe, pooled into 23 lots (8 of wild and 15 of cultured fish), and analyzed. The ratio of n-3 to n-6 polyunsaturates was significantly lower in cultured than in wild fish (2 vs 7 in trout, 2 vs 5 in eel, and 6 vs 11 in salmon). Hunted fish are a better source of n-3 polyunsaturates than are cultured fish.