Effects of n-3 long chain polyunsaturated fatty acids on depressed mood: Systematic review of published trials.

Background: Greater dietary intakes of n–3 long-chain polyunsaturated fatty acids (n–3 PUFAs) may be beneficial for depressed mood. Objective: This study aimed to systematically review all published randomized controlled trials investigating the effects of n–3 PUFAs on depressed mood. Design: Eight medical and health databases were searched over all years of records until June 2006 for trials that exposed participants to n–3 PUFAs or fish, measured depressed mood, were conducted on human participants, and included a comparison group. Results: Eighteen randomized controlled trials were identified; 12 were included in a meta-analysis. The pooled standardized difference in mean outcome (fixed-effects model) was 0.13 SDs (95% CI: 0.01, 0.25) in those receiving n–3 PUFAs compared with placebo, with strong evidence of heterogeneity (I2 = 79%, P <0.001). The presence of funnel plot asymmetry suggested that publication bias was the likely source of heterogeneity. Sensitivity analyses that excluded one large trial increased the effect size estimates but did not reduce heterogeneity. Metaregression provided some evidence that the effect was stronger in trials involving populations with major depression—the difference in the effect size estimates was 0.73 (95% CI: 0.05, 1.41; P = 0.04), but there was still considerable heterogeneity when trials that involved populations with major depression were pooled separately (I2 = 72%, P <0.001). Conclusions: Trial evidence that examines the effects of n–3 PUFAs on depressed mood is limited and is difficult to summarize and evaluate because of considerable heterogeneity. The evidence available provides little support for the use of n–3 PUFAs to improve depressed mood. Larger trials with adequate power to detect clinically important benefits are required.

Red meat consumption: An overview of the risks and benefits

Red meat is long established as an important dietary source of protein and essential nutrients including iron, zinc and vitamin B12, yet recent reports that its consumption may increase the risk of cardiovascular disease (CVD) and colon cancer have led to a negative perception of the role of red meat in health. The aim of this paper is to review existing literature for both the risks and benefits of red meat consumption, focusing on case-control and prospective studies. Despite many studies reporting an association between red meat and the risk of CVD and colon cancer, several methodological limitations and inconsistencies were identified which may impact on the validity of their findings. Overall, there is no strong evidence to support the recent conclusion from the World Cancer Research Fund (WCRF) report that red meat has a convincing role to play in colon cancer. A substantial amount of evidence supports the role of lean red meat as a positive moderator of lipid profiles with recent Studies identifying it as a dietary source of the anti-inflammatory long chain (LC) n-3 PUFAs and conjugated linoleic acid (CIA). In conclusion. moderate consumption of lean red meat as part of a balanced diet is unlikely to increase risk for CVD or colon cancer, but may positively influence nutrient intakes and fatty acid profiles, thereby impacting positively on long-term health. (C) 2009 Elsevier Ltd. All rights reserved

Docosahexaenoic Acid Improves the Nitroso-Redox Balance and Reduces VEGF-Mediated Angiogenic Signaling in Microvascular Endothelial Cells

Purpose. Disturbances to the cellular production of nitric oxide (NO) and superoxide (O2-) can have deleterious effects on retinal vascular integrity and angiogenic signaling. Dietary agents that could modulate the production of these signaling molecules from their likely enzymatic sources, endothelial nitric oxide synthase (eNOS) and NADPH oxidase, would therefore have a major beneficial effect on retinal vascular disease. The effect of ?-3 polyunsaturated fatty acids (PUFAs) on angiogenic signaling and NO/superoxide production in retinal microvascular endothelial cells (RMECs) was investigated.

Methods. Primary RMECs were treated with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) for 48 hours. RMEC migration was determined by scratch-wound assay, proliferation by the incorporation of BrdU, and angiogenic sprouting using a three-dimensional model of in vitro angiogenesis. NO production was quantified by Griess assay, and phospho-eNOS accumulation and superoxide were measured using the fluorescent probe dihydroethidine. eNOS localization to caveolin-rich microdomains was determined by Western blot analysis after subfractionation on a linear sucrose gradient.

Results. DHA treatment increased nitrite and decreased superoxide production, which correlated with the displacement of eNOS from caveolar subdomains and colocalization with the negative regulator caveolin-1. In addition, both ?-3 PUFAs demonstrated reduced responsiveness to VEGF-stimulated superoxide and nitrite release and significantly impaired endothelial wound healing, proliferation, and angiogenic sprout formation.

Conclusions. DHA improves NO bioavailability, decreases O2- production, and blunts VEGF-mediated angiogenic signaling. These findings suggest a role for ?-3 PUFAs, particularly DHA, in maintaining vascular integrity while reducing pathologic retinal neovascularization.

Platelet Redox Balance in Diabetic Patients with Hypertension improved by n-3 fatty acids

OBJECTIVE:
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease, largely as a result of defective production of cardioprotective nitric oxide and a concomitant rise in oxidative stress. Dietary interventions that could reverse this trend would be extremely beneficial. Here we investigated whether dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation positively affected platelet nitroso-redox imbalance.
RESEARCH DESIGN AND METHODS:
We randomized hypertensive T2DM patients (T2DM HT; n = 22) and age-and-sex matched hypertensive study participants without diabetes (HT alone; n = 23) in a double-blind, crossover fashion to receive 8 weeks of n-3 PUFAs (1.8 g eicosapentaenoic acid and 1.5 g docosahexaenoic acid) or identical olive oil capsules (placebo), with an intervening 8-week washout period. Platelet nitrite and superoxide were measured and compared before and after treatment; 8-isoprostane was determined by ELISA and subcellular compartmentalization of the NAD(P)H oxidase subunit p47-phox examined by Western blotting.
RESULTS:
The n-3 PUFA supplementation reduced 8-isoprostane and superoxide levels in platelets from T2DM HT, but not HT alone, participants, without effect on nitrite production. This coincided with a significant decrease in p47-phox membrane localization and a similar reduction in superoxide to that achieved with apocynin. At baseline, a subcohort of T2DM HT and HT alone participants showed evidence of nitric oxide synthase (NOS)-derived superoxide production, indicating defective enzymatic activity. This was reversed significantly in T2DM HT participants after treatment, demonstrating improved NOS function.
CONCLUSIONS:
Our finding that n-3 PUFAs diminish platelet superoxide production in T2DM HT patients in vivo suggests a therapeutic role for these agents in reducing the vascular-derived oxidative stress associated with diabetes.

Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood

Background: The debate over a role for n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) in depressed mood continues.

The anti-atherogenic effects of eicosapentaenoic and docosahexaenoic acid are dependent on the stage of THP-1 macrophage differentiation.

In this study LC n-3 PUFA-specific effects on the degree of monocyte differentiation and macrophage foam cell formation were investigated by treating PMA-induced immature and mature macrophage models with LC n-3/n-6 PUFA during and post-differentiation. During immature macrophage differentiation LC n-3 PUFA alone decreased TNFα mRNA levels. EPA, and the n-6 PUFAs, linoleic acid and arachidonic acid, decreased CD36 mRNA levels, and EPA also downregulated CD49d cell-surface expression. Both LC n-3 PUFA reduced LDLr mRNA levels in immature macrophages, while DHA alone reduced levels in mature macrophages. Post-differentiation, n-3 and -6 PUFA reduced basal, but not oxidised LDL dependent cholesterol levels in immature macrophages. LC n-3 PUFA-specific reductions in LDLr and LOX-1 mRNA expression were also observed.

This study found LC n-3 PUFA specific, anti-atherogenic effects were more significant in immature macrophages. LC n-3 PUFA effects may be modulated by the extent of monocyte to macrophage differentiation.