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Acute Ingestion of Long-Chain (n-3) Polyunsaturated Fatty Acids Decreases Fibrinolysis in Men with Metabolic Syndrome. Montegaard C, Tulk HM, Lauritzen L, Tholstrup T, Robinson LE. J Nutr. 2009 Nov 4. [Epub ahead of print] PMID: 19889809 doi:10.3945/jn.109.111427 Individuals with metabolic syndrome (MetS) often have elevated plasma plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA), contributing to an increased risk of cardiovascular disease. PAI-1 and t-PA may be affected by chronic (n-3) long-chain PUFA [(n-3)LCPUFA] supplementation; however, the acute impact of fat ingestion on these risk factors has not been established. Our objective was to investigate the acute effect of (n-3)LCPUFA on plasma PAI-1, t-PA, and platelet aggregation. We conducted a randomized crossover study in which men (n = 8, ≥45 y) with MetS consumed water or a high-saturated fat beverage (1 g fat/kg body weight) with either a high or low content of (n-3)LCPUFA. Blood samples were collected over 8 h to measure triacylglycerol (TAG), PAI-1, t-PA, and platelet aggregation. Both fat loads resulted in a significant increase in whole blood TAG concentration, plasma PAI-1 and t-PA concentrations, and PAI-1 activity, as well as a significant decrease in t-PA activity during the postprandial period. Interestingly, PAI-1 concentration and activity increased more following the high (n-3)LCPUFA compared with the low (n-3)LCPUFA beverage (P < 0.05). Furthermore, the high (n-3)LCPUFA beverage resulted in a lower t-PA activity (P < 0.05), whereas the effects of the 2 fat loads on the plasma t-PA concentration and platelet aggregation did not differ. Overall, acute intake of a high (n-3)LCPUFA beverage shifted the balance between plasma PAI-1 and t-PA, which might indicate a lower capacity for fibrinolysis

n-3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Calder PC. Clin Sci (Lond). 2004 Jul;107(1):1-11. Review. PMID: 15132735 DIETARY RECOMMENDATIONS FOR INTAKE OF LONG-CHAIN n-3 PUFAS It is clear from the forgoing discussion that long-chain n-3 fatty acids have been proven to be effective in secondary prevention of MI, with a particularly marked effect on sudden death. Thus it would be prudent to advise post-MI patients to increase long-chain n-3 PUFA consumption. Epidemiological studies, studies investigating effects on classic and emerging risk factors and mechanistic studies indicate that long-chain n-3 fatty acids also play a key role in primary prevention. This is supported by studies in animal models, including monkeys. Thus long-chain n-3 fatty acid consumption should be promoted for all individuals especially those at risk of developing cardiovascular disease. This is the reason why a number of organizations have now made recommendations relating to the intake of fatty fish (for example [3]) and of long-chain n-3 PUFAs (Table 6). It is clear that there is a wide gap between current intakes of long-chain n-3 PUFAs and many of these recommendations (Table 6). To meet these recommendations strategies other than increased consumption of fatty fish may be required.

Melanoma growth is reduced in fat-1 transgenic mice: impact of omega-6/omega-3 essential fatty acids. Xia S, Lu Y, Wang J, He C, Hong S, Serhan CN, Kang JX. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12499-504. Epub 2006 Aug 3. PMID: 16888035 doi: 10.1073/pnas.0605394103 In vitro experiments showed that addition of the n-3 fatty acid eicosapentaenoic acid or PGE(3) inhibited the growth of B16 cell line and increased the expression of PTEN, which could be partially attenuated by inhibition of PGE(3) production, suggesting that PGE(3) may act as an antitumor mediator. These data demonstrate an anticancer (antimelanoma) effect of n-3 fatty acids through, at least in part, activation of PTEN pathway mediated by PGE(3).

"Not everyone has access to pastured eggs. "Omega-3 eggs" come from hens fed an omega-3 enriched diet*. Not only do they have a much higher omega-3 content than conventional eggs, they also contain less AA. One study found that omega-3 eggs contain 39% less AA than conventional and organic eggs. Omega-3 eggs were also rich in short- and long-chain omega-3 fats. Omega-3 eggs are certainly not nutritionally equivalent to pastured eggs, but they're a step in the right direction. "

n-3 fatty acids and gene expression. Deckelbaum RJ, Worgall TS, Seo T. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1520S-1525S. Review. Erratum in: Am J Clin Nutr. 2006 Oct;84(4):949. PMID: 16841862 Accumulating evidence in both humans and animal models clearly indicates that a group of very-long-chain polyunsaturated fatty acids, the n-3 fatty acids (or omega-3), have distinct and important bioactive properties compared with other groups of fatty acids. n-3 Fatty acids are known to reduce many risk factors associated with several diseases, such as cardiovascular diseases, diabetes, and cancer. The mechanisms whereby n-3 fatty acids affect gene expression are complex and involve multiple processes. As examples, n-3 fatty acids regulate 2 groups of transcription factors, such as sterol-regulatory-element binding proteins and peroxisome proliferator-activated receptors, that are critical for modulating the expression of genes controlling both systemic and tissue-specific lipid homeostasis. Modulation of specific genes by n-3 fatty acids and cross-talk between these genes are responsible for many effects of n-3 fatty acids.

The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A. Eur J Cancer. 2009 Aug;45(12):2077-86. Epub 2009 Jun 1. Review. PMID: 19493674 Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. This review explores the evidence and the mechanisms by which omega-3 FA may act as angiogenesis inhibitors and identifies opportunities for original research trialling omega-3 FAs as anti-cancer agents in humans. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFKB), matrix metalloproteinases and beta-catenin

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Biochemical effects of consumption of eggs containing omega-3 polyunsaturated fatty acids. Ohman M, Akerfeldt T, Nilsson I, Rosen C, Hansson LO, Carlsson M, Larsson A. Ups J Med Sci. 2008;113(3):315-23.P MID: 18991244 Today, eggs with an increased content of -3 fatty acids are available but there are few publications on the effects of consumption of such eggs on the lipoproteins and acute phase markers in humans. The aim of the present study was to evaluate the effects of consumption of standard eggs and -3 enriched eggs on lipoproteins, glucose and inflammation markers. Nineteen healthy volunteers consumed one extra egg per day of either standard eggs or omega-3 enriched eggs in a double-blind, cross-over study. The duration of each period was 1 month. The effects of the different egg diets on apolipoprotein A1 and B (Apo A1 and B), lipoprotein (a), creatinine, cystatin C, C-reactive protein, serum amyloid protein A, interleukin 6, triglycerides, glucose, total-, high-density lipoprotein and low-density lipo-protein cholesterol concentrations were analyzed. Addition of one regular egg per day to the normal diet had no negative impact on blood lipids or inflammation markers. Consumption of omega-3 enriched eggs resulted in higher levels of ApoA1, lower ApoB/ApoA1 ratio and lower plasma glucose. These effects have been associated in previous studies with a reduced risk for cardiovascular mortality and diabetes.

n-3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects. Jung UJ, Torrejon C, Tighe AP, Deckelbaum RJ. Am J Clin Nutr. 2008 Jun;87(6):2003S-9S. PMID: 18541602 Dietary n-3 fatty acids, particularly eicosapentaenoic acid and docosahexaenoic acid, are important nutrients through the life cycle. Evidence from observational, clinical, animal, and in vitro studies indicates a beneficial role of n-3 fatty acids in the prevention and management of cardiovascular disease. Although the precise mechanisms are still unclear, clinical and preclinical studies indicate that the cardioprotective effects of n-3 fatty acids may be attributed to a number of distinct biological effects on lipid and lipoprotein metabolism, blood pressure, platelet function, arterial cholesterol delivery, vascular function, and inflammatory responses. Substantial evidence supports n-3 fatty acids as a practical, therapeutic adjuvant for promoting cardiovascular health and preventing and treating disease. n-3 Fatty acids modulate a number of important physiologic responses that can contribute to their cardioprotective effects. The multiple and complex mechanisms through which DHA and EPA exert their action appear to be distinct but also complementary. However, more studies are needed to quantify their protective effects and to define exact mechanisms of action.

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Egg fortification with n-3 polyunsaturated fatty acids (PUFA): nutritional benefits versus high n-6 PUFA western diets, and consumer acceptance. Shapira N, Weill P, Loewenbach R. Isr Med Assoc J. 2008 Apr;10(4):262-5. PMID: 18548978 Egg fortification with n-3 polyunsaturated fatty acids (PUFA): nutritional benefits versus high n-6 PUFA western diets, and consumer acceptance. Shapira N, Weill P, Loewenbach R. Isr Med Assoc J. 2008 Apr;10(4):262-5. PMID: 18548978 CONCLUSIONS: Effective concentration and transformation of supplemental n-3 PUFA/LCPUFA from feed to egg substantially enhanced egg n-3 PUFA %DRI, particularly of DHA, critical for health but often deficient. Such land-based n-3 PUFA/LCPUFA fortification may be applicable to high n-6 PUFA diets, fitting within cholesterol limitations and market criteria. It may contribute to general health and specific requirements (i.e., pregnancy and lactation), with possibilities of wide accessibility and standardization.

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Gogos CA, Ginopoulos P, Salsa B, Apostolidou E, Zoumbos NC, Kalfarentzos F. Cancer. 1998 Jan 15;82(2):395-402. PMID: 9445198 DOI: 10.1002/(SICI)1097-0142(19980115)82:23.0.CO;2-1 Dietary supplementation with omega-3 PUFA (18 g/day) restored both the Th/Ts cell ratio and TNF production by endotoxin-stimulated PBMC. Our finding is not in accordance with former reports that long term consumption of omega-3 PUFA decreases T cell mitogenic response, DTH, and the percentage of T-helper cells,[28] and this may be the result of the parallel antioxidant effect of vit E. Most significantly, omega-3 PUFA increased the survival of all our patients, ...

Are omega-3 fatty acids options for prevention and treatment of cognitive decline and dementia? Cederholm T, Palmblad J. Curr Opin Clin Nutr Metab Care. 2009 Dec 16. [Epub ahead of print] PMID: 20019606 PURPOSE OF REVIEW: To report recent data on the potential role of omega-3 fatty acids (n-3 FA) found in oily fish, especially docosahexaenoic acid (DHA), to prevent and treat cognitive decline and Alzheimer's disease. RECENT FINDINGS: Observational studies still provide conflicting results, in which the majority indicate beneficial effects on cognition, both when assessed as a continuous variable or as incident dementia, mainly Alzheimer's disease. Experimental studies have demonstrated potentially ameliorating effects of eicosapentaenoic acid (EPA) and DHA on amyloid fragment formation, signal transduction including upregulation of the apolipoprotein receptor SorLA, as well as on angiogenesis. The role of EPA and DHA metabolites on Alzheimer's disease pathology is under investigation. Recently, three randomized intervention studies, with duration up to 6 months have been reported. In contrast to a small study from Taiwan, no positive overall effects were reported from the Swedish OmegAD Study or from a Dutch study, although post hoc analyses indicate that selected individuals with mild forms of Alzheimer's disease or cognitive decline may respond to treatment. SUMMARY: No firm conclusions can be drawn. Based on epidemiological data, fish including oily fish could be advised as part of a balanced diet for public health purpose, although the evidence for better cognition is only fairly consistent. It is unlikely that n-3 FA will emerge as a treatment option in general for improving cognitive function in patients with Alzheimer's disease. n-3 FA, especially DHA, may turn out as an adjuvant therapy in selected cases. Further long-term intervention studies on individuals with mild cognitive reductions are awaite"

n-3 fatty acids and cardiovascular disease. Breslow JL. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1477S-1482S. Review. PMID: 16841857 The results of prospective cohort studies indicate that consuming fish or fish oil containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with decreased cardiovascular death, whereas consumption of the vegetable oil-derived n-3 fatty acid {alpha}-linolenic acid is not as effective. Randomized control trials (RCTs) in the context of secondary prevention also indicate that the consumption of EPA plus DHA is protective at doses 3 g/d, EPA plus DHA can improve cardiovascular disease risk factors, including decreasing plasma triacylglycerols, blood pressure, platelet aggregation, and inflammation, while improving vascular reactivity. Mainly on the basis of the results of RCTs, the American Heart Association recommends that everyone eat oily fish twice per week and that those with coronary heart disease eat 1 g/d of EPA plus DHA from oily fish or supplements. Directions for future research include 1) RCTs to confirm the initial trials showing that EPA plus DHA decreases cardiovascular death and additional studies to determine whether this effect is due to EPA, DHA, or the combination; the dosage of the effective components; and whether the mechanism of action in humans is prevention of fatal arrhythmias. 2) Clinical studies to determine whether the reduction in cardiovascular disease risk factors is due to EPA, DHA, or the combination and the dosage of the effective components. 3) Clinical studies to determine whether vegetable oil-derived {alpha}-linolenic acid added to a diet enriched in n-6 fatty acids can effectively substitute for fish oil-derived EPA plus DHA.

"THURSDAY, Dec. 17 (HealthDay News) -- In a surprise finding, Canadian researchers report that the immediate effect of the fish oil fatty acids that are good for the heart is a short-term increase in blood fats and the molecules that help them form clots. "We were surprised to find that the acute response has some potentially negative effects in comparison to what you might expect from chronic, long-term intake," said Lindsay E. Robinson, an associate professor of nutrition at the University of Guelph, and leader of the group reporting the finding in the January issue of the Journal of Nutrition. However, the study results shouldn't affect the current recommendation for eating more oily fish to get the omega-3 polyunsaturated acids that reduce the risk of blood clots that can cause heart attacks and stroke, Robinson said. "The recommendation to increase intake is very well-studied, and this doesn't change it," she said. And the effects were seen in a selected group of middle-aged men with metabolic syndrome, a combination of high blood pressure, obesity and elevated blood fat levels, Robinson noted. In the study, eight men had controlled intake of three regimens: high doses of omega-3 fatty acids, low doses of them and just plain water. Robinson and her colleagues measured several blood components involved in clotting, including fats and clotting factors such as plasminogen-activator inhibitor-1 (PAI-1) for the following eight hours. PAI-1 inhibits the destruction of blood clots, so high levels of it in the blood increase the risk of artery-blocking clots. The researchers found that both omega-3 fatty acid regimens increased blood fat and clotting factor activity. But the increase in clotting factor was greater for the higher doses of omega-3 fatty acids than for the lower intakes. Robinson said her group hopes to do further studies of the immediate effects of omega-3 fatty acid intake. "We need to look at the mechanisms, why blood lipid levels go up," she

Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Leaf A, Kang JX, Xiao YF, Billman GE. Circulation. 2003 Jun 3;107(21):2646-52. Review. PMID: 12782616 doi: 10.1161/01.CIR.0000069566.78305.33 This review will be limited specifically to the beneficial prevention by the n-3 polyunsaturated fatty acids (PUFAs) of arrhythmic deaths, including sudden cardiac death, which annually causes some 300 000 deaths in the United States and millions more worldwide. We will also show that the growing body of positive clinical studies is supported by what has been learned in animal and laboratory studies regarding the mechanism by which n-3 PUFAs prevent cardiac arrhythmias.

Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, Gallagher PJ, Calder PC, Grimble RF. Lancet. 2003 Feb 8;361(9356):477-85. PMID: 12583947 doi:10.1016/S0140-6736(03)12468-3 Interpretation Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation, inducing changes that can enhance stability of atherosclerotic plaques. By contrast, increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here. Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake

Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial. Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS. JAMA. 2009 Oct 21;302(15):1651-7. PMID: 19843899 Conclusions Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega-3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3 monotherapy can improve depression in patients with CHD remains to be determined

July 29, 2008 - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1]. The study, known as Electron-Beam Tomography, Risk Factor Assessment Among Japanese and US Men in the Post-World War II Birth Cohort (ERA JUMP) included 868 randomly selected men aged 40 to 49. Of these, 281 were Japanese men living in Japan; 306 were white men living in the US, and 281 were third- or fourth-generation Japanese American men from Hawaii. All study participants had a physical examination, completed a lifestyle questionnaire, and had blood tests to measure cholesterol levels and levels of omega-3 fatty acids. Atherosclerosis was assessed by measuring carotid intima-medial thickness (IMT) and coronary artery calcification (CAC). Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans. The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan). They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids - a finding that was independently linked to low levels of atherosclerosis.

Pittsburgh, PA and Shiga, Japan - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1]. The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan). They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids-a finding that was independently linked to low levels of atherosclerosis. "The death rate from coronary heart disease in Japan has always been puzzlingly low. Our study suggests that the very low rates of coronary heart disease among Japanese living in Japan may be due to their lifelong high consumption of fish," Sekikawa said." Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans. In addition, the significant differences between Japanese and American men in multivariable-adjusted IMT and CAC prevalence became nonsignificant after adjustment further for marine-derived omega-3 fatty acids.