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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

"I know what you may be thinking: "Fish oil?! I thought fish oil was supposed to be healthy! One day you say we should take it, now you're saying it puts us at risk for Swine Flu?" Well, there is a reasonable answer, but it doesn't come in the form of a simple "fish oil is good" or "fish oil is bad" kind of package. The truth is that eating fish and taking fish oil is very often extremely beneficial for a great number of health conditions. But there is no substance on Earth that is 100% healthy under every conceivable circumstance. Take water, for example. Drinking plenty of pure water is a healthful practice. On the other hand, drinking excessive amounts (water intoxication) can lead to serious bodily damage and even death. The August issue of the Journal of Nutrition reports on a study conducted on two groups of mice fed either a fish oil or corn oil enriched diet. (4) All the mice were infected with the flu virus and were then examined over a two week period. Several interesting observations were made at the conclusion of the trial: * The mice receiving the fish oil exhibited lower levels of lung tissue inflammation. This confirms the known anti-inflammatory activity of omega-3 fatty acids found in fish. * However, these same mice suffered a "40% higher mortality rate", a "70% higher lung viral load" and "a prolonged recovery period following infection". * The researchers also noted a decline in NK (natural killer) cells in the spleens of the mice that were fed fish oil and a decrease in CD8+ T cells. NK cells and cytotoxic T cells are vital players in the body's ability to deal with infections."

"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

October 17, 2006 | Steve Stiles Boston, MA - A review of the literature on the health effects of dietary fish or fish-oil intake has a reassuring message for seafood lovers, anyone eating fish for health reasons, and perhaps most everyone else [1]. Levels of mercury and other contaminants in commercially bought fish are low, and their potential risks are overwhelmed by likely reductions in cardiovascular mortality, according to a report in the October 18, 2006 issue of the Journal of the American Medical Association. "The main message is really that everybody should be eating one or two servings of fish or seafood per week for their health," Dr Dariush Mozaffarian (Harvard School of Public Health, Boston, MA) told heartwire. In his analysis, coauthored with Dr Eric B Rimm (Brigham and Women's Hospital, Boston, MA), regular "modest" intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two long-chain n-3 polyunsaturated fatty acids (PUFAs) abundant in finfish and shellfish (collectively referred to as "fish" in the article), is associated with a 36% drop in coronary disease mortality (p Those potential benefits are immense compared with the highly publicized but apparently low health risks associated with methylmercury, dioxins, and polychlorinated biphenyls (PCBs) that have been found in some fish species, they write. The evidence suggests a potential for neurodevelopmental deficits from early exposure to methylmercury, but the risk is likely diminished by limiting intake of fish with high methylmercur

"Study Shows Baked Fish Is Better for Heart Health Than Fried, Salted, or Dried Nov. 19, 2009 (Orlando, Fla.) -- When it comes to reaping the heart-healthy benefits of omega-3 fatty acids in fish, it often comes down to how you prepare it, a study shows. "The take-home message is that it's better to bake or boil the fish instead of frying it," says study researcher Lixin Meng, MS, a doctoral candidate at the University of Hawaii at Manoa. And adding a dash of low-sodium soy sauce will enhance the heart-healthy benefits, she tells WebMD. Eating salted, dried, or fried fish, on the other hand, is not beneficial, Meng says. "But if it's a fun occasion and you really want fried fish, do it the Japanese way -- stir-fry, rather than deep-fry it.""

"The omega-3 essential fatty acids commonly found in fatty fish and algae help animals avoid sensory overload, according to research published by the American Psychological Association. The finding connects low omega-3s to the information-processing problems found in people with schizophrenia; bipolar, obsessive-compulsive, and attention-deficit hyperactivity disorders; Huntington's disease; and other afflictions of the nervous system. The study, reported in the journal Behavioral Neuroscience, provides more evidence that fish is brain food. The key finding was that two omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) appear to be most useful in the nervous system, maybe by maintaining nerve-cell membranes. "It is an uphill battle now to reverse the message that 'fats are bad,' and to increase omega-3 fats in our diet," said Norman Salem Jr., PhD, who led this study at the Laboratory of Membrane Biochemistry and Biophysics at the National Institute on Alcohol Abuse and Alcoholism.

Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study. Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES. BMC Cancer. 2009 Jun 30;9:216. PMID: 19566923 doi: 10.1186/1471-2407-9-216 Conclusion These results suggest that high consumption of fatty fish is associated with a reduced risk for breast cancer, and that the intake of omega-3 fatty acids from fish is inversely associated with postmenopausal breast cancer risk

"Lipoprotein(a), or Lp(a), is a problem area in coronary plaque reversal. While our current Track Your Plaque record holder for largest percentage reduction in heart scan score has Lp(a), it remains among the more troublesome lipoprotein patterns. One unique treatment for Lp(a) is high-dose omega-3 fatty acids from fish oil. While the data are relatively meager, there is one solid study from Lp(a) expert, Dr. Santica Marcovina of the University of Washington, called "The Lugalawa Study." In this unique set of observations, 1300 members of a Bantu tribe living in Tanzania were studied. What made this population unusual is the fact that two groups of Bantus lived under different circumstances. One group lived on Nyasa Lake (3rd largest lake in Africa and reputed to have the greatest number of species of fish of any lake in the world) and ate large quantities of freshwater fish providing up to 500 mg of omega-3s, EPA and DHA, per day. Another Bantu group lived away from the lake as farmers, eating a pure vegetarian diet without fish. "

Fish consumption shifts lipoprotein subfractions to a less atherogenic pattern in humans. Li Z, Lamon-Fava S, Otvos J, Lichtenstein AH, Velez-Carrasco W, McNamara JR, Ordovas JM, Schaefer EJ. J Nutr. 2004 Jul;134(7):1724-8. PMID: 15226460 The effect of fish consumption on plasma lipoprotein subfraction concentrations was studied in 22 men and women (age > 40 y). Subjects were provided an average American diet (AAD, 35% of energy as fat, 14% as saturated fat, and 35 mg cholesterol/MJ) for 6 wk before being assigned to a National Cholesterol Education Program (NCEP) Step 2 high-fish diet (n = 11, 26% of energy as fat, 4.5% as saturated fat, and 15 mg cholesterol/MJ) or a NCEP Step 2 low-fish diet (n = 11, 26% of energy as fat, 4.0% as saturated fat, and 11 mg cholesterol/MJ) for 24 wk. All food and drink were provided to study participants. Consumption of the high-fish NCEP Step 2 diet was associated with a significant reduction in medium and small VLDL, compared with the AAD diet, whereas the low-fish diet did not affect VLDL subfractions. Both diets significantly reduced LDL cholesterol concentrations, without modifying LDL subfractions. Both diets also lowered HDL cholesterol concentrations. However, the high-fish diet significantly lowered only the HDL fraction containing both apolipoprotein (apo) AI and AII (LpAI:AII) and did not change HDL subfractions assessed by NMR, whereas the low-fish diet significantly lowered the HDL fraction containing only apo AI (LpAI) and the large NMR HDL fractions, resulting in a significant reduction in HDL particle size. Neither diet affected VLDL and LDL particle size. Our data indicate that within the context of a diet restricted in fat and cholesterol, a higher fish content favorably affects VLDL and HDL subspecies

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.

"June 29, 2009 | Shelley Wood Boston, MA - A massive, National Institutes of Health-sponsored study looking at whether vitamin-D and/or omega-3 fatty-acid supplementation can reduce the risk of developing heart disease, stroke, or cancer will get under way in January 2010, according to a website for the study. Drs JoAnn Manson and Julie Buring (Harvard Medical School/ Brigham and Women's Hospital, Boston, MA) will head up the Vitamin D and Omega-3 Trial (VITAL). The study is aiming to enroll 20 000 men and women, one-quarter of whom will be black. According to a Brigham and Women's Hospital press release, the study is intentionally aiming to illuminate a potential racial and ethnic disparity hypothesized to be linked to vitamin D [1]. "African Americans have a higher risk of vitamin-D deficiency as well as a greater frequency of diabetes, hypertension, and certain types of cancer," a press release notes. For VITAL, women need to be over age 65 to enter the study; men need to be over age 60. Study participants will be randomized to one of four groups: daily vitamin D (2000 IU) and fish oil (1 g); daily vitamin D and fish-oil placebo; daily vitamin-D placebo and fish oil; or daily vitamin-D placebo and fish-oil placebo. The trial will run for five years and is expected to cost US $20 million."

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"

Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study. Mozaffarian D, Lemaitre RN, Kuller LH, Burke GL, Tracy RP, Siscovick DS; Cardiovascular Health Study. Circulation. 2003 Mar 18;107(10):1372-7. PMID: 12642356 doi: 10.1161/01.CIR.0000055315.79177.16 Conclusions- Among adults aged >=65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.

"ScienceDaily (Dec. 16, 2009) - The omega-3 essential fatty acids commonly found in fatty fish and algae help animals avoid sensory overload, according to research published by the American Psychological Association. The finding connects low omega-3s to the information-processing problems found in people with schizophrenia; bipolar, obsessive-compulsive, and attention-deficit hyperactivity disorders; Huntington's disease; and other afflictions of the nervous system The study, reported in the journal Behavioral Neuroscience, provides more evidence that fish is brain food. The key finding was that two omega-3 fatty acids -- docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) -- appear to be most useful in the nervous system, maybe by maintaining nerve-cell membranes"

"NEW YORK (Reuters Health) - Want to keep your eyesight sharp as you age? Eating lots of fish packed with healthy omega-3 fatty acids could help, new research suggests. Among 1,837 people who had early signs of age-related macular degeneration (AMD), those with the highest consumption of omega-3 fatty acids were 30 percent less likely to progress to the advanced form of the disease over a 12-year period than those with the lowest omega-3 intake, researchers found."

Mice fed fish oil and curcumin showed a significantly reduced tumor volume, 25% (P < 0.04) and 43% (P < 0.005), respectively, and importantly, a combination of curcumin and fish oil diet showed > 72% (P < 0.0001) tumor volume reduction. Expression and activity of iNOS, COX-2, and 5-LOX are downregulated, and p21 is upregulated in tumor xenograft fed curcumin combined with fish oil diet when compared to individual diets. The preceding results evidence for the first time that curcumin combined with omega-3 fatty acids provide synergistic pancreatic tumor inhibitory properties. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Swamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. Nutr Cancer. 2008;60 Suppl 1:81-9. PMID: 19003584

Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. Seddon JM, George S, Rosner B. Arch Ophthalmol. 2006 Jul;124(7):995-1001. PMID: 16832023 Conclusions This study of twins provides further evidence that cigarette smoking increases risk while fish consumption and omega-3 fatty acid intake reduce risk of AMD

Omega-3s have been shown to help reverse heart disease, boost immune function, and improve mental health. An adequate supply of omega 3s makes you less vulnerable to inflammation, depression and Alzheimer's disease. But is eating enough fish to obtain an adequate amount of omega-3s really safe?

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.

ScienceDaily (Feb. 12, 2009) - According to a recent study, diets rich in omega-3 fatty acids protect the liver from damage caused by obesity and the insulin resistance it provokes. This research should give doctors and nutritionists valuable information when recommending and formulating weight-loss diets and help explain why some obese patients are more likely to suffer some complications associated with obesity. Omega-3 fatty acids can be found in canola oil and fish.