FISH OIL / OMEGA-3 AND CANCER

FISH OIL / OMEGA-3 AND CANCER

http://www.ncbi.nlm.nih.gov/pubmed/11223421
"DHA oil intake negatively influenced lipid peroxidation in both plasma and liver. Phospholipid peroxidation in plasma and liver was significantly higher than control in rats fed DHA-TG or DHA-EE, but not DHA-PL. [...] During NADPH-dependent peroxidation of microsomes, the accumulation of phospholipid hydroperoxides, as well as TBARS, were elevated and alpha-tocopherol levels were significantly exhausted in DHA-TG and DHA-EE groups. During microsomal lipid peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n-6 fatty acids, including arachidonic acid (20:4n-6). These results indicate that polyunsaturation of n-3 fatty acids is the most important target for lipid peroxidation. This suggests that the ingestion of large amounts of DHA oil enhances lipid peroxidation in the target membranes where greater amounts of n-3 fatty acids are incorporated, thereby increasing the peroxidizability and possibly accelerating the atherosclerotic process."


http://www.ncbi.nlm.nih.gov/pubmed/11110863
"The DHA oil diets markedly increased (P: < 0.05) the levels of DHA in the plasma, liver and kidney, 1.5-1.9, 2.5-3.8 and 2.2-2.5 times the control values, respectively, whereas there was a concomitant reduction (P: < 0.05) in arachidonic acid. [...] rats fed DHA-containing oils had more thiobarbituric reactive substances in these organs than the controls. Thus, high incorporation of (n-3) fatty acids (mainly DHA) into plasma and tissue lipids due to DHA-containing oil ingestion may undesirably affect tissues by enhancing susceptibility of membranes to lipid peroxidation and by disrupting the antioxidant system."


http://www.ncbi.nlm.nih.gov/pubmed/6256498
"The involvement of superoxide free radicals and lipid peroxidation in brain swelling induced by free fatty acids has been studied in brain slices and homogenates. The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3), arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in superoxide and membrane lipid peroxidation. [...] Furthermore, superoxide formation was stimulated by NADPH and scavenged by the addition of exogenous superoxide dismutase in cortical slice homogenates. These in vitro data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the mechanism of polyunsaturated fatty acid-induced brain edema."


http://www.ncbi.nlm.nih.gov/pubmed/12792664
"To assess the oxidative burden of a highly concentrated compound of n-3 PUFAs as compared to corn oil by measuring thiobarbituric acid-malondialdehyde complex (TBA-MDA) by HPLC. [...] After 1 y TBA-MDA increased modestly in the n-3 PUFA group (n=125), as compared to the corn oil group (n=130), P=0.027. Multiple linear regression analyses of fatty acids in serum total phospholipids (n=56) on TBA-MDA measured after 12 months intervention, showed no dependency. [...] TBA-MDA increased modestly after long-term intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological changes induced by n-3 PUFAs, rather than simply reflecting their concentration differences."


http://www.ncbi.nlm.nih.gov/pubmed/2522813
"The fish oil diet increased the frequency of myeloid progenitor cells in normal mice and in mice bearing small or large tumors. Concurrently, the fish oil diet stimulated the appearance of bone marrow-derived suppressor cells. When administered after the establishment of palpable primary tumors, a fish oil diet also increased the formation of pulmonary lung nodules. [...] These data show that a fish oil diet can minimize the immune suppression in tumor bearers when suppression is mediated by PGE2-producing suppressor cells, but can also induce myelopoietic stimulation leading to the appearance of bone marrow-derived suppressor cells and increased tumor metastasis."


http://www.ncbi.nlm.nih.gov/pubmed/11467768
"Recently, it was demonstrated that dietary omega-3 polyunsaturated fatty acids (PUFAs) induce 10-fold more metastases in number and 1000-fold in volume in an animal model of colon cancer metastasis in rat liver. It was observed that tumors of rats on a fish oil diet lacked peritumoral stroma unlike tumors in livers of rats on a low fat diet or a diet containing omega-6 PUFAs. [...] As most of the tumors in fish oil-treated rats contained intratumoral stroma only, this suggests that transformation of fat storing cells into myofibroblasts was highest in tumor stroma of fish oil-treated rats. Therefore, it is unlikely that the lack of stroma around tumors in fish oil-treated rats is due to inhibition of transformation of fat storing cells into myofibroblasts, but lack of peritumoral stroma is rather a consequence of rapid development of tumors in livers of fish oil-treated rats."


http://www.ncbi.nlm.nih.gov/pubmed/9589432
"An increase in the n-3/n-6 ratio did not suppress the incidence or reduce the latency of mammary tumor development. The number and weight of mammary tumors per tumor-bearing rat tended to be large in the group with an n-3/n-6 ratio of 7.84 compared with those in the other groups. As the n-3/n-6 ratios were elevated, the total number and weight of tumors increased gradually. [...] These results suggested that the increase in the n-3/n-6 ratio of dietary fat with the fixed PUFA-to-saturated fatty acid ratio cannot suppress the mammary carcinogenesis but can promote development of tumors, despite reduced PGE2 concentration in the tumor."


http://aje.oxfordjournals.org/content/173/12/1429.full
"This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. [...] In the European Prospective Investigation into Cancer and Nutrition (EPIC, ncases = 962) (12), the highest quintile of percent DHA was associated with elevated risks of both low-grade (relative risk (RR) = 1.53, 95% CI: 0.96, 2.44) and high-grade (RR = 1.41, 95% CI: 0.76, 2.62) prostate cancer. They also reported significant positive associations of the percent EPA with high-grade prostate cancer (RR = 2.00, 95% CI: 1.07, 3.76). [...] In conclusion, this large prospective investigation of inflammation-associated phospholipid fatty acids and prostate cancer risk found no support that ω-3 fatty acids reduce [...] prostate cancer risk. Indeed, our findings are disconcerting as they suggest that ω-3 fatty acids, considered beneficial for coronary artery disease prevention, may increase high-grade prostate cancer risk [...]"


http://www.ncbi.nlm.nih.gov/pubmed/23134890
"Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. [...] Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). [...] Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology."


http://www.ncbi.nlm.nih.gov/pubmed/9168460
"In those supplemented with n-3 fatty acids, EPA and DHA increased in plasma phospholipids (P < 0.0001) and plasma MDA and lipid peroxides increased (P < 0.001 and P < 0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation."


http://www.ncbi.nlm.nih.gov/pubmed/1432259
"The AIN-recommended level of antioxidant addition (butylated hydroxytoluene, 0.02 g/100 g oil) and even the addition of 100 times this level (2 g/100 g oil), although decreasing the level of oxidation products, failed to totally prevent oxidative deterioration in diets high in fish oil. Furthermore, other antioxidants added in excess to the fish oil diets also failed to completely suppress oxidative deterioration of the diets and, in addition, when fed daily to mice for a period of 4 wk, caused an accumulation of lipid peroxidation products in certain organs (e.g., heart, skeletal muscle, mammary glands) and in the carcass. These results provide evidence that in the preparation of fish oil diets, the addition of antioxidants at the AIN-recommended level, or even levels substantially higher, does not completely suppress oxidative deterioration of experimental diets."


http://www.ncbi.nlm.nih.gov/pubmed/22710344
"Dietary intake of omega-3 polyunsaturated fatty acids (ω3PUFAs) and consequently the increase in ω3PUFA content of membrane lipids may be disadvantageous to the health because ROS-induced oxidative peroxidation of ω3PUFAs within membrane phospholipids can lead to the formation of toxic products. Mitochondrial control of lipid peroxidation is one of the mechanisms that protect cell against oxidative damage. [...] The susceptibility to peroxidation of PUFAs by ROS raises the question of the adverse effects of ω3PUFA dietary supplementation on embryonic development and prenatal developmental outcomes.


http://www.ncbi.nlm.nih.gov/pubmed/20691812
"Our study compared the effects of different oils on oxidative stress in rat heart mitochondria, as well as on plasma parameters used as risk factors for cardiovascular disease. The rats were fed for 16 weeks with coconut, olive, or fish oil diet (saturated, monounsaturated, or polyunsaturated fatty acids, respectively). [...] The fish oil diet leads to the highest oxidative stress in cardiac mitochondria, an effect that could be partly prevented by the antioxidant probucol."


http://www.ncbi.nlm.nih.gov/pubmed/18615261
"Atlantic salmon (Salmo salar) (90 g) were fed four different diets for 21 weeks (final weight 344 g). The levels of n-3 highly unsaturated fatty acids (HUFA) ranged from 11% of the total fatty acids (FA) in the low n-3 diet to 21% in the intermediate n-3 diet, to 55 and 58% in the high n-3 diets. The high n-3 diets were enriched with either docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA). Increasing dietary levels of n-3 HUFA led to increasing percentages (from 31 to 52%) of these FA in liver lipids. The group fed the highest level of DHA had higher expressions of peroxisome proliferator-activated receptor (PPAR) beta and the FA beta-oxidation genes acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase (CPT)-II, compared to the low n-3 groups. [...] These data clearly show an increased incidence of oxidative stress in the liver of fish fed the high n-3 diets."