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Saturday, March 30, 2019

Role of Omega-3 and Vitamin B6 in Cancer Prevention

aim of Omega-3 and Vitamin B6 in genus Cancer PreventionA critical summary of the role of omega-3 and vitamin B6 in crabby person prevention received exhibit, proposed mechanisms and incoming directionsAbstractA critical analysis of the role of omega-3 and vitamin B6 in crabby person prevention current evidence, proposed mechanisms and in store(predicate) directionsCancer is a tip ca hire of death worldwide and according to the foundation wellness Organization(WHO discovered for 8.2 cardinal deaths in 2012(1). The complex and dynamic nature of genus Cancer is evident, however 30% of good dealcers could be prevented by modifying factors such as diet, not smoking, physical use and moderate use of alcohol(2). Scientific evidence suggests that nutritional supple handstation of approximately nutrients can affect the take chances of different crabmeats. For the purposive of this essay I will per turn a critical analysis of the role of omega-3 and vitamin B6 in cancer prevention by reviewing the current evidence, proposed mechanisms and investigation the future directions of omega-3 and vitamin B6 use in cancer prevention.Omega-3(n-3) and omega-6(n-6) polyunsaturated fat person panellings(PUFAs) be essential butterball acids that cannot be made by the benignant tree trunk and therefore must be obtained from the diet. The use of n-3 PUFAs in a numeral of chronic diseases such as coronary artery disease, psoriasis, irritable gut syndrome and rheumatoid arteritis has been associated with health benefits. Increasing evidence from animal and in vitro studies specify that n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic(DHA) acid flow a role in interdicting cancer progression(3). even epidemiological data on the association in the midst of n-3 PUFA in obtain and cancer endangerment appears to be somewhat less consistent. proud fat phthisis, typically seen in western diets is associated with an increased run a take a chance for cancer develop custodyt. N-3 PUFAs are an exception as studies train institute that n-3 PUFAs stand over nourishive functions in prostatic, pancreatic, breast and colon cancer. Western diets typically contain a soaring n-6 to n-3 ratio which has been engraft is positively associated with prostate cancer development. A involve carried out in Jamaican men who had a high ratio of dietetical n-6 to n-3 ratio, found that n-6 PUFAs was positively cor associate with prostate carcinogenesis bandage n-3 PUFAs inhibited cancer return(4). In agreement with this train a wooing control study of 79 prostate cancer cases and 187 controls, found a high ratio of n-6 to n-3 PUFAs increased the overall risk of prostate cancer in white men and possibly increase the risk of a high fool prostate cancer in all men(5). population based studies have found that the use of n-3 PUFAs are protective against cancer development. A population based prospective cohort study of 90,296 sub jects found that a diet rich in n-3 fish or n-3 PUFA appeared to protect against the development of hepato cellular teleph bingleular carcinoma (6). In agreement with this study a population-based prospective study in Japan found an inverse relationship between n-3 PUFA intake and the risk of cancer in the proximal site of the large bowel(7). However not all studies have found secure effects of the use of n-3 PUFAs in cancer prevention. A French study comprising of over 56,000 women, who were fol abjected for eighter years found no associated between n-3 PUFA and breast cancer risk(8). many mechanisms have been proposed for the beneficial effects of n-3 PUFAs in cancer prevention. PUFAs are open(a) of influencing the juicy acid composition of glycerophospho lipoids in cell membranes. N-3 PUFAs can sub n-6 PUFAs in glycerophospholipids(9) and a high n-3 to n-6 ratio has been found to affect cell membrane guideling. Lipid rafts are important signalling domains within the cell m embrane which contain receptors such as epidermal growth factor receptor(10). As DHA has a poor affinity for cholesterol in lipid rafts it can supress raft associated signal transduction(10). This is important as in many cancers signalling pathways can be over activated. It has also been suggested that n-3 PUFAs may defecate apoptosis and reduce proliferation in human cancer cells by diminish signalling done AKT/NFkB and by modulating the PI3k/AKT/p38 MAPK pathway(11).N-3 PUFAs are involved in the suppression of arachadonic acid (4n-6) derived eicosanoids, which are involved in cellular growth, cell differentiation and have proinflammatory effects (12). Arachadonic derived eicosanoids such as PGE2, have been positively coupled to cancer (13), unlike EPA eicosanoids which have anticancer effects(14). As mentioned above internalisation of n-3 PUFAs into the phospholipid membrane replaces n-6 arachadonic acid precursors, decreasing arachadonic derived eicosanoids and increasing E PA eicosanoids. N-3 PUFAs have also been found to supress cyclooxygenase-2 (15), which has anti-tumour affects as cyclooxygenase-2 down regulates apoptotic pathways(16). This is in contrast to n-6 PUFAs which have been found to upregulate COX-2(17). It is also interesting to note that in breast, colon and prostate cancer COX-2 is overexpressed (18, 19). Taking this into account it is likely that suppression of COX-2 by n-3 PUFAs may be a preventative measure in these cancers.In conclusion there is evidence for the beneficial effects of n-3 PUFAs in cancer prevention, however due to inconsistencies in epidemiological data it is overly early to recommend the use of n-3 PUFAs for cancer prevention. Possible explanations to explain these inconsistencies may be that population-based studies rely heavily on data from self-reported dietary PUFA intake. This form of data collection may poorly correlate with accurate PUFA intake. some other possible explanation is that the amount of n-3 PU FA administered in studies, may not be of a sufficient quantity to have a protective functions in cancer prevention. Further studies are needed to be carried out to account for the current variation in published studies before recommending n-3 PUFAs for cancer prevention. fit in to the latest report from the National Cancer Registry Colorectal cancer (CRC) is the second most(prenominal) common cancer in both men and women in Ireland (20). Environmental factors such as diet have been place as playing a role in the risk of CRC development. Preventability estimates from the World Cancer Research Fund show that 47% of cases of CRC in the UK can be prevented by modifying factors such as eating and drinking healthily, cosmos physically active and maintaining a healthy weight(21). According to the National Health and provender Examination Survey 2003-2004 24% of people (who did not take supplements containing vitamin B6) have suboptimal active B6 plasma concentrations (22).Vitamin B6 i s a water soluble vitamin, which in its active form pyridoxal 5-phostphate (PIP) is involved in to a greater extent than 100 coenzyme reactions, including lipid, carbohydrate and protein metabolism(23). Vitamin B6 may play a role in CRC prevention through its role in one carbon related DNA synthesis and methylation(24). Vitamin B6 has also been shown to reduce the formation of nitric oxide(25), inhibit angiogenesis(26) and reduce oxidative stress(27), creating an unfavourable environment for tumour development.Despite the mechanical evidence supporting for the role of vitamin B6 in CRC cancer prevention, epidemiological evidence has been inconsistent. A meta-analysis of 9 studies carried out between 2002-2009 on Vitamin B6 intake in relation to CRC risk, found inconsistent results with both an inverse and positive association(28). The resembling meta-analysis included four nestled case-control studies investigating serum PLP on CRC risk. every(prenominal) four studies found an in verse relationship between PLP levels and CRC risk, with an overall trim back risk of CRC for every 100-pmol/mL increase in serum PLP(28). In the 9 studies of vitamin B6 intake and CRC risk it seems that highest vs lowest category of vitamin B6 intake was most important. When the studys results were pooled together, a 21% significant reduction in CRC risk was found when comparing high vs low vitamin B6 intake in studies with a wider range of exposure (1.5-mg difference)(28).A different study prospectively followed up 26,440 women and 44,410 men to assess whether a high vitamin B6 intake in the world(prenominal) past(12-16years prior to diagnosis) was more strongly associated with a lower risk of growing CRC than an intake in the recent past (4 years prior to diagnosis)(23). The results of this study did not support a strong role of vitamin B6 intake in preventing CRC development. However most of the participants were relatively well nourished, with only 5-10% of people having a vitamin B6 intake below the recommended daily allowance(23). This limited the study as it is not the most accurate measures of determining the potential effects on suboptimal vitamin B6 on CRC risk.The Japan Public Health Centre-based Prospective study investigated the association of dietary pteroylglutamic acid, vitamin B6, vitamin B12 and methionine on CRC risk(29). The study included 81,184 participants (38,107 men and 43,077 women) who were followed from 1995-98 to the end of 2002. A importantly inverse relationship between vitamin B6 intake and CRC was found in men. men in the highest quartile of vitamin B6 intake had a 35% decreased risk of CRC compared with men in the lowest quartile. No association was found in vitamin B6 intake and CRC in women. Interestingly a higher(prenominal) intake of vitamin B6 appeared to be beneficial in men with higher alcohol intake. The study found that the risk of CRC associated with alcohol intake was significantly higher in those who had a low vitamin B6 intake, however this risk was found to decrease in those who had a higher vitamin B6 intake(29).In conclusion there is evidence to suggest that vitamin B6 may play a role in CRC prevention, however it appears that plasma PLP appears to be more strongly linked to a reduced risk in CRC. Studies investigating the effect of vitamin B6 intake on CRC risk appear to be inconsistent. In contrast studies on PLP have found higher plasma PLP CRC risk by 30-50%(23). It is also important to note that studies have found that individuals with higher military action levels, higher dietary intakes of folate and calcium and individuals who do not smoke have higher vitamin B6 levels and a decreased risk of CRC(23). In these individuals it is unmanageable to determine if it is these healthier behaviours or the increased B6 levels that decreases CRC risk. It is also difficult to assess the impact of dietary vitamin B6 on its own on CRC risk, as most foods containing vitamin B6 contain various other nutrients such as folate and vitamin D. Further studies are needed to be carried out to explain the currentinconsistencies in the use of vitamin B6 and CRC risk before vitamin B6 can be recommended as a preventive measure.1.International Agency for Research on Cancer WHO. GLOBOCAN 2012 Estimated Cancer Incidence, Mortality and Prevalence in 2012 2012. Available from http//globocan.iarc.fr/Pages/fact_ canvas tents_cancer.aspx.2.Organization WH. Cancer fact sheet 2014 updated February 2014. Available from http//www.who.int/mediacentre/factsheets/fs297/en/index.html.3.Parada B, Reis F, Cerejo R, Garrido P, Sereno J, Xavier-Cunha M, et al. Omega-3 fat person acids inhibit tumor growth in a rat model of bladder cancer. BioMed inquiry international. 20132013368178.4.Ritch CR, demented RL, Stephens LB, Taxy JB, Huo D, Gong EM, et al. Dietary fatty acids correlate with prostate cancer biopsy grade and volume in Jamaican men. The Journal of urology. 2007177(1)97-101 discussi on5.Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, et al. A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. Nutrition research (New York, NY). 201131(1)1-8.6.Sawada N, Inoue M, Iwasaki M, Sasazuki S, Shimazu T, Yamaji T, et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology. 2012142(7)1468-75.7.Sasazuki S, Inoue M, Iwasaki M, Sawada N, Shimazu T, Yamaji T, et al. Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite Japan Public Health Center-based prospective study. International ledger of cancer Journal international du cancer. 2011129(7)1718-29.8.Thiebaut AC, Chajes V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, et al. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. International ledger of cancer Journal international du cancer. 2009124(4)924-31.9.G u Z, Wu J, Wang S, Suburu J, Chen H, Thomas MJ, et al. Polyunsaturated fatty acids affect the localization and signaling of PIP3/AKT in prostate cancer cells. Carcinogenesis. 201334(9)1968-75.10.Turk HF, Barhoumi R, Chapkin RS. Alteration of EGFR spatiotemporal dynamics suppresses signal transduction. PloS one. 20127(6)e39682.11.Schley PD, Jijon HB, Robinson LE, Field CJ. Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast cancer research and treatment. 200592(2)187-95.12.Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A. Dietary long-chain n-3 fatty acids for the prevention of cancer a review of potential mechanisms. The American journal of clinical nutrition. 200479(6)935-45.13.Cheuk BL, Chew SB, Fiscus RR, Wong PY. cyclooxygenase-2 regulates apoptosis in rat epididymis through prostaglandin D2. Biology of reproduction. 200266(2)374-80.14.Cockbain AJ, Volpato M, Race AD, Munarini A, Fazio C, Belluzzi A, et al. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut. 2014.15.Hamid R, Singh J, Reddy BS, Cohen LA. Inhibition by dietary menhaden oil of cyclooxygenase-1 and -2 in N-nitrosomethylurea-induced rat mammary tumors. International journal of oncology. 199914(3)523-8.16.Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacology therapeutics. 199983(3)217-44.17.Badawi AF, Archer MC. Effect of hormonal attitude on the expression of the cyclooxygenase 1 and 2 genes and prostaglandin synthesis in rat mammary glands. Prostaglandins other lipid mediators. 199856(2-3)167-81.18.Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 199918(55)7908-16.19.Dempke W, Rie C, Grothey A, Schmoll HJ. Cyclooxygenase-2 a novel target for cancer chemotherapy? Journal of cancer research and clinical oncology. 2001127(7)411-7.20.Registry NC. Cancer In Ireland Annual report of the National Registry. 2013.21.Fund WCR. polity and Action for Cancer Prevention. Food, Nutrition, and Physical activity a Global Perspective. 2009 updated 2011.22.Morris MS, Picciano MF, Jacques PF, Selhub J. plasma pyridoxal 5-phosphate in the US population the National Health and Nutrition Examination Survey, 2003-2004. The American journal of clinical nutrition. 200887(5)1446-54.23.Zhang XH, Ma J, Smith-Warner SA, Lee JE, Giovannucci E. Vitamin B6 and colorectal cancer current evidence and future directions. World journal of gastroenterology WJG. 201319(7)1005-10.24.Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. The journal of nutrition, health aging. 20026(1)39-42.25.Komatsu S, Watanabe H, Oka T, Tsuge H, Kat N. Dietary vitamin B6 suppresses colon tumorigenesis, 8-hydroxyguanosine, 4-hydroxynonenal, and inducible nitric oxide synthase protein in azoxymethane-treated mice. Journal of nutritional science and vitaminology. 200248(1)65-8.26.Matsubara K, Mori M, Mats uura Y, Kato N. Pyridoxal 5-phosphate and pyridoxal inhibit angiogenesis in serum-free rat aortic ring assay. International journal of molecular medicine. 20018(5)505-8.27.Jain SK, Lim G. Pyridoxine and pyridoxamine inhibits superoxide radicals and prevents lipid peroxidation, protein glycosylation, and (Na+ + K+)-ATPase activity reduction in high glucose-treated human erythrocytes. Free radical biology medicine. 200130(3)232-7.28.Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer a meta-analysis of prospective studies. JAMA the journal of the American Medical Association. 2010303(11)1077-83.29.Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. The Journal of nutrition. 2007137(7)1808-14.

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