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"Ann Arbor, MI - New laboratory research suggests that the COX-2 inhibitor celecoxib (Celebrex, Pfizer), might impede the action of "baby" aspirin [1]. Dr Gilad Rimon (University of Michigan, Ann Arbor) and colleagues found evidence that this was the case in a dog model and say that "it will be important to determine" whether the same is true in humans. The report was published online December 1, 2009 in the Proceedings of the National Academy of Medicine. Celecoxib is the only COX-2 inhibitor to have remained on the market in the US, and doctors who recommend this painkiller often coprescribe a daily low dose of 81 mg of aspirin (known as a "baby" dose) to counteract any possible prothrombotic effects of the coxib, while minimizing potential gastrointestinal toxicity of the aspirin. Senior author of the new work, Dr William L Smith (University of Michigan, Ann Arbor), explained to heartwire that previous studies in humans have shown that celecoxib does not interfere with the effect of a standard dose of aspirin (325 mg), but any potential interaction of celecoxib with the lower dose has not been examined. Stagger dosing to avoid any potential problems First, Smith explained that he and his colleagues looked in vitro at celecoxib and found that it binds to one of two available sites on the COX-1 enzyme. "This surprised us," he commented. "It appears to interfere with the ability of some other drugs to affect COX-1, most notably aspirin." Second, in beagles, they administered the dog-equivalent of a baby dose of aspirin in humans and then gave some of the animals the equivalent of 100 mg of celecoxib twice daily in addition. "Celecoxib plus aspirin interfered with the normal effect of low-dose aspirin on platelets," he notes. Smith says this observation obviously requires confirmation in humans, but in the meantime he suggests "getting around the problem" by patients taking the low-dose aspirin at least 15 to 30 minutes before the celecoxib is taken, "because

Cyclooxygenase (COX) is an enzyme (EC 1.14.99.1) that is responsible for formation of important biological mediators called prostanoids (including prostaglandins, prostacyclin and thromboxane). Pharmacological inhibition of COX can provide relief from the

Egg consumption in relation to cardiovascular disease and mortality: the Physicians' Health Study. Djoussé L, Gaziano JM. Am J Clin Nutr. 2008 Apr;87(4):964-9. PMID: 18400720 Results: In an average follow-up of 20 y, 1550 new myocardial infarctions (MIs), 1342 incident strokes, and 5169 deaths occurred. Egg consumption was not associated with incident MI or stroke in a multivariate Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87, 1.02), 1.03 (0.95, 1.11), 1.05 (0.93, 1.19), and 1.23 (1.11, 1.36) for the consumption of < 0.0001). This association was stronger among diabetic subjects, in whom the risk of death in a comparison of the highest with the lowest category of egg consumption was twofold (hazard ratio: 2.01; 95% CI: 1.26, 3.20; P for interaction = 0.09). Conclusions: Infrequent egg consumption does not seem to influence the risk of CVD in male physicians. In addition, egg consumption was positively related to mortality, more strongly so in diabetic subjects, in the study population.

Thromboxane B2 is an inactive metabolite/product of thromboxane A2. It is almost completely cleared in the urine. It itself is not involved in platelet activation and aggregation in case of a wound, but its precursor, thromboxane A2, is. Thromboxane A2 synthesis is the target of the drug aspirin, which inhibits the COX-1 enzyme (the source of thromboxane A2 in platelets).

Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Cerchietti LC, Navigante AH, Castro MA. Nutr Cancer. 2007;59(1):14-20. PMID: 17927497

Egg consumption, serum cholesterol, and cause-specific and all-cause mortality: the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged, 1980 (NIPPON DATA80). Nakamura Y, Okamura T, Tamaki S, Kadowaki T, Hayakawa T, Kita Y, Okayama A, Ueshima H; NIPPON DATA80 Research Group. Am J Clin Nutr. 2004 Jul;80(1):58-63. PMID: 15213028 Results: The subjects were categorized into 5 egg consumption groups on the basis of their responses to a questionnaire (≥2/d, 1/d, 1/2 d, 1-2/wk, and seldom). There were 69, 1396, 1667, 1742, and 315 women in each of the 5 groups, respectively. Age-adjusted total cholesterol (5.21, 5.04, 4.95, 4.91, and 4.92 mmol/L in the 5 egg consumption categories, respectively) was related to egg consumption (P < 0.0001, analysis of covariance). In women, unadjusted IHD mortality and all-cause mortality differed significantly between the groups [IHD mortality: 1.1, 0.5, 0.4, 0.5, and 2.0 per 1000 person-years, respectively (P = 0.008, chi-square test); all-cause mortality: 14.8, 8.0, 7.5, 7.5, and 14.5 per 1000 person-years, respectively (P < 0.0001, chi-square test)]. In men, egg consumption was not related to age-adjusted total cholesterol. Cox analysis found that, in women, all-cause mortality in the 1-2-eggs/wk group was significantly lower than that in the 1-egg/d group, whereas no such relations were noted in men. Conclusion: Limiting egg consumption may have some health benefits, at least in women in geographic areas where egg consumption makes a relatively large contribution to total dietary cholesterol intake.

Prostacyclin (or PGI2) is a member of the family of lipid molecules known as eicosanoids.\nAs a drug, it is also known as "epoprostenol".[1] The terms are sometimes used interchangeably Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane (TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage.

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

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

Effects of dietary flaxseed on intestinal tumorigenesis in Apc(Min) mouse. Bommareddy A, Zhang X, Schrader D, Kaushik RS, Zeman D, Matthees DP, Dwivedi C. Nutr Cancer. 2009;61(2):276-83. PMID: 19235044 DOI: 10.1080/01635580802419764

In biochemistry, eicosanoids are signaling molecules derived from omega-3 (ω-3) or omega-6 (ω-6) fats. They exert complex control over many bodily systems, especially in inflammation, immunity and as messengers in the central nervous system. The network

Egg consumption, serum cholesterol, and cause-specific and all-cause mortality: the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged, 1980 (NIPPON DATA80). Nakamura Y, Okamura T, Tamaki S, Kadowaki T, Hayakawa T, Kita Y, Okayama A, Ueshima H; NIPPON DATA80 Research Group. Am J Clin Nutr. 2004 Jul;80(1):58-63. PMID: 15213028 In men, egg consumption was not related to age-adjusted total cholesterol. Cox analysis found that, in women, all-cause mortality in the 1-2-eggs/wk group was significantly lower than that in the 1-egg/d group, whereas no such relations were noted in men. CONCLUSION: Limiting egg consumption may have some health benefits, at least in women in geographic areas where egg consumption makes a relatively large contribution to total dietary cholesterol intake.

Thromboxane A2 (TXA2) is a thromboxane. It is generated from prostaglandin H2 by thromboxane-A synthase. It is also a major component of blood clots. Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2. TXA2 is very unstable in aqueous solution, since it is hydrolyzed within about 30 seconds to the biologically inactive thromboxane B2. Due to its very short half life, TXA2 primarily functions as an autocrine or paracrine mediator in the nearby tissues surrounding its site of production.

Rosmarinic acid antagonizes activator protein-1-dependent activation of cyclooxygenase-2 expression in human cancer and nonmalignant cell lines. Scheckel KA, Degner SC, Romagnolo DF. J Nutr. 2008 Nov;138(11):2098-105. PMID: 18936204

Targeting lipoxygenases with care. de Souza PM, Newson J, Gilroy DW. Chem Biol. 2006 Nov;13(11):1121-2. PMID: 17113992 doi:10.1016/j.chembiol.2006.11.002  

March 7, 2005 Boston, MA - The anti-inflammatory effect of fish oils appears to be due to a powerful anti-inflammatory compound called resolvin (resolution-phase interaction product) E1, which is produced from eicosapentaenoic acid (EPA), Dr Makoto Arita (Brigham and Women's Hospital and Harvard Medical School, Boston, MA) and colleagues report in the March 7, 2005 issue of the Journal of Experimental Medicine [1]. Arita writes, "At nanomolar levels, resolvin E1 dramatically reduced dermal inflammation, peritonitis, dendritic cell migration, and interleukin (IL)-12 production.

A plethora of research documents the role of chronic inflammatory mediators such as 5-lipooxygenase (5-LOX) and tumor necrosis factor-alpha (TNF-α) in the manifestation and progression of prostate and other cancers.7-19,30,31,33,49,52-54,87,88 The typical American diet is high in omega-6 fatty acids, saturated fats, and arachidonic acid. Over-consumption of these foods, and under-consumption of omega-3 fatty acids, contribute significantly to systemic chronic inflammatory states. Boswellia extracts have been thoroughly studied as natural remedies for inflammatory disorders. A patented extract from boswellia called 5-LOXIN® has potent ability to inhibit the enzyme 5-LOX, preventing the formation of protein-degrading enzymes, and protecting against inflammation-induced events that can promote tumor angiogenesis.

Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy. Kelavkar UP, Hutzley J, Dhir R, Kim P, Allen KG, McHugh K. Neoplasia. 2006 Feb;8(2):112-24. PMID: 16611404