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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.

Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Prostate. 2007 Jun 15;67(9):911-23. PMID: 17440943 DOI: 10.1002/pros.20570 RESULTS No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum 7; P = 0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum 7) (P for interaction = 0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D. CONCLUSION In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC. Carriers of the variant Cdx2 A allele with low plasma 25-hydroxyvitamin D may experience a reduction in risk of total and poorly differentiated prostate cancers compared to non-carriers with adequate 25-hydroxyvitamin D.

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

Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y. Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC. Am J Clin Nutr. 2001 Mar;73(3):539-48. PMID: 11237929

Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mantena SK, Sharma SD, Katiyar SK. Mol Cancer Ther. 2006 Feb;5(2):296-308. PMID: 16505103 doi: 10.1158/1535-7163.MCT-05-0448 The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy. The evaluation of ancient herbal medicines may indicate novel strategies for the treatment of prostate cancer, which remains the leading cause of cancer-related deaths in American men (1). In our present investigation, we show that a naturally occurring isoquinoline alkaloid, berberine, significantly inhibits the proliferation and reduces the viability of DU145 and PC-3 as well as LNCaP cells (Fig. 1), which suggests that berberine may be an effective chemotherapeutic agent against both androgen-sensitive and androgen-insensitive prostate cancer cells. Importantly, we found that berberine did not exhibit toxicity to nonneoplastic human prostate epithelial cells under the conditions used, except for a moderate reduction in cell viability at higher concentrations when cells were treated in vitro for an extended period of time. In conclusion, the results of the present study indicate that berberine inhibits proliferation and induces G1-phase arrest and apoptosis in human prostate cancer cells but not in normal human prostate epithelial cells. In addition, we provide mechanistic evidence that berberine-induced apoptosis in prostate carcinoma cells, particularly hormone-refractory prostate carcinoma cells, is mediated through enhanced expression of Bax, disruption of the mitochondrial membrane potential, and activation of caspase-3.

Apoptotic effects of dietary and synthetic sphingolipids in androgen-independent (PC-3) prostate cancer cells. Kent KD, Clubbs EA, Harper WJ, Bomser JA. Lipids. 2008 Feb;43(2):143-9. Epub 2008 Jan 10. PMID: 18188632 DOI: 10.1007/s11745-007-3148-

Docosahexaenoic acid decreases phospholipase A2 activity in the neurites/nerve growth cones of PC12 cells. Martin RE. J Neurosci Res. 1998 Dec 15;54(6):805-13. PMID: 9856864 DOI: 10.1002/(SICI)1097-4547(19981215)54:63.0.CO;2-4

Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Trebble TM, Wootton SA, Miles EA, Mullee M, Arden NK, Ballinger AB, Stroud MA, Burdge GC, Calder PC. Am J Clin Nutr. 2003 Sep;78(3):376-82. PMID: 12936918

Immunological parameters: what do they mean? Calder PC. J Nutr. 2007 Mar;137(3 Suppl 2):773S-80S. Review. PMID: 17311974

Immunomodulation by omega-3 fatty acids. Calder PC. Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):327-35. Epub 2007 Nov 26. Review. PMID: 18032006 doi:10.1016/j.plefa.2007.10.015

Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids. Calder PC. Braz J Med Biol Res. 1998 Apr;31(4):467-90. Review. PMID: 9698798

Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease. Sijben JW, Calder PC. Proc Nutr Soc. 2007 May;66(2):237-59. Review. PMID: 17466105 doi:10.1017/S0029665107005472

Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Jones EL, Grimble RF, Williams CM, Yaqoob P, Calder PC. Am J Clin Nutr. 2004 Sep;80(3):614-20. PMID: 15321800 Conclusion: Divergent effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA appear on the blood lipid profile in healthy humans: trans-10,cis-12 CLA increases LDL:HDL cholesterol and total:HDL cholesterol, whereas cis-9,trans-11 CLA decreases them.

The relationship between the fatty acid composition of immune cells and their function. Calder PC. Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov;79(3-5):101-8. Epub 2008 Oct 23. Review. PMID: 18951005 doi:10.1016/j.plefa.2008.09.016

Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Wallace FA, Miles EA, Calder PC. Br J Nutr. 2003 May;89(5):679-89. PMID: 12720588

Limited effect of eicosapentaenoic acid on T-lymphocyte and natural killer cell numbers and functions in healthy young males. Miles EA, Banerjee T, Wells SJ, Calder PC. Nutrition. 2006 May;22(5):512-9. PMID: 16600816 doi:10.1016/j.nut.2005.11.011

Differential effects of selenium on benign and malignant prostate epithelial cells: stimulation of LNCaP cell growth by noncytotoxic, low selenite concentrations. Kandaş NO, Randolph C, Bosland MC. Nutr Cancer. 2009;61(2):251-64. PMID: 19235042