The effects of omega-3 fatty acid on vitamin D activation in hemodialysis patients: a pilot study

Su Mi Lee, Young Ki Son, Seong Eun Kim, Won Suk An, Su Mi Lee, Young Ki Son, Seong Eun Kim, Won Suk An

Abstract

The high incidence of cardiovascular disease and vitamin D deficiency in chronic kidney disease patients is well known. Vitamin D activation by omega-3 fatty acid (FA) supplementation may explain the cardioprotective effects exerted by omega-3 FA. We hypothesized that omega-3 FA and 25-hydroxyvitamin D (25(OH)D) supplementation may increase 1,25-dihydroxyvitamin D (1,25(OH)2D) levels compared to 25(OH)D supplementation alone in hemodialysis (HD) patients that have insufficient or deficient 25(OH)D levels. We enrolled patients that were treated for at least six months with 25(OH)D < 30 ng/mL (NCT01596842). Patients were randomized to treatment for 12 weeks with cholecalciferol supplemented with omega-3 FA or a placebo. Levels of 25(OH)D and 1,25(OH)2D were measured after 12 weeks. The erythrocyte membrane FA contents were also measured. Levels of 25(OH)D were increased in both groups at 12 weeks compared to baseline. The 1,25(OH)2D levels at 12 weeks compared to baseline showed a tendency to increase in the omega-3 FA group. The oleic acid and monounsaturated FA content decreased, while the omega-3 index increased in the omega-3 FA group. Omega-3 FA supplementation may be partly associated with vitamin D activation, although increased 25(OH)D levels caused by short-term cholecalciferol supplementation were not associated with vitamin D activation in HD patients.

Figures

Figure 1
Figure 1
(A) Change of 25-hydroxyvitamin D level by cholecalciferol with omega-3 FA supplementation. (B) Change of 1,25-dihydroxyvitamin D level by cholecalciferol with omega-3 FA supplementation. * p-value < 0.05 (mean values are significantly different from baseline). Repeated-measure analysis of variance was used to compare baseline data with six-week and 12-week data.
Figure 2
Figure 2
Change in 1,25-dihydroxyvitamin D level according to each patient.

References

    1. Go A.S., Chertow G.M., Fan D., McCulloch C.E., Hsu C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 2004;351:1296–1305. doi: 10.1056/NEJMoa041031.
    1. Tonelli M., Wiebe N., Culleton B., House A., Rabbat C., Fok M., McAlister F., Garg A.X. Chronic kidney disease and mortality risk: A systematic review. JASN. 2006;17:2034–2047. doi: 10.1681/ASN.2005101085.
    1. Foley R.N., Parfrey P.S., Sarnak M.J. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am. J. Kidney Dis. 1998;32:S112–S119. doi: 10.1053/ajkd.1998.v32.pm9820470.
    1. Vanholder R., Massy Z., Argiles A., Spasovski G., Verbeke F., Lameire N. Chronic kidney disease as cause of cardiovascular morbidity and mortality. Nephrol. Dial. Transplant. 2005;20:1048–1056. doi: 10.1093/ndt/gfh813.
    1. Stenvinkel P., Heimburger O., Lindholm B., Kaysen G.A., Bergstrom J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (mia syndrome) Nephrol. Dial. Transplant. 2000;15:953–960. doi: 10.1093/ndt/15.7.953.
    1. Vaziri N.D. Role of dyslipidemia in impairment of energy metabolism, oxidative stress, inflammation and cardiovascular disease in chronic kidney disease. Clin. Exp. Nephrol. 2014;18:265–268. doi: 10.1007/s10157-013-0847-z.
    1. Mizobuchi M., Towler D., Slatopolsky E. Vascular calcification: The killer of patients with chronic kidney disease. JASN. 2009;20:1453–1464. doi: 10.1681/ASN.2008070692.
    1. LaClair R.E., Hellman R.N., Karp S.L., Kraus M., Ofner S., Li Q., Graves K.L., Moe S.M. Prevalence of calcidiol deficiency in ckd: A cross-sectional study across latitudes in the united states. Am. J. Kidney Dis. 2005;45:1026–1033. doi: 10.1053/j.ajkd.2005.02.029.
    1. Holick M.F. Vitamin d deficiency. N. Engl. J. Med. 2007;357:266–281. doi: 10.1056/NEJMra070553.
    1. Pilz S., Iodice S., Zittermann A., Grant W.B., Gandini S. Vitamin d status and mortality risk in CKD: A meta-analysis of prospective studies. Am. J. Kidney Dis. 2011;58:374–382.
    1. Pilz S., Tomaschitz A., Friedl C., Amrein K., Drechsler C., Ritz E., Boehm B.O., Grammer T.B., Marz W. Vitamin D status and mortality in chronic kidney disease. Nephrol. Dial. Transplant. 2011;26:3603–3609. doi: 10.1093/ndt/gfr076.
    1. Wolf M., Shah A., Gutierrez O., Ankers E., Monroy M., Tamez H., Steele D., Chang Y., Camargo C.A., Jr., Tonelli M., et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int. 2007;72:1004–1013. doi: 10.1038/sj.ki.5002451.
    1. Pecovnik-Balon B., Jakopin E., Bevc S., Knehtl M., Gorenjak M. Vitamin D as a novel nontraditional risk factor for mortality in hemodialysis patients. Ther. Apher. Dial. 2009;13:268–272. doi: 10.1111/j.1744-9987.2009.00722.x.
    1. Drechsler C., Pilz S., Obermayer-Pietsch B., Verduijn M., Tomaschitz A., Krane V., Espe K., Dekker F., Brandenburg V., Marz W., et al. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur. Heart J. 2010;31:2253–2261. doi: 10.1093/eurheartj/ehq246.
    1. Melamed M.L., Astor B., Michos E.D., Hostetter T.H., Powe N.R., Muntner P. 25-hydroxyvitamin D levels, race, and the progression of kidney disease. JASN. 2009;20:2631–2639. doi: 10.1681/ASN.2009030283.
    1. Dusso A.S., Brown A.J., Slatopolsky E. Vitamin D. Am. J. Physiol. Ren. Physiol. 2005;289:F8–F28. doi: 10.1152/ajprenal.00336.2004.
    1. Zehnder D., Bland R., Williams M.C., McNinch R.W., Howie A.J., Stewart P.M., Hewison M. Extrarenal expression of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase. J. Clin. Endocrinol. Metab. 2001;86:888–894.
    1. Hewison M., Zehnder D., Chakraverty R., Adams J.S. Vitamin d and barrier function: A novel role for extra-renal 1 alpha-hydroxylase. Mol. Cell. Endocrinol. 2004;215:31–38. doi: 10.1016/j.mce.2003.11.017.
    1. Matias P.J., Jorge C., Ferreira C., Borges M., Aires I., Amaral T., Gil C., Cortez J., Ferreira A. Cholecalciferol supplementation in hemodialysis patients: Effects on mineral metabolism, inflammation, and cardiac dimension parameters. CJASN. 2010;5:905–911.
    1. An W.S., Lee S.M., Son Y.K., Kim S.E., Kim K.H., Han J.Y., Bae H.R., Rha S.H., Park Y. Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis patients. Nutr. Res. 2012;32:495–502. doi: 10.1016/j.nutres.2012.06.005.
    1. Li Y.C., Qiao G., Uskokovic M., Xiang W., Zheng W., Kong J. Vitamin D: A negative endocrine regulator of the renin-angiotensin system and blood pressure. J. Steroid Biochem. Mol. Biol. 2004;89–90:387–392. doi: 10.1016/j.jsbmb.2004.03.004.
    1. Rigby W.F., Denome S., Fanger M.W. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin d3. Specific inhibition at the level of messenger RNA. J. Clin. Investig. 1987;79:1659–1664. doi: 10.1172/JCI113004.
    1. Chen S., Law C.S., Grigsby C.L., Olsen K., Gardner D.G. A role for the cell cycle phosphatase Cdc25a in vitamin D-dependent inhibition of adult rat vascular smooth muscle cell proliferation. J. Steroid Biochem. Mol. Biol. 2010;122:326–332. doi: 10.1016/j.jsbmb.2010.08.007.
    1. Martinesi M., Bruni S., Stio M., Treves C. 1,25-dihydroxyvitamin D3 inhibits tumor necrosis factor-alpha-induced adhesion molecule expression in endothelial cells. Cell Biol. Int. 2006;30:365–375. doi: 10.1016/j.cellbi.2006.01.004.
    1. Lambert P.W., Stern P.H., Avioli R.C., Brackett N.C., Turner R.T., Greene A., Fu I.Y., Bell N.H. Evidence for extrarenal production of 1 alpha, 25-dihydroxyvitamin D in man. J. Clin. Investig. 1982;69:722–725. doi: 10.1172/JCI110501.
    1. Jean G., Souberbielle J.C., Chazot C. Monthly cholecalciferol administration in haemodialysis patients: A simple and efficient strategy for vitamin D supplementation. Nephrol. Dial. Transplant. 2009;24:3799–3805. doi: 10.1093/ndt/gfp370.
    1. Hewison M., Burke F., Evans K.N., Lammas D.A., Sansom D.M., Liu P., Modlin R.L., Adams J.S. Extra-renal 25-hydroxyvitamin D3–1alpha-hydroxylase in human health and disease. J. Steroid Biochem. Mol. Biol. 2007;103:316–321. doi: 10.1016/j.jsbmb.2006.12.078.
    1. Tokmak F., Quack I., Schieren G., Sellin L., Rattensperger D., Holland-Letz T., Weiner S.M., Rump L.C. High-dose cholecalciferol to correct vitamin D deficiency in haemodialysis patients. Nephrol. Dial. Transplant. 2008;23:4016–4020. doi: 10.1093/ndt/gfn367.
    1. Leaf A., Kang J.X., Xiao Y.F., Billman G.E. Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation. 2003;107:2646–2652. doi: 10.1161/01.CIR.0000069566.78305.33.
    1. An W.S., Lee S.M., Son Y.K., Kim S.E., Kim K.H., Han J.Y., Bae H.R., Park Y. Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients. Prostaglandins Leukot Essent Fat. Acids. 2012;86:29–34. doi: 10.1016/j.plefa.2011.10.009.
    1. Siguel E.N., Lerman R.H. Altered fatty acid metabolism in patients with angiographically documented coronary artery disease. Metabolism. 1994;43:982–993. doi: 10.1016/0026-0495(94)90178-3.
    1. Paganelli F., Maixent J.M., Duran M.J., Parhizgar R., Pieroni G., Sennoune S. Altered erythrocyte n-3 fatty acids in mediterranean patients with coronary artery disease. Int. J. Cardiol. 2001;78:27–32. doi: 10.1016/S0167-5273(00)00442-3.
    1. Block R.C., Harris W.S., Reid K.J., Spertus J.A. Omega-6 and trans fatty acids in blood cell membranes: A risk factor for acute coronary syndromes? Am. Heart J. 2008;156:1117–1123. doi: 10.1016/j.ahj.2008.07.014.
    1. Jo S., An W.S., Park Y. Erythrocyte n-3 polyunsaturated fatty acids and the risk of type 2 diabetes in koreans: A case-control study. Ann. Nutr. Metab. 2013;63:283–290.
    1. Willett W.C., Stampfer M.J., Manson J.E., Colditz G.A., Speizer F.E., Rosner B.A., Sampson L.A., Hennekens C.H. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet. 1993;341:581–585. doi: 10.1016/0140-6736(93)90350-P.
    1. Oomen C.M., Ocke M.C., Feskens E.J., van Erp-Baart M.A., Kok F.J., Kromhout D. Association between trans fatty acid intake and 10-year risk of coronary heart disease in the zutphen elderly study: A prospective population-based study. Lancet. 2001;357:746–751. doi: 10.1016/S0140-6736(00)04166-0.
    1. Lemaitre R.N., King I.B., Raghunathan T.E., Pearce R.M., Weinmann S., Knopp R.H., Copass M.K., Cobb L.A., Siscovick D.S. Cell membrane trans-fatty acids and the risk of primary cardiac arrest. Circulation. 2002;105:697–701. doi: 10.1161/hc0602.103583.
    1. Lemaitre R.N., King I.B., Mozaffarian D., Sotoodehnia N., Rea T.D., Kuller L.H., Tracy R.P., Siscovick D.S. Plasma phospholipid trans fatty acids, fatal ischemic heart disease, and sudden cardiac death in older adults: The cardiovascular health study. Circulation. 2006;114:209–215. doi: 10.1161/CIRCULATIONAHA.106.620336.
    1. Mozaffarian D., Cao H., King I.B., Lemaitre R.N., Song X., Siscovick D.S., Hotamisligil G.S. Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. Adults: A cohort study. Ann. Int. Med. 2010;153:790–799. doi: 10.7326/0003-4819-153-12-201012210-00005.
    1. Mozaffarian D., de Oliveira Otto M.C., Lemaitre R.N., Fretts A.M., Hotamisligil G., Tsai M.Y., Siscovick D.S., Nettleton J.A. Trans-palmitoleic acid, other dairy fat biomarkers, and incident diabetes: The multi-ethnic study of atherosclerosis (mesa) Am. J. Clin. Nutr. 2013;97:854–861. doi: 10.3945/ajcn.112.045468.
    1. Lebreton J.P., Joisel F., Raoult J.P., Lannuzel B., Rogez J.P., Humbert G. Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: Evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant. J. Clin. Investig. 1979;64:1118–1129. doi: 10.1172/JCI109551.
    1. Triffitt J.T., Gebauer U., Ashton B.A., Owen M.E., Reynolds J.J. Origin of plasma alpha2HS-glycoprotein and its accumulation in bone. Nature. 1976;262:226–227. doi: 10.1038/262226a0.
    1. Schafer C., Heiss A., Schwarz A., Westenfeld R., Ketteler M., Floege J., Muller-Esterl W., Schinke T., Jahnen-Dechent W. The serum protein alpha 2-heremans-schmid glycoprotein/fetuin-a is a systemically acting inhibitor of ectopic calcification. J. Clin. Investig. 2003;112:357–366. doi: 10.1172/JCI17202.
    1. Stefan N., Hennige A.M., Staiger H., Machann J., Schick F., Krober S.M., Machicao F., Fritsche A., Haring H.U. Alpha2-heremans-schmid glycoprotein/fetuin-a is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care. 2006;29:853–857. doi: 10.2337/diacare.29.04.06.dc05-1938.
    1. Ix J.H., Shlipak M.G., Brandenburg V.M., Ali S., Ketteler M., Whooley M.A. Association between human fetuin-A and the metabolic syndrome: Data from the heart and soul study. Circulation. 2006;113:1760–1767. doi: 10.1161/CIRCULATIONAHA.105.588723.
    1. Weikert C., Stefan N., Schulze M.B., Pischon T., Berger K., Joost H.G., Haring H.U., Boeing H., Fritsche A. Plasma fetuin-a levels and the risk of myocardial infarction and ischemic stroke. Circulation. 2008;118:2555–2562. doi: 10.1161/CIRCULATIONAHA.108.814418.
    1. Wang A.Y., Woo J., Lam C.W., Wang M., Chan I.H., Gao P., Lui S.F., Li P.K., Sanderson J.E. Associations of serum fetuin-a with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol. Dial. Transplant. 2005;20:1676–1685. doi: 10.1093/ndt/gfh891.
    1. Stenvinkel P., Wang K., Qureshi A.R., Axelsson J., Pecoits-Filho R., Gao P., Barany P., Lindholm B., Jogestrand T., Heimburger O., et al. Low fetuin-a levels are associated with cardiovascular death: Impact of variations in the gene encoding fetuin. Kidney Int. 2005;67:2383–2392. doi: 10.1111/j.1523-1755.2005.00345.x.
    1. Park M.K., Kim D.W., Kim J., Park S., Joung H., Song W.O., Paik H.Y. Development of a dish-based, semi-quantitative FFQ for the korean diet and cancer research using a database approach. Br. J. Nutr. 2011;105:1065–1072. doi: 10.1017/S0007114510004599.

Source: PubMed

3
Prenumerera