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Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial.
Nutrients 2017; 9(11)N

Abstract

Fibroblast growth factor 23 (FGF23) is an independent risk factor for cardiovascular mortality in chronic kidney disease. Omega-3 (n-3) fatty acid consumption has been inversely associated with FGF23 levels and with cardiovascular risk. We examined the effect of marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and plant-derived alpha-linolenic acid (ALA) on plasma FGF23 levels in post-myocardial infarction patients with chronic kidney disease. In the randomized double-blind Alpha Omega Trial, 4837 patients with a history of myocardial infarction aged 60-80 years (81% men) were randomized to one of four trial margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day ALA, EPA-DHA plus ALA, or placebo for 41 months. In a subcohort of 336 patients with an eGFR < 60 mL/min/1.73 m² (creatinine-cystatin C-based CKD-EPI formula), plasma C-terminal FGF23 was measured by ELISA at baseline and end of follow-up. We used analysis of covariance to examine treatment effects on FGF23 levels adjusted for baseline FGF23. Patients consumed 19.8 g margarine/day on average, providing an additional amount of 236 mg/day EPA with 158 mg/day DHA, 1.99 g/day ALA or both, in the active intervention groups. Over 79% of patients were treated with antihypertensive and antithrombotic medication and statins. At baseline, plasma FGF23 was 150 (128 to 172) RU/mL (mean (95% CI)). After 41 months, overall FGF23 levels had increased significantly (p < 0.0001) to 212 (183 to 241) RU/mL. Relative to the placebo, the treatment effect of EPA-DHA was indifferent, with a mean change in FGF23 (95% CI) of -17 (-97, 62) RU/mL (p = 0.7). Results were similar for ALA (36 (-42, 115) RU/mL) and combined EPA-DHA and ALA (34 (-44, 113) RU/mL). Multivariable adjustment, pooled analyses, and subgroup analyses yielded similar non-significant results. Long-term supplementation with modest quantities of EPA-DHA or ALA does not reduce plasma FGF23 levels when added to cardiovascular medication in post-myocardial patients with chronic kidney disease.

Authors+Show Affiliations

Department of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. m.h.de.borst@umcg.nl.Department of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. leandronut@yahoo.com.br. Department of Nephrology, UNIFESP, Rua Botucatu, 740, Vila Clementino, São Paulo 04023900, SP, Brazil. leandronut@yahoo.com.br.Department of Internal Medicine and Nephrology, Jeroen Bosch Hospital, Henri Dunantstraat 1, 5223 GZ Den Bosch, The Netherlands. e.k.hoogeveen@lumc.nl. Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. e.k.hoogeveen@lumc.nl.Department of Psychiatry, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. e.j.giltay@lumc.nl.Department of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. g.j.navis@umcg.nl.Department of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. s.j.l.bakker@umcg.nl.Division of Human Nutrition, Wageningen University & Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands. marianne.geleijnse@wur.nl.Division of Human Nutrition, Wageningen University & Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands. daan.kromhout@wur.nl.Division of Human Nutrition, Wageningen University & Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands. sabita.soedamah-muthu@wur.nl.

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

29137111

Citation

de Borst, Martin H., et al. "Effect of Omega-3 Fatty Acid Supplementation On Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients With Chronic Kidney Disease: the Alpha Omega Trial." Nutrients, vol. 9, no. 11, 2017.
de Borst MH, Baia LC, Hoogeveen EK, et al. Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial. Nutrients. 2017;9(11).
de Borst, M. H., Baia, L. C., Hoogeveen, E. K., Giltay, E. J., Navis, G., Bakker, S. J. L., ... Soedamah-Muthu, S. S. (2017). Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial. Nutrients, 9(11), doi:10.3390/nu9111233.
de Borst MH, et al. Effect of Omega-3 Fatty Acid Supplementation On Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients With Chronic Kidney Disease: the Alpha Omega Trial. Nutrients. 2017 Nov 11;9(11) PubMed PMID: 29137111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial. AU - de Borst,Martin H, AU - Baia,Leandro C, AU - Hoogeveen,Ellen K, AU - Giltay,Erik J, AU - Navis,Gerjan, AU - Bakker,Stephan J L, AU - Geleijnse,Johanna M, AU - Kromhout,Daan, AU - Soedamah-Muthu,Sabita S, Y1 - 2017/11/11/ PY - 2017/09/06/received PY - 2017/11/03/revised PY - 2017/11/08/accepted PY - 2017/11/16/entrez PY - 2017/11/16/pubmed PY - 2018/7/10/medline KW - cardiovascular KW - chronic kidney disease KW - fibroblast growth factor 23 KW - myocardial infarction KW - n-3 polyunsaturated fatty acids JF - Nutrients JO - Nutrients VL - 9 IS - 11 N2 - Fibroblast growth factor 23 (FGF23) is an independent risk factor for cardiovascular mortality in chronic kidney disease. Omega-3 (n-3) fatty acid consumption has been inversely associated with FGF23 levels and with cardiovascular risk. We examined the effect of marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and plant-derived alpha-linolenic acid (ALA) on plasma FGF23 levels in post-myocardial infarction patients with chronic kidney disease. In the randomized double-blind Alpha Omega Trial, 4837 patients with a history of myocardial infarction aged 60-80 years (81% men) were randomized to one of four trial margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day ALA, EPA-DHA plus ALA, or placebo for 41 months. In a subcohort of 336 patients with an eGFR < 60 mL/min/1.73 m² (creatinine-cystatin C-based CKD-EPI formula), plasma C-terminal FGF23 was measured by ELISA at baseline and end of follow-up. We used analysis of covariance to examine treatment effects on FGF23 levels adjusted for baseline FGF23. Patients consumed 19.8 g margarine/day on average, providing an additional amount of 236 mg/day EPA with 158 mg/day DHA, 1.99 g/day ALA or both, in the active intervention groups. Over 79% of patients were treated with antihypertensive and antithrombotic medication and statins. At baseline, plasma FGF23 was 150 (128 to 172) RU/mL (mean (95% CI)). After 41 months, overall FGF23 levels had increased significantly (p < 0.0001) to 212 (183 to 241) RU/mL. Relative to the placebo, the treatment effect of EPA-DHA was indifferent, with a mean change in FGF23 (95% CI) of -17 (-97, 62) RU/mL (p = 0.7). Results were similar for ALA (36 (-42, 115) RU/mL) and combined EPA-DHA and ALA (34 (-44, 113) RU/mL). Multivariable adjustment, pooled analyses, and subgroup analyses yielded similar non-significant results. Long-term supplementation with modest quantities of EPA-DHA or ALA does not reduce plasma FGF23 levels when added to cardiovascular medication in post-myocardial patients with chronic kidney disease. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/29137111/Effect_of_Omega_3_Fatty_Acid_Supplementation_on_Plasma_Fibroblast_Growth_Factor_23_Levels_in_Post_Myocardial_Infarction_Patients_with_Chronic_Kidney_Disease:_The_Alpha_Omega_Trial_ L2 - http://www.mdpi.com/resolver?pii=nu9111233 DB - PRIME DP - Unbound Medicine ER -