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Nutrients 2017, 9(11), 1233; doi:10.3390/nu9111233

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

1
Department of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
2
Department of Nephrology, UNIFESP, Rua Botucatu, 740, Vila Clementino, São Paulo 04023900, SP, Brazil
3
Department of Internal Medicine and Nephrology, Jeroen Bosch Hospital, Henri Dunantstraat 1, 5223 GZ Den Bosch, The Netherlands
4
Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
5
Department of Psychiatry, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
6
Division of Human Nutrition, Wageningen University & Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands
*
Author to whom correspondence should be addressed.
Received: 6 September 2017 / Revised: 3 November 2017 / Accepted: 8 November 2017 / Published: 11 November 2017
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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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. View Full-Text
Keywords: n-3 polyunsaturated fatty acids; fibroblast growth factor 23; myocardial infarction; chronic kidney disease; cardiovascular n-3 polyunsaturated fatty acids; fibroblast growth factor 23; myocardial infarction; chronic kidney disease; cardiovascular
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MDPI and ACS Style

de Borst, M.H.; Baia, L.C.; Hoogeveen, E.K.; Giltay, E.J.; Navis, G.; Bakker, S.J.L.; Geleijnse, J.M.; Kromhout, D.; Soedamah-Muthu, S.S. 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, 1233.

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