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

Martin De Borst, Leandro Baia, Ellen Hoogeveen, Erik Giltay, Gerjan Navis, Stephan Bakker, Johanna Geleijnse, Daan Kromhout, S.S. Soedamah-Muthu

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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. Keywords: n-3 polyunsaturated fatty acids; fibroblast growth factor 23; myocardial infarction; chronic kidney disease; cardiovascular
Original languageEnglish
Article number1233
JournalNutrients
Volume9
Issue number11
DOIs
Publication statusPublished - 2017

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alpha-Linolenic Acid
Eicosapentaenoic Acid
Margarine
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cystatin C
Creatinine
Placebos

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De Borst, Martin ; Baia, Leandro ; Hoogeveen, Ellen ; Giltay, Erik ; Navis, Gerjan ; Bakker, Stephan ; Geleijnse, Johanna ; Kromhout, Daan ; 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. In: Nutrients. 2017 ; Vol. 9, No. 11.
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title = "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",
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. Keywords: n-3 polyunsaturated fatty acids; fibroblast growth factor 23; myocardial infarction; chronic kidney disease; cardiovascular",
author = "{De Borst}, Martin and Leandro Baia and Ellen Hoogeveen and Erik Giltay and Gerjan Navis and Stephan Bakker and Johanna Geleijnse and Daan Kromhout and S.S. Soedamah-Muthu",
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journal = "Nutrients",
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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. / De Borst, Martin; Baia, Leandro; Hoogeveen, Ellen; Giltay, Erik; Navis, Gerjan; Bakker, Stephan; Geleijnse, Johanna; Kromhout, Daan; Soedamah-Muthu, S.S.

In: Nutrients, Vol. 9, No. 11, 1233, 2017.

Research output: Contribution to journalArticleScientificpeer-review

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

T2 - The alpha omega trial

AU - De Borst, Martin

AU - Baia, Leandro

AU - Hoogeveen, Ellen

AU - Giltay, Erik

AU - Navis, Gerjan

AU - Bakker, Stephan

AU - Geleijnse, Johanna

AU - Kromhout, Daan

AU - Soedamah-Muthu, S.S.

PY - 2017

Y1 - 2017

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. Keywords: n-3 polyunsaturated fatty acids; fibroblast growth factor 23; myocardial infarction; chronic kidney disease; cardiovascular

AB - 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. Keywords: n-3 polyunsaturated fatty acids; fibroblast growth factor 23; myocardial infarction; chronic kidney disease; cardiovascular

U2 - 10.3390/nu9111233

DO - 10.3390/nu9111233

M3 - Article

VL - 9

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 11

M1 - 1233

ER -