Department of Nephrology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Department of Nephrology, UNIFESP, Rua Botucatu, 740, Vila Clementino, São Paulo 04023900, SP, Brazil.
Nutrients. 2017 Nov 11;9(11):1233. doi: 10.3390/nu9111233.
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 ( < 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 ( = 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.
成纤维细胞生长因子 23（FGF23）是慢性肾脏病心血管死亡率的独立危险因素。ω-3（n-3）脂肪酸的摄入与 FGF23 水平呈负相关，与心血管风险也呈负相关。我们研究了海洋 n-3 脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）和植物衍生的α-亚麻酸（ALA）对心肌梗死后慢性肾脏病患者血浆 FGF23 水平的影响。在随机双盲 Alpha Omega 试验中，4837 名年龄在 60-80 岁（81%为男性）的有心肌梗死病史的患者被随机分配至四种试验涂抹酱中的一种，这些试验涂抹酱补充了 400mg/天的 EPA 和 DHA、2g/天的 ALA、EPA-DHA 加 ALA 或安慰剂，随访时间为 41 个月。在 eGFR<60mL/min/1.73m²（基于肌酐-胱抑素 C 的 CKD-EPI 公式）的 336 名患者亚组中，基线和随访结束时通过 ELISA 测量血浆 C 端 FGF23。我们使用协方差分析来检查调整基线 FGF23 后治疗对 FGF23 水平的影响。患者平均每天食用 19.8g 涂抹酱，在活性干预组中提供了额外的 236mg/天 EPA 和 158mg/天 DHA、1.99g/天 ALA 或两者兼有。超过 79%的患者接受了降压和抗血栓药物以及他汀类药物治疗。在基线时，血浆 FGF23 为 150（128-172）RU/mL（平均值（95%CI））。41 个月后，总体 FGF23 水平显著升高（<0.0001）至 212（183-241）RU/mL。与安慰剂相比，EPA-DHA 的治疗效果无差异，FGF23 的平均变化（95%CI）为-17（-97，62）RU/mL（=0.7）。ALA（-42，115）RU/mL）和 EPA-DHA 和 ALA 联合（-44，113）RU/mL）的结果也类似。多变量调整、汇总分析和亚组分析得出了类似的非显著结果。在慢性肾脏病心肌梗死后患者中，添加心血管药物时，长期补充适量的 EPA-DHA 或 ALA 并不能降低血浆 FGF23 水平。
