Yimin Zhao1, Huihui Xu2, Zezhong Tian1, Xu Wang2, Lin Xu1, Kongyao Li1, Xiaoli Gao1, Die Fan2, Xilin Ma1, Wenhua Ling2, Yan Yang3. 1. School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong, China. 2. Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong, China; Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China. 3. School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: yangyan3@mail.sysu.edu.cn.
Abstract
BACKGROUND & AIMS: Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. METHODS: In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. RESULTS: A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values < 0.05). Specifically, 320 mg/day anthocyanins effectively lowered plasma N-palmitoylsphingosine (Cer 16:0, mean change: -28.3 ± 41.2 versus 2.9 ± 38.2, nmol/L, P = 0.018) and N-tetracosanoylsphingosine (Cer 24:0, mean change: -157.1 ± 493.9 versus 10.7 ± 439.9, nmol/L, P = 0.002) compared with the placebo. The declines in plasma Cer 16:0 and Cer 24:0 were significantly correlated with the decreases in plasma non-high-density lipoprotein cholesterol (nonHDL-C, Spearman's r = 0.32, P = 0.040 for Cer 16:0; Spearman's r = 0.35, P = 0.026 for Cer 24:0), apolipoprotein B (Spearman's r = 0.33, P = 0.031 for Cer 16:0; Spearman's r = 0.48, P = 0.002 for Cer 24:0), and total cholesterol (Spearman's r = 0.34, P = 0.026 for Cer 16:0; Spearman's r = 0.31, P = 0.042 for Cer 24:0) after 12-week 320 mg/day anthocyanin administration. Besides, we found that anthocyanins at 320 mg/day also markedly enhanced cholesterol efflux capacity in the dyslipidemia, the changes of which were positively associated with the reductions in Cer 16:0 (Spearman's r = 0.42, P = 0.006) independent of HDL-C and apolipoprotein A-I. CONCLUSIONS: Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.
RCT Entities:
BACKGROUND & AIMS: Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. METHODS: In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. RESULTS: A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values < 0.05). Specifically, 320 mg/day anthocyanins effectively lowered plasma N-palmitoylsphingosine (Cer 16:0, mean change: -28.3 ± 41.2 versus 2.9 ± 38.2, nmol/L, P = 0.018) and N-tetracosanoylsphingosine (Cer 24:0, mean change: -157.1 ± 493.9 versus 10.7 ± 439.9, nmol/L, P = 0.002) compared with the placebo. The declines in plasma Cer 16:0 and Cer 24:0 were significantly correlated with the decreases in plasma non-high-density lipoprotein cholesterol (nonHDL-C, Spearman's r = 0.32, P = 0.040 for Cer 16:0; Spearman's r = 0.35, P = 0.026 for Cer 24:0), apolipoprotein B (Spearman's r = 0.33, P = 0.031 for Cer 16:0; Spearman's r = 0.48, P = 0.002 for Cer 24:0), and total cholesterol (Spearman's r = 0.34, P = 0.026 for Cer 16:0; Spearman's r = 0.31, P = 0.042 for Cer 24:0) after 12-week 320 mg/day anthocyanin administration. Besides, we found that anthocyanins at 320 mg/day also markedly enhanced cholesterol efflux capacity in the dyslipidemia, the changes of which were positively associated with the reductions in Cer 16:0 (Spearman's r = 0.42, P = 0.006) independent of HDL-C and apolipoprotein A-I. CONCLUSIONS: Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.
Authors: Henrique J C B Gouveia; Mercedes V Urquiza-Martínez; Raul Manhães-de-Castro; Bárbara J R Costa-de-Santana; José Pérez Villarreal; Rosalío Mercado-Camargo; Luz Torner; Jailane de Souza Aquino; Ana E Toscano; Omar Guzmán-Quevedo Journal: Int J Mol Sci Date: 2022-07-28 Impact factor: 6.208