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Meta-Analysis
. 2022 Sep 2;116(3):699-729.
doi: 10.1093/ajcn/nqac153.

A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis

Juanita J Fewkes  1   2 , Nicole J Kellow  1   3 , Stephanie F Cowan  1 , Gary Williamson  1   2 , Aimee L Dordevic  1   2
Affiliations
Meta-Analysis

A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis

Juanita J Fewkes et al. Am J Clin Nutr. .

Abstract

Background: Endothelial dysfunction is a predictive risk factor for the development of atherosclerosis and is assessed by flow-mediated dilation (FMD). Although it is known that NO-dependent endothelial dysfunction occurs after consuming a high-fat meal, the magnitude of the effect and the factors that affect the response are unquantified.

Objectives: We conducted a systematic review and meta-analysis exploring the quantitative effects of a single high-fat meal on endothelial function and determined the factors that modify the FMD response.

Methods: Six databases were systematically searched for original research published up to January 2022. Eligible studies measured fasting and postprandial FMD following consumption of a high-fat meal. Meta-regression was used to analyze the effect of moderator variables.

Results: There were 131 studies included, of which 90 were suitable for quantitative meta-analysis. A high-fat meal challenge transiently caused endothelial dysfunction, decreasing postprandial FMD at 2 hours [-1.02 percentage points (pp); 95% CI: -1.34 to -0.70 pp; P < 0.01; I2 = 93.3%], 3 hours [-1.04 pp; 95% CI: -1.48 to -0.59 pp; P < 0.001; I2 = 84.5%], and 4 hours [-1.19 pp; 95% CI: -1.53 to -0.84 pp; P < 0.01; I2 = 94.6%]. Younger, healthy-weight participants exhibited a greater postprandial reduction in the FMD percentage change than older, heavier, at-risk groups after a high-fat meal ( P < 0.05). The percentage of fat in the meals was inversely associated with the magnitude of postprandial changes in FMD at 3 hours (P < 0.01).

Conclusions: A single, high-fat meal adversely impacts endothelial function, with the magnitude of the impact on postprandial FMD moderated by the fasting FMD, participant age, BMI, and fat content of the meal. Recommendations are made to standardize the design of future postprandial FMD studies and optimize interpretation of results, as high-fat meals are commonly used in clinical studies as a challenge to assess endothelial function and therapeutics. This trial was registered at PROSPERO as CRD42020187244.

Keywords: cardiovascular risk; dietary fats; flow-mediated dilation; postprandial; vascular endothelium.

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Figures

FIGURE 1
FIGURE 1
Flow diagram showing the progression through the literature search and screening process. Abbreviation: FMD, flow-mediated dilation.
FIGURE 2
FIGURE 2
A summary of the average mean difference of FMD% between postprandial and fasting measurements (postprandial FMD% − fasting FMD%) after a high–fat meal (mean ± SEM), across (A) all studies and (B) NO-dependent FMD studies. The sample size is indicated above or below the bar. ^Time points at which a meta-regression analysis was performed. Abbreviations: FMD%, flow-mediated dilation percentage change; NO, nitric oxide.
FIGURE 3
FIGURE 3
Forest plots of the impactof a single, high-fat meal on endothelial function at (A) 2 hours, (B) 3 hours, and (C) 4 hours after consumption. Mean FMD% differences and 95% CIs are indicated by white dots and black horizontal lines. The size of each box is proportionally scaled to the effect size for each group in the restricted maximum likelihood model. The black diamond represents the average mean difference for all groups. FMD is measured as the relative percentage change in the peak reactive hyperemia diameter from the baseline diameter (FMD%). The mean difference in the FMD% was calculated as the fasting FMD% subtracted from the postprandial FMD%, termed the FMD change; the units of the FMD change are pp. The heterogeneity analysis is also presented. *Groups with the same participants consuming different types of meals. Specific meal contents are described in Table 1. #Groups with the same participants consuming the same meal before and after different diet interventions. Abbreviations: CVD, cardiovascular disease; En%, percentage of total meal energy; FMD, flow-mediated dilation; FMD%, flow-mediated dilation percentage change; pp, percentage points; REML, restricted maximum likelihood method.
FIGURE 3
FIGURE 3
Forest plots of the impactof a single, high-fat meal on endothelial function at (A) 2 hours, (B) 3 hours, and (C) 4 hours after consumption. Mean FMD% differences and 95% CIs are indicated by white dots and black horizontal lines. The size of each box is proportionally scaled to the effect size for each group in the restricted maximum likelihood model. The black diamond represents the average mean difference for all groups. FMD is measured as the relative percentage change in the peak reactive hyperemia diameter from the baseline diameter (FMD%). The mean difference in the FMD% was calculated as the fasting FMD% subtracted from the postprandial FMD%, termed the FMD change; the units of the FMD change are pp. The heterogeneity analysis is also presented. *Groups with the same participants consuming different types of meals. Specific meal contents are described in Table 1. #Groups with the same participants consuming the same meal before and after different diet interventions. Abbreviations: CVD, cardiovascular disease; En%, percentage of total meal energy; FMD, flow-mediated dilation; FMD%, flow-mediated dilation percentage change; pp, percentage points; REML, restricted maximum likelihood method.
FIGURE 3
FIGURE 3
Forest plots of the impactof a single, high-fat meal on endothelial function at (A) 2 hours, (B) 3 hours, and (C) 4 hours after consumption. Mean FMD% differences and 95% CIs are indicated by white dots and black horizontal lines. The size of each box is proportionally scaled to the effect size for each group in the restricted maximum likelihood model. The black diamond represents the average mean difference for all groups. FMD is measured as the relative percentage change in the peak reactive hyperemia diameter from the baseline diameter (FMD%). The mean difference in the FMD% was calculated as the fasting FMD% subtracted from the postprandial FMD%, termed the FMD change; the units of the FMD change are pp. The heterogeneity analysis is also presented. *Groups with the same participants consuming different types of meals. Specific meal contents are described in Table 1. #Groups with the same participants consuming the same meal before and after different diet interventions. Abbreviations: CVD, cardiovascular disease; En%, percentage of total meal energy; FMD, flow-mediated dilation; FMD%, flow-mediated dilation percentage change; pp, percentage points; REML, restricted maximum likelihood method.
FIGURE 4
FIGURE 4
Diagrammatic representation of the arterial responses to FMD during fasting and after a high-fat meal in healthy and at-risk participants. Artery cross-sections show the diameter, FMD%, and FMD change. The at-risk participant group included individuals who presented with at least 1 CVD risk factor or were diagnosed with coronary artery disease. Diagrams are not to scale. Abbreviations: CVD, cardiovascular disease; FMD, flow-mediated dilation; FMD%, flow-mediated dilation percentage change; HFM, high-fat meal; pp, percentage points.
FIGURE 5
FIGURE 5
Publication bias was assessed by funnel plot of all studies in the meta-analysis at (A) 2 hours, (B) 3 hours, and (C) 4 hours after high-fat meal consumption. Abbreviation: FMD%, flow-mediated dilation percentage change.
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