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

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 nitric oxide-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 To conduct a systematic review and meta-analysis exploring the quantitative effect of a single high-fat meal on endothelial function and determine the factors that modify the FMD response. Design 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. The protocol was pre-registered in the Prospero database (ID# CRD42020187244). 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, -0.70], P < 0.01, I2 = 93.3%), 3-hours: -1.04 pp ([-1.48, -0.59], P < 0.001, I2 = 84.5%), and 4-hours: -1.19 pp ([-1.53, -0.84], P < 0.01, I2 = 94.6%). Younger, healthy-weight participants exhibited a greater postprandial reduction in FMD% than older, heavier, at-risk groups after a high-fat meal (P < 0.05). Percent fat of the meals was inversely associated with the magnitude of postprandial change in FMD at 3-hours (P < 0.01). Conclusion A single high-fat meal adversely impacts endothelial function, with the magnitude of the impact on postprandial FMD moderated by fasting FMD, participant age, body mass index, 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.

Nutrition Interactions With Exercise Training on Endothelial Function

“…The reason for such decline is not entirely clear, but it is suggested to relate to younger individuals, men, and those with baseline hyperglycemia as well as high fasting FMD (12). Interestingly, this is consistent with recent work reporting that high-fat meals result in a reduction of 1% FMD at 2-, 3-, and 4-h postingestion ( P < 0.01), with a higher amount of fat intake and energy related to declines in endothelial function at only 3 and 4 h postingestion, respectively (13). Because meal ingestion can impact NO bioavailability (12), it is important to understand the impact of nutrients surrounding exercise to optimize vascular function.…”

Nutrition Interactions With Exercise Training on Endothelial Function

“…The reason for such decline is not entirely clear, but it is suggested to relate to younger individuals, men, and those with baseline hyperglycemia as well as high fasting FMD (12). Interestingly, this is consistent with recent work reporting that high-fat meals result in a reduction of 1% FMD at 2-, 3-, and 4-h postingestion ( P < 0.01), with a higher amount of fat intake and energy related to declines in endothelial function at only 3 and 4 h postingestion, respectively (13). Because meal ingestion can impact NO bioavailability (12), it is important to understand the impact of nutrients surrounding exercise to optimize vascular function.…”

From meal to malfunction: exploring molecular pathways, biomarkers and interventions in postprandial cardiometabolic health

“…Superoxide reacts with endothelial NO to generate peroxynitrite; the associated NO loss aligns with an approximately 1 absolute percentage-point decrement in brachial-artery FMD at 2–4 h after a single high-fat meal ( 76 – 78 ). ROS also signal through IKKβ/JNK to promote NLRP3 inflammasome assembly, increasing IL-1β and IL-18 ( 79 , 80 ).…”

Atypical monocyte dynamics in healthy humans in response to fasting and refeeding are distinguished by fasting HDL and postprandial cortisol

“…3 C ). Considering that non-classical monocytes are important for surveilling endothelium and maintaining vascular integrity that is known to be impaired following consumption of a single high-fat meal ( 31 – 33 ), we measured peripheral microvascular endothelial function by reactive hyperemia. Compared with Group 1 , Group 2 had a lower reactive hyperemia index ( P = 0.0037, Fig.…”

Nutrition Interactions With Exercise Training on Endothelial Function

“…The reason for such decline is not entirely clear, but it is suggested to relate to younger individuals, men, and those with baseline hyperglycemia as well as high fasting FMD (12). Interestingly, this is consistent with recent work reporting that high-fat meals result in a reduction of 1% FMD at 2-, 3-, and 4-h postingestion ( P < 0.01), with a higher amount of fat intake and energy related to declines in endothelial function at only 3 and 4 h postingestion, respectively (13). Because meal ingestion can impact NO bioavailability (12), it is important to understand the impact of nutrients surrounding exercise to optimize vascular function.…”

From meal to malfunction: exploring molecular pathways, biomarkers and interventions in postprandial cardiometabolic health

“…Superoxide reacts with endothelial NO to generate peroxynitrite; the associated NO loss aligns with an approximately 1 absolute percentage-point decrement in brachial-artery FMD at 2–4 h after a single high-fat meal ( 76 – 78 ). ROS also signal through IKKβ/JNK to promote NLRP3 inflammasome assembly, increasing IL-1β and IL-18 ( 79 , 80 ).…”

Atypical monocyte dynamics in healthy humans in response to fasting and refeeding are distinguished by fasting HDL and postprandial cortisol

“…3 C ). Considering that non-classical monocytes are important for surveilling endothelium and maintaining vascular integrity that is known to be impaired following consumption of a single high-fat meal ( 31 – 33 ), we measured peripheral microvascular endothelial function by reactive hyperemia. Compared with Group 1 , Group 2 had a lower reactive hyperemia index ( P = 0.0037, Fig.…”

Nutrition Interactions With Exercise Training on Endothelial Function

“…The reason for such decline is not entirely clear, but it is suggested to relate to younger individuals, men, and those with baseline hyperglycemia as well as high fasting FMD (12). Interestingly, this is consistent with recent work reporting that high-fat meals result in a reduction of 1% FMD at 2-, 3-, and 4-h postingestion ( P < 0.01), with a higher amount of fat intake and energy related to declines in endothelial function at only 3 and 4 h postingestion, respectively (13). Because meal ingestion can impact NO bioavailability (12), it is important to understand the impact of nutrients surrounding exercise to optimize vascular function.…”

From meal to malfunction: exploring molecular pathways, biomarkers and interventions in postprandial cardiometabolic health

“…Superoxide reacts with endothelial NO to generate peroxynitrite; the associated NO loss aligns with an approximately 1 absolute percentage-point decrement in brachial-artery FMD at 2–4 h after a single high-fat meal ( 76 – 78 ). ROS also signal through IKKβ/JNK to promote NLRP3 inflammasome assembly, increasing IL-1β and IL-18 ( 79 , 80 ).…”

Atypical monocyte dynamics in healthy humans in response to fasting and refeeding are distinguished by fasting HDL and postprandial cortisol

“…3 C ). Considering that non-classical monocytes are important for surveilling endothelium and maintaining vascular integrity that is known to be impaired following consumption of a single high-fat meal ( 31 – 33 ), we measured peripheral microvascular endothelial function by reactive hyperemia. Compared with Group 1 , Group 2 had a lower reactive hyperemia index ( P = 0.0037, Fig.…”