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Impact of Red Beetroot Juice on Vascular Endothelial Function and Cardiometabolic Responses to a High-Fat Meal in Middle-Aged/Older Adults With Overweight and Obesity: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

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Impact of Red Beetroot Juice on Vascular Endothelial Function and Cardiometabolic Responses to a High-Fat Meal in Middle-Aged/Older Adults With Overweight and Obesity: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Nicole S Litwin et al. Curr Dev Nutr.

Abstract

Background: High-fat meal (HFM) consumption may induce transient postprandial atherogenic responses, including impairment of vascular endothelial function, in individuals with overweight/obesity. Red beetroot juice (RBJ) may modulate endothelial function and other measures of cardiometabolic health.

Objective: This study investigated the impact of acute and chronic RBJ consumption, including nitrate-dependent and -independent effects, on postprandial endothelial function and other cardiometabolic responses to a HFM.

Methods: Fifteen men and postmenopausal women with overweight/obesity were enrolled in this randomized, double-blind, placebo-controlled, 4-period, crossover clinical trial. Following an overnight fast, participants underwent baseline assessment of endothelial function (reactive hyperemia index; RHI) and hemodynamics, and biological sample collection. In random order, participants consumed 70 mL (acute visit) of: 1) RBJ, 2) nitrate-free RBJ (NF-RBJ), 3) placebo + nitrate (PBO + NIT), or 4) placebo (PBO), followed by a HFM. RHI was remeasured 4 h post-HFM, and hemodynamic assessment and biological sample collection were performed 1, 2, and 4 h post-HFM consumption. Participants consumed treatments daily for 4 wk (chronic visit), and assessments were repeated before/after the HFM (without consuming treatments).

Results: HFM consumption did not induce significant impairment of postprandial RHI. No significant differences in RHI were detected across treatment groups following acute or chronic exposure, despite increases in circulating nitrate/nitrite (NOx) concentrations in the RBJ and PBO + NIT groups compared with PBO and NF-RBJ (P < 0.0001 for all time points at the acute visit; P < 0.05 for all time points at the chronic visit). Although the HFM led to significant alterations in several secondary outcomes, there were no consistent treatment effects on postprandial cardiometabolic responses.

Conclusions: HFM consumption did not impair postprandial endothelial function in this population, and RBJ exposure did not alter postprandial endothelial function or other outcomes despite increasing NOx concentrations. This trial is registered at clinicaltrials.gov as NCT02949115.

Keywords: betalains; cardiovascular disease; dietary nitrate; inflammation; nitric oxide; oxidative stress; postprandial dysmetabolism; vascular function; vasodilation.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram of participants through the trial.
FIGURE 2
FIGURE 2
(A) Overall study design and schedule of participant study visits. After enrollment, participants were randomized to receive four 70 mL treatments in random order: 1) placebo (PBO), 2) red beetroot juice (RBJ), 3) placebo + nitrate (PBO + NIT), and 4) nitrate-free RBJ (NF-RBJ). Each treatment period consisted of 2 postprandial challenges (i.e. first and last day of each 4-wk treatment period), followed by 4 wk of daily treatment consumption. Each treatment period was separated by a 4-wk washout period. Participants were enrolled in the trial for an 8-mo period. (B) Schematic of the test day timeline for data collection and measurements. Participants were randomly assigned to treatments A, B, C, or D for each treatment period in random order. BP, blood pressure; EC, endothelial cell; HFM, high-fat meal; i.v., intravenous; PAT, peripheral arterial tonometry; PBMC, peripheral blood mononuclear cell; PWA, pulse wave analysis; Tx, treatment.
FIGURE 3
FIGURE 3
Effects of PBO, RBJ, PBO + NIT, and NF-RBJ on RHI (A) and F-RHI (B) before (0 h) and 4 h after consuming a high-fat meal at the acute visit. Data are least square means ± SEM, n = 15. Means were compared with the use of the PROC MIXED procedure in SAS version 9.4. There were no significant effects of time, treatment, or interaction effect of time*treatment of RHI or F-RHI in the model. Solid color = before meal (T0), and patterned color = 4 h after meal and treatment consumption (T4). RHI, reactive hyperemia index; F-RHI, Framingham-RHI; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 4
FIGURE 4
Individual effects of PBO (A), RBJ (B), PBO + NIT (C), and NF-RBJ (D) on RHI before (0 h) and 4 h after consuming a high-fat meal at the acute visit. Data are least square means ± SEM, n = 15. Values were obtained with the use of the PROC MIXED procedure in SAS version 9.4. RHI, reactive hyperemia index; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 5
FIGURE 5
Effects of PBO, RBJ, PBO + NIT, and NF-RBJ on AIx (A) and Aix@75 (B) before (0 h) and 1, 2, and 4 h after consuming a high-fat meal at the acute visit. Data are least square means ± SEM, n = 15. Values were compared with the use of the PROC MIXED procedure in SAS version 9.4. Time points annotated with symbols represent a significant time*treatment interaction between treatment groups. *PBO significantly different than RBJ and PBO + NIT (both P < 0.05). No other significant effects for AIx or AIx@75 were observed. AIx, augmentation index; AIx@75, augmentation index at 75 beats per min; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 6
FIGURE 6
Plasma concentrations of glucose (A), insulin (B), and triglycerides (C) at baseline (0 h), and 1, 2, and 4 h after a high-fat meal and PBO, RBJ, PBO + NIT, and NF-RBJ treatment ingestion, and postprandial (0–240 min) glucose (D), insulin (E), and triglyceride (F) incremental AUC (iAUC) at the acute visit. Data in A–C are presented as log-transformed least square means ± SEM, n = 15. Data in D–F are presented as untransformed mean ± SEM. Values in A–C were compared with the use of the PROC MIXED procedure, whereas iAUC values in D–F were compared by use of the PROC GLM procedure with Tukey's multiple comparison test in SAS version 9.4. All time points were significantly different from baseline for plasma insulin and triglyceride concentrations among all treatment groups. Time points annotated with symbols represent significant time*treatment interaction between treatment groups. *PBO + NIT significantly different than NF-RBJ; $PBO + NIT significantly different than PBO; #RBJ significantly different than PBO, all P < 0.05. No significant differences between treatment groups at any time point for postprandial triglyceride concentrations were observed. There were no significant differences in postprandial glucose, insulin, or triglyceride AUC between treatment groups. PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 7
FIGURE 7
Plasma NOx concentrations (A) and saliva NOx concentrations (B) at baseline (0 h) and 1, 2, and 4 h after a high-fat meal and PBO, RBJ, PBO + NIT, and NF-RBJ treatment ingestion, and postprandial (0–240 min) plasma NOx (C) and saliva NOx (D) AUC at the acute visit. Data in A–C are presented as log-transformed least square means ± SEM, n = 15. Data in D–F are presented as untransformed mean ± SEM. Values in A–C were compared with the use of the PROC MIXED procedure, whereas AUC values in D–F were compared by use of the PROC GLM procedure with Tukey's multiple comparison test in SAS version 9.4. All time points were significantly different than baseline for plasma and saliva NOx concentrations in the RBJ and PBO + NIT groups. Time points annotated with symbols represent significant time*treatment interactions between treatment groups. #RBJ significantly different from PBO and NF-RBJ, P < 0.0001. *PBO + NIT significantly different from PBO and NF-RBJ, P < 0.0001. Treatment groups annotated with different letters were significantly different from one another, < 0.05. NOx, nitrate/nitrite; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free-RBJ.
FIGURE 8
FIGURE 8
Effects of PBO, RBJ, PBO + NIT, and NF-RBJ on RHI (A) and F-RHI (B) after 4 wk treatment ingestion at baseline (0 h) and 4 h after consuming a high-fat meal at the chronic visit. Data are least square means ± SEM, n = 15. Means were compared with the use of the PROC MIXED procedure in SAS version 9.4. There were no significant effects of time, treatment, or interaction effect of time*treatment of RHI or F-RHI in the model. Solid color = before meal (T0), and patterned color = 4 h after meal and treatment consumption (T4). RHI, reactive hyperemia index, F-RHI, Framingham-RHI; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 9
FIGURE 9
Individual effects of PBO (A), RBJ (B), PBO + NIT (C), and NF-RBJ (D) on RHI after 4-wk treatment ingestion at baseline (0 h) and 4 h after consuming a high-fat meal at the chronic visit. Data are least square means ± SEM, n = 15. Values were obtained with the use of the PROC MIXED procedure in SAS version 9.4. RHI, reactive hyperemia index; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 10
FIGURE 10
AIx (A) and Aix@75 (B) after 4 wk PBO, RBJ, PBO + NIT, and NF-RBJ treatment ingestion at baseline (0 h) and 1, 2, and 4 h after consuming a high-fat meal at the chronic visit. Data are least square means ± SEM, n = 15. Values were compared with the use of the PROC MIXED procedure in SAS version 9.4. For both outcomes, there were no significant effects of time, treatment, or main interaction effect of time*treatment in the models. AIx, augmentation index; AIx@75, augmentation index at 75 beats per min; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 11
FIGURE 11
Plasma concentrations of glucose (A), insulin (B), and triglycerides (C) after 4 wk PBO, RBJ, PBO + NIT, and NF-RBJ treatment ingestion at baseline (0 h) and 1, 2, and 4 h after consuming a high-fat meal, and postprandial (0–240 min) glucose (D), insulin (E), and triglyceride (F) incremental AUC (iAUC) at the chronic visit. Data in A–C are presented as log-transformed least square means ± SEM, n = 15. Data in D–F are presented as untransformed mean ± SEM. Values in A–C were compared with the use of the PROC MIXED procedure, whereas iAUC values in D–F were compared by use of the PROC GLM procedure with Tukey's multiple comparison test in SAS version 9.4. All time points were significantly different from baseline for plasma insulin and triglyceride concentrations among all treatment groups. For plasma glucose, insulin, and triglyceride responses, there were no significant effects of time, treatment, or interaction effect of time*treatment. PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 12
FIGURE 12
Plasma NOx concentrations (A) and saliva NOx concentrations (B) after 4 wk PBO, RBJ, PBO + NIT, and NF-RBJ treatment ingestion at baseline (0 h) and 1, 2, and 4 h after consuming a high-fat meal, and postprandial (0–240 min) plasma NOx (C) and saliva NOx (D) AUC at the chronic visit. Data in A–C are presented as log-transformed least square means ± SEM, n = 15. Data in D–F are presented as untransformed mean ± SEM. Values in A–C were compared with the use of the PROC MIXED procedure, whereas AUC values in D–F were compared by use of the PROC GLM procedure with Tukey's multiple comparison test in SAS version 9.4. All time points were significantly different than baseline for plasma NOx concentrations in the RBJ and PBO + NIT groups. Time points annotated with symbols represent significant time*treatment interactions between treatment groups. #RBJ significantly different from PBO and NF-RBJ; *PBO + NIT significantly different from PBO and NF-RBJ; $PBO + NIT significantly different than NF-RBJ; all < 0.01. Treatment groups annotated with different letters were significantly different from one another, < 0.05. NOx, nitrate/nitrite; PBO, placebo; RBJ, red beetroot juice; PBO + NIT, PBO + nitrate; NF-RBJ, nitrate-free RBJ.
FIGURE 13
FIGURE 13
Mean endothelial cell protein expression at baseline and after 4 weeks of PBO, RBJ, PBO+NIT, and NF-RBJ consumption. Data are normalized to human umbilical vein endothelial cell protein expression via immunofluorescence. Values represent least square mean AU ± SEM, n = 15. Values were compared with the use of the PROC MIXED procedure in SAS version 9.4. There were no significant main effects of time, treatment, or main interaction effect of time*treatment in the model. There were no significant differences in endothelial protein expression of p47phox within or between treatment groups at any time point. Abbreviations: AU, arbitrary units; PBO, placebo; RBJ, red beetroot juice; PBO+NIT, PBO+nitrate; NF-RBJ, nitrate-free-RBJ.

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