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, 149 (12), 2133-2144

Whole Grain Wheat Consumption Affects Postprandial Inflammatory Response in a Randomized Controlled Trial in Overweight and Obese Adults With Mild Hypercholesterolemia in the Graandioos Study

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Whole Grain Wheat Consumption Affects Postprandial Inflammatory Response in a Randomized Controlled Trial in Overweight and Obese Adults With Mild Hypercholesterolemia in the Graandioos Study

Femke P M Hoevenaars et al. J Nutr.

Abstract

Background: Whole grain wheat (WGW) consumption is associated with health benefits in observational studies. However, WGW randomized controlled trial (RCT) studies show mixed effects.

Objectives: The health impact of WGW consumption was investigated by quantification of the body's resilience, which was defined as the "ability to adapt to a standardized challenge."

Methods: A double-blind RCT was performed with overweight and obese (BMI: 25-35 kg/m2) men (n = 19) and postmenopausal women (n = 31) aged 45-70 y, with mildly elevated plasma total cholesterol (>5 mmol/L), who were randomly assigned to either 12-wk WGW (98 g/d) or refined wheat (RW). Before and after the intervention a standardized mixed-meal challenge was performed. Plasma samples were taken after overnight fasting and postprandially (30, 60, 120, and 240 min). Thirty-one biomarkers were quantified focusing on metabolism, liver, cardiovascular health, and inflammation. Linear mixed-models evaluated fasting compared with postprandial intervention effects. Health space models were used to evaluate intervention effects as composite markers representing resilience of inflammation, liver, and metabolism.

Results: Postprandial biomarker changes related to liver showed decreased alanine aminotransferase by WGW (P = 0.03) and increased β-hydroxybutyrate (P = 0.001) response in RW. Postprandial changes related to inflammation showed increased C-reactive protein (P = 0.001), IL-6 (P = 0.02), IL-8 (P = 0.007), and decreased IL-1B (P = 0.0002) in RW and decreased C-reactive protein (P < 0.0001), serum amyloid A (P < 0.0001), IL-8 (P = 0.02), and IL-10 (P < 0.0001) in WGW. Health space visualization demonstrated diminished inflammatory (P < 0.01) and liver resilience (P < 0.01) by RW, whereas liver resilience was rejuvenated by WGW (P < 0.05).

Conclusions: Twelve-week 98 g/d WGW consumption can promote liver and inflammatory resilience in overweight and obese subjects with mildly elevated plasma cholesterol. The health space approach appeared appropriate to evaluate intervention effects as composite markers. This trial was registered at www.clinicaltrials.gov as NCT02385149.

Keywords: (compromised) healthy subjects; challenge test; composite biomarkers; inflammation; liver; metabolic health; phenotypic flexibility; resilience; whole grain wheat.

Figures

FIGURE 2
FIGURE 2
Lipid metabolism in overweight and obese adults with mild hypercholesterolemia before and after a 12-wk intervention period with RW (RW0, RW12) or WGW (WGW0, WGW12) products. NEFA (A), TG (B), total cholesterol (C) concentration, and ratio cholesterol to HDL cholesterol (D), and HDL cholesterol concentration (E) in plasma before (Week 0) and after a 12-wk (Week 12) intervention upon RW or WGW are shown in response to the PFT (76.3 g carbohydrates, 17.6 g protein, 60.0 g fat). Data are means ± 95% CI. RW: n = 25, WGW: n = 25. * < 0.05 on the basis of 2-way interaction of the AUCt between week and treatment, # < 0.05 on the basis of a 2-way interaction of the PFT patterns between week and treatment. aPost hoc difference between week 0 and week 12 in the WGW group, bpost hoc difference between week 0 and week 12 in the RW group (full statistical evaluation in Supplemental Tables 4 and 5). AUCt, total AUC; NEFA, nonesterified fatty acid; PFT, PhenFlex challenge test; RW, refined wheat; WGW, whole grain wheat.
FIGURE 1
FIGURE 1
Glucose metabolism in overweight and obese adults with mild hypercholesterolemia before and after a 12-wk intervention period with RW (RW0, RW12) or WGW (WGW0, WGW12) products. Glucose (A), insulin (B), glucagon (C), GLP-1 (D), and GIP (E) concentrations in plasma before (Week 0) and after a 12-wk (Week 12) intervention of RW or WGW are shown in response to the PhenFlex challenge test (76.3 g carbohydrates, 17.6 g protein, 60.0 g fat). Data are means ± 95% CI. RW: n = 25, WGW: n = 25, statistical evaluation in Supplemental Tables 4 and 5. GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide 1; RW, refined wheat; WGW, whole grain wheat.
FIGURE 3
FIGURE 3
Liver metabolism in overweight and obese adults with mild hypercholesterolemia before and after a 12-wk intervention period with RW (RW0, RW12) or WGW (WGW0, WGW12) products. ALT (A), AST (B), GGT (C), and BH B (D) concentrations in plasma before (Week 0) and after a 12-wk (Week 12) intervention upon RW or WGW are shown in response to the PFT (76.3 g carbohydrates, 17.6 g protein, 60.0 g fat). Data are means ± 95% CI. RW: n = 25, WGW: n = 25. * < 0.05 on the basis of 2-way interaction of the AUCt between week and treatment, # < 0.05 on the basis of a 2-way interaction of the PFT patterns between week and treatment, + < 0.05 on the basis of a 3-way interaction of the PFT patterns between week, treatment, and postprandial time point. aPost hoc difference between week 0 and week 12 in the WGW group, bpost hoc difference between week 0 and week 12 in the RW group (full statistical evaluation in Supplemental Tables 4 and 5). ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUCt, total AUC; BHB, β-hydroxybutyrate; GGT, γ-glutamyl transferase; PFT, PhenFlex challenge test; RW, refined wheat; WGW, whole grain wheat.
FIGURE 4
FIGURE 4
Vascular health markers in overweight and obese adults with mild hypercholesterolemia before and after a 12-wk intervention period with RW (RW0, RW12) or WGW (WGW0, WGW12) products. Systolic blood pressure (A), diastolic blood pressure (B), augmentation index (C), E-selectin (D), sICAM1 (E), sICAM3 (F), P-selectin (G), thrombomodulin (H), and sVCAM1 (I) concentrations in plasma before (Week 0) and after a 12-wk (Week 12) intervention upon RW or WGW are shown in response to the PhenFlex challenge test (76.3 g carbohydrates, 17.6 g protein, 60.0 g fat). Data are means ± 95% CI. RW: n = 25, WGW: n = 25, full statistical evaluation in Supplemental Tables 4 and 5. RW, refined wheat; sICAM1, intercellular adhesion molecule 1; sICAM3, secreted intercellular adhesion molecule 3; sVCAM1, secreted vascular cell adhesion molecule-1; WGW, whole grain wheat.
FIGURE 5
FIGURE 5
Inflammation markers in overweight and obese adults with mild hypercholesterolemia before and after a 12-wk intervention period with RW (RW0, RW12) or WGW (WGW0, WGW12) products. CRP (A), IL-8 (B), SAA (C), IL-10 (D), IL-6 (E), IL-1B (F), and TNFα (G) concentration in plasma before (Week 0) and after a 12-wk (Week 12) intervention upon RW or WGW are shown in response to the PFT (76.3 g carbohydrates, 17.6 g protein, 60.0 g fat). Data are means ± 95% CI. RW: n = 25, WGW: n = 25 * < 0.05 on the basis of 2-way interaction of the AUCt between week and treatment, # < 0.05 on the basis of a 2-way interaction of the PFT patterns between week and treatment, + < 0.05 on the basis of a 3-way interaction of the PFT patterns between week, treatment, and postprandial time point. aPost hoc difference between week 0 and week 12 in the WGW group, bpost hoc difference between week 0 and week 12 in the RW group (full statistical evaluation in Supplemental Tables 4 and 5). AUCt, total AUC; CRP, C-reactive protein; PFT, PhenFlex challenge test; RW, refined wheat; SAA, serum amyloid A; WGW, whole grain wheat.
FIGURE 6
FIGURE 6
Health space resembling the individual resilience before and after 12-wk RW (RW0, RW12) or WGW (WGW0, WGW12) intervention in overweight and obese adults with mild hypercholesterolemia. Data were projected on inflammation and metabolism axes (A), and inflammation and liver axes (B) between young and old reference populations to show the individual and average health scores of the RW and the WGW groups, respectively. One-dimensional visualization in boxplots of the inflammation (C), metabolism (D), and liver (E) axis for RW and WGW relative to the reference population (23). RW: n = 25, WGW: n = 25. *P < 0.05, **P < 0.01, ***P < 0.001. RW, refined wheat; WGW, whole grain wheat.

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References

    1. Aune D, Keum N, Giovannucci E, Fadnes LT, Boffetta P, Greenwood DC, Tonstad S, Vatten LJ, Riboli E, Norat T. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. BMJ. 2016;353353:i2716. - PMC - PubMed
    1. Chen G-C, Tong X, Xu J-Y, Han S-F, Wan Z-X, Qin J-B, Qin L-Q. Whole-grain intake and total, cardiovascular, and cancer mortality: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr. 2016;104:164–72. - PubMed
    1. Zong G, Gao A, Hu FB, Sun Q, Slavin J, Fardet A, Ferruzzi M, Jonnalagadda S, Liu S, Marquart L et al. . Whole grain intake and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis of prospective cohort studies. Circulation. 2016;133:2370–80. - PMC - PubMed
    1. Fardet A. New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?. Nutr Res Rev. 2010;23:65–134. - PubMed
    1. Steffen LM, Jacobs DR, Stevens J, Shahar E, Carithers T, Folsom AR. Associations of whole-grain, refined-grain, and fruit and vegetable consumption with risks of all-cause mortality and incident coronary artery disease and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr. 2003;78:383–90. - PubMed

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