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Background: Although relationships between the intake of whole grains and refined grains and the incidence of cardiovascular disease (CVD) events and all-cause mortality have been investigated, the conclusions have been inconclusive. Objectives: We aimed to comprehensively summarize the evidence about the correlation between consuming whole grains and refined grains and risks of CVD events and all-cause mortality and to evaluate the meta-evidence quality. Methods: We searched PubMed, Embase, and Web of Science until 15 March, 2022. Random-effects models were employed to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). We explored potential linear or nonlinear relationships using restricted cubic splines. The NutriGrade tool was employed to rate meta-evidence quality. Results: Twenty-four articles (68 studies; 46 for whole grains and 22 for refined grains) with 1,624,407 participants were included. Per 30-g increase in daily whole grain consumption, the RRs and 95% CIs of stroke, coronary heart disease (CHD), heart failure (HF), CVD, and all-cause mortality were 0.98 (0.96, 1.00), 0.94 (0.92, 0.97), 0.97 (0.89, 1.07), 0.92 (0.88, 0.96), and 0.94 (0.92, 0.97), respectively. Whole grain consumption was linearly associated with CHD (Pnonlinearity = 0.231) and nonlinearly associated with CVD (Pnonlinearity = 0.002) and all-cause mortality (Pnonlinearity = 0.001). Except for a positive correlation between refined grain consumption and all-cause mortality in the restricted cubic spline, no significant influence of refined grain intake on stroke, CHD, HF, and CVD was detected. The meta-evidence quality for the association of whole grain consumption with stroke, CHD, HF, CVD, and all-cause mortality was moderate, moderate, low, high, and high, respectively. For refined grains, all meta-evidence was of low quality. Conclusions: Consuming whole grains, rather than refined grains, can assist in preventing CHD, CVD, and all-cause mortality. Relationships between consumption of refined grains and health outcomes should be interpreted cautiously because of the low quality of meta-evidence. [ABSTRACT FROM AUTHOR]

Background: Whole grain (WG) consumption is linked with a reduced risk of chronic disease. However, the recommendations of the Nova classification system tend to contradict this evidence as high WG-containing foods, such as bread and cereals, are considered ultraprocessed, and intake is discouraged., Objectives: This study aimed to explore associations of cardiometabolic risk measures with ultraprocessed food (UPF) intake as classified by Nova compared with when foods with ≥25% and ≥50% WG are removed from the Nova UPF category., Methods: A cross-sectional analysis of the 2015-18 National Health and Nutrition Examination Survey. Nova was used to identify UPFs, and the WG Initiative's definition of a WG food and front-of-pack labeling requirements was used to identify high WG foods. Regression models were used to explore impacts on the association of UPF intake (quintiles) and cardiometabolic risk measures when high WG foods were excluded from the Nova UPF category., Results: Participants in the highest quintile of UPF intake had significantly higher weight [83.6 kg (0.8)], BMI (in kg/m 2 ) [30.6 (0.3)], waist circumference [103.1 cm (0.6)], and weight-to-height ratio [0.63 (0.003)] compared to those in the lowest quintile (P < 0.0001 for all). The same was found when foods with ≥25% and ≥50% WG were removed. Positive associations for C-reactive protein were found when ≥25% and ≥50% WG-containing foods were removed only [2.32 mg/L (0.1), P = 0.0209; 2.37 mg/L (0.1), P = 0.0179, respectively]. Participants in the highest quintile had significantly lower total cholesterol after adjustment when foods with ≥50% WG were removed [4.98 mmol/L (0.04), P = 0.0292]. Adjusted R 2 values remained relatively unchanged across each approach for all outcomes., Conclusions: Foods high in WG may not significantly contribute to the deleterious associations previously observed between UPF intake and cardiometabolic risk factors. Consideration of their contribution to healthful dietary patterns and diet quality in the United States population should be made prior to the endorsement of Nova., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background Whole grains and other foods containing fiber are thought to be inversely related to colorectal cancer (CRC). However, whether these associations reflect fiber or fiber source remains unclear. Objectives We evaluated associations of whole grain and dietary fiber intake with CRC risk in the large NIH-AARP Diet and Health Study. Methods We used Cox proportional hazard models to estimate HRs and 95% CIs for whole grain and dietary fiber intake and risk of CRC among 478,994 US adults, aged 50–71 y. Diet was assessed using a self-administered FFQ at baseline in 1995–1996, and 10,200 incident CRC cases occurred over 16 y and 6,464,527 person-years of follow-up. We used 24-h dietary recall data, collected on a subset of participants, to evaluate the impact of measurement error on risk estimates. Results After multivariable adjustment for potential confounders, including folate, we observed an inverse association for intake of whole grains (HRQ5 vs.Q1 : 0.84; 95% CI: 0.79, 0.90; P -trend < 0.001), but not dietary fiber (HRQ5 vs. Q1: 0.96; 95% CI: 0.88, 1.04; P -trend = 0.40), with CRC incidence. Intake of whole grains was inversely associated with all CRC cancer subsites, particularly rectal cancer (HRQ5 vs. Q1: 0.76; 95% CI: 0.67, 0.87; P -trend < 0.001). Fiber from grains, but not other sources, was associated with lower incidence of CRC (HRQ5 vs. Q1: 0.89; 95% CI: 0.83, 0.96; P -trend < 0.001), particularly distal colon (HRQ5 vs. Q1: 0.84; 95% CI: 0.73, 0.96; P -trend = 0.005) and rectal cancer (HRQ5 vs. Q1: 0.77; 95% CI: 0.66, 0.88; P- trend < 0.001). Conclusions Dietary guidance for CRC prevention should focus on intake of whole grains as a source of fiber. [ABSTRACT FROM AUTHOR]

Background: Low–glycemic load dietary patterns, characterized by consumption of whole grains, legumes, fruits, and vegetables, are associated with reduced risk of several chronic diseases. Methods: Using samples from a randomized, controlled, crossover feeding trial, we evaluated the effects on metabolic profiles of a low-glycemic whole-grain dietary pattern (WG) compared with a dietary pattern high in refined grains and added sugars (RG) for 28 d. LC-MS-based targeted metabolomics analysis was performed on fasting plasma samples from 80 healthy participants (n = 40 men, n = 40 women) aged 18–45 y. Linear mixed models were used to evaluate differences in response between diets for individual metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG)– defined pathways and 2 novel data-driven analyses were conducted to consider differences at the pathway level. Results: There were 121 metabolites with detectable signal in >98% of all plasma samples. Eighteen metabolites were significantly different between diets at day 28 [false discovery rate (FDR) < 0.05]. Inositol, hydroxyphenylpyruvate, citrulline, ornithine, 13-hydroxyoctadecadienoic acid, glutamine, and oxaloacetate were higher after the WG diet than after the RG diet, whereas melatonin, betaine, creatine, acetylcholine, aspartate, hydroxyproline, methylhistidine, tryptophan, cystamine, carnitine, and trimethylamine were lower. Analyses using KEGG-defined pathways revealed statistically significant differences in tryptophan metabolism between diets, with kynurenine and melatonin positively associated with serum C-reactive protein concentrations. Novel data-driven methods at the metabolite and network levels found correlations among metabolites involved in branched-chain amino acid (BCAA) degradation, trimethylamine-N-oxide production, and β oxidation of fatty acids (FDR < 0.1) that differed between diets, with more favorable metabolic profiles detected after the WG diet. Higher BCAAs and trimethylamine were positively associated with homeostasis model assessment-insulin resistance. Conclusions: These exploratory metabolomics results support beneficial effects of a low–glycemic load dietary pattern characterized by whole grains, legumes, fruits, and vegetables, compared with a diet high in refined grains and added sugars on inflammation and energy metabolism pathways. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives: The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods: A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography–tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results: Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions: Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption. [ABSTRACT FROM AUTHOR]

Background: Whole grains are often referred to collectively, despite differences in their composition, physical structure, processing, and potential health benefits. Objective: The aim of this study was to compare the postprandial blood glucose response of whole-grain with refined wheat, rice, or rye, while controlling for the food delivery matrix and the processing of the grain (e.g., grinding, germination). Design: Eleven electronic databases were systematically searched to identify studies published up to and including November 2017. Randomized controlled trials comparing the effects of whole-grain wheat, rice, or rye with those of each grain's refined counterpart on postprandial blood glucose area under the curve (AUC) were included. Pooled effect sizes were computed by using the difference in the blood glucose AUC after the consumption of the whole compared with the refined grain. Results: Twenty publications were included, with 10, 14, and 5 strata (or active-control comparisons) on whole-grain wheat, rice, and rye, respectively. The consumption of ground (wholemeal) wheat, compared with white wheat, was not associated with a significant reduction in blood glucose AUC (−6.7 mmol/L ⋅ min; 95% CI: −25.1, 11.7 mmol/L ⋅ min; P = 0.477). The consumption of wholemeal rye, compared with endosperm rye, was not associated with a significant reduction in blood glucose AUC (−5.5 mmol/L ⋅ min; 95% CI: −24.8, 13.8 mmol/L ⋅ min; P = 0.576). The consumption of intact (whole-grain) rice, compared with white rice, was associated with a significant reduction in blood glucose AUC (−40.5 mmol/L ⋅ min; 95% CI: −59.6, −21.3 mmol/L ⋅ min; P < 0.001). Conclusions: Compared with white rice, whole-grain rice significantly attenuates the postprandial blood glucose response. In most of the studies on wheat and rye, the postprandial blood glucose responses to foods formulated with wholemeal compared with refined flours were compared. Whether reductions in the blood glucose AUC can be achieved with whole-grain (as opposed to wholemeal) wheat and rye requires further investigation. [ABSTRACT FROM AUTHOR]

Background: The carbohydrate-to-fiber ratio is a recommended measure of carbohydrate quality; however, its relation to incident coronary heart disease (CHD) is not currently known. Objective:We aimed to assess the relation between various measures of carbohydrate quality and incident CHD. Design: Data on diet and lifestyle behaviors were prospectively collected on 75,020 women and 42,865 men participating in the Nurses' Health Study (NHS) and the Health Professionals Follow- Up Study (HPFS) starting in 1984 and 1986, respectively, and every 2-4 y thereafter until 2012. All participants were free of known diabetes mellitus, cancer, or cardiovascular disease at baseline. Cox proportional hazards regression models were used to assess the relation between dietary measures of carbohydrate quality and incident CHD. Results: After 1,905,047 (NHS) and 921,975 (HPFS) person-years of follow-up, we identified 7,320 cases of incident CHD. In models adjusted for age, lifestyle behaviors, and dietary variables, the highest quintile of carbohydrate intake was not associated with incident CHD (pooled-RR = 1.04; 95% CI: 0.96, 1.14; P-trend = 0.31). Total fiber intake was not associated with risk of CHD (pooled-RR = 0.94; 95% CI: 0.85, 1.03; P-trend = 0.72), while cereal fiber was associated with a lower risk for incident CHD (pooled-RR = 0.80; 95% CI: 0.74, 0.87; P-trend < 0.0001). In fully adjusted models, the carbohydrate-to-total fiber ratio was not associated with incident CHD (pooled-RR = 1.04; 95% CI: 0.96, 1.13; P-trend = 0.46). However, the carbohydrate-to-cereal fiber ratio and the starch-to-cereal fiber ratio were associated with an increased risk for incident CHD (pooled-RR = 1.20; 95% CI: 1.11, 1.29; P-trend < 0.0001, and pooled-RR = 1.17; 95%CI: 1.09, 1.27; P-trend < 0.0001, respectively). Conclusion: Dietary cereal fiber appears to be an important component of carbohydrate quality. The carbohydrate-to-cereal fiber ratio and the starch-to-cereal fiber ratio, but not the carbohydrate-tofiber ratio, was associated with an increased risk for incident CHD. Future research should focus on how various measures of carbohydrate quality are associated with CHD prevention. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity. Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights. Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m2) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk. Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) (P < 0.0001), stool weight (P < 0.0001), stool frequency (P = 0.02), and shortchain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate (P = 0.02) and total SCFAs (P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells (P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-a (P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations. Conclusion: The short-term consumption of WGs in a weightmaintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394. [ABSTRACT FROM AUTHOR]

Background: The current school meal nutrition standards, established in 2010, are not fully aligned with the 2020-2025 Dietary Guideline for Americans (DGA). This study evaluates the potential short-term and long-term health and economic benefits of strengthening the school meal standards on added sugars, sodium, and whole grains to be aligned with current guidelines., Methods: We used comparative risk assessment frameworks based on nationally representative data incorporating current demographics, dietary habits, and risk factors of United States children aged 5-18 y from 3 cycles of the National Health and Nutrition Examination Survey (2013-2018). To estimate short-term impact, the model incorporated estimated dietary changes owing to potential new DGA-aligned school meal nutrition standards and the effect of these changes on childhood body mass index (in kg/m 2 ) and blood pressure. To estimate long-term impact, the model further incorporated data on the sustainability of childhood dietary changes into adulthood, and on demographics and risk factors of United States adults, diet-disease associations, and disease-specific national mortality., Results: In a best-case scenario assuming full school compliance, implementing new DGA-aligned nutritional standards would lower elementary children's BMI by an average 0.14 (95% UI: 0.08-0.20) kg/m 2 and systolic blood pressure by 0.13 (95% UI: 0.06-0.19) (95% mm Hg. Later in life, the new standards were estimated to prevent 10,600 [95% uncertainty interval (UI): 4820-16,800) annual deaths from cardiovascular disease (CVD), diabetes, and cancer in adulthood; and save 355,000 (95% UI: 175,000-538,000) disability-adjusted life years and $19.3 (95% UI: 9.35-30.3) B in direct and indirect medical costs each year. Accounting for plausible (incomplete) school compliance, implementation would save an estimated 9110 (95% UI: 2740-15,100) deaths, 302,000 (95% UI: 120,000-479,000) disability-adjusted life years, and $15.9 (95% UI: 4.54-27.2) B in healthcare-related costs per year in later adulthood., Conclusions: Stronger school meal nutrition standards on added sugars, sodium, and whole grains aligned with the 2020-2025 DGA recommendations may improve diet, childhood health, and future adult burdens of CVD, diabetes, cancer, and associated economic costs., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies that use dietary biomarkers to investigate the association between whole-grain intake and the risk of developing type 2 diabetes (T2D) are lacking. Objective: We examined the association between plasma total alkylresorcinols and the alkylresorcinol C17:0-to-C21:0 ratio, biomarkers of whole-grain wheat and rye intake and relative wholegrain rye over whole-grain wheat intake, respectively, and the risk of T2D among Scandinavian men and women. Design: A nested case-control study was established within the Northern Sweden Health and Disease Study and the Danish Diet, Cancer and Health cohort. Alkylresorcinol concentrations and the ratios of C17:0 to C21:0 were determined in plasma samples from 931 case-control pairs. ORs for T2D were calculated for plasma total alkylresorcinol concentration or C17: 0 to-C21:0 ratio in quartiles with the use of conditional logistic regression that was adjusted for potential confounders. Additional analyses with whole-grain wheat and rye intake estimated from food-frequency questionnaires (FFQs) as exposures were also performed. Results: The plasmatotalalkylresorcinol concentration was not associated with T2D risk (OR: 1.34; 95% CI: 0.95, 1.88) for the highest compared with the lowest quartiles in multivariable adjusted models. However, the C17:0-to-C21:0 ratio was associated with a lower diabetes risk (OR: 0.54; 95% CI: 0.37, 0.78). Analyses with whole-grain intake estimated from FFQs yielded similar results. Conclusions: Total whole-grain wheat and rye intake, reflected by alkylresorcinols in plasma, was not associated with a lower risk of T2D in a population with high whole-grain intake. In contrast, the proportion of whole-grain rye to whole-grain wheat intake, indicated by the plasma C17:0-to-C21:0 ratio, was inversely associated with T2D. This suggests that whole-grain intake dominated by rye may be favorable for T2D prevention. [ABSTRACT FROM AUTHOR]

Background: High intake of whole grains has been associated with lower risk of coronary heart disease; however, the research that has been used to evaluate different effects of different whole-grain cereals (e.g., wheat, rye, and oats) has been sparse. Objective: We investigated the association between whole-grain intake in terms of total intake and intakes of different cereals and myocardial infarction. Design: This prospective study included 54,871 Danish adults aged 50-64 y, of whom 2329 individuals developed myocardial infarction (13.6 y of follow-up). Detailed information on daily intake of whole-grain products was available from a self-administered foodfrequency questionnaire, and intakes of total whole grain and whole-grain species (wheat, rye, and oats) were estimated. The association between intake of whole grains and risk of myocardial infarction was examined with the use of a Cox proportional hazards model adjusted for potential confounders. Results: For both men and women with total whole-grain intake in the highest quartile, lower risks of myocardial infarction were shown [HRs: 0.75 (95% CI: 0.65, 0.86) and 0.73 (95% CI: 0.58, 0.91), respectively] than for individuals with intake in the lowest quartile. When the specific cereal species were considered, rye and oats, but not wheat, were associated with lower myocardial infarction risk in men. No significant associations were seen in women. For total whole-grain products, significantly lower myocardial infarction risks were seen with higher intakes in both men and women. Rye bread (in men and women) and oatmeal (in men) were associated with significantly lower risk of myocardial infarction, whereas no significant association was shown for whole-grain bread, crispbread, and wheat. Conclusion: In this study, we provide support for the hypothesis that whole-grain intake is related to lower risk of myocardial infarction and suggest that the cereals rye and oats might especially hold a beneficial effect. [ABSTRACT FROM AUTHOR]

Background: Although relationships between the intake of whole grains and refined grains and the incidence of cardiovascular disease (CVD) events and all-cause mortality have been investigated, the conclusions have been inconclusive., Objectives: We aimed to comprehensively summarize the evidence about the correlation between consuming whole grains and refined grains and risks of CVD events and all-cause mortality and to evaluate the meta-evidence quality., Methods: We searched PubMed, Embase, and Web of Science until 15 March, 2022. Random-effects models were employed to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). We explored potential linear or nonlinear relationships using restricted cubic splines. The NutriGrade tool was employed to rate meta-evidence quality., Results: Twenty-four articles (68 studies; 46 for whole grains and 22 for refined grains) with 1,624,407 participants were included. Per 30-g increase in daily whole grain consumption, the RRs and 95% CIs of stroke, coronary heart disease (CHD), heart failure (HF), CVD, and all-cause mortality were 0.98 (0.96, 1.00), 0.94 (0.92, 0.97), 0.97 (0.89, 1.07), 0.92 (0.88, 0.96), and 0.94 (0.92, 0.97), respectively. Whole grain consumption was linearly associated with CHD (P nonlinearity = 0.231) and nonlinearly associated with CVD (P nonlinearity = 0.002) and all-cause mortality (P nonlinearity = 0.001). Except for a positive correlation between refined grain consumption and all-cause mortality in the restricted cubic spline, no significant influence of refined grain intake on stroke, CHD, HF, and CVD was detected. The meta-evidence quality for the association of whole grain consumption with stroke, CHD, HF, CVD, and all-cause mortality was moderate, moderate, low, high, and high, respectively. For refined grains, all meta-evidence was of low quality., Conclusions: Consuming whole grains, rather than refined grains, can assist in preventing CHD, CVD, and all-cause mortality. Relationships between consumption of refined grains and health outcomes should be interpreted cautiously because of the low quality of meta-evidence., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Whole grains are recognized for their potential role in preventing cardiovascular diseases; however, results from randomized controlled studies on blood lipids are inconsistent, potentially because of compositional differences between individual grain types for some nutrients, including dietary fiber. Objective: Using a meta-analytic approach, we assessed the effect of whole-grain compared with non-whole-grain foods on changes in total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides. Design: We conducted a systematic literature search in selected databases. Studies were included if they were randomized controlled comparisons between whole-grain foods and a non-whole-grain control in adults. A total of 6069 articles were screened for eligibility, and data were extracted from 24 studies. Weighted mean differences were calculated, and meta-regression analyses were performed for whole-grain dose, study duration, and baseline TC concentration. Results: Overall, whole-grain intake lowered LDL cholesterol (weighted difference: −0.09 mmol/L; 95% CI: −0.15, −0.03 mmol/L; P < 0.01) and TC (weighted difference: −0.12 mmol/L; 95% CI: −0.19, −0.05 mmol/L; P < 0.001) compared with the control. Whole-grain oat had the greatest effect on TC (weighted difference: −0.17 mmol/L; 95% CI: −0.10, −0.25 mmol/L; P < 0.001). No effect of whole-grain foods on HDL cholesterol was seen, whereas whole-grain foods tended to lower triglycerides compared with the control (weighted difference: −0.04 mmol/L; 95% CI: −0.08, 0.01; P = 0.10). No association was found between whole-grain dose or baseline TC concentration and any of the outcomes, whereas study duration was positively associated with changes in TC and LDL cholesterol. Conclusions: Consumption of whole-grain diets lowers LDL cholesterol and TC, but not HDL cholesterol or triglycerides, compared with consumption of non-whole-grain control diets. Whole-grain oat appears to be the most effective whole grain for lowering cholesterol. [ABSTRACT FROM AUTHOR]

Background: Whole-grain (WG) foods are defined by the Dietary Guidelines for Americans (DGA), FDA, AHA, American Association of Cereal Chemists International (AACCI), and Whole Grains Council (WGC) in different ways with diverse focuses on grain components only, whole foods, or nutrient contents., Objectives: We aimed to compare estimated WG food intake among US adults using different definitions., Methods: For each definition, we estimated the mean intake and trends of WG food consumption using survey-weighted 24-h dietary recalls from nationally representative samples of 39,755 US adults aged 20+ y from 8 cycles (2003-2018) of the NHANES. This is an observational study that used deidentified and publicly available datasets., Results: The estimated mean consumption of WG foods (ounces equivalents/2000 kcal/d, oz. eq./d) varied by definition. In 2017-2018, the AHA (mean [SEM]: 1.05 [0.07] oz. eq./d) and WGC (0.95 [0.07]) definitions yielded the highest amounts, followed by the DGA (0.81 [0.06]), AACCI (0.73 [0.05]), and FDA (0.53 [0.04]). Using all definitions except for WGC, US adults increased WG food intake from 2003-2004 to 2017-2018 with the largest increase (61.5%) using the AHA (from 0.65 to 1.05 oz. eq./d), followed by DGA (0.50 to 0.81) and AACCI (0.51 to 0.73) definitions. For each definition, the main sources of WG foods consumed by US adults were ready-to-eat cereals, cooked grains and cereals, and breads (including rolls and tortillas). For all definitions except the AHA, non-Hispanic White adults and individuals with college degrees or above consumed higher levels of WG foods than non-Hispanic Blacks and those with lower levels of education., Conclusions: Different definitions affect the determination of WG foods, estimated intakes, and associated trends in WG food consumption among US adults. These findings call for a standardized definition of WG foods to guide consumers, industry, and policymakers in promoting WG intake in the US.Clinical Trial Registration: Not Applicable., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Intake of whole grains is inversely associated with risk of diabetes and ischemic heart disease in observational studies. The lower risk associated with high whole-grain intakes may be mediated through improvements in glycemic control, lipid profiles, or reduced inflammation. Objective: The aim was to examine whether the intake of whole grains, bran, and germ is related to homocysteine, plasma markers of glycemic control (fasting insulin, hemoglobin A1c, C-peptide, and leptin), lipids (total cholesterol, triacylglycerol, HDL cholesterol, and LDL cholesterol), and inflammation (C-reactive protein, fibrinogen, and interleukin 6). Design: This was a cross-sectional study of the relations of whole grains, bran, and germ intakes with homocysteine and markers of glycemic control, lipids, and inflammation in 938 healthy men and women. Results: Whole-grain intake was inversely associated with homocysteine and markers of glycemic control. Compared with participants in the bottom quintile of whole-grain intake, participants in the highest quintile had 17%, 14%, 14%, and 11% lower concentrations of homocysteine (P < 0.01), insulin (P = 0.12), C-peptide (P = 0.03), and leptin (P=0.03), respectively. Inverse associations were also observed with total cholesterol (P = 0.02), HDL cholesterol (P=0.05), andLDLcholesterol (P=0.10). Whole-grain intake was not associated with the markers of inflammation. Whole-grain intake was most strongly inversely associated with markers of glycemic control in this population. Conclusion: The results suggest a lower risk of diabetes and heart disease in persons who consume diets high in whole grains. [ABSTRACT FROM AUTHOR]

Background: Whole-grain intake has been inversely associated with the metabolic syndrome in middle-aged populations, but the association has not been investigated in older adults. The metabolic consequence of consuming high whole-grain diets may differ in elderly persons, who are prone to greater insulin resistance and impaired glucose tolerance. Objective: The aim of the present study was to examine the cross-sectional association between whole- and refined-grain intake, cardiovascular disease risk factors, prevalence of the metabolic syndrome, and the incidence of cardiovascular disease mortality in the same cohort of older adults. Design: The nutritional status of 535 healthy persons aged 60-98 y was determined from 1981 to 1984. The subjects kept a 3-d food record and had their blood tested for metabolic risk factors. The metabolic syndrome was defined based on criteria set by the third report of the National Cholesterol Education Program. The vital status of the subjects was identified in October 1995. Results: The results showed a significant inverse trend between whole-grain intake and the metabolic syndrome (P for trend = 0.005) and mortality from cardiovascular disease (P for trend = 0.04), independent of demographic, lifestyle, and dietary factors. Fasting glucose concentrations and body mass index decreased across increasing quartile categories of whole-grain intake (P for trend = 0.01 and 0.03, respectively), independent of confounders, whereas intake of refined grain was positively associated with higher fasting glucose concentrations (P for trend = 0.04) and a higher prevalence of the metabolic syndrome (P for trend = 0.01). Conclusion: Whole-grain intake is a modifiable dietary risk factor, and older and young adults should be encouraged to increase their daily intake to ⩾3 servings/d. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that a daily intake of 3 servings of whole-grain foods is associated with a reduced risk of coronary heart disease (CHD). However, methods for the assessment of whole-grain intake differ. Furthermore, any additional effects of added bran and germ, which are components of whole grains, have not been reported. Objective: The objective was to evaluate the association of wholegrain, bran, and germ intakes (with the use of new quantitative measures) with the incidence of CHD. Design: This was a prospective cohort study of 42 850 male health professionals aged 40-75 y at baseline in 1986 who were free from cardiovascular disease, cancer, and diabetes. Daily whole-grain, bran, and germ intakes were derived in grams per day from a detailed semiquantitative dietary questionnaire. Results: During 14 y of follow-up, we documented 1818 incident cases of CHD. After cardiovascular disease risk factors and the intakes of bran and germ added to foods were controlled for, the hazard ratio of CHD between extreme quintiles of whole-grain intake was 0.82 (95% CI: 0.70, 0.96; P for trend = 0.01). The hazard ratio of CHD in men with the highest intake of added bran was 0.70 (95% CI: 0.60, 0.82) compared with men with no intake of added bran (P for trend ≤ 0.001). Added germ was not associated with CHD risk. Conclusion: This study supports the reported beneficial association of whole-grain intake with CHD and suggests that the bran component of whole grains could be a key factor in this relation. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse, and characterization of this association has been obscured by methodologic inconsistencies in the assessment of whole grains. Objective: We aimed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men. Design: The study was conducted in a prospective cohort of 27 082 men aged 40-75 y at baseline in 1986. Data on lifestyle factors were obtained periodically by using self-reported questionnaires, and participants measured and reported their body weight in 1986 and 1994. Results: In multivariate analyses, an increase in whole-grain intake was inversely associated with long-term weight gain (P for trend < 0.0001). A dose-response relation was observed, and for every 40-g/d increment in whole-grain intake from all foods, weight gain was reduced by 0.49 kg. Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain (P for trend = 0.01), and, for every 20 g/d increase in intake, weight gain was reduced by 0.36 kg. Changes in cereal and fruit fiber were inversely related to weight gain. No associations were observed between changes in refined-grain or added germ consumption and body weight. Conclusions: The increased consumption of whole grains was inversely related to weight gain, and the associations persisted after changes in added bran or fiber intakes were accounted for. This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain. [ABSTRACT FROM AUTHOR]

Background: Barley has high amounts of soluble fiber but is not extensively consumed in the US diet. Objective: This study investigated whether consumption of barley would reduce cardiovascular disease risk factors comparably with that of other sources of soluble fiber. Design: Mildly hypercholesterolemic subjects (9 postmenopausal women, 9 premenopausal women, and 7 men) consumed controlled American Heart Association Step 1 diets for 17 wk. After a 2-wk adaptation period, whole-grain foods containing 0, 3, or 6 g β- glucan/d from barley were included in the Step 1 diet menus. Diets were consumed for 5 wk each and were fed in a Latin-square design. Fasting blood samples were collected twice weekly. Results: Total cholesterol was significantly lower when the diet contained 3 or 6 g β-glucan/d from barley than when it contained no β-glucan; the greatest change occurred in the men and postmenopausal women. HDL and triacylglycerol concentrations did not differ with the 3 amounts of dietary β-glucan. Large LDL and small VLDL fractions and mean LDL particle size significantly decreased whenwhole grains were incorporated into the 3 diets. LargeLDLand large and intermediate HDL fractions were significantly higher, mean LDL particle size was significantly greater, and intermediate VLDL fractions were significantly lower in the postmenopausal women than in the other 2 groups.Agroup-by-diet interaction effect was observed on LDL fractions and small LDL particle size. Conclusion: The addition of barley to a healthy dietmaybe effective in lowering total and LDL cholesterol in both men and women. [ABSTRACT FROM AUTHOR]

Background: Although increased consumption of dietary fiber and grain products is widely recommended to maintain healthy body weight, little is known about the relation of whole grains to body weight and long-term weight changes. Objective: We examined the associations between the intakes of dietary fiber and whole- or refined-grain products and weight gain over time. Design: In a prospective cohort study, 74 091 US female nurses, aged 38-63 y in 1984 and free of known cardiovascular disease, cancer, and diabetes at baseline, were followed from 1984 to 1996; their dietary habits were assessed in 1984, 1986, 1990, and 1994 with validated food-frequency questionnaires. Using multiple models to adjust for covariates, we calculated average weight, body mass index (BMI; in kg/m2), long-term weight changes, and the odds ratio of developing obesity (BMI ≥ 30) according to change in dietary intake. Results: Women who consumed more whole grains consistently weighed less than did women who consumed less whole grains (P for trend < 0.0001). Over 12 y, those with the greatest increase in intake of dietary fiber gained an average of 1.52 kg less than did those with the smallest increase in intake of dietary fiber (P for trend < 0.0001) independent of body weight at baseline, age, and changes in covariate status. Women in the highest quintile of dietary fiber intake had a 49% lower risk of major weight gain than did women in the highest quintile (OR = 0.51; 95% CI: 0.39, 0.67; P < 0.0001 for trend). Conclusion: Weight gain was inversely associated with the intake of high-fiber, whole-grain foods but positively related to the intake of refined-grain foods, which indicated the importance of distinguishing whole-grain products from refined-grain products to aid in weight control. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic evidence of a preventive effect of whole grain against type 2 diabetes is mainly based on data from women. Information specific to men and women is needed. Objective: The objective was to study the relation between the intake of whole grain and fiber and the subsequent incidence of type 2 diabetes. Design: The design was a cohort study of 2286 men and 2030 women aged 40-69 y and initially free of diabetes. Food consumption data were collected from 1966 through 1972 with the use of a dietary history interview covering the habitual diet during the previous year. During a 10-y follow-up, incident type 2 diabetes cases were identified in 54 men and 102 women from a nationwide register. Results: Whole-grain consumption was associated with a reduced risk of type 2 diabetes. The relative risk (adjusted for age, sex, geographic area, smoking status, body mass index, energy intake, and intakes of vegetables, fruit, and berries) between the highest and lowest quartiles of whole-grain consumption was 0.65 (95% CI: 0.36, 1.18; P for trend = 0.02). Cereal fiber intake was also associated with a reduced risk of type 2 diabetes. The relative risk between the extreme quartiles of cereal fiber intake was 0.39 (95% CI: 0.20, 0.77; P = 0.01). Conclusions: An inverse association between whole-grain intake and the risk of type 2 diabetes was found. The similar result for cereal fiber intake suggests that the whole-grain association is due to cereal fiber or another factor related to cereal fiber intake. [ABSTRACT FROM AUTHOR]

Background: High body iron stores may increase the risk of several chronic diseases. Whether dietary factors contribute to the risk of high iron stores is unknown. Objective: We assessed the relation between dietary factors and the risk of high iron stores in the elderly Framingham Heart Study cohort. Design: We examined the relation between the usual intake of dietary factors (food-frequency questionnaire) and the risk of high iron stores (serum ferritin > 300 and 200 μg/L in men and women, respectively) in 614 subjects aged 68-93 y. Results: The risk of high iron stores was significantly higher 1) in subjects who took ⩾ 30 mg supplemental Fe/d than in nonusers [odds ratio (OR): 4.32; 95% CI: 1.63, 11.47], 2) in subjects who consumed > 21 servings of fruit/wk than in those who consumed ⩽ 14 servings/wk (OR: 2.88; 95% CI: 1.26, 6.61), and 3) in subjects who consumed > 4 but < 7 or ⩾ 7 servings of red meat/wk than in those who consumed ⩽ 4 servings/wk (ORs: 2.94 and 3.61, respectively; 95% CIs: 1.33, 6.47 and 1.57, 8.27, respectively). Whole-grain intake (> 7 servings/wk) was inversely associated (OR: 0.23; 95% CI: 0.07, 0.75). Conclusions: Among elders, intakes of highly bioavailable forms of iron (supplemental iron and red meat) and of fruit, a dietary source of an enhancer of nonheme-iron absorption (vitamin C), promote high iron stores, whereas foods containing phytate (whole grains) decrease these stores. Individual dietary patterns may be important modulators of high iron stores. [ABSTRACT FROM AUTHOR]

Background: Certain dietary components may play a role in the prevention of type 2 diabetes. Objective: We examined prospectively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men. Design: Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 (n = 42 898) were followed for ⩽ 12 y. Intakes of whole and refined grains, measured every 4 y by use of food-frequency questionnaires, were used to predict subsequent type 2 diabetes risk through multivariate analysis. Results:We ascertained 1197 cases of incident type 2 diabetes. After adjustment for age; physical activity; cigarette smoking; alcohol consumption; family history of diabetes; and fruit, vegetable, and energy intakes, the relative risk of type 2 diabetes was 0.58 (95% CI: 0.47, 0.70; P for trend < 0.0001) comparing the highest with the lowest quintile of whole-grain intake. The association was moderately attenuated when additionally adjusted for body mass index (relative risk: 0.70; 95% CI: 0.57, 0.85; P for trend = 0.0006). Intake of refined grains was not significantly associated with risk of type 2 diabetes. After further adjustment for magnesium intake, cereal fiber intake, and glycemic load, the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant. Conclusions: In men, a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber. Efforts should be made to replace refined-grain with whole-grain foods. [ABSTRACT FROM AUTHOR]

Background: The influence of whole grains on cardiovascular disease risk may be mediated through multiple pathways, eg, a reduction in blood lipids and blood pressure, an enhancement of insulin sensitivity, and an improvement in blood glucose control. Objective: The objective was to examine the association between diets rich in whole- or refined-grain foods and several metabolic markers of disease risk in the Framingham Offspring Study cohort. Design: Whole-grain intake and metabolic risk markers were assessed in a cross-sectional study of 2941 subjects. Results: After adjustment for potential confounding factors, whole-grain intake was inversely associated with body mass index (x: 26.9 in the lowest and 26.4 in the highest quintile of intake; P for trend = 0.06), waist-to-hip ratio (0.92 and 0.91, respectively; P for trend = 0.005), total cholesterol (5.20 and 5.09 mmol/L, respectively; P for trend = 0.06), LDL cholesterol (3.16 and 3.04 mmol/L, respectively; P for trend = 0.02), and fasting insulin (205 and 199 pmol/L, respectively; P for trend = 0.03). There were no significant trends in metabolic risk factor concentrations across quintile categories of refined-grain intake. The inverse association between whole-grain intake and fasting insulin was most striking among overweight participants. The association between wholegrain intake and fasting insulin was attenuated after adjustment for dietary fiber and magnesium. Conclusion: Increased intakes of whole grains may reduce disease risk by means of favorable effects on metabolic risk factors. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease. Objective: We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults. Design: This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/ d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese [body mass index (in kg/m2): 27-36] hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered. Results: Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 ± 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol · min/L; 95% CI: -18 720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the wholegrain diet (0.07 × 10-4 mmol·kg-1·min-1 per pmol/L; 95% CI: 0.003 × 10-4, 0.144 × 10-4). Conclusion: Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic and some clinical studies support the view that whole grain foods have lower glycemic response than refined grain foods. However, from the perspective of food material properties, it is not clear why whole grain cereals containing mostly insoluble and nonviscous dietary fibers (e.g., wheat) would reduce postprandial glycemia., Objectives: We hypothesized that glycemic response for whole grain wheat milled products would not differ from that of refined wheat when potentially confounding variables (wheat source, food form, particle size, viscosity) were matched. Our objective was to study the effect of whole grain wheat compared with refined wheat milled products on postprandial glycemia, gastric emptying, and subjective appetite., Methods: Using a randomized crossover design, healthy participants (n = 16) consumed 6 different medium-viscosity porridges made from whole grain wheat or refined wheat milled products, all from the same grain source and mill: whole wheat flour, refined wheat flour, cracked wheat, semolina, reconstituted wheat flour with fine bran, and reconstituted wheat flour with coarse bran. Postprandial glycemia, gastric emptying, and appetitive response were measured using continuous glucose monitors, the 13C-octanoic acid (8:0) breath test, and visual analog scale (VAS) ratings. Bayes factors were implemented to draw inferences about null effects., Results: Little-to-no differences were observed in glycemic responses, with lower incremental AUC between 0 and 120 min glycemic responses only for semolina [mean difference (MD): -966 mg min/dL; 95% CI: -1775, -156 mg min/dL; P = 0.02) and cracked wheat (MD: -721 mg min/dL; 95% CI: -1426, -16 mg min/dL; P = 0.04) than for whole wheat flour porridge. Bayes factors suggested weak to strong evidence for a null effect (i.e., no effect of treatment type) in glycemic response, gastric emptying, and VAS ratings., Conclusions: Although whole grain wheat foods provide other health benefits, they did not in their natural composition confer lower postprandial glycemia or gastric emptying than their refined wheat counterparts.This trial was registered at clinicaltrials.gov as NCT03467659., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Glucose and insulin responses to bread products were evaluated in healthy subjects. Also studied were the rate of in vitro starch digestion and the content of in vitro resistant starch (RS). Three white-wheat-bread (WWB) products varying in crust-crumb ratio and monoglyceride addition, three bread products with a high soluble fiber content (HSFB), and two coarse-wheat breads (CB) were included. The metabolic responses to WWBs were in general higher than those to CB and HSFB products. The most prominent reduction in metabolic responses was noted with the CBs with intact kernels and the HSFBs with oat bran. The starch in these products was also more slowly released from a dialysis tubing after enzyme incubation of chewed samples. The RS content ranged from 0 to 1.7 g/100 g starch. HSFBs and the CB with intact kernels showed a higher satiety score than did the WWBs immediately after the test meal. [ABSTRACT FROM AUTHOR]

Background: Plasma trimethylamine N-oxide (TMAO) has drawn much attention as a marker of several chronic diseases. Data on the relation between diet and TMAO are discordant and few human intervention studies have assessed causality for this association., Objectives: We aimed to evaluate the effects on plasma TMAO of diets based on foods rich in polyphenols (PP) and/or long-chain n-3 fatty acids (LCn3) or whole-grain cereals (WGCs), in individuals at high cardiometabolic risk., Methods: An ancillary study was performed within 2 randomized controlled trials, aimed at evaluating the medium-term effects on cardiometabolic risk factors of diets naturally rich in PP and/or LCn3 (Etherpaths Project) or WGCs (HealthGrain Project)., Results: In the Etherpaths study (n = 78), the changes in TMAO (8-wk minus baseline) were statistically significant for the diets rich in LCn3 (+1.15 ± 11.58 μmol/L) (P = 0.007), whereas they were not for the diets rich in PP (-0.14 ± 9.66 μmol/L) (P = 0.905) or their interaction (P = 0.655) (2-factor ANOVA). In the HealthGrain Study (n = 48), the TMAO change (12-wk minus baseline) in the WGC group (+0.94 ± 3.58 μmol/L) was significantly different from that in the Refined Cereal group (-1.29 ± 3.09 μmol/L) (P = 0.037). Considering the pooled baseline data of the participants in the 2 studies, TMAO concentrations directly correlated with LCn3, EPA (20:5n-3), and protein intake, but not SFAs, fiber, MUFAs, and PP intake. Among food groups, TMAO directly correlated with the intake of fish, vegetables, and whole-grain products, but not meat, processed meat, and dairy products., Conclusions: Diets rich in LCn3 of marine origin or WGCs significantly increased plasma TMAO concentration. These changes mirrored the direct associations between TMAO concentrations and intakes of fish and WGCs, suggesting that TMAO reflects intakes of these healthy foods and, therefore, it is not a universally valid biomarker of cardiometabolic risk independent of the background diet.These trials were registered at clinicaltrials.gov as NCT01154478 and NCT00945854., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Higher intakes of whole grains and dietary fiber have been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for cancer., Objectives: Because the evidence of association with bladder cancer (BC) is limited, we aimed to assess associations with BC risk for intakes of whole grains, refined grains, and dietary fiber., Methods: We pooled individual data from 574,726 participants in 13 cohort studies, 3214 of whom developed incident BC. HRs, with corresponding 95% CIs, were estimated using Cox regression models stratified on cohort. Dose-response relations were examined using fractional polynomial regression models., Results: We found that higher intake of total whole grain was associated with lower risk of BC (comparing highest with lowest intake tertile: HR: 0.87; 95% CI: 0.77, 0.98; HR per 1-SD increment: 0.95; 95% CI: 0.91, 0.99; P for trend: 0.023). No association was observed for intake of total refined grain. Intake of total dietary fiber was also inversely associated with BC risk (comparing highest with lowest intake tertile: HR: 0.86; 95% CI: 0.76, 0.98; HR per 1-SD increment: 0.91; 95% CI: 0.82, 0.98; P for trend: 0.021). In addition, dose-response analyses gave estimated HRs of 0.97 (95% CI: 0.95, 0.99) for intake of total whole grain and 0.96 (95% CI: 0.94, 0.98) for intake of total dietary fiber per 5-g daily increment. When considered jointly, highest intake of whole grains with the highest intake of dietary fiber showed 28% reduced risk (95% CI: 0.54, 0.93; P for trend: 0.031) of BC compared with the lowest intakes, suggesting potential synergism., Conclusions: Higher intakes of total whole grain and total dietary fiber are associated with reduced risk of BC individually and jointly. Further studies are needed to clarify the underlying mechanisms for these findings., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Recently, a group of betainized compounds have been suggested to play a role in health effects in relation to a whole-grain-rich diet., Objectives: The aims of this study were to develop a quantitative mass spectrometric method for selected betainized compounds in human plasma, and to investigate their association with nutrient intake and measures of metabolic health in participants of the SYSDIET study., Methods: The SYSDIET study was a controlled randomized intervention including individuals with metabolic syndrome, where the healthy Nordic diet (HND) group increased intakes of whole grains, canola oil, berries, and fish, whereas the control diet (CD) group consumed low-fiber cereal products, milk fat, and restricted amounts of fish and berries. A quantitative LC combined with triple quadrupole MS method for betainized compounds was developed and applied to fasting plasma samples from baseline (week 0) and the end of the intervention (week 18 or 24). Concentrations of betainized compounds were correlated with intakes of selected nutrients and fiber and measures of metabolic health., Results: Pipecolic acid betaine (PAB) concentrations were significantly higher in the HND group than in the CD group (P = 0.00032) at the end of the intervention and correlated directly (P < 0.0001) with intakes of dietary fiber (r = 0.376) and a biomarker related to whole-grain rye intake, namely the ratio of alkylresorcinol C17:0 to C21:0 (r = 0.442). PAB was associated inversely with fasting plasma insulin consistently at the beginning and at the end of the intervention (P < 0.001, r = -0.300; P < 0.01, r = -0.250, respectively), as well as IL-1 receptor antagonist (P < 0.01, r = -0.232 at the beginning; P < 0.01, r = -0.236 at the end) and serum LDL/HDL cholesterol (P < 0.01, r = -0.239 at the beginning; P < 0.01, r = -0.241 at the end)., Conclusions: Among adults with the metabolic syndrome, PAB plasma concentrations were associated with fasting insulin, inflammation, and lipids and were significantly increased with adoption of the HND. Further studies are needed to clarify the biological functions of betainized compounds. This trial was registered at clinicaltrials.gov as NCT00992641., (Copyright © American Society for Nutrition 2019.)

Background: Whole-grain wheat (WGW) is described as nutritionally superior to refined wheat (RW) and thus advocated as the healthy choice, although evidence from intervention studies is often inconsistent. The liver, as the central organ in energy metabolism, might be an important target organ for WGW interventions., Objective: The aim of this study was to investigate the potential benefits of WGW consumption compared with RW consumption on liver health and associated parameters., Design: We performed a double-blind, parallel trial in which 50 overweight 45- to 70-y-old men and postmenopausal women were randomly allocated to a 12-wk intervention with either WGW (98 g/d) or RW (98 g/d) products. Before and after the intervention we assessed intrahepatic triglycerides (IHTGs) and fat distribution by proton magnetic resonance spectroscopy/magnetic resonance imaging, fecal microbiota composition, adipose tissue gene expression, and several fasting plasma parameters, as well as postprandial plasma lipids after a mixed meal., Results: Fasting plasma cholesterol, triglycerides, nonesterified fatty acids, and insulin were not affected by RW or WGW intervention. We observed a substantial increase of 49.1% in IHTGs in the RW when compared with the WGW group (P = 0.033). Baseline microbiota composition could not predict the increase in IHTGs after RW, but gut microbiota diversity decreased in the RW group when compared with the WGW group (P = 0.010). In the WGW group, we observed increased postprandial triglyceride levels compared with the RW group (P = 0.020). In addition, the WGW intervention resulted in a trend towards lower fasting levels of the liver acute-phase proteins serum amyloid A (P = 0.057) and C-reactive protein (P = 0.064) when compared to the RW intervention., Conclusions: A 12-wk RW intervention increases liver fat and might contribute to the development of nonalcoholic fatty liver disease, whereas a 12-wk 98-g/d WGW intervention prevents a substantial increase in liver fat. Our results show that incorporating feasible doses of WGW in the diet at the expense of RW maintains liver health. The study was registered at clinicaltrials.gov as NCT02385149.

Background: Epidemiologic evidence suggests that diets rich in whole grains are associated with a reduced risk of developing chronic diseases and all-cause mortality. However, the molecular mechanisms behind these beneficial metabolic effects are poorly understood., Objective: Our aim was to investigate novel trimethylated (betainized) compounds from mice and humans, and their association with whole grain-rich diets and insulin resistance and insulin secretion., Design: Fasting plasma samples were obtained in a mouse (C57BL/6J male) feeding trial and a controlled dietary intervention. The mouse trial involved feeding the mice a rye and wheat bran-enriched feed which was compared with a high-fat diet. In the human trial, participants recruited from Kuopio, Finland (n = 69) and Naples, Italy (n = 54) with characteristics of the metabolic syndrome were randomly assigned to either a whole grain-enriched diet or a control diet for 12 wk. Plasma concentrations of betainized compounds were analyzed with the use of liquid chromatography-tandem mass spectrometry. Insulin resistance and insulin secretion were assessed in an oral-glucose-tolerance test and a meal-glucose-tolerance test., Results: The betaines that were increased in mouse plasma after bran-enriched feeding were identified de novo via chemical synthesis and liquid chromatography-tandem mass spectrometry, and confirmed to be associated with an increased intake of whole-grain products in humans. In particular, the concentrations of pipecolic acid betaine were increased at the end of the whole-grain intervention in both the Kuopio cohort (P < 0.001) and the Naples cohort (P < 0.05), and these concentrations inversely correlated with the postprandial glucose concentration. Furthermore, the concentration of valine betaine was substantially increased during the intervention in Naples (P < 0.001) with an inverse correlation with the postprandial insulin concentration. In addition, the concentrations of other betaines, e.g., glycine betaine and proline betaine, correlated with glucose and insulin concentrations at the end of the intervention., Conclusions: Novel betainized compounds in humans are associated with diets rich in whole grains, and they improve insulin resistance and insulin secretion. These results suggest that these novel compounds may contribute to the beneficial effects of whole grain-rich diets. The studies were registered at clinicaltrials.gov as NCT00945854 (Naples) and NCT00573781 (Kuopio).

Background: Epidemiologic evidence on the association of a healthy Nordic diet and future type 2 diabetes (T2D) is limited. Exploring metabolites as biomarkers of healthy Nordic dietary patterns may facilitate investigation of associations between such patterns and T2D., Objectives: We aimed to identify metabolites related to a priori-defined healthy Nordic dietary indexes, the Baltic Sea Diet Score (BSDS) and Healthy Nordic Food Index (HNFI), and evaluate associations with the T2D risk in a case-control study nested in a Swedish population-based prospective cohort., Design: Plasma samples from 421 case-control pairs at baseline and samples from a subset of 151 healthy controls at a 10-y follow-up were analyzed with the use of untargeted liquid chromatography-mass spectrometry metabolomics. Index-related metabolites were identified through the use of random forest modelling followed by partial correlation analysis adjustment for lifestyle confounders. Metabolite patterns were derived via principal component analysis (PCA). ORs of T2D were estimated via conditional logistic regression. Reproducibility of metabolites was assessed by intraclass correlation (ICC) in healthy controls. Associations were also assessed for 10 metabolites previously identified as linking a healthy Nordic diet with T2D., Results: In total, 31 metabolites were associated with BSDS and/or HNFI (-0.19 ≤ r ≤ 0.21, 0.10 ≤ ICC ≤ 0.59). Two PCs were determined from index-related metabolites: PC1 strongly correlated to the indexes (r = 0.27 for BSDS, r = 0.25 for HNFI, ICC = 0.45) but showed no association with T2D risk. PC2 was weakly associated with the indexes, but more strongly with foods not part of the indexes, e.g., pizza, sausages, and hamburgers. PC2 was also significantly associated with T2D risk. Predefined metabolites were confirmed to be reflective of consumption of whole grains, fish, or vegetables, but not related to T2D risk., Conclusions: Our study did not support an association between healthy Nordic dietary indexes and T2D. However, foods such as hamburger, sausage, and pizza not covered by the indexes appeared to be more important for T2D risk in the current population.

Background: In previous meta-analyses of prospective observational studies, we investigated the association between food groups and risk of chronic disease., Objective: The aim of the present network meta-analysis (NMA) was to assess the effects of these food groups on intermediate-disease markers across randomized intervention trials., Design: Literature searches were performed until January 2018. The following inclusion criteria were defined a priori: 1) randomized trial (≥4 wk duration) comparing ≥2 of the following food groups: refined grains, whole grains, nuts, legumes, fruits and vegetables, eggs, dairy, fish, red meat, and sugar-sweetened beverages (SSBs); 2) LDL cholesterol and triacylglycerol (TG) were defined as primary outcomes; total cholesterol, HDL cholesterol, fasting glucose, glycated hemoglobin, homeostasis model assessment insulin resistance, systolic and diastolic blood pressure, and C-reactive protein were defined as secondary outcomes. For each outcome, a random NMA was performed, and for the ranking, the surface under the cumulative ranking curves (SUCRA) was determined., Results: A total of 66 randomized trials (86 reports) comparing 10 food groups and enrolling 3595 participants was identified. Nuts were ranked as the best food group at reducing LDL cholesterol (SUCRA: 93%), followed by legumes (85%) and whole grains (70%). For reducing TG, fish (97%) was ranked best, followed by nuts (78%) and red meat (72%). However, these findings are limited by the low quality of the evidence. When combining all 10 outcomes, the highest SUCRA values were found for nuts (66%), legumes (62%), and whole grains (62%), whereas SSBs performed worst (29%)., Conclusion: The present NMA provides evidence that increased intake of nuts, legumes, and whole grains is more effective at improving metabolic health than other food groups. For the credibility of diet-disease relations, high-quality randomized trials focusing on well-established intermediate-disease markers could play an important role. This systematic review was registered at PROSPERO (www.crd.york.ac.uk/PROSPERO) as CRD42018086753.

Background: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking., Objective: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans., Design: An RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country., Results: A total of 1294 participants (mean ± SD age: 70.9 ±4.0 y; 44% male) were recruited to the study and 1142 completed the 1-y trial. The Mediterranean-like dietary pattern had no effect on BMD (site-specific or whole-body); the inclusion of compliance to the intervention in the statistical model did not change the findings. There was also no effect of the intervention on the urinary biomarkers free pyridinoline or free deoxypyridinoline. Serum 25-hydroxyvitamin D significantly increased and parathyroid hormone decreased (P < 0.001) in the MD compared with the control group. Subgroup analysis of individuals with osteoporosis at baseline (site-specific BMD T-score ≤ -2.5 SDs) showed that the MD attenuated the expected decline in femoral neck BMD (n = 24 and 30 in MD and control groups, respectively; P = 0.04) but had no effect on lumbar spine or whole-body BMD., Conclusions: A 1-y intervention of the Mediterranean-like diet together with vitamin D3 supplements (10 µg/d) had no effect on BMD in the normal age-related range, but it significantly reduced the rate of loss of bone at the femoral neck in individuals with osteoporosis. The NU-AGE trial is registered at clinicaltrials.gov as NCT01754012.

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined. Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation. Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8. Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation. Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394., (© 2017 American Society for Nutrition.)

Background: Which diet is optimal for weight loss and maintenance remains controversial and implies that no diet fits all patients. Objective: We studied concentrations of fasting plasma glucose (FPG) and fasting insulin (FI) as prognostic markers for successful weight loss and maintenance through diets with different glycemic loads or different fiber and whole-grain content, assessed in 3 randomized trials of overweight participants. Design: After an 8-wk weight loss, participants in the DiOGenes (Diet, Obesity, and Genes) trial consumed ad libitum for 26 wk a diet with either a high or a low glycemic load. Participants in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) Supermarket intervention (SHOPUS) trial consumed ad libitum for 26 wk the New Nordic Diet, which is high in fiber and whole grains, or a control diet. Participants in the NUGENOB (Nutrient-Gene Interactions in Human Obesity) trial consumed a hypocaloric low-fat and high-carbohydrate or a high-fat and low-carbohydrate diet for 10 wk. On the basis of FPG before treatment, participants were categorized as normoglycemic (FPG <5.6 mmol/L), prediabetic (FPG 5.6-6.9 mmol/L), or diabetic (FPG ≥7.0 mmol/L). Modifications of the dietary effects of FPG and FI before treatment were examined with linear mixed models. Results: In the DiOGenes trial, prediabetic individuals regained a mean of 5.83 kg (95% CI: 3.34, 8.32 kg; P < 0.001) more on the high- than on the low-glycemic load diet, whereas normoglycemic individuals regained a mean of 1.44 kg (95% CI: 0.48, 2.41 kg; P = 0.003) more [mean group difference: 4.39 kg (95% CI: 1.76, 7.02 kg); P = 0.001]. In SHOPUS, prediabetic individuals lost a mean of 6.04 kg (95% CI: 4.05, 8.02 kg; P < 0.001) more on the New Nordic Diet than on the control diet, whereas normoglycemic individuals lost a mean of 2.20 kg (95% CI: 1.21, 3.18 kg; P < 0.001) more [mean group difference: 3.84 kg (95% CI: 1.62, 6.06 kg); P = 0.001]. In NUGENOB, diabetic individuals lost a mean of 2.04 kg (95% CI: -0.20, 4.28 kg; P = 0.07) more on the high-fat and low-carbohydrate diet than on the low-fat and high-carbohydrate diet, whereas normoglycemic individuals lost a mean of 0.43 kg (95% CI: 0.03, 0.83 kg; P = 0.03) more on the low-fat and high-carbohydrate diet [mean group difference: 2.47 kg (95% CI: 0.20, 4.75 kg); P = 0.03]. The addition of FI strengthened these associations. Conclusion: Elevated FPG before treatment indicates success with dietary weight loss and maintenance among overweight patients consuming diets with a low glycemic load or with large amounts of fiber and whole grains. These trials were registered at clinicaltrials.gov as NCT00390637 (DiOGenes) and NCT01195610 (SHOPUS), and at ISRNCT.com as ISRCTN25867281 (NUGENOB)., (© 2017 American Society for Nutrition.)

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking. Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM). Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors. Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P -trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth. Conclusions: Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with offspring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted., (© 2017 American Society for Nutrition.)

Background: The effect of whole grains on the regulation of energy balance remains controversial. Objective: We aimed to determine the effects of substituting whole grains for refined grains, independent of body weight changes, on energy-metabolism metrics and glycemic control. Design: The study was a randomized, controlled, parallel-arm controlled-feeding trial that was conducted in 81 men and postmenopausal women [49 men and 32 women; age range: 40-65 y; body mass index (in kg/m 2 ): <35.0]. After a 2-wk run-in period, participants were randomly assigned to consume 1 of 2 weight-maintenance diets for 6 wk. Diets differed in whole-grain and fiber contents [mean ± SDs: whole grain-rich diet: 207 ± 39 g whole grains plus 40 ± 5 g dietary fiber/d; refined grain-based diet: 0 g whole grains plus 21 ± 3 g dietary fiber/d] but were otherwise similar. Energy metabolism and body-composition metrics, appetite, markers of glycemic control, and gut microbiota were measured at 2 and 8 wk. Results: By design, body weight was maintained in both groups. Plasma alkylresorcinols, which are biomarkers of whole-grain intake, increased in the whole grain-rich diet group (WG) but not in the refined grain-based diet group (RG) ( P -diet-by-time interaction < 0.0001). Beta ± SE changes (ΔWG compared with ΔRG) in the resting metabolic rate (RMR) (43 ± 25 kcal/d; P = 0.04), stool weight (76 ± 12 g/d; P < 0.0001), and stool energy content (57 ± 17 kcal/d; P = 0.003), but not in stool energy density, were higher in the WG. When combined, the favorable energetic effects in the WG translated into a 92-kcal/d (95% CI: 28, 156-kcal/d) higher net daily energy loss compared with that of the RG ( P = 0.005). Prospective consumption ( P = 0.07) and glycemia after an oral-glucose-tolerance test ( P = 0.10) trended toward being lower in the WG than in the RG. When nonadherent participants were excluded, between-group differences in stool energy content and glucose tolerance increased, and between-group differences in the RMR and prospective consumption were not statistically significant. Conclusion: These findings suggest positive effects of whole grains on the RMR and stool energy excretion that favorably influence energy balance and may help explain epidemiologic associations between whole-grain consumption and reduced body weight and adiposity. This trial was registered at clinicaltrials.gov as NCT01902394., (© 2017 American Society for Nutrition.)