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The Relationship between Whole-Grain Intake and Measures of Cognitive Decline, Mood, and Anxiety-A Systematic Review.
Ross, AB, Shertukde, SP, Livingston Staffier, K, Chung, M, Jacques, PF, McKeown, NM
Advances in nutrition (Bethesda, Md.). 2023;(4):652-670
Abstract
Greater intake of whole grains, compared to refined grains, is consistently associated with a reduced risk of cardiovascular disease and type 2 diabetes, both of which are associated with cognitive decline. To better understand the relationship between whole-grain intake, cognition, mood, and anxiety, a systematic review was conducted to synthesize available evidence linking whole grains to these outcomes. Four electronic databases were searched from inception to August 2021 for potentially relevant observational and interventional studies. Risk of bias (RoB) assessments were performed using the newly developed Nutrition Quality Evaluation Strengthening Tools, and the Grades of Recommendation, Assessment, Development, and Evaluation approach was used to determine the strength of evidence for each outcome. In total, 23 studies [4 randomized controlled trials (RCTs) and 19 observational studies] met the predefined eligibility criteria. Of these,12 studies included analysis of whole-grain intake and cognitive decline, 9 included mood outcomes, and 2 included both cognition and mood outcomes. The overall evidence for an association between whole-grain intake and cognition is inconclusive. With respect to mood outcomes, evidence from RCTs prospective cohort and case-control studies suggest that higher intake is linked to improved outcomes for mood and depression although the evidence is mixed for cross-sectional studies. Reporting of whole-grain intake fell short of suggested standards, and the strength of available evidence was low or very low for all outcomes. A high RoB toward studies reporting results was also noted, complicating both the interpretation of some studies and the combined evidence. Of note, few well-designed RCTs assessing the effect of whole-grain intake on measures of cognition, mood, and anxiety were identified, highlighting the need for more studies in this area. The available, although limited, evidence suggests that greater whole-grain intake is associated with better mood and anxiety-related scores and is inconclusive regarding cognitive outcomes. PROSPERO registration: CRD42021266355.
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Brain foods - the role of diet in brain performance and health.
Ekstrand, B, Scheers, N, Rasmussen, MK, Young, JF, Ross, AB, Landberg, R
Nutrition reviews. 2021;(6):693-708
Abstract
The performance of the human brain is based on an interplay between the inherited genotype and external environmental factors, including diet. Food and nutrition, essential in maintenance of brain performance, also aid in prevention and treatment of mental disorders. Both the overall composition of the human diet and specific dietary components have been shown to have an impact on brain function in various experimental models and epidemiological studies. This narrative review provides an overview of the role of diet in 5 key areas of brain function related to mental health and performance, including: (1) brain development, (2) signaling networks and neurotransmitters in the brain, (3) cognition and memory, (4) the balance between protein formation and degradation, and (5) deteriorative effects due to chronic inflammatory processes. Finally, the role of diet in epigenetic regulation of brain physiology is discussed.
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A Whole-Grain Diet Increases Whole-Body Protein Balance Compared with a Macronutrient-Matched Refined-Grain Diet.
Mey, JT, Godin, JP, Scelsi, AR, Kullman, EL, Malin, SK, Yang, S, Floyd, ZE, Poulev, A, Fielding, RA, Ross, AB, et al
Current developments in nutrition. 2021;(11):nzab121
Abstract
BACKGROUND There are limited data from randomized control trials to support or refute the contention that whole-grains can enhance protein metabolism in humans. OBJECTIVES To examine: 1) the clinical effects of a whole-grain diet on whole-body protein turnover; 2) the cellular effects of whole-grains on protein synthesis in skeletal muscle cells; and 3) the population effects of whole-grain intake on age-related muscle loss. METHODS Adults with overweight/obesity (n = 14; age = 40 ± 7 y; BMI = 33 ± 5 kg/m2) were recruited into a crossover, randomized controlled trial (NCT01411540) in which isocaloric, macronutrient-matched whole-grain and refined-grain diets were fully provisioned for two 8-wk periods. Diets differed only in the presence of whole-grains (50 g/1000 kcal). Whole-body protein kinetics were assessed at baseline and after each diet in the fasted-state (13C-leucine) and integrated over 24 h (15N-glycine). In vitro studies using C2C12 cells assessed global protein synthesis by surface sensing of translation and anabolic signaling by Western blot. Complementary epidemiological assessments using the NHANES database assessed the effect of whole-grain intake on muscle function assessed by gait speed in older adults (n = 2783). RESULTS Integrated 24-h net protein balance was 3-fold higher on a whole-grain diet compared with a refined-grain diet (P = 0.04). A whole-grain wheat extract increased submaximal rates of global protein synthesis (27%, P < 0.05) in vitro. In a large sample of older adults, whole-grain intake was associated with greater muscle function (OR = 0.92; 95% CI: 0.86, 0.98). CONCLUSIONS Consuming 50 g/1000 kcal whole-grains per day promotes greater protein turnover and enhances net protein balance in adults. Whole-grains impact skeletal muscle at the cellular level, and are associated with greater muscle function in older adults. Collectively, these data point to a new mechanism whereby whole-grain consumption favorably enhances protein turnover and improves health outcomes.This clinical trial is registered on clinicaltrials.gov (identifier: NCT01411540).
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Whole-Grain Processing and Glycemic Control in Type 2 Diabetes: A Randomized Crossover Trial.
Åberg, S, Mann, J, Neumann, S, Ross, AB, Reynolds, AN
Diabetes care. 2020;(8):1717-1723
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OBJECTIVE To consider the effects of whole-grain processing, specifically milling, on glycemic control in free-living adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Participants of this crossover trial were randomized to two interventions of 2 weeks, separated by washout. They were advised to replace the grain foods they normally consumed with intervention foods. Intervention foods were nutrient-matched whole-grain products of wheat, oats, and brown rice that differed in their degree of processing. No other lifestyle advice was given. Continuous glucose monitoring systems were worn. Other cardiometabolic risk factors and alkylresorcinols (a biomarker of whole-grain intake) were measured pre- and postintervention. RESULTS Thirty-one adults with type 2 diabetes (63 ± 13 years old, BMI 32.4 ± 7 kg/m2, HbA1c 7.5 ± 3.4% [59 ± 14 mmol/mol]) commenced the trial; 28 (90%) completed both interventions. The increase in alkylresorcinols did not differ between interventions, and there was no difference in reported energy intake. Postprandial responses were 9% (95% CI 3-15) lower following breakfast and 6% (1-10) lower following all meals of less-processed whole grains when compared with finely milled grains. Day-long glycemic variability also was reduced when measured by 24-h SD (-0.16 mmol/L [95% CI -0.25 to -0.06]) and mean amplitude of glycemic excursion (-0.36 [95% CI -0.65 to -0.08]). Mean change in body weight differed by 0.81 kg (95% CI 0.62-1.05) between interventions, increasing during the finely milled intervention and decreasing during the less-processed whole-grain intervention. This was not a mediating factor for the glycemic variables considered. CONCLUSIONS Consuming less-processed whole-grain foods over 2 weeks improved measures of glycemia in free-living adults with type 2 diabetes compared with an equivalent amount of whole-grain foods that were finely milled. Dietary advice should promote the consumption of minimally processed whole grains.
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A Whole-Grain Diet Increases Glucose-Stimulated Insulin Secretion Independent of Gut Hormones in Adults at Risk for Type 2 Diabetes.
Malin, SK, Kullman, EL, Scelsi, AR, Godin, JP, Ross, AB, Kirwan, JP
Molecular nutrition & food research. 2019;(7):e1800967
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INTRODUCTION The effect of whole-grain (WG) versus refined-grain (RG) diets on glucose-stimulated insulin secretion (GSIS) and β-cell function is unclear. METHODS In a double-blind crossover randomized controlled trial, 13 prediabetic adults (37.2 ± 1.8 y, BMI: 33.6 ± 1.4 kg m-2 , 2 h glucose: 146.9 ± 11.6 mg dL-1 ) are provided isocaloric-matched WG and RG diets for 8-weeks each, with an 8-10 week washout between diets. Glucose, insulin, and C-peptide are studied over 240 min following a 75 g OGTT. Incretins (GLP-1 and GIP), PYY, and total ghrelin are assessed at 0, 30, and 60 min. Mixed-meal diets for carbohydrate (54%), fat (28%), and protein (18%) contain either WG (50 g/1000 kcal) or equivalent RG. RESULTS Both diets induce fat loss (≈2 kg). While neither diet impacts early phase GSIS, the WG diet increases total GSIS (iAUC of C-peptide0-240 /Glc0-240 , p = 0.02) and β-cell function (disposition index; GSIS × insulin sensitivity, p = 0.02). GIP and PYY are unaltered by either diet, but GLP-1 is higher at 30 min following RG versus WG (p = 0.04). Ghrelin levels are higher at 60 min of the OGTT following both interventions (p = 0.01). CONCLUSION A WG-rich diet increases β-cell function independent of gut hormones in adults with prediabetes.
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Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials.
Lind, MV, Lauritzen, L, Kristensen, M, Ross, AB, Eriksen, JN
The American journal of clinical nutrition. 2019;(1):29-42
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BACKGROUND Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes. OBJECTIVE The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes. DESIGN We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine. RESULTS When compared with placebo, folate supplementation lowered fasting insulin (WMD: -13.47 pmol/L; 95% CI: -21.41, -5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: -0.57 units; 95% CI: -0.76, -0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16). CONCLUSION Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.
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Reply to RB Yarandi.
Lind, MV, Lauritzen, L, Kristensen, M, Ross, AB, Eriksen, JN
The American journal of clinical nutrition. 2019;(4):1233-1234
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Low-phytate wholegrain bread instead of high-phytate wholegrain bread in a total diet context did not improve iron status of healthy Swedish females: a 12-week, randomized, parallel-design intervention study.
Hoppe, M, Ross, AB, Svelander, C, Sandberg, AS, Hulthén, L
European journal of nutrition. 2019;(2):853-864
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PURPOSE To investigate the effects of eating wholegrain rye bread with high or low amounts of phytate on iron status in women under free-living conditions. METHODS In this 12-week, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low-phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addition to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post-intervention. RESULTS Fifty-five females completed the study. There was a significant difference in change over time in total body iron stores between the two groups (p < 0.035). In the low-phytate bread group (n = 24) there were significant within-group decreases in both ferritin (mean 12%; from 32 ± 7 to 27 ± 6 μg/L, geometric mean ± SEM, p < 0.018) and total body iron (mean 12%; from 6.9 ± 1.4 to 5.4 ± 1.1 mg/kg, p < 0.035). Plasma alkylresorcinols indicated that most subjects complied with the intervention CONCLUSIONS In Swedish females of reproductive age, no statistically significant difference in iron status was detected after 12 weeks of high-phytate wholegrain bread consumption. However, consumption of low-phytate wholegrain bread for 12 weeks resulted in a reduction of markers of iron status. Although single-meal studies clearly show an increase in iron bioavailability from dephytinization of cereals, medium-term consumption of reduced phytate bread under free-living conditions suggests that this strategy does not work to improve iron status in healthy women of reproductive age.
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.
Roager, HM, Vogt, JK, Kristensen, M, Hansen, LBS, Ibrügger, S, Mærkedahl, RB, Bahl, MI, Lind, MV, Nielsen, RL, Frøkiær, H, et al
Gut. 2019;68(1):83-93
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Plain language summary
Whole grain consumption has been linked with decreased risk of lifestyle-related diseases. While animal studies have shown the gut microbiome to be a mediator of metabolic health, human studies examining the effect of whole grain intake of the gut remain inconclusive. The aim of this study was to investigate the effects of a whole grain diet on the gut microbiome, gut functionality and biomarkers of metabolic health. In this randomised, controlled, crossover study, 50 participants completed two 8-week dietary intervention periods comprising of a whole grain diet and a refined grain diet with a 6-week washout period. Examinations were done at the beginning and end of each intervention period to assess anthropometry and various plasma and gut markers. This study found that a whole grain diet as compared with a refined grain diet reduced energy intake and body weight as well as circulating markers of inflammation. Contrary to the hypothesis, these benefits were all observed independent of changes in the gut microbiome. Based on these results, the authors conclude higher intake of whole grains should be recommended to those at risk of inflammation-related disease.
Abstract
OBJECTIVE To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER NCT01731366; Results.
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults.
Hansen, LBS, Roager, HM, Søndertoft, NB, Gøbel, RJ, Kristensen, M, Vallès-Colomer, M, Vieira-Silva, S, Ibrügger, S, Lind, MV, Mærkedahl, RB, et al
Nature communications. 2018;(1):4630
Abstract
Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.