Impact of rye-based evening meals on cognitive functions, mood and cardiometabolic risk factors: a randomized controlled study in healthy middle-aged subjects.

BACKGROUND: Whole grain (WG) intake is associated with reduced risk of obesity, type 2 diabetes and cardiovascular disease, whereas type 2 diabetes increases the risk of cognitive decline and dementia. The purpose of this study was to investigate the effects of short-term intervention with WG rye on cognitive functions, mood and cardiometabolic risk markers in middle-aged test subjects. METHOD: Rye-based breads were provided to 38 healthy test subjects (aged 52-70y) during three consecutive days in a crossover study design, using white wheat flour bread (WWB) as a reference. The rye-based bread consisted of a WG rye kernel/flour mixture (1:1 ratio) supplemented with resistant starch type 2 (RS2) (RB + RS2). The last bread portion was ingested at 2100 h, and cognitive function, mood and cardiometabolic risk markers were determined the following morning, 11 - 14 h post intake. RESULTS: In comparison to WWB, the RB + RS2 product increased ratings of mood parameters (valance, P < 0.001; activation P < 0.05). No differences were seen in the cognitive tests depending on intervention (P > 0.05). RB + RS2 increased insulin sensitivity (P < 0.05), fasting levels of gut hormones (PYY, P < 0.05; GLP-2, P < 0.01) and fasting concentrations of plasma acetate, butyrate and total SCFA (P < 0.001). In contrast, fasting levels of IL - 1ß were decreased (P < 0.05). Insulin sensitivity was positively correlated with working memory test performance (P < 0.05). CONCLUSIONS: This study display novel findings regarding effects of WG rye products on mood, and glucose and appetite regulation in middle-aged subjects, indicating anti-diabetic properties of WG rye. The beneficial effects are suggested to be mediated through gut fermentation of dietary fiber in the RB + RS2 product. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov, register number NCT03275948 . Registered September 8 2017.

Increased Plasma Brain-Derived Neurotrophic Factor 10.5 h after Intake of Whole Grain Rye-Based Products in Healthy Subjects.

It has previously been shown in short-term interventions that kernel-based whole grain (WG) rye products have beneficial effects on test markers related to obesity and type 2 diabetes (T2D). T2D increases the risk of several severe health issues, including declined cognitive functions. The protein brain-derived neurotrophic factor (BDNF) is suggested to be a potential biomarker for neuronal integrity. The aim of this study was to investigate the effect on plasma BDNF concentrations, 10.5 h after the intake of WG rye. Healthy young adults were provided late evening meals consisting of WG rye kernel-based bread (RKB) or a white wheat flour-based bread (reference product (WWB)), in a randomized cross-over design. The BDNF concentrations were investigated at fasting in the morning 10.5 h after single evening meals with RKB and WWB, and also after three consecutive evening meals with RKB and WWB, respectively. No difference was observed in the BDNF concentrations depending on the priming setting (p > 0.05). The RKB evening meals increased the BDNF concentrations by 27% at fasting (p = 0.001), compared to WWB. The increase of BDNF after the RKB indicate that, in addition to anti-diabetic properties, the dietary fiber in WG rye may support neuronal integrity.

Effects of whole grain rye, with and without resistant starch type 2 supplementation, on glucose tolerance, gut hormones, inflammation and appetite regulation in an 11-14.5 hour perspective; a randomized controlled study in healthy subjects.

BACKGROUND: The prevalence of obesity is increasing worldwide and prevention is needed. Whole grain has shown potential to lower the risk of obesity, cardiovascular disease and type 2 diabetes. One possible mechanism behind the benefits of whole grain is the gut fermentation of dietary fiber (DF), e.g. non-starch polysaccharides and resistant starch (RS), in whole grain. The purpose of the study is to investigate the effect of whole grain rye-based products on glucose- and appetite regulation. METHOD: Twenty-one healthy subjects were provided four rye-based evening test meals in a crossover overnight study design. The test evening meals consisted of either whole grain rye flour bread (RFB) or a 1:1 ratio of whole grain rye flour and rye kernels bread (RFB/RKB), with or without added resistant starch (+RS). White wheat flour bread (WWB) was used as reference evening meal. Blood glucose, insulin, PYY, FFA, IL-6 as well as breath H2 and subjective rating of appetite were measured the following morning at fasting and repeatedly up to 3.5 h after a standardized breakfast consisting of WWB. Ad libitum energy intake was determined at lunch, 14.5 h after evening test and reference meals, respectively. RESULTS: The evening meal with RFB/RKB + RS decreased postprandial glucose- and insulin responses (iAUC) (P < 0.05) and increased the gut hormone PYY in plasma the following morning 0-120 min after the standardized breakfast, compared to WWB (P = 0.01). Moreover, RFB increased subjective satiety and decreased desire to eat, and both RFB and RFB/RKB decreased feeling of hunger (AUC 0-210 min). All rye-based evening meals decreased or tended to decrease fasting FFA (P < 0.05, RFB/RKB: P = 0.057) and increased breath hydrogen concentration (0-120 min, P < 0.001). No effects were noted on energy intake at lunch or inflammatory marker IL-6 (0 + 180 min) after the rye-based evening meals, compared to WWB. CONCLUSION: Whole grain rye bread has the potential to improve cardiometabolic variables in an 11-14.5 h perspective in healthy humans. The combination RFB/RKB + RS positively affected biomarkers of glucose- and appetite regulation in a semi-acute perspective. Meanwhile, RFB and RFB/RKB improved subjective appetite ratings. The effects probably emanate from gut fermentation events. TRIAL REGISTRATION: The study was registered at: ClinicalTrials.gov, register number NCT02347293 ( www.clinicaltrials.gov/ct2/show/NCT02347293 ). Registered 15 January 2015.

Rye-Based Evening Meals Favorably Affected Glucose Regulation and Appetite Variables at the Following Breakfast; A Randomized Controlled Study in Healthy Subjects.

BACKGROUND: Whole grain has shown potential to prevent obesity, cardiovascular disease and type 2 diabetes. Possible mechanism could be related to colonic fermentation of specific indigestible carbohydrates, i.e. dietary fiber (DF). The aim of this study was to investigate effects on cardiometabolic risk factors and appetite regulation the next day when ingesting rye kernel bread rich in DF as an evening meal. METHOD: Whole grain rye kernel test bread (RKB) or a white wheat flour based bread (reference product, WWB) was provided as late evening meals to healthy young adults in a randomized cross-over design. The test products RKB and WWB were provided in two priming settings: as a single evening meal or as three consecutive evening meals prior to the experimental days. Test variables were measured in the morning, 10.5-13.5 hours after ingestion of RKB or WWB. The postprandial phase was analyzed for measures of glucose metabolism, inflammatory markers, appetite regulating hormones and short chain fatty acids (SCFA) in blood, hydrogen excretion in breath and subjective appetite ratings. RESULTS: With the exception of serum CRP, no significant differences in test variables were observed depending on length of priming (P>0.05). The RKB evening meal increased plasma concentrations of PYY (0-120 min, P<0.001), GLP-1 (0-90 min, P<0.05) and fasting SCFA (acetate and butyrate, P<0.05, propionate, P = 0.05), compared to WWB. Moreover, RKB decreased blood glucose (0-120 min, P = 0.001), serum insulin response (0-120 min, P<0.05) and fasting FFA concentrations (P<0.05). Additionally, RKB improved subjective appetite ratings during the whole experimental period (P<0.05), and increased breath hydrogen excretion (P<0.001), indicating increased colonic fermentation activity. CONCLUSION: The results indicate that RKB evening meal has an anti-diabetic potential and that the increased release of satiety hormones and improvements of appetite sensation could be beneficial in preventing obesity. These effects could possibly be mediated through colonic fermentation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02093481.

Effects of wheat bran extract rich in arabinoxylan oligosaccharides and resistant starch on overnight glucose tolerance and markers of gut fermentation in healthy young adults.

PURPOSE: Specific combinations of dietary fiber (DF) have been observed to result in improved glucose tolerance at a subsequent standardized breakfast. Arabinoxylan oligosaccharides (AXOS) are considered as DF with prebiotic potential, but so far no studies have investigated their metabolic effects in humans. This randomized cross-over study evaluated the overnight impact of breads containing AXOS-rich wheat bran extract and resistant starch (RS, Hi-Maize), separately or combined, on glucose tolerance, related metabolic parameters and markers of gut fermentation in healthy subjects. METHODS: Evening reference and test products were: (1) reference white wheat flour bread (WWB), WWB supplemented with (2) AXOS and RS (WWB + AXOS + RS), (3) an increased content of either AXOS (WWB + hiAXOS) or (4) RS (WWB + hiRS). At the subsequent standardized breakfast, blood was sampled for 3 h to monitor glucose, insulin, nonesterified fatty acids, glucagon-like peptide (GLP)-1 and GLP-2. Breath hydrogen (H2) and short chain fatty acids (SCFA) were measured as markers of gut fermentation, and subjective appetite was rated using visual analog scales. RESULTS: Dose-dependent decreases in glucose responses were observed with increased AXOS over the duration of 3 h. Insulin sensitivity index was improved in the morning after the WWB + hiAXOS evening meal. An increase in breath H2 concentration and circulating SCFA was observed in the morning after both evening meals containing AXOS. CONCLUSION: The present study indicates that AXOS have the potential of improving glucose tolerance in an overnight perspective and suggested mechanisms are improved insulin sensitivity and increased gut fermentation.

Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects.

Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota-mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56%) and postprandially (p-glucagon-like peptide-2; 13% and p-peptide YY; 18%). Breath H2 excretion and fasting serum (s) SCFA concentrations were increased (363 and 18%, respectively), and b-glucose (22%) and s-insulin responses (17%) were decreased after BB intervention. Insulin sensitivity index (ISI(composite)) was also improved (25%) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome.

Effects of indigestible carbohydrates in barley on glucose metabolism, appetite and voluntary food intake over 16 h in healthy adults.

BACKGROUND: Recent knowledge in animals suggests that gut microbial metabolism may affect host metabolism, including appetite regulating hormones. The aim of the present study was to evaluate the potential effects of a whole grain barley kernel product, rich in intrinsic indigestible carbohydrates (dietary fibre and resistant starch), on markers of metabolism and appetite regulation in healthy subjects. METHODS: Boiled barley kernels (BK) or white wheat bread (WWB; reference) were provided as late evening meals to 19 young adults in random order using a cross-over design. During subsequent ad libitum standardized breakfast and lunch meals (10.5-16 h), blood was collected for analysis of glucose, plasma insulin, adiponectin, ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), serum free fatty acids (FFA) and interleukin (IL)-6. In addition, appetite sensations, voluntary energy intake and breath H2 were determined. RESULTS: BK as evening meal increased plasma GLP-1 at fasting (P < 0.05) and during the experimental day (P < 0.01) compared with WWB. In addition the BK evening meal decreased fasting serum FFA (P < 0.05) and tended to decrease fasting serum IL-6 (P = 0.06). At lunch, preceded by BK evening meal, voluntary energy intake was decreased (P < 0.05) when compared to WWB evening meal. The BK evening meal decreased incremental blood glucose area (P < 0.01), promoted higher breath H2 (P < 0.001), maintained adiponectin concentrations (P < 0.05) and reduced perceived hunger (P < 0.05) during 10.5-16 h after the meal. CONCLUSIONS: The results indicate that the BK evening meal, facilitate glucose regulation, increase the release of GLP-1, reduce subsequent energy intake while at the same time decreasing hunger over 2 subsequent meals, and reduce fasting FFA the subsequent morning, possibly mediated through gut microbial fermentation of the indigestible carbohydrates.

A cereal-based evening meal rich in indigestible carbohydrates increases plasma butyrate the next morning.

Epidemiological studies have shown an inverse relation between a whole grain consumption and risk of type-2 diabetes and cardiovascular disease. One tentative mechanism relates to colonic metabolism of indigestible carbohydrates. In a previous study, we reported a positive relation between colonic fermentation and improved glucose tolerance. This work can be seen as an extension of that study, focusing on the tentative role of specific colonic metabolites, i.e. SCFA. Plasma concentrations of acetate, propionate, and butyrate were determined in the morning in healthy participants (5 women and 10 men, mean ± SD: 25.9 ± 3.2 y, BMI < 25) following 8 different cereal-based evening meals (50 g available starch) varying in content of indigestible carbohydrates. Each participant consumed all test meals in a random order on separate evenings. At a standardized breakfast following evening test meals, the postprandial glucose response (incremental area under the curve, 0-120 min) was inversely related to plasma butyrate (r = -0.26; P < 0.01) and acetate (r = -0.20; P < 0.05) concentrations. Evening meals composed of high-amylose barley kernels or high-ß-glucan barley kernels resulted in higher plasma butyrate concentrations the following morning compared with an evening meal with white wheat bread (P < 0.05). The results support the view that cereal products rich in indigestible carbohydrates may improve glucose tolerance through a mechanism involving colonic fermentation and generation of SCFA, where in particular butyric acid may be involved. This mechanism may be one explanation by which whole grain is protective against type 2 diabetes and cardiovascular disease.

Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast.

Low-glycemic index (GI) foods and foods rich in whole grain are associated with reduced risk of type 2 diabetes and cardiovascular disease. We studied the effect of cereal-based bread evening meals (50 g available starch), varying in GI and content of indigestible carbohydrates, on glucose tolerance and related variables after a subsequent standardized breakfast in healthy subjects (n = 15). At breakfast, blood was sampled for 3 h for analysis of blood glucose, serum insulin, serum FFA, serum triacylglycerides, plasma glucagon, plasma gastric-inhibitory peptide, plasma glucagon-like peptide-1 (GLP-1), serum interleukin (IL)-6, serum IL-8, and plasma adiponectin. Satiety was subjectively rated after breakfast and the gastric emptying rate (GER) was determined using paracetamol as a marker. Breath hydrogen was measured as an indicator of colonic fermentation. Evening meals with barley kernel based bread (ordinary, high-amylose- or beta-glucan-rich genotypes) or an evening meal with white wheat flour bread (WWB) enriched with a mixture of barley fiber and resistant starch improved glucose tolerance at the subsequent breakfast compared with unsupplemented WWB (P < 0.05). At breakfast, the glucose response was inversely correlated with colonic fermentation (r = -0.25; P < 0.05) and GLP-1 (r = -0.26; P < 0.05) and positively correlated with FFA (r = 0.37; P < 0.001). IL-6 was lower (P < 0.01) and adiponectin was higher (P < 0.05) at breakfast following an evening meal with barley-kernel bread compared with WWB. Breath hydrogen correlated positively with satiety (r = 0.27; P < 0.01) and inversely with GER (r = -0.23; P < 0.05). In conclusion, the composition of indigestible carbohydrates of the evening meal may affect glycemic excursions and related metabolic risk variables at breakfast through a mechanism involving colonic fermentation. The results provide evidence for a link between gut microbial metabolism and key factors associated with insulin resistance.

Effect of cereal test breakfasts differing in glycemic index and content of indigestible carbohydrates on daylong glucose tolerance in healthy subjects.

BACKGROUND: Frequent hyperglycemic episodes are increasingly being associated with an increased risk of type 2 diabetes and cardiovascular disease. OBJECTIVE: We studied the extent to which acute glycemia and glycemia after subsequent meals can be modulated by the characteristics of cereal foods, such as glycemic index (GI) and content of indigestible carbohydrates. DESIGN: Twelve healthy subjects consumed test meals in a random order. In series 1, the test meals were consumed at breakfast, and postprandial blood glucose incremental areas under the curve (IAUCs) were calculated after the test breakfast, standardized lunch, and standardized dinner. In series 2, the subjects consumed test evening meals and IAUCs were calculated after a subsequent standardized breakfast. Breath hydrogen was measured as an indicator of colonic fermentation. RESULTS: Barley or rye kernel breakfasts lowered the blood glucose IAUC (0-120 min) at breakfast, at a subsequent lunch, and the cumulative IAUCs (breakfast+lunch+dinner) when compared with white-wheat bread (P < 0.05). The lunch blood glucose IAUCs were positively correlated with breakfast IAUCs (r = 0.30, P < 0.05). Breath hydrogen excretion was negatively correlated with blood glucose IAUCs after lunch (r = -0.33, P < 0.05) and dinner (r = -0.22, P < 0.05). A barley kernel evening meal resulted in lower IAUCs (P < 0.05) and higher breath hydrogen (P < 0.001) after a subsequent breakfast compared with white-wheat bread. CONCLUSIONS: Glucose tolerance at subsequent meals can be notably improved during the course of a whole day or overnight by choosing specific low-GI, whole-grain cereal products. A low GI may be sufficient to achieve a second-meal effect from breakfast to lunch. A specific indigestible carbohydrate mixture appears to be required to show benefits on glucose tolerance in a longer time frame (9.5 h), most likely mediated through colonic fermentation.