Varying roles of glucoregulatory function measures in postprandial cognition following milk consumption.

PURPOSE: Past work suggests milk consumption may facilitate cognition in children and college students with higher fasting glucose compared to other beverages (e.g., fruit juice). However, no studies have evaluated this phenomenon in adults, or considered other measures of glucoregulatory function. This open-label study assessed the role of glucoregulatory function in postprandial cognition after milk intake in adults. We hypothesized participants with lower fasting or post-consumption plasma glucose following a glucose excursion challenge (glucose response) would demonstrate better cognition following beverages of higher (juice) versus lower (milk) or no (water) glycemic content. METHODS: Forty-four nondiabetic, overnight-fasted adults attended three laboratory visits, ingesting 237 mL of 2% fat milk, apple juice, or water at each visit in a randomized, counterbalanced, crossover design. Participants completed cognitive testing (CNS Vital Signs) at baseline and 30, 90, and 150 min post-ingestion; primary outcomes were CNS Vital Signs composite scores. Fasting and post-consumption plasma glucose levels were assessed, with glucose response indexed as the change in plasma glucose from baseline to 30 min after juice (ΔGlucose). RESULTS: Mixed modeling revealed participants with higher fasting glucose demonstrated better complex attention after water versus juice at 30 min, but better performance after juice versus water at 150 min (p = 0.02). Participants with a larger ΔGlucose demonstrated better processing speed (p = 0.01) 30 min after milk versus water; this effect also reversed at 150 min. CONCLUSION: Different methods of measuring glucoregulatory function reveal its differing roles in postprandial cognition. Time since ingestion may also determine which beverages best optimize cognition.

Substituting Lean Beef for Carbohydrate in a Healthy Dietary Pattern Does Not Adversely Affect the Cardiometabolic Risk Factor Profile in Men and Women at Risk for Type 2 Diabetes.

BACKGROUND: Observational evidence suggests that red meat intake is associated with type 2 diabetes (T2D) and cardiovascular disease incidence, but few randomized controlled trials have assessed effects of lean, unprocessed red meat intake on insulin sensitivity and other cardiometabolic risk factors. OBJECTIVE: This study compared the USDA Healthy US-Style Eating Pattern, low in saturated fat and red meat (<40 g/d red meat; USDA-CON), with a modified version with an additional 150 g/d lean beef as an isocaloric replacement for carbohydrate (USDA-LB) on insulin sensitivity and cardiometabolic risk markers. METHODS: Participants (7 men, 26 women; 44.4 y old) with overweight/obesity [BMI (kg/m2) = 31.3] and prediabetes and/or metabolic syndrome completed this randomized, crossover, controlled-feeding trial consisting of two 28-d treatments (USDA-CON and USDA-LB) separated by a ≥14-day washout. Insulin sensitivity (primary outcome variable), lipoprotein lipids, apolipoproteins (apoA-I and apoB), and high-sensitivity C-reactive protein (hs-CRP) (secondary outcome variables), in plasma or serum, and blood pressures were assessed at baseline and the end of each diet period. RESULTS: USDA-LB and USDA-CON did not differ significantly in effects on whole-body insulin sensitivity and other indicators of carbohydrate metabolism, lipoprotein lipids, apoA-I and apoB, hs-CRP, and blood pressures. USDA-LB produced a shift toward less cholesterol carried by smaller LDL subfractions compared with USDA-CON [least-squares geometric mean ratios for LDL1+2 cholesterol of 1.20 (P = 0.016) and LDL3+4 cholesterol of 0.89 (P = 0.044)] and increased peak LDL time versus USDA-CON (1.01; P = 0.008). CONCLUSIONS: Substituting lean, unprocessed beef for carbohydrate in a Healthy US-Style Eating Pattern resulted in a shift toward larger, more buoyant LDL subfractions, but otherwise had no significant effects on the cardiometabolic risk factor profile in men and women with prediabetes and/or metabolic syndrome.This trial was registered at clinicaltrials.gov as NCT03202680.

Effects of substituting eggs for high-carbohydrate breakfast foods on the cardiometabolic risk-factor profile in adults at risk for type 2 diabetes mellitus.

OBJECTIVES: To assess effects of egg-based versus non-egg, higher-carbohydrate (CHO) breakfast meals on cardiometabolic health markers in overweight or obese adults with prediabetes and/or metabolic syndrome. METHODS: This randomized, crossover study included two 4-week dietary interventions, separated by a ≥4-week washout. Subjects incorporated into their habitual diets breakfast meals containing either 2 eggs/day for 6 days/week (Egg condition), or energy-matched, non-egg, higher-CHO-based foods (Non-Egg condition). Dietary intakes, insulin sensitivity, and other CHO metabolism indices, lipid biomarkers, high-sensitivity C-reactive protein, and blood pressures were measured. RESULTS: Thirty men and women with mean age 54.1 ± 1.9 years and body mass index 31.9 ± 0.7 kg/m2 provided data. Neither diet condition significantly altered insulin sensitivity indices, but the homeostasis model assessment for insulin resistance was significantly (p = 0.028) higher after the Non-Egg vs. the Egg condition. Low-density lipoprotein cholesterol (LDL-C) was decreased from baseline (119 mg/dL) by 2.9 and 6.0% with Egg and Non-Egg breakfasts, respectively (p = 0.023). Systolic blood pressure was reduced from baseline (127 mm Hg) by 2.7 and 0.0% with Egg and Non-Egg, respectively (p = 0.018). Diet records indicated 149 kcal/day higher (p = 0.008) energy intake from non-study foods during the Egg condition; however, weight change from baseline did not differ between conditions. CONCLUSION: Compared with the baseline diet, consumption of 12 eggs/week for 4 weeks at breakfast was associated with less reduction in LDL-C, and more lowering of systolic blood pressure, than observed with non-egg-based, energy-matched, control foods higher in CHO.

Effects of Consuming Almonds on Insulin Sensitivity and Other Cardiometabolic Health Markers in Adults With Prediabetes.

Objective: This study was designed to assess the effects of replacing high-carbohydrate (CHO) foods with raw almonds on insulin sensitivity and cardiometabolic health markers in overweight or obese adults with prediabetes.Method: This randomized crossover study consisted of two 6-week dietary intervention periods, separated by a ≥ 4-week washout. Subjects incorporated 1.5 oz of raw almonds twice daily or isocaloric CHO-based foods into their diets, with instructions to maintain body weight. Dietary intakes as well as insulin sensitivity, CHO metabolism indices, lipoprotein lipids and particles, and inflammatory markers were assessed.Results: Thirty-three subjects (17 male, 16 female), mean age 48.3 ± 2.2 years and body mass index 30.5 ± 0.7 kg/m2, provided evaluable data. Compared to CHO, almonds resulted in significantly (p < 0.01) higher intakes of protein, fat (unsaturated fatty acids), fiber, and magnesium and significantly (p < 0.001) lower intakes of CHO and sugars. No differences were observed between diet conditions for changes from baseline in the insulin sensitivity index from a short intravenous glucose tolerance test or other indices of glucose homeostasis. No significant differences were observed in biomarkers of cardiovascular risk except that the CHO intervention led to a shift toward a higher concentration of cholesterol in small, dense low-density lipoprotein subfraction 3+4 (LDL3 + 4) particles (p = 0.024 vs almonds).Conclusions: Intake of 3.0 oz/d raw almonds, vs energy-matched CHO foods, improved the dietary nutrient profile, but did not significantly affect insulin sensitivity and most markers of cardiometabolic health in overweight and obese men and women with prediabetes.

The Relationship between Whole Grain Intake and Body Weight: Results of Meta-Analyses of Observational Studies and Randomized Controlled Trials.

Results from some observational studies suggest that higher whole grain (WG) intake is associated with lower risk of weight gain. Ovid Medline was used to conduct a literature search for observational studies and randomized controlled trials (RCTs) assessing WG food intake and weight status in adults. A meta-regression analysis of cross-sectional data from 12 observational studies (136,834 subjects) and a meta-analysis of nine RCTs (973 subjects) was conducted; six prospective cohort publications were qualitatively reviewed. Cross-sectional data meta-regression results indicate a significant, inverse correlation between WG intake and body mass index (BMI): weighted slope, -0.0141 kg/m2 per g/day of WG intake (95% confidence interval (CI): -0.0207, -0.0077; r = -0.526, p = 0.0001). Prospective cohort results generally showed inverse associations between WG intake and weight change with typical follow-up periods of five to 20 years. RCT meta-analysis results show a nonsignificant pooled standardized effect size of -0.049 kg (95% CI -0.297, 0.199, p = 0.698) for mean difference in weight change (WG versus control interventions). Higher WG intake is significantly inversely associated with BMI in observational studies but not RCTs up to 16 weeks in length; RCTs with longer intervention periods are warranted.

Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol.

Background: Elevated low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Dietary guidance recommends reducing saturated fatty acid, trans fatty acid, and cholesterol intakes to reduce circulating LDL cholesterol. Cholesterol intake may also affect high-density lipoprotein (HDL)-cholesterol concentrations, but its impact has not been fully quantified. Objectives: The aims of this study were to investigate the dose-response relation between changes in dietary cholesterol intake and changes in lipoprotein-cholesterol markers for cardiovascular disease risk and to provide a reference for clinicians on how changes in dietary cholesterol intake affect circulating cholesterol concentrations, after accounting for intakes of fatty acids. Methods: We used a Bayesian approach to meta-regression analysis, which uses Markov chain Monte Carlo techniques, to assess the relation between the change in dietary cholesterol (adjusted for dietary fatty acids) and changes in LDL and HDL cholesterol based on the use of data from randomized dietary intervention trials. Results: Fifty-five studies (2652 subjects) were included in the analysis. The nonlinear Michaelis-Menten (MM) and Hill models best described the data across the full spectrum of dietary cholesterol changes studied (0-1500 mg/d). Mean predicted changes in LDL cholesterol for an increase of 100 mg dietary cholesterol/d were 1.90, 4.46, and 4.58 mg/dL for the linear, nonlinear MM, and Hill models, respectively. Conclusions: The change in dietary cholesterol was positively associated with the change in LDL-cholesterol concentration. The linear and MM models indicate that the change in dietary cholesterol is modestly inversely related to the change in circulating HDL-cholesterol concentrations in men but is positively related in women. The clinical implications of HDL-cholesterol changes associated with dietary cholesterol remain uncertain.

Diet and prevention of type 2 diabetes mellitus: beyond weight loss and exercise.

INTRODUCTION: Insulin resistance (IR) and pancreatic beta-cell dysfunction are core pathophysiologic features of type 2 diabetes mellitus (T2DM). Select lifestyle and pharmacologic interventions, including weight loss, physical activity, a Mediterranean diet intervention, and hypoglycemic agents, have been shown to prevent or delay T2DM. However, dietary factors other than weight loss may also impact risk, mainly through effects to enhance insulin sensitivity, although some may also directly or indirectly impact pancreatic beta-cell function. AREAS COVERED: A literature review of observational studies and randomized controlled trials (RCTs) was conducted, and the research indicates dietary factors showing promise for reducing T2DM risk include higher intakes of cereal fibers, unsaturated fatty acids, magnesium, and polyphenols (e.g. anthocyanins), while reducing dietary glycemic load, added sugars, and high-sugar beverages. EXPERT COMMENTARY: While these dietary factors are mainly supported by evidence from observational studies and RCTs of surrogate markers for T2DM, they are consistent with current recommendations to emphasize consumption of whole grains, nuts, seeds, legumes, seafood, fruits, and vegetables, while limiting intakes of saturated fatty acids, refined carbohydrates, and processed meats. Additional dietary intervention RCTs are needed to assess the efficacy of these promising dietary interventions for delaying or preventing the onset of T2DM.

Effects of a Self-micro-emulsifying Delivery System Formulation Versus a Standard ω-3 Acid Ethyl Ester Product on the Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid: A Study in Healthy Men and Women in a Fasted State.

PURPOSE: Intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with several potential health benefits, but standard ethyl ester (EE) formulations of these ω-3 fatty acids require the co-ingestion of fat for adequate absorption. The objective of this research was to assess the relative bioavailability of EPA and DHA administered in a proprietary self-micro-emulsifying delivery system (SMEDS) formulation compared with EPA and DHA in a standard ω-3 acid EE product in healthy men and women in a fasted state. METHODS: This randomized crossover study investigated the bioavailability of 2 encapsulated formulations of EPA and DHA, a capsule containing 500 mg EPA + DHA administered in a SMEDS formulation (SMEDS treatment), and a capsule containing 840 mg EPA + DHA in a standard ω-3 acid EE formulation (EE treatment). Subjects consumed a single dose of their assigned capsule in a fasting state, and plasma was collected before and for 24 h after dosing. Subjects underwent a ≥14-day washout and were crossed over to the other treatment condition. Plasma concentrations of EPA, DHA, and EPA + DHA were assessed. FINDINGS: Twenty-three subjects (11 women, 12 men; mean [SEM] age, 33.8 [2.1] years; and body mass index, 24.9 [0.7] kg/m2) completed the trial. The baseline-adjusted, dose-normalized, arithmetic means (SD) of the incremental (i)-AUC0-24h for EPA + DHA were 543 (266) and 102 (88.2) h · µg/mL/g for the SMEDS and EE formulations, respectively (P < 0.001). The iAUC0-24h least-squares geometric mean ratio (90% CI) for SMEDS:standard EE was 475/58 = 8.2 (4.8-13.9), indicating markedly higher bioavailability of EPA + DHA with the SMEDS formulation compared to the standard EE formulation. This finding was also true for EPA (geometric mean ratio [90% CI], 18.2 [11.3-29.3]) and DHA (geometric mean ratio [90% CI], 4.5 [2.9-7.0]). IMPLICATIONS: The SMEDS delivery system markedly enhanced appearance in plasma of EPA and DHA, compared to a standard EE formulation, when ingested in the fasting state. ClinicalTrials.gov identifier: NCT03443076.

A Lean Pork-Containing Breakfast Reduces Hunger and Glycemic Response Compared to a Refined Carbohydrate-Containing Breakfast in Adults with Prediabetes.

OBJECTIVE: Replacing dietary refined carbohydrates (CHO) with protein may impact appetite and glucose and lipid metabolism in metabolically at-risk individuals. The objectives of this study were to assess the effects of consumption of a lean pork-containing, high-protein (pPro) breakfast versus a refined-CHO-rich breakfast for 2 weeks on appetite and cardiometabolic parameters in overweight or obese adults with prediabetes. METHODS: In this crossover study, overweight or obese men and women with prediabetes were provided with either a pPro breakfast meal or a refined-CHO breakfast meal to consume each day (2-week intervention, ≥ 2-week washout). On the last day of each period, fasting and postprandial glucose, insulin, and lipid values were assessed. Visual analog scales were used to evaluate appetite, mental energy, and focus; energy intake at a lunch meal was also evaluated. RESULTS: Data from 21 participants (13 females and 8 males) were analyzed and participants had a mean (± standard error of the mean) age of 44.4 ± 3.1 years and body mass index of 30.4 ± 0.9 kg/m2. Mean hunger net incremental area under the curve to 240 minutes postmeal (niAUC0-240 min) and desire to eat niAUC0-240 min were both significantly (p < 0.05) lower following the pPro breakfast intakes compared to the refined-CHO breakfast intakes. Mean incremental area under the curve to 240 minutes postmeal for glucose and insulin were significantly lower (p = 0.003 and p = 0.001, respectively) following the pPro breakfast versus refined-CHO breakfast, and mean percentage change from baseline for triglycerides (TG) at 120 minutes was also less pronounced, 10.0% ± 6.8% versus 32.3% ± 7.7%, respectively (p = 0.001). No other significant differences were observed for outcome variables. CONCLUSIONS: Intake of a higher-protein, lean pork-containing breakfast may favorably impact appetite and lower postprandial glucose, insulin, and TG values, although longer-term studies are warranted.

Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: An updated meta-analysis and review of research gaps.

BACKGROUND: Randomized controlled trials (RCTs) assessing use of long-chain omega-3 polyunsaturated fatty acids (LC-OM3), primarily eicosapentaenoic acid, and/or docosahexaenoic acid have shown mixed results. OBJECTIVE: The objectives of the study were to update and further explore the available RCT data regarding LC-OM3 supplementation and risk for cardiac death and to propose testable hypotheses for the mixed results obtained in RCTs regarding supplemental LC-OM3 use and cardiac risk. METHODS: A literature search was conducted using PubMed and Ovid/MEDLINE for RCTs assessing LC-OM3 supplements or pharmaceuticals with intervention periods of at least 6 months and reporting on the outcome of cardiac death. Meta-analysis was used to compare cumulative frequencies of cardiac death events between the LC-OM3 and control groups, including sensitivity and subset analyses. RESULTS: Fourteen RCTs were identified for the primary analysis (71,899 subjects). In the LC-OM3 arms, 1613 cardiac deaths were recorded (4.48% of subjects), compared with 1746 cardiac deaths in the control groups (4.87% of subjects). The pooled relative risk estimate showed an 8.0% (95% confidence interval 1.6%, 13.9%, P = .015) lower risk in the LC-OM3 arms vs controls. Subset analyses showed numerically larger effects (12.9%-29.1% lower risks, all P < .05) in subsets of RCTs with eicosapentaenoic acid + docosahexaenoic acid dosages >1 g/d and higher risk samples (secondary prevention, baseline mean or median triglycerides ≥150 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, statin use <40% of subjects). Heterogeneity was low (I2 ≤ 15.5%, P > .05) for the primary and subset analyses. CONCLUSION: LC-OM3 supplementation is associated with a modest reduction in cardiac death.

Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides.

Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles.Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations.Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (∼8% of energy) and vegetable oil (∼8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (∼16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA.Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m2), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042) and LDL peak particle size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18.5% (-35.7%, -6.9%) and 18.6% (-34.8%, -7.4%), respectively, after the Epro and UFA condition and by 2.5% (-13.4%, 17.0%) and 3.6% (-12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002).Conclusions: The replacement of refined carbohydrates with a combination of Epro and UFA increased the MISI value and altered several markers of cardiometabolic health in overweight or obese adults with elevated TG concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.

NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10.

A member of the sirtuin family of NAD(+)-dependent deacetylases, SIRT3, is located in mammalian mitochondria and is important for regulation of mitochondrial metabolism, cell survival, and longevity. In this study, MRPL10 (mitochondrial ribosomal protein L10) was identified as the major acetylated protein in the mitochondrial ribosome. Ribosome-associated SIRT3 was found to be responsible for deacetylation of MRPL10 in an NAD(+)-dependent manner. We mapped the acetylated Lys residues by tandem mass spectrometry and determined the role of these residues in acetylation of MRPL10 by site-directed mutagenesis. Furthermore, we observed that the increased acetylation of MRPL10 led to an increase in translational activity of mitochondrial ribosomes in Sirt3(-/-) mice. In a similar manner, ectopic expression and knockdown of SIRT3 in C2C12 cells resulted in the suppression and enhancement of mitochondrial protein synthesis, respectively. Our findings constitute the first evidence for the regulation of mitochondrial protein synthesis by the reversible acetylation of the mitochondrial ribosome and characterize MRPL10 as a novel substrate of the NAD(+)-dependent deacetylase, SIRT3.

Measuring acceptance of milk and milk substitutes among younger and older children.

Appropriate nutrient-dense foods and beverages are crucial for children for proper growth and development and to develop healthful lifelong habits. This study investigated children's (ages 8 to 16 y old) perception of sensory intensity, attribute liking and overall liking of unflavored and chocolate lactose-free cow's milk and soy beverages. Products were not identified as to whether they were soy or milk. Children showed greater acceptance of lactose-free cow's milk compared to milk substitute beverages, within flavor category. No differences in acceptance emerged by ethnic group (Caucasian, African American, Hispanic), but a large difference emerged by age group. All product acceptance differences perceived by older children reoccurred among the younger children and in the same direction, but the older children used a larger range of numbers, especially at the lower end, rather than at the higher end of acceptance. The effect of age is not a simple scaling bias but may suggest a reduced criticism by younger respondents of less-acceptable products.

Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle.

SIRT3 is a member of the sirtuin family of NAD(+)-dependent deacetylases, which is localized to the mitochondria and is enriched in kidney, brown adipose tissue, heart, and other metabolically active tissues. We report here that SIRT3 responds dynamically to both exercise and nutritional signals in skeletal muscle to coordinate downstream molecular responses. We show that exercise training increases SIRT3 expression as well as associated CREB phosphorylation and PGC-1alpha up-regulation. Furthermore, we show that SIRT3 is more highly expressed in slow oxidative type I soleus muscle compared to fast type II extensor digitorum longus or gastrocnemius muscles. Additionally, we find that SIRT3 protein levels in skeletal muscle are sensitive to diet, for SIRT3 expression increases by fasting and caloric restriction, yet it is decreased by high-fat diet. Interestingly, the caloric restriction regimen also leads to phospho-activation of AMPK in muscle. Conversely in SIRT3 knockout mice, we find that the phosphorylation of both AMPK and CREB and the expression of PGC-1alpha are down regulated, suggesting that these key cellular factors may be important components of SIRT3-mediated biological signals in vivo.