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Kevin C Maki,1 Tia M Rains,1 Arianne L Schild,1 Mary R Dicklin,1 Keigan M Park,2 Andrea L Lawless,1 Kathleen M Kelley1 1Biofortis Clinical Research, Addison, IL, USA; 2Dairy Research Institute/National Dairy Council, Rosemont, IL, USA Objective: This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt) versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar) on systolic and diastolic blood pressures (SBP and DBP), vascular function (reactive hyperemia index [RHI] and augmentation index), and plasma lipids. Methods: Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m2) with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg) while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period. Results: Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg), premeal (2.35 versus 2.20) or 2 hours postmeal (2.33 versus 2.30) RHI, and premeal (22.5 versus 23.8) or 2 hours postmeal (12.4 versus 13.2) augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14) during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002). Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses. Conclusion: No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses were consistent with the hypothesis that dairy foods might improve RHI in those with endothelial dysfunction. Keywords: blood pressure, dairy, endothelial function, hypertension, lipids

Kevin C Maki1, Mary R Dicklin1, Michael H Davidson2, Patrick D Mize3, Krishnaji R Kulkarni31Provident Clinical Research/Biofortis North America, Glen Ellyn, IL, 2The University of Chicago Pritzker School of Medicine, Chicago, IL, 3Atherotech, Birmingham, AL, USAObjective: Progression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis.Methods: The study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common CIMT in men (45–75 years of age) and women (55–74 years of age) in the control arm of a clinical trial. Participants had baseline posterior wall CIMT 0.7–2.0 mm, without significant stenosis. CIMT was assessed using B-mode ultrasound at baseline, and 12 and ~18 months. A DGU cholesterol panel that assessed the major lipoprotein classes and subclasses, plus triglycerides, lipoprotein (a) cholesterol, low-density lipoprotein (LDL) peak time (inversely related to LDL particle density), and Apo B were performed on fasting baseline samples. Apo B was also measured using an enzyme linked immunosorbent assay.Results: Baseline CIMT was inversely associated (P < 0.001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of posterior wall CIMT progression in linear regression analyses included LDL peak time (inverse, P = 0.045), total high-density lipoprotein cholesterol (HDL-C) (inverse, P = 0.001), HDL2-C (inverse, P = 0.005), HDL3-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL1+2-C (P = 0.016).Conclusion: These data indicate that DGU-derived indicators of the “atherogenic lipoprotein phenotype,” including increased TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and a greater proportion of LDL-C carried by more dense LDL particles, are associated with CIMT progression in men and women at moderate risk for coronary heart disease.Keywords: carotid intima media thickness, density gradient ultracentrifugation, coronary heart disease risk, lipids, atherosclerosis, lipoprotein subfractions

This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (S(I)) in participants with waist circumference ≥89 (women) or ≥102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model S(I) was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean ± SEM) age 49.5 ± 1.6 y, with a BMI of 30.6 ± 0.5 kg/m2 and waist circumference 105.3 ± 1.3 cm. A treatment main effect (P = 0.018) and a treatment × sex interaction (P = 0.033) were present. In men, least squares geometric mean analysis for S(I) did not differ after intake of 15 g/d HAM-RS2 (6.90 × 10⁻⁵ pmol⁻¹ · L⁻¹ × min⁻¹) and 30 g/d HAM-RS2 (7.13 × 10⁻⁵ pmol⁻¹ · L⁻¹ × min⁻¹), but both were higher than after the control treatment (4.66 × 10⁻⁵ pmol⁻¹ · L⁻¹ × min⁻¹) (P < 0.05). In women, there was no difference among the treatments (overall least squares ln-transformed mean ± pooled SEM = 1.80 ± 0.08; geometric mean = 6.05 × 10⁻⁵ pmol⁻¹ · L⁻¹ × min⁻¹). These results suggest that consumption of 15-30 g/d of HAM-RS2 improves S(I) in men. Additional research is needed to understand the mechanisms that might account for the treatment × sex interaction observed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose fiber that produces a viscous gel in the gastrointestinal tract. Clinical trials demonstrate that consumption of HV-HPMC significantly lowers cholesterol, but limited information has been available on the influence of HV-HPMC on postprandial insulin and glucose responses. The objective of this investigation was to assess the influence of HV-HPMC on postprandial glucose and insulin responses in overweight and obese men and women. RESEARCH DESIGN AND METHODS: Participants were 31 overweight or obese men and women without diabetes who underwent three breakfast meal tests in random order, separated by > or = 72 h. Test meals containing 75 g carbohydrate plus 4 or 8 g HV-HPMC or control meals containing 8 g cellulose were delivered in a double-blind fashion. RESULTS: Peak glucose was significantly lower (P < 0.001) after both HV-HPMC-containing meals (7.4 mmol/l [4 g] and 7.4 mmol/l [8 g]) compared with the control meal (8.6 mmol/l). Peak insulin concentrations and the incremental areas for glucose and insulin from 0 to 120 min were also significantly reduced after both HV-HPMC doses versus control (all P < 0.01). CONCLUSIONS: These findings indicate that HV-HPMC consumption reduces postprandial glucose and insulin excursions, which may favorably alter risks for diabetes and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the effects of colesevelam on plasma lipids. aortic plaque area, and reverse cholesterol transport enzymes and genes in a rabbit model of atherosclerosis. Methods: Thirty New Zealand white rabbits were fed standard chow for 1 week, placed on a 0,5% cholesterol diet for 2 weeks, then randomized equally to receive either the 0.5% cholesterol diet (control) or the 0.5% cholesterol diet with 1.5 g of colesevelam for 11 weeks. Serum total cholesterol and high density lipoprotein cholesterol concentrations and lecithin-cholesterol acythansferase (LCAT) activity were measured before randomization and at treatment endpoint. Rabbits were killed and plaque area was measured in one aorta segment. Gene expression was measured by reverse transcription polymerase chain reaction in liver RNA extracts. Results: Colesevelam markedly reduced the circulating cholesterol concentration and decreased plaque area by 81% compared with controls (P<0.001). LCAT fractional rate was markedly increased versus controls (12.6% and 0.2%. respectively: P<0.001). Colesevelam enhanced fecal cholesterol concentrations more than two-fold. Colesevelam significantly increased hepatic gene expression for scavenger receptor type BI, apolipoprotein A1, LCAT. cholesterol ester transfer protein, cholesterol 7-[alpha]-hydroxylase (CYP7A1), low-density lipoprotein receptor, and liver X receptor (LXR). Conclusions: In cholesterol-fed rabbits, colesevelam reduced atherosclerosis through cholesterol lowering and potentially by enhancing reverse cholesterol transport, mediated by changes in LXR-regulated proteins. [ABSTRACT FROM AUTHOR]

Seven subjects with chronic paralysis due to spinal cord injury completed a series of experiments to 1) determine and compare the metabolic cost of propelling the Handbike and Rowcycle, and 2) evaluate the potential of these upper body-powered devices for improving the cardiorespiratory fitness of persons with lower limb disabilities. Mean intrasubject differences between the Handbike and Rowcycle rides for heart rate, minute ventilation, oxygen uptake, and net locomotive energy cost were small and did not reach statistical significance for any of the ride conditions. Lower net locomotive energy cost (greater economy) during a 5.5 mi-hr(-1) ride condition predicted vehicle preference in all cases (P=0.008). The range of values for percent peak oxygen uptake suggests that all but one of the subjects were able to utilize either vehicle at an intensity sufficient for improving and maintaining cardiorespiratory fitness without undue fatigue. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol (HDL-C) levels in atorvastatin-treated patients with elevated non-HDL-C and triglyceride levels.Patients and Methods: This study, conducted between February 15, 2007, and October 22, 2007, randomized patients with elevated non-HDL-C (>160 mg/dL) and triglyceride (>or=250 mg/dL and Results: Prescription omega-3-acid ethyl esters plus atorvastatin, 10, 20, and 40 mg/d, reduced median non-HDL-C levels by 40.2% vs 33.7% (P<.001), 46.9% vs 39.0% (P<.001), and 50.4% vs 46.3% (P<.001) compared with placebo plus the same doses of atorvastatin at the end of 8, 12, and 16 weeks, respectively. Prescription omega-3-acid ethyl esters plus atorvastatin also reduced median total cholesterol, triglyceride, and very low-density lipoprotein cholesterol levels and increased HDL-C levels to a significantly greater extent than placebo plus atorvastatin. Percent changes from baseline low-density lipoprotein-cholesterol, apolipoprotein A-I, and apolipoprotein B levels were not significantly different between groups at the end of the study.Conclusion: Prescription omega-3-acid ethyl esters plus atorvastatin produced significant improvements in non-HDL-C and other lipid parameters in patients with elevated non-HDL-C and triglyceride levels. [ABSTRACT FROM AUTHOR]

Protein is the most thermogenic macronutrient, but it is unclear how different amounts and types of protein impact diet-induced thermogenesis (DIT). The purpose of this meta-analysis was to compare the impact of isocaloric meals/diets containing different amounts or types of protein on energy metabolism. Databases were searched in June 2024 for studies that compare DIT or total daily energy expenditure (TDEE) in response to isocaloric acute meals or longer-term diets containing different amounts or types of protein. After identifying 3894 records, 52 studies were included. Standardized mean difference (SMD) estimates and 95% confidence intervals (CIs) were calculated for each outcome. In acute studies, intake of higher compared with lower-protein meals resulted in greater DIT (SMD: 0.45; 95% CI: 0.26, 0.65; P < 0.001) and TDEE (SMD: 0.52; 95% CI: 0.30, 0.73; P < 0.001). Notably, the subgroup analysis indicated that this effect on DIT was statistically significant for studies involving participants with normal weight but not overweight/obesity, although it is not clear if this finding was a true effect or because of study design characteristics. In chronic studies (ranging from 4 d to 1 y), intake of higher compared with lower-protein diets resulted in greater TDEE (SMD: 0.29; 95% CI: 0.10, 0.48; P = 0.003) and resting energy expenditure (SMD: 0.18; 95% CI: 0.01, 0.35; P = 0.039), but no differences in DIT (SMD: 0.10; 95% CI: -0.08, 0.28; P = 0.27). There was no evidence that different types of protein impacted energy metabolism. Higher protein meals/diets increase components of energy expenditure. This trial was registered at the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero; PROSPERO 2023) as CRD42023389642., Competing Interests: Conflict of interest As employees of Midwest Biomedical Research, LLG, CGA, MLW, and KCM have received funding and/or consulting fees in the last 24 mo from 89bio, Inc., Acasti Pharma Inc., Beren Therapeutics, Bragg Live Products, Campbell’s, Cargill, Eli Lilly and Company, General Mills, Greenyn Biotechnology, Hass Avocado Board, Helaina Inc., Indiana University Foundation, Matinas BioPharma, Medifast, National Cattlemen’s Beef Association, National Dairy Council, Naturmega, New Amsterdam Pharma, NeuroEnergy VenturesPepsiCo, Pharmavite, and Seed. KK and BG-J are employees of General Mills and had a role in the conceptualization of the study, the analysis, and contributed to the decision to submit the manuscript for publication. The authors declare no additional conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk., Methods: This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership., Results: Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles., Conclusions: Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD., (© 2024 The Author(s).)

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Therapeutic agents, such as those that lower low-density lipoprotein cholesterol, have been a critical factor in mitigating CVD event risk and demonstrate the important role that drug discovery plays in reducing morbidity and mortality. However, rapidly rising development costs, diminishing returns, and an increasingly challenging regulatory environment have all contributed to a declining number of cardiovascular (CV) therapeutic agents entering the health care marketplace. For pharmaceutical companies, a traditional cardiovascular outcomes trial (CVOT) can be a major financial burden and impediment to CV agent development. They can take as long as a decade to conduct, delaying potential investment return while carrying risk of failure. For patients, lengthy CVOTs delay drug accessibility. Without cost-effective CVOTs, drug innovation may be compromised, with CV patients bearing the consequences. This paper reviews potential approaches for making CV drug development more cost-effective., Competing Interests: Dr Davidson is the Chief Executive Officer of NewAmsterdam Pharma and holds stock or stock options. Dr Hsieh is the Executive Director of Research and Development of NewAmsterdam Pharma and holds stock or stock options. Drs Ducjkub abd Naju are employees of Midwest Biomedical Research, which has received consulting fees and grant funding from NewAmsterdam Pharma, Acasti Pharma, Beren Therapeutics, Eli Lilly and Company, Indiana University and Foundation, Matinas BioPharma, NorthSea Therapeutics, and 89Bio., (© 2024 The Authors.)

Objective: There is substantial inter-individual variability in response to weight loss interventions and emerging evidence suggests that weight loss during the early weeks of an intervention may be predictive of longer-term weight loss. This secondary analysis of data from a commercial program therefore examined 1) the associations between early weight loss (i.e., week 4) with final visit weight loss and duration on the program, and 2) other predictors of lower weight loss at final visit., Methods: Client charts of adults with overweight or obesity ( N  = 748) were analyzed. Clients were stratified into categories of weight loss at the week 4 (< and ≥2%, 3% and 4%) and final visits (< and ≥5% and 10%). Multivariate logistic regression was used to assess predictors of <5% and <10% final visit weight loss., Results: The odds ratios for losing <5% or <10% of weight at the final visit were higher (49.0 (95% CI: 13.84, 173.63) and 20.1 (95% CI: 6.96, 58.06)) for clients who lost <2% or <3% compared to those who lost ≥2% or ≥3% at week 4. Other predictors of not losing a clinically relevant amount of weight included female sex, use of higher calorie meal plans and shorter time in the program, among others. Those who lost ≥2% at week 4 also had a significantly greater percent program completion (109.2 ± 75.2% vs. 82.3 ± 82.4, p  < 0.01) compared with those who did not meet the 2% threshold., Conclusions: Lower 4-week weight loss was identified as a strong predictor of not losing a clinically relevant amount of weight. These results may be useful for the early identification of individuals who can be targeted for additional counseling and support to aid in attaining weight loss goals., Competing Interests: CDC, JRK, and SSJ are employees of Medifast, Inc. JLU is a member of the Medifast Scientific Advisory Board and receives consulting fees associated with that appointment. Within the prior 24 months, KCM has received consulting fees from entities that provide products or services related to weight management, including Medifast, Eli Lilly, Pharmavite, General Mills, and 89Bio; he also has current research grant funding from the National Dairy Council, Hass Avocado Board, Greenyn, the Indiana University Foundation, Naturmega, Cargill, and National Cattlemen's Beef Association. MLW and LLG are employees of and MB is a contractor for Midwest Biomedical Research, which has received consulting fees from entities that provide products or services related to weight management, including Medifast, Eli Lilly, Pharmavite, General Mills, and 89Bio., (© 2023 Jason Pharmaceuticals, Inc and The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Results from observational studies indicate that consumption of ready-to-eat cereal (RTEC) is associated with higher diet quality and lower incidence of overweight and obesity in adults compared with other breakfasts or skipping breakfast. However, randomized controlled trials (RCTs) have had inconsistent results regarding effects of RTEC consumption on body weight and composition. This systematic review aimed to evaluate the effect of RTEC intake on body weight outcomes in observational studies and RCTs in adults. A search of PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases yielded 28 relevant studies, including 14 observational studies and 14 RCTs. Results from observational studies demonstrate that frequent RTEC consumers (usually ≥4 servings/wk) have lower BMI, lower prevalence of overweight/obesity, less weight gain over time, and less anthropometric evidence of abdominal adiposity compared with nonconsumers, or less frequent consumers. RCT results suggest that RTEC may be used as a meal or snack replacement as part of a hypocaloric diet, but this approach is not superior to other options for those attempting to achieve an energy deficit. In addition, RTEC consumption was not associated with significantly less loss of body weight, or with weight gain, in any of the RCTs. RTEC intake is associated with favorable body weight outcomes in adults in observational studies. RTEC does not hinder weight loss when used as a meal or snack replacement within a hypocaloric diet. Additional long-term RCTs (≥6 mo) in both hypocaloric and ad libitum conditions are recommended to evaluate further the potential effects of RTEC consumption on body weight outcomes. PROSPERO (CRD42022311805)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chickpeas are an affordable and nutrient-dense legume, but there is limited United States data on consumption patterns and the relationship between chickpea consumption and dietary intakes., Objectives: This study examined trends and sociodemographic patterns among chickpea consumers and the relationship between chickpea consumption and dietary intake., Methods: Adults consuming chickpeas or chickpea-containing foods on 1 or both of the 24-h dietary recalls were categorized as chickpea consumers. Data from NHANES 2003-2018 were used to evaluate trends and sociodemographic patterns in chickpea consumption (n = 35,029). The association between chickpea consumption and dietary intakes was compared to other legume consumers and nonlegume consumers from 2015-2018 (n = 8,342)., Results: The proportion of chickpea consumers increased from 1.9% in 2003-2006 to 4.5% in 2015-2018 (P value for trend < 0.001). This trend was consistent across age group, sex, race/ethnicity, education, and income. In 2015-2018, chickpea consumption was highest among individuals with higher incomes (2.4% among those with incomes <185% of the federal poverty guideline compared with 6.4% with incomes ≥300%), education levels (1.0% for less than high school compared with 10.2% for college graduates), physical activity levels (1.9% for no physical activity compared with 7.7% for ≥430 min of moderate-equivalent physical activity per week), and those with better self-reported health (1.7% fair/poor compared with 6.5% for excellent/very good, P-trend < 0.001 for each). Chickpea consumers had greater intakes of whole grains (1.48 oz/d for chickpea consumers compared with 0.91 for nonlegume consumers) and nuts/seeds (1.47 compared with 0.72 oz/d), less intake of red meat (0.96 compared with 1.55 oz/d), and higher Healthy Eating Index scores (62.1 compared with 51.2) compared with both nonlegume and other legume consumers (P value < 0.05 for each)., Conclusions: Chickpea consumption among United States adults has doubled between 2003 and 2018, yet intake remains low. Chickpea consumers have higher socioeconomic status and better health status, and their overall diets are more consistent with a healthy dietary pattern., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Results from observational studies suggest that children and adolescents consuming ready-to-eat cereals (RTECs) have a healthier BMI and lower odds of overweight and obesity than consumers of other breakfasts or breakfast skippers. However, randomized controlled trials in children and adolescents are few and have been inconsistent in demonstrating a causal relationship between RTEC intake and body weight or body composition. The objective of this study was to evaluate the effect of RTEC intake on body weight and body composition outcomes in children and adolescents. Prospective cohort, cross-sectional and controlled trials in children or adolescents were included. Retrospective studies and studies in subjects with disease, other than obesity, type-2 diabetes (T2D), metabolic syndrome, or prediabetes, were excluded. A search in PubMed and CENTRAL databases yielded 25 relevant studies, which were qualitatively analyzed. Fourteen of the 20 observational studies demonstrated that children and adolescents consuming RTEC have a lower BMI, lower prevalence and odds of overweight/obesity and more favorable indicators of abdominal obesity than nonconsumers or less frequent consumers. Controlled trials were few and only one reported a loss of 0.9 kg in overweight/obese children with RTEC consumption when accompanied by nutrition education. The risk of bias was low for most studies, but six had some concerns or high risk. The results were similar with presweetened and nonpresweetened RTEC. No studies reported a positive association of RTEC intake with body weight or body composition. Although controlled trials do not show a direct effect of RTEC consumption on body weight or body composition, the preponderance of observational data supports the inclusion of RTEC as part of a healthy dietary pattern for children and adolescents. Evidence also suggests similar benefits on body weight and body composition regardless of the sugar content. Additional trials are needed to determine the causality between RTEC intake and body weight and body composition outcomes. PROSPERO REGISTRATION: CRD42022311805., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest: K.C.M. and M.R.D. received no funding for the preparation of this manuscript, but K.C.M. received honoraria for giving invited presentations on this topic at the European Atherosclerosis Society 2022 Congress and the National Lipid Association 2022 Scientific Sessions. KCM discloses that he has received consulting fees from 89bio, New Amsterdam Pharma and Pepsico; research grants from Cargill, Hass Avocado Board and Indiana University Foundation; and both consulting fees and research grants from Acasti Pharma, Eli Lilly and Company, General Mills, Kellogg, Matinas BioPharma, National Cattlemen’s Beef Association, National Dairy Council and Pharmavite. As an employee of Midwest Biomedical Research, M.R.D. has received consulting fees from New Amsterdam Pharma and Pepsico and research grants from Cargill, Hass Avocado Board, Indiana University Foundation, Acasti Pharma, Eli Lilly and Company, General Mills, Kellogg, Matinas BioPharma, National Cattlemen’s Beef Association, National Dairy Council and Pharmavite.

Background MAT9001 is an omega-3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA-ethyl esters [EE]), EPA+DPA-FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very-low fat diet. This trial compared pharmacodynamic responses and plasma omega-3 levels following twice daily dosing, with meals, of EPA+DPA-FFA and EPA-EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. Methods and Results This open-label, randomized, 2-way crossover trial, with 28-day treatment periods separated by ≥28-day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150-499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA-FFA and EPA-EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively ( P =not significant). EPA+DPA-FFA reduced least squares geometric mean high-sensitivity C-reactive protein by 5.8%; EPA-EE increased high-sensitivity C-reactive protein by 8.5% ( P =0.034). EPA+DPA-FFA increased least squares geometric mean plasma EPA, DPA, and total omega-3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA-EE of 692%, 140%, and 165% (all P <0.001). EPA+DPA-FFA increased docosahexaenoic acid by 1.7%; EPA-EE decreased docosahexaenoic acid by 3.3% ( P =0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments. Conclusions EPA+DPA-FFA raised plasma EPA, DPA, and total omega-3 significantly more than did EPA-EE. EPA+DPA-FFA also reduced triglycerides and high-sensitivity C-reactive protein without increasing low-density lipoprotein cholesterol. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04177680.

Despite medical, dietary, and lifestyle recommendations and drug advancements, hypertension persists as among the most prevalent noncommunicable diseases in the US population, and control remains elusive. Uncontrolled hypertension may increase the risk of serious illness from various other health challenges, including cardiovascular and renal responses. Adoption of a healthy diet is a consistent core element of lifestyle modifications that are recommended for mitigation of hypertension. The dietary sodium-to-potassium ratio is recognized as having promising potential in the regulation of blood pressure. In fact, the understanding of the relation between this ratio and blood pressure was documented as a key evidence gap in the 2019 National Academies of Sciences, Engineering, and Medicine report that revised recommended intake levels for both sodium and potassium. Although notable animal and human evidence supports this point, fundamental to developing a specific dietary recommendation for a sodium-to-potassium ratio is a well-designed human intervention trial. The successful translatability of such a trial will require careful consideration of study elements, including the study population, duration, blood pressure measurement, and dietary intervention, among other factors. This paper addresses these decision points and serves as supporting documentation for a research group or organization with the interest and means to address this important data gap, which will undoubtedly be foundational for advancing dietary guidance and would inform the next iteration of Dietary Reference Intakes for sodium and potassium., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

Background: Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD., Methods: The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined., Results: The meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16., Conclusions: These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD., (© 2022. The Author(s).)

Importance: Intense interest exists in novel ω-3 formulations with high bioavailability to reduce blood triglyceride (TG) levels., Objective: To determine the phase 3 efficacy and safety of a naturally derived krill oil with eicosapentaenoic acid and docosahexaenoic acid as both phospholipid esters (PLs) and free fatty acids (FFAs) (ω-3-PL/FFA [CaPre]), measured by fasting TG levels and other lipid parameters in severe hypertriglyceridemia., Design, Setting, and Participants: This study pooled the results of 2 identical randomized, double-blind, placebo-controlled trials. TRILOGY 1 (Study of CaPre in Lowering Very High Triglycerides) enrolled participants at 71 US centers from January 23, 2018, to November 20, 2019; TRILOGY 2 enrolled participants at 93 US, Canadian, and Mexican centers from April 6, 2018, to January 9, 2020. Patients with fasting TG levels from 500 to 1500 mg/dL, with or without stable treatment with statins, fibrates, or other agents to lower cholesterol levels, were eligible to participate., Interventions: Randomization (2.5:1.0) to ω-3-PL/FFA, 4 g/d, vs placebo (cornstarch) for 26 weeks., Main Outcomes and Measures: The primary outcome was the mean percentage of change in TG levels at 12 weeks; persistence at 26 weeks was the key secondary outcome. Other prespecified secondary outcomes were effects on levels of non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), HDL-C, and low-density lipoprotein cholesterol (LDL-C); safety and tolerability; and TG level changes in prespecified subgroups., Results: A total of 520 patients were randomized, with a mean (SD) age of 54.9 (11.2) years (339 men [65.2%]), mean (SD) body mass index of 31.5 (5.1), and baseline mean (SD) TG level of 701 (222) mg/dL. Two hundred fifty-six patients (49.2%) were of Hispanic or Latino ethnicity; 275 (52.9%) had diabetes; and 248 (47.7%) were receiving statins. In the intention-to-treat analysis, TG levels were reduced by 26.0% (95% CI, 20.5%-31.5%) in the ω-3-PL/FFA group and 15.1% (95% CI, 6.6%-23.5%) in the placebo group at 12 weeks (mean treatment difference, -10.9% [95% CI, -20.4% to -1.5%]; P = .02), with reductions persisting at 26 weeks (mean treatment difference, -12.7% [95% CI, -23.1% to -2.4%]; P = .02). Compared with placebo, ω-3-PL/FFA had no significant effect at 12 weeks on mean treatment differences for non-HDL-C (-3.2% [95% CI, -8.0% to 1.6%]; P = .18), VLDL-C (-3.8% [95% CI, -12.2% to 4.7%]; P = .38), HDL-C (0.7% [95% CI, -3.7% to 5.1%]; P = .77), or LDL-C (4.5% [95% CI, -5.9% to 14.8%]; P = .40) levels; corresponding differences at 26 weeks were -5.8% (95% CI, -11.3% to -0.3%; P = .04) for non-HDL-C levels, -9.1% (95% CI, -21.5% to 3.2%; P = .15) for VLDL-C levels, 1.9% (95% CI, -4.8% to 8.6%; P = .57) for HDL-C levels, and 6.3% (95% CI, -12.4% to 25.0%; P = .51) for LDL-C levels. Effects on the primary end point did not vary significantly by age, sex, race and ethnicity, country, qualifying TG level, diabetes, or fibrate use but tended to be larger among patients taking statins or cholesterol absorption inhibitors at baseline (mean treatment difference, -19.5% [95% CI, -34.5% to -4.6%]; P = .08 for interaction) and with lower (less than median) baseline blood eicosapentaenoic acid plus docosahexaenoic acid levels (-19.5% [95% CI, -33.8% to -5.3%]; P = .08 for interaction). ω-3-PL/FFA was well tolerated, with a safety profile similar to that of placebo., Conclusions and Relevance: This study found that ω-3 -PL/FFA, a novel krill oil-derived ω-3 formulation, reduced TG levels and was safe and well tolerated in patients with severe hypertriglyceridemia., Trial Registration: ClinicalTrials.gov Identifiers: NCT03398005 and NCT03361501.

Appropriate planning, execution, and reporting of statistical methods and results is critical for research transparency, validity, and reproducibility. This paper provides an overview of best practices for developing a statistical analysis plan a priori, conducting statistical analyses, and reporting statistical methods and results for human nutrition randomized controlled trials (RCTs). Readers are referred to the other NURISH (NUtrition inteRventIon reSearcH) publications for detailed information about the preparation and conduct of human nutrition RCTs. Collectively, the NURISH series outlines best practices for conducting human nutrition research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Results from observational studies indicate that whole grain (WG) intake is inversely associated with BMI and risk of weight gain. WG intake may influence energy balance and body composition through effects on appetite and energy intake. To evaluate the impact of WG food consumption on appetite and energy intake, a systematic review and meta-analysis was performed of results from randomized controlled trials (RCTs) assessing WG food consumption, appetite, and energy intake in adults. A search of PubMed, Scopus, and Food Science and Technology Abstracts yielded 36 RCTs measuring subjective appetite ratings after consuming WG foods compared with refined grain (RG) controls. Thirty-two of these studies reported AUCs for subjective appetite (hunger, fullness, satiety, desire to eat, or prospective consumption) and/or energy intake and were included in the meta-analysis. Pooled estimates from meta-analyses are expressed as standardized mean differences (SMDs). Compared with RG foods, intake of WG foods resulted in significant differences in AUCs for subjective hunger (SMD: -0.34; 95% CI: -0.46, -0.22; P < 0.001), fullness (SMD: 0.49; 95% CI: 0.31, 0.66; P < 0.001), satiety (SMD: 0.33; 95% CI: 0.18, 0.47; P < 0.001), and desire to eat (SMD: -0.33; 95% CI: -0.46, -0.20; P < 0.001). There were small, nonsignificant reductions in prospective consumption ratings (P = 0.08) and energy intake (P = 0.07) with WG intake compared with RG. These results support the view that consumption of WG foods, compared with RG foods, significantly impacts subjective appetite, and might partly explain the inverse associations between WG food intake and risk of overweight, obesity, and weight gain over time. PROSPERO registration: CRD42020148217., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

In human nutrition randomized controlled trials (RCTs), planning, and careful execution of clinical data collection and management are vital for producing valid and reliable results. In this article, we provide an overview of best practices for biospecimen collection and analyses, and for the fundamentals of clinical data management, including preparation and study startup; data collection, entry, cleaning, and authentication; and database lock. The reader is also referred to additional resources for information to assist in the planning and conduct of human RCTs. The tools and strategies described are expected to improve the quality of data produced in human nutrition research that can, therefore, be used to support food and nutrition policies., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Resistant starch is a non-digestible starch fraction and is classified as fiber. Beyond naturally occurring fiber sources, starches can be modified to resist digestion, increase their fiber content and provide physiological benefits. The current study examined acute postprandial glycemic responses of VERSAFIBE™ 1490 resistant starch type-4, containing 90% total dietary fiber (TDF, AOAC (Association of Official Analytical Collaboration International) 991.43 method). In a double-blind, randomized, placebo-controlled, cross-over study, healthy adults ( n = 38) consumed a nutritional bar containing either control (2 g), medium (21 g) or high (30 g) fiber. The test bars were matched with control for available carbohydrates, fat and protein. Venous glucose, insulin, and capillary glucose were measured. Mean ± SEM capillary glucose incremental area-under-curve (iAUC0)-120 min in min*mmol/L was lower ( p < 0.005) for both fiber bars (136.2 ± 9.2 and 137.0 ± 10.4 for the medium and high fiber bars, respectively) compared to the control bar (174.9 ± 13.5). Mean venous insulin iAUC0-120 min in min*pmol/L was also lower for medium (8096.3 ± 894.5) and high fiber (7533.8 ± 932.9) bars, respectively, compared to the control bar (11871.6 ± 1123.9, p < 0.001). Peak capillary glucose and venous insulin concentrations were also significantly reduced ( p < 0.001) after consumption of both fiber bars compared to the control bar. The results of this study suggest that nutritional bars containing potato based RS4 fiber reduced post-consumption glycemic and insulinemic responses when consumed by generally healthy adults.

Despite consensus that excessive circulating concentrations of apoB-lipoproteins is a key driver for the atherosclerotic process and that treatments that low-density lipoprotein cholesterol lowering by up-regulation of low-density lipoprotein cholesterol receptor expression reduces that risk, divergent viewpoints on interpretation of study data have resulted in substantial differences in European and American lipid guideline recommendations. This article explores those differences and highlights the importance of understanding guideline-based lipid management to improve patient care and reduce the risk of clinical atherosclerotic cardiovascular disease.

Allocation of statin therapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in borderline- and intermediate-risk patients has traditionally been based on population-based global risk assessment and other clinical and laboratory characteristics. Patient-specific treatment decisions are needed to provide maximal benefit and avoid unnecessary treatment. Guideline-based lipid management proposes that coronary artery calcium scoring is reasonable to implement in patients with a 10-year risk of 5.0% to 19.9% (borderline to intermediate risk) by using the pooled cohort equations when the decision about whether to initiate statin therapy is uncertain. We report data from both observational studies and a large primary prevention randomized controlled trial that support the position that this decision is, in fact, uncertain in about half of such patients because of risk misclassification. Such misclassification can be largely avoided by more widespread implementation of coronary calcium scoring, which helps to identify those with coronary artery calcium scores of 0, a finding associated with a less than 5.0% 10-year probability of an ASCVD event. Deferral of statin therapy in such patients, in the absence of smoking, diabetes, or a family history of premature ASCVD, provides more individualized and appropriate care and avoids the expense and potential adverse effects of statin therapy in those with low potential for absolute risk reduction. A rationale is also provided for the importance of coronary artery calcium scoring in women 50 years and older, possibly in place of 1 screening mammogram in women at least 55 years of age to avoid incremental radiation exposure, on the basis of the substantially higher lifetime risk of morbidity and mortality from ASCVD than from breast cancer. In patients with borderline or intermediate ASCVD risk, coronary artery calcium scoring should be used, whenever possible, as an aid to rational statin allocation for the primary prevention of ASCVD., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Since their inception in 1980, the Dietary Guidelines for Americans have promoted low- or fat-free dairy foods. Removing fat from dairy does not reduce putatively beneficial nutrients per serving, including calcium, vitamin D, and potassium. Additionally, links between saturated fat and dietary cholesterol intakes with cardiovascular disease risk have helped to sustain the view that low-fat dairy foods should be recommended. Emerging evidence shows that the consumption of full-fat dairy foods has a neutral or inverse association with adverse cardiometabolic health outcomes, including atherosclerotic cardiovascular disease, type 2 diabetes, and associated risk factors. Thus, although low-fat dairy is a practical, practice-based recommendation, its superiority compared with full-fat dairy is not obviously supported by results from recent prospective cohort studies or intervention trials. To evaluate the emerging science on full-fat dairy, a group of nutrition experts convened to summarize and discuss the scientific evidence regarding the health effects of consuming full-fat dairy foods. Future studies should focus on full-fat dairy foods (milk, yogurt, and cheese) in the context of recommended dietary patterns and consider meal composition and metabolic phenotype in assessing the relation between full-fat dairy consumption and cardiometabolic health., (Copyright © The Author(s) 2020.)

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/m 2 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.

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.

The 2015 Dietary Guidelines for Americans recommend limiting the intake of saturated fatty acids (SFAs) to <10% of energy/d and replacing dietary SFAs with unsaturated fatty acids. A Presidential Advisory from the American Heart Association recently released its evaluation of the relation between dietary fats and cardiovascular disease (CVD), and also recommended a shift from SFAs to unsaturated fatty acids, especially polyunsaturated fatty acids (PUFAs), in conjunction with a healthy dietary pattern. However, the suggestion to increase the intake of PUFAs in general, and omega-6 (n-6) PUFAs in particular, continues to be controversial. This review was undertaken to provide an overview of the evidence and controversies regarding the effects of ω-6 PUFAs on cardiometabolic health, with emphasis on risks and risk factors for CVD (coronary heart disease and stroke) and type 2 diabetes mellitus (T2D). Results from observational studies show that higher intake of ω-6 PUFAs, when compared with SFAs or carbohydrate, is associated with lower risks for CVD events (10-30%), CVD and total mortality (10-40%), and T2D (20-50%). Findings from intervention studies on cardiometabolic risk factors suggest that ω-6 PUFAs reduce concentrations of LDL cholesterol and non-HDL cholesterol in a dose-dependent manner compared with dietary carbohydrate, and have a neutral effect on blood pressure. Despite the concern that ω-6 fatty acids increase inflammation, current evidence from studies in humans does not support this view. In conclusion, these findings support current recommendations to emphasize consumption of ω-6 PUFAs as a replacement of SFAs; additional randomized controlled trials with cardiometabolic disease outcomes will help to more clearly define the benefits and risks of this policy.

Background: Few trials have examined the effects of coconut oil consumption in comparison with polyunsaturated fatty acid-rich oils such as corn oil., Objective: This trial assessed the effects of consuming foods made with corn oil compared with coconut oil on lipids, glucose homeostasis, and inflammation., Methods: This was a preliminary randomized crossover study of men (n = 12) and women (n = 13) with a mean age of 45.2 y, mean body mass index (in kg/m2) of 27.7, fasting LDL cholesterol ≥115 mg/dL and <190 mg/dL, and triglycerides (TGs) ≤375 mg/dL. Subjects consumed muffins and rolls providing 4 tablespoons (∼54 g) per day of corn oil or coconut oil as part of their habitual diets for 4 wk, with a 3-wk washout between conditions. Fasting plasma lipids and high-sensitivity C-reactive protein (hs-CRP) and glucose metabolism were assessed via an intravenous glucose tolerance test at baseline and 15 and 29 d of treatment. Responses were compared between treatments by ANCOVA., Results: Median baseline concentrations of LDL cholesterol, non-HDL cholesterol, total cholesterol (total-C), HDL cholesterol, total-C:HDL cholesterol, and TGs were 123, 144, 188, 46.0, 4.21, and 92.5 mg/dL, respectively. Changes from baseline for corn oil and coconut oil conditions, respectively, were: LDL cholesterol (primary outcome; -2.7% compared with +4.6%), non-HDL cholesterol (-3.0% compared with +5.8%), total-C (-0.5% compared with +7.1%), HDL cholesterol (+5.4% compared with +6.5%), total-C:HDL cholesterol (-4.3% compared with -3.3%), and TGs (-2.1% compared with +6.0%). Non-HDL cholesterol responses were significantly different between corn and coconut oil conditions (P = 0.034); differences between conditions in total-C and LDL cholesterol approached significance (both P = 0.06). Responses for hs-CRP and carbohydrate homeostasis parameters did not differ significantly between diet conditions., Conclusions: When incorporated into the habitual diet, consumption of foods providing ∼54 g of corn oil/d produced a more favorable plasma lipid profile than did coconut oil in adults with elevated cholesterol. This trial was registered at clinicaltrials.gov as NCT03202654.

There has been a great deal of controversy in recent years about the potential role of dietary supplementation with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) in the prevention of cardiovascular disease (CVD). Four recent meta-analyses have been published that evaluated randomized, controlled trial (RCT) data from studies that assessed the effects of supplemental n-3 PUFA intake on CVD endpoints. The authors of those reports reached disparate conclusions. This review explores the reasons informed experts have drawn different conclusions from the evidence, and addresses implications for future investigation. Although RCT data accumulated to date have failed to provide unequivocal evidence of CVD risk reduction with n-3 PUFA supplementation, many studies were limited by design issues, including low dosage, no assessment of n-3 status, and absence of a clear biological target or pathophysiologic hypothesis for the intervention. The most promising evidence supports n-3 PUFA supplementation for prevention of cardiac death. Two ongoing trials have enrolled high cardiovascular risk subjects with hypertriglyceridemia and are administering larger dosages of n-3 PUFA than employed in previous RCTs. These are expected to clarify the potential role of long-chain n-3 PUFA supplementation in CVD risk management.

Resistant starch (RS) is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. The primary aim of this randomized, double-blind, controlled study was to characterize the postprandial glucose response in healthy adults after consuming a high fiber scone containing a novel RS4 or a low fiber control scone without RS4. Secondary aims included assessment of postprandial insulin response, postprandial satiety, and gastrointestinal tolerance. The fiber scone significantly reduced postprandial glucose and insulin incremental areas under the curves (43-45% reduction, 35-40% reduction, respectively) and postprandial glucose and insulin maximum concentrations (8-10% and 22% reduction, respectively). The fiber scone significantly reduced hunger and desire to eat during the 180 min following consumption and yielded no gastrointestinal side effects compared with the control scone. The results from this study demonstrate that a ready-to-eat baked-good, such as a scone, can be formulated with RS4 replacing refined wheat flour to yield statistically significant and clinically meaningful reductions in blood glucose and insulin excursions. This is the first study to report increased satiety after short-term RS4 intake, which warrants further investigation in long-term feeding studies., Competing Interests: M.L.S. is an employee of Ingredion Incorporated.

Background: Higher-protein (HP) energy-restriction diets improve weight management to a greater extent than normal-protein (NP) versions. Potential mechanisms of action with regard to assessment of eating behaviors across the day have not been widely examined during energy restriction. Objectives: The objectives of this study were to test whether the consumption of an HP energy-restriction diet reduces carbohydrate and fat intakes through improvements in daily appetite, satiety, and food cravings compared with NP versions and to test whether protein type within the NP diets alters protein-related satiety. Methods: Seventeen overweight women [mean ± SEM age: 36 ± 1 y; body mass index (kg/m 2 ): 28.4 ± 0.1] completed a randomized, controlled-feeding crossover study. Participants were provided with the following ∼1250-kcal/d energy-restricted (-750-kcal/d deficit) diets, each for 6 d: HP [124 g protein/d; 60% from beef and 40% from plant sources (HP-BEEF)] or NP (48 g protein/d) that was protein-type matched (NP-BEEF) or unmatched [100% from plant-based sources (NP-PLANT)]. On day 6 of each diet period, participants completed a 12-h testing day containing repetitive appetite, satiety, and food-craving questionnaires. On day 7, the participants were asked to consume their protein requirement within each respective diet but were provided with a surplus of carbohydrate- and fat-rich foods to consume, ad libitum, at each eating occasion across the day. All outcomes reported were primary study outcomes. Results: The HP-BEEF diet reduced daily hunger by 16%, desire to eat by 15%, prospective food consumption by 14%, and fast-food cravings by 15% but increased daily fullness by 25% compared with the NP-BEEF and NP-PLANT diets (all P < 0.05). However, consuming more protein throughout the day did not reduce the energy consumed ad libitum from the fat- and carbohydrate-rich foods (HP-BEEF: 2000 ± 180 kcal/d; NP-BEEF: 2120 ± 190 kcal/d; NP-PLANT: 2070 ± 180 kcal/d). None of the outcomes differed between the NP-BEEF and NP-PLANT treatments. Conclusions: Although appetite control, satiety, and food cravings improved after an HP energy-restriction diet, increased protein consumption did not reduce carbohydrate and fat intakes throughout the free-living test day in overweight healthy women exposed to highly palatable foods. This trial was registered at clinicaltrials.gov as NCT02614729., Competing Interests: Author disclosures: JAG, no conflicts of interest. KCM and HJL serve on the speaker board for the National Cattlemen’s Beef Association. The Beef Checkoff supplied the funds to complete the study but was not involved in the design, implementation, analysis, or interpretation of data., (© 2017 American Society for Nutrition.)

With the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n 24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (P<0·05) and baseline adjusted AUC for plasma lutein at 48 and 336 h (P<0·001) as compared with subjects given lutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0-48 and 0-336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

Background: The effects of meal-specific protein quantity and protein distribution throughout the day on daily food intake are relatively unknown. Objectives: The aims were to test 1 ) whether the consumption of higher-protein (HP) compared with normal-protein (NP) meals consumed at each eating occasion reduce free-living, daily carbohydrate and fat intakes in overweight women during energy balance conditions and 2 ) whether the distribution of protein consumed throughout the day affects food intake outcomes. Methods: Seventeen women [mean ± SEM age: 33 ± 1 y; body mass index (in kg/m 2 ): 27.8 ± 0.1] completed the following tightly controlled, crossover design study. Participants were provided with and randomly consumed three 6-d eucaloric diets containing NP or HP (15% or 25% of energy as protein, respectively). The protein content within the NP diet used an even distribution pattern (EVEN; 21 ± 1 g protein/meal) throughout the day, whereas the protein contents within the HP diets used either EVEN (35 ± 1 g protein/meal) or an uneven distribution pattern (UNEVEN; 19 ± 1 g protein/breakfast, 26 ± 1 g protein/lunch, 63 g protein/dinner). On day 7 of each diet, the participants were asked to consume the diet-specific absolute protein quantity (in grams) at each eating occasion but were provided with a surplus of carbohydrate- and fat-rich foods to consume, ad libitum, during each eating occasion. Results: Eating more protein (HP compared with NP) or evenly distributing protein throughout the day (HP-EVEN compared with HP-UNEVEN) did not reduce the consumption of ad libitum fat- and carbohydrate-rich foods throughout the day (NP-EVEN: 2850 ± 240 kcal/d; HP-EVEN: 2910 ± 240 kcal/d; HP-UNEVEN: 3160 ± 200 kcal/d). Despite the lack of differences in daily energy intake, the breakfast meal within the HP-EVEN diet led to lower ad libitum carbohydrate and fat intakes than the breakfast meals in the NP-EVEN and HP-UNEVEN diet conditions ( P < 0.05). Conclusion: Providing 30 g protein/meal at each eating occasion throughout the day did not influence free-living, daily intake of highly palatable, carbohydrate- and fat-rich foods in overweight women. This trial was registered at clinicaltrials.gov as NCT02614729.

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/m 2 ), 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., Competing Interests: Author disclosures: KC Maki, OM Palacios, E Lindner, KM Nieman, M Bell, and J Sorce, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption., Objective: We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs., Design: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time., Results: The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use-adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman-years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914)., Conclusion: The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021., (© 2016 American Society for Nutrition.)