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BackgroundDietary intake provides nutrients for humans and their gastrointestinal microorganisms, as some dietary constituents bypass human digestion. These undigested components affect the composition and function of the microorganisms present. Metagenomic analyses allow researchers to study functional capacity. As dietary components affect the composition and function of the gastrointestinal microbiome, there is potential for developing objective biomarkers of food intake using metagenomic data.ObjectiveWe aimed to utilize a computationally intensive, multivariate, machine learning approach to identify fecal Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO) categories as biomarkers that accurately predict food intake.DesignData were aggregated from five controlled feeding studies in adults that studied the impact of specific foods (almonds, avocados, broccoli, walnuts, barley, and oats) on the gastrointestinal microbiota. DNA from pre- and post-intervention fecal samples underwent shotgun genomic sequencing. After pre-processing, sequences were aligned (DIAMONDv2.0.11.149) and functionally annotated (MEGANv6.12.2). After count normalization, the log of the fold change ratio for resulting features between pre- and post-intervention of the treatment group against its corresponding control was utilized to conduct differential KO abundance analysis. Differentially abundant KOs were used to train machine learning models examining potential biomarkers in both single-food and multi-food models.ResultsWe identified differentially abundant KOs for almond (n = 54), broccoli (n = 2,474), and walnut (n = 732) (q < 0.20). Using the differentially abundant KOs, prediction accuracies were 80%, 87%, and 86% prediction accuracies for the almond, broccoli, and walnut groups, respectively using a random forest model to classify food intake. The mixed-food random forest achieved 81% prediction accuracy.ConclusionsOur findings reveal promise in utilizing fecal metagenomics to objectively complement self-reported measures of food intake. Future research on various foods and dietary patterns will expand these exploratory analyses for eventual use in feeding study compliance and clinical settings.

Background It remains unclear whether red meat consumption is causatively associated with cardiovascular disease (CVD) risk, and few randomized controlled studies have examined the effect of incorporating lean beef into a healthy dietary pattern. Objectives To evaluate the effects of a Mediterranean (MED) diet (carbohydrate 42%, protein 17%, fat 41%, SFAs 8%, MUFAs 26%, PUFAs 8%) with 14 (MED0.5; 0.5 oz), 71 (MED2.5; 2.5 oz), and 156 (MED5.5; 5.5 oz) g/d/2000 kcal lean beef compared with an average American diet (AAD; carbohydrate 52%, protein 15%, fat 33%, SFAs 12%, MUFAs 13%, PUFAs 8%) on lipid and lipoprotein concentrations, particle number, and size. Methods This was a multicenter, 4-period controlled feeding, randomized crossover study. Fifty-nine generally healthy males and females (BMI 20–38 kg/m2; age 30–65 y) consumed each diet for 4 wk with a ≥1-wk washout between the diets. Fasting blood samples were collected at baseline and at the end of each 4-wk period. Lipid subfractions were measured by NMR. Results Compared with the AAD, all 3 MED diets decreased LDL cholesterol (MED0.5: −10.3 mg/dL; 95% CI: −5.4, −15.7 mg/dL; MED2.5: −9.1 mg/dL; 95% CI: −3.9, −14.3 mg/dL; MED5.5: −6.9 mg/dL; 95% CI: −1.7, −12.1 mg/dL; P

Numerous governmental and health organizations recommend reduced intake of added sugars due to the health risks associated with excess intake, including the risk of obesity. Some organizations further recommend avoiding dietary sweetness, regardless of the source. A scoping review and evidence map were completed to characterize the research that investigated associations between dietary sweetness and body weight. The aim was to identify and map published studies that have investigated total dietary sweetness, sweet food/beverages, sugar, or sweetener intake, and body weight-related outcomes and/or energy intake. Using preregistered search terms (osf.io/my7pb), 36,779 publications (duplicates removed) were identified from PubMed, Cochrane Library, and Scopus and screened for inclusion. Eligible studies were clinical trials, longitudinal cohorts, case-control studies, cross-sectional studies, and systematic reviews conducted among adults (age ≥18 y), which were performed to investigate associations between dietary sweetness, sweet foods/beverages, sugar, or sweetener (energetic or nonenergetic) intake and body weight, BMI, adiposity, and/or energy intake. A total of 833 eligible publications were identified, detailing 804 studies. Only 7 studies (0.9% of included studies; 2 clinical trials, 4 cross-sectional studies, and 1 with another design type) investigated associations between total dietary sweetness and body weight-related outcome and/or energy intake. An additional 608 (75.6%) studies investigated intakes of sweet foods/beverages, sugar, or sweetener, and body weight-related outcomes and/or energy intake, including 225 clinical trials, 81 longitudinal cohorts, 4 case-control studies, and 280 cross-sectional studies. Most studies (90.6%) did not measure the sweetness of the diet or individual foods consumed. Ninety-two (11.4%) publications reported data from studies on dietary patterns that included sweet foods/beverages alongside other dietary components and 97 (12.1%) systematic reviews addressed different but related research questions. Although there is a breadth of evidence from studies that have investigated associations between intakes of sweet foods and beverages, sugars, and sweeteners and body weight, there is a limited depth of evidence on the association between total dietary sweetness and body weight.

The fecal metabolome is impacted by diet and includes metabolites generated by human and microbial metabolism. Advances in -omics technologies and analytic approaches have allowed researchers to identify metabolites and better utilize large datasets to generate usable information. One promising aspect of these advancements is the ability to determine objective biomarkers of food intake.We aimed to utilize a multivariate, machine learning approach to identify metabolite biomarkers that accurately predict food intake.Data were aggregated from five controlled feeding studies in adults that tested the impact of specific foods (almonds, avocados, broccoli, walnuts, barley, and oats) on the gastrointestinal microbiota. Fecal samples underwent gas chromatography-mass spectrometry (GC-MS) metabolomic analysis; 307 metabolites were detected. Changes in metabolite relative concentration (treatment post-intervention minus pre-intervention) were utilized in random forest models to 1) examine the relationship between food consumption and fecal metabolome changes and 2) rank the fecal metabolites by their predictive power (i.e., feature importance score).Using the change in relative concentration of fecal metabolites, six single-food random forest models for almond, avocado, broccoli, walnuts, whole-grain barley, and whole-grain oats revealed prediction accuracies between 47% and 89%. When comparing foods to one another, almond intake was differentiated from walnut intake with 91% classification accuracy.Our findings reveal promise in utilizing fecal metabolites as objective complements to certain self-reported food intake estimates. Future research on other foods at different doses and dietary patterns is needed to identify biomarkers that can be applied in feeding study compliance and clinical settings.

Background Diet affects the human gastrointestinal microbiota. Blood and urine samples have been used to determine nutritional biomarkers. However, there is a dearth of knowledge on the utility of fecal biomarkers, including microbes, as biomarkers of food intake. Objectives This study aimed to identify a compact set of fecal microbial biomarkers of food intake with high predictive accuracy. Methods Data were aggregated from 5 controlled feeding studies in metabolically healthy adults (n = 285; 21–75 y; BMI 19–59 kg/m2; 340 data observations) that studied the impact of specific foods (almonds, avocados, broccoli, walnuts, and whole-grain barley and whole-grain oats) on the human gastrointestinal microbiota. Fecal DNA was sequenced using 16S ribosomal RNA gene sequencing. Marginal screening was performed on all species-level taxa to examine the differences between the 6 foods and their respective controls. The top 20 species were selected and pooled together to predict study food consumption using a random forest model and out-of-bag estimation. The number of taxa was further decreased based on variable importance scores to determine the most compact, yet accurate feature set. Results Using the change in relative abundance of the 22 taxa remaining after feature selection, the overall model classification accuracy of all 6 foods was 70%. Collapsing barley and oats into 1 grains category increased the model accuracy to 77% with 23 unique taxa. Overall model accuracy was 85% using 15 unique taxa when classifying almonds (76% accurate), avocados (88% accurate), walnuts (72% accurate), and whole grains (96% accurate). Additional statistical validation was conducted to confirm that the model was predictive of specific food intake and not the studies themselves. Conclusions Food consumption by healthy adults can be predicted using fecal bacteria as biomarkers. The fecal microbiota may provide useful fidelity measures to ascertain nutrition study compliance.

Partially hydrogenated oils (PHO) have been removed from the food supply due to adverse effects on risk for coronary heart disease (CHD). High‐oleic soybean oils (HOSBO) are alternatives that provide functionality for different food applications. The objective of this study was to determine how consumption of diets containing HOSBO compared to other alternative oils, with similar functional properties, modifies LDL cholesterol (LDLc) and other risk factors and biomarkers of CHD. A triple‐blind, crossover, randomized controlled trial was conducted in humans (n = 60) with four highly‐controlled diets containing (1) HOSBO, (2) 80:20 blend of HOSBO and fully hydrogenated soybean oil (HOSBO+FHSBO), (3) soybean oil (SBO), and (4) 50:50 blend of palm oil and palm kernel oil (PO + PKO). Before and after 29 days of feeding, lipids/lipoproteins, blood pressure, body composition, and markers of inflammation, oxidation, and hemostasis were measured. LDLc, apolipoprotein B (apoB), NonHDL‐cholesterol (HDLc), ratios of total cholesterol (TC)‐to‐HDLc and LDLc‐to‐HDL cholesterol, and LDL particle number and small LDL particles concentration were lower after HOSBO and HOSBO+FHSBO compared to PO (specific comparisons p

Various global public health agencies recommend minimizing exposure to sweet-tasting foods or beverages. The underlying rationale is that reducing exposure to the perception of sweet tastes, without regard to the source of sweetness, may reduce preferences for sweetness, added sugar intake, caloric intake, and body weight. However, the veracity of this sequence of outcomes has yet to be documented, as revealed by findings from recent systematic reviews on the topic. Efforts to examine and document the effects of sweetness exposure are needed to support evidence-based recommendations. They require a generally agreed-upon methodology for measuring sweetness in foods, beverages, and the overall diet. Although well-established sensory evaluation techniques exist for individual foods in laboratory settings, they are expensive and time-consuming, and agreement on the optimal approach for measuring the sweetness of the total diet is lacking. If such a measure could be developed, it would permit researchers to combine data from different studies and populations and facilitate the design and conduct of new studies to address unresolved research questions about dietary sweetness. This narrative review includes an overview of available sensory techniques, their strengths and limitations, recent efforts to measure the sweetness of foods and diets across countries and cultures, and a proposed future direction for improving methods for measuring sweetness toward developing the data required to support evidence-based recommendations around dietary sweetness.

Many epidemiologic studies use metabolomics for discovery-based research. The degree to which sample handling may influence findings, however, is poorly understood. In 2016, serum samples from 13 volunteers from the US Department of Agriculture’s Beltsville Human Nutrition Research Center were subjected to different clotting (30 minutes/120 minutes) and refrigeration (0 minutes/24 hours) conditions, as well as different numbers (0/1/4) and temperatures (ice/refrigerator/room temperature) of thaws. The median absolute percent difference (APD) between metabolite levels and correlations between levels across conditions were estimated for 628 metabolites. The potential for handling artifacts to induce false-positive associations was estimated using variable hypothetical scenarios in which 1%–100% of case samples had different handling than control samples. All handling conditions influenced metabolite levels. Across metabolites, the median APD when extending clotting time was 9.08%. When increasing the number of thaws from 0 to 4, the median APD was 10.05% for ice and 5.54% for room temperature. Metabolite levels were correlated highly across conditions (all r’s ≥ 0.84), indicating that relative ranks were preserved. However, if handling varied even modestly by case status, our hypotheticals showed that results can be biased and can result in false-positive findings. Sample handling affects levels of metabolites, and special care should be taken to minimize effects. Shorter room-temperature thaws should be preferred over longer ice thaws, and handling should be meticulously matched by case status.

Nuts are high nutrient-dense foods containing healthy lipids, dietary fiber, and bioactive phytochemicals, including vitamins and minerals. Although the beneficial effect of nut consumption on different chronic diseases has been well documented, especially in relation to their cardiometabolic benefits, less scientific evidence is available on their possible beneficial effects on gastrointestinal health. In this narrative review, we summarize the most important findings and new research perspectives in relation to the importance of nut consumption on gastrointestinal health. The integrity of the cell wall structure, cell size and particle size after mastication are known to play a crucial role in energy, nutrient and bioactive release from nuts during digestion, therefore affecting bioaccessibility. Other mechanisms, such as cell wall composition, thickness and porosity, as well as stability of the membranes surrounding the oil bodies within the cell, are also important for energy extraction. As the undigested nutrients and phytochemicals are delivered to the colon, effects on gut microbiota composition are predicted. Although the overall effect of nut consumption on microbial alpha- and beta-diversity has been inconsistent, some scientific evidence suggests an increase in fecal butyrate after almond consumption, and a beneficial role of walnuts on the prevention of ulcerative colitis and protection against the development of gastric mucosal lesions.

Berries and other anthocyanin-rich foods have demonstrated anti-obesity effects in rodents and humans. However, the bioactive components of these foods and their mechanisms of action are unclear. We conducted an intervention study with overweight and obese adults to isolate the effects of different berry components on bioenergetics. Subjects consumed whole mixed berries (high anthocyanin, high fiber), pressed berry juice (high anthocyanin, low fiber), berry-flavored gelatin (low anthocyanin, low fiber), or fiber-enriched gelatin (low anthocyanin, high fiber) for one week prior to a meal challenge with the same treatment food as the pre-feed period. Peripheral blood mononuclear cells were collected 2 h after the meal challenge, and cellular respiration was assessed via high-resolution respirometry. The high-anthocyanin, low-fiber treatment (berry juice) and the low-anthocyanin, high-fiber treatment (fiber-enriched gelatin) had opposite effects on cellular respiration. In the fasted state, berry juice resulted in the highest oxygen-consumption rate (OCR), while fiber-enriched gelatin resulted in the highest OCR in the fed state. Differences were observed in multiple respiration states (basal, state 3, state 4, uncoupled), with the greatest differences being between the pressed berry juice and the fiber-enriched gelatin. Different components of berries, specifically anthocyanins/flavonoids and fiber, appear to have differential effects on cellular respiration.

Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45–86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for energy were 0.07, 0.07, and 0.19 for a single FFQ, 24HR, and FR, respectively. Correlation coefficients for energy were 0.24, 0.23, and 0.40, respectively. Excluding energy, the average attenuation factors across nutrients and studies were 0.22 for a single FFQ, 0.22 for a single 24HR, and 0.51 for a single FR. Corresponding correlation coefficients were 0.31, 0.34, and 0.53, respectively. For densities (nutrient expressed relative to energy), the average attenuation factors across studies were 0.37, 0.17, and 0.50, respectively. The findings support prior research suggesting different instruments have unique strengths that should be leveraged in epidemiologic research.

Over several decades, the health benefits of consuming nuts have been investigated, resulting in a large body of evidence that nuts can reduce the risk of chronic diseases. The consumption of nuts, being a higher-fat plant food, is restricted by some in order to minimize weight gain. In this review, we discuss several factors related to energy intake from nuts, including food matrix and its impact on digestibility, and the role of nuts in regulating appetite. We review the data from randomized controlled trials and observational studies conducted to examine the relationship between nut intake and body weight or body mass index. Consistently, the evidence from RCTs and observational cohorts indicates that higher nut consumption does not cause greater weight gain; rather, nuts may be beneficial for weight control and prevention of long-term weight gain. Multiple mechanisms likely contribute to these findings, including aspects of nut composition which affect nutrient and energy availability as well as satiety signaling.

Estimating the individualized treatment effect has become one of the most popular topics in statistics and machine learning communities in recent years. Most existing methods focus on modeling the heterogeneous treatment effects for univariate outcomes. However, many biomedical studies are interested in studying multiple highly correlated endpoints at the same time. We propose a random forest model that simultaneously estimates individualized treatment effects of multivariate outcomes. We consider a popular study design where covariates and outcomes are measured both before and after the intervention. The proposed model uses oblique splitting rules to partition population space to the neighborhood that experiences distinct treatment effects. An extensive simulation study suggests that the proposed method outperforms existing methods in various nonlinear settings. We further apply the proposed method to two nutrition studies investigating the effects of food consumption on gastrointestinal microbiota composition and clinical biomarkers. The method has been implemented in a freely available R package MOTE.RF at https://github.com/boyiguo1/MOTE.RF .

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.

International audience; The number of nutrigenetic studies dedicated to the identification of single nucleotide polymorphisms (SNPs) modulating blood lipid profiles in response to dietary interventions has increased considerably over the last decade. However, the robustness of the evidence-based science supporting the area remains to be evaluated. The objective of this review was to present recent findings concerning the effects of interactions between SNPs in genes involved in cholesterol metabolism and transport, and dietary intakes or interventions on circulating cholesterol concentrations, which are causally involved in cardiovascular diseases and established biomarkers of cardiovascular health. We identified recent studies (2014–2020) that reported significant SNP–diet interactions in 14 cholesterol-related genes (NPC1L1, ABCA1, ABCG5, ABCG8, APOA1, APOA2, APOA5, APOB, APOE, CETP, CYP7A1, DHCR7, LPL, and LIPC), and which replicated associations observed in previous studies. Some studies have also shown that combinations of SNPs could explain a higher proportion of variability in response to dietary interventions. Although some findings still need replication, including in larger and more diverse study populations, there is good evidence that some SNPs are consistently associated with differing circulating cholesterol concentrations in response to dietary interventions. These results could help clinicians provide patients with more personalized dietary recommendations, in order to lower their risk for cardiovascular disease.

OBJECTIVES: To evaluate the effects of Mediterranean (MED) diets with different quantities of lean beef (0.5, 2.5 and 5.5 oz/day) compared to an Average American diet (AAD) on brachial and central blood pressure, pulse wave velocity (PWV) and augmentation index (AI). METHODS: We conducted a multicenter, 4-period controlled feeding, randomized crossover study at Penn State University and USDA-Beltsville to evaluate the effects of MED diets (CHO 42%, PRO 17%, FAT 41%, SFA 8%, MUFA 26%, PUFA 8%) with different quantities of lean beef (0.5, 2.5 and 5.5 oz/day) compared to an average American diet (AAD; CHO 52%, PRO 15%, FAT 33%, SFA 12%, MUFA 13%, PUFA 8%) on vascular health. Participants (n = 66) included generally healthy males and females (BMI = 20–38 kg/m(2)) 30 to 67 years. Participants were randomized to each of the 4 diets for 4 weeks with an approximate 2-week break between treatments. Central blood pressure, PWV and AI were measured using the SphygmoCor ECEL-System. Endpoints were assessed at baseline and the end of each 4-week diet period. RESULTS: There was a significant treatment effect for PWV (P

OBJECTIVES: To determine the impact of garlic on the metabolic profile of urine. METHODS: On the first day 17 fasting subjects were fed a breakfast of bread and butter. Urines were collected before and 3 hours after the meal. On a second day, the same 17 fasting subjects were fed a meal of bread, butter, and garlic. Urines were again collected before and 3 hours after the meal. Samples were analyzed by metabolomics using liquid chromatography-mass spectrometry (LC-MS) and data were subjected to analysis of variance-principal component analysis (ANOVA-PCA). RESULTS: 637 compounds were found in the urines and 277 were identified. PCA of urine profiles were dominated by variation between individual. Removal of individual variance by ANOVA allowed differentiation of fasting urines from bread and butter urines from bread, butter, and garlic urines. PCA loadings identified compounds that led to discrimination between treatments. Influence of the loading identified compounds were verified by examination of the LC-MS data for individual compounds. Three unique sulfur containing compounds were identified. Loadings showed, however, that a change in the metabolite profiles (ratios of compounds) and not the unique compounds) were most informative. CONCLUSIONS: Removal of variance between individuals is essential to properly analyze the data. Changes in the patterns of compounds routinely observed in urine were the major result of the garlic meal. ANOVA-PCA is an excellent tool for isolating experimental factors. FUNDING SOURCES: Agricultural Research Service, US Department of Agriculture and Office of Dietary Supplements, National Institutes of Health.

In the field of human nutrition, randomized controlled trials (RCTs) are considered the gold standard for establishing causal relations between exposure to nutrients, foods, or dietary patterns and prespecified outcome measures, such as body composition, biomarkers, or event rates. Evidence-based dietary guidance is frequently derived from systematic reviews and meta-analyses of these RCTs. Each decision made during the design and conduct of human nutrition RCTs will affect the utility and generalizability of the study results. Within the context of limited resources, the goal is to maximize the generalizability of the findings while producing the highest quality data and maintaining the highest levels of ethics and scientific integrity. The aim of this document is to discuss critical aspects of conducting human nutrition RCTs, including considerations for study design (parallel, crossover, factorial, cluster), institutional ethics approval (institutional review boards), recruitment and screening, intervention implementation, adherence and retention assessment, and statistical analyses considerations. Additional topics include distinguishing between efficacy and effectiveness, defining the research question(s), monitoring biomarker and outcome measures, and collecting and archiving data. Addressed are specific aspects of planning and conducting human nutrition RCTs, including types of interventions, inclusion/exclusion criteria, participant burden, randomization and blinding, trial initiation and monitoring, and the analysis plan.

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking. International Plant Sterol and Stanol Association (IPSSA); National Center for Complementary and Integrative Health (NCCIH); National Center for Advancing Translational Sciences [IR13AT009270-01]

An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: −2.4, −4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: −3.6 kg [IQR: −3.0, −4.1] vs. intermittent CR: −3.0 kg [IQR: −1.95, −4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.

Background Epidemiologic data suggest that diets rich in nuts have beneficial health effects, including reducing total and cause-specific mortality from cancer and heart disease. Although there is accumulating preclinical evidence that walnuts beneficially affect the gastrointestinal microbiota and gut and metabolic health, these relations have not been investigated in humans. Objective We aimed to assess the impact of walnut consumption on the human gastrointestinal microbiota and metabolic markers of health. Methods A controlled-feeding, randomized crossover study was undertaken in healthy men and women [n = 18; mean age = 53.1 y; body mass index (kg/m2): 28.8]. Study participants received isocaloric diets containing 0 or 42 g walnuts/d for two 3-wk periods, with a 1-wk washout between diet periods. Fecal and blood samples were collected at baseline and at the end of each period to assess secondary outcomes of the study, including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health. Results Compared with after the control period, walnut consumption resulted in a 49–160% higher relative abundance of Faecalibacterium, Clostridium, Dialister, and Roseburia and 16–38% lower relative abundances of Ruminococcus, Dorea, Oscillospira, and Bifidobacterium (P

Phytosterols (plant sterols) occur in the cells of all plants. They are important structural components that stabilize the biological membranes of plants. Sterols can occur in the "free" unbound form or they can be covalently bound via an ester or glycosidic bond. Since our previous 2002 review on phytosterols and phytosterol conjugates, phytosterol glucosides have been found to be important structural components in the lipid rafts of the plasma membrane of plant cells, where they are thought to be essential to the function of plasma membrane enzymes and perhaps other proteins. Phytosterols also serve as precursors in the synthesis of important bioactive compounds such as steroidal saponins, steroidal glycoalkaloids, phytoecdysteroids, and brassinosteroids. Methods for the analysis of phytosterols range from traditional gas chromatography of free phytosterols to modern sophisticated forms of mass spectrometry which have been used for the new field of sterol lipidomics, sometimes called "sterolomics." Phytosterol-enriched functional foods first appeared about twenty years ago and many clinical studies have confirmed the low density lipoprotein (LDL) cholesterol-lowering properties of various types of phytosterols. In recent years additional clinical studies and more than ten important meta-analyses have provided insights to better understand the cholesterol-lowering and other biological effects of plant sterols.

Calibrating dietary self-report instruments is recommended as a way to adjust for measurement error when estimating diet-disease associations. Because biomarkers available for calibration are limited, most investigators use self-reports (e.g., 24-hour recalls (24HRs)) as the reference instrument. We evaluated the performance of 24HRs as reference instruments for calibrating food frequency questionnaires (FFQs), using data from the Validation Studies Pooling Project, comprising 5 large validation studies using recovery biomarkers. Using 24HRs as reference instruments, we estimated attenuation factors, correlations with truth, and calibration equations for FFQ-reported intakes of energy and for protein, potassium, and sodium and their densities, and we compared them with values derived using biomarkers. Based on 24HRs, FFQ attenuation factors were substantially overestimated for energy and sodium intakes, less for protein and potassium, and minimally for nutrient densities. FFQ correlations with truth, based on 24HRs, were substantially overestimated for all dietary components. Calibration equations did not capture dependencies on body mass index. We also compared predicted bias in estimated relative risks adjusted using 24HRs as reference instruments with bias when making no adjustment. In disease models with energy and 1 or more nutrient intakes, predicted bias in estimated nutrient relative risks was reduced on average, but bias in the energy risk coefficient was unchanged.

Evidence supports the beneficial effects of berries on glucoregulation, possibly related to flavonoid content, fiber content, or both. The purpose of this study was to assess the potential of mixed berries to improve insulin sensitivity and to identify the potential role of flavonoids and fiber. In a randomized cross-over trial with four treatment periods, overweight/obese men and women were fed a controlled 45% fat diet for one week prior to a meal-based glucose tolerance test. The same base diet was provided during each feeding period with the addition of one of four treatments: whole mixed berries, sugar matched mixed berry juice, sugar matched gelatin, and sugar/fiber matched gelatin. Subjects then completed a meal-based oral glucose tolerance test. Serum glucose, insulin and non-esterified fatty acids were not different between individual treatments. However, in a secondary analysis, the combined berry preparations resulted in a lower serum insulin area under the curve (difference of 0.15 &plusmn, 0.066 ln pmol min/mL, mean &plusmn, SE, p = 0.0228), compared to the combined gelatin treatments, while the difference for serum glucose did not quite meet statistical significance (difference of 0.17 &plusmn, 0.093 ln mg&middot, min/dL, mean &plusmn, SE, p = 0.0738). These results suggest the potential for mixed berry preparations to improve post-prandial insulin response.

Disease course in people with multiple sclerosis (MS) is heterogeneous. The impact of dietary and nutritional factors on MS prognosis is of interest to both patients and clinicians; differences in diet are hypothesized to contribute to disease evolution over time. However, studying diet, especially in people with MS, introduces methodologic complexity that should be recognized. In this review, we focus on methodological aspects relevant to the conduct of dietary interventions in people with MS, given our experience in leading such studies and the challenges we encountered in the realization of this work. We summarize key aspects of study design and important considerations, regardless of the specifics of the actual study (e.g. the particular diet of interest, target MS population, etc.). We discuss strategies for the design of the intervention as well as the selection of appropriate study endpoints. Finally, we provide an overview of strategies to improve the rigor of conducting dietary studies in people with MS.

Background Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) is a self-administered web-based tool designed to collect detailed dietary data at low cost in observational studies. Objective The objectives of this study were to describe, overall and by demographic groups, the performance and feasibility of ASA24-2011 recalls and compare Healthy Eating Index-2015 (HEI-2015) total and component scores to 4-day food records (4DFRs) and food frequency questionnaires (FFQs). Design Over 12 months, participants completed up to 6 ASA24 recalls, 2 web-based FFQs, and 2 unweighed paper-and-pencil 4DFRs. Up to 3 attempts were made to obtain each ASA24 recall. Participants were administered doubly-labeled water to provide a measure of total energy expenditure and collected two 24-hour urine samples to assess concentrations of nitrogen, sodium, and potassium. Participants/setting From January through September 2012, 1,110 adult members of AARP, 50 to 74 years of age, were recruited from the Pittsburgh, PA, area to participate in the Interactive Diet and Activity Tracking in AARP (IDATA) study. After excluding 33 participants who had not completed any dietary assessments, 531 men and 546 women remained. Main outcome measures Response rates, nutrient intakes compared to recovery biomarkers across each ASA24 administration day, and HEI-2015 total and component scores were measured. Statistical analyses performed Means, medians, standard deviations, interquartile ranges, and HEI-2015 total and component scores computed using a multivariate measurement error model are presented. Results Ninety-one percent of men and 86% of women completed 3 ASA24 recalls. Approximately three-quarters completed 5 or more, higher than the completion rates for 2 4DFRs and 2 FFQs. Approximately, three-quarters of men and 70% of women completed ASA24 on the first attempt; 1 in 5 completed it on the second. Completion rates varied slightly by age and body mass index. Median time to complete ASA24-2011 (current version: ASA24-2020) declined with subsequent recalls from 55 to 41 minutes in men and from 58 to 42 minutes in women and was lowest in those younger than 60 years. Mean nutrient intakes were similar across recalls. For each recording day, energy intakes estimated by ASA24 were lower than energy expenditure. Reported intakes for protein, potassium, and sodium were closer to recovery biomarkers for women, but not for men. Geometric means of reported intakes of these nutrients did not systematically vary across ASA24 administrations, but differences between reported intakes and biomarkers differed by nutrient. Of 100 possible points, HEI-2015 total scores were nearly identical for 4DFRs and ASA24 recalls and higher for FFQs (men: 61, 60, and 68; women: 64, 64, and 72, respectively). Conclusions ASA24, a freely available dietary assessment tool for use in large-scale nutrition research, was found to be highly feasible. Similar to previously reported data for nutrient intakes, HEI-2015 total and component scores for ASA24 recalls were comparable to those for 4DFRs, but not FFQs. Trial registration ClinicalTrials.gov identifier: NCT03268577 ( http://www.clinicaltrials.gov ).

OBJECTIVES: To better understand host-microbe interactions, a more computationally intensive, multivariate, machine learning approach must be utilized. Accordingly, we aimed to identify biomarkers with high predictive accuracy for dietary intake. METHODS: Data were aggregated from five randomized, controlled, feeding studies in adults (n = 199) that provided avocados, almonds, broccoli, walnuts, or whole grain oats and whole grain barley. Fecal samples were collected during treatment and control periods for each study for DNA extraction. Subsequently, the 16S rRNA gene (V4 region) was amplified and sequenced. Sequence data were analyzed using DADA2 and QIIME2. Marginal screening using the Kruskal-Wallis test was performed on all species-level taxa to examine the differences between each of the 6 treatment groups and respective control groups. The top 20 species from each diet were selected and pooled together for multiclass classification using random forest. The resultant bacterial species were further decreased in a stepwise fashion and iteratively analyzed with the variable importance generated from random forest to determine a compact feature set with a minor loss of accuracy in the prediction of food consumed. RESULT: When all six foods were analyzed together using the top 20 species of each diet, oats and barley were frequently confused for each other, with 44% and 47% classification error, respectively, and the overall model accuracy was 66%. Collapsing oats and barley into one category, whole grains, reduced the classification error of the whole grain category to 6% and improved the overall model accuracy to 73%. Refitting the random forest with the top 30, 20, and 10 important species resulted in correct identification of the 5 foods (avocados, almonds, broccoli, walnuts, and whole grains) 75%, 74%, and 70% of the time, respectively. CONCLUSIONS: These results reveal promise in accurately predicting foods consumed using bacterial species as biomarkers. Ongoing analyses include incorporation of metagenomic and metabolomic data into the models to improve predictive accuracy and utilize the multi-omics dataset to predict health status. Long-term, these approaches may inform diet-microbiota-tailored recommendations. FUNDING SOURCES: This research was funded by The Foundation for Food and Agriculture Research, USDA, Hass Avocado Board, and USDA National Institute of Food and Agriculture, Hatch project 1009249.

A Mediterranean dietary pattern is widely recommended because of an extensive evidence base showing beneficial effects on cardiovascular disease (CVD) risk and mortality. The reduction in cardiovascular mortality is due, in part, to the improvements in lipids and lipoproteins versus a Western dietary pattern. Plant-based diets such as a Mediterranean diet are recommended for CVD risk reduction. However, adherence to plant-based diets is often hampered by the limited or restricted intake of red meat, a staple of the American diet. We conducted a multicenter, 4-period controlled feeding, randomized crossover study at Penn State University and USDA-Beltsville to evaluate the effects of a Mediterranean diet (CHO 42%, PRO 17%, FAT 41%, SFA 8%, MUFA 26%, PUFA 8%) with different quantities of lean beef (0.5, 2.5 and 5.5 oz/day) compared to an Average American diet (AAD; CHO 52%, PRO 15%, FAT 33%, SFA 12%, MUFA 13%, PUFA 8%) on CVD risk factors. We tested the hypothesis that including 0.5, 2.5 or 5.5 oz/d (based on 2100 kcals) of lean beef in a healthy Mediterranean style diet will confer similar cardioprotective benefits, and be superior to an AAD. Each Mediterranean diet included 7oz. equivalents of protein, of which 0.5, 2.5 or 5.5 oz. came from beef and the remainder from fish, poultry, pork, nuts, eggs, and legumes. The quantities of beef reflect amounts consumed in a traditional Mediterranean diet (0.5 oz.), current consumption in the U.S. (2.5 oz.), and an amount that represents all animal protein equivalents (5.5 oz.). Participants (n=60; 30 per site) included generally healthy normal to overweight/obese males and females (BMI= 20-38 kg/m 2 ) 30 to 60 years. Participants were randomized to each of the 4 diets for 4 weeks with an approximate 2-week break between treatments. Fasting blood samples were collected on two consecutive days at baseline (start of study) and at the end of each 4-week period. All three Mediterranean diets elicited similar lowering of total cholesterol (TC; p

OBJECTIVES: Metabolomic studies can be utilized to generate biomarkers of food intake. Undigested food components affect the fecal microbiota and metabolome. Accordingly, we aimed to identify fecal metabolites unique to almond and walnut consumption. METHODS: Untargeted metabolomic analyses were completed on 66 endpoint fecal samples from two separate 3-week randomized, controlled-feeding, crossover studies examining almond (n = 30) and walnut (n = 36) consumption in adults (25–75 yr). Control diets, representative of the typical American diet, were fed at weight maintenance with 0 g/day of nuts. During the treatment arms, the base diet was scaled down to allow isocaloric inclusion of 42 g/day of almonds or walnuts. The Kruskal-Wallis H test was used to determine statistically significant metabolites between treatment and control groups with Benjamini-Hochberg false discovery rate adjustments (reported as q-values). RESULTS: Of the 318 quantifiable fecal metabolites, 42 were significantly different when comparing the treatment groups to their respective controls after adjustment (q

High intakes of industrial trans fatty acids (iTFA) increase circulating low density lipoprotein cholesterol (LDL-C) levels, which has implicated iTFA in coronary heart disease (CHD) risk. Published data on iTFA and LDL-C, however, represent higher intake levels than the U.S. population currently consume. This study used state-of-the-art evidence mapping approaches to characterize the full body of literature on LDL-C and iTFA at low intake levels. A total of 32 independent clinical trials that included at least one intervention or control group with iTFA at ≤3%en were found. Findings indicated that a wide range of oils and interventions were used, limiting the ability to determine an isolated effect of iTFA intake. Few data points were found for iTFA at

Recent studies have demonstrated that the energy provided by several tree nuts is less than that predicted by the Atwater factors, though energy available from cashews has never been assessed. The objective of this study was to evaluate the metabolizable energy in cashew nuts. Eighteen healthy adults were enrolled in a randomized, crossover study with two treatment periods. Subjects were fed a fully controlled base diet for 4 weeks with either no additions or with the addition of 42 g/day (1.5 servings) of cashew nuts, with the final treatment diets being isocaloric. Complete diet collections were analyzed for nitrogen (for protein), fat, energy, and carbohydrate by difference. During the final week of each intervention phase, subjects collected all feces and urine produced, and these were also analyzed for nitrogen (feces and urine), energy (feces and urine), and fat (feces). The resulting data were used to calculate the metabolizable energy of cashews and the digestibility of macronutrients. The average available energy (calorie) content of a 28 g serving of cashew nuts was 137 kcal (&plusmn, 3.4 kcal SEM) and ranged from 105 to 151 kcal. The mean value of 137 kcal/serving is 16% lower (p &lt, 0.0001) than what is typically found on food labels. Digestibility of energy, fat, protein, and carbohydrate was lower for the cashew-containing diet compared to the control diet (92.9% vs. 94.9%, p &lt, 0.0001 for energy, 96.1% vs. 97.8%, p = 0.0009 for fat, 90.1% vs. 91.2%, p = 0.0012 for protein, 92.9% vs. 94.9%, p &lt, 0.0001 for carbohydrate, for the cashew-containing diet vs. the control diet, respectively). In conclusion, cashews provide fewer calories than the values predicted by the Atwater factors, as found on current food labels.

The gut microbiome metabolizes choline and carnitine to release trimethylamine (TMA), which subsequently undergoes hepatic conversion to trimethylamine N-oxide (TMAO). Elevated TMAO levels are associated with cardiovascular disease and all-cause mortality risk. Dietary flavanols modulate the composition and function of the gut microbiome. Therefore, the possibility exists that these compounds could reduce intestinal TMA production and lower circulating TMAO. However, this hypothesis has never been tested in humans. A secondary analysis was performed on blood samples from a clinical study in which obese subjects at risk for insulin resistance consumed tea or cocoa flavanols in a randomized crossover design while consuming a controlled diet. These subjects generally had elevated TMAO levels (approximate to 5 M) compared to levels previously measured in healthy subjects (approximate to 1 M). None of the interventions significantly altered TMAO levels. Individual variability for choline and carnitine was relatively low. However, TMAO exhibited somewhat greater inter-individual variability. No differences in mean TMAO concentrations observed across interventions were seen based on separating subjects by glycemic status, body mass index (BMI), race, age, or gender. However, subject minimum and maximum values observed across the interventions appeared to be more strongly associated with glycemic status and age than mean values across interventions, suggesting that average TMAO values over time may be less useful than maximum or minimum values as markers of disease risk. Traditional physiological characteristics do not appear to predict TMAO responsiveness to flavanol interventions. However, African-American subjects appeared less responsive compared to non-Hispanic white subjects for both green tea and high cocoa treatments, and female subjects appeared less responsive than males for the high cocoa treatment. The present results suggest that a short-term flavanol intervention does not generally reduce fasting TMAO levels in subjects with elevated circulating TMAO. Virginia Agricultural Experiment Station; Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture; U.S. Department of AgricultureUnited States Department of Agriculture (USDA); Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education program (TOR IGEP) Funding for the present work was provided, in part, by the Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture (APN, KPD). Funding for the original study was provided by the U.S. Department of Agriculture (DJB, JAN). Funding for LEG was provided by the Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education program (TOR IGEP). Public domain – authored by a U.S. government employee

Berries and other anthocyanin-rich treatments have prevented weight gain and adiposity in rodent models of diet-induced obesity. Their efficacy may be explained by modulation of energy substrate utilization. However, this effect has never been translated to humans. The objective of this study was to evaluate the effects of berry intake on energy substrate use and glucoregulation in volunteers consuming a high-fat diet. Twenty-seven overweight or obese men were enrolled in a randomized, placebo-controlled crossover study with two treatment periods. Subjects were fed an investigator controlled, high-fat (40% of energy from fat) diet which contained either 600 g/day blackberries (BB, 1500 mg/day flavonoids) or a calorie and carbohydrate matched amount of gelatin (GEL, flavonoid-free control) for seven days prior to a meal-based glucose tolerance test (MTT) in combination with a 24 h stay in a room-sized indirect calorimeter. The washout period that separated the treatment periods was also seven days. The BB treatment resulted in a significant reduction in average 24 h respiratory quotient (RQ) (0.810 vs. 0.817, BB vs. GEL, p = 0.040), indicating increased fat oxidation. RQ during the MTT was significantly lower with the BB treatment (0.84) compared to GEL control (0.85), p = 0.004. A 4 h time isolation during dinner showed similar treatment effects, where RQ was reduced and fat oxidation increased with BB (0.818 vs. 0.836, 28 vs. 25 g, respectively, BB vs. GEL treatments). The glucose AUC was not different between the BB and GEL treatments during the MTT (3488 vs. 4070 mg&middot, min/dL, respectively, p = 0.12). However, the insulin AUC was significantly lower with the BB compared to the GEL control (6485 vs. 8245 &micro, U&middot, min/mL, p = 0.0002), and HOMA-IR improved with BB (p = 0.0318). Blackberry consumption may promote increased fat oxidation and improved insulin sensitivity in overweight or obese males fed a high fat diet.

Background: The National Health and Nutrition Examination Survey physical activity questionnaire (PAQ) is used to estimate activity energy expenditure (AEE) and moderate to vigorous physical activity (MVPA). Bias and variance in estimates of AEE and MVPA from the PAQ have not been described, nor the impact of measurement error when utilizing the PAQ to predict biomarkers and categorize individuals. Methods: The PAQ was administered to 385 adults to estimate AEE (AEE:PAQ) and MVPA (MVPA:PAQ), while simultaneously measuring AEE with doubly labeled water (DLW; AEE:DLW) and MVPA with an accelerometer (MVPA:A). Results: Although AEE:PAQ [3.4 (2.2) MJ·d−1] was not significantly different from AEE:DLW [3.6 (1.6) MJ·d−1; P > .14], MVPA:PAQ [36.2 (24.4) min·d−1] was significantly higher than MVPA:A [8.0 (10.4) min·d−1; P Conclusions: Group-level bias in AEE:PAQ was small, but large for MVPA:PAQ. Poor within-participant estimates of AEE:PAQ and MVPA:PAQ lead to attenuated relationships with biomarkers and misclassifications of participants who met or who did not meet the Physical Activity Guidelines for Americans.

BACKGROUND Previous studies have shown that the metabolizable energy (ME) content (energy available to the body) of certain nuts is less than predicted by the Atwater factors. However, very few nuts have been investigated to date, and no information is available regarding the ME of walnuts. OBJECTIVE A study was conducted to determine the ME of walnuts when consumed as part of a typical American diet. METHODS Healthy adults (n = 18; mean age = 53.1 y; body mass index = 28.8 kg/m(2)) participated in a randomized crossover study with 2 treatment periods (3 wk each). The study was a fully controlled dietary feeding intervention in which the same base diet was consumed during each treatment period; the base diet was unsupplemented during one feeding period and supplemented with 42 g walnuts/d during the other feeding period. Base diet foods were reduced in equal proportions during the walnut period to achieve isocaloric food intake during the 2 periods. After a 9 d diet acclimation period, subjects collected all urine and feces for ∼1 wk (as marked by a Brilliant Blue fecal collection marker) for analysis of energy content. Administered diets, walnuts, and fecal and urine samples were subjected to bomb calorimetry, and the resulting data were used to calculate the ME of the walnuts. RESULTS One 28-g serving of walnuts contained 146 kcal (5.22 kcal/g), 39 kcal/serving less than the calculated value of 185 kcal/serving (6.61 kcal/g). The ME of the walnuts was 21% less than that predicted by the Atwater factors (P < 0.0001). CONCLUSION Consistent with other tree nuts, Atwater factors overestimate the metabolizable energy value of walnuts. These results could help explain the observations that consumers of nuts do not gain excessive weight and could improve the accuracy of food labeling. This trial was registered at clinicaltrials.gov as NCT01832909.

Inflammation and hemostasis contribute to the etiology of cardiovascular disease. We previously demonstrated that moderate alcohol consumption (1-2 drinks/day) may decrease risk for cardiovascular disease because of an improved lipid profile. In addition to these beneficial changes, the alcohol-mediated reduction in risk may be through its effect on inflammation and hemostasis. The objective of the study was to evaluate the effect of moderate alcohol consumption on biomarkers of inflammation and hemostasis in postmenopausal women.As part of a controlled diet study, 53 postmenopausal women each consumed a weight-maintaining diet plus 0, 15 and 30 g/day of alcohol for 8 weeks, in a randomized crossover design. The controlled diet contained 15%, 53% and 32% of energy from protein, carbohydrate and fat, respectively.Soluble intercellular adhesion molecule-1 decreased by 5% (P0.05) with consumption of both 15 and 30 g of alcohol. Fibrinogen concentrations decreased by 4% and 6% (P0.05) after consumption of 15 and 30 g alcohol, respectively. Fibrin D-dimer decreased by 24% (P0.05) after consumption of 30 g of alcohol. Plasminogen activator inhibitor-1 (PAI-1) concentrations were increased 27 and 54% (P0.05) after consumption of 15 and 30 g of alcohol. Plasma high-sensitivity C-reactive protein, interleukin-6 and factor VII coagulant activity did not change with alcohol consumption.These data suggest that moderate alcohol consumption may have beneficial effects on inflammation and hemostasis in postmenopausal women, and this may be somewhat mitigated by an increase in PAI-1.

Recent work suggests that plant sterol (PS) consumption may lower triglyceride (TG) concentrations; however, human clinical trial evidence is inconsistent. We associated SNP r5882 in cholesteryl ester transfer protein with changes in TG concentrations following PS consumption (2 g/day for 4 weeks) in a dual-centre, single-blind, randomized, crossover trial. TG concentrations were lowered in homozygotes for the minor G-allele of rs5882 (–0.46 ± 0.13 mmol/L, p = 0.002, n = 10); there was no effect in the A-allele carriers.

Background: Benefits of plant sterols (PS) for cholesterol loweringare compromised by large variability in efficacy across individuals.High fractional cholesterol synthesis measured by deuterium incor-poration has been associated with nonresponse to PS consumption;however, prospective studies that show this association have yet tobe conducted.Objective: Thegoalwastotestwhetherthelathosterol-to-cholesterolratio (L:C), a surrogate marker of endogenous cholesterol synthesis,serves as an a priori predictor of cholesterol lowering in response toPS consumption.Design: Sixty-three mildly hypercholesterolemic adults who werepreselected as possessing either high endogenous cholesterol synthe-sis [HS;n = 24;L:C = 2.036 0.39mmol/mmol(mean 6 SD)]orlowendogenous cholesterol synthesis [LS; n = 39; L:C = 0.99 6 0.28mmol/mmol (mean 6 SD)] on the basis of baseline L:C consumed2 g PS/d or a placebo for 28 d with the use of a dual-center, single-blind, randomized crossover design. Plasma lipid and noncholesterolsterol concentrations were measured at the end of each phase.Results: PS consumption lowered total cholesterol (TC; 20.25 60.05 mmol/L; P , 0.0001) and LDL cholesterol (20.17 6 0.04mmol/L; P , 0.0001) overall. Specifically, LS individuals respondedto PS treatment with a reduction in TC (20.40 6 0.07 mmol/L; P ,0.0001) and LDL cholesterol (20.29 6 0.05 mmol/L; P = 0.0002),whereas HS individuals failed to show cholesterol lowering (TC:20.09 6 0.09 mmol/L; P = 0.2843; LDL cholesterol: 20.05 60.07 mmol/L; P = 0.4917). The odds of LS participants respondingwith cholesterol lowering better thanthe mean cholesterol lowering inall participants to PS consumption were 4.25 (95% CI: 1.242, 14.556;P = 0.0211) for TC and 3.36 (95% CI: 1.112, 10.161; P = 0.0317) forLDL cholesterol, which was higher than for HS participants.Conclusions: The L:C ratio predicts the extent of reduction incirculating TC and LDL cholesterol in response to PS consumption.Cholesterol synthesis assessment may thus have a use in identifyingresponders and nonresponders to PS therapy. This trial was regis-tered at clinicaltrials.govas NCT01131832. Am J Clin Nutr doi:10.3945/ajcn.114.095356.Keywords cholesterol lowering, interindividual variability, non-cholesterol sterols, plant sterols, randomized controlled trialINTRODUCTIONPlant sterols (PS)

Background: Almond processing has been shown to differentially impact metabolizable energy; however, the effect of food form on the gastrointestinal microbiota is under-investigated. Objective: We aimed to assess the interrelationship of almond consumption and processing on the gastrointestinal microbiota. Design: A controlled-feeding, randomized, five-period, crossover study with washouts between diet periods was conducted in healthy adults (n = 18). Treatments included: (1) zero servings/day of almonds (control); (2) 1.5 servings (42 g)/day of whole almonds; (3) 1.5 servings/day of whole, roasted almonds; (4) 1.5 servings/day of roasted, chopped almonds; and (5) 1.5 servings/day of almond butter. Fecal samples were collected at the end of each three-week diet period. Results: Almond consumption increased the relative abundances of Lachnospira, Roseburia, and Dialister (p ≤ 0.05). Comparisons between control and the four almond treatments revealed that chopped almonds increased Lachnospira, Roseburia, and Oscillospira compared to control (p < 0.05), while whole almonds increased Dialister compared to control (p = 0.007). There were no differences between almond butter and control. Conclusions: These results reveal that almond consumption induced changes in the microbial community composition of the human gastrointestinal microbiota. Furthermore, the degree of almond processing (e.g., roasting, chopping, and grinding into butter) differentially impacted the relative abundances of bacterial genera.

Background A limited number of studies have evaluated self-reported dietary intakes against objective recovery biomarkers. Objective The aim was to compare dietary intakes of multiple Automated Self-Administered 24-h recalls (ASA24s), 4-d food records (4DFRs), and food-frequency questionnaires (FFQs) against recovery biomarkers and to estimate the prevalence of under- and overreporting. Design Over 12 mo, 530 men and 545 women, aged 50-74 y, were asked to complete 6 ASA24s (2011 version), 2 unweighed 4DFRs, 2 FFQs, two 24-h urine collections (biomarkers for protein, potassium, and sodium intakes), and 1 administration of doubly labeled water (biomarker for energy intake). Absolute and density-based energy-adjusted nutrient intakes were calculated. The prevalence of under- and overreporting of self-report against biomarkers was estimated. Results Ninety-two percent of men and 87% of women completed ≥3 ASA24s (mean ASA24s completed: 5.4 and 5.1 for men and women, respectively). Absolute intakes of energy, protein, potassium, and sodium assessed by all self-reported instruments were systematically lower than those from recovery biomarkers, with underreporting greater for energy than for other nutrients. On average, compared with the energy biomarker, intake was underestimated by 15-17% on ASA24s, 18-21% on 4DFRs, and 29-34% on FFQs. Underreporting was more prevalent on FFQs than on ASA24s and 4DFRs and among obese individuals. Mean protein and sodium densities on ASA24s, 4DFRs, and FFQs were similar to biomarker values, but potassium density on FFQs was 26-40% higher, leading to a substantial increase in the prevalence of overreporting compared with absolute potassium intake. Conclusions Although misreporting is present in all self-report dietary assessment tools, multiple ASA24s and a 4DFR provided the best estimates of absolute dietary intakes for these few nutrients and outperformed FFQs. Energy adjustment improved estimates from FFQs for protein and sodium but not for potassium. The ASA24, which now can be used to collect both recalls and records, is a feasible means to collect dietary data for nutrition research.

Wild blueberries have a high content of polyphenols, but there is limited data evaluating their health benefits in adults at risk for type 2 diabetes. The objective of the study was to investigate whether consumption of 100% wild blueberry juice improves cardiometabolic biomarkers associated with type 2 diabetes risk. A single-blind, randomized, placebo-controlled, crossover design trial was conducted in which adults (women, n = 19, ages 39–64 y) at risk for type 2 diabetes consumed 240 mL of wild blueberry juice or a placebo beverage as part of their free-living diet for 7 days. Blood was collected to determine various biomarkers such as fasting plasma glucose, fasting serum insulin, surrogate markers of insulin sensitivity, triglycerides, inflammation (interleukin-6, interleukin-10, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, serum amyloid A), adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1), oxidative stress (LDL-oxidation, total 8-isoprostanes), and nitric oxide. Endothelial function and blood pressure were also assessed. Wild blueberry juice consumption for 7 days produced no significant changes in glucose, insulin, insulin sensitivity, triglycerides, inflammatory markers, adhesion molecules, oxidative stress, endothelial function or blood pressure. However, wild blueberry juice consumption showed a trend for lowering systolic blood pressure: 120.8 ± 2.2 mmHg in the placebo group vs 116.0 ± 2.2 mmHg in the blueberry juice group (P = 0.088). Serum concentrations of nitrates and nitrites, an index of nitric oxide production, increased from 2.9 ± 0.4 μM after placebo drink to 4.1 ± 0.4 μM after drinking wild blueberry juice (P = 0.039). Short-term consumption of wild blueberry juice may promote cardioprotective effects, by improving systolic blood pressure, possibly through nitric oxide production, in adults at risk for type 2 diabetes. This outcome warrants longer-term human studies of blueberries, including defined amounts of either the whole fruit or juice, to clarify whether polyphenol-rich foods can be efficacious for improving cardiometabolic biomarkers in adults at risk for type 2 diabetes. NCT02139878 , clinicaltrials.gov; date of registration: May 4, 2014.

The objective of this study was to evaluate the effect of 8 weeks of no alcohol, low (1 drink or 15 g/day) and moderate (2 drinks or 30 g/day) alcohol consumption on markers of bone health: fasting serum 25-hydroxy vitamin D (25(OH)D), osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), urine deoxypyridinoline (DPD) and helical peptide (HP) in postmenopausal women (n=51). Compared with no alcohol, 1 or 2 drinks/day for 8 weeks had no significant impact on any of the bone markers. Within each alcohol group, obese women had significantly lower serum 25(OH)D and higher DPD concentrations than normal weight women. Season significantly affected the concentrations of serum 25(OH)D, but there was no significant interaction between alcohol and season on serum 25(OH)D concentrations. Low or moderate alcohol consumption for 8 weeks had no significant impact on markers of bone health in postmenopausal women.

When food is heated to high temperatures, the characteristic “browning” generates advanced glycation end products (AGEs). AGEs are associated with an increased risk of cardiovascular disease, diabetes, and other adverse outcomes. Whether dietary AGEs are absorbed and are harmful to human health remains highly controversial. The objective of this study was to compare the effects of a diet high or low in AGEs on endothelial function, circulating AGEs, inflammatory mediators, and circulating receptors for AGEs in healthy adults. A randomized, parallel-arm, controlled dietary intervention was conducted for 6 wk with 24 healthy adults, aged 50–69 y, that compared isocaloric, food-equivalent diets that were prepared at either high or mild temperatures. Peripheral arterial tonometry, serum and urine carboxymethyl-lysine (CML), inflammatory mediators (interleukin-6, C-reactive protein, vascular adhesion molecule-1, and tumor necrosis factor-α receptors I and II), soluble receptor for AGEs, and endogenous secretory receptor for AGEs were measured at baseline and after 6 wk of dietary intervention. In the low-AGE diet group, the following changed from baseline to 6 wk (mean ± SE): serum CML from 763 ± 24 to 679 ± 29 ng/mL (P = 0.03) and urine CML from 1.37 ± 1.47 to 0.77 ± 2.01 μg/mL creatinine (P = 0.02). There were no significant changes in serum and urinary CML concentrations from baseline to follow-up in the high-AGE diet group. A high- or low-AGE diet had no significant impact on peripheral arterial tonometry or any inflammatory mediators after 6 wk of dietary intervention. In healthy middle-aged to older adults, consumption of a diet high or low in AGEs for 6 wk had no impact on endothelial function and inflammatory mediators, 2 precursors of cardiovascular disease. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT01402973","term_id":"NCT01402973"}}NCT01402973.

OBJECTIVES: To evaluate the effects of a Mediterranean (Med) style diet with varying quantities of lean beef on non-HDL and HDL lipid subspecies. We hypothesized that a Med diet with lean beef would confer cardiovascular benefits beyond a standard lipid panel and be superior to an average American diet (AAD). METHODS: We conducted a multicenter, 4-period controlled feeding, randomized crossover study at Penn State University and USDA-Beltsville to evaluate the effects of a Med diet (CHO 42%, PRO 17%, FAT 41%, SFA 8%, MUFA 26%, PUFA 8%) with different quantities of lean beef (0.5, 2.5 and 5.5 oz/day) compared to an average American diet (AAD; CHO 52%, PRO 15%, FAT 33%, SFA 12%, MUFA 13%, PUFA 8%) on CVD risk factors. Participants (n = 66) included generally healthy normal to overweight/obese males and females (BMI = 20–38 kg/m(2)) 30 to 67 years. Participants were randomized to each of the 4 diets for 4 weeks with an approximate 2-week break between treatments. Fasting blood samples were collected on two consecutive days at baseline (start of study), and at the end of each diet period. RESULTS: All three Med diets decreased LDL-C versus AAD (−10.5 ± 2.0, −9.0 ± 2.0, −6.8 ± 2.0 mg/dL, P