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Effects of butter and 2 types of margarine on blood lipid and lipoprotein concentrations were compared in a controlled diet study with 23 men and 23 women. Table spreads, added to a common basal diet, provided 8.3% of energy as fat. Diets averaged 34.6% of energy as fat and 15.5% as protein. Each diet was fed for 5 wk in a 3 x 3 Latin-square design. One margarine (TFA-M) approximated the average trans monoene content of trans fatty acid-containing margarines in the United States (17% trans fatty acids by dry wt). The other margarine (PUFA-M) was free of trans unsaturated fatty acids; it contained approximately twice the polyunsaturated fatty acid content of TFA-M (49% compared with 27% polyunsaturated fatty acids). The tub-type margarines had similar physical properties at ambient temperature. Fasting blood lipids and lipoproteins were determined in 2 samples taken from the subjects during the fifth week of each dietary treatment. Compared with butter, total cholesterol was 3.5% lower (P=0.009) after consumption of TFA-M and 5.4% lower (P< 0.001) after consumption of PUFA-M. Similarly, LDL cholesterol was 4.9% lower (P=0.005) and 6.7% lower (P< 0.001) after consumption of TFA-M and PUFA-M, respectively. Neither margarine differed from butter in its effect on HDL cholesterol or triacylglycerols. Thus, consumption of TFA-M or PUFA-M improved blood lipid profiles for the major lipoproteins associated with cardiovascular risk when compared with butter, with a greater improvement with PUFA-M than with TFA-M. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Diabetes mellitus and its sequelae are a major and growing public health problem. The prevalence of diabetes worldwide is 194 million persons, or 5.1% of the population, and is projected to increase to 333 million, or 6.3% of the population, by 2025. Type 2 diabetes accounts for approximately 90-95% of those with diabetes in the United States and other developed countries. Tea is the most widely consumed beverage in the world, second only to water. Tea contains polyphenols and other components that may reduce the risk of developing chronic diseases such as cardiovascular disease and cancer. Some evidence also shows that tea may affect glucose metabolism and insulin signaling, which, as a result, has spurred interest in the health effects of tea consumption on diabetes. Epidemiologic studies suggest some relation between tea consumption and a reduced risk of type 2 diabetes, although the mechanisms for these observations are uncertain. Findings from in vitro and animal models suggest that tea and its components may influence glucose metabolism and diabetes through several mechanisms, such as enhancing insulin sensitivity. Some human clinical studies evaluating tea and its components show improvement in glucoregulatory control and endothelial function. However, further controlled clinical trials are required to gain a better understanding of the long-term effects of tea consumption in persons with diabetes. [ABSTRACT FROM AUTHOR]

Background: Activity monitors (AM) are small, electronic devices used to quantify the amount and intensity of physical activity (PA). Unfortunately, it has been demonstrated that data loss that occurs when AMs are not worn by subjects (removals during sleeping and waking hours) tend to result in biased estimates of PA and total energy expenditure (TEE). No study has reported the degree of data loss in a large study of adults, and/or the degree to which the estimates of PA and TEE are affected. Also, no study in adults has proposed a methodology to minimize the effects of AM removals.Methods: Adherence estimates were generated from a pool of 524 women and men that wore AMs for 13 - 15 consecutive days. To simulate the effect of data loss due to AM removal, a reference dataset was first compiled from a subset consisting of 35 highly adherent subjects (24 HR; minimum of 20 hrs/day for seven consecutive days). AM removals were then simulated during sleep and between one and ten waking hours using this 24 HR dataset. Differences in the mean values for PA and TEE between the 24 HR reference dataset and the different simulations were compared using paired t-tests and/or coefficients of variation.Results: The estimated average adherence of the pool of 524 subjects was 15.8 +/- 3.4 hrs/day for approximately 11.7 +/- 2.0 days. Simulated data loss due to AM removals during sleeping hours in the 24 HR database (n = 35), resulted in biased estimates of PA (p < 0.05), but not TEE. Losing as little as one hour of data from the 24 HR dataset during waking hours results in significant biases (p < 0.0001) and variability (coefficients of variation between 7 and 21%) in the estimates of PA. Inserting a constant value for sleep and imputing estimates for missing data during waking hours significantly improved the estimates of PA.Conclusion: Although estimated adherence was good, measurements of PA can be improved by relatively simple imputation of missing AM data. [ABSTRACT FROM AUTHOR]

Epidemiology studies evaluate associations between the metabolome and disease risk. Urine is a common biospecimen used for such studies due to its wide availability and non-invasive collection. Evaluating the robustness of urinary metabolomic profiles under varying preanalytical conditions is thus of interest. Here we evaluate the impact of sample handling conditions on urine metabolome profiles relative to the gold standard condition (no preservative, no refrigeration storage, single freeze thaw). Conditions tested included the use of borate or chlorhexidine preservatives, various storage and freeze/thaw cycles. We demonstrate that sample handling conditions impact metabolite levels, with borate showing the largest impact with 125 of 1048 altered metabolites (adjusted P < 0.05). When simulating a case-control study with expected inconsistencies in sample handling, we predicted the occurrence of false positive altered metabolites to be low (< 11). Predicted false positives increased substantially (≥63) when cases were simulated to undergo alternate handling. Finally, we demonstrate that sample handling impacts on the urinary metabolome were markedly smaller than those in serum. While changes in urine metabolites incurred by sample handling are generally small, we recommend implementing consistent handling conditions and evaluating robustness of metabolite measurements for those showing significant associations with disease outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Numerous systematic reviews (SR) and meta-analyses (MA) on low calorie sweeteners (LCS) have been published in recent years, concluding that LCS have beneficial, neutral, or detrimental effects on various health outcomes, depending on the review., Objectives: The objective of this overview of reviews was to determine how the methodologies of SR investigating the association between LCS consumption and body weight (BW) influence their findings and whether MA results can provide a consistent estimated effect., Methods: Systematic searches of PubMed, Scopus, and Cochrane Library were conducted in November 2022 to identify SR of randomized controlled trials (RCT) or non-randomized studies (NRS) investigating the association between LCS consumption and BW. The methods, MA results, and conclusions were extracted from each eligible SR., Results: Of the 985 search results, 20 SR evaluated the association between LCS and BW, drawing from publications of 75 RCT, 42 prospective cohort studies, and 10 cross-sectional studies. There was a considerable lack of overlap of studies included within each SR attributed, in part, to the inclusion of studies based on design; thus, each SR synthesized results from distinctly different studies. Evidence synthesis methods were heterogeneous and often opaque, making it difficult to determine why results from certain studies were excluded or why disparate results were observed between SR., Conclusions: SR investigating the effect of LCS on BW implement different methodologies to answer allegedly the same question, drawing from a different set of heterogeneous studies, ignoring the basic assumptions required for MA, resulting in disparate results and conclusions. Previous MA show the large effects of study design, which results in inconsistent estimates of the effect of LCS on BW between MA of RCT and NRS. Given the availability of long-term RCT, these studies should be the basis of determining causal relationships (or lack thereof) between LCS and BW. This trial was registered at PROSPERO as CRD42022351200., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: Underreporting of concussion symptoms in college athletics presents a challenge for sports medicine clinicians in evaluating and diagnosing such injuries. Some athletes do not report concussion symptoms because they do not recognize that they have a brain injury, however many athletes intentionally withhold symptoms to avoid removal from sport participation., Objective: To examine individual factors that influence college athletes' intentions to report concussion symptoms., Design: Cross-sectional study., Setting: Collegiate athletics., Participants: 2,649 student-athletes from 23 sports, across 22 colleges/universities., Main Outcome Measures: The primary outcome was intention to report concussion symptoms. Predictor variables included demographics (age, race/ethnicity, sex, sport type, number of years in sport, number of previous concussions, and perceived concussion symptom knowledge), athletic identity, attitudes toward symptom reporting, perceived social pressure (injunctive and descriptive norms), and perceived behavioral control (capacity and autonomy)., Results: Hierarchical ordinary least squares regression revealed positive effects of attitude (b = .063; P = .005), descriptive norms (b = .131; P < .001), injunctive norms (b = .107; P < .001), and capacity (b = .196; P < .001) on intention to report symptoms. Athletic identity and participation in collision sports had small negative indirect effects on intention, while perceived concussion knowledge had a small positive indirect effect. The full regression model explained 14.24% of the variance in concussion reporting intention., Conclusions: These findings may help clinicians develop more focused interventions that address key social and individual determinants of underreporting, including attitude, injunctive and descriptive norms, and capacity to report. Athletic identity, sport type, and perceived understanding of concussion symptoms also influence reporting intention to a lesser extent. Previous research in this area has often failed to address a diverse population of college-age athletes from different sports and NCAA divisions.

Background: Undigested components of the human diet affect the composition and function of the microorganisms present in the gastrointestinal tract. Techniques like metagenomic analyses allow researchers to study functional capacity, thus revealing the potential of using metagenomic data for developing objective biomarkers of food intake., Objectives: As a continuation of our previous work using 16S and metabolomic datasets, we aimed to utilize a computationally intensive, multivariate, machine-learning approach to identify fecal KEGG (Kyoto encyclopedia of genes and genomes) Orthology (KO) categories as biomarkers that accurately classify food intake., Methods: Data were aggregated from 5 controlled feeding studies that studied the individual impact of almonds, avocados, broccoli, walnuts, barley, and oats on the adult gastrointestinal microbiota. Deoxyribonucleic acid from preintervention and postintervention fecal samples underwent shotgun genomic sequencing. After preprocessing, sequences were aligned and functionally annotated with Double Index AlignMent Of Next-generation sequencing Data v2.0.11.149 and MEtaGenome ANalyzer v6.12.2, respectively. After the count normalization, the log of the fold change ratio for resulting KOs between pre- and postintervention of the treatment group against its corresponding control was utilized to conduct differential abundance analysis. Differentially abundant KOs were used to train machine-learning models examining potential biomarkers in both single-food and multi-food models., Results: We identified differentially abundant KOs in the almond (n = 54), broccoli (n = 2474), and walnut (n = 732) groups (q < 0.20), which demonstrated classification accuracies of 80%, 87%, and 86% for the almond, broccoli, and walnut groups using a random forest model to classify food intake into each food group's respective treatment and control arms, respectively. The mixed-food random forest achieved 81% accuracy., Conclusions: Our 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., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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.

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.

Background: The fecal metabolome is affected 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 data sets to generate usable information. One promising aspect of these advancements is the ability to determine objective biomarkers of food intake., Objectives: We aimed to utilize a multivariate, machine learning approach to identify metabolite biomarkers that accurately predict food intake., Methods: Data were aggregated from 5 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 GC-MS metabolomic analysis; 344 metabolites were detected in preintervention samples, whereas 307 metabolites were detected postintervention. After removing metabolites that were only detected in either pre- or postintervention and those undetectable in ≥80% of samples in all study groups, changes in 96 metabolites relative concentrations (treatment postintervention minus preintervention) were utilized in random forest models to 1) examine the relation between food consumption and fecal metabolome changes and 2) rank the fecal metabolites by their predictive power (i.e., feature importance score)., Results: Using the change in relative concentration of 96 fecal metabolites, 6 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 with one another, almond intake was differentiated from walnut intake with 91% classification accuracy., Conclusions: 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (Published by Oxford University Press on behalf of the American Society for Nutrition 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse., Methods: We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets: 1) a control diet, in which the participant received 100% of his or her calorie needs 7 days per week, 2) a daily CR diet, in which the participant received 78% of his or her calorie needs 7 days per week, or 3) an intermittent CR diet, in which the participant received 100% of his or her calorie needs on 5 days per week and 25% of his or her calorie needs 2 days per week (i.e., a "5:2" style diet). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD3 + ;CD4 + (CD4 + ) and CD3 + ;CD4 - (as a proxy for CD8 + ) T cell subsets including effector memory, central memory, and naïve cells., Findings: 31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in effector memory (for CD4 - EM : -3.82%; 95%CI: -7.44, -0.21; for CD4 - : -6.96%; 95%CI: -11.96, -1.97) and Th1 subsets (-4.26%; 95% CI: -7.11, -1.40) and proportional increases in naïve subsets (for CD4 - : 10.11%; 95%CI: 3.30, 16.92%). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets., Interpretation: In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets and certain biologically-relevant lipid markers., Funding: National MS Society, NIH, Johns Hopkins Catalyst Award., Competing Interests: Declaration of interests Mr. Smith, Ms. Henry-Barron, Ms. Vizthum, Dr. Cassard, Dr. Kappogiannis, Mr. Sullivan, and Dr. Baer report no disclosures. Dr. Fitzgerald and Dr. Bhargava reports grants from NIH, grants from National MS Society, during the conduct of the study. Dr. Kornberg has received consulting fees from Biogen Idec, Janssen Pharmaceuticals, Novartis, OptumRx, and TG Therapeutics and received grants from NIH and the Department of Defense. Dr. Calabresi has received consulting fees from Disarm, NervGen, and Biogen and is PI on grants to JHU from Genentech. Dr. Mowry has grants from Biogen, is site PI for studies sponsored by Biogen and Genentech, has received free medication for a clinical trial from Teva, and receives royalties for editorial duties from UpToDate., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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: 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 < 0.0001). All MED diets elicited similar reductions in total LDL particle number compared with baseline (P < 0.005); however, significant decreases only occurred with MED0.5 (-91.2 nmol/L; 95% CI: -31.4, -151.0 nmol/L) and MED2.5 (-85.3 nmol/L; 95% CI: -25.4, -145.2 nmol/L) compared with AAD (P < 0.003). Compared with the AAD, non-HDL cholesterol (P < 0.01) and apoB (P < 0.01) were lower following the 3 MED diets; there were no differences between the MED diets. All diets reduced HDL-cholesterol and HDL particle number from baseline (P < 0.01)., Conclusions: Lipid and lipoprotein lowering was not attenuated with the inclusion of lean beef in amounts ≤71 g (2.5 oz)/d as part of a healthy low-saturated-fat Mediterranean-style diet.This study is registered at clinicaltrials.gov as NCT02723617., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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 < 0.05). Other than TC:HDL, there were no differences in lipid/lipoprotein markers when comparing HOSBO+FHSBO with HOSBO. LDLc and apoB were higher after HOSBO compared to SBO (p < 0.05). PO + PKO increased HDLc (p < 0.001) and apolipoprotein AI (p < 0.03) compared to HOSBO and HOSBO+FHSBO. With the exception of lipid hydroperoxides, dietary treatments did not affect other CHD markers. HOSBO, and blends thereof, is a PHO replacement that results in more favorable lipid/lipoprotein profiles compared to PO + PKO (an alternative fat with similar functional properties)., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Lipids published by Wiley Periodicals LLC on behalf of American Oil Chemists' Society.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Society for Nutrition.)

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., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Society for Nutrition.)

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)., (Copyright © 2020 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest We certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which they are associated and we certify that all financial and material support for this research and work are clearly identified in the Acknowledgments Section., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 ± 0.066 ln pmol min/mL, mean ± 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 ± 0.093 ln mg·min/dL, mean ± SE, p = 0.0738). These results suggest the potential for mixed berry preparations to improve post-prandial insulin response.

Background: The US Food and Drug Administration (FDA) approved a qualified health claim for tree nuts and reduction of cardiovascular disease. However, cashews are excluded from that claim due to their content of saturated fats, which is predominantly stearic acid. Because stearic acid is neutral with respect to blood lipids, several studies have been conducted to test the effect of cashew nuts on blood lipids, and these studies have produced conflicting results., Objectives: The aim of this study was to conduct a highly controlled intervention to determine the effect of cashews fed at the amount specified in the health claim on risk factors for cardiovascular disease., Methods: A total of 42 adults participated in a controlled-feeding study conducted as a randomized crossover trial with 2 treatment phases. The volunteers were provided the same base diet in both treatment phases, with no additions during the control phase and with the addition of 1.5 servings (42 g) of cashews/d for the cashew nut phase. During the cashew nut phase, the amount of all foods was decreased proportionally to achieve isocaloric overall diets in the 2 phases. After 4 wk of intervention, assessments included blood lipids, blood pressure, central (aortic) pressure, augmentation index, blood glucose, endothelin, proprotein convertase subtilisin/kexin type 9 (PCSK9), adhesion molecules, and clotting and inflammatory factors., Results: There were no significant differences in blood lipids, blood pressure, augmentation index, blood glucose, endothelin, adhesion molecules, or clotting factors in this weight-stable cohort. PCSK9 was significantly decreased after cashew consumption, although there was no change in LDL cholesterol., Conclusions: Consumption of 1.5 servings of cashew nuts/d, the amount associated with the FDA qualified health claim for tree nuts and cardiovascular disease, did not positively or adversely affect any of the primary risk factors for cardiovascular disease. This trial was registered at clinicaltrials.gov as NCT02628171.

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 (±3.4 kcal SEM) and ranged from 105 to 151 kcal. The mean value of 137 kcal/serving is 16% lower ( p < 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 < 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 < 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 (∼5 μM) compared to levels previously measured in healthy subjects (∼1 μM). 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.

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.

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·min/dL, respectively, p = 0.12). However, the insulin AUC was significantly lower with the BB compared to the GEL control (6485 vs. 8245 µU·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.

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., (Copyright © 2018. Published by Elsevier B.V.)

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 < .0001]. AEE:PAQ regressed on AEE:DLW and MVPA:PAQ regressed on MVPA:A yielded not only significant positive relationships but also large residual variances. The relationships between AEE and MVPA, and 10 of the 12 biomarkers were underestimated by the PAQ. When compared with accelerometers, the PAQ overestimated the number of participants who met the Physical Activity Guidelines for Americans., 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: 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 < 0.05). Fecal secondary bile acids, deoxycholic acid and lithocholic acid, were 25% and 45% lower, respectively, after the walnut treatment compared with the control treatment (P < 0.05). Serum LDL cholesterol and the noncholesterol sterol campesterol concentrations were 7% and 6% lower, respectively, after walnut consumption compared with after the control treatment (P < 0.01)., Conclusion: Walnut consumption affected the composition and function of the human gastrointestinal microbiota, increasing the relative abundances of Firmicutes species in butyrate-producing Clostridium clusters XIVa and IV, including Faecalibacterium and Roseburia, and reducing microbially derived, proinflammatory secondary bile acids and LDL cholesterol. These results suggest that the gastrointestinal microbiota may contribute to the underlying mechanisms of the beneficial health effects of walnut consumption. This trial was registered at www.clinicaltrials.gov as NCT01832909.

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., (Published by Elsevier Ltd.)

We have previously reported on the low lipid bioaccessibility from almond seeds during digestion in the upper gastrointestinal tract (GIT). In the present study, we quantified the lipid released during artificial mastication from four almond meals: natural raw almonds (NA), roasted almonds (RA), roasted diced almonds (DA) and almond butter from roasted almonds (AB). Lipid release after mastication (8.9% from NA, 11.8% from RA, 12.4% from DA and 6.2% from AB) was used to validate our theoretical mathematical model of lipid bioaccessibility. The total lipid potentially available for digestion in AB was 94.0%, which included the freely available lipid resulting from the initial sample processing and the further small amount of lipid released from the intact almond particles during mastication. Particle size distributions measured after mastication in NA, RA and DA showed most of the particles had a size of 1000 µm and above, whereas AB bolus mainly contained small particles (<850 µm). Microstructural analysis of faecal samples from volunteers consuming NA, RA, DA and AB confirmed that some lipid in NA, RA and DA remained encapsulated within the plant tissue throughout digestion, whereas almost complete digestion was observed in the AB sample. We conclude that the structure and particle size of the almond meals are the main factors in regulating lipid bioaccessibility in the gut., Competing Interests: None of the authors reported a conflict of interest related to the study.

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., Competing Interests: Partial support for this project was provided by the Almond Board of California and the USDA ARS. Baer and Novotny are employed by the USDA ARS and have received funding from the Almond Board of California. Holscher and Swanson have received funding from the USDA ARS. Taylor was funded by a Department of Food Science and Human Nutrition Graduate Fellowship and a College of Agricultural, Consumer, and Environmental Sciences Undergraduate Research Scholarship.

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., (Published by Oxford University Press on behalf of the American Society for Nutrition 2018.)

Scope: Evidence suggests that dietary pattern may affect polyphenol absorption and/or metabolism. Further, obesity is associated with lower circulating nutrients, though the reason is unclear. We investigated the pharmacokinetic (PK) response of polyphenols in obese/overweight versus lean individuals before and after repeated dosing of grape polyphenols., Methods and Results: A pilot study was conducted in which PK challenges were administered before and after 10 days of repeated dosing with polyphenols. Volunteers (6 lean, 6 overweight/obese) consumed resveratrol, grape seed extract, and grape juice (2125 mg total polyphenols) daily. On days 1 and 11, blood samples were collected for 6 h after the polyphenol dose and analyzed for deconjugated catechin, epicatechin, resveratrol, and quercetin. Area under the plasma polyphenol mass by time curves (AUCs) were greater for catechin, epicatechin, and quercetin on day 11 versus day 1 for low BMI individuals (p = 0.039) but not high BMI individuals. Further, AUCs were greater for epicatechin and resveratrol for low versus high BMI individuals (p = 0.041), with a similar trend for catechin (p = 0.065), on day 11 but not day 1., Conclusion: These results suggest that that obesity and repeated exposure may modify polyphenol absorption and/or metabolism in humans., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Heavy alcohol drinking is associated with increased breast cancer risk, but associations with low-to-moderate alcohol consumption are less clear and the biological mechanisms are not well defined. The objective of this study was to evaluate the effects of 8 weeks of low (15 g/d) and moderate (30 g/d) alcohol ingestion on concentrations of 15 urinary estrogen metabolites (EMs) in postmenopausal women (n = 51) in a controlled feeding study with a randomized crossover design. Compared to no alcohol, 15 g/day for 8 weeks had no effect on urinary EMs. However, compared to no alcohol, 30 g/day for 8 weeks decreased urinary 2-hydroestrone (2-OHE1) by 3.3% (P = 0.055) and increased 16-epiestriol (16-EpiE3) by 26.6% (P = 0.037). Trends for reduced urinary 2-OHE1 (P = 0.045), reduced ratio of 2-OH:16OH pathways (P = 0.008), and increased 16-EpiE3 (P = 0.035) were observed as alcohol ingestion increased from 0 g to 15 g to 30 g/d. Moderate alcohol consumption for 8 weeks had modest effects on urinary concentrations of 2-OHE1 and 16-EpiE3 among postmenopausal women in a carefully controlled feeding study., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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., Trial Registration: NCT02139878, clinicaltrials.gov; date of registration: May 4, 2014., Competing Interests: KSS, MIS and KTG received grant support from the Wild Blueberry Association of North American. TK, DJB, JAN, NLS, AC, PC and JAM reported no competing interest., (© The Author(s). 2017.)

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 <3%en, with the majority of low-level exposures actually representing control group interventions containing non-partially hydrogenated (PHO) oils. Further, it appears that few dose-response data points are available to assess the relationship of low levels of iTFA, particularly from PHO exposure, and LDL-C. Therefore, limited evidence is available to determine the effect of iTFA at current consumption levels on CHD risk., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The measured metabolizable energy (ME) of whole almonds has been shown to be less than predicted by Atwater factors. However, data are lacking on the effects of processing (roasting, chopping or grinding) on the ME of almonds. A 5-period randomized, crossover study in healthy individuals (n = 18) was conducted to measure the ME of different forms of almonds (42 g per day), as part of a controlled diet: whole, natural almonds; whole, roasted almonds; chopped almonds; almond butter; and control (0 g per day). After 9 days of adaptation to each diet, participants collected all urine and fecal samples for 9 days. Diets, urine, and feces were analyzed to determine ME. Fracture force and fracture properties of whole and chopped almonds were measured. Measured ME (kcal g -1 ) of whole natural almonds (4.42), whole roasted almonds (4.86), and chopped almonds (5.04) was significantly lower than predicted with Atwater factors (P < 0.001); ME of almond butter (6.53 kcal g -1 ) was similar to predicted (P = 0.08). The ME of whole roasted and chopped almonds was lower than almond butter (P < 0.0001). ME of whole natural almonds was lower than whole roasted almonds (P < 0.05). This may be due to lower hardness of whole roasted (298 ± 1.3 N) compared to whole natural almonds (345 ± 1.6 N) (P < 0.05), and to whole natural almonds fracturing into fewer, larger particles, thus inhibiting the release of lipids. Atwater factors overestimate the ME of whole (natural and roasted) and chopped almonds. The amount of calories absorbed from almonds is dependent on the form in which they are consumed.