Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

BACKGROUND: Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. METHODS AND RESULTS: HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. CONCLUSIONS: Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

The underappreciated diversity of bile acid modifications.

The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.

One Avocado per Day as Part of Usual Intake Improves Diet Quality: Exploratory Results from a Randomized Controlled Trial.

Background: Few clinical trials have evaluated diet quality change as a predictor of intervention effectiveness. Objectives: The aim of this study was to examine changes in the Healthy Eating Index (HEI)-2015 after a food-based intervention, and assess the associations between HEI-2015 change and intervention effects on cardiometabolic risk-related outcomes. Methods: The Habitual Diet and Avocado Trial was a 26-wk, multicenter, randomized, controlled parallel-arm study. Participants were 1008 individuals aged ≥25 y with abdominal obesity (females ≥ 35 inches; males ≥ 40 inches). The avocado-supplemented diet group was provided 1 avocado per day, and the habitual diet group maintained their usual diet. Change in diet quality was assessed using the HEI-2015 from a single 24-h recall conducted at 4 time points. Mixed models were used for analysis. Results: The avocado-supplemented diet group had a greater increase in the HEI-2015 (4.74 points; 95% CI: 2.93, 6.55) at 26 wk than the habitual diet group. Compared with the habitual diet group, the avocado-supplemented diet group had greater increases in the following HEI-2015 components from baseline: total vegetables (0.99 points; 95% CI: 0.77, 1.21), fatty acid ratio (2.25 points; 95% CI: 1.74, 2.77), sodium (1.03 points; 95% CI: 0.52, 1.55), refined grains (0.82 points; 95% CI: 0.32, 1.31), and added sugars (0.84 points; 95% CI: 0.49, 1.19). No differences in HEI-2015 improvements were observed by race, ethnicity, study site, body mass index, or age category. In the avocado-supplemented diet compared with the habitual diet group, the HEI-2015 increased in females (6.50 points; 95% CI: 4.39, 8.62) but not in males (0.02 points; 95% CI: -3.44, 3.48). Median HEI-2015 change was not associated with intervention-related changes in cardiometabolic disease risk factors. Conclusions: Intake of 1 avocado per day for 26 wk in adults with abdominal obesity increased adherence to the Dietary Guidelines for Americans. Changes in diet quality did not predict changes in risk factors for cardiometabolic disease.This trial was registered at clinicaltrials.gov as NCT03528031 (https://clinicaltrials.gov/study/NCT03528031).

Berry Consumption in Relation to Allostatic Load in US Adults: The National Health and Nutrition Examination Survey, 2003-2010.

INTRODUCTION: Berries are a rich source of antioxidant polyphenols and other nutrients that are associated with good health. Allostatic load (AL) is an aggregate measure of chronic stress-induced physiological dysregulations across cardiovascular, metabolic, autonomic, and immune systems; the extent of these dysregulations, collectively or in each system, can be characterized by a composite score or a domain score assessed by integrated biomarkers. It was hypothesized that the anti-inflammatory and other effects of berries lower AL. The association was determined between berry consumption and AL composite and domain scores in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). METHODS: Berry intake was measured using two 24 h dietary recalls collected from US adults in the 2003-2010 NHANES (n = 7684). The association with AL and its specific domains was examined using population weight-adjusted multivariable linear regression. RESULTS: The mean AL composite scores for consumers of any berries (11.9), strawberries (11.6), and blueberries (11.6), respectively, were significantly lower than nonconsumers (12.3), after fully adjusting for sociodemographic, lifestyle, and dietary confounders. A significant dose-response relationship was determined between greater consumption of total berries, strawberries, and blueberries and lower mean AL composite scores (p-trend < 0.05, for all). Consistently, mean cardiovascular and metabolic domain scores remained significantly lower in the consumers of total berries (mean cardiovascular domain score: 4.73 versus 4.97 for nonconsumers; mean metabolic domain score: 2.97 versus 3.1), strawberries (4.73 versus 4.95; 2.99 versus 3.1), and blueberries (4.6 versus 4.95; 2.92 versus 3.11). Berry consumers also had significantly lower mean AL immune scores (1.52 versus 1.56) and lower mean AL autonomic scores (2.49 versus 2.57) than nonconsumers (initial sample: n = 15,620). CONCLUSIONS: The current study indicates that consumption of berries lowers the AL composite scores and potentially reduces stress-related disease risks in the US adult population.

The Epidemiology of Berry Consumption and Association of Berry Consumption with Diet Quality and Cardiometabolic Risk Factors in United States Adults: The National Health and Nutrition Examination Survey, 2003-2018.

BACKGROUND: Berries are rich in important nutrients and bioactive compounds, which could potentially contribute to maintenance of normal lipid and glucose profiles. OBJECTIVE: We reported the epidemiology of berry consumption and examined associations of berry consumption with diet quality [measured by Healthy Eating Index (HEI-2015)] and levels of cardiometabolic risk factors, including body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), glycated hemoglobin, and fasting biomarkers: triglycerides, low-density lipoprotein cholesterol (LDL cholesterol), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: We evaluated 33,082 adults (aged ≥20 y) using two 24-h diet recalls from National Health and Nutrition Examination Survey (2003-2018). Multivariable linear regression models were applied to examine the associations of total and individual berry intake with diet quality and cardiometabolic risk factors using appropriate sample weights. RESULTS: Approximately 25 % of the United States adults consumed berries (0.08 ± 0.003 cup-equivalents/d), representing ∼10 % of the daily mean total fruit intake. Among berry consumers, the mean intake of strawberries (0.31 ± 0.01 cup-equivalents) was higher than for other berries. Berry consumers had a significantly higher HEI-2015 score than nonconsumers (mean HEI-2015 score = 58.8 compared with 52.3, P < 0.0001). Berry consumers had significantly lower concentrations of cardiometabolic indices than nonconsumers, including BMI, WC, SBP, total cholesterol, LDL cholesterol, triglycerides, fasting insulin, HOMA-IR, and higher mean HDL cholesterol, after adjusting for sociodemographic, lifestyle, and dietary confounders (all P < 0.05). CONCLUSIONS: United States adult berry consumers had a higher diet quality and lower concentrations of cardiometabolic risk factors, suggesting a favorable role for berries in diets and cardiometabolic disease prevention in United States adult population.

Intake of Pistachios as a Nighttime Snack Has Similar Effects on Short- and Longer-Term Glycemic Control Compared with Education to Consume 1-2 Carbohydrate Exchanges in Adults with Prediabetes: A 12-Wk Randomized Crossover Trial.

BACKGROUND: Nut intake is associated with better glycemic control and lower cardiovascular disease (CVD) risk. It remains unclear if nut intake timing affects glycemic control and CVD risk factors. Intake of pistachios as a nighttime snack may attenuate morning glucose production and lower fasting plasma glucose (FPG). OBJECTIVES: We assessed the effects of a nighttime (after dinner and before bedtime) pistachio snack (57 g/d) on glycemic control markers, vascular health, lipids/lipoproteins, and diet quality compared with education to consume 1-2 carbohydrate (CHO) exchanges (usual care) in individuals with prediabetes. METHODS: A 2-period, randomized crossover trial was conducted. Participants were provided 57 g/d of dry roasted unsalted pistachios (319 kcal; fat 26 g; CHO 16 g; protein 12 g; fiber 6 g) as a nighttime snack or received usual care for 12 wk. Primary (FPG) and secondary outcomes [hemoglobin A1c (HbA1c), insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipids/lipoproteins, vascular health, and Healthy Eating Index-2015 (HEI-2015)] were measured before and after each condition. RESULTS: A total of 66 participants (50.9 ± 11.6 y, FPG: 106.2 ± 6.4 mg/dL) were randomly assigned, and 51 participants completed the trial. No between-condition differences in FPG {0.9 mg/dL [95% confidence interval (CI): -1.2, 3.1]}, HbA1c, insulin, HOMA-IR, lipids/lipoproteins, blood pressure, or vascular health were observed. The HEI-2015 score was higher after the pistachio condition [6.8 points (95% CI: 1.5, 12.1)] than after usual care driven by higher component scores for seafood and plant proteins [2.0 points (95% CI: 1.0, 2.9)], refined grains [2.3 points (95% CI: 1.1, 3.5)], and the fatty acid ratio [1.7 points (95% CI: 0.0, 3.5)]. CONCLUSIONS: In adults with prediabetes, consuming 57 g/d of pistachios as a nighttime snack increased diet quality but had similar effects on glycemic markers, lipids/lipoproteins, blood pressure, and vascular health compared with the usual care comparator. Pistachios may be a healthful alternative to carbohydrate-rich nighttime snacks to increase alignment with Dietary Guidelines for Americans. This trial was registered at clinicaltrials.gov as NCT04056208.

Metabolomics and Risk of Dementia: A Systematic Review of Prospective Studies.

BACKGROUND: The projected increase in the prevalence of dementia has sparked interest in understanding the pathophysiology and underlying causal factors in its development and progression. Identifying novel biomarkers in the preclinical or prodromal phase of dementia may be important for predicting early disease risk. Applying metabolomic techniques to prediagnostic samples in prospective studies provides the opportunity to identify potential disease biomarkers. OBJECTIVE: The objective of this systematic review was to summarize the evidence on the associations between metabolite markers and risk of dementia and related dementia subtypes in human studies with a prospective design. DESIGN: We searched PubMed, PsycINFO, and Web of Science databases from inception through December 8, 2023. Thirteen studies (mean/median follow-up years: 2.1-21.0 y) were included in the review. RESULTS: Several metabolites detected in biological samples, including amino acids, fatty acids, acylcarnitines, lipid and lipoprotein variations, hormones, and other related metabolites, were associated with risk of developing dementia. Our systematic review summarized the adjusted associations between metabolites and dementia risk; however, our findings should be interpreted with caution because of the heterogeneity across the included studies and potential sources of bias. Further studies are warranted with well-designed prospective cohort studies that have defined study populations, longer follow-up durations, the inclusion of additional diverse biological samples, standardization of techniques in metabolomics and ascertainment methods for diagnosing dementia, and inclusion of other related dementia subtypes. CONCLUSIONS: This study contributes to the limited systematic reviews on metabolomics and dementia by summarizing the prospective associations between metabolites in prediagnostic biological samples with dementia risk. Our review discovered additional metabolite markers associated with the onset of developing dementia and may help aid in the understanding of dementia etiology. The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (https://www.crd.york.ac.uk/prospero/; registration ID: CRD42022357521).

Consumption of Berries and Flavonoids in Relation to Mortality in NHANES, 1999-2014.

BACKGROUND: Berries are foods that are abundant in nutrients, especially flavonoids, that promote good health; however, the effects of total berries on mortality are not well characterized. OBJECTIVES: We evaluated whether intakes of total berries and specific berry types including blueberries, strawberries, cranberries, flavonoids, and subclasses of flavonoids (anthocyanidins, flavonols, flavones, flavanones, flavan-3-ols, and isoflavones) in relation to mortality risk in United States adults. METHODS: A nationally representative sample of the United States adult population was obtained using data from the 1994-2014 NHANES (n = 37,232). Intake of berries was estimated using 24-h food recalls (1999-2014), and flavonoids intake was calculated using the matched USDA's expanded flavonoid database. Mortality outcomes based on 8 y of follow-up were obtained using linked death certificates. RESULTS: Compared with nonconsumers, the multivariable-adjusted hazard ratio for all-cause mortality was 0.79 [95% confidence intervals (CI): 0.7, 0.89] for any berry consumption, 0.86 (0.75, 0.99) for strawberry consumption 0.79 (0.66, 0.95) for blueberries, and 0.69 (0.51, 0.93) for cranberries. Compared with the lower median of intake, risk of all-cause mortality for greater intake was 0.85 (0.74, 0.97) for total flavonoids, 0.85 (0.76, 0.95) for anthocyanidins, 0.9 (0.82, 0.99) for flavan-3-ols, 0.89 (0.79, 0.9) for flavanols, and 0.89 (0.8, 0.99) for flavones. There was a dose-response relationship between intakes of total flavonoids, anthocyanidins, and flavones and lower all-cause mortality risks (Ptrend < 0.05). Risk for cardiometabolic mortality was 0.75 (0.58, 0.98) for berry consumers and 0.49 (0.25, 0.98) for cranberry consumers. For respiratory disease mortality, risk was 0.41 (0.2, 0.86), compared with blueberry nonconsumers. CONCLUSION: Higher intakes of berries and flavonoids were associated with a lower overall mortality risk in adult Americans. Few adults regularly consume berries, indicating that increased intake of berries and flavonoid-rich foods may be beneficial to health.

Berry Consumption and Sleep in the Adult US General Population: Results from the National Health and Nutrition Examination Survey 2005-2018.

INTRODUCTION: Poor sleep is associated with numerous adverse health outcomes. Berries are rich in micronutrients and antioxidants that may improve sleep quality and duration. We determined the association of berry consumption and sleep duration and sleep difficulty among adult participants in NHANES. METHODS: We analyzed the diet of US adults aged ≥ 20 y using two non-consecutive 24 h recalls from the National Health and Nutrition Examination Survey 2005 to 2018 (N = 29,217). Poor sleep quality was measured by sleep duration (short sleep duration: <7 h), long sleep (≥9 h), and reported sleep difficulty. The relative risk of poor sleep outcomes for berry consumers vs. nonconsumers was modelled using population weight-adjusted multivariable general logistic regression. RESULTS: About 46% of participants reported inadequate sleep duration, and 27% reported sleep difficulties. Twenty-two percent reported consuming berries. Berry consumers had a 10-17% decreased risk of short sleep. The findings were consistent for specific berry types including strawberries and blueberries (p < 0.05). No significant associations with long sleep were found for total berries and any berry types. A decreased risk of sleep difficulties was found to be linked to blackberry consumption (adjusted OR = 0.63, 95% CI: 0.40-0.97; p = 0.036) but not for other berries. CONCLUSIONS: US adult berry consumers had a decreased risk of reporting short sleep compared to nonconsumers. Berries are underconsumed foods in the US adult population, and increased berry consumption may improve sleep quality.

Walnut consumption and gut microbial metabolism: Results of an exploratory analysis from a randomized, crossover, controlled-feeding study.

BACKGROUND & AIMS: The effect of walnut-related modulation of gut microbiota composition on microbiota functionality is unknown. The aim was to characterize the effect of a walnut-enriched diet (WD), compared to a fatty acid-matched diet devoid of walnuts (WFMD) and a diet where oleic acid replaces alpha-linolenic acid (ORAD), on bacterial gene expression. METHODS: A 3-period, randomized, crossover, controlled-feeding study was conducted. Participants were provided a 2-week run-in standard western diet (SWD; 50% kcal carbohydrate, 16% protein, 34% fat, 12% SFA). Following the SWD in random sequence order, participants were provided the WD, WFMD, and ORAD (48% carbohydrate; 17% protein; fat 35%; 7% SFA). The WD contained 18% of energy from walnuts (57 g/d/2100 kcal). The WFMD and ORAD were devoid of walnuts; liquid non-tropical plant oils were included in these diets. Metatranscriptomic analyses were performed as an exploratory outcome. RESULTS: The analytical sample included 35 participants (40% female) with a mean ± SD age of 43 ± 10 y and BMI of 30.3 ± 4.9 kg/m2. The ⍺-diversity of taxa actively expressing genes, assessed by observed species (p = 0.27) and Pielou's Evenness (p = 0.09), did not differ among the diets. The ⍺-diversity of actively expressed genes was greater following the WD compared to the WFMD and ORAD as assessed by the observed genes and Pielou's Evenness metrics (p < 0.05). ß-Diversity of the actively expressed genes differed following the WD compared to the WFMD (p = 0.001) and ORAD (p = 0.001); ß-diversity did not differ between the WFMD and ORAD. Active composition analyses showed increased Gordonibacter (p < 0.001) activity following the WD vs. the ORAD. Greater expression of many genes was observed following the WD compared to the WFMD and ORAD. Following the WD, greater expression of metabolism-related genes encoding glycine amidinotransferase (GATM; K00613) and arginine deiminase (K01478) was observed compared to the WFMD. Greater expression of glycine amidinotransferase (GATM; K00613) by Gordonibacter was also observed following the WD vs. the WFMD and ORAD. CONCLUSION: Our results suggest walnut intake may increase endogenous production of homoarginine through gut microbiota-mediated upregulation of GATM, which is a novel mechanism by which walnuts may lower cardiovascular disease risk. However, given the exploratory nature replication is needed. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT02210767).

The effect of cottonseed oil on lipids/lipoproteins: a systematic review and plasma cholesterol predictive equations estimations.

CONTEXT: Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils. OBJECTIVES: To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations. DATA SOURCES: A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population. DATA ANALYSES: The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic). RESULTS: In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ -7.7 mg/dL) and triglycerides (≈ -7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ -14.8 mg/dL), LDL-C (≈ -14.0 mg/dL), and non-high-density lipoprotein cholesterol (≈ -14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (-8.1 mg/dL) and LDL-C (-7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (-1.1 mg/dL). Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL. CONCLUSION: Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins.

A Mediterranean Dietary Pattern Is Associated with Greater Participation in Physical Activity and Better Health-Related Quality of Life among Students and Professors at the Melilla Campus (University of Granada).

The objective of this study was to assess Mediterranean diet (MD) scores (i.e., alignment with a MD pattern) among students and professors, in addition to assessing how adherence to the MD was associated with other lifestyle behaviors. A cross-sectional observational study was conducted with a sample of 127 university professors and 272 students of the Melilla Campus at the University of Granada (Spain). Students were more physically active than professors (mean difference = 1058 METs, p < 0.001) and reported lower negative affect (NA; mean difference = -1.70, p < 0.001) whereas professors reported nominally better perceived mental health. For the total sample, the physical health component (ß = 0.03, p = 0.03) and physical activity (ß = 0.0001, p = 0.01) were significantly associated with higher MD scores. Health behaviors, including MD scores and physical activity, were suboptimal among both students and professors. The results suggest that a dietary pattern reflective of the MD is positively associated with both physical and mental health outcomes among students and professors, though the direction of the associations remains to be clarified.

Diet-derived and diet-related endogenously produced palmitic acid: Effects on metabolic regulation and cardiovascular disease risk.

Palmitic acid is the predominant dietary saturated fatty acid (SFA) in the US diet. Plasma palmitic acid is derived from dietary fat and also endogenously from de novo lipogenesis (DNL) and lipolysis. DNL is affected by excess energy intake resulting in overweight and obesity, and the macronutrient profile of the diet. A low-fat diet (higher carbohydrate and/or protein) promotes palmitic acid synthesis in adipocytes and the liver. A high-fat diet is another source of palmitic acid that is taken up by adipose tissue, liver, heart and skeletal muscle via lipolytic mechanisms. Moreover, overweight/obesity and accompanying insulin resistance increase non-esterified fatty acid (NEFA) production. Palmitic acid may affect cardiovascular disease (CVD) risk via mechanisms beyond increasing low-density lipoprotein-cholesterol (LDL-C), notably synthesis of ceramides and possibly through branched fatty acid esters of hydroxy fatty acids (FAHFAs) from palmitic acid. Ceramides are positively associated with incident CVD, whereas the role of FAHFAs is uncertain. Given the new evidence about dietary regulation of palmitic acid metabolism there is interest in learning more about how diet modulates circulating palmitic acid concentrations and, hence, potentially CVD risk. This is important because of the heightened interest in low carbohydrate (carbohydrate controlled) and high carbohydrate (low-fat) diets coupled with the ongoing overweight/obesity epidemic, all of which can increase plasma palmitic acid levels by different mechanisms. Consequently, learning more about palmitic acid biochemistry, trafficking and how its metabolites affect CVD risk will inform future dietary guidance to further lower the burden of CVD.

Translating Evidence-based Approaches into optimal Care for individuals at High-risk of ASCVD: Pilot testing of case-based e-learning modules and design of the TEACH-ASCVD study.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the United States. Case-based learning using electronic delivery of the modules can educate clinicians and improve translation of evidence-based guidelines into practice for high-risk ASCVD patients. OBJECTIVE: To develop and optimize module design, content, and usability of e-learning modules to teach clinicians evidence-based management in accordance with multi-society guidelines for high-risk ASCVD patients that will be implemented and evaluated in U.S. health systems in the TEACH-ASCVD study. METHODS: Seven e-learning modules were created by a committee of lipid experts. Focus groups were conducted with lipid experts to elicit feedback on case content followed by interviews with a target audience of clinicians to assess usability of the online module platform. Responses from both groups were evaluated, and appropriate changes were made to improve the e-learning modules. Design of the TEACH-ASCVD study is presented. RESULTS: Feedback regarding case content by lipid experts included providing more detailed patient histories, clarifying various diagnostic criteria, and emphasizing clinical best practices based on evidence-based guidelines. The target audience clinician group reported an agreeable experience with the e-learning modules but noted a discordance between the evidence-based guidelines and clinical decision-making in their own practices. Participants felt the modules would help educate clinicians in managing high-risk ASCVD patients. CONCLUSION: Clinicians must be informed of best practices as the field of lipidology continues to evolve. E-learning modules provide a concise, valuable, and accessible mechanism for educating clinicians regarding changes in the field to deliver the best patient care.

Contribution of Circulating Host and Microbial Tryptophan Metabolites Toward Ah Receptor Activation.

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that plays an integral role in homeostatic maintenance by regulating cellular functions such as cellular differentiation, metabolism, barrier function, and immune response. An important but poorly understood class of AHR activators are compounds derived from host and bacterial metabolism of tryptophan. The commensal bacteria of the gut microbiome are major producers of tryptophan metabolites known to activate the AHR, while the host also produces AHR activators through tryptophan metabolism. We used targeted mass spectrometry-based metabolite profiling to determine the presence and metabolic source of these metabolites in the sera of conventional mice, germ-free mice, and humans. Surprisingly, sera concentrations of many tryptophan metabolites are comparable between germ-free and conventional mice. Therefore, many major AHR-activating tryptophan metabolites in mouse sera are produced by the host, despite their presence in feces and mouse cecal contents. Here we present an investigation of AHR activation using a complex mixture of tryptophan metabolites to examine the biological relevance of circulating tryptophan metabolites. AHR activation is rarely studied in the context of a mixture at relevant concentrations, as we present here. The AHR activation potentials of individual and pooled metabolites were explored using cell-based assays, while ligand binding competition assays and ligand docking simulations were used to assess the detected metabolites as AHR agonists. The physiological and biomedical relevance of the identified metabolites was investigated in the context of a cell-based model for rheumatoid arthritis. We present data that reframe AHR biology to include the presence of a mixture of ubiquitous tryptophan metabolites, improving our understanding of homeostatic AHR activity and models of AHR-linked diseases.

Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association.

Lifestyle habits can have a profound impact on atherosclerotic cardiovascular disease (ASCVD) risk. The National Lipid Association previously published recommendations for lifestyle therapies to manage dyslipidemia. This Clinical Perspective provides an update with a focus on nutrition interventions for the three most common dyslipidemias in adults: 1) low-density lipoprotein cholesterol (LDL-C) elevation; 2) triglyceride (TG) elevation, including severe hypertriglyceridemia with chylomicronemia; and 3) combined dyslipidemia, with elevations in both LDL-C and TG levels. Lowering LDL-C and non-high-density lipoprotein cholesterol are the primary objectives for reducing ASCVD risk. With severe TG elevation (≥500 mg/dL), the primary objective is to prevent pancreatitis and ASCVD risk reduction is secondary. Nutrition interventions that lower LDL-C levels include reducing cholesterol-raising fatty acids and dietary cholesterol, as well as increasing intakes of unsaturated fatty acids, plant proteins, viscous fibers, and reducing adiposity for patients with overweight or obesity. Selected dietary supplements may be employed as dietary adjuncts. Nutrition interventions for all patients with elevated TG levels include restricting intakes of alcohol, added sugars, and refined starches. Additional lifestyle factors that reduce TG levels are participating in daily physical activity and reducing adiposity in patients with overweight or obesity. For patients with severe hypertriglyceridemia, an individualized approach is essential. Nutrition interventions for addressing concurrent elevations in LDL-C and TG include a combination of the strategies described for lowering LDL-C and TG. A multidisciplinary approach is recommended to facilitate success in making and sustaining dietary changes and the assistance of a registered dietitian nutritionist is highly recommended.

Dried Fruits: Bioactives, Effects on Gut Microbiota, and Possible Health Benefits-An Update.

Dried fruits contain many bioactive compounds broadly classified as phytochemicals including phenolics, flavonoids, carotenoids, proanthocyanidins, stilbenes, chalcones/dihydrochalcones, and phytoestrogens. These compounds have antioxidant effects that may benefit health. Dried fruits are also a diverse group of foods with varying fibre contents. The evaluation of the biological activity of these bioactive compounds, including their bioaccessibility and bioavailability, may contribute to the understanding of the health effects of dried fruits. Limited evidence suggests that dried fruits (raisins, cranberries, dates, and prunes) affect human gut microbiota composition in a potentially beneficial manner (in terms of effects on Bifidobacteria, Faecalibacterium prausnitzii, Lactobacillus, Ruminococcaceae, Klebsiella spp., and Prevotella spp.). There is little epidemiological evidence about the association of dried fruit consumption with cardiovascular disease incidence and mortality, as well as the risk of type 2 diabetes or obesity. Clinical trial evidence for the effects of dried fruit consumption on cardiovascular risk factors, including glycaemic control, is mixed. Clinical trial evidence suggests prunes might preserve bone mineral density in postmenopausal women. Consumption of dried fruits is associated with higher-quality diets. Studies are needed to increase our understanding of the health effects of dried fruits and the underlying biological mechanisms.

Effect of omega-3 ethyl esters on the triglyceride-rich lipoprotein response to endotoxin challenge in healthy young men.

Oxylipins are produced enzymatically from polyunsaturated fatty acids, are abundant in triglyceride-rich lipoproteins (TGRLs), and mediate inflammatory processes. Inflammation elevates TGRL concentrations, but it is unknown if the fatty acid and oxylipin compositions change. In this study, we investigated the effect of prescription ω-3 acid ethyl esters (P-OM3; 3.4 g/d EPA + DHA) on the lipid response to an endotoxin challenge (lipopolysaccharide; 0.6 ng/kg body weight). Healthy young men (N = 17) were assigned 8-12 weeks of P-OM3 and olive oil control in a randomized order crossover study. Following each treatment period, subjects received endotoxin challenge, and the time-dependent TGRL composition was observed. Postchallenge, arachidonic acid was 16% [95% CI: 4%, 28%] lower than baseline at 8 h with control. P-OM3 increased TGRL ω-3 fatty acids (EPA 24% [15%, 34%]; DHA 14% [5%, 24%]). The timing of ω-6 oxylipin responses differed by class; arachidonic acid-derived alcohols peaked at 2 h, while linoleic acid-derived alcohols peaked at 4 h (pint = 0.006). P-OM3 increased EPA alcohols by 161% [68%, 305%] and DHA epoxides by 178% [47%, 427%] at 4 h compared to control. In conclusion, this study shows that TGRL fatty acid and oxylipin composition changes following endotoxin challenge. P-OM3 alters the TGRL response to endotoxin challenge by increasing availability of ω-3 oxylipins for resolution of the inflammatory response.

Effects of Nut Consumption on Blood Lipids and Lipoproteins: A Comprehensive Literature Update.

In the present review, we provide a comprehensive narrative overview of the current knowledge on the effects of total and specific types of nut consumption (excluding nut oil) on blood lipids and lipoproteins. We identified a total of 19 systematic reviews and meta-analyses of randomized controlled trials (RCTs) that were available in PubMed from the inception date to November 2022. A consistent beneficial effect of most nuts, namely total nuts and tree nuts, including walnuts, almonds, cashews, peanuts, and pistachios, has been reported across meta-analyses in decreasing total cholesterol (mean difference, MD, -0.09 to -0.28 mmol/L), LDL-cholesterol (MD, -0.09 to -0.26 mmol/L), and triglycerides (MD, -0.05 to -0.17 mmol/L). However, no effects on HDL-cholesterol have been uncovered. Preliminary evidence indicates that adding nuts into the regular diet reduces blood levels of apolipoprotein B and improves HDL function. There is also evidence that nuts dose-dependently improve lipids and lipoproteins. Sex, age, or nut processing are not effect modifiers, while a lower BMI and higher baseline lipid concentrations enhance blood lipid/lipoprotein responses. While research is still emerging, the evidence thus far indicates that nut-enriched diets are associated with a reduced number of total LDL particles and small, dense LDL particles. In conclusion, evidence from clinical trials has shown that the consumption of total and specific nuts improves blood lipid profiles by multiple mechanisms. Future directions in this field should include more lipoprotein particle, apolipoprotein B, and HDL function studies.