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Background: Avocado intake has been associated with improvements in diet quality. Whether this response is because of avocado intake, per se, or combined with a food and/or nutrient displacement (D) has yet to be determined. Objectives: This secondary analysis, conducted using dietary data from the Habitual Diet and Avocado Trial, sought to assess the effect of consuming a large avocado (168 g, 281 kcal) daily in the avocado-supplemented diet (AD) group compared with the habitual diet (HD) group on food and nutrient D. Methods: Using data from 3 unannounced telephone 24-h dietary recalls conducted during the 6-mo intervention period, food intake data were evaluated for 898 participants, aged 25–87 y, and a BMI range of 20.5–60.3 kg/m2. The food group distribution, energy, and nutrient intake of the AD group (n = 436) were calculated and compared with those of the HD group (n = 462). Results: The AD group had a higher daily intake of energy (159 ± 575 kcal) (P < 0.001), potassium (3193 ± 817 mg compared with 2419 ± 843 mg) (P < 0.005), fiber (30 ± 8 g compared with 19 ± 9 g) (P < 0.05), and a lower daily intake of animal protein (49 ± 33 g compared with 55 ± 24 g) (P = 0.02) compared with the HD group. Partial D with an avocado was observed for energy (43%), total fat (23%), and carbohydrate (87%), indicating a lower intake of these nutrients from non-avocado sources in the AD group. Food group analysis revealed a lower consumption of animal-derived protein from red meat, processed meats, poultry, and fish in the AD group, with no significant differences observed in dairy and egg intake between groups. Conclusions: Incorporating 1 avocado daily led to favorable modifications in the dietary composition of participants, including an increase in potassium and fiber intake, which can improve diet quality.This trial was registered at https://clinicaltrials.gov as NCT03528031.

The purpose of this study was to examine associations between the Walk Score and physical activity in young, overweight/obese urban women. Project Health included 45 White or African American women (BMI 31.5±3.9 kg/m2; age 26.5±4.6 years; 62% African American) living in the Boston area. An accelerometer estimated steps/day and mins/day in light physical activity (100-2019 counts-per-minute) and moderate-to-vigorous-physical activity (≥2020 cpm). Walk Score was used to estimate the walkability of home address by analyzing proximity to nearby amenities. General linear regression models estimated associations between total Walk Score and physical activity (light physical activity, moderate-to-vigorous-physical activity, steps, total activity counts, METs), adjusting for body mass index, age, race/ethnicity, seasonality, wear time, employment and student status. For physical activity variables that had significant associations with Walk Score (steps/day and steps/min), regression models were estimated for Walk Score sub-scores (parks, grocery, errands, shopping, dining/drinking, culture/entertainment and schools). Logistic regression models estimated the odds of meeting the guidelines for steps (≥10,000/day) and moderate-to-vigorous-physical activity (≥150mins MVPA/week) based on Walk Score. Participants had a Walk Score of 63.9±26.4, took 14,143±3,934 steps/day, and spent 206.2±66.0 mins/day in light physical activity and 46.7±17.5 mins/day in moderate-to-vigorous- physical activity. Walk Score was significantly and positively associated with steps/day (β = 51.4, p = 0.01) and steps/min (β = 0.06, p = 0.009) but was not associated with mins/day of light physical activity, moderate-to-vigorous-physical activity, total activity counts or METs. Parks, grocery, errands, shopping, dining/drinking, and culture/entertainment Walk Score sub-scores were significantly associated with steps and steps/min (all p

Few studies have examined dietary data or objective measures of physical activity (PA) and sedentary behavior among metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Thus, the purpose is to determine whether PA, sedentary behavior and/or diet differ between MHO and MUO in a sample of young women.Forty-six overweight/obese (BMI ≥25 kg/m2) African American and Caucasian women 19-35 years were classified by cardiometabolic risk factors, including elevated blood pressure, triglyceride, glucose and C-reactive protein, low high density lipoprotein, and insulin resistance (MUO ≥2; MHO,

Abstract Background Childhood overweight/obesity has been associated with an elevated risk of insulin resistance and cardiometabolic disorders. Waist-to-height ratio (WHtR) may be a simple screening tool to quickly identify children at elevated risk for cardiometabolic disorders. The primary objective of the present study was to create sex-specific tertile cut points of WHtR and assess its association with Insulin resistance and elevated liver enzyme concentrations in children, factors using cross-sectional data from the randomized, controlled Family Weight Management Study. Methods Baseline data from 360 children (7–12 years, mean Body Mass Index (BMI) ≥ 85th percentile for age and sex) were used to calculate WHtR tertiles by sex, male: ≤ 0.55 (T1), > 0.55- ≤ 0.59 (T2), > 0.59 (T3); female: ≤ 0.56 (T1), > 0.56- ≤ 0.6 (T2), > 0.6 (T3). The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used to categorize participants as insulin-resistant (HOMA-IR ≥ 2.6) and insulin-sensitive (HOMA-IR 26 µkat/L males, > 22 µkat/L females). We examined differences in baseline cardiometabolic risk factors by WHtR tertiles and sex-specific multivariable logistic regression models to predict HOMA-IR and elevation of liver enzymes. Results Study participants had a mean WHtR of 0.59 ([SD: 0.06]). Irrespective of sex, children in WHtR T3 had higher BMIz scores, blood pressure, triglycerides, 2-h glucose, fasting 2-h insulin, and lower high-density lipoprotein cholesterol (HDL-C) concentrations than those in T2 and T1. After adjusting for covariates, the odds of elevated HOMA-IR (> 2.6) were over five-fold higher among males in T3 versus T1 [OR, 95%CI: 5.83, 2.34–14.52] and T2 [OR, 95%CI: 4.81, 1.94–11.92] and females in T3 [OR, 95%CI: 5.06, 2.10–12.20] versus T1. The odds of elevated ALT values (≥ 30) were 2.9 [95%CI: 1.01–8.41] fold higher among females in T3 compared to T1. Conclusion In public health settings, WHtR may be a practical screening tool in pediatric populations to identify children at risk of metabolic syndrome.

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large‐scale proteomic profiling was conducted in serum specimens (SomaLogic) collected at the end of 8‐week and 4‐week DASH diet interventions in multicenter, randomized controlled feeding studies of the DASH trial (N=215) and the DASH‐Sodium trial (N=396), respectively. Multivariable linear regression models were used to compare the relative abundance of 7241 proteins between the DASH and control diet interventions. Estimates from the 2 trials were meta‐analyzed using fixed‐effects models. We validated significant proteins in the ARIC study (N=10 490) using the DASH diet score. At a false discovery rate

Abstract Sexual dimorphism in the immune system is evidenced by a higher prevalence of autoimmune diseases in women and higher susceptibility to infectious diseases in men. However, the molecular basis of these sex-based differences is not fully understood. We have characterized the transcriptome profiles of peripheral blood monocytes from males and postmenopausal females with chronic low-grade inflammation. We identified 41 sexually differentially expressed genes [adjusted p value (FDR)

Abstract Background The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short‐term well‐controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel‐arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free‐living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [−0.024 L, 0.058 L], P=0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high‐sensitivity C‐reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low‐density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low‐density lipoprotein concentrations, and total cholesterol:high‐density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free‐living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03528031.

Partially-hydrogenated fat/trans fatty acid intake has been associated with adverse effects on cardiometabolic risk factors. Comparatively unexplored is the effect of unmodified oil relative to partially-hydrogenated fat on the plasma metabolite profile and lipid-related pathways. To address this gap, we conducted secondary analyses using a subset of samples randomly selected from a controlled dietary intervention trial involving moderately hypercholesterolemic individuals. Participants (N = 10, 63 ± 8 y, BMI, 26.2 ± 4.2 kg/m2, LDL-C, 3.9 ± 0.5 mmol/L) were provided with diets enriched in soybean oil (SO) and partially-hydrogenated soybean oil (PHSO). Plasma metabolite concentrations were determined using an untargeted approach and pathway analysis using LIPIDMAPS. Data were assessed using a volcano plot, receiver operating characteristics curve, partial least square-discrimination analysis and Pearson correlations. Among the known metabolites higher in plasma after the PHSO diet than the SO diet, the majority were phospholipids (53%) and di- and triglycerides (DG/TG, 34%). Pathway analysis indicated upregulation of phosphatidylcholine synthesis from DG and phosphatidylethanolamine. We identified seven metabolites (TG_56:9, TG_54:8, TG_54:7, TG_54:6, TG_48:5, DG_36:5 and benproperine) as potential biomarkers for PHSO intake. These data indicate that TG-related metabolites were the most affected lipid species, and glycerophospholipid biosynthesis was the most active pathway in response to PHSO compared to SO intake.

Abstract Background Studies regarding whether light to moderate alcohol consumption is associated with a lower risk of cardiovascular diseases (CVD) have generated mixed results. Further, few studies have examined the potential impact of alcohol consumption on diverse disease outcomes simultaneously. We aimed to prospectively study the dose-response association between alcohol consumption and risk of CVD, cancer, and mortality. Methods This study included 83,732 adult Chinese participants, free of CVD and cancer at baseline. Participants were categorized into 6 groups based on self-report alcohol consumption: 0, 1–25, 26–150, 151–350, 351–750, and > 750 g alcohol/wk. Incident cases of CVD, cancers, and mortality were confirmed by medical records. Hazard ratios (HRs) for the composite risk of these three outcomes, and each individual outcome, were calculated using Cox proportional hazard model. Results During a median follow-up of 10.0 years, there were 6411 incident cases of CVD, 2947 cancers and 6646 deaths. We observed a J-shaped relation between alcohol intake and risk of CVD, cancer, and mortality, with the lowest risk at 25 g/wk., which is equivalent to ~ 2 servings/wk. Compared to consuming 1–25 g/wk., the adjusted HR for composite outcomes was 1.38 (95% confidence interval (CI):1.29–1.49) for non-drinker, 1.15 (95% CI: 1.04–1.27) for 26–150 g/wk., 1.22 (95% CI: 1.10–1.34) for 151–350 g/wk., 1.33 (95% CI: 1.21–1.46) for 351–750 g/wk., and 1.57 (95% CI: 1.30–1.90) for > 750 g/wk., after adjusting for age, sex, lifestyle, social economic status, and medication use. Conclusions Light alcohol consumption at ~ 25 g/wk was associated with lower risk of CVD, cancer, and mortality than none or higher consumption in Chinese adults.

Background: Healthy dietary patterns are related to better cognitive health in aging populations. While levels of individual nutrients in neural tissues are individually associated with cognitive function, the investigation of nutrient patterns in human brain tissue has not been conducted.Methods: Brain tissues were acquired from frontal and temporal cortices of 47 centenarians from the Georgia Centenarian Study. Fat-soluble nutrients (carotenoids, vitamins A, E, K, and fatty acids [FA]) were measured and averaged from the two brain regions. Nutrient patterns were constructed using principal component analysis. Cognitive composite scores were constructed from cognitive assessment from the time point closest to death. Dementia status was rated by Global Deterioration Scale (GDS). Pearson's correlation coefficients between NP scores and cognitive composite scores were calculated controlling for sex, education, hypertension, diabetes, and APOE ε4 allele.Result: Among non-demented subjects (GDS = 1–3, n = 23), a nutrient pattern higher in carotenoids was consistently associated with better performance on global cognition (r = 0.38, p = 0.070), memory (r = 0.38, p = 0.073), language (r = 0.42, p = 0.046), and lower depression (r = −0.40, p = 0.090). The findings were confirmed with univariate analysis.Conclusion: Both multivariate and univariate analyses demonstrate that brain nutrient pattern explained mainly by carotenoid concentrations is correlated with cognitive function among subjects who had no dementia. Investigation of their synergistic roles on the prevention of age-related cognitive impairment remains to be performed.

Food intake data collected using subjective tools are prone to inaccuracies and biases. An objective assessment of food intake, such as metabolomic profiling, may offer a more accurate method if unique metabolites can be identified. To explore this option, we used samples generated from a randomized and controlled cross-over trial during which participants (N = 10; 65 ± 8 year, BMI, 29.8 ± 3.2 kg/m2) consumed each of the three diets enriched in different types of carbohydrate. Plasma metabolite concentrations were measured at the end of each diet phase using gas chromatography/time-of-flight mass spectrometry and ultra-high pressure liquid chromatography/quadrupole time-of-flight tandem mass spectrometry. Participants were provided, in random order, with diets enriched in three carbohydrate types (simple carbohydrate (SC), refined carbohydrate (RC) and unrefined carbohydrate (URC)) for 4.5 weeks per phase and separated by two-week washout periods. Data were analyzed using partial least square-discrimination analysis, receiver operating characteristics (ROC curve) and hierarchical analysis. Among the known metabolites, 3-methylhistidine, phenylethylamine, cysteine, betaine and pipecolic acid were identified as biomarkers in the URC diet compared to the RC diet, and the later three metabolites were differentiated and compared to SC diet. Hierarchical analysis indicated that the plasma metabolites at the end of each diet phase were more strongly clustered by the participant than the carbohydrate type. Hence, although differences in plasma metabolite concentrations were observed after participants consumed diets differing in carbohydrate type, individual variation was a stronger predictor of plasma metabolite concentrations than dietary carbohydrate type. These findings limited the potential of metabolic profiling to address this variable.

Background Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n‐6 and n‐3], and trans fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. Methods and Results CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996–1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow‐up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P=0.0328) and dihomo‐γ‐linolenic acid (20:3n‐6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02–1.76; P=0.0351). Elaidic acid (18:1n‐7t) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01–2.12; P=0.0445). No significant associations were observed for NEFA subclass and any outcomes. Conclusions In CHS participants, 2 NEFAs, dihomo‐γ‐linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.

Among school employees, it has been reported that poor physical and mental health, as well as high stress and large workloads, have resulted in high absenteeism and low retention. The consequences of unhealthy behaviors and stress can extend to students, impacting academic achievement and school costs. Our objective was to examine the impact of school employees’ physical activity (PA), diet quality and perceived occupational stress on cardiometabolic health, and explore how stress may influence the impact of PA and diet on health.In this cross-sectional study, employees from lower-income Massachusetts schools participated in Wellness Assessments (2015–2016), including measured height, weight, and lipids [total (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C)]. Self-administered surveys were used to collect demographic, stress, PA and 24-hour food intake data. Linear regression models were used to examine the relationship among health behaviors (PA and diet), stress and cardiometabolic health. An interaction between stress and health behaviors was also explored.Seventy-four employees (66% teachers) participated. Overweight/obesity (mean BMI: 25.6 kg/m2), high TC and LDL-C were observed in 47%, 4%, and 34%, respectively, and moderate-to-vigorous PA (MVPA) was low (median: 17 min/day). Positive associations were identified between MVPA and cardiometabolic health, but not diet. The effect of MVPA on BMI was modified by stress (p-for-interaction = 0.001), with higher levels of stress associated with a diminished protective association between MVPA and BMI.Higher levels of PA were associated with more favorable cardiometabolic health, with increasing levels of stress minimizing the beneficial effect of PA on BMI.

Background Night eating has been associated with an elevated risk of obesity, dyslipidemia, and cardiovascular disease. However, there is no longitudinal study on whether habitual night eating, regardless of diet quality and energy intake, is associated with arterial stiffness, a major etiological factor in the development of cardiovascular disease. Methods and Results The study included 7771 adult participants without cardiovascular disease, cancer, or diabetes mellitus prior to dietary assessment by a validated food frequency questionnaire in 2014 through 2015. Participants were categorized into 3 groups based on self‐reported night‐eating habits: never or rarely, some days (1–5 times per week), or most days (6+ times per week). Arterial stiffness was assessed by brachial‐ankle pulse wave velocity at baseline and repeatedly during follow‐ups. Mean differences and 95% CIs in the yearly change rate of brachial‐ankle pulse wave velocity across the 3 groups were calculated, adjusting for age, sex, socioeconomic status, total energy intake, diet quality, sleep quality, and other cardiovascular disease risk factors. At baseline, 6625 (85.2%), 610 (7.8%), and 536 (6.9%) participants reported night eating as never or rarely, some days, or most days, respectively. During a mean 3.19 years, we observed a positive association between night‐eating frequency and progression of arterial stiffness (P trend=0.01). The adjusted difference in brachial‐ankle pulse wave velocity change rate between the group that ate at night most days and the group that never or rarely ate at night was 14.1 (95% CI, 0.6–27.5) cm/s per year. This association was only significant in women, but not in men (P interaction=0.03). Conclusions In an adult population free of major chronic diseases, habitual night eating was positively associated with the progression of arterial stiffness, a hallmark of arteriosclerosis and biological aging. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR‐TNRC‐11001489.

Background Limited data are available on the prospective relationship between beverage consumption and plasma lipid and lipoprotein concentrations. Two major sources of sugar in the US diet are sugar‐sweetened beverages (SSBs) and 100% fruit juices. Low‐calorie sweetened beverages are common replacements. Methods and Results Fasting plasma lipoprotein concentrations were measured in the FOS (Framingham Offspring Study) (1991–2014; N=3146) and Generation Three (2002–2001; N=3584) cohorts. Beverage intakes were estimated from food frequency questionnaires and grouped into 5 intake categories. Mixed‐effect linear regression models were used to examine 4‐year changes in lipoprotein measures, and Cox proportional hazard models were used to estimate hazard ratios for incident dyslipidemia, adjusting for potential confounding factors. We found that regular (>1 serving per day) versus low (

Backgrounds and aims: Elevated common carotid artery intima-media thickness (carotid IMT) and diminished flow-mediated dilation (FMD) are early subclinical indicators of atherosclerosis. Serum total non-esterified fatty acid (NEFA) concentrations have been positively associated with subclinical atherosclerosis. The relations between individual NEFA, carotid IMT and FMD have as yet to be assessed. Methods: We investigated the associations between fasting serum individual NEFA, carotid IMT and FMD among Cardiovascular Health Study (CHS) participants with (n = 255 for carotid IMT, 301 for FMD) or without (n = 1314 for carotid IMT, 1462 for FMD) known atherosclerotic cardiovascular disease (ASCVD). Using archived samples (fasting) collected from 1996–1997 (baseline), 35 individual NEFAs were measured using gas chromatography. Carotid IMT and estimated plaque thickness (mean of maximum internal carotid IMT) were determined in 1998–1999. FMD was measured in 1997–1998. Linear regression adjusted by the Holm-Bonferroni method was used to assess relations between individual NEFA, carotid IMT and FMD. Results: In multivariable adjusted linear regression models per SD increment, the non-esterified trans fatty acid conjugated linoleic acid (trans-18:2 CLA) was positively associated with carotid IMT [β (95% CI): 44.8 (19.2, 70.4), p = 0.025] among participants with, but not without, ASCVD [2.16 (−6.74, 11.5), p = 1.000]. Non-esterified cis-palmitoleic acid (16:1n-7c) was positively associated with FMD [19.7 (8.34, 31.0), p = 0.024] among participants without, but not with ASCVD. No significant associations between NEFAs and estimated plaque thickness were observed. Conclusions: In older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for arteriopathy.

Background Weight regain after weight loss is common. The impact on cardiometabolic risk factors is not well established. Methods and Results Publicly available data were analyzed from participants of the Look AHEAD (Action for Health in Diabetes) trial with ≥3% initial weight loss (n=1561) during a 1‐year intensive lifestyle intervention and with year 4 follow‐up data. Participants who regained (regainers) or maintained (maintainers) weight loss were defined with 5 dichotomized cut points (0%, 25%, 50%, 75%, and 100%) of percentage weight loss regained (weight change from years 1–4 as percentage of first year weight loss). Change in cardiometabolic risk factors after initial weight loss was compared in maintainers and regainers, after controlling for demographics, medications, and baseline and year 1 change in body mass index. The effect was assessed separately in participants with

The long-term impact of carbohydrate quality on abdominal weight gain is not fully understood. We aimed to examine the prospective relation of a carbohydrate quality index (CQI; defined by four criteria: dietary fiber, glycemic index, whole grain-to-total grain ratio, and solid-to-total carbohydrate ratio), total, cereal grain, vegetable, and fruit fiber, carbohydrate-to-total fiber ratio, and carbohydrate-to-cereal fiber ratio with changes in waist circumference (WC). Subjects were middle-aged to older, mostly white, participants in the Framingham Offspring cohort (n = 3101 subjects), with mean baseline age 54.9 ± 0.2 years (mean ± SE) and body mass index (BMI) 27.2 ± 0.1 kg/m2. Food frequency questionnaire (FFQ), health, and lifestyle data were collected approximately every four years over a median total follow-up of 18 years. Repeated measure mixed models were used to estimate adjusted mean change in WC per four-year interval across quartiles of carbohydrate variables. In the most adjusted model, a higher CQI was marginally associated with a smaller increase in WC (2.0 ± 0.1 vs. 2.4 ± 0.1 cm in highest vs. lowest quartile, p-trend = 0.04). Higher ratios of carbohydrate-to-fiber and carbohydrate-to-cereal fiber were associated with greater increases in WC per four-year interval (2.6 ± 0.1 vs. 2.0 ± 0.1 cm, p-trend < 0.001, and 2.5 ± 0.1 vs. 2.1 ± 0.1 cm in highest versus lowest categories, p-trend = 0.007, respectively); whereas higher intake of total fiber (1.8 ± 0.1 vs. 2.7 ± 0.1 cm, p-trend < 0.001), cereal fiber (2.0 ± 0.1 vs. 2.5 ± 0.1 cm, p-trend = 0.001), and fruit fiber (2.0 ± 0.1 vs. 2.7 ± 0.1 cm, p-trend < 0.001) were associated with smaller increases in WC compared to lower intakes. There was a significant interaction between total fiber and total carbohydrate (as % of total energy intake). After stratification, the association between fiber intake and change in WC was not maintained in the context of a high carbohydrate diet. Better carbohydrate quality, primarily higher fiber intake and lower carbohydrate-to-fiber ratios, may help attenuate increases in abdominal adiposity over time.

Background The relation between tea consumption and age‐related changes in high‐density lipoprotein cholesterol (HDL‐C) concentrations remains unclear, and longitudinal human data are limited. The aim of current study was to examine the relation between tea intake and longitudinal change in HDL‐C concentrations. Methods and Results Baseline (2006) tea consumption was assessed via a questionnaire, and plasma HDL‐C concentrations were measured in 2006, 2008, 2010, and 2012 among 80 182 individuals (49±12 years of age) who did not have cardiovascular diseases or cancer, or did not use cholesterol‐lowering agents both at baseline (2006) and during the follow‐up period (2006–2012). The associations between baseline tea consumption and rate of change in HDL‐C concentrations were examined using generalized estimating equation models. Tea consumption was inversely associated with a decreased rate of HDL‐C concentrations (P‐trend

Despite a considerable amount of data available on the relationship between dietary glycemic index (GI) or load (GL) and cardiovascular disease (CVD) risk factors, in aggregate, the area remains unsettled. The aim of the present review was to summarize the effect of diets differing in GI/GL on CVD risk factors, by examining randomized controlled-feeding trials that provided all food and beverages to adult participants. The studies included a low and high GI/GL diet phase for a minimum of four weeks duration, and reported at least one outcome related to CVD risk; glucose homeostasis, lipid profile or inflammatory status. Ten publications representing five trials were identified. The low GI/GL compared to the high GI/GL diet unexpectedly resulted in significantly higher fasting glucose concentrations in two of the trials, and a lower area under the curve for glucose and insulin in one of the two studies during an oral glucose tolerance test. Response of plasma total, low density lipoprotein and high density lipoprotein cholesterol concentrations was conflicting in two of the studies for which data were available. There was either weak or no effect on inflammatory markers. The results of the five randomized controlled trials satisfying the inclusion criteria suggest inconsistent effects of the GI/GL value of the diet on CVD risk factors.

We investigated the effect of weight loss, independent of change in diet composition, on HDL and apoAI metabolism in men with metabolic syndrome (MetS). Subjects (19 men with MetS [NCEP-ATPIII]) were fed an isoenergetic Mediterranean-style diet for 5 weeks (all foods provided). Participants then underwent a 20-week free-living period during which they were counseled to restrict energy intake, after which they were again fed an isoenergetic Mediterranean-style diet for 5 weeks. At the end of the two controlled diets, participants received a single bolus of [5,5,5-2H3] L-leucine, and fasting blood samples were collected over a 96 h period. ApoAI kinetic was assessed using multicompartmental modeling of the tracer enrichment data. Participants achieved a 9.1 ± 2.8% reduction in body weight (P < 0.001). Weight loss resulted in an increase in plasma HDL-cholesterol (HDL-C) concentrations of 6.0% (P = 0.059) and HDL3-C of 7.9% (P = 0.045), attributable to a reduction in apoAI fractional catabolic rate (−7.8%; P = 0.046) with no change in apoAI production rate (2.2%; P = 0.58). These data indicate that weight loss, independent of variation in diet composition, increases plasma HDL primarily by delaying the catabolism of apoAI.

The effects of Therapeutic Lifestyle Change (TLC) diets, low and high in dietary fish, on apolipoprotein metabolism were examined. Subjects were provided with a Western diet for 6 weeks, followed by 24 weeks of either of two TLC diets (10/group). Apolipoprotein kinetics were determined in the fed state using stable isotope methods and compartmental modeling at the end of each phase. Only the high-fish diet decreased median triglyceride-rich lipoprotein (TRL) apoB-100 concentration (−23%), production rate (PR, −9%), and direct catabolism (−53%), and increased TRL-to-LDL apoB-100 conversion (+39%) as compared with the baseline diet (all P < 0.05). This diet also decreased TRL apoB-48 concentration (−24%), fractional catabolic rate (FCR, −20%), and PR (−50%) as compared with the baseline diet (all P < 0.05). The high-fish and low-fish diets decreased LDL apoB-100 concentration (−9%, −23%), increased LDL apoB-100 FCR (+44%, +48%), and decreased HDL apoA-I concentration (−15%, −14%) and PR (−11%, −12%) as compared with the baseline diet (all P < 0.05). On the high-fish diet, changes in TRL apoB-100 PR were negatively correlated with changes in plasma eicosapentaenoic and docosahexaenoic acids. In conclusion, the high-fish diet decreased TRL apoB-100 and TRL apoB-48 concentrations chiefly by decreasing their PR. Both diets decreased LDL apoB-100 concentration by increasing LDL apoB-100 FCR and decreased HDL apoA-I concentration by decreasing HDL apoA-I PR.

Fatty acid profiles of biological specimens from epidemiological/clinical studies can serve as biomarkers to assess potential relationships between diet and chronic disease risk. However, data are limited regarding fatty acid stability in archived specimens following long-term storage, a variable that could affect result validity. Our objective was to determine the effect of prolonged storage at −80°C on the fatty acid profiles of serum cholesteryl ester (CE), triglyceride (TG), and phospholipid (PL) fractions. This was accomplished by determining the fatty acid profile of frozen, archived, previously unthawed serum samples from 22 subjects who participated in a controlled feeding trial. Initial analysis was performed after trial completion and the repeat analysis after 8–10 years of storage using GC. No significant differences were observed among the majority of fatty acids regardless of lipid fraction. Reliability coefficients were high for the fatty acid classes (saturated fatty acid : 0.70, MUFA : 0.90, PUFA : 0.80). When differences were identified, they were limited to low abundance fatty acids (≤1.5 mol%). These differences were quantitatively small and likely attributable to technical improvements in GC methodology rather than sample degradation. Thus, our data demonstrate that storage at −80°C up to 10 years does not significantly influence serum CE, TG, or PL fatty acid profiles.

Cholesterol homeostasis, defined as the balance between absorption and synthesis, influences circulating cholesterol concentrations and subsequent coronary heart disease (CHD) risk. Statin therapy targets the rate-limiting enzyme in cholesterol biosynthesis and is efficacious in lowering CHD events and mortality. Nonetheless, CHD events still occur in some treated patients. To address differences in outcome during pravastatin therapy (40 mg/day), plasma markers of cholesterol synthesis (desmosterol, lathosterol) and fractional cholesterol absorption (campesterol, sitosterol) were measured, baseline and on treatment, in the Prospective Study of Pravastatin in the Elderly at Risk trial participants with (cases, n = 223) and without (controls, n = 257) a CHD event. Pravastatin therapy decreased plasma LDL-cholesterol and triglycerides and increased HDL-cholesterol concentrations to a similar extent in cases and controls. Decreased concentrations of the cholesterol synthesis markers desmosterol (−12% and −11%) and lathosterol (−50% and −56%) and increased concentrations of the cholesterol absorption markers campesterol (48% and 51%) and sitosterol (25% and 26%) were observed on treatment, but the magnitude of change was similar between cases and controls. These data suggest that decreases in cholesterol synthesis in response to pravastatin treatment were accompanied by modest compensatory increases in fractional cholesterol absorption. The magnitude of these alterations were similar between cases and controls and do not explain differences in outcomes with pravastatin treatment.

The relative influence of genetics and the environment on factors associated with cardiovascular disease (CVD) and metabolic syndrome (MetS) remains unclear. We performed model-fitting analyses to quantify genetic, common environmental, and unique environmental variance components of factors associated with CVD and MetS [waist circumference, blood pressure, fasting plasma glucose and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and fasting plasma lipids] in adult male and female monozygotic twins reared apart or together. We also investigated whether MetS components share common influences. Plasma cholesterol and triglyceride concentrations were highly heritable (56–77%, statistically significant). Waist circumference, plasma glucose and insulin, HOMA-IR, and blood pressure were moderately heritable (43–57%, statistically significant). Unique environmental factors contributed to the variance of all variables (20–38%, perforce statistically significant). Common environmental factors contributed 23, 30, and 42% (statistically significant) of the variance of waist circumference, systolic blood pressure, and plasma glucose, respectively. Two shared factors influenced MetS components; one influenced all components except HDL cholesterol, another influenced only lipid (triglyceride and HDL cholesterol) concentrations. These results suggest that genetic variance has a dominant influence on total variance of factors associated with CVD and MetS and support the proposal of one or more underlying pathologies of MetS.

Data is limited on measures influencing cholesterol homeostasis in subjects at high risk of developing cardiovascular disease (CVD) relative to established risk factors. To address this, we quantified circulating indicators of cholesterol homeostasis (plasma phytosterols and cholesterol precursor concentrations as surrogate measures of cholesterol absorption and synthesis, respectively) in Framingham Offspring Study Cycle-6 participants diagnosed with established CVD and/or ≥50% carotid stenosis not taking lipid lowering medication (cases, N = 155) and matched controls (N = 414). Cases and controls had similar plasma LDL-cholesterol; HDL-cholesterol was significantly lower in males, while triglyceride concentrations were significantly higher in female cases relative to their respective controls. Cholesterol absorption markers were significantly higher (229 ± 7 vs. 196 ± 4, 169 ± 6 vs. 149 ± 3 and 144 ± 5 vs. 135 ± 3 for campesterol, sitosterol, and cholestanol, respectively), whereas cholesterol synthesis markers were significantly lower (116 ± 4 vs. 138 ± 3, 73 ± 3 vs. 75 ± 2 for lathosterol and desmosterol, respectively) in cases compared with controls, irrespective of sex. After controlling for standard risk factors, campesterol (2.47 [1.71-3.56]; P < 0.0001), sitosterol (1.86 [1.38-2.50]; P < 0.0001), cholestanol (1.57 [1.09-2.27]; P = 0.02), desmosterol (0.59 [0.42-0.84]; P = 0.003), and lathosterol (0.58 [0.43-0.77]; P = 0.0002) were significantly associated with CVD (odds ratio [95% confidence interval]). These data suggest that impaired cholesterol homeostasis, reflected by lower synthesis and higher absorption marker concentrations, are highly significant independent predictors of prevalent CVD in this study population.

The purpose of this study was to examine whether changes in cholesterol metabolism after weight loss were affected by single nucleotide polymorphisms (SNPs) in ABCG5 and ABCG8 genes. Thirty-five hypercholesterolemic women lost 11.7 ± 2.5 kg (P < 0.001). Cholesterol kinetics were assessed using stable isotope techniques. TaqMan PCR was used to detect SNPs in ABCG5/G8. Homozygous Q604E variants in ABCG5 had larger (P < 0.05) reductions in cholesterol absorption and greater increases (P < 0.05) in synthesis in contrast to heterozygous and homozygous wild-type carriers. Heterozygous C54Y carriers had smaller declines (P = 0.047) in synthesis compared with homozygous variant individuals. The presence of at least one Y54 variant was associated with higher (P = 0.042) post-weight-loss synthesis compared with carriers of the C54 genotype. The direction of the results is consistent with cross-sectional studies on the effects of Q604E and C54Y polymorphisms on plasma cholesterol. SNPs in ABCG5/G8 were found to be associated with the response of cholesterol metabolism to weight loss. The evidence for associations between SNPs in ABCG5/G8 and various parameters of cholesterol metabolism indicates the potential effectiveness of establishing genetic screening tools to determine optimal lipid-lowering treatment routes for individuals during weight reduction.

Nine hypercholesterolemic and hypertriglyceridemic subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study to test the effect of atorvastatin 20 mg/day and 80 mg/day on the kinetics of apolipoprotein B-100 (apoB-100) in triglyceride-rich lipoprotein (TRL), intermediate density lipoprotein (IDL), and LDL, of apoB-48 in TRL, and of apoA-I in HDL. Compared with placebo, atorvastatin 20 mg/day was associated with significant reductions in TRL, IDL, and LDL apoB-100 pool size as a result of significant increases in fractional catabolic rate (FCR) without changes in production rate (PR). Compared with the 20 mg/day dose, atorvastatin 80 mg/day caused a further significant reduction in the LDL apoB-100 pool size as a result of a further increase in FCR. ApoB-48 pool size was reduced significantly by both atorvastatin doses, and this reduction was associated with nonsignificant increases in FCR. The lathosterol-campesterol ratio was decreased by atorvastatin treatment, and changes in this ratio were inversely correlated with changes in TRL apoB-100 and apoB-48 PR. No significant effect on apoA-I kinetics was observed at either dose of atorvastatin. Our data indicate that atorvastatin reduces apoB-100- and apoB-48-containing lipoproteins by increasing their catabolism and has a dose-dependent effect on LDL apoB-100 kinetics. Atorvastatin-mediated changes in cholesterol homeostasis may contribute to apoB PR regulation.

Fish intake, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and in some cases α-linolenic acid (ALA) have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and the progression of coronary artery atherosclerosis was assessed among women with established coronary artery disease (CAD). A prospective cohort study involved postmenopausal women (n = 228) participating in the Estrogen Replacement and Atherosclerosis Trial. Quantitative coronary angiography was performed at baseline and after 3.2 ± 0.6 (mean ± SD) years. Women with plasma phospholipid (PL) DHA levels above the median, compared with below, exhibited less atherosclerosis progression, as expressed by decline in minimum coronary artery diameter (−0.04 ± 0.02 and −0.10 ± 0.02 mm, respectively; P = 0.007) or increase in percentage stenosis (1.34 ± 0.76% and 3.75 ± 0.74%, respectively; P = 0.006), and had fewer new lesions [2.0% (0.5–3.5%) of measured segments (95% confidence interval) and 4.2% (2.8–5.6%), respectively; P = 0.009] after adjustments for cardiovascular risk factors. Similar results were observed for DHA in the triglycerides (TGs). EPA and ALA in plasma lipids were not significantly associated with atherosclerosis progression. Consistent with higher reported fish intake, higher levels of plasma TG and PL DHA are associated with less progression of coronary atherosclerosis in postmenopausal women with CAD.

In general, under isoweight conditions, different types of dietary protein or individual amino acids have little effect on lipoprotein patterns. Dietary carbohydrate tends to increase plasma triglyceride when it displaces fat, accompanied by a decrease in HDL cholesterol concentrations. Potential differential effects of types of carbohydrate are difficult to assess because of differences in rates of absorption and confounding of dietary fiber. Saturated fatty acids increase LDL and HDL cholesterol, whereas trans fatty acids increase LDL but not HDL cholesterol. Unsaturated fatty acids decrease LDL and HDL cholesterol, polyunsaturated more so than monounsaturated. There has been considerable interest in the potential benefit of major shifts in dietary macronutrients on weight loss and lipoprotein patterns. Short-term data favor substituting protein and fat for carbohydrate, whereas long-term data have failed to show a benefit for weight loss. During an active weight loss period low-carbohydrate diets more favorably affect triglyceride and HDL and less favorably affect LDL cholesterol concentrations. Additional efforts need to be focused on gaining a better understanding of the effect of dietary macronutrient profiles on established and emerging cardiovascular disease risk factors, mechanisms for changes observed and contributors to individual variability. Such data are needed to allow reassessment and, if necessary, modification of current recommendations.

Hypercholesterolemia is a risk factor for coronary heart disease (CHD) and also could contribute to impaired immune response. The National Cholesterol Education Program Expert Panel recommends a therapeutic lifestyle change (TLC) diet to reduce the risk for CHD. We investigated the effects of changing from a high-fat Western diet to a low-fat diet in accordance with a TLC diet on immune functions of older adults with hypercholesterolemia to determine whether improving the lipid profile via dietary intervention would have beneficial effects on immune functions. In a double-blind study, 18 subjects consumed both a Western diet (38% fat) and a TLC diet (28% fat) for 32 days in a randomized order. Measures of cellular immune responses, including delayed-type hypersensitivity (DTH) response, in vitro lymphocyte proliferation, and interleukin (IL)-2 production, and production of proinflammatory mediators, including tumor necrosis factor-α, IL-6, IL-1β, and prostaglandin E2, were determined. DTH response and lymphocyte proliferative response increased significantly (29% and 27%, respectively) after consumption of a TLC diet.Our results indicate that consumption of a TLC diet enhances T cell-mediated immune functions in older adults with elevated cholesterol level. This might be a clinically important benefit, considering the decline of T cell-mediated immune functions with aging and evidence of impaired immune function associated with hypercholesterolemia.

The HDL Atherosclerosis Treatment Study (HATS) demonstrated a clinical benefit in coronary artery disease patients with low HDL cholesterol (HDL-C) levels treated with simvastatin and niacin (S-N) or S-N plus antioxidants (S-N+A) compared with antioxidants alone or placebo. Angiographically documented stenosis regressed in the S-N group but progressed in all other groups. To assess the mechanism(s) responsible for these observations, surrogate markers of cholesterol absorption and synthesis were measured in a subset of 123 HATS participants at 24 months (on treatment) and at 38 months (off treatment). Treatment with S-N reduced desmosterol and lathosterol levels (cholesterol synthesis indicators) 46% and 36% (P < 0.05), respectively, and elevated campesterol and β-sitosterol levels (cholesterol absorption indicators) 70% and 59% (P < 0.05), respectively, relative to placebo and antioxidant but not S-N+A. Treatment with antioxidants alone had no significant effect. Combining S-N with antioxidants reduced desmosterol and lathosterol by 37% and 31%, and elevated campesterol and β-sitosterol levels by 54% and 46%, but differences did not attain significance. Mean change in percent stenosis was positively associated with a percent change in lathosterol (r = 0.26, P < 0.005) and negatively associated with a percent change in β-sitosterol (r = −0.21, P < 0.01).These data suggest that changes in stenosis were attributable, in part, to changes in cholesterol metabolism.

Consumption of diets high in hydrogenated fat/trans fatty acids has been shown to have an adverse affect on lipoprotein profiles with respect to cardiovascular disease risk. Dietary fat and cholesterol play an important role in the regulation of immune and inflammatory responses shown to be involved in atherogenesis. We investigated the effects of diets containing hydrogenated fat on cellular immune response and production of inflammatory cytokines in human subjects with moderately elevated cholesterol levels (LDL cholesterol >130 mg/dl). In a double blind crossover study, 19 subjects consumed three diets, 30% of calories as fat, of which two thirds were provided as soybean oil, soybean oil-based stick margarine, or butter for 32 days, each in a randomized order. Production of proinflammatory mediators, prostaglandin (PG)E2, interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α); delayed type hypersensitivity (DTH) response, in vitro lymphocyte proliferation, and production of IL-2 were determined. Production of IL-6 and TNF-α was significantly higher after consumption of stick margarine diet compared with soybean oil diet. IL-1β and TNF-α production correlated positively with ratios of total cholesterol to HDL cholesterol (r = 0.499, P < 0.001 and r = 0.291, P = 0.04, respectively). There was no significant difference in DTH response, lymphocyte proliferation, or levels of IL-2 and PGE2 produced among three groups. Our results indicate that consumption of a diet high in hydrogenated fat does not adversely affect cellular immunity but increases production of inflammatory cytokines that have been associated with the pathophysiology of atherosclerosis. —Han, S. N., L. S. Leka, A. H. Lichtenstein, L. M. Ausman, E. J. Schaefer, and S. N. Meydani. Effect of hydrogenated and saturated, relative to polyunsaturated, fat on immune and inflammatory responses of adults with moderate hypercholesterolemia.

Lifestyle modification to decrease cardiovascular disease (CVD) risk has recently been reaffirmed by both the National Cholesterol Education Program and American Heart Association (AHA). Using a randomized crossover design, the Therapeutic Lifestyle Change (TLC)/Step 2 diet relative to a typical Western diet was assessed in 36 moderately hypercholesterolemic subjects in a clinical setting under iso-weight conditions. Mean lipoprotein and apolipoprotein levels (fasting and non-fasting), fatty acid profiles, parameters of HDL metabolism, and glucose homeostasis were determined. Relative to the Western diet, the TLC/Step 2 diet resulted in 11% and 7% lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), respectively, with no significant change in TG levels or total cholesterol-HDL-C ratio. Similar responses were observed in the non-fasting state. Linoleic (18:2n-6c) and α-linolenic (18:3n-3) acids increased at the expense of oleic acid (18:1n-9c) in the cholesteryl ester, TG, and phospholipid subfractions. The dietary changes had no significant effect on fractional esterification rate of HDL, phospholipid transfer protein (PLTP), or cholesterol ester transfer protein activities, or glucose and insulin levels. Female and male subjects responded similarly. The TLC/Step 2 diet resulted in a decrease in some CVD risk factors and no apparent adverse effects in others.—Lichtenstein, A. H., L. M. Ausman, S. M. Jalbert, M. Vilella-Bach, M. Jauhiainen, S. McGladdery, A. T. Erkkilä, C. Ehnholm, J. Frohlich, and E. J. Schaefer. Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects.

To determine whether hydrogenated fat consumption alters triglyceride metabolism and cholesterol esterification rates, 14 women (65–71 years of age) were provided with each of four diets for 5-week periods according to a randomized cross-over design. The experimental diets contained either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines. Triglyceride uptake by adipose tissue was determined by measuring plasma acylation-stimulating protein (ASP), FFA, glucose, and insulin levels, while rates of transfer and esterification rate of newly synthesized cholesterol (ER) were derived by using plasma CETP levels and the deuterium incorporation methodology. Plasma ASP levels were lowest (P < 0.05) in subjects on the SM diet (33.4 ± 12.7 nM) compared with the SO (48.7 ± 17.0 nM) and SQM (50.7 ± 15.7 nM) diets. Conversely, FFA were highest (P < 0.05) on the SM diet (0.86 ± 0.45 mM) relative to all the other diets. No differences were observed in plasma glucose and insulin levels among diets. A trend toward higher CETP levels after consumption of the SM diet was observed. However, the ER was lowest (P < 0.05) after the SM (0.111 ± 0.062 g·day−1) diet and highest after consumption of the SQM (0.216 ± 0.123 g·day−1) diet. In addition, ASP levels were negatively correlated with FFA (r = −0.63, P < 0.05), LDL cholesterol (r = −0.56, P < 0.05), and TG (r = −0.41, P < 0.05), whereas FFA was positively correlated with apolipoprotein B-containing lipoproteins (r = 0.58 and 0.47, for VLDL and LDL cholesterol, P < 0.05), and negatively correlated with HDL cholesterol (r = −0.51, P < 0.05). The ER was found to positively correlate with HDL cholesterol and HDL2 subfraction (r = 0.53 and 0.45, respectively, P < 0.05). Taken together, these data demonstrate that the alterations in circulating lipid levels, commonly observed with consumption of hydrogenated fat-rich diets, can be explained in part by changes in ASP activity as well as newly synthesized cholesterol ER.—Matthan, N. R., K. Cianflone, A. H. Lichtenstein, L. M. Ausman, M. Jauhiainen, and P. J. H. Jones. Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women.

To determine mechanisms by which hydrogenated fat influences plasma lipid levels, 14 women (65–71 yrs with LDL-C ≥ 130 mg·dl−1) consumed, for 5-week periods each, a baseline (BL) diet (39% kcal fat, 164 mg chol·1000 kcal−1) and reduced fat diets (30% kcal) where two-thirds of the fat was either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines, or butter (BT). Plasma lipid levels were analyzed at the end of each phase. Fractional synthesis rates (FSR) in pools/day (p·d−1) and absolute synthesis rates (ASR) in grams/day (g·d−1) of free cholesterol (FC) were measured using the deuterium incorporation methodology. Plasma total (P < 0.01) and low density lipoprotein (P < 0.05) cholesterol levels increased with increasing degree of hydrogenation or saturated fat intake. High density lipoprotein cholesterol levels (P < 0.05) were lowest on the SM diet when compared to the BT diet. Low trans SQM (0.081 ± 0.019 p·d−1) and medium trans TM (0.086 ± 0.029 p·d−1) diets elicited responses similar to the SO (0.078 ± 0.024 p·d−1) diet, whereas high trans SM (0.053 ± 0.029 p·d−1) diet mimicked the BT (0.062 ± 0.017 p·d−1) and high fat BL (0.053 ± 0.023 p·d−1) diet in its suppression (P < 0.05) of FSR-FC. ASR-FC, which is an approximation of the daily production of newly synthesized cholesterol, showed a trend similar to the FSR-FC data. These results indicate that reduced synthesis is not responsible for the higher plasma TC levels seen with consumption of the SM, BT, and BL diets, and suggest that another mechanism, possibly impairment of the catabolic pathway of cholesterol, is involved.—Matthan, N. R., L. M. Ausman, A. H. Lichtenstein, and P. J. H. Jones. Hydrogenated fat consumption affects cholesterol synthesis in moderately hypercholesterolemic women. J. Lipid Res. 2000. 41: 834–839.

Stable isotope methodology was used to determine the kinetic behavior of apolipoprotein (apo) A-I within the triglyceride-rich lipoprotein (TRL) fraction and to compare TRL apoA-I kinetics with that of apoA-I in high density lipoprotein (HDL) and TRL apoB-48. Eight subjects (5 males and 3 females) over the age of 40 were placed on a baseline average American diet and after 6 weeks received a primed-constant infusion of [5,5,5-2H3]-l-leucine for 15 h while consuming small hourly meals of identical composition. HDL and TRL apoA-I and TRL apoB-48 tracer/tracee enrichment curves were obtained by gas chromatography–mass spectrometry. Data were fitted to a compartmental model to determine the fractional secretion rates of apoA-I and apoB-48 within each lipoprotein fraction. Mean plasma apoA-I levels in TRL and HDL fractions were 0.204 ± 0.057 and 134 ± 15 mg/dl, respectively. The mean fractional catabolic rate (FCR) of TRL apoA-I was 0.250 ± 0.069 and HDL apoA-I was 0.239 ± 0.054 pools/day, with mean estimated residence times (RT) of 4.27 and 4.37 days, respectively. The mean TRL apoB-48 FCR was 5.2 ± 2.0 pools/day and the estimated mean RT was 5.1 ± 1.8 h. Our results indicate that apoA-I is catabolized at a slower rate than apoB-48 within TRL, and that apoA-I within TRL and HDL fractions are catabolized at similar rates.—Vélez-Carrasco, W., A. H. Lichtenstein, P. H. R. Barrett, Z. Sun, G. G. Dolnikowski, F. K. Welty, and E. J. Schaefer. Human apolipoprotein A-I kinetics within triglyceride-rich lipoproteins and high density lipoproteins. J. Lipid Res. 1999. 40: 1695–1700.

Observational data have identified associations between carotenoids, folic acid, and vitamin E, or metabolites altered by these nutrients, and cardiovascular disease (CVD) risk. Despite biological plausibility, for the most part, data derived from nutrient supplement trials using moderate to high doses of single nutrients or nutrient combinations (exceeding amounts to avoid nutrient deficiency) have been disappointing. The data for vitamin D is not yet adequate to evaluate; observational data suggest were a relationship to exist it would be related to nutrient insufficiency. There is some evidence that use of nutrient supplements intended to decrease CVD risk has resulted in unanticipated adverse consequences. Potential discrepancies between observational and interventional data include concerns of residual confounding by diet and lifestyle patterns, publication bias against studies with null or negative outcomes, reliance on secondary rather than primary prevention trials, and unaccounted for contribution of genotypic variations. At this time there are insufficient data to recommend the routine use of nutrient supplements to prevent or treat CVD. In the recent past we have learned a great deal about anticipated and unanticipated consequences of nutrient supplementation and cardiovascular outcomes. As a result, we are in a better position to adjudicate new potential relationships as data emerge.

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and trans fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996–1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)‐6 polyunsaturated, n‐3 polyunsaturated, and trans fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5‐year follow‐up period. Total n‐3 (hazard ratio [HR], 0.77 [95% CI, 0.61–0.97]) and n‐6 (HR, 1.32 [95% CI, 1.01–1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo‐γ‐linolenic acid (20:3n‐6) was associated with higher risk (HR, 1.29 [95% CI, 1.02–1.63]), whereas cis‐7‐hexadecenoic acid (16:1n‐9c) and arachidonic acid (20:4n‐6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47–0.97]; HR, 0.81 [95% CI. 0.65–1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n‐3 subclass and dihomo‐γ‐linolenic acid are diet derived and may be potential biomarkers for total stroke risk.

Subjective reporting of food intake can be unreliable. No objective method is available to distinguish between diets differing in protein type. To address this gap, a secondary analysis of a randomized controlled cross-over feeding trial was conducted. Assessed were fasting plasma metabolite profiles and their associations with cardiometabolic risk factors (CMRFs). Hypercholesterolemic post-menopausal women (N = 11) were provided with diets containing predominantly animal protein (AP) and soy protein (SP). Untargeted metabolomics were used to determine the plasma metabolite profiles at the end of each diet phase. Concentrations of identified metabolites (N = 829) were compared using paired t-tests adjusted for false discovery rate, partial least square-discrimination analysis (PLS-DA) and receiver operating characteristics (ROC). Among the identified metabolites, 58 differed significantly between the AP and SP diets; the majority were phospholipids (n = 36), then amino acids (n = 10), xenobiotics (n = 7), vitamin/vitamin-related (n = 3) and lipids (n = 2). Of the top 10 metabolites, amino acid-derived metabolites, phospholipids and xenobiotics comprised the main categories differing due to dietary protein type. ROC curves confirmed that the top 10 metabolites were potential discriminating biomarkers for AP- and SP-rich diets. In conclusion, amino acid-derived metabolites, phosphatidylethanolamine-derived metabolites and isoflavones were identified as potential metabolite biomarkers distinguishing between dietary protein type.

Abstract Background Implementing evidence-based recommendations for treating pediatric overweight and obesity is challenging in low-resource settings. We conducted a randomized controlled trial to evaluate the effects of implementing the American Academy of Pediatrics overweight/obesity recommendations using a Standard Care approach alone or with the addition of an enhanced program in a safety-net pediatric primary care setting (located in Bronx, New York, United States). Methods In a 12-month trial, families of children (age 7–12 years; body mass index ≥85th American percentile for age and sex; 74% self-identified as Hispanic/Latino; n = 360) were randomly assigned to receive Standard Care Alone or Standard Care + Enhanced Program. An English/Spanish bilingual staff provided the Standard Care Alone consisting of quarterly semi-structured pediatrician visits targeting family-based behavioral changes. The Standard Care + Enhanced Program was enriched with eight Skill-Building Core and monthly Post-Core Support sessions. Results The mean body mass index Z-score declined in both arms (P

Taste perception is a primary driver of food choices; however, little is known about how perception of all five tastes (sweet, salt, sour, bitter, umami) collectively inform dietary patterns. Our aim was to examine the associations between a multivariable measure of taste perception—taste perception profiles—and empirically derived dietary patterns. The cohort included 367 community-dwelling adults (55–75 years; 55% female; BMI = 32.2 ± 3.6 kg/m2) with metabolic syndrome from PREDIMED-Plus, Valencia. Six taste perception profiles were previously derived via data-driven clustering (Low All, High Bitter, High Umami, Low Bitter and Umami, High All But Bitter, High All But Umami); three dietary patterns were derived via principal component analysis (% variance explained = 20.2). Cross-sectional associations between profiles and tertials of dietary pattern adherence were examined by multinomial logistic regression. Overall, there were several significant differences in dietary pattern adherence between profiles: the vegetables, fruits, and whole grains pattern was significantly more common for the High All But Umami profile (OR range for high vs. low adherence relative to other profiles (1.45–1.99; 95% CI minimum lower, maximum upper bounds: 1.05, 2.74), the non-extra virgin olive oils, sweets, and refined grains pattern tended to be less common for Low All or High Bitter profiles (OR range: 0.54–0.82), while the alcohol, salty foods, and animal fats pattern tended to be less common for Low Bitter and Umami and more common for High All But Bitter profiles (OR range: 0.55–0.75 and 1.11–1.81, respectively). In conclusion, among older adults with metabolic syndrome, taste perception profiles were differentially associated with dietary patterns, suggesting the benefit of integrating taste perception into personalized nutrition guidance.

The consumption of sugar-sweetened beverages (SSB), which includes soft drinks, fruit drinks, and other energy drinks, is associated with excess energy intake and increased risk for chronic metabolic disease among children and adults. Thus, reducing SSB consumption is an important strategy to prevent the onset of chronic diseases, and achieve and maintain a healthy body weight. The mechanisms by which excessive SSB consumption may contribute to complex chronic diseases may partially depend on an individual’s genetic predisposition. Gene–SSB interaction investigations, either limited to single genetic loci or including multiple genetic variants, aim to use genomic information to define mechanistic pathways linking added sugar consumption from SSBs to those complex diseases. The purpose of this review is to summarize the available gene-SSB interaction studies investigating the relationships between genetics, SSB consumption, and various health outcomes. Current evidence suggests there are genetic predispositions for an association between SSB intake and adiposity; evidence for a genetic predisposition between SSB and type 2 diabetes or cardiovascular disease is limited.

Background and Aims: The association of fatty acids with coronary heart disease (CHD) has been examined, mainly through dietary measurements, and has generated inconsistent results due to measurement error. Large observational studies and randomized controlled trials have shown that plasma phospholipid fatty acids (PL-FA), especially those less likely to be endogenously synthesized, are good biomarkers of dietary fatty acids. Thus, PL-FA profiles may better predict CHD risk with less measurement error. Methods: We performed a matched case-control study of 2428 postmenopausal women nested in the Women’s Health Initiative Observational Study. Plasma PL-FA were measured using gas chromatography and expressed as molar percentage (moL %). Multivariable conditional logistic regression was used to calculate odds ratios (95% CIs) for CHD associated with 1 moL % change in PL-FA. Results: Higher plasma PL long-chain saturated fatty acids (SFA) were associated with increased CHD risk, while higher n-3 polyunsaturated fatty acids (PUFA) were associated with decreased risk. No significant associations were observed for very-long-chain SFA, monounsaturated fatty acids (MUFA), PUFA n-6 or trans fatty acids (TFA). Substituting 1 moL % PUFA n-6 or TFA with an equivalent proportion of PUFA n-3 were associated with lower CHD risk. Conclusions: Higher plasma PL long-chain SFA and lower PUFA n-3 were associated with increased CHD risk. A change in diet by limiting foods that are associated with plasma PL long-chain SFA and TFA while enhancing foods high in PUFA n-3 may be beneficial in CHD among postmenopausal women.

Public interest in popular diets is increasing, in particular whole-food plant-based (WFPB) and vegan diets. Whether these diets, as theoretically implemented, meet current food-based and nutrient-based recommendations has not been evaluated in detail. Self-identified WFPB and vegan diet followers in the Adhering to Dietary Approaches for Personal Taste (ADAPT) Feasibility Survey reported their most frequently used sources of information on nutrition and cooking. Thirty representative days of meal plans were created for each diet. Weighted mean food group and nutrient levels were calculated using the Nutrition Data System for Research (NDSR) and data were compared to DRIs and/or USDA Dietary Guidelines/MyPlate meal plan recommendations. The calculated HEI-2015 scores were 88 out of 100 for both WFPB and vegan meal plans. Because of similar nutrient composition, only WFPB results are presented. In comparison to MyPlate, WFPB meal plans provide more total vegetables (180%), green leafy vegetables (238%), legumes (460%), whole fruit (100%), whole grains (132%), and less refined grains (−74%). Fiber level exceeds the adequate intakes (AI) across all age groups. WFPB meal plans failed to meet the Recommended Dietary Allowances (RDA)s for vitamin B12 and D without supplementation, as well as the RDA for calcium for women aged 51–70. Individuals who adhere to WFBP meal plans would have higher overall dietary quality as defined by the HEI-2015 score as compared to typical US intakes with the exceptions of calcium for older women and vitamins B12 and D without supplementation. Future research should compare actual self-reported dietary intakes to theoretical targets.

ABSTRACT Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal drugs prevents C. albicans-associated mortalities. C. albicans provides a clinically relevant system for studying the relationship between diet and the microbiota as it relates to commensalism and pathogenicity. As a first step toward a dietary intervention to reduce C. albicans GI colonization, we investigated the impact of dietary lipids on murine colonization by C. albicans. Coconut oil and its constituent fatty acids have antifungal activity in vitro; we hypothesized that dietary coconut oil would reduce GI colonization by C. albicans. Colonization was lower in mice fed a coconut oil-rich diet than in mice fed diets rich in beef tallow or soybean oil. Switching beef tallow-fed mice to a coconut oil diet reduced preexisting colonization. Coconut oil reduced colonization even when the diet also contained beef tallow. Dietary coconut oil also altered the metabolic program of colonizing C. albicans cells. Long-chain fatty acids were less abundant in the cecal contents of coconut oil-fed mice than in the cecal contents of beef tallow-fed mice; the expression of genes involved in fatty acid utilization was lower in C. albicans from coconut oil-fed mice than in C. albicans from beef tallow-fed mice. Extrapolating to humans, these findings suggest that coconut oil could become the first dietary intervention to reduce C. albicans GI colonization. IMPORTANCE Candida albicans, the most common human fungal pathogen, can cause infections with a mortality rate of ~40%. C. albicans is part of the normal gut flora, but when a patient’s immune system is compromised, it can leave the gut and cause infections. By reducing the amount of C. albicans in the gut of susceptible patients, infections (and the resulting fatalities) can be prevented. Currently, this is done using antimicrobial drugs; to “preserve” drugs for treating infections, we looked for a dietary change to reduce the amount of C. albicans in the gut. Using a mouse model, we showed that adding coconut oil to the diet could become the first drug-free way to reduce C. albicans in the gut. More broadly, this model lets us study the interactions between our diet and the microbes in our body and the reasons why some of those microbes, under certain conditions, cause disease. Podcast: A podcast concerning this article is available.

We summarize the 2016 update of the 2004 Agency of Healthcare Research and Quality′s evidence review of omega-3 fatty acids and cardiovascular disease (CVD). The overall findings for the effects of marine oil supplements on intermediate CVD outcomes remain largely unchanged. There is high strength of evidence, based on numerous trials, of no significant effects of marine oils on systolic or diastolic blood pressures, but there are small, yet statistically significant increases in high density lipoprotein and low density lipoprotein cholesterol concentrations. The clinical significance of these small changes, particularly in combination, is unclear. The strongest effect of marine oils is on triglyceride concentrations. Across studies, this effect was dose-dependent and related to studies′ mean baseline triglyceride concentration. In observational studies, there is low strength of evidence that increased marine oil intake lowers ischemic stroke risk. Among randomized controlled trials and observational studies, there is evidence of variable strength of no association with increased marine oil intake and lower CVD event risk. Evidence regarding alpha-linolenic acid intake is sparser. There is moderate strength of evidence of no effect on blood pressure or lipoprotein concentrations and low strength of evidence of no association with coronary heart disease, atrial fibrillation and congestive heart failure.

IntroductionCardiovascular disease (CVD) is the leading cause of death for women in the United States. A healthy diet and appropriate physical activity can help reduce the risk for CVD. However, many women do not follow recommendations for these behaviors. In this study, we used qualitative methods to better understand knowledge and awareness about CVD in women, perceived threat of CVD, barriers to heart-healthy eating and physical activity, and intervention strategies for behavior change.MethodsWe conducted four focus groups with 38 white women aged 40 years or older in Kansas and Arkansas. We also interviewed 25 Cooperative State Research, Education, and Extension Service agents in those states. Environmental audits of grocery stores and the physical environment were done in three communities.ResultsMost women were aware of the modifiable risk factors for CVD. Although they realized they were susceptible, they thought CVD was something they could overcome. Common barriers to achieving a heart-healthy diet included time and concern about wasting food. Most women had positive attitudes toward physical activity and reported exercising in the past, but found it difficult to resume when their routine was disrupted. The environmental audits suggested that there are opportunities to be physically active and that with the exception of fresh fish in Kansas, healthful foods are readily available in local food stores.ConclusionInterventions to change behavior should be hands-on, have a goal-setting component, and include opportunities for social interaction. It is especially important to offer interventions as awareness increases and women seek opportunities to build skills to change behavior.