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.

Matrix Effects on the Delivery Efficacy of Bifidobacterium animalis subsp. lactis BB-12 on Fecal Microbiota, Gut Transit Time, and Short-Chain Fatty Acids in Healthy Young Adults.

Probiotics are consumed in fermented dairy products or as capsules for their putative health benefits. However, little research has been done to evaluate the effects of the delivery matrix on the health benefits of probiotics in humans. To examine the effects of delivering Bifidobacterium animalis subsp. lactis BB-12 (BB-12) (log10 10 ± 0.5 CFU/day) via a yogurt smoothie versus a capsule, we monitored the fecal microbiota, gut transit times (GTTs), and fecal excretion of short-chain fatty acids (SCFAs) in healthy adults. In a randomized, four-period, crossover study performed in a partially blind manner, 36 adults were recruited and randomly assigned to four treatments: control yogurt smoothie (YS), yogurt smoothie with BB-12 added prefermentation (PRE), yogurt smoothie with BB-12 added postfermentation (POST), and capsule containing BB-12 (CAP). Participants' fecal microbiota was assessed using 16S rRNA sequencing, GTTs via SmartPill, and fecal SCFAs by gas chromatography (GC) before (baseline) and after each intervention. Participants had significantly higher percentage of Streptococcus after consuming YS versus CAP (P = 0.01). Bifidobacterium-specific terminal restriction fragment length polymorphism analysis revealed a significantly higher percentage of B. animalis after consuming PRE and POST compared to baseline, YS, CAP, and final washout (P < 0.0001). The predominant SCFAs were negatively correlated with GTTs. Consumption of BB-12 delivered in a yogurt smoothie or capsule did not significantly alter the composition of the gut microbiota, GTTs, or fecal SCFA concentration of the study cohort. However, daily consumption of BB-12 in yogurt smoothie may result in higher relative abundance of B. animalis in healthy adults. (This trial has been registered at ClinicalTrials.gov under identifier NCT01399996.) IMPORTANCE Bifidobacterium animalis subsp. lactis BB-12 is a probiotic strain that has been used worldwide since 1985. It has commonly been delivered in fermented dairy products for perceived benefits associated with gut health and enhanced immune function. In addition to fermented dairy products, many new probiotic-containing alternatives such as probiotic-containing juice, probiotic-containing chocolate, and capsules have been developed. While these products provide more options for people to access probiotics, little research has been done on the effect of delivery matrix (dairy versus nondairy) on their efficacy in humans. In addition, it was unclear how yogurt fermentation may influence the survival of BB-12 in the product or on its performance in vivo. The significance of our study is in simultaneously assessing the effect of BB-12, alone and in different delivery vehicles, on the gut transit time, fecal short-chain fatty acids, and the composition of the gut microbiota of the study cohort.

Effect of varying quantities of lean beef as part of a Mediterranean-style dietary pattern on lipids and lipoproteins: a randomized crossover controlled feeding trial.

BACKGROUND: It remains unclear whether red meat consumption is causatively associated with cardiovascular disease (CVD) risk, and few randomized controlled studies have examined the effect of incorporating lean beef into a healthy dietary pattern. OBJECTIVES: To evaluate the effects of a Mediterranean (MED) diet (carbohydrate 42%, protein 17%, fat 41%, SFAs 8%, MUFAs 26%, PUFAs 8%) with 14 (MED0.5; 0.5 oz), 71 (MED2.5; 2.5 oz), and 156 (MED5.5; 5.5 oz) g/d/2000 kcal lean beef compared with an average American diet (AAD; carbohydrate 52%, protein 15%, fat 33%, SFAs 12%, MUFAs 13%, PUFAs 8%) on lipid and lipoprotein concentrations, particle number, and size. METHODS: This was a multicenter, 4-period controlled feeding, randomized crossover study. Fifty-nine generally healthy males and females (BMI 20-38 kg/m2; age 30-65 y) consumed each diet for 4 wk with a ≥1-wk washout between the diets. Fasting blood samples were collected at baseline and at the end of each 4-wk period. Lipid subfractions were measured by NMR. RESULTS: Compared with the AAD, all 3 MED diets decreased LDL cholesterol (MED0.5: -10.3 mg/dL; 95% CI: -5.4, -15.7 mg/dL; MED2.5: -9.1 mg/dL; 95% CI: -3.9, -14.3 mg/dL; MED5.5: -6.9 mg/dL; 95% CI: -1.7, -12.1 mg/dL; P < 0.0001). All MED diets elicited similar reductions in total LDL particle number compared with baseline (P < 0.005); however, significant decreases only occurred with MED0.5 (-91.2 nmol/L; 95% CI: -31.4, -151.0 nmol/L) and MED2.5 (-85.3 nmol/L; 95% CI: -25.4, -145.2 nmol/L) compared with AAD (P < 0.003). Compared with the AAD, non-HDL cholesterol (P < 0.01) and apoB (P < 0.01) were lower following the 3 MED diets; there were no differences between the MED diets. All diets reduced HDL-cholesterol and HDL particle number from baseline (P < 0.01). CONCLUSIONS: Lipid and lipoprotein lowering was not attenuated with the inclusion of lean beef in amounts ≤71 g (2.5 oz)/d as part of a healthy low-saturated-fat Mediterranean-style diet.This study is registered at clinicaltrials.gov as NCT02723617.

The Effect of Inflammation and Insulin Resistance on Lipid and Lipoprotein Responsiveness to Dietary Intervention.

Lipids and lipoproteins are major targets for cardiovascular disease (CVD) prevention. Findings from a limited number of clinical trials suggest diet-induced atherogenic lipoprotein lowering can be altered in the presence of chronic low-grade inflammation or insulin resistance. This review summarizes results from randomized controlled trials that have examined diet-induced changes in lipids/lipoproteins by inflammatory or insulin sensitivity status. In addition, mechanisms to explain these clinical observations are explored. Post hoc analyses of data from a limited number of randomized controlled trials suggest attenuation of diet-induced lipid/lipoprotein lowering in individuals with inflammation and/or insulin resistance. These findings are supported by experimental studies showing that inflammatory stimuli and hyperinsulinemia alter genes involved in endogenous cholesterol synthesis and cholesterol uptake, reduce cholesterol efflux, and increase fatty acid biosynthesis. Further a priori defined research is required to better characterize how chronic low-grade inflammation and insulin resistance modulate lipid and lipoprotein responsiveness to guide CVD risk reduction in individuals presenting with these phenotypes.

Diets Enriched with Conventional or High-Oleic Acid Canola Oils Lower Atherogenic Lipids and Lipoproteins Compared to a Diet with a Western Fatty Acid Profile in Adults with Central Adiposity.

BACKGROUND: Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists. OBJECTIVES: We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial. METHODS: In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model. RESULTS: Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations. CONCLUSIONS: HOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833.

Diets Low in Saturated Fat with Different Unsaturated Fatty Acid Profiles Similarly Increase Serum-Mediated Cholesterol Efflux from THP-1 Macrophages in a Population with or at Risk for Metabolic Syndrome: The Canola Oil Multicenter Intervention Trial.

Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear. Objective: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity. Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure. Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively). Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012.

Effects of Dark Chocolate and Almonds on Cardiovascular Risk Factors in Overweight and Obese Individuals: A Randomized Controlled-Feeding Trial.

BACKGROUND: Consumption of almonds or dark chocolate and cocoa has favorable effects on markers of coronary heart disease; however, the combined effects have not been evaluated in a well-controlled feeding study. The aim of this study was to examine the individual and combined effects of consumption of dark chocolate and cocoa and almonds on markers of coronary heart disease risk. METHODS AND RESULTS: A randomized controlled, 4-period, crossover, feeding trial was conducted in overweight and obese individuals aged 30 to 70 years. Forty-eight participants were randomized, and 31 participants completed the entire study. Each diet period was 4 weeks long, followed by a 2-week compliance break. Participants consumed each of 4 isocaloric, weight maintenance diets: (1) no treatment foods (average American diet), (2) 42.5 g/d of almonds (almond diet [ALD]), (3) 18 g/d of cocoa powder and 43 g/d of dark chocolate (chocolate diet [CHOC]), or (4) all 3 foods (CHOC+ALD). Compared with the average American diet, total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol after the ALD were lower by 4%, 5%, and 7%, respectively (P<0.05). The CHOC+ALD decreased apolipoprotein B by 5% compared with the average American diet. For low-density lipoprotein subclasses, compared with the average American diet, the ALD showed a greater reduction in large buoyant low-density lipoprotein particles (-5.7±2.3 versus -0.3±2.3 mg/dL; P=0.04), whereas the CHOC+ALD had a greater decrease in small dense low-density lipoprotein particles (-12.0±2.8 versus -5.3±2.8 mg/dL; P=0.04). There were no significant differences between diets for measures of vascular health and oxidative stress. CONCLUSIONS: Our results demonstrate that consumption of almonds alone or combined with dark chocolate under controlled-feeding conditions improves lipid profiles. Incorporating almonds, dark chocolate, and cocoa into a typical American diet without exceeding energy needs may reduce the risk of coronary heart disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01882881.

Effects of Bifidobacterium animalis subsp. lactis BB-12® on the lipid/lipoprotein profile and short chain fatty acids in healthy young adults: a randomized controlled trial.

BACKGROUND: Some probiotics have hypocholesterolemic effects in animal studies, which are mediated, in part, by increases in fecal short chain fatty acids (SCFAs). Clinical trials of probiotics on lipids/lipoproteins are inconsistent. OBJECTIVE: We examined the effects of Bifidobacterium animalis subsp. lactis BB-12® (BB-12®) (3.16 × 109 CFUs/day) on lipids and lipoproteins and fecal excretion of SCFAs in healthy adults. METHODS: In a randomized, partially blinded, 4-period, crossover study, 30 adults (11 men, 19 women) aged 18-40 years were randomly assigned to: 1) yogurt smoothie with no BB-12® (YS), 2) yogurt smoothie with BB-12® added pre-fermentation (PRE), 3) yogurt smoothie with BB-12® added post-fermentation (POST), 4) BB-12® containing capsule (CAP). We measured serum lipids/lipoproteins, glucose, insulin, C-reactive protein (CRP), and fecal SCFAs at baseline and after each treatment period. RESULTS: Total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TGs) did not differ after the PRE, POST, and CAP periods versus the YS or between treatments. Compared to baseline, fecal acetate was significantly increased after the YS (Δ = 211.89 ± 75.87 µg/g, P = 0.007) and PRE (Δ = 204.98 ± 75.70 µg/g, P = 0.009) periods. The percent increase in fecal acetate was significantly greater after the YS versus the POST period (52.2 ± 13.2% vs. 24.5 ± 13.2%, P = 0.023). Fecal total SCFAs, propionate and butyrate did not differ between treatment periods. Fecal total SCFAs were negatively associated with TC (r = -0.22, P = 0.01), LDL-C (r = -0.24, P = 0.004), age (r = -0.33, P < 0.001), and waist circumference (r = -0.25, P = 0.003). CONCLUSIONS: BB-12® supplementation did not improve lipids, lipoproteins and total and individual fecal SCFAs. Fecal SCFAs were negatively associated with TC, LDL-C, age, and waist circumference. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT01399996 .

Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose-response randomised controlled trial.

Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (-2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.

Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.

Background: Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function.Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes.Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants (n = 48) and in normal-weight (body mass index: <25; n = 14) and overweight or obese (≥25; n = 34) participants by using linear mixed models.Results: The almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-ß-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-ß-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL (P < 0.05). No diet effects were observed in the overweight or obese group.Conclusions: Substituting almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable circulating HDL subpopulation distribution and improve cholesterol efflux in normal-weight individuals with elevated LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01101230.

Acute Peanut Consumption Alters Postprandial Lipids and Vascular Responses in Healthy Overweight or Obese Men.

Background: Postprandial hyperlipidemia is associated with impaired endothelial function. Peanut consumption favorably affects the lipid and lipoprotein profile; however, the effects on endothelial function remain unclear.Objective: The purpose of the study was to evaluate the effects of acute peanut consumption as part of a high-fat meal on postprandial endothelial function.Methods: We conducted a randomized, controlled, crossover postprandial study to evaluate the effect of acute peanut consumption on postprandial lipids and endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery in 15 healthy overweight or obese men [mean age: 26.7 y; mean body mass index (in kg/m2): 31.4]. Participants consumed, in a randomized order, a peanut meal containing 3 ounces (85 g) ground peanuts (1198 kcal; 40.0% carbohydrate, 47.7% fat, 19.4% saturated fat, 13.2% protein) and a control meal matched for energy and macronutrient content. Meals were in the form of a shake, scheduled ≥1 wk apart. Lipids, lipoproteins, glucose, and insulin were measured at baseline (0 min) and at 30, 60, 120, and 240 min after shake consumption. FMD was measured at baseline and at 240 min.Results: Acute peanut consumption blunted the serum triglyceride (TG) response 120 and 240 min after consumption compared with the control meal (means ± SEMs-120 min: 188.9 ± 19.4 compared with 197.5 ± 20.7 mg/dL; 240 min: 189.9 ± 24.3 compared with 197.3 ± 18.4 mg/dL; P < 0.05 for both). Total, LDL, and HDL cholesterol and glucose and insulin responses were similar between the test meals. Compared with baseline, only the control meal significantly decreased FMD at 240 min (control: -1.2% ± 0.5%; P = 0.029; peanut: -0.6% ± 0.5%; P = 0.3). Participants with higher baseline total (>150 mg/dL) and LDL (>100 mg/dL)-cholesterol concentrations showed a significant decrease in FMD after the control meal (-1.8%, P = 0.017; -2.0%, P = 0.038), whereas the peanut meal maintained endothelial function in all participants irrespective of total- and LDL-cholesterol concentrations.Conclusion: The inclusion of 85 g peanuts (3 ounces) as part of a high-fat meal improved the postprandial TG response and preserved endothelial function in healthy overweight or obese men. This trial was registered at clinicaltrials.gov as NCT01405300.

Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults.

PURPOSE: Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix. METHODS: Healthy adults (n = 30) aged 18-40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed. RESULTS: BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14+HLA-DR+ cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14+HLA-DR+ cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline. CONCLUSIONS: These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.

Effects of canola and high-oleic-acid canola oils on abdominal fat mass in individuals with central obesity.

OBJECTIVE: To determine the effect of diets low in saturated fatty acids and high in monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids on body composition in participants at risk for metabolic syndrome (MetS). METHODS: This study was a randomized, crossover, controlled feeding study. Participants (n = 101, ages 49.5 ± 1.2, BMI 29.4 ± 0.4 kg/m2 ) were randomized to five isocaloric diets containing treatment oils: Canola, CanolaOleic, CanolaDHA, Corn/Safflower, and Flax/Safflower. Each diet period was 4 weeks followed by a 2- to 4-week washout period. RESULTS: Canola (3.1 kg, P = 0.026) and CanolaOleic oil diets (3.09 kg, P = 0.03) reduced android fat mass compared with the Flax/Saff oil diet (3.2 kg), particularly in men. The decrease in abdominal fat mass was correlated with the reduction in blood pressure after the Canola (systolic blood pressure: r = 0.26, P = 0.062; diastolic blood pressure: r = 0.38, P = 0.0049) and CanolaOleic oil diets (systolic blood pressure: r = 0.39 P = 0.004; diastolic blood pressure: r = 0.45, P = 0.0006). The decrease in abdominal fat mass also was associated with a reduction in triglyceride levels after the CanolaOleic oil diet (r = 0.42, P = 0.002). CONCLUSIONS: Diets high in MUFA (compared with PUFA) reduced central obesity with an accompanying improvement in MetS risk factors. Diets high in MUFA may be beneficial for treating and perhaps preventing MetS.

Macronutrient Content of the Diet: What Do We Know About Energy Balance and Weight Maintenance?

The 2013 AHA/ACC Clinical Guideline for the Management of Overweight and Obesity recommends a reduced energy diet for weight loss regardless of the macronutrient content. However, diet composition may affect the maintenance of weight loss. In general, a healthful dietary pattern with reduced portion sizes, low energy dense foods, and physical activity are successful for many. Certain populations, such as those with insulin resistance, may find reductions in carbohydrate and higher levels of unsaturated fats to be more effective and promote greater adherence. Of importance is that metabolic adaptations following weight loss also may impact weight loss maintenance and should be considered in the transition from weight loss to weight stabilization. Thus, weight loss and weight maintenance strategies are both important in an intervention for sustaining long-term behavior change.

Consumption of Bifidobacterium animalis subsp. lactis BB-12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults.

SCOPE: Probiotics can modulate immunity and reduce upper respiratory tract infections (URTI) in humans; however few studies have examined both outcomes in the same trial. The goal of the current study was to investigate the effect of Bifidobacterium animalis subsp. lactis BB-12, on natural killer (NK) and T-cell function in conjunction with self-reported cold/flu outcomes in healthy adults. METHODS AND RESULTS: In a randomized, partially blinded, four-period crossover study, healthy adults (n = 30) were recruited, and received four treatments for 4 weeks in a random order: (i) yogurt smoothies alone (YS); smoothies with BB-12 added (ii) before (PRE) or (iii) after (POST) yogurt fermentation, or (iv) BB-12 capsule (CAP). NK- and T-cell function was assessed at baseline and after each treatment. Incidence and severity of cold/flu infection was quantified using self-reported URTI questionnaires. Participants on YS, PRE, or CAP treatments had elevated IL-2 secretion and NK-cell cytotoxicity, concurrently with fewer days with URTI. However, the POST treatment did not change immune outcomes or the severity of URTI. CONCLUSION: The timing of BB-12 addition to yogurt smoothies in relation to the fermentation process influenced the impact of BB-12 on immune function and cold/flu severity in young healthy adults.

Emerging nutrition science on fatty acids and cardiovascular disease: nutritionists' perspectives.

Recent dietary guidance for heart health recommends a reduction (by ∼50%) in saturated fatty acid (SFA) intake to reduce LDL cholesterol and to decrease risk of cardiovascular disease (CVD). The 2010 Dietary Guidelines for Americans recommends substituting unsaturated fat [both polyunsaturated and monounsaturated fatty acids (PUFAs and MUFAs, respectively)] for SFAs. There are many dietary options that can be implemented to replace SFAs, given the different sources of unsaturated fats in the food supply. Compelling evidence exists for the cardioprotective benefits of n-3 (ω-3) PUFAs, both marine- and plant-derived. In addition, the evidence of cardioprotective benefits of n-6 (ω-6) PUFAs is strong, whereas that for MUFAs is mixed, although there is emerging evidence of benefits. Quantitatively, lowering SFAs by 50% will require, in part, substituting food sources of n-6 and n-3 PUFAs and MUFAs for food sources of SFAs. The use of n-3 PUFAs as a replacement for SFAs will result in a shortfall in reaching the SFA goal because of the relatively low amounts that can be incorporated in the diet, even with very high n-3 PUFA substitution. SFAs also can be replaced with dietary carbohydrate and/or protein. Replacing SFAs with carbohydrate, specifically refined sources, however, has little impact on reducing CVD risk. There is evidence about the health benefits of dietary protein on CVD risk, which merits study. Dietary guidelines have advanced considerably with the "replacement of SFA with unsaturated fat message" instead of recommending decreasing SFAs alone. A key question that remains is what is the optimal mix of macronutrients to maximally reduce CVD risk.

In vitro Production of IL-6 and IFN-γ is Influenced by Dietary Variables and Predicts Upper Respiratory Tract Infection Incidence and Severity Respectively in Young Adults.

Assessment of immune responses in healthy adults following dietary or lifestyle interventions is challenging due to significant inter-individual variability. Thus, gaining a better understanding of host factors that contribute to the heterogeneity in immunity is necessary. To address this question, healthy adults [n = 36, 18-40 years old, body mass index (BMI) 20-35 kg/m(2)] were recruited. Dietary intake was obtained via 3-day dietary recall records, physical activity level was evaluated using the International Physical Activity Questionnaire, and peripheral blood mononuclear cells were isolated from peripheral blood. Expression of activation markers on unstimulated immune subsets was assessed by flow cytometry. T-cell proliferation and cytokine secretion was assessed following in vitro stimulation with anti-CD3 or lipopolysaccharide. Furthermore, the incidence and severity of cold or flu symptoms were obtained from self-reported upper respiratory tract infection (URTI) questionnaires. The relationship between activation marker expression on T cells and T-cell effector functions; and in vitro cytokine secretion and URTI was determined by linear or logistic regression. CD69 and CD25 expression on unstimulated T cells was significantly associated with T-cell proliferation and interleukin-2 secretion. Incidence and severity of cold or flu symptoms was significantly associated with in vitro interleukin-6 and interferon-gamma secretion, respectively. Furthermore, host factors (e.g., age, BMI, physical activity, and diet) contributed significantly to the relationship between activation marker expression and T-cell effector function, and cytokine secretion and cold and flu status. In conclusion, these results suggest that lifestyle and dietary factors are important variables that contribute to immune responses and should be included in human clinical trials that assess immune endpoints.

Effects of daily almond consumption on cardiometabolic risk and abdominal adiposity in healthy adults with elevated LDL-cholesterol: a randomized controlled trial.

BACKGROUND: Evidence consistently shows that almond consumption beneficially affects lipids and lipoproteins. Almonds, however, have not been evaluated in a controlled-feeding setting using a diet design with only a single, calorie-matched food substitution to assess their specific effects on cardiometabolic risk factors. METHODS AND RESULTS: In a randomized, 2-period (6 week/period), crossover, controlled-feeding study of 48 individuals with elevated LDL-C (149±3 mg/dL), a cholesterol-lowering diet with almonds (1.5 oz. of almonds/day) was compared to an identical diet with an isocaloric muffin substitution (no almonds/day). Differences in the nutrient profiles of the control (58% CHO, 15% PRO, 26% total fat) and almond (51% CHO, 16% PRO, 32% total fat) diets were due to nutrients inherent to each snack; diets did not differ in saturated fat or cholesterol. The almond diet, compared with the control diet, decreased non-HDL-C (-6.9±2.4 mg/dL; P=0.01) and LDL-C (-5.3±1.9 mg/dL; P=0.01); furthermore, the control diet decreased HDL-C (-1.7±0.6 mg/dL; P<0.01). Almond consumption also reduced abdominal fat (-0.07±0.03 kg; P=0.02) and leg fat (-0.12±0.05 kg; P=0.02), despite no differences in total body weight. CONCLUSIONS: Almonds reduced non-HDL-C, LDL-C, and central adiposity, important risk factors for cardiometabolic dysfunction, while maintaining HDL-C concentrations. Therefore, daily consumption of almonds (1.5 oz.), substituted for a high-carbohydrate snack, may be a simple dietary strategy to prevent the onset of cardiometabolic diseases in healthy individuals. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov; Unique Identifier: NCT01101230.

Effect of a moderate fat diet with and without avocados on lipoprotein particle number, size and subclasses in overweight and obese adults: a randomized, controlled trial.

BACKGROUND: Avocados are a nutrient-dense source of monounsaturated fatty acids (MUFA) that can be used to replace saturated fatty acids (SFA) in a diet to lower low density lipoprotein cholesterol (LDL-C). Well-controlled studies are lacking on the effect of avocado consumption on cardiovascular disease (CVD) risk factors. METHODS AND RESULTS: A randomized, crossover, controlled feeding trial was conducted with 45 overweight or obese participants with baseline LDL-C in the 25th to 90th percentile. Three cholesterol-lowering diets (6% to 7% SFA) were fed (5 weeks each): a lower-fat diet (LF: 24% fat); 2 moderate-fat diets (34% fat) provided similar foods and were matched for macronutrients and fatty acids: the avocado diet (AV) included one fresh Hass avocado (136 g) per day, and the moderate-fat diet (MF) mainly used high oleic acid oils to match the fatty acid content of one avocado. Compared with baseline, the reduction in LDL-C and non-high-density lipoprotein (HDL) cholesterol on the AV diet (-13.5 mg/dL, -14.6 mg/dL) was greater (P<0.05) than the MF (-8.3 mg/dL, -8.7 mg/dL) and LF (-7.4 mg/dL, -4.8 mg/dL) diets. Furthermore, only the AV diet significantly decreased LDL particle number (LDL-P, -80.1 nmol/L, P=0.0001), small dense LDL cholesterol (LDL(3+4), -4.1 mg/dL, P=0.04), and the ratio of LDL/HDL (-6.6%, P<0.0001) from baseline. CONCLUSIONS: Inclusion of one avocado per day as part of a moderate-fat, cholesterol-lowering diet has additional LDL-C, LDL-P, and non-HDL-C lowering effects, especially for small, dense LDL. Our results demonstrate that avocados have beneficial effects on cardio-metabolic risk factors that extend beyond their heart-healthy fatty acid profile. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01235832.

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans.

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets: 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p = 0.0005 and p = 0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p = 0.0243) and DHA-enriched high oleic canola oil (p = 0.0249), although high-oleic canola oil had the lowest binding at baseline (p = 0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding.