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• Wheat germ improved markers of glucose homeostasis in overweight adults. • Wheat germ reduced the pro-inflammatory adipokine, resistin. • Gut microbiota and gut integrity markers were unaffected by wheat germ. Wheat germ (WG), a by-product of flour milling, is rich in bioactive substances that may help improve health complications associated with increased adiposity. This study investigated the effects of WG on gut health, metabolic, and inflammatory markers in adults classified as overweight. We hypothesized that WG, because of its many bioactive components, would improve gut health and metabolic, and inflammatory markers in overweight adults. Forty adults (18–45 years old) and with a body mass index between 25 and 30 kg/m2 participated in this single-blinded randomized controlled pilot study. Participants consumed the study supplements containing 30 g of either cornmeal (control, CL) or WG daily for 4 weeks. Primary outcome variables were gut health markers including gut microbiota, gut integrity markers, and fecal short-chain fatty acids, whereas secondary outcome variables included metabolic and inflammatory parameters assessed at baseline and at the end of supplementation. Thirty-nine participants (n = 19 and 20 for CL and WG group, respectively) completed the study. The genus Faecalibacterium was significantly higher in the WG group compared to CL post-supplementation but no significant changes in other gut health markers, short-chain fatty acids, inflammatory markers, and lipid profiles were observed. Compared with baseline, WG improved markers of glucose homeostasis including insulin (P =.02), homeostatic model assessment of insulin resistance (P =.03), glycated hemoglobin (P =.07), and the pro-inflammatory adipokine, resistin (P =.04). However, these parameters after intervention were not different with control. Our findings suggest that WG supplementation have modest effects on gut health but may provide an economical option for individuals to improve glycemic control. Daily consumption of 30 g of wheat germ supplement for 4 weeks by adults classified as overweight maintained the bacterial genus Faecalibacterium and improved several markers of glucose homeostasis including insulin, HOMA-IR, and HbA1c, and reduced the pro-inflammatory adipokine, resistin. Abbreviations: HbA1c, glycated hemoglobin; HOMA-IR, homeostatic model assessment of insulin resistance. [Display omitted] [ABSTRACT FROM AUTHOR]

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P =.023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P <.0001) and γ-valerolactones (P =.0001). Fecal calprotectin (P =.029) and myeloperoxidase (P =.048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P =.043) but not sucralose/erythritol (P >.05) was decreased by GTE regardless of health status. No between-treatment differences (P >.05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P =.029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation. • A novel green tea extract (GTE) confection was provided to healthy adults and adults with metabolic syndrome. • GTE increased circulating catechins and valerolactones regardless of health status. • GTE decreased intestinal inflammation and small intestinal permeability. • GTE decreased circulating endotoxin. • GTE decreased fasting glucose without affecting systemic inflammation. • Gut-level benefits by GTE support research translation for cardioprotection by green tea. Healthy adults and adults with metabolic syndrome were randomized to a placebo or GTE (1 g; 890 mg catechins) confection for 1 month and then crossed-over to the alternative treatment following a 1-month washout. Regardless of health status, the GTE confection decreased fecal biomarkers of intestinal inflammation (calprotectin and myeloperoxidase) and small intestinal permeability based on a differential sugar absorption test while decreasing serum endotoxin. Abbreviations: GTE, green tea extract; MetS, metabolic syndrome [Display omitted] [ABSTRACT FROM AUTHOR]

• Exemestane administration significantly increased LDL-C. • Exemestane administration significantly decreased HDL-C and TC. • Exemestane prescription only lowered TG concentrations when it was administered for < 12 months. Postmenopausal women are prone to develop cardiovascular disorders. In addition, cardiovascular risk in women can be influenced by the long-term prescription of drugs that lead to estrogen deprivation, e.g., aromatase inhibitors, and that can cause dyslipidemia. Little is known about the impact of exemestane, an aromatase inhibitor, on serum lipids' concentration in women. Hence, we conducted a meta -analysis of randomized controlled trials (RCTs) to assess the influence of this pharmacological agent on the lipid profile in women. The Scopus, Web of Science, PubMed/Medline and EMBASE databases were searched by two surveyors for manuscripts published from the inception of these databases until April 3rd, 2023. No language restrictions were applied to the search. The random effects model was used to generate the combined results as weighted mean difference (WMD) and 95% confidence interval (CI). In total, 8 eligible RCTs were included in the meta -analysis. Overall results from the random effects model indicate that exemestane administration increases LDL-C (WMD: 4.42 mg/dL, 95 % CI: 0.44, 8.41, P = 0.02) and decreases HDL-C (WMD: −6.03 mg/dL, 95 % CI: −7.77, −4.29, P < 0.001) and TC (WMD: −5.40 mg/dL, 95 % CI: −9.95, −0.86, P = 0.02) levels, respectively. Moreover, exemestane prescription only lowered TG concentrations when it was administered for < 12 months (WMD: −14.60 mg/dL, 95 % CI: –23.57 to −5.62, P = 0.001). Currently available evidence suggests that the administration of exemestane in females increases LDL-C values and reduces HDL-C, TC, and, when prescribed for less than 12 months, TG concentrations. [ABSTRACT FROM AUTHOR]

Euglena gracilis (Euglena) is a microalgae found in most freshwater environments that produces paramylon, an insoluble β-1,3-glucan linked to human immunity. We hypothesized that Euglena powder has effects on immune function in apparently healthy adults. The study included male or female volunteers between the ages of 20 and 70 years who had white blood cell counts ranging from 4 × 103/µL to 10 × 103/µL, a "severe" rating on the stress questionnaire from the Korea National Health and Nutrition Examination Survey, and at least 2 upper respiratory infections with cold-like symptoms in the previous year. Participants received either a placebo or 700 mg of Euglena powder daily for 8 weeks. The study measured natural killer cell activity, cytokine concentrations, and blood lipid profiles to confirm the immune effect of Euglena consumption. In conclusion, Euglena improved immunological function through natural killer cell activity. Safety assessment showed no significant changes in vital signs or clinical chemistry indicators, and there were no adverse events associated with Euglena consumption. Euglena supplementation may help boost the immune systems of healthy individuals. Euglena gracilis is a freshwater microalgae that produces paramylon, which benefits human immunity. This study examined the effects of Euglena on immune function in apparently healthy subjects. Participants received either a placebo or 700 mg of Euglena powder daily for 8 weeks. Results showed improved immune function through natural killer (NK) cell activity, with no adverse events or safety concerns. Euglena supplementation may enhance the immune systems of apparently healthy individuals. [Display omitted] [ABSTRACT FROM AUTHOR]

Unintentional weight loss is common in persons with chronic and acute disease and is often caused by insufficient intake or malabsorption. A new lysophosphatidylcholine (LPC)-rich structured lipid powder has micelle-like activity that facilitates digestion and absorption, independent of lipase and bile acids. The aim of this secondary analysis was to determine if recycled LPC increased fat absorption of coingested food. Fasting plasma fatty acid (FA) concentrations were measured at baseline and 3 mo in children (n = 84) with cystic fibrosis and pancreatic insufficiency. Plasma palmitic acid was selected because of its dietary prevalence and was a minor component of the LPC product. Palmitic acid increased 15% in the LPC product-treated total subjects (P = 0.01) and 23% in the subgroup with more severe malabsorption (P = 0.007), with no change in either group on placebo. Total FAs increased 11% (P = 0.009) and 20% (P = 0.005), respectively. Increased palmitic acid and total FA suggest that LPC provided by the product created an intraluminal environment that increased coingested dietary fat absorption and provided more calories. [ABSTRACT FROM AUTHOR]

Pecan-enriched diets have been linked to improved lipid metabolism; however, the impact of pecans on vascular health has yet to be examined. We hypothesized that 4 weeks of a pecan-enriched diet would improve fasting and postprandial blood lipids and vascular function compared with a nut-free diet. In this randomized control study, 44 older adults (59 ± 6 years) consumed 68 g of pecans/d (pecan; n = 21) or avoided all nuts (control; n = 23) for 4 weeks. At pre- and post-diet visits, fasting and postprandial blood lipids, macrovascular (by flow-mediated dilation), and microvascular (tissue saturation index reactive hyperemia [RH] kinetics by continuous-wave near-infrared spectroscopy) function were assessed. From the pre- to post-diet visit, there were greater reductions in fasting total cholesterol (pecan: –14 ± 4.0 vs control: –0.2 ± 5.4 mg/dL; P =.04), low-density lipoprotein (LDL) cholesterol (pecan: –15 ± 3.7 vs control: +1.9 ± 4.4 mg/dL; P =.01), non–high-density lipoprotein cholesterol (pecan: –15 ± 3.6 vs control: –0.5 ± 4.8 mg/dL; P =.02), LDL particle number (pecan: –126 ± 51 vs control: +43 ± 42 nmol/L; P =.01), and LDL medium (pecan: –34 ± 13 vs control: +16 ± 11 nmol/L; P <.01), for pecan vs control. Further, postprandial triglyceride was suppressed for pecan (P =.01) compared with control (P =.78). Postprandial RH slope (P =.04) and RH time to half (P =.004) was different by group, driven by improvements in pecan vs control. However, fasting macro- and microvascular function was unaffected. Daily pecan consumption for 4 weeks improved fasting and postprandial blood lipids and microvascular reactivity in older adults. Because changes in microvascular function typically precipitate macrovascular changes, long-term pecan consumption may improve vascular health and reduce risk for cardiovascular events. This trial was registered at clinicaltrials.gov (NCT04385537). Fasting and postprandial blood lipids and vascular function were assessed before and after 4 weeks of a pecan-enriched or nut-free diet. Daily pecan consumption for 4 weeks improved fasting and postprandial blood lipids and microvascular reactivity in older adults. Because changes in microvascular function typically precipitate macrovascular changes, long-term pecan consumption may improve vascular health and reduce risk for cardiovascular events. [Display omitted] [ABSTRACT FROM AUTHOR]

• In familial dysbetalipoproteinemia (FD), evolocumab reduced non-HDL-C by 49%. • Non-HDL-C treatment goals were achieved by 89% of patients using evolocumab. • Evolocumab likely results in CVD reduction in FD. Familial dysbetalipoproteinemia (FD) is the second most common monogenic lipid disorder (prevalence 1 in 850-3500), characterized by postprandial remnant accumulation and associated with increased cardiovascular disease (CVD) risk. Many FD patients do not achieve non-HDL-C treatment goals, indicating the need for additional lipid-lowering treatment options. To evaluate the effect of the PCSK9 monoclonal antibody evolocumab added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in patients with FD. A randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. At the start and end of each treatment period patients received an oral fat load. The primary endpoint was the 8-hour post fat load non-HDL-C area under the curve (AUC). Secondary endpoints included fasting and post fat load lipids and lipoproteins. In total, 28 patients completed the study. Mean age was 62±9 years and 93% had an Ɛ2Ɛ2 genotype. Evolocumab reduced the 8-hour post fat load non-HDL-C AUC with 49% (95%CI 42-55) and apolipoprotein B (apoB) AUC with 47% (95%CI 41-53). Other fasting and absolute post fat load lipids and lipoproteins including triglycerides and remnant-cholesterol were also significantly reduced by evolocumab. However, evolocumab did not have significant effects on the rise above fasting levels that occurred after consumption of the oral fat load. Evolocumab added to standard lipid-lowering therapy significantly reduced fasting and absolute post fat load concentrations of non-HDL-C, apoB and other atherogenic lipids and lipoproteins in FD patients. The clinically significant decrease in lipids and lipoproteins can be expected to translate into a reduction in CVD risk in these high-risk patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Almonds contain lipid, fiber, and polyphenols and possess physicochemical properties that affect nutrient bioaccessibility, which are hypothesized to affect gut physiology and microbiota. Objectives To investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition, and gut transit time. Methods Healthy adults (n  = 87) participated in a parallel, 3-arm randomized controlled trial. Participants received whole almonds (56 g/d), ground almonds (56 g/d), or an isocaloric control in place of habitual snacks for 4 wk. Gut microbiota composition and diversity (16S rRNA gene sequencing), SCFAs (GC), volatile organic compounds (GC-MS), gut transit time (wireless motility capsule), stool output and gut symptoms (7-d diary) were measured at baseline and endpoint. The impact of almond form on particle size distribution (PSD) and predicted lipid release was measured (n  = 31). Results Modified intention-to-treat analysis was performed on 79 participants. There were no significant differences in mean ± SD abundance of fecal bifidobacteria after consumption of whole almonds (8.7% ± 7.7%), ground almonds (7.8% ± 6.9%), or control (13.0% ± 10.2%; q  = 0.613). Consumption of almonds (whole and ground pooled) resulted in higher mean ± SD butyrate (24.1 ± 15.0 μmol/g) than control (18.2 ± 9.1 μmol/g; P  = 0.046). There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency, or gut symptoms. Almond form (whole compared with ground) had no effect on study outcomes. Ground almonds resulted in significantly smaller PSD and higher mean ± SD predicted lipid release (10.4% ± 1.8%) than whole almonds (9.3% ± 2.0%; P  = 0.017). Conclusions Almond consumption has limited impact on microbiota composition but increases butyrate in adults, suggesting positive alterations to microbiota functionality. Almonds can be incorporated into the diet to increase fiber consumption without gut symptoms. This trial was registered at clinicaltrials.gov as NCT03581812. [ABSTRACT FROM AUTHOR]

Background Gestational weight gain (GWG) below or above the Institute of Medicine (IOM) recommendations has been associated with adverse perinatal outcomes. Few studies have examined the effect of prenatal nutrient supplementations on GWG in low- and middle-income countries (LMICs). Objectives We aimed to investigate the effects of multiple micronutrient supplements (MMSs) and small-quantity lipid-based nutrient supplements (LNSs) on GWG in LMICs. Methods A 2-stage meta-analysis of individual participant data was conducted to examine the effects of MMSs (45,507 women from 14 trials) and small-quantity LNSs (6237 women from 4 trials) on GWG compared with iron and folic acid supplements only. Percentage adequacy of GWG and total weight gain at delivery were calculated according to the IOM 2009 guidelines. Binary outcomes included severely inadequate (percentage adequacy <70%), inadequate (<90%), and excessive (>125%) GWG. Results from individual trials were pooled using fixed-effects inverse-variance models. Heterogeneity was examined using I 2, stratified analysis, and meta-regression. Results MMSs resulted in a greater percentage adequacy of GWG [weighted mean difference (WMD): 0.86%; 95% CI: 0.28%, 1.44%; P  < 0.01] and higher GWG at delivery (WMD: 209 g; 95% CI: 139, 280 g; P  < 0.01) than among those in the control arm. Women who received MMSs had a 2.9% reduced risk of severely inadequate GWG (RR: 0.971; 95% CI: 0.956, 0.987; P  < 0.01). No association was found between small-quantity LNSs and GWG percentage adequacy (WMD: 1.51%; 95% CI: −0.38%, 3.40%; P  = 0.21). Neither MMSs nor small-quantity LNSs were associated with excessive GWG. Conclusions Maternal MMSs were associated with greater GWG percentage adequacy and total GWG at delivery than was iron and folic acid only. This finding is consistent with previous results on birth outcomes and will inform policy development and local recommendations of switching routine prenatal iron and folic acid supplements to MMSs. [ABSTRACT FROM AUTHOR]

• EPA and DHA lowered plasma TG concentrations. • Changes in TG concentrations were inversely associated with changes in LPL activity. • DHA increased LDL-C concentrations. • EPA and DHA plasma lipid changes varied by sex. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to similarly lower plasma TG concentrations but differentially regulate plasma LDL-C and HDL-C concentrations. The aim of this study was to evaluate the common and differential effects of these ω-3 fatty acids on plasma lipids and lipoproteins and to assess the metabolic mechanisms of the effects. In a randomized, double-blind, crossover study, we assessed the effect of 10-week supplementation with 3 g/d pure EPA and pure DHA (both as ethyl ester, ≥97% purity) on plasma lipid and lipoprotein concentrations and activities of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 older (>50 y) men and postmenopausal women with some characteristics of metabolic syndrome and low-grade chronic inflammation. Both EPA and DHA lowered plasma TG concentrations and increased LDL-C/apoB and HDL-C/apoA-I ratios, but only DHA increased LDL-C concentrations. The reductions in plasma TG were inversely associated with the changes in LPL activity after both EPA and DHA supplementation. EPA lowered CETP, while DHA lowered LCAT activity. EPA and DHA worked differently in men and women, with DHA increasing LPL activity and LDL-C concentrations in women, but not in men. EPA and DHA exerted similar effects on plasma TG, but differences were observed in LDL-C concentrations and activities of some enzymes involved in lipoprotein metabolism. It was also noted that EPA and DHA worked differently in men and women, supporting sex-specific variations in lipoprotein metabolism. [ABSTRACT FROM AUTHOR]

Background Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option. Objectives We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes. Methods One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants. Results Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (−5.9 kg; 95% CI: −6.5, −5.28 kg; and −5.23 kg; 95% CI: −5.84, −4.62 kg), glycated hemoglobin (−0.99%; 95% CI: −1.07, −0.9%; and −0.88%; 95% CI: −0.97, −0.8%), systolic blood pressure (−4 mmHg; 95% CI: −7, −2 mmHg; and −6 mmHg; 95% CI: −8, −3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of −0.63 kgCO2/d (95% CI: −0.99, −0.27 kgCO2/d) favoring the low-carbohydrate vegan diet. Conclusions Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions. Trial registration number: clinicaltrials.gov identifier NCT02245399. [ABSTRACT FROM AUTHOR]

Background: Increasing unsaturated fat intake is beneficial for cardiovascular health, but the type of unsaturated fat to recommend remains equivocal.Objectives: We investigated the effects of an 8-week diet intervention that was rich in either cottonseed oil (CSO; PUFA rich) or olive oil (OO; MUFA rich) on blood lipids in hypercholesterolemic adults.Methods: Forty-three men and women with hypercholesterolemia (53 ± 10 years; BMI, 27.6 ± 4.8 kg/m2) completed this randomized parallel clinical trial consisting of an 8-week partial outpatient feeding intervention. Participants were given meals and snacks accounting for ∼60% of their daily energy needs, with 30% of energy needs from either CSO (n = 21) or OO (n = 22). At pre- and postdiet intervention visits, participants consumed a high-SFA meal (35% of total energy needs; 70% of energy from fat). The primary outcomes of fasting cholesterol profiles and secondary outcomes of postprandial blood lipids and glycemic markers were assessed over a 5-hour period.Results: There were greater reductions from baseline to week 8 in fasting serum total cholesterol (TC; -17.0 ± 3.94 mg/dL compared with -2.18 ± 3.72 mg/dL, respectively; P = 0.008), LDL cholesterol (-19.7 ± 3.94 mg/dL compared with -5.72 ± 4.23 mg/dL, respectively; P = 0.018), non-HDL cholesterol (-20.8 mg/dL ± 4.00 compared with -6.61 ± 4.01 mg/dL, respectively; P = 0.014), and apoB (-11.8 mg/dL ± 2.37 compared with -3.10 ± 2.99 mg/dL, respectively; P = 0.05), in CSO compared with OO. There were also visit effects from baseline to week 8 for increases in HDL cholesterol (CSO, 56.5 ± 2.79 mg/dL to 60.2 ± 3.35 mg/dL, respectively; OO: 59.7 ± 2.63 mg/dL to 64.1 ± 2.24 mg/dL, respectively; P < 0.001), and decreases in the TC:HDL-cholesterol ratio (CSO, 4.30 ± 0.27 mg/dL to 3.78 ± 0.27 mg/dL, respectively; OO, 3.94 ± 0.16 mg/dL to 3.57 ± 0.11 mg/dL, respectively; P < 0.001), regardless of group assignment. In response to the high-SFA meal, there were differences in postprandial plasma glucose (P = 0.003) and triglyceride (P = 0.004) responses and a trend in nonesterified fatty acids (P = 0.11) between groups, showing protection in the postprandial state from an occasional high-SFA fat meal with CSO, but not OO, diet enrichment.Conclusions: CSO, but not OO, diet enrichment caused substantial improvements in fasting and postprandial blood lipids and postprandial glycemia in hypercholesterolemic adults. This trial was registered at clinicaltrials.gov as NCT04397055. [ABSTRACT FROM AUTHOR]

Vegetable oils having unsaturated fatty acids in the sn-2 position of triglyceride (TG) backbone might not raise serum cholesterol levels. We investigated the chronic effects of diets enriched with palm olein (IV64) (PO), cocoa butter (CB), or extra virgin olive oil (EVOO) with oleic acid primarily at the sn-2 position (66%, 75%, 87% sn-2 oleic acid, respectively) of the TG molecule in 40 healthy volunteers participated in this randomized, controlled, single-blinded, crossover trial. Following a 2-week run-in period, the subjects were given standardization meals (breakfast, lunch, and dinner) cooked with palm olein (IV72). Subjects were randomized to 1 of the 3 intervention groups; receiving baked products (brownies for breakfast and cookies for teatime) prepared with respective test fats accompanied with standardized low-fat meals for breakfast, lunch, and dinner prepared with palm olein (IV72) for all groups for 4 weeks in a crossover manner with 2-week washout period (given standardization meals). Anthropometric measurements, blood samples, and dietary intakes were measured before run-in and pre- and post-intervention. No significant difference was observed on the primary outcome of the study total: high-density lipoprotein cholesterol. All 3 test fats were found to exhibit similar lipid responses (total cholesterol, TG, lipoprotein (a), apolipoprotein-A1, apolipoprotein-B/A-1). Statistical difference was found on low-density lipoprotein cholesterol (CB>EVOO by 0.3 mmol/L, P =.003), high-density lipoprotein cholesterol (PO>CB by 0.04 mmol/L, P =.02) and apolipoprotein-B (EVOO

Background Osteoarthritis (OA) is a major cause of chronic pain and disability worldwide. Treatment generally focuses on symptom relief through nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, which may incur side effects. Krill oil, rich in anti-inflammatory long-chain (LC) omega-3 (ω–3) PUFAs and astaxanthin, may be a safe and effective alternative treatment. Objectives This study sought to investigate the effects of a commercially available krill oil supplement on knee pain in adults with mild to moderate knee OA. Secondary outcomes were knee stiffness; physical function; NSAID use; Omega-3 Index; and lipid, inflammatory, and safety markers. Methods Healthy adults (n  = 235, 40–65 y old, BMI >18.5 to <35 kg/m2), clinically diagnosed with mild to moderate knee OA, regular knee pain, and consuming <0.5 g/d LC ω-3 PUFAs, participated in a 6-mo double-blind, randomized, placebo-controlled, multicenter trial. Participants consumed either 4 g krill oil/d (0.60 g EPA/d, 0.28 g DHA/d, 0.45 g astaxanthin/d) or placebo (mixed vegetable oil). Knee outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) numeric scale (normalized to scores of 0–100). Outcomes were assessed at baseline, 3 mo, and 6 mo. Results Omega-3 Index increased with the krill oil supplement compared with placebo (from 6.0% to 8.9% compared with from 5.5% to 5.4%, P  < 0.001). Knee pain score improved in both groups with greater improvements for krill oil than for placebo (difference in adjusted mean change between groups at 6 mo: −5.18; 95% CI: −10.0, −0.32; P  = 0.04). Knee stiffness and physical function also had greater improvements with krill oil than with placebo (difference in adjusted mean change between groups at 6 mo: −6.45; 95% CI: −12.1, −0.9 and −4.67; 95% CI: −9.26, −0.05, respectively; P  < 0.05). NSAID use, serum lipids, and inflammatory and safety markers did not differ between groups. Conclusions Krill oil was safe to consume and resulted in modest improvements in knee pain, stiffness, and physical function in adults with mild to moderate knee OA. This trial was registered at clinicaltrials.gov as NCT03483090. [ABSTRACT FROM AUTHOR]

Background Prenatal multiple micronutrient supplementation (MMS) and lipid-based nutrient supplementation (LNS) can improve birth outcomes relative to iron-folic acid supplementation (IFA); however, effects on child postnatal growth remain unclear. Objectives The aim was to compare the effect of prenatal MMS, medium-quantity LNS (MQ-LNS), and IFA on child growth up to 2 y of age. Methods We conducted a cluster randomized controlled trial of prenatal nutritional supplementation in Madarounfa, Niger. Villages were randomly assigned for pregnant women to receive IFA (17 villages, 1105 women), MMS (18 villages, 1083 women) or MQ-LNS (18 villages, 1144 women). Pregnant women received nutritional supplements weekly until delivery, and children were followed up monthly from 6-8 wk to 24 mo of age. We assessed the effect of prenatal MMS and MQ-LNS compared with IFA and the effect of prenatal MMS compared with MQ-LNS on child length-for-age z scores (LAZ), weight-for-age z scores (WAZ), and weight-for-length z scores (WLZ) at 24 mo of age using generalized linear models. In secondary analyses, we used mixed-effects models to assess the trajectories of anthropometric z scores longitudinally from 6–8 wk to 24 mo. Results Compared with IFA, MMS and MQ-LNS had no effect on child LAZ, WAZ, or WLZ at 24 mo of age (P > 0.05). Children in the MQ-LNS arm had significantly higher mid-upper arm circumference at 24 mo than children in the MMS arm: mean difference 0.50 cm (95% CI 0.10, 0.91 cm). WAZ and WLZ trajectories were more negative in the MQ-LNS arm compared with IFA and MMS, with lower z scores from 14 to 20 mo of age. However, WAZ and WLZ trajectories converged after 20 mo of age, and there were no differences by 24 mo of age. Conclusions Prenatal MMS and MQ-LNS had limited effect on anthropometric measures of child growth up to 24 mo of age as compared with IFA in rural Niger. [ABSTRACT FROM AUTHOR]

Background The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. Objective This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. Methods In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/d (n  = 40) or an isocaloric placebo (n  = 41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n–3, n–6, and n–9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed. Results Compared with placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 compared with 0.08 ± 0.06%, P  <0.001), its elongation product EPA (0 ± 0.5 compared with 0.16 ± 0.65%, P  <0.05), and the n–9 gondoic acid (GA; 0 ± 0.04 compared with 0.08 ± 0.04%, P  <0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r = 0.26, P  = 0.03). Compared with placebo, camelina oil increased fasting glycemia (–0.2 ± 0.6 compared with 0.3 ± 0.5 mmol/L, P  <0.001) and HOMA-IR index (–0.8 ± 2.5 compared with 0.5 ± 0.9, P  <0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r = 0.32, P  <0.01). Nutritional intake remained similar between groups. Conclusion ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background In Pakistan, the prevalence of stunting among children younger than 5 y has remained above WHO critical thresholds (≥30%) over the past 2 decades. Objectives We hypothesized that an unconditional cash transfer (UCT) combined with lipid-based nutrient supplement (LNS) and/or social and behavior change communication (SBCC) will prevent stunting among children 6–23 mo of age. Methods This was a 4-arm, community-based cluster randomized controlled trial conducted in the district of Rahim Yar Khan, Pakistan. A total of 1729 children (UCT, n  = 434; UCT + SBCC, n  = 433; UCT + LNS, n  = 430; and UCT + LNS + SBCC, n  = 432) were enrolled at 6 mo of age and measured monthly for 18 mo until the age of 24 mo. Results At 24 mo of age, children who received UCT + LNS [rate ratio (RR): 0.85; 95% CI: 0.74, 0.97; P  = 0.015) and UCT + LNS + SBCC (RR: 0.86; 95% CI: 0.77, 0.96; P  = 0.007) had a significantly lower risk of being stunted compared with the UCT arm. No significant difference was noted among children who received UCT + SBCC (RR: 1.03; 95% CI: 0.91, 1.16; P  = 0.675) in the risk of being stunted compared with the UCT arm. The pooled prevalence of stunting among children aged 6–23 mo was 41.7%, 44.8%, 38.5%, and 39.3% in UCT, UCT + SBCC, UCT + LNS, and UCT + LNS + SBCC, respectively. In pairwise comparisons, a significant impact on stunting among children in UCT + LNS (P  = 0.029) and UCT + LNS + SBCC (P = <0.001) was noted compared with the UCT arm. Conclusions UCT combined with LNS and UCT + LNS + SBCC were effective in reducing the prevalence of stunting among children aged 6–23 mo in marginalized populations. UCT + SBCC was not effective in reducing the child stunting prevalence. This trial was registered at clinicaltrials.gov as NCT03299218. [ABSTRACT FROM AUTHOR]

Guideline-recommended use of risk calculators to select for statin therapy in primary prevention has never been tested in a randomized controlled trial (RCT). We determined the extent to which guideline-based statin recommendations from the American College of Cardiology/American Heart Association (ACC/AHA), Canadian Cardiovascular Society(CCS), UK National Institute for Health and Care Excellence (NICE), and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) is supported by available evidence from RCTs. 79,171 individuals from the Copenhagen General Population Study who were free of ASCVD and statin use at baseline were included. RCT evidence supporting guideline-recommended statin allocation and the estimated number needed to treat (NNT) to prevent one ASCVD event were assessed. During 8.2 years of follow-up, 4031 ASCVD events occurred. Of individuals eligible for statin therapy with the ACC/AHA, CCS, NICE and ESC/EAS guidelines, 86%, 88%, 88% and 84% had direct RCT evidence of statin efficacy, respectively (guideline-positive&RCT-positive). This group represented 26–37% of all 79,171 individuals, while guideline-positive&RCT-negative individuals represented 5–7%, guideline-negative&RCT-positive individuals 28–39%, and guideline-negative&RCT-negative individuals represented 30–31%. The ASCVD events per 1000 person-years were 11.4–12.7 (guideline-positive&RCT-positive), 6.3–8.0 (guideline-positive&RCT-negative), 4.2–5.2 (guideline-negative&RCT-positive), and 2.3–2.5 (guideline-negative&RCT-negative), respectively, while the corresponding NNT to prevent one event in 10 years using high-intensity statin were 19–21, 30–32, 48–60, and 105–125, respectively. The far majority of individuals eligible for guideline-recommended primary prevention with statins have direct RCT evidence supporting statin use. Allocating statins based on guideline-criteria is more efficient with lower NNT for preventing ASCVD events than allocating statin therapy based solely on RCT evidence. [Display omitted] • There is a strong correlation between estimated risk and the presence of randomized controlled trial (RCT) evidence. • ≈ 90 % of those recommended statins by guidelines have RCT evidence supporting efficacy. • Allocating statins based on guideline-criteria is superior to RCT criteria. • Our results strongly support the guideline-recommended use of risk calculators. [ABSTRACT FROM AUTHOR]

Background Evidence is emerging that interdaily meal pattern variability potentially affects response such as thermic effect of food (TEF), macronutrient metabolism, and appetite. Objectives To investigate the effect of irregular meal pattern on TEF, glucose, insulin, lipid profile, and appetite regulation in women who are overweight or with obesity and confirmed insulin resistance. Design In a randomized crossover trial, 9 women [mean ± SD BMI (in kg/m2): 33.3 ± 3.1] with confirmed insulin resistance consumed a regular (14 d; 6 meals/d) and an irregular (14 d; 3–9 meals/d) meal pattern separated by a 14-d washout interval. Identical foods were provided during the interventions, and at the start and end of each meal pattern, participants attended the laboratory after an overnight fast. Energy expenditure, glucose, insulin, lipids, adiponectin, leptin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin were measured at baseline and for 3 h after consumption of a test drink, after which an ad libitum test meal was offered. Subjective appetite ratings were recorded before and after the test drink, after the ad libitum meal, and during the intervention. Continuous interstitial glucose monitoring was undertaken for 7 consecutive days during each intervention. Results TEF (over 3 h) was significantly lower postirregular intervention compared with postregular (97.7 ± 19.2 kJ*3 h in postregular visit and 76.7 ± 35.2 kJ*3 h in postirregular visit, paired t test, P = 0.048). Differences in HOMA-IR between the 2 interventions (3.3 ± 1.7 and 3.6 ± 1.6 in postregular and postirregular meal pattern, respectively) were not significant. Net incremental AUC for GLP-1 concentrations (over 3 h) for the postregular meal pattern were higher (864.9 ± 456.1 pmol/L*3 h) than the postirregular meal pattern (487.6 ± 271.7 pmol/L*3 h, paired t test, P = 0.005). Conclusions Following a 14-d period of an irregular meal pattern, TEF was significantly less than following a regular meal pattern, potentially compromising weight management if sustained long term. This study was registered at www.clinicaltrials.gov as NCT02582606. [ABSTRACT FROM AUTHOR]

Background Intake of a single meal containing herbs and spices attenuates postprandial lipemia, hyperglycemia, and oxidative stress, and improves endothelial function. There has been limited investigation of the effect of longer-term intake of mixed herbs and spices on risk factors for cardiometabolic diseases. Objectives The objective was to assess the effect of an average American diet containing herbs and spices at 0.5 (low-spice diet; LSD), 3.3 (moderate-spice diet; MSD), and 6.6 (high-spice diet; HSD) g · d−1 · 2100 kcal−1 on lipids and lipoproteins as well as other risk factors for cardiometabolic diseases in at-risk adults. Methods A 3-period, randomized, crossover, controlled-feeding study with 71 participants was conducted at the Pennsylvania State University. Each diet was consumed for 4 wk with a minimum 2-wk washout period. Outcomes were assessed at baseline and the end of each diet period. Results No between-diet effects were observed for LDL cholesterol, the primary outcome. Between-diet differences were observed for mean 24-h systolic (P  = 0.02) and diastolic (P  = 0.005) ambulatory blood pressure. The HSD lowered mean 24-h systolic blood pressure compared with the MSD (−1.9 mm Hg; 95% CI: −3.6, −0.2 mm Hg; P  = 0.02); the difference between the HSD and LSD was not statistically significant (−1.6 mm Hg; 95% CI: −3.3, 0.04 mm Hg; P  = 0.058). The HSD lowered mean 24-h diastolic blood pressure compared with the LSD (−1.5 mm Hg; 95% CI: −2.5, −0.4 mm Hg; P  = 0.003). No differences were detected between the LSD and MSD. No between-diet effects were observed for clinic-measured blood pressure, markers of glycemia, or vascular function. Conclusions In the context of a suboptimal US-style diet, addition of a relatively high culinary dosage of mixed herbs and spices (6.6 g · d−1 · 2100 kcal−1) tended to improve 24-h blood pressure after 4 wk, compared with lower dosages (0.5 and 3.3 g · d−1 · 2100 kcal−1), in adults at elevated risk of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT03064932. [ABSTRACT FROM AUTHOR]

Background Uncertainty remains about the estimates of the effects for resveratrol supplementation, including the certainty of the evidence for each estimate and the magnitude of the observed impact based on the minimal important difference. Objective We aimed to provide an overview of the effects of resveratrol supplementation, in comparison to control groups, for the management of cardiometabolic risk factors in patients with type 2 diabetes (T2D), metabolic syndrome (MetS), and nonalcoholic fatty liver disease (NAFLD). Methods PubMed, Scopus, and ISI Web of Science were searched from inception to May 2021. For each meta-analysis, the mean difference and its 95% CI were recalculated using a random-effects model. The certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results We identified 11 meta-analyses corresponding to 29 outcomes in 1476 individuals with T2D, 17 meta-analyses reporting 26 outcomes in 727 participants with the MetS, and 10 meta-analyses reporting 24 outcomes in 271 patients with NAFLD. Resveratrol supplementation had beneficial effects on some outcomes such as blood pressure, lipid profile, glycemic control, and insulin resistance in T2D, waist circumference in MetS, and body-weight and inflammation markers in NAFLD; however, for almost all outcomes, the magnitude of the effect was trivial, the certainty of evidence was very low to low, or the number of trials was too few. In the case of glycated hemoglobin (HbA1c), there was evidence that resveratrol can exert favorable and clinically important effects in the short term (<12 wk; mean difference: −1.05%, 95% CI: −2.09%, −0.02%; n  = 6; GRADE = moderate). Conclusions Current evidence does not support supplementation with resveratrol for the management of cardiometabolic risk factors in patients with T2D, MetS, and NAFLD. In the case of HbA1c, subject to the limitations such as short-term follow-up and small sample size, there was a clinically important effect. The protocol of the present systematic review was registered in Open Science Framework (https://osf.io/ake85 ; registration doi: 10.17605/OSF.IO/AKE85). [ABSTRACT FROM AUTHOR]

Background The dairy matrix may influence digestion and absorption of lipids and thereby risk of cardiovascular diseases (CVDs). However, few postprandial studies have compared dairy products that differed only in terms of their matrix. Objectives We aimed to investigate acute 8-h postprandial lipid, glycemic, and appetite responses after intake of isoenergetic dairy meals with different matrixes, but similar nutritional composition. Methods Twenty-five normal-weight men (18–40 y old) were enrolled in a randomized controlled crossover trial. On 4 test days, a meal with 1 of 4 dairy products was served: cheddar cheese (Cheese), homogenized Cheese (Hom. Cheese), micellar casein isolate (MCI) with cream (MCI Drink), and a gel produced from the MCI Drink by addition of Glucono Delta-Lactone (MCI Gel). The fat- and protein-matched dairy products differed in terms of their casein network, fat droplet size, and/or texture. Blood biochemistry and appetite responses were collected. Results Eighteen participants completed the trial. Postprandial triglycerides (TGs) (primary outcome) increased by (mean ± SEM) 0.24 ± 0.07 and 0.19 ± 0.07 mmol/L after MCI Gel compared with Cheese and Hom. Cheese, respectively (both P  ≤ 0.05). Likewise, MCI Gel increased TG incremental AUC compared with Cheese and Hom. Cheese (both P <  0.05), and peak compared with Cheese (P  < 0.05). ApoB-48 (primary outcome) was unaffected by dairy matrix. For free fatty acids (FFAs), glucose, and insulin, time × meal interactions were observed (all P  < 0.001). During the first 2 h, FFAs were lower for Cheese than for MCI products, whereas the opposite was observed for glucose and insulin. Conclusions Postprandial TG but not apoB-48 response was higher after MCI Gel, indicating that the type of casein network influences lipid responses. This suggests that the dairy matrix may also affect risk factors for CVDs. Reducing fat droplet size (i.e. Hom. Cheese) did not affect blood biochemistry. This trial was registered at clinicaltrials.gov as NCT03656367. [ABSTRACT FROM AUTHOR]

Background: Research indicates that tree nuts are cardioprotective, but studies on pecans are limited.Objectives: We examined the impact of daily pecan consumption on blood lipids and glycemia in adults at-risk for cardiovascular disease (CVD).Methods: This was a randomized, controlled trial where 56 adults (BMI ≥28 kg/m2 or hypercholesterolemia) were randomly allocated into a control group (n = 18) or 1 of 2 pecan groups. The ADD group (n = 16) consumed pecans (68 g) as part of a free-living diet. The SUB group (n = 18) substituted the pecans (68 g) for isocaloric foods from their diet. At baseline and 8 wk, a high-fat meal was consumed with 4-h postprandial blood draws to determine changes in blood lipids and glycemia.Results: There was a significant reduction from baseline to 8 wk in fasting total cholesterol (TC) (204 ± 8.76 to 195 ± 8.12; 205 ± 8.06 to 195 ± 6.94 mg/dL), LDL cholesterol (143 ± 8.09 to 129 ± 7.71; 144 ± 6.60 to 135 ± 6.16 mg/dL), triglycerides (TGs) (139 ± 12.1 to 125 ± 14.6; 133 ± 10.7 to 120 ± 10.3 mg/dL), TC/HDL cholesterol ratio (3.92 ± 0.206 to 3.58 ± 0.175; 4.08 ± 0.167 to 3.79 ± 0.151), non-HDL cholesterol (151 ± 8.24 to 140 ± 7.95; 155 ± 6.87 to 143 ± 6.00 mg/dL), and apolipoprotein B (99.1 ± 5.96 to 93.0 ± 5.35; 104 ± 3.43 to 97.1 ± 3.11 mg/dL) in the ADD and SUB groups, respectively (P ≤ 0.05 for all), with no changes in control. There was a reduction in postprandial TGs (P ≤ 0.01) in ADD, and a reduction in postprandial glucose (P < 0.05) in SUB.Conclusions: Pecan consumption improves fasting and postprandial blood lipids in CVD at-risk adults. This trial was registered at clinicaltrials.gov as NCT04376632. [ABSTRACT FROM AUTHOR]

Background: Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to address undernutrition during the complementary feeding period. SQ-LNS contains added sugars, but limited research has assessed whether infants' acceptance varies between versions with and without sugars.Objectives: Our objective was to examine the effects of repeated exposure on children's acceptance of sweetened and unsweetened SQ-LNS. We aimed to understand caregivers' perceptions of children's liking of the 2 SQ-LNS versions and their influences on infant acceptance of SQ-LNS.Methods: Caregivers (86% non-Hispanic White) and children (7-24 mo), participated in a randomized, 2-week home-exposure study and baseline and post-home exposure assessments. Children were randomized to receive sweetened or unsweetened SQ-LNS versions, mixed with infant oatmeal. At in-person visits, caregivers fed both SQ-LNS versions to children and rated their child's liking for each. Caregivers fed the SQ-LNS version to which their child was randomized until the child refused to eat more. Acceptance was measured as total grams consumed. Mixed-effects linear models tested the change in SQ-LNS consumed between baseline and postexposure by the SQ-LNS version and number of home exposures. Covariates included the amount of SQ-LNS consumed at baseline, child BMI z-score, child age, and breastfeeding experience.Results: Children's acceptance of both SQ-LNS versions increased from baseline to postexposure (β, 0.71 g; 95% CI: 0.54-0.89 g; P = 0.04), regardless of SQ-LNS version (P = 0.88) or number of home exposures (P = 0.55). Caregivers rated children's liking of unsweetened SQ-LNS higher at baseline (P = 0.02). Children with lower liking ratings at baseline showed the greatest increases in acceptance between baseline and postexposure (P = 0.01).Conclusions: Children's acceptance of SQ-LNS increased with repeated exposure, whether offered the sweetened or unsweetened version, providing preliminary support that adding sugar to SQ-LNS may not improve acceptance in young children. Children who initially like the supplement less may need repeated experience to learn to accept SQ-LNS. This trial was registered at clinicaltrials.gov as NCT04544332. [ABSTRACT FROM AUTHOR]

Background Dietary guidelines traditionally recommend low-fat dairy because dairy's high saturated fat content is thought to promote cardiovascular disease (CVD). However, emerging evidence indicates that dairy fat may not negatively impact CVD risk factors when consumed in foods with a complex matrix. Objective The aim was to compare the effects of diets limited in dairy or rich in either low-fat or full-fat dairy on CVD risk factors. Methods In this randomized controlled trial, 72 participants with metabolic syndrome completed a 4-wk run-in period, limiting their dairy intake to ≤3 servings/wk of nonfat milk. Participants were then randomly assigned to 1 of 3 diets, either continuing the limited-dairy diet or switching to a diet containing 3.3 servings/d of either low-fat or full-fat milk, yogurt, and cheese for 12 wk. Exploratory outcome measures included changes in the fasting lipid profile and blood pressure. Results In the per-protocol analysis (n  = 66), there was no intervention effect on fasting serum total, LDL, and HDL cholesterol; triglycerides; free fatty acids; or cholesterol content in 38 isolated plasma lipoprotein fractions (P  > 0.1 for all variables in repeated-measures ANOVA). There was also no intervention effect on diastolic blood pressure, but a significant intervention effect for systolic blood pressure (P  = 0.048), with a trend for a decrease in the low-fat dairy diet (−1.6 ± 8.6 mm Hg) compared with the limited-dairy diet (+2.5 ± 8.2 mm Hg) in post hoc testing. Intent-to-treat results were consistent for all endpoints, with the exception that systolic blood pressure became nonsignificant (P  = 0.08). Conclusions In men and women with metabolic syndrome, a diet rich in full-fat dairy had no effects on fasting lipid profile or blood pressure compared with diets limited in dairy or rich in low-fat dairy. Therefore, dairy fat, when consumed as part of complex whole foods, does not adversely impact these classic CVD risk factors. This trial was registered at clinicaltrials.gov as NCT02663544. [ABSTRACT FROM AUTHOR]

Objective: To study the reprometabolic syndrome in normal-weight, eumenorrheic women by infusing a combination of insulin and lipid. Women with obesity have been shown to have reduced gonadotropins and impaired luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (GnRH).Design: Randomized crossover.Setting: Academic medical center.Participant(s): Fifteen women, median age 32 (interquartile ranged [IQR] 26, 36) years and body mass index 21.9 (IQR 20.2, 22.9) kg/m2 were recruited.Intervention(s): Early follicular phase, 6-hour infusions of insulin (20-40 mU/m2 per minute) and lipid (Intralipid)-insulin/lipid infusion; or saline infusion (controls). The first 4 hours of each study assessed endogenous gonadotropins; at 4 hours, GnRH (75 ng/kg) bolus was administered and sampling continued until 6 hours.Main Outcome Measure(s): Linear mixed model analysis was used to determine differences between insulin/lipid and saline influence on endogenous LH pulse amplitude (primary outcome), mean FSH, and area under the curve (AUC) response to GnRH (secondary outcomes).Result(s): Twelve women completed both intended studies and an additional 3 women completed only 1 of the 2 studies. LH pulse amplitude, mean FSH, and both AUC responses to GnRH were reduced by insulin/lipid, mean FSH and AUC for LH were at or near statistical significance. LH response to GnRH was significantly reduced when 1 participant with very high LH and antimullerian hormone levels was excluded.Conclusion(s): Acute infusion of insulin/lipid to eumenorrheic, normal-weight women recapitulated the reprometabolic syndrome of obesity. These findings imply that specific circulating factors in obese women contribute to their subfertility and thus may be amenable to discovery and treatment.Clinical Trial Registration Number: NCT02653092. [ABSTRACT FROM AUTHOR]

Background Obesity-associated low-grade inflammation contributes to the development of cardiovascular disease (CVD). Apples are rich in anti-inflammatory bioactives including polyphenols and fiber. Objectives We aimed to determine the effects of regular apple consumption on fasting plasma biomarkers of inflammation (primary outcome), endotoxemia, carbohydrate and lipid metabolism (glucose, insulin, triacylglycerol; secondary outcomes), and peripheral blood mononuclear cell (PBMC)-secreted cytokines (secondary outcome) in individuals with overweight and obesity. Methods A randomized, controlled, parallel-arm trial was conducted with n  = 46 participants. After avoiding foods and beverages rich in polyphenols and fiber for 2 wk, participants consumed 3 whole Gala apples (∼200 g edible parts)/d as part of their habitual diet (n  = 23) or avoided apples (control, n  = 23) for 6 wk. All participants limited consumption of polyphenols and fiber during the 6-wk trial. Fasting blood samples were collected before and after 6 wk for analysis of plasma biomarkers and isolation of PBMCs, which were cultured for 24 h unstimulated or stimulated with LPS (10 ng/mL). Results Forty-four participants completed the trial (30 female, 14 male; mean ± SEM age: 45.4 ± 2.2 y; BMI: 33.4 ± 0.9 kg/m2). After ANCOVA and correcting for multiple comparisons, apples decreased fasting plasma C-reactive protein by 17.0% (range: 14.3%–19.6%, P =  0.005), IL-6 by 12.4% (range: 6.7%–17.5%, P <  0.001), and LPS-binding protein by 20.7% (range: 14.1%–26.4%, P <  0.001) compared with control. Apples also decreased PBMC-secreted IL-6 by 28.3% (range: 22.4%–33.5%, P <  0.001) and IL-17 by 11.0% (range 5.8–15.6%, P =  0.003) in the unstimulated condition compared with control. Exploratory analysis showed apples also increased plasma total antioxidant capacity by 9.6% (range: 1.7–18.9%, P =  0.002) compared with control. However, apples had no effect on anthropometric or other CVD risk markers. Conclusions Six-week daily whole Gala apple consumption may be an effective dietary strategy to mitigate the obesity-associated inflammation that exacerbates CVD risk, without weight loss. This trial was registered at clinicaltrials.gov as NCT03523403. [ABSTRACT FROM AUTHOR]

Background Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes. Objective We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions. Design In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n–6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression. Results Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18 ± 0.04, butter: 3.31 ± 0.04, MUFA: 3.00 ± 0.04, PUFA: 2.81 ± 0.04, CHO: 3.11 ± 0.04 mmol/L; P  < 0.001) while endpoint TG concentrations were not (P  = 0.117). Both displayed consistently elevated interindividual variability following the dietary interventions (CVs of 34.5 ± 2.2% and 55.8 ± 1.8%, respectively). Among the 22 candidate SNPs, only ABCA1- rs2066714 and apolipoprotein E (APOE) isoforms exhibited consistent significant effects, namely on LDL cholesterol concentrations. However, several SNPs were significantly associated with changes in LDL cholesterol and TG concentrations in a diet-specific fashion. Generated multivariate models explained from 16.0 to 33.6% of the interindividual variability in LDL cholesterol concentration changes and from 17.5 to 32.0% of that in TG concentration changes. Conclusions We report combinations of SNPs associated with a significant part of the variability in LDL cholesterol and TG concentrations following dietary interventions differing in their fatty acid profiles. [ABSTRACT FROM AUTHOR]

Background The consumption of wolfberry (Lycium barbarum), a rich source of carotenoids and bioactive polysaccharides, may serve as a potential dietary strategy for cardiovascular disease (CVD) risk management although limited studies examined its effects as whole fruits. Objectives To investigate the impact of wolfberry consumption as part of a healthy dietary pattern on vascular health-related outcomes and classical CVD risk factors in middle-aged and older adults in Singapore. Methods This is a 16-week, parallel design, randomized controlled trial. All participants (n  = 40) received dietary counselling to follow healthy dietary pattern recommendations with the wolfberry group given additional instructions to cook and consume 15 g/d whole, dried wolfberry with their main meals. Biomarkers of vascular function (flow-mediated dilation, plasma total nitrate/nitrite, endothelin-1, and intercellular adhesion molecule-1), vascular structure (carotid intima-media thickness) and vascular regeneration (endothelial progenitor cell count, plasma angiopoietin 1 and angiopoietin 2), were assessed at baseline and postintervention. Serum lipid−lipoproteins and blood pressure were evaluated every 4 weeks. Results All participants showed an improved compliance toward the healthy dietary pattern. This was coupled with marked rises in total nitrate/nitrite concentrations (mean change wolfberry: 3.92 ± 1.73 nmol/mL; control: 5.01 ± 2.55 nmol/L) and reductions in endothelin-1 concentrations (wolfberry: -0.19 ± 0.06 pg/mL; control: -0.15 ± 0.08 pg/mL). Compared with the control which depicted no changes from baseline, the wolfberry group had a significantly higher HDL cholesterol (0.08 ± 0.04 mmol/L), as well as lower Framingham predicted long-term CVD risk (-0.8 ± 0.5%) and vascular age (-1.9 ± 1.0 y) postintervention. No differences were observed in the other vascular health-related outcomes. Conclusions In middle-aged and older adults, adherence to a healthy dietary pattern improves vascular tone. Incorporating wolfberry to the diet further improves blood lipid−lipoprotein profile and may lower long-term CVD risk. This study was registered at clinicatrials.gov as NCT03535844. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a growing public health concern and maternal obesity and poor dietary intakes could be implicated. Dietary polyphenols and fiber mitigate the risk of diabetes and its complications, but little is known about their efficacy in preventing GDM.Objectives: We examined the effects of whole blueberry and soluble fiber supplementation on primary outcomes of cardiometabolic profiles in women at high risk of developing GDM.Methods: Women (n = 34; mean ± SD age: 27 ± 5 y; BMI: 35.5 ± 4.0 kg/m2; previous history of GDM ∼56%; Hispanic ∼79%) were recruited in early pregnancy (<20 weeks of gestation) and randomly assigned to 1 of the following 2 groups for 18 wk: intervention (280 g whole blueberries and 12 g soluble fiber per day) and standard prenatal care (control). Both groups received nutrition education and maintained 24-h food recalls throughout the study. Data on anthropometrics, blood pressure, and blood samples for biochemical analyses were collected at baseline (<20 weeks), midpoint (24-28 weeks), and end (32-36 weeks) of gestation. Diagnosis of GDM was based on a 2-step glucose challenge test (GCT). Data were analyzed using a mixed-model ANOVA.Results: Maternal weight gain was significantly lower in the dietary intervention than in the control group at the end of the trial (mean ± SD: 6.8 ± 3.2 kg compared with 12.0 ± 4.1 kg, P = 0.001). C-reactive protein was also lower in the intervention than in the control group (baseline: 6.1 ± 4.0 compared with 6.8 ± 7.2 mg/L; midpoint: 6.1 ± 3.7 compared with 7.5 ± 7.3 mg/L; end: 5.5 ± 2.2 compared with 9.5 ± 6.6 mg/L, respectively, P = 0.002). Blood glucose based on GCT was lower in the intervention than in the control (100 ± 33 mg/dL compared with 131 ± 40 mg/dL, P < 0.05). Conventional lipids (total, LDL, and HDL cholesterol and triglycerides) did not differ between groups over time. No differences were noted in infant birth weight.Conclusions: Whole blueberry and soluble fiber supplementation may prevent excess gestational weight gain and improve glycemic control and inflammation in women with obesity.This trial was registered at clinicaltrials.gov as NCT03467503. [ABSTRACT FROM AUTHOR]

Clinical trials have demonstrated reductions in major adverse cardiovascular events with purified high-dose eicosapentaenoic acid (EPA), independent of effects on lipids. We aimed to investigate whether omega-3 fatty acids reduce vascular inflammation, a critical mediator of atherosclerosis, and hypothesised that EPA is superior to docosahexaenoic acid (DHA). In a double-blind randomised controlled trial and cell-culture study, 40 healthy volunteers were supplemented with 4 g daily of either EPA, DHA, fish oil (2:1 EPA:DHA), or placebo for 30 days. Serum was incubated with TNF-stimulated human umbilical vein endothelial cells (HUVECs), and markers of acute vascular inflammation (AVI) were measured. The effects of EPA, DHA (600 mg/kg/day), olive oil, or no treatment were also measured in preclinical models of [1] AVI using a periarterial collar (C57Bl/6J; n = 40 mice) and [2] atherosclerosis where ApoE −/− mice (n = 40) were fed a 16-week atherogenic diet. EPA supplementation reduced expression of C–C motif chemokine ligand 2 (CCL2) by 25% compared to placebo (p = 0.03). In the AVI model, EPA reduced vascular expression of VCAM1 by 43% (p = 0.02) and CCL2 by 41% (p = 0.03). Significant inverse correlations were observed between EPA levels and vascular expression of VCAM1 (r = −0.56, p = 0.001) and CCL2 (r = −0.56, p = 0.001). In ApoE −/- mice, EPA reduced aortic expression of Il1b by 44% (p = 0.04) and Tnf by 49% (p = 0.04), with similar inverse correlations between EPA levels and both Il1b (r = −0.63, p = 0.009) and Tnf (r = −0.50, p = 0.04). Supplementation with EPA, more so than DHA, ameliorates acute and chronic vascular inflammation, providing a rationale for the cardiovascular benefit observed with high dose omega-3 fatty acid administration. [Display omitted] • Eicosapentaenoic acid (EPA) reduced expression of markers of acute vascular inflammation after inflammatory stimuli, in in vitro and in vivo models. • EPA reduced expression of markers of chronic vascular inflammation but not plaque burden, in an atherogenic mouse model. • Blood EPA and docosahexaenoic acid (DHA) levels correlated inversely with markers of vascular inflammation, with EPA having a stronger correlation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The effect of MPA on the lipid profile and CVD risk is still controversial; hence, this comprehensive dose–response meta -analysis of randomized controlled trials was conducted to assess the effect of MPA on lipid profiles in women. A comprehensive search was conducted in the following databases: Web of Science, Scopus, PubMed/Medline, and Embase, up to October 20, 2023. A random-effects meta -analysis approach based on the DerSimonian and Laird method was used to compute the combined estimates of the intervention's impact on the lipid profile. 35 eligible studies with 58 arms were included in our meta -analyses analysis. Combined effect sizes suggested a significant effect of MPA on total cholesterol (TC) levels (WMD: −3.43 mg/dL, 95 % CI: −5.38 to −1.48, p < 0.001), HDL-C levels (WMD: −3.34 mg/dL, 95 % CI: −3.77 to −2.91, p < 0.001), and triglyceride (TG) levels (WMD: −9.13 mg/dL, 95 % CI: −10.92 to −7.33, p < 0.001). The subgroup meta -analysis revealed a more substantial reduction in TC in studies with dosages > 2.5 mg/day (WMD: −4.10 mg/dL), mean participant age lower than 60 years (WMD: −3.80 mg/dL), mean BMI lower than 25 kg/m2 (WMD: −5.61 mg/dL), duration of intervention of 12 months or more (WMD: −3.98 mg/dL), and when the baseline TC value was equal to or greater than 200 mg/dL (WMD: −4.13 mg/dL). The current meta -analysis showed a statistically significant decrease in TC, TG, and HDL-C levels and a non-significant increase in LDL-C levels after MPA administration in women. [ABSTRACT FROM AUTHOR]

Background We previously reported results from a randomized controlled trial in which we found that Swedish infants consuming an experimental low-energy, low-protein formula (EF) supplemented with bovine milk fat globule membranes (MFGMs) until 6 mo of age had several positive outcomes, including better performance in the cognitive domain of Bayley Scales of Infant and Toddler Development 3rd Edition at 12 mo of age, and higher plasma cholesterol concentrations during the intervention, than infants consuming standard formula (SF). Objectives We aimed to evaluate neurodevelopment, growth, and plasma cholesterol status at 6 and 6.5 y of age in the same study population. Methods We assessed cognitive and executive functions using the Wechsler Intelligence Scale for Children 4th Edition (WISC-IV), Brown Attention-Deficit Disorder Scales for Children and Adolescents (Brown-ADD), and Quantified Behavior (Qb) tests, and behavior using the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF), at 6.5 y of age. Anthropometrics and plasma lipids were assessed at 6 y of age. Results There were no differences between the EF and SF groups in any of the subscales in WISC-IV or Brown-ADD at 6.5 y of age, in the proportion of children with scores outside the normal range in the Qb test, nor in clinical or borderline indications of problems in adaptive functioning from parental and teacher's scoring using the CBCL and TRF. There were no differences between the EF and SF groups in weight, length, or head or abdominal circumferences, nor in plasma concentrations of homocysteine, lipids, insulin, or glucose. Conclusions Among children who as infants consumed a low-energy, low-protein formula supplemented with bovine MFGMs, there were no effects on neurodevelopment, growth, or plasma cholesterol status 6–6.5 y later. [ABSTRACT FROM AUTHOR]

Background Effects of dietary fat quality on liver fat remain to be elucidated. Inconsistent evidence may be influenced by fatty acid saturation, chain-length, and regio-specificity within triacylglycerol (TAG) molecules. Objectives We aimed to compare eucaloric diets enriched in palm olein (POo), cocoa butter (COB), and soybean oil (SBO) on liver fat concentration in healthy participants. Secondary outcomes included visceral (VAT) and abdominal subcutaneous (aSCAT) adipose tissue, plus other obesity and cardiometabolic health outcomes. Methods Eighty-three healthy participants (20–45 y, BMI 18.5–27.5 kg/m2) commenced and 64 completed a 16-wk randomized parallel intervention, preceded by a 2-wk run-in. Participants consumed identical eucaloric background diets differing in test fats [contributing 20% total energy intake (%E)], providing 33%E total fat with the following ratios for PUFAs/SFAs/MUFAs: POo, 4.2/13.5/15%E; SBO, 14.4/8.8/9.4%E; COB, 2.3/19.5/11%E. Liver fat and abdominal adiposity were measured at weeks 0 and 16 using 1H-magnetic resonance spectroscopy/imaging; all other outcomes were measured at 0, 4, 8, 12, and 16 wk. Results Fat quality did not affect liver fat concentration, VAT, aSCAT, obesity indexes, blood pressure, liver enzymes, leptin, or fasting glucose. Body fat mass decreased with SBO and COB compared with POo. SBO decreased serum total cholesterol (TC), LDL cholesterol, and TC:HDL cholesterol relative to POo [estimated marginal mean (95% CI) differences: −0.57 (−0.94, −0.20) mmol/L; −0.37 (−0.68, −0.07) mmol/L; and −0.42 (−0.73, −0.11) mmol/L, respectively]. No diet differences were observed on HDL cholesterol, TAG, apoA1, apoB, apoB:apoA1, or fecal free fatty acids (FFAs), except for lower FFA pentadecanoic acid (15:0) with COB than with SBO and POo. Conclusions In healthy adults, when consumed as part of eucaloric typical Australian diets, 3 different dietary fat sources did not differentially affect liver fat concentration and amounts of adipose tissue. Effects on serum lipids were inconsistent across lipid profiles. The findings must be confirmed in metabolically impaired individuals before recommendations can be made. [ABSTRACT FROM AUTHOR]

Background There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease. Objectives The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator. Methods Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (<7.5 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center. Results Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: −57.0 g/d; 95% CI: −77.9, −39.5 g/d; and −38.8 μmol/d; 95% CI: −91.2, −10.7 μmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P  < 0.001 and P  = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: −0.7% point, 95% CI: −2.0, −0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups. Conclusions Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group. This trial was registered at clinicaltrials.gov as NCT03067428. [ABSTRACT FROM AUTHOR]

Background: A recent systematic review of epidemiological evidence suggests that higher amounts of tea intake are associated with lower risks of cardiovascular disease (CVD) incidence and mortality.Objectives: Our study objective was to assess mechanisms by which tea consumption may influence CVD risks.Methods: A systematic review and meta-analysis was conducted to investigate the effects of green and/or black tea consumption (≥4 wk) on systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride (TG) in healthy populations and among at-risk adults (analyzed separately) with metabolic syndrome, prediabetes, and hypercholesterolemia. The Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the strength of evidence (SoE).Results: A total of 14 unique RCTs which randomly assigned 798 participants to either green tea, black tea, or placebo controls were included in our analyses. Intervention durations ranged from 4 to 24 wk (mean: 7.4 wk). Individual studies were judged as moderate to high quality based on risk of bias assessments. SoE was low to moderate owing to low sample sizes and insufficient power for most included studies to observe changes in the measured CVD biomarkers. Meta-analyses showed no significant effects of tea consumption on SBP, DBP, total cholesterol, LDL cholesterol, HDL cholesterol, and TG in healthy and at-risk adults (i.e., adults with obesity, prediabetes, borderline hypercholesterolemia, and metabolic syndrome).Conclusions: Short-term (4-24 wk) tea consumption does not appear to significantly affect blood pressure or lipids in healthy or at-risk adults, although the evidence is limited by insufficient power to detect changes in these CVD biomarkers. High-quality RCTs with longer durations and sufficient sample sizes are needed to fully elucidate the effects of tea. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020134513. [ABSTRACT FROM AUTHOR]

Background: Individual vegetable oils have a characteristic fatty acids (FA) composition and unique phytonutrient profiles, enabling formulation of oil blends that may have health-promoting effects.Objective: The primary objective of this study was to investigate effects of 2 oil blends made with refined rice bran, flaxseed, and sesame oils, with distinct monounsaturated to saturated FA, polyunsaturated to saturated FA, and omega-3 (n-3) to omega-6 FA ratios and different phytonutrient concentrations on blood lipid profile, compared with refined olive oil as a control. The secondary outcomes were other markers of cardiometabolic health.Methods: A parallel-design, randomized controlled trial compared consumption of 30 g of allocated intervention oil per day for a period of 8 wk. The study recruited 143 borderline hypercholesterolemic (LDL cholesterol: 3.06-4.51 mmol/L) Chinese volunteers between 50 and 70 y old and with a BMI (kg/m2) ≤27.5. All outcomes were measured every 2 wk, and the time × treatment interactions and the main effects of treatment and time were analyzed using an intention-to-treat approach.Results: Compared with baseline (week 0), there were significant reductions during the post-intervention time points in serum total cholesterol (-3.47%; P < 0.0001), LDL cholesterol (-4.16%; P < 0.0001), triglycerides (-10.3%; P < 0.0001), apoB (-3.93%; P < 0.0001), total to HDL-cholesterol (-3.44%; P < 0.0001) and apoB to apoA1 (-3.99%; P < 0.0001) ratios, systolic and diastolic blood pressures (-3.32% and -3.16%, respectively; both P < 0.0001), and serum glucose (-1.51%; P < 0.05) and a small but significant increase in body weight (+0.7%; P < 0.001) for all 3 intervention oils but no effects of intervention on HDL-cholesterol or apoA1 concentration. No significant effects of treatment or time × treatment interactions were found.Conclusions: Using blended vegetable oils that are extensively consumed in Asia, this study found that specific oil blends can improve blood lipid profile and other cardiometabolic parameters, to a similar extent as refined olive oil, in Chinese adults with borderline hypercholesterolemia. This trial is registered at www.clinicaltrials.gov as NCT03964857. [ABSTRACT FROM AUTHOR]

The US military Meal, Ready-to-Eat food ration is approved as a nutritionally adequate sole source of nutrition for ≤21 days. However, the ration continuously evolves, requiring periodic reassessment of its influence on nutritional status and health. To determine the effects of consuming the US Armed Services Meal, Ready-to-Eat ration for 21 days, relative to usual diets, on nutrient intake, and indicators of nutritional status and cardiometabolic health. Parallel-arm, randomized, controlled trial, secondary analysis. Sixty healthy, weight stable, free-living adults from the Natick, MA, area participated between June 2015 and March 2017. Participants were randomized to consume their usual diet for 31days (CON), or a strictly controlled Meal, Ready-to-Eat-only diet for 21 days followed by their usual diet for 10 days (MRE). Nutrient intake (absolute and adjusted) throughout the study period, and indicators of nutrition status (vitamins B, D, folate, homocysteine, iron, magnesium, and zinc) and cardiometabolic health (glucose, insulin, and blood lipid levels) before (Day 0), during (Day 10 through Day 21), and after (Day 31) the intervention period. Between-group differences over time were assessed using marginal models. Models for nutritional status and cardiometabolic health indicators were adjusted for age, initial body mass index, and baseline value of the dependent variable. Energy-adjusted fiber; polyunsaturated fatty acids; vitamins A, thiamin, riboflavin, B-6, C, D, and E; and magnesium and zinc intakes all increased in MRE during the intervention and were higher compared with CON (P <0.05), whereas relative protein intake decreased and was lower (P <0.05). Serum triglyceride concentrations averaged 19% (95% CI 0% to 41%) higher in MRE relative to CON during Days 10 to 31 (P =0.05). No statistically significant effects of diet on any other nutritional status or cardiometabolic health indicators were observed. Findings demonstrate that a Meal, Ready-to-Eat ration diet can provide a more micronutrient-dense diet than usual dietary intake aiding in maintenance of nutritional status over 21 days. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Evaluate the lipid profile, Body Mass Index (BMI) and weight gain of pregnant women with obesity and the effect of a low dose (1000 mg/day) of metformin hydrochloride on these parameters. A randomized clinical trial was performed from October 31th, 2014 to January 25th, 2018 with pregnant women diagnosed with obesity by arrival BMI ≥ 30.0 kg/m2. The participants were randomized into two groups: metformin and control. All pregnant women received standard prenatal follow-up and the same instructions of diet and physical exercise. Laboratory tests were performed at three different times: first moment with gestational age (GA) < 20 weeks, second (GA 24−28 weeks) and third (GA 32–34 weeks) measuring maternal serum levels of total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides (TG) as well as weight gain and BMI were monitored. A total of 424 pregnant women with obesity were evaluated. Of these, 218 (51.41%) composed the control group and 206 (48.59%) the metformin group. There was no difference of lipid profile, BMI and weight gain values between groups during the 1st, 2nd and 3rd evaluation moments. A significant difference was observed, only in the BMI, HDL and TG values from 1st to 3rd evaluation moments. Low dose (1000 mg/day) of the drug showed no effect on the lipid profile, BMI and weight gain in pregnant women with obesity in metformin group during the evaluation moments. [ABSTRACT FROM AUTHOR]

Objectives: We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.Methods: The Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.Results: We observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.Conclusions: Atorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. [ABSTRACT FROM AUTHOR]

Background Exercise and increased dietary protein have been linked to improved muscle and cognitive health, but the combination may be more effective. Objective In this study performed in community-dwelling older adults undergoing a 3-d/wk resistance-based exercise training program, we investigated whether those who consumed lean red meat compared to carbohydrates on the 3 training days per wk would experience greater exercise-induced improvements in total body and leg lean mass (LM), muscle strength, and executive function (multiple primary outcomes), as well as muscle size and density, functional performance, cognition, inflammatory and neurotrophic markers, blood pressure, and lipid concentrations. Design In a 24-wk, 2-arm parallel randomized controlled trial, 154 adults aged ≥65 y participated in a multicomponent 3-d/wk resistance-based exercise program with random allocation to either a lean red meat group (two 80-g servings of cooked red meat), the exercise plus lean red meat (Ex + Meat) group (n = 77) or a control group receiving carbohydrates in the form of one-half cup (approximately 225 g cooked weight) of rice or pasta or 1 medium potato, the exercise plus carbohydrate control (C + Ex) group (n  = 77), on the training days. Results Exercise-induced improvements (mean within group changes) did not significantly differ between groups for the primary outcomes of total body LM (0.6 to 0.8 kg), leg LM (0.1 to 0.2 kg), thigh muscle cross-sectional area (3.7% to 4.9%), leg and back muscle strength (26% to 40%), and executive function (z -score SD: 0.33 to 0.39), nor the secondary outcomes of global cognition function (0.17 to 0.23 SD), fat mass (−0.65 to −0.75 kg), physical function measures (sit-to-stand, both 15%; 4-square step test, 2% to 7%), or systolic blood pressure (−3.2 to −4.1 mm Hg). The Ex + Meat group experienced greater improvements than the C + Ex in arm LM (0.07 kg; 95% CI: 0.01, 0.14; P  = 0.029), gait speed (0.05 m/s; 95% CI: 0.00, 0.11; P  = 0.042), muscle density (1.0%; 95% CI: 0.2, 1.9; P  = 0.015), and appendicular LM in the per-protocol analysis (0.21 kg; 95% CI: 0.02, 0.40; P  = 0.03). The C + Ex group had greater net improvements in working memory/learning after 12 wk (SD: 0.24; 95% CI: 0.05, 0.43; P  = 0.011) and 24 wk (SD: 0.27; 95% CI: 0.06, 0.49; P  = 0.007). Inflammatory and neurotrophic markers did not change in either group. Conclusion In healthy community-dwelling older adults undertaking resistance-based exercise training 3-d/wk, participants who consumed lean red meat in line with current Australian dietary recommendations did not experience any significant additional benefits in the primary outcome measures of muscle mass, strength, or cognitive function compared to participants consuming carbohydrates. This trial is registered with the Australian and New Zealand Clinical Trials Registry as ACTRN12613001153707. [ABSTRACT FROM AUTHOR]

Background: PRIMVAC is a VAR2CSA-derived placental malaria vaccine candidate aiming to prevent serious clinical outcomes of Plasmodium falciparum infection during pregnancy. We assessed the safety and immunogenicity of PRIMVAC adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) in French and Burkinabe women who were not pregnant.Methods: This first-in-human, randomised, double-blind, placebo-controlled, dose escalation trial was done in two staggered phases, a phase 1A trial in 18-35-year-old women who were malaria naive in a hospital in France and a subsequent phase 1B trial in women who were naturally exposed to P falciparum and nulligravid in the clinical site of a research centre in Burkina Faso. Volunteers were recruited into four sequential cohorts receiving PRIMVAC intramuscularly at day 0, 28, and 56: two cohorts in France receiving 20 μg or 50 μg of PRIMVAC and then two in Burkina Faso receiving 50 μg or 100 μg of PRIMVAC. Volunteers were randomly assigned (1:1) to two groups (PRIMVAC adjuvanted with either Alhydrogel or GLA-SE) in France and randomly assigned (2:2:1) to three groups (PRIMVAC adjuvanted with either Alhydrogel, GLA-SE, or placebo) in Burkina Faso. Randomisation was centralised, using stratification by cohort and blocks of variable size, and syringes were masked by opaque labels. The primary endpoint was the proportion of participants with any grade 3 or higher adverse reaction to vaccination up until day 35. Safety at later time points as well as humoral and cellular immunogenicity were assessed in secondary endpoints. This trial is registered with ClinicalTrials.gov, NCT02658253.Findings: Between April 19, 2016, and July 13, 2017, 68 women (18 in France, 50 in Burkina Faso) of 101 assessed for eligibility were included. No serious adverse event related to the vaccine occurred. PRIMVAC antibody titres increased with each dose and seroconversion was observed in all women vaccinated with PRIMVAC (n=57). PRIMVAC antibody titres reached a peak (geometric mean 11 843·0, optical density [OD] 1·0, 95% CI 7559·8-18 552·9 with 100 μg dose and GLA-SE) 1 week after the third vaccination (day 63). Compared with Alhydrogel, GLA-SE tended to improve the PRIMVAC antibody response (geometric mean 2163·5, OD 1·0, 95% CI 1315·7-3557·7 with 100 μg dose and Alhydrogel at day 63). 1 year after the last vaccination, 20 (71%) of 28 women who were vaccinated with PRIMVAC/Alhydrogel and 26 (93%) of 28 women who were vaccinated with PRIMVAC/GLA-SE still had anti-PRIMVAC antibodies, although antibody magnitude was markedly lower (452·4, OD 1·0, 95% CI 321·8-636·1 with 100 μg dose and GLA-SE). These antibodies reacted with native homologous VAR2CSA expressed by NF54-CSA infected erythrocytes (fold change from baseline at day 63 with 100 μg dose and GLA-SE: 10·74, 95% CI 8·36-13·79). Limited cross-recognition, restricted to sera collected from women that received the 100 μg PRIMVAC dose, was observed against heterologous VAR2CSA variants expressed by FCR3-CSA (fold change from baseline at day 63: 1·49, 95% CI 1·19-1·88) and 7G8-CSA infected erythrocytes (1·2, 1·08-1·34).Interpretation: PRIMVAC adjuvanted with Alhydrogel or GLA-SE had an acceptable safety profile, was immunogenic, and induced functional antibodies reacting with the homologous VAR2CSA variant expressed by NF54-CSA infected erythrocytes. Cross-reactivity against heterologous VAR2CSA variants was limited and only observed in the higher dose group. An alternate schedule of immunisation, antigen dose, and combinations with other VAR2CSA-based vaccines are envisaged to improve the cross-reactivity against heterologous VAR2CSA variants.Funding: Bundesministerium für Bildung und Forschung, through Kreditanstalt für Wiederaufbau, Germany; Inserm, and Institut National de Transfusion Sanguine, France; Irish Aid, Department of Foreign Affairs and Trade, Ireland. [ABSTRACT FROM AUTHOR]

Background: Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood.Objectives: We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9).Methods: A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis.Results: Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets.Conclusions: In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9. This trial was registered at clinicaltrials.gov as NCT01235832. [ABSTRACT FROM AUTHOR]

Time-restricted feeding (TRF) has been shown to improve body composition, blood lipids, and reduce markers of inflammation and oxidative stress. However, most of these studies come from rodent models and small human samples, and it is not clear if the benefits are dependent upon a caloric deficit, or the time restriction nature of TRF. Based off of previous research, we hypothesized that humans following an ad libitum TRF protocol would reduce caloric intake and this caloric deficit would be associated with greater improvements in cardiometabolic health including blood pressure, body composition, blood lipids, and markers of inflammation and antioxidant status compared to an isocaloric TRF protocol. The purpose of this study was to: (1) examine the impact of TRF on markers of cardio-metabolic health and antioxidant status and (2) determine if the adaptations from TRF would differ under ad libitum compared to isocaloric conditions. Twenty-three healthy men were randomized to either an ad libitum or isocaloric 16:8 (fasting: feeding) TRF protocol. A total of 22 men completed the 28-day TRF protocol (mean ± SD; age: 22 ± 2.5 yrs.; height: 178.4 ± 6.9 cm; weight: 90.3 ± 24 kg; BMI: 28.5 ± 8.3 kg/m2). Fasting blood samples were analyzed for glucose, lipids, as well as adiponectin, human growth hormone, insulin, cortisol, C-reactive protein, superoxide dismutase, total nitrate/nitrite, and glutathione. Time-restricted feeding in both groups was associated with significant (P <.05) reductions in body fat, blood pressure, and significant increases in adiponectin and HDL-c. No changes in caloric intake were detected. In summary, the results from this pilot study in metabolically healthy, active young men, suggest that TRF can improve markers of cardiometabolic health. [ABSTRACT FROM AUTHOR]

Consumption of added sugars in the US is estimated to be approximately 1.5 times recommended levels and has been linked to increased risk for developing chronic diseases. We hypothesized that relative to sugar, honey would reduce energy intake and improve serum lipid profiles. To test this, we assessed the short-term (1-week) and relatively long-term (1-month) effects of honey versus sucrose on changes in dietary intake and serum lipid concentrations. Thirty-seven apparently healthy subjects (21 males; 16 females) aged 24–57 years (BMI = 17.6–37.2 kg/m2) completed two 4-week trials in a randomized, cross-over design separated by ≥4-week washout. During each trial, subjects consumed either clover honey or sucrose providing 1.2 g/kg/day of carbohydrate under free-living conditions with instructions to avoid changing their habitual food intake. Serum triglyceride (TG) concentrations were elevated (P <.05) after 1 week for both trials but only remained elevated (P <.05) at the 4-week time-point during sucrose consumption. The elevation after 1 week during the honey trial was concurrent with a transient increase (P <.05) in body weight. No effects on serum concentrations of insulin, total cholesterol, low density lipoprotein-cholesterol, or high density lipoprotein-cholesterol were detected for either trial. Subjects consumed significantly less energy (P <.05), carbohydrate (P <.005), sugars (P <.05), and saturated fat (P <.05) during the honey trial. These data suggest that honey may serve as a favorable substitute for sucrose with regard to reduced energy intake, carbohydrate and sugars, without negatively influencing serum lipid concentrations. [ABSTRACT FROM AUTHOR]

Background: Adequate knowledge about the safety of consumption of small-quantity lipid-based nutrient supplements (SQ-LNSs) is needed.Objective: We aimed to test the hypothesis that SQ-LNS consumption is noninferior to control with respect to child morbidity.Methods: Women (n = 1320) ≤20 wk pregnant were assigned to iron and folic acid until delivery with no supplementation for offspring; or multiple micronutrient supplements until 6 mo postpartum with no supplementation for offspring; or SQ-LNSs until 6 mo postpartum, and SQ-LNSs for offspring (6 mg Fe/d) from 6 to 18 mo of age [the lipid-based nutrient supplement (LNS) group]. We assessed noninferiority (margin ≤20%) between any 2 groups during 0-6 mo of age, and between the non-LNS and LNS groups during 6-18 mo of age for caregiver-reported acute respiratory infection, diarrhea, gastroenteritis, fever/suspected malaria, poor appetite, and "other illnesses."Results: During 0-6 mo of age, 1197 infants contributed 190,503 infant-days. For all morbidity combined, overall mean incidence (per 100 infant-days) was 3.3 episodes, overall mean prevalence (percentage of infant-days) was 19.3%, and the 95% CIs of the incidence rate ratio (IRR) and longitudinal prevalence rate ratio (LPRR) between any 2 groups were ≤1.20. During 6-18 mo, there were 240,097 infant-days for the non-LNS group and 118,698 for the LNS group. For all morbidity combined, group mean incidences were 4.3 and 4.3, respectively (IRR: 1.0; 95% CI: 1.0, 1.1), and mean prevalences were 28.2% and 29.3%, respectively (LPRR: 1.0; 95% CI: 1.0, 1.1). Noninferiority was inconclusive for diarrhea, fever/suspected malaria, and poor appetite.Conclusions: SQ-LNS consumption does not increase reported overall child morbidity in this population compared with the 2 other treatments.This trial was registered at clinicaltrials.gov as NCT00970866. [ABSTRACT FROM AUTHOR]

Background Overall quality of dietary carbohydrate intake rather than total carbohydrate intake may determine the risk of cardiovascular disease (CVD). Objective We examined 6- and 12-mo changes in carbohydrate quality index (CQI) and concurrent changes in several CVD risk factors in a multicenter, randomized, primary-prevention trial (PREDIMED-Plus) based on an intensive weight-loss lifestyle intervention program. Methods Prospective analysis of 5373 overweight/obese Spanish adults (aged 55–75 y) with metabolic syndrome (MetS). Dietary intake information obtained from a validated 143-item semiquantitative food-frequency questionnaire was used to calculate 6- and 12-mo changes in CQI (categorized in quintiles), based on 4 criteria (total dietary fiber intake, glycemic index, whole grain/total grain ratio, and solid carbohydrate/total carbohydrate ratio). The outcomes were changes in intermediate markers of CVD. Results During the 12-mo follow-up, the majority of participants improved their CQI by increasing their consumption of fruits, vegetables, legumes, fish, and nuts and decreasing their consumption of refined cereals, added sugars, and sugar-sweetened beverages. After 6 mo, body weight, waist circumference (WC), systolic and diastolic blood pressure (BP), fasting blood glucose, glycated hemoglobin (HbA1c), triglyceride levels, triglycerides and glucose (TyG) index, and TyG-WC decreased across successive quintiles of improvement in the CQI. After 12 mo, improvements were additionally observed for HDL cholesterol and for the ratio of total to HDL cholesterol. Favorable improvements (expressed in common units of SD and 95% CI) for quintile 5 compared with quintile 1 of CQI change were observed for most risk factors, including TyG-WC (SD −0.20; 95% CI −0.26, −0.15), HbA1c (SD −0.16; 95% CI −0.23, −0.10), weight (SD −0.12; 95% CI −0.14, −0.09), systolic BP (SD −0.11; 95% CI −0.19, −0.02) and diastolic BP (SD −0.11; 95% CI −0.19, −0.04). Conclusions Improvements in CQI were strongly associated with concurrent favorable CVD risk factor changes maintained over time in overweight/obese adults with MetS. This trial was registered as ISRCTN 89898870. [ABSTRACT FROM AUTHOR]