PCSK9 Activity Is Potentiated Through HDL Binding.

Rationale: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates in a free and lipoprotein-bound form, yet the functional consequence of the association between PCSK9 and high-density lipoprotein (HDL) remains unexplored. Objective: This study sought to interrogate the novel relationship between PCSK9 and HDL in humans. Methods and Results: Comparing lipoprotein and apolipoprotein profiles by nuclear magnetic resonance and targeted mass spectrometry measurements with PCSK9 levels in the community-based Bruneck (n=656) study revealed a positive association of plasma PCSK9 with small HDL, alongside a highly significant positive correlation between plasma levels of PCSK9 and apolipoprotein-C3, an inhibitor of lipoprotein lipase. The latter association was replicated in an independent cohort, the SAPHIR study (n=270). Thus, PCSK9-HDL association was determined during the postprandial response in two dietary studies (n=20 participants each, 8 times points). Peak triglyceride levels coincided with an attenuation of the PCSK9-HDL association, a loss of apolipoprotein-C3 from HDL and lower levels of small HDL as measured by nuclear magnetic resonance. Crosslinking mass spectrometry (XLMS) upon isolated HDL identified PCSK9 as a potential HDL-binding partner. PCSK9 association with HDL was confirmed through size-exclusion chromatography and immuno-isolation. Quantitative proteomics upon HDL isolated from patients with coronary artery disease (n=172) returned PCSK9 as a core member of the HDL proteome. Combined interrogation of the HDL proteome and lipidome revealed a distinct cluster of PCSK9, phospholipid transfer protein, clusterin and apolipoprotein-E within the HDL proteome, that was altered by sex and positively correlated with sphingomyelin content. Mechanistically, HDL facilitated PCSK9-mediated low-density lipoprotein receptor degradation and reduced low-density lipoprotein uptake through the modulation of PCSK9 internalisation and multimerisation. Conclusions: This study reports HDL as a binder of PCSK9 and regulator of its function. The combination of -omic technologies revealed postprandial lipaemia as a driver of PCSK9 and apolipoprotein-C3 release from HDL.

Exploring the relationship between social jetlag with gut microbial composition, diet and cardiometabolic health, in the ZOE PREDICT 1 cohort.

PURPOSE: In this study, we explore the relationship between social jetlag (SJL), a parameter of circadian misalignment, and gut microbial composition, diet and cardiometabolic health in the ZOE PREDICT 1 cohort (NCT03479866). METHODS: We assessed demographic, diet, cardiometabolic, stool metagenomics and postprandial metabolic measures (n = 1002). We used self-reported habitual sleep (n = 934) to calculate SJL (difference in mid-sleep time point of ≥ 1.5 h on week versus weekend days). We tested group differences (SJL vs no-SJL) in cardiometabolic markers and diet (ANCOVA) adjusting for sex, age, BMI, ethnicity, and socio-economic status. We performed comparisons of gut microbial composition using machine learning and association analyses on the species level genome bins present in at least 20% of the samples. RESULTS: The SJL group (16%, n = 145) had a greater proportion of males (39% vs 25%), shorter sleepers (average sleep < 7 h; 5% vs 3%), and were younger (38.4 ± 11.3y vs 46.8 ± 11.7y) compared to the no-SJL group. SJL was associated with a higher relative abundance of 9 gut bacteria and lower abundance of 8 gut bacteria (q < 0.2 and absolute Cohen's effect size > 0.2), in part mediated by diet. SJL was associated with unfavourable diet quality (less healthful Plant-based Diet Index), higher intakes of potatoes and sugar-sweetened beverages, and lower intakes of fruits, and nuts, and slightly higher markers of inflammation (GlycA and IL-6) compared with no-SJL (P < 0.05 adjusted for covariates); rendered non-significant after multiple testing adjustments. CONCLUSIONS: Novel associations between SJL and a more disadvantageous gut microbiome in a cohort of predominantly adequate sleepers highlight the potential implications of SJL for health.

The emerging importance of tackling sleep-diet interactions in lifestyle interventions for weight management.

Sleep habits are directly related to risk of obesity, and this relationship may be partly mediated through food choices and eating behaviour. Short sleep duration, impaired sleep quality and suboptimal sleep timing are all implicated in weight gain and adverse cardiometabolic health, at least partly mediated through their associations with diet quality. Short-term sleep restriction leads to increased energy intake, and habitually short sleepers report dietary intakes that indicate a less healthy diet compared with adequate sleepers. Evidence is emerging that sleep extension interventions in short sleepers may reduce intake of sugars and overall energy intake. Poor sleep quality, night shift work patterns and social jetlag are also associated with lower diet quality and consumption of energy-dense foods. Incorporating sleep advice into weight management interventions may be more effective than energy-restricted diets and exercise advice alone. However, there are a lack of intervention studies that aim to lengthen sleep, improve sleep quality or adjust irregular sleep timing to investigate the impact on dietary intakes and eating behaviour in participants aiming to lose weight or maintain weight loss. Finally, future research should take account of individual characteristics such as age, sex, life stage and changing working practices when designing combined lifestyle interventions including sleep behaviour change for health and well-being.

Short sleep and social jetlag are associated with higher intakes of non-milk extrinsic sugars, and social jetlag is associated with lower fibre intakes in those with adequate sleep duration: a cross-sectional analysis from the National Diet and Nutrition Survey Rolling Programme (Years 1-9).

OBJECTIVE: To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population. DESIGN: A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008-2017. SETTING: UK free-living population. SUBJECTS: Totally, 5015 adults aged 19-64 years. RESULTS: Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). Compared to those reporting optimal sleep duration (≥ 7-< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (-0·5 g/d, 95 % CI -0·8, -0·2). There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk. CONCLUSIONS: The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices.

Whole almond consumption is associated with better diet quality and cardiovascular disease risk factors in the UK adult population: National Diet and Nutrition Survey (NDNS) 2008-2017.

PURPOSE:  This work aimed to estimate whole almond consumption in a nationally representative UK survey population and examine associations with diet quality and cardiovascular disease (CVD) risk. METHODS:  Four-day food record data from the National Diet and Nutrition Survey (NDNS) 2008-2017 (n = 6802, age ≥ 19 year) were analyzed to investigate associations between whole almond consumption and diet quality, measured by the modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS), and CVD risk markers, using survey-adjusted multivariable linear regression. RESULTS:  Whole almond consumption was reported in 7.6% of the population. Median intake in whole almond consumers was 5.0 g/day (IQR 9.3). Consumers had higher diet quality scores relative to non-consumers; higher intakes of protein, total fat, monounsaturated, n-3 and n-6 polyunsaturated fats, fiber, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, and iron; and lower intakes of trans-fatty acids, total carbohydrate, sugar, and sodium. BMI and WC were lower in whole almond consumers compared to non-consumers: 25.5 kg/m2 (95% CI 24.9, 26.2) vs 26.3 kg/m2 (25.9, 26.7), and 88.0 cm (86.2, 89.8) vs 90.1 cm (89.1, 91.2), respectively. However, there were no dose-related fully adjusted significant associations between increasing almond intake (g per 1000 kcal energy intake) and lower CVD risk markers. CONCLUSIONS:  Almond intake is low in the UK population, but consumption was associated with better dietary quality and lower CVD risk factors. Habitual consumption of whole almonds should be encouraged as part of a healthy diet.

Tree nut snack consumption is associated with better diet quality and CVD risk in the UK adult population: National Diet and Nutrition Survey (NDNS) 2008-2014.

OBJECTIVES: To examine associations of tree nut snack (TNS) consumption with diet quality and cardiovascular disease (CVD) risk in UK adults from National Diet and Nutrition Survey (NDNS) 2008-2014. DESIGN: Cross-sectional analysis using data from 4-d food diaries, blood samples and physical measurements for CVD risk markers. To estimate diet quality, modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS) were applied. Associations of TNS consumption with diet quality and markers of CVD risk were investigated using survey-adjusted multivariable linear regression adjusted for sex, age, ethnicity, socio-economic and smoking status, region of residency and total energy and alcohol intake. SETTING: UK free-living population. SUBJECTS: 4738 adults (≥19 years). RESULTS: TNS consumers had higher modified MDS and HDS relative to non-consumers. TNS consumers also had lower BMI, WC, SBP and DBP and higher HDL compared to non-consumers, although a dose-related fully adjusted significant association between increasing nut intake (g per 4184 kJ/1000 kcal energy intake) and lower marker of CVD risk was only observed for SBP. TNS consumption was also associated with higher intake of total fat, mono-, n-3 and n-6 polyunsaturated fatty acids, fibre, vitamin A, thiamin, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, selenium and iron; and lower intake of saturated fatty acids, trans fatty acids, total carbohydrate, starch, free sugar, sodium and chloride. CONCLUSIONS: TNS consumers report better dietary quality and consumption was associated with lower CVD risk factors. Encouraging replacement of less healthy snacks with TNS should be encouraged as part of general dietary guidelines.

Adherence to UK dietary guidelines is associated with higher dietary intake of total and specific polyphenols compared with a traditional UK diet: further analysis of data from the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach (CRESSIDA) randomised controlled trial.

Adherence to dietary guidelines (DG) may result in higher intake of polyphenols via increased consumption of fruits, vegetables and whole grains. We compared polyphenol dietary intake and urinary excretion between two intervention groups in the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach study: a 12-week parallel-arm, randomised controlled trial (n 161; sixty-four males, ninety-seven females; aged 40-70 years). One group adhered to UK DG, whereas the other group consumed a representative UK diet (control). We estimated polyphenol dietary intake, using a 4-d food diary (4-DFD) and FFQ, and analysed 24-h polyphenol urinary excretion by liquid chromatography-tandem MS on a subset of participants (n 46 control; n 45 DG). A polyphenol food composition database for 4-DFD analysis was generated using Phenol-Explorer and USDA databases. Total polyphenol intake by 4-DFD at endpoint (geometric means with 95 % CI, adjusted for baseline and sex) was significantly higher in the DG group (1279 mg/d per 10 MJ; 1158, 1412) compared with the control group (1084 mg/d per 10 MJ; 980, 1197). The greater total polyphenol intake in the DG group was attributed to higher intake of anthocyanins, proanthocyanidins and hydroxycinnamic acids, with the primary food sources being fruits, cereal products, nuts and seeds. FFQ estimates of flavonoid intake also detected greater intake in DG compared with the control group. 24-h urinary excretion showed consistency with 4-DFD in their ability to discriminate between dietary intervention groups for six out of ten selected, individual polyphenols. In conclusion, following UK DG increased total polyphenol intake by approximately 20 %, but not all polyphenol subclasses corresponded with this finding.

A comparison of heart rate variability, n-3 PUFA status and lipid mediator profile in age- and BMI-matched middle-aged vegans and omnivores.

Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20-C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40-70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference -67 ms; 95 % CI -130, -3·4, P50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.

Modulation of postprandial lipaemia by a single meal containing a commonly consumed interesterified palmitic acid-rich fat blend compared to a non-interesterified equivalent.

PURPOSE: Interesterification of palm stearin and palm kernal (PSt/PK) is widely used by the food industry to create fats with desirable functional characteristics for applications in spreads and bakery products, negating the need for trans fatty acids. Previous studies have reported reduced postprandial lipaemia, an independent risk factor for CVD, following interesterified (IE) palmitic and stearic acid-rich fats that are not currently widely used by the food industry. The current study investigates the effect of the most commonly consumed PSt/PK IE blend on postprandial lipaemia. METHODS: A randomised, controlled, crossover (1 week washout) double-blind design study (n = 12 healthy males, 18-45 years), compared the postprandial (0-4 h) effects of meals containing 50 g fat [PSt/PK (80:20); IE vs. non-IE] on changes in plasma triacylglycerol (TAG), glucose, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), insulin, gastric emptying (paracetamol concentrations) and satiety (visual analogue scales). RESULTS: The postprandial increase in plasma TAG was higher following the IE PSt/PK versus the non-IE PSt/PK, with a 51 % greater incremental area under the curve [mean difference with 95 % CI 41 (23, 58) mmol/L min P = 0.001]. The pattern of lipaemia was different between meals; at 4-h plasma TAG concentrations declined following the IE fat but continued to rise following the non-IE fat. Insulin, glucose, paracetamol, PYY and GIP concentrations increased significantly after the test meals (time effect; P < 0.001 for all), but did not differ between test meals. Feelings of fullness were higher following the non-IE PSt/PK meal (diet effect; P = 0.034). No other significant differences were noted. CONCLUSIONS: Interesterification of PSt/PK increases early phase postprandial lipaemia (0-4 h); however, further investigation during the late postprandial phase (4-8 h) is warranted to determine the rate of return to baseline values. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov as NCT02365987.

Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women.

PURPOSE: Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet). METHODS: A 12-week randomized controlled trial in men and women aged 40-70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density). RESULTS: Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control. CONCLUSIONS: Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at www.isrctn.com as ISRCTN92382106.

Does Intragastric Balloon Treatment for Obesity in Chronic Kidney Disease Heighten Acute Kidney Injury Risk?

BACKGROUND: The outcomes of intragastric balloon (IGB) placement to achieve weight loss in obese patients with chronic kidney disease (CKD) have not been reported to date. This study aimed to assess the safety and efficacy of the IGB as a weight-loss treatment among this patient population. METHODS: A prospective, single-arm, 'first in CKD' interventional study was conducted in patients with a body mass index >35 kg/m2 and CKD stages 3-4, referred for weight loss. After clinical assessment, the IGB was endoscopically inserted into the stomach and kept in place for 6 months. Complications, adverse events, acceptability, weight loss and metabolic responses were monitored over 6 months. RESULTS: Eleven participants were recruited over 18 months. Two patients withdrew (1 prior to IGB insertion and 1 early removal after 3 days due to persistent vomiting) from the study; 9 patients completed the study. There were 5 episodes of acute kidney injury (AKI), occurring in 3 patients. After 6 months, the mean body mass decreased by 9.6% (SD ±6.8). Median waist circumference and total cholesterol decreased significantly (-7.7 cm; interquartile range (IQR) -15.3 to -3.9; and -0.2 mmol/l; IQR -0.6 to -0.05, respectively), with no changes in estimated glomerular filtration rate, blood pressure, triglycerides, adipokines, inflammation, or arterial stiffness measured by carotid-femoral pulse wave velocity. At IGB removal, there was 1 new case each of gastritis and esophagitis. CONCLUSIONS: Treatment with IGB has only moderate efficacy on weight loss; yet it results in a high rate of complications in obese patients with established CKD. The risk of AKI may be raised due to increased risk of dehydration secondary to gastrointestinal symptoms associated with IGB placement and reduced baseline kidney function.

Risk for chronic kidney disease increases with obesity: Health Survey for England 2010.

OBJECTIVE: Studies of the relationship between obesity and chronic kidney disease (CKD) in nationally representative population samples are limited. Our study aimed to determine if overweight and obesity were independently associated with the risk for CKD in the 2010 Health Survey for England (HSE). DESIGN: The HSE is an annually conducted cross-sectional study. In 2010 serum creatinine was included to determine the incidence of CKD in the population. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Multivariable logistic regression models were developed to calculate odds ratios and 95% confidence intervals for CKD risk by BMI (reference category: BMI=18.5-24.9 kg/m2) and adjusted for age, gender, ethnicity, smoking, diabetes and hypertension. SETTING: A random sample of nationally representative households in England. SUBJECTS: Adults (n 3463) with calculable eGFR and BMI were included. RESULTS: The prevalence of CKD was 5.9%. The risk of CKD was over 2.5 times higher in obese participants compared with normal-weight participants in the fully adjusted model (BMI=30.0-39.9 kg/m2: adjusted OR=2.78 (95% CI 1.75, 4.43); BMI ≥ 40.0 kg/m2: adjusted OR=2.68 (95% CI 1.05, 6.85)). CONCLUSIONS: Obesity is associated with an increased risk of CKD in a national sample of the UK population, even after adjustment for known CKD risk factors, which may have implications for CKD screening and future national health service planning and delivery.

Participation in a Structured Weight Loss Program and All-Cause Mortality and Cardiovascular Morbidity in Obese Patients With Chronic Kidney Disease.

OBJECTIVE: To determine if participation in a weight loss program impacted upon a composite end point of all-cause mortality and cardiovascular morbidity in obese patients with chronic kidney disease (CKD). DESIGN: Retrospective cohort study. SUBJECTS: All patients with a body mass index (BMI) >30 kg/m(2) or >28 kg/m(2) with at least 1 comorbidity (hypertension, diabetes, or dyslipidemia) referred to an established weight management program (WMP) from 2005 to 2009 at a metropolitan tertiary teaching hospital were eligible for inclusion in the study cohort. INTERVENTION: Twelve-month structured weight loss program. MAIN OUTCOME MEASURES: Combined outcome of all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure; kidney transplantation waitlisting. RESULTS: A total of 169 obese patients with CKD commenced the WMP and 169 did not-becoming the observational control group (CON). There were no significant differences between groups for age, BMI, sex, ethnicity, smoking, hypertension, or kidney function at baseline, although CON included more patients with diabetes than WMP (49% vs. 38%, P = .03). Kaplan-Meier survival analysis with log-rank test differed between groups for the combined outcome (P = .03). Cox regression analysis with adjustment for age, sex, ethnicity, hypertension, diabetes, kidney function, baseline BMI, and smoking status, indicated that patients in WMP had a significantly longer event-free period for the combined outcome, than those in CON (adjusted hazard ratio 0.53; 95% confidence interval [CI] 0.29-0.97; P = .04). Participation in the WMP did not increase the likelihood of kidney transplantation waitlisting (odds ratio [OR] 1.06; 95% CI 0.39-2.87; P = .9). Lower baseline BMI and greater weight loss over 12 months were the only factors related to kidney transplantation waitlisting (adjusted R(2) = 0.426). CONCLUSIONS: Participation in a structured weight loss program may be associated with improved outcomes in obese patients with CKD.

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation.

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 µl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 µl/cm(2) in 24-well (10 µl) or 96-well (2 µl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy.

Interaction between a CSK gene variant and fish oil intake influences blood pressure in healthy adults.

Blood pressure is a heritable determinant of cardiovascular disease (CVD) risk. Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) associated with blood pressure, including rs1378942 in the c-Src tyrosine kinase (CSK) gene. Fish oil supplementation provides inconsistent protection from CVD, which may reflect genetic variation. We investigated the effect of rs1378942 genotype interaction with fish oil dosage on blood pressure measurements in the MARINA (Modulation of Atherosclerosis Risk by Increasing doses of N-3 fatty Acids) study, a parallel, double-blind, controlled trial in 367 participants randomly assigned to receive treatment with 0.45, 0.9, and 1.8 g/d eicosapentaenoic acid [EPA (20:5n-3)] and docosahexaenoic acid [DHA (22:6n-3)] (1.51:1) or an olive oil placebo for 12 mo. A total of 310 participants were genotyped. There were no significant associations with blood pressure measures at baseline; however, the interaction between genotype and treatment was a significant determinant of systolic blood pressure (SBP) (P = 0.010), diastolic blood pressure (DBP) (P = 0.037), and mean arterial blood pressure (MABP) (P = 0.014). After the 1.8 g/d dose, noncarriers of the rs1378942 variant allele showed significantly lower SBP (P = 0.010), DBP (P = 0.016), and MABP (P = 0.032) at follow-up, adjusted for baseline values, than did carriers. We found no evidence of SNP genotype association with endothelial function (brachial artery diameter and flow-mediated dilatation), arterial stiffness (carotid-femoral pulse wave velocity and digital volume pulse), and resting heart rate. A high intake of EPA and DHA could help protect noncarriers but not carriers of the risk allele. Dietary recommendations to reduce blood pressure in the general population may not necessarily benefit those most at risk. This trial was registered at controlled-trials.com as ISRCTN66664610.

Postprandial lipid and vascular responses following consumption of a commercially-relevant interesterified palmitic acid-rich spread in comparison to functionally-equivalent non-interesterified spread and spreadable butter: a randomised controlled trial in healthy adults.

Background: Interesterification is an industrial processing technique used widely where hard fats are essential for functionality and consumer acceptability, e.g. margarines and lower fat spreads. Objective: The aim of this study was to compare acute cardiovascular effects of functionally equivalent spreads (similar solid fat content) made with interesterified (IE) or non-IE palm-based fats, or spreadable butter. Methods: A randomised, controlled, 4-armed crossover, double-blind study (25 men, 25 women; 35-75 years; healthy; mean BMI 24.5, SD 3.8), compared effects of mixed nutrient meals containing 50 g fat from functionally equivalent products [IE spread, non-IE spread and spreadable butter (SB), with rapeseed oil (RO) as a reference treatment: with 16.7%, 27.9%, 19.3% and 4% palmitic acid, respectively] on 8 h postprandial changes in plasma triacylglycerol (TAG) and endothelial dysfunction (flow-mediated dilatation; FMD). Circulating reactive oxygen species (estimated using a neutrophil oxidative burst assay), glucose, insulin, NEFA, lipoprotein particle profiles, inflammatory markers (glycoprotein acetylation (Glyc-A) and IL-6), and biomarkers of endotoxemia were measured. Results: Postprandial plasma TAG concentrations after test meals were similar. However following RO versus the 3 spreads, there were significantly higher postprandial apolipoprotein B concentrations, and small HDL and LDL particle concentrations, and lower postprandial extra-large, large, and medium HDL particle concentrations, as well as smaller average HDL and LDL particle sizes. There were no differences following IE compared to the other spreads. Postprandial FMD% did not decrease after high-fat test meals, and there were no differences between treatments. Postprandial serum IL-6 increased similarly after test meals, but RO provoked a greater increase in postprandial concentrations of glycoprotein acetyls (GlycA), as well as 8 h sCD14, an endotoxemia marker. All other postprandial outcomes were not different between treatments. Conclusions: In healthy adults, a commercially-available IE-based spread did not evoke a different postprandial triacylglycerol, lipoprotein subclass, oxidative stress, inflammatory or endotoxemic response to functionally-equivalent, but compositionally-distinct alternative spreads. Clinical trial registry number: NCT03438084 (https://ClinicalTrials.gov).

Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial.

Large variability exists in people's responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020-2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41-70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = -0.13 mmol l-1; log-transformed 95% confidence interval = -0.07 to -0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268 .

Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement.

Delta-5 and delta-6 desaturases (D5D and D6D) are key enzymes in endogenous synthesis of long-chain PUFAs. In this sample of healthy subjects (n = 310), genotypes of single nucleotide polymorphisms (SNPs) rs174537, rs174561, and rs3834458 in the FADS1-FADS2 gene cluster were strongly associated with proportions of LC-PUFAs and desaturase activities estimated in plasma and erythrocytes. Minor allele carriage associated with decreased activities of D5D (FADS1) (5.84 × 10(-19) ≤ P ≤ 4.5 × 10(-18)) and D6D (FADS2) (6.05 × 10(-8) ≤ P ≤ 4.20 × 10(-7)) was accompanied by increased substrate and decreased product proportions (0.05 ≤ P ≤ 2.49 × 10(-16)). The significance of haplotype association with D5D activity (P = 2.19 × 10(-17)) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39 × 10(-28)) was much stronger. In a randomized controlled dietary intervention, increasing eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) intake significantly increased D5D (P = 4.0 × 10(-9)) and decreased D6D activity (P = 9.16 × 10(-6)) after doses of 0.45, 0.9, and 1.8 g/day for six months. Interaction of rs174537 genotype with treatment was a determinant of D5D activity estimated in plasma (P = 0.05). In conclusion, different sites at the FADS1-FADS2 locus appear to influence D5D and D6D activity, and rs174537 genotype interacts with dietary EPA+DHA to modulate D5D.

Adiponectin gene variant interacts with fish oil supplementation to influence serum adiponectin in older individuals.

Marine n3 polyunsaturated fatty acids (PUFAs) activate the transcription factor peroxisome proliferator-activated receptor (PPARγ), which modulates the expression of adiponectin. We investigated the interaction of dietary n3 PUFAs with adiponectin gene (ADIPOQ) single nucleotide polymorphism (SNP) genotypes as a determinant of serum adiponectin concentration. The Modulation of Atherosclerosis Risk by Increasing Doses of n3 Fatty Acids study is a parallel design, double-blind, controlled trial. Serum adiponectin was measured in 142 healthy men and 225 women aged 45-70 y randomized to treatment with doses of 0.45, 0.9, and 1.8 g/d 20:5n3 and 22:6n3 (1.51:1), or placebo for 12 mo. The 310 participants who completed the study were genotyped for 5 SNPs at the ADIPOQ locus: -11391 G/A (rs17300539), -11377 C/G (rs266729), -10066 G/A (rs182052), +45 T/G (rs2241766), and +276 G/T (rs1501299). The -11391 A-allele was associated with a higher serum adiponectin concentration at baseline (n = 290; P < 0.001). The interaction between treatment and age as a determinant of adiponectin was significant in participants aged >58 y after the highest dose (n = 92; P = 0.020). The interaction between +45 T/G and treatment and age was a nominally significant determinant of serum adiponectin after adjustment for BMI, gender, and ethnicity (P = 0.029). Individuals homozygous for the +45 T-allele aged >58 y had a 22% increase in serum adiponectin concentration compared with baseline after the highest dose (P-treatment effect = 0.008). If substantiated in a larger sample, a diet high in n3 PUFAs may be recommended for older individuals, especially those of the +45 TT genotype who have reported increased risk of hypoadiponectinemia, type 2 diabetes, and obesity.

Content and Availability of Minerals in Plant-Based Burgers Compared with a Meat Burger.

Increasing numbers of individuals follow plant-based diets. This has sparked interest in the nutritional evaluation of the meat substitute sector. Nutritional understanding of these products is vital as plant-based eating becomes more common. For example, animal products are rich sources of iron and zinc, and plant-based foods could be inadequate in these minerals. The main aim was to analyse the mineral composition and absorption from a range of plant-based meat-free burgers and compare them to a typical beef burger. Total and bioaccessible mineral contents of plant-based burgers and a beef burger were determined using microwave digestion and in vitro simulated gastrointestinal digestion, respectively. Mineral bioavailability was analysed by in vitro simulated gastrointestinal digestion of foods, followed by exposure of Caco-2 cells to the sample digests and assessment of mineral uptake. Mineral quantification for all samples was achieved using inductively coupled ICP-optical emission spectrometry (ICP-OES). The content of minerals varied significantly amongst the burgers. Significantly greater quantities of Fe and Zn were found in the beef burger compared to most meat substitutes. Bioaccessible Fe was significantly higher in the beef compared to most of the plant-based meat alternatives; however, bioavailable Fe of most plant-based burgers was comparable to beef (p > 0.05). Similarly, bioaccessible Zn was significantly (p < 0.001) higher from the beef burger. Moreover, beef was superior regarding bioavailable Zn (p ≤ 0.05-0.0001), with only the mycoprotein burger displaying comparable Zn bioavailability (p > 0.05). Beef is an excellent source of bioaccessible Fe and Zn compared to most plant-based substitutes; however, these plant-based substitutes were superior sources of Ca, Cu, Mg and Mn. The quantity of bioaccessible and absorbable Fe varies dramatically among the meat alternatives. Plant-based burgers have the potential to provide adequate quantities of iron and zinc to those consuming such burgers as part of a varied diet. Thus, guiding consumer choices will depend on the variety of the vegetable constituents and their iron nutritional quality in different burgers.