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In epidemiological studies, dairy food consumption has been associated with minimal effect or decreased risk of some cardiometabolic diseases (CMD). However, current methods of dietary assessment do not provide objective and accurate measures of food intakes. Thus, the identification of valid and reliable biomarkers of dairy product intake is an important challenge to best determine the relationship between dairy consumption and health status. This review investigated potential biomarkers of dairy fat consumption, such as odd-chain, trans- and branched-chain fatty acids (FA), which may improve the assessment of full-fat dairy product consumption. Overall, the current use of serum/plasma FA as biomarkers of dairy fat consumption is mostly based on observational evidence, with a lack of well-controlled, dose–response intervention studies to accurately assess the strength of the relationship. Circulating odd-chain SFA and trans-palmitoleic acid are increasingly studied in relation to CMD risk and seem to be consistently associated with a reduced risk of type 2 diabetes in prospective cohort studies. However, associations with CVD are less clear. Overall, adding less studied FA such as vaccenic and phytanic acids to the current available evidence may provide a more complete assessment of dairy fat intake and minimise potential confounding from endogenous synthesis. Finally, the current evidence base on the direct effect of dairy fatty acids on established biomarkers of CMD risk (e.g. fasting lipid profiles and markers of glycaemic control) mostly derives from cross-sectional, animal and in vitro studies and should be strengthened by well-controlled human intervention studies.

Little is known of the impact of individual saturated fatty acids (SFAs) and their isoenergetic substitution with other SFAs or unsaturated fatty acids (UFAs) on the prevention of cardiometabolic disease (CMD). This systematic literature review (POSPERO registration: CRD42020084241) assessed the impact of such dietary substitutions on a range of fasting CMD risk markers, including lipid profile, markers of glycemic control and inflammation, and metabolic hormone concentrations. Eligible randomized controlled trials (RCTs) investigated the effect of isoenergetic replacements of individual dietary SFAs for at least 14 days on one or more CMD risk markers in humans. Searches of PubMed, Embase, Scopus and Cochrane CENTRAL databases on 14th February 2021 identified 44 RCTs conducted in participants aged 39.9y (SD 15.2). Studies' risk of bias was assessed using the Cochrane Risk of Bias tool 2.0 for RCTs. Random-effect meta-analyses assessed the effect of at least three similar dietary substitutions on the same CMD risk marker. Other dietary interventions were described in qualitative syntheses. We observed reductions in low-density lipoprotein cholesterol concentrations after the replacement of palmitic acid (C16:0) with UFA (-0.36 mmol/L, 95%CI [-0.50, -0.21], I2 = 96.0%, n = 18 RCTs) or oleic acid (C18:1) (-0.16 mmol/L, 95% CI [-0.28, -0.03], I2 = 89.6%, n = 9 RCTs), with a similar impact on total cholesterol and apolipoprotein B concentrations. No effects on other CMD risk markers, including high-density lipoprotein cholesterol, triacylglycerol, glucose, insulin, or C-reactive protein concentrations, were evident. Similarly, we found no evidence of a benefit from replacing dietary stearic acid with UFA on CMD risk markers (n = 4 RCTs). In conclusion, the impact of replacing dietary palmitic acid with UFA on lipid biomarkers is aligned with current public health recommendations. However, due to the high heterogeneity and limited studies, relationships between all individual SFAs and biomarkers of cardiometabolic health need further confirmation from RCTs.

Background: Chronic consumption of dairy products with a saturated fatty acid (SFA)-reduced, monounsaturated fatty acid (MUFA)-enriched content was shown to impact favourably on brachial artery flow-mediated dilatation (FMD). However, their acute effect on postprandial cardiometabolic risk biomarkers requires investigation.\ud \ud Objective: The effects of sequential high-fat mixed meals rich in fatty acid (FA)-modified or conventional (control) dairy products on postprandial FMD (primary outcome) and systemic cardiometabolic biomarkers in adults with moderate cardiovascular risk (≥50% above population mean) were compared. \ud \ud Methods: In a randomized cross-over trial, fifty-two participants (mean ± SEM age 53 ± 2 y; BMI 25.9 ± 0.5 kg/m2) consumed high-dairy fat breakfast (0 min; ~50 g total fat: Modified: 25 g SFAs, 20 g MUFAs; Control: 32 g SFAs, 12 g MUFAs) and lunch (330 min; ~30 g total fat; Modified: 15 g SFAs, 12 g MUFAs; Control: 19 g SFAs, 7 g MUFAs). Blood samples were obtained before and until 480 min after breakfast, with FMD assessed at 0, 180, 300 and 420 min. Data were analysed by linear mixed models.\ud Results: Postprandial changes in cardiometabolic biomarkers were comparable between the different dairy meals, with the exception of a tendency for a 4% higher area under the curve (AUC) for the %FMD response following the modified dairy fat meals (P = 0.075). Plasma total lipid FA analysis revealed that incremental AUC responses were 53% lower for total SFAs, 214% and 258% higher for total cis-MUFAs (predominantly cis-9 18:1), and trans-18:1 respectively following the modified, relative to control dairy meals (all P < 0.0001). \ud \ud Conclusions: In adults at moderate cardiovascular risk, acute consumption of sequential high-fat meals containing FA-modified dairy products had little impact on postprandial endothelial function or systemic cardiometabolic biomarkers, but a differential effect on the plasma total lipid FA profile, relative to conventional dairy fat meals.

Body mass index (BMI) has been suggested to play an important role in the relationship between the

Background: Previous acute studies suggest the Glu298Asp polymorphism (rs1799983) may influence vascular reactivity in response to long-chain n-3 polyunsaturated fat (PUFA) intake. However, the effects of this genotype on postprandial vascular function following meals rich in saturated (SFA), n-6 PUFA and monounsaturated (MUFA) fats are unclear. Objective: This study determined the impact of the Glu298Asp polymorphism on changes in vascular function and cardiometabolic risk biomarkers in response to sequential meals of varying fat composition. Methods: In a randomized, double-blind, cross-over, acute study, 32 postmenopausal women (mean±SD age 58±5 y; BMI 25.9±4.1 kg/m2) consumed mixed meals (breakfast: 0 min, 50 g fat; lunch: 330 min, 30 g fat) containing SFA, n-6 PUFA or MUFA on 3 occasions. Blood samples for cardiometabolic disease risk markers and real-time measures of vascular reactivity (including flow-mediated dilatation (FMD, primary outcome)) were collected/performed before and regularly for 480 min after breakfast. Participants were retrospectively genotyped for the Glu298Asp (rs1799983) polymorphism. Data were analysed using linear mixed models. Results: For the postprandial %FMD response, a test fat x genotype interaction was observed for the area under the curve (AUC; P=0.019) but not incremental AUC, with the AUC being ~24% greater after MUFA than SFA and n-6 PUFA-rich meals in the Glu298 homozygotes (P≤0.026). Test fat x genotype interactions were also evident for postprandial insulin (P≤0.005), with the MUFA-rich meals demonstrating significantly higher AUC (12.8%/14.9%), incremental AUC (14.6%/20.0%) and maximum concentration (20.0%/34.5%) versus the SFA and n-6 PUFA-rich meals (respectively) in Asp298 carriers (P

There is increasing evidence for the health benefits of dietary nitrates including lowering blood pressure and enhancing cardiovascular health. Although commensal oral bacteria play an important role in converting dietary nitrate to nitrite, very little is known about the potential role of these bacteria in blood pressure regulation and maintenance of vascular tone. The main purpose of this review is to present the current evidence on the involvement of the oral microbiome in mediating the beneficial effects of dietary nitrate on vascular function and to identify sources of inter-individual differences in bacterial composition. A systematic approach was used to identify the relevant articles published on PubMed and Web of Science in English from January 1950 until September 2019 examining the effects of dietary nitrate on oral microbiome composition and association with blood pressure and vascular tone. To date, only a limited number of studies have been conducted, with nine in human subjects and three in animals focusing mainly on blood pressure. In general, elimination of oral bacteria with use of a chlorhexidine-based antiseptic mouthwash reduced the conversion of nitrate to nitrite and was accompanied in some studies by an increase in blood pressure in normotensive subjects. In conclusion, our findings suggest that oral bacteria may play an important role in mediating the beneficial effects of nitrate-rich foods on blood pressure. Further human intervention studies assessing the potential effects of dietary nitrate on oral bacteria composition and relationship to real-time measures of vascular function are needed, particularly in individuals with hypertension and those at risk of developing CVD.

Scope Dietary fat composition is an important modulator of vascular function. Non-esterified fatty acids (NEFA) enriched in saturated fatty acids (SFA) are thought to reduce vascular reactivity by attenuating insulin signalling via vasodilator pathways (phosphoinositide 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS)) and enhancing signalling via pro-inflammatory pathways. Methods To examine the effects of fatty acids on these pathways, human aortic endothelial cells were incubated with single fatty acids, and mixtures of these fatty acids to mimic typical NEFA composition and concentrations achieved in our previous human study. RNA was extracted to determine gene expression using real-time RT-PCR and cell lysates prepared to assess protein phosphorylation by Western blotting. Results Oleic acid (OA, 100 µM) was shown to down regulate expression of the insulin receptor, PTEN and a PI3K catalytic (p110β) and regulatory (p85α) subunit compared to palmitic, linoleic and stearic acids (P 1177. Both concentration and composition of the SFA and SFA plus n-3 polyunsaturated fatty acids (PUFA) mixtures had significant effects on genes involved in the PI3K/Akt pathway. Greater up-regulation was found with 800 than 400 µM concentration (respective of concentrations in insulin resistant and normal individuals), whereas greater down-regulation was evident with SFA plus n-3 PUFA than SFA mixture alone. Conclusion Our findings provide novel insights into the modulation of the PI3K/Akt/eNOS pathway by single fatty acids and fatty acid mixtures. In particular, OA appears to promote signalling via this pathway, with further work required to determine the primary molecular site(s) of action.

Cardiovascular diseases (CVD) are a significant and growing burden on global health services, and it is now accepted that impairment of vascular function represents a major preliminary step in the development of CVD. There is considerable interest in identifying both causal factors of impaired vascular function, as well as related nutritional factors that may lower the risk of developing CVD, and food-derived bioactive peptides and amino acids have emerged as one such area. Dairy foods contain two groups of proteins, whey proteins and caseins, which represent a rich source of bioactive peptides that are released during food processing and/or digestion. These peptides have a number of physiological activities including the potential to reduce blood pressure. Research, including acute and longer-term randomised controlled trials, animal models and in vitro models has demonstrated the potential impact of dairy proteins on vascular function. The purpose of this paper is to narratively review the evidence, primarily from randomised controlled trials, examining the effects of whey proteins, their peptides and amino acids on vascular function and related issues including blood pressure. In addition, it will explore the potential underlying mechanisms responsible for these effects. It concludes that there is increasing evidence that whey proteins, and notably the bioactive peptides and amino acids released during their digestion, can have beneficial effects on aspects of vascular function and thus contribute to CVD risk reduction. It also highlights a number of beneficial effects of whey proteins including those on blood pressure, arterial stiffness, nitric oxide production and inflammation.

Background: Longer-term consumption of saturated fatty acid (SFA)-reduced, monounsaturated fatty acid (MUFA)-enriched dairy products have been reported to improve fasting flow-mediated vasodilation (FMD). Yet, their impact on endothelial function in the postprandial state warrants investigation. \ud Objective: To compare the impact of a fatty acid (FA)-modified with a conventional (control) dairy diet on the postprandial %FMD (primary outcome) and systemic cardiometabolic responses to representative meals, and retrospectively explore whether treatment effects differ by apolipoprotein (APO)E or endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphisms. \ud Methods: In a crossover-design randomized controlled study, 52 adults with moderate cardiovascular disease risk consumed dairy products [38% total energy intake (%TE) from fat: FA-modified (target: 16%TE SFAs; 14%TE MUFAs) or control (19%TE SFAs; 11%TE MUFAs)] for 12-wk, separated by an 8-wk washout. Blood sampling and FMD measurements (0-480 min) were performed pre- and post-intervention after sequential mixed meals that were representative of the assigned dairy diets (0 min; ~50 g fat; 330 min; ~30 g fat).\ud Results: Relative to pre-intervention (∆), the FA-modified dairy diet and meals (treatment) attenuated the increase in the incremental AUC (iAUC), but not AUC, for the %FMD response observed with the conventional treatment (-135 ± 69 vs +199 ± 82 % x min; P = 0.005). The ∆ iAUC, but not AUC, for the apoB response decreased after FA-modified yet increased after the conventional treatment (-4 ± 3 vs +3 ± 3 mg/mL x min; P = 0.004). The ∆ iAUC decreased for total plasma SFAs (P = 0.003) and trans 18:1 (P < 0.0001) and increased for cis-MUFAs (P < 0.0001) following conventional, relative to the FA-modified treatment. No treatment x APOE- or eNOS-genotype interactions were evident for any outcome. \ud Conclusions: This study provides novel insights into the longer-term effects of FA-modified dairy food consumption on postprandial cardiometabolic responses.

In France, dairy products contribute to dietary saturated fat intake, of which reduced consumption is often recommended for CVD prevention. Epidemiological evidence on the association between dairy consumption and CVD risk remains unclear, suggesting either null or inverse associations. This study aimed to investigate the associations between dairy consumption (overall and specific foods) and CVD risk in a large cohort of French adults. This prospective analysis included participants aged ≥18 years from the NutriNet-Santé cohort (2009–2019). Daily dietary intakes were collected using 24-h dietary records. Total dairy, milk, cheese, yogurts, fermented and reduced-fat dairy intakes were investigated. CVD cases (n 1952) included cerebrovascular disease (n 878 cases) and CHD (n 1219 cases). Multivariable Cox models were performed to investigate associations. This analysis included 104 805 French adults (mean age at baseline 42·8 (sd 14·6) years, mean follow-up 5·5 (sd 3·0) years, i.e. 579 155 person-years). There were no significant associations between dairy intakes and total CVD or CHD risks. However, the consumption of at least 160 g/d of fermented dairy (e.g. cheese and yogurts) was associated with a reduced risk of cerebrovascular diseases compared with intakes below 57 g/d (hazard ratio = 0·81 (95 % CI 0·66, 0·98), Ptrend = 0·01). Despite being a major dietary source of saturated fats, dairy consumption was not associated with CVD or CHD risks in this study. However, fermented dairy was associated with a lower cerebrovascular disease risk. Robust randomised controlled trials are needed to further assess the impact of consuming different dairy foods on CVD risk and potential underlying mechanisms.

Background: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. Methods: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Results: Sixty-nine lipids associated (false discovery rate Conclusions: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.

Background: Modifying dairy fat composition by increasing the MUFA content is a potential strategy to reduce dietary SFA intake for cardiovascular disease (CVD) prevention in the population.Objectives: To determine the effects of consuming SFA-reduced, MUFA-enriched (modified) dairy products, compared with conventional dairy products (control), on the fasting cholesterol profile (primary outcome), endothelial function assessed by flow-mediated dilatation (FMD; key secondary outcome), and other cardiometabolic risk markers.Methods: A double-blind, randomized, controlled crossover 12-wk intervention was conducted. Participants with a 1.5-fold higher (moderate) CVD risk than the population mean replaced habitual dairy products with study products (milk, cheese, and butter) to achieve a high-fat, high-dairy isoenergetic daily dietary exchange [38% of total energy intake (%TE) from fat: control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA) diet].Results: Fifty-four participants (57.4% men; mean ± SEM age: 52 ± 3 y; BMI: 25.8 ± 0.5 kg/m2) completed the study. The modified diet attenuated the rise in fasting LDL cholesterol observed with the control diet (0.03 ± 0.06 mmol/L and 0.19 ± 0.05 mmol/L, respectively; P = 0.03). Relative to baseline, the %FMD response increased after the modified diet (0.35% ± 0.15%), whereas a decrease was observed after the control diet (−0.51% ± 0.15%; P < 0.0001). In addition, fasting plasma nitrite concentrations increased after the modified diet, yet decreased after the control diet (0.02 ± 0.01 μmol/L and −0.03 ± 0.02 μmol/L, respectively; P = 0.01).Conclusions: In adults at moderate CVD risk, consumption of a high-fat diet containing SFA-reduced, MUFA-enriched dairy products for 12 wk showed beneficial effects on fasting LDL cholesterol and endothelial function compared with conventional dairy products. Our findings indicate that fatty acid modification of dairy products may have potential as a public health strategy aimed at CVD risk reduction. This trial was registered at clinicaltrials.gov as NCT02089035. Am J Clin Nutr 2020;00:1–10.

Scope: Fructose exacerbates post-prandial hypertriacylglycerolaemia. This may be partly due to increased enterocyte de novo lipogenesis (DNL). It is unknown whether this is concentration-dependent or whether fructose has a greater effect on lipid synthesis than glucose. The dose-dependent effects of fructose and glucose on DNL and de novo triacylglycerol (TAG)-glycerol synthesis were investigated in an enterocyte model, Caco-2 cells. Methods and results: Caco-2 cells were treated for 96h with 5mM, 25mM or 50mM fructose or glucose, or 12.5mM fructose/12.5mM glucose mix. DNL was measured following addition of [13C2]-acetate to apical media. In separate experiments, [13C6]-fructose and [13C6]-glucose were used to measure DNL and de novo TAG-glycerol synthesis. DNL from [13C2]-acetate was detected following all treatments, with greater amounts in intracellular than secreted (media) samples (all P

The renin–angiotensin system (RAS) is a key regulator of blood pressure and hypertension. Angiotensin-converting enzyme 2 (ACE2) and angiotensin-converting enzyme I (ACE) are two main components of the RAS that play a major role in blood pressure homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 as a receptor to enter cells. Despite some controversies, numerous studies have reported a significant association between the use of ACE inhibitors and reduced risk of COVID-19. In our previous studies, we produced and identified peptide sequences present in whey hydrolysates exhibiting high ACE inhibitory activity. Therefore, the aim of this work is to obtain an improved understanding of the function of these natural peptides as RAS inhibitors and investigate their potential therapeutic role in the COVID-19 pandemic. The molecular interactions between peptides IPP, LIVTQ, IIAE, LVYPFP, and human ACE2 were assessed by employing a molecular docking approach. The results show that natural whey-derived peptides have a dual inhibitory action against both ACE and ACE2. This dual activity distinguishes these ACE inhibitory peptides from synthetic drugs, such as Captopril and Lisinopril which were not shown to inhibit ACE2 activity, and may represent a potential strategy in the treatment of COVID-19.

OBJECTIVES: To investigate the relationship between dietary nitrate consumption from vegetables (root and green leafy varieties), drinking water and cured meat, and cardiovascular disease (CVD) risk factors in a representative UK population, and determine whether the source (vegetables vs cured meats) impacts on these relationships. METHODS: For this analysis, we used data from the UK cross-sectional National Diet and Nutrition Survey (NDNS) years 1–8, which included 3407 men and women aged 19–64 y. Since data available on dietary analysis software for nitrate levels in vegetables and vegetable-based foods is very limited, a comprehensive database was first developed to evaluate the nitrate and nitrite levels in water, vegetables, cured meats and composite dishes to more accurately estimate the dietary nitrate intakes of the participants. The population was then classified into quartiles based on increasing daily nitrate intakes from vegetables (including drinking water) and meats. ANCOVA analysis determined the relationship between the level of nitrate intake from each dietary source with available data on biomarkers of CVD risk (BP, lipid profile, C-reactive protein (CRP), anthropometric measures and glycaemic control). RESULTS: Across increasing quartiles of dietary nitrate intake from vegetables, there were significant differences in systolic (P = 0.038) and diastolic (P = 0.014) BP, with significantly lower BP in Q3 than all other quartiles. Furthermore, nitrate intake from vegetables was significantly associated with lower glucose, glycated haemoglobin, CRP and total cholesterol concentrations in Q4 compare to Q1 (p = 0.046, p = 0.01, p = 0.03 and p = 0.04) respectively. In contrast, there were no changes in CVD markers including BP across quartiles of nitrate from meats. CONCLUSIONS: Our findings suggest the source of dietary nitrate may play an important role in determining the relationship with BP, with an intake of between 95–130 mg/day from vegetables and drinking water associated with a lower BP. FUNDING SOURCES: Hayat was supported by King Saud University (Saudi Arabia).

Lactating cow diets were supplemented with high oleic acid sunflower oil over two production periods spanning two years, to modify the milk fat, partially replacing saturated fatty acids (SFA) with cis-monounsaturated fatty acids (MUFA). The resulting milk was used for ultra-high temperature (UHT) milk, butter and Cheddar cheese production, and fatty acid profiles were compared with those of conventionally-produced products. Fat from products made with modified milk had lower SFA and higher cis- and trans-MUFA concentrations than that of conventional products. This was consistent over production periods, demonstrating that this food chain approach could be adopted on a wider scale.

A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (&lt, 2% energy) for 11 h. Oral 2H2O was administered to measure fasting and postprandial DNL. Postprandial chylomicron (CM)-TAG and very low-density lipoprotein (VLDL)-TAG kinetics were measured with an intravenous bolus of [2H5]-glycerol. CM and VLDL were separated by their apolipoprotein B content using antibodies. Plasma TAG (p &lt, 0.005) and VLDL-TAG (p = 0.003) were greater, and CM-TAG production rate (PR, p = 0.046) and CM-TAG fractional catabolic rate (FCR, p = 0.073) lower when high-fructose was consumed, with no differences in VLDL-TAG kinetics. Insulin was lower (p = 0.005) and apoB48 (p = 0.039), apoB100 (p = 0.013) and non-esterified fatty acids (NEFA) (p = 0.013) were higher after high-fructose. Postprandial hepatic fractional DNL was higher than intestinal fractional DNL with high-fructose (p = 0.043) and low-fructose (p = 0.043). Fructose consumption had no effect on the rate of intestinal or hepatic DNL. We provide the first measurement of the rate of intestinal DNL in humans. Lower CM-TAG PR and CM-TAG FCR with high-fructose consumption suggests lower clearance of CM, rather than elevated production, may contribute to elevated plasma TAG, possibly due to lower insulin-mediated stimulation of lipoprotein lipase.

Background:Diets higher in fibre have been associated with beneficial effects on cardiometabolic disease (CMD) risk markers including obesity, blood pressure and cholesterol levels. However, the relationship between dietary fibre intake and body composition is unclear. Therefore, the objective of the study was to further assess the association between fibre intake, body composition and CMD risk markers.Materials and Methods:A single-centred cross-sectional study was conducted in 277 healthy adults (n = 107 men and n = 170) women with a mean age of 41 (SD 16) y and body mass index (BMI) of 23.9 (SD 3.8) kg/m2. Total body composition was measured by dual energy x-ray absorptiometry and dietary intake was assessed with a 4-day weighed food diary.CMD risk markers included fasting lipids and glucose quantified using an ILAB 600 clinical chemistry analyser and clinic blood pressure measured using an Omron blood pressure monitor.Results:Average AOAC fibre intake in the cohort was 23.0 (SD 9) g/day, with higher intakes found in men (25.0 (SD 10.3) g/day) than women (21.9 (SD 7.8) g/day; P = 0.015). AOAC fibre intakes were significantly weakly correlated with weight (rs = 0.142), percentage body fat (rs = 0.193), bone mineral density (rs = 0.156) and fat free mass (rs = 0.257; P ≤ 0.009), and inversely correlated with fasting total cholesterol (rs = -0.124), low-density lipoprotein (LDL)-cholesterol (rs = 0.144) and total to high-density lipoprotein-cholesterol ratio (rs = -0.129; P ≤ 0.042). After stratifying data according to quartiles of AOAC fibre intake and adjusting for covariates (including age, sex, BMI, weight, energy expended per day through physical activity and total energy intake per day) total and LDL-cholesterol concentrations were significantly lower in quartiles (Q)3 (21.0–29.5 g/d) and Q4 (30–63.5 g/d) than Q1 (3.0–18.8 g/d) and Q2 (19.3–20.9 g/d). Systolic blood pressure was also lower in Q4 than Q1 and Q2 (P < 0.05). Anthropometric and body composition measures were not found to be different across quartiles of increasing AOAC fibre intake.Discussion:Findings from this cross-sectional study have revealed daily fibre consumption greater than 21 g to be associated with lower fasting total and LDL cholesterol, and intakes ≥ 30 g also associated with lower systolic blood pressure. With only 9% of UK adults meeting the current recommended intake, raising public awareness of the importance of dietary fibre is an important strategy for CMD prevention.

Dietary inorganic nitrate has been shown to lower blood pressure (BP) and improve endothelial function(1). The main sources of dietary nitrate are vegetables (root and green leafy varieties) as well as drinking water but data available on dietary analysis software on nitrate levels in vegetables and vegetable-based foods is very limited. To date, very few studies have investigated the relationship between the level of consumption of dietary nitrate on BP and other cardiovascular disease (CVD) risk factors in a representative UK population. The aim of the study was to address this knowledge gap using data from the National Diet and Nutrition Survey (NDNS) years 1–8, a cross-sectional study conducted in 3339 men and women aged 19–64 y between 2008/09–2011/12. A comprehensive database was first developed to evaluate the nitrate and nitrite levels in vegetables, cured meats and composite dishes to more accurately estimate the dietary nitrate intakes of the NDNS participants. The population was then classified into quartiles of daily nitrate intake, with quartile 1 (Q1: 26–106 mg/d) and quartile 4 (Q4: 183–559 mg/d) representing diets with the lowest and highest intakes, respectively. ANCOVA analysis was performed to determine the relationship between the level of daily nitrate intake with available data on biomarkers of CVD risk (including BP (systolic, diastolic and pulse pressure), lipid profile, (total, high-density lipoprotein and low-density lipoprotein (LDL-C) cholesterol), C-reactive protein, anthropometric measures (body mass index and waist to hip ratio) and glycaemic control (glucose and glycated haemoglobin). There were significant differences in systolic (P-trend = 0.008) and diastolic (P-trend = 0.025) BP across increasing quartiles of dietary nitrate intake, with BP significantly lower in Q3 than all other quartiles. Pulse pressure (calculated as systolic–diastolic BP) was also found to be significantly different across quartiles (P-trend = 0.001), with diets of participants in Q3 and Q4 being associated with significantly lower pulse pressures than those in Q1 (P-Q1 vs. Q3 = 0.005, P-Q1 vs. Q4 = 0.007). All of the other CVD risk markers were not different between quartile groups. Our preliminary results suggest that the level of dietary nitrate intake may be significantly associated with BP, a key independent CVD risk factor. There is an urgent need to more accurately estimate the dietary nitrate intake in the UK population and to determine whether the source of dietary nitrate (vegetables vs cured meats) impacts on the significant relationship with BP.

Endothelial progenitor cells (EPCs) and microparticles are emerging as novel markers of cardiovascular disease (CVD) risk, which could potentially be modified by dietary fat. We have previously shown that replacing dietary saturated fatty acids (SFAs) with monounsaturated or n-6 (ω-6) polyunsaturated fatty acids (MUFAs or PUFAs, respectively) improved lipid biomarkers, blood pressure, and markers of endothelial activation, but their effects on circulating EPCs and microparticles are unclear.The Dietary Intervention and VAScular function (DIVAS) Study investigated the replacement of 9.5-9.6% of total energy (%TE) contributed by SFAs with MUFAs or n-6 PUFAs for 16 wk on EPC and microparticle numbers in United Kingdom adults with moderate CVD risk.In this randomized, controlled, single-blind, parallel-group dietary intervention, men and women aged 21-60 y (n = 190) with moderate CVD risk (≥50% above the population mean) consumed 1 of three 16-wk isoenergetic diets. Target compositions for total fat, SFAs, MUFAs, and n-6 PUFAs (%TE) were as follows: SFA-rich diet (36:17:11:4; n = 64), MUFA-rich diet (36:9:19:4; n = 62), and n-6 PUFA-rich diet (36:9:13:10; n = 66). Circulating EPC, endothelial microparticle (EMP), and platelet microparticle (PMP) numbers were analyzed by flow cytometry. Dietary intake, vascular function, and other cardiometabolic risk factors were determined at baseline.Relative to the SFA-rich diet, MUFA- and n-6 PUFA-rich diets decreased EMP (-47.3%, -44.9%) respectively and PMP (-36.8%, -39.1%) numbers (overall diet effects, P 0.01). The MUFA-rich diet increased EPC numbers (+28.4%; P = 0.023). Additional analyses that used stepwise regression models identified the augmentation index (measuring arterial stiffness determined by pulse-wave analysis) as an independent predictor of baseline EPC and microparticle numbers.Replacement of 9.5-9.6%TE dietary SFAs with MUFAs increased EPC numbers, and replacement with either MUFAs or n-6 PUFAs decreased microparticle numbers, suggesting beneficial effects on endothelial repair and maintenance. Further studies are warranted to determine the mechanisms underlying the favorable effects on EPC and microparticle numbers after SFA replacement. This trial was registered at www.clinicaltrials.gov as NCT01478958.

CVD are the leading cause of death in women globally, with ageing associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting TAG concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in SFA and MUFA are often associated with greater postprandial TAG responses compared with those containingn-6 PUFA, but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. The present review aimed to evaluate the acute effects of test meals rich in SFA, MUFA andn-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic search of the literature identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described in three papers. An additional study determined the impact of a high-fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high-fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk.

Background Elevated postprandial triacylglycerol concentrations, impaired vascular function, and hypertension are important independent cardiovascular disease (CVD) risk factors in women. However, the effects of meal fat composition on postprandial lipemia and vascular function in postmenopausal women are unknown. Objective This study investigated the impact of sequential meals rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on postprandial flow-mediated dilatation (FMD; primary outcome measure), vascular function, and associated CVD risk biomarkers (secondary outcomes) in postmenopausal women. Methods A double-blind, randomized, crossover, postprandial study was conducted in 32 postmenopausal women [mean ± SEM ages: 58 ± 1 y; mean ± SEM body mass index (in kg/m2): 25.9 ± 0.7]. After fasting overnight, participants consumed high-fat meals at breakfast (0 min; 50 g fat, containing 33-36 g SFAs, MUFAs, or n-6 PUFAs) and lunch (330 min; 30 g fat, containing 19-20 g SFAs, MUFAs, or n-6 PUFAs), on separate occasions. Blood samples were collected before breakfast and regularly after the meals for 480 min, with specific time points selected for measuring vascular function and blood pressure. Results Postprandial FMD, laser Doppler imaging, and digital volume pulse responses were not different after consuming the test fats. The incremental area under the curve (iAUC) for diastolic blood pressure was lower after the MUFA-rich meals than after the SFA-rich meals (mean ± SEM: -2.3 ± 0.3 compared with -1.5 ± 0.3 mm Hg × 450 min × 103; P = 0.009), with a similar trend for systolic blood pressure (P = 0.012). This corresponded to a lower iAUC for the plasma nitrite response after the SFA-rich meals than after the MUFA-rich meals (-1.23 ± 0.7 compared with -0.17 ± 0.4 μmol/L × 420 min P = 0.010). The soluble intercellular adhesion molecule 1 (sICAM-1) time-course profile, AUC, and iAUC were lower after the n-6 PUFA-rich meals than after the SFA- and MUFA-rich meals (P ≤ 0.001). Lipids, glucose, and markers of insulin sensitivity did not differ between the test fats. Conclusion Our study showed a differential impact of meal fat composition on blood pressure, plasma nitrite, and sICAM-1, but no effect on postprandial FMD or lipemia in postmenopausal women. This trial was registered at www.clinicaltrials.gov as NCT02144454.

Specific flavonoid-rich foods/beverages are reported to exert positive effects on vascular function; however, data relating to effects in the postprandial state are limited. The present study investigated the postprandial, time-dependent (0–7 h) impact of citrus flavanone intake on vascular function. An acute, randomised, controlled, double-masked, cross-over intervention study was conducted by including middle-aged healthy men (30–65 years, n 28) to assess the impact of flavanone intake (orange juice: 128·9 mg; flavanone-rich orange juice: 272·1 mg; homogenised whole orange: 452·8 mg; isoenergetic control: 0 mg flavanones) on postprandial (double meal delivering a total of 81 g of fat) endothelial function. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at 0, 2, 5 and 7 h. Plasma levels of naringenin/hesperetin metabolites (sulphates and glucuronides) and nitric oxide species were also measured. All flavanone interventions were effective at attenuating transient impairments in FMD induced by the double meal (7 h post intake; P

Apolipoprotein (APO) E (&epsilon, ) genotype is considered to play an important role in lipid responses to dietary fat manipulation but the impact on novel cardiometabolic risk markers is unclear. To address this knowledge gap, we investigated the relationship between the APOE genotype and cardiometabolic risk markers in response to acute and chronic dietary fat intakes. Associations with fasting (baseline) outcome measures (n = 218) were determined using data from the chronic DIVAS (n = 191/195 adults at moderate cardiovascular disease risk) and acute DIVAS-2 (n = 27/32 postmenopausal women) studies examining the effects of diets/meals varying in saturated, polyunsaturated and monounsaturated (MUFA) fatty acid composition. Participants were retrospectively genotyped for APOE (rs429358, rs7412). For baseline cardiometabolic outcomes, E4 carriers had higher fasting total and low-density lipoprotein-cholesterol (LDL-C), total cholesterol: high-density lipoprotein-cholesterol (HDL-C) and LDL-C: HDL-C ratios, but lower C-reactive protein (CRP) than E3/E3 and E2 carriers (p &le, 0.003). Digital volume pulse stiffness index was higher in E2 carriers than the E3/E3 group (p = 0.011). Following chronic dietary fat intake, the significant diet &times, genotype interaction was found for fasting triacylglycerol (p = 0.010), with indication of a differential responsiveness to MUFA intake between the E3/E3 and E4 carriers (p = 0.006). Test fat &times, genotype interactions were observed for the incremental area under the curve for the postprandial apolipoprotein B (apoB, p = 0.022) and digital volume pulse reflection index (DVP-RI, p = 0.030) responses after the MUFA-rich meals, with a reduction in E4 carriers and increase in the E3/E3 group for the apoB response, but an increase in E4 carriers and decrease in the E3/E3 group for the DVP-RI response. In conclusion, baseline associations between the APOE genotype and fasting lipids and CRP confirm previous findings, although a novel interaction with digital volume pulse arterial stiffness was observed in the fasted state and differential postprandial apoB and DVP-RI responses after the MUFA-rich meals. The reported differential impact of the APOE genotype on cardiometabolic markers in the acute and chronic state requires confirmation.

Background: Prospective cohort studies show that higher dietary fiber intake is associated with reduced cardiovascular disease risk, yet the impact on postprandial glucose and insulin responses is unclear. Objective: This study aims to evaluate the effects of orange beverages with differing fiber concentrations on postprandial glycemic responses (secondary outcome measure) after a sequential breakfast and lunch challenge in men with increased cardiometabolic risk. Methods: Thirty-six men (aged 30–65 y; body mass index 25–30 kg/m2: fasting triacylglycerol or total cholesterol concentrations: 0.8–2.2 or 6.0–8.0 mmol/L, respectively) were provided with a high-fat mixed breakfast and were randomly assigned to consume 240 mL Tropicana (PepsiCo, Inc.) pure premium orange juice without pulp (OJ), OJ with 5.5 g added orange pomace fiber (OPF), juice made from lightly blended whole orange, or an isocaloric sugar-matched control (Control) on 4 occasions separated by 2 wk. A medium-fat mixed lunch was provided at 330 min. Blood samples were collected before breakfast and on 11 subsequent occasions for 420 min (3 time points postlunch) to determine postprandial glucose, insulin, lipid, and inflammatory biomarker responses. Repeated-measures ANOVA was used for data analysis. Results: OPF significantly (P < 0.05) reduced the maximal change in glucose concentrations (1.9 6 0.21 mmol/L) reached after breakfast compared with other treatments (2.3–2.4 mmol/L) and after lunch (3.0 6 0.05 mmol/L) compared with OJ (3.6 6 0.05 mmol/L). The maximal change in insulin concentration (313 6 25 pmol/L) was also lower compared with Control (387 6 30 pmol/L) and OJ (418 6 39 pmol/L) after breakfast. OPF significantly delayed the time to reach the peak glucose concentration compared with Control and OJ, and of insulin compared with Control after breakfast. Conclusion: OPF consumed with breakfast may lower postprandial glycemic and insulinemic responses to typical meal ingestion in men with increased cardiometabolic risk. This trial is registered at clinicaltrials.gov as NCT01963416.

The Hugh Sinclair Unit of Human Nutrition (HSUHN) at the University of Reading was founded in October 1995 with the appointment of Christine Williams OBE as the first Hugh Sinclair Chair in Human Nutrition. This was made possible by the competitively won funds from the estate and legacy of the late Professor Hugh Macdonald Sinclair (1910–1990). The vision for the newly established HSUHN was to ‘strengthen the evidence base for dietary recommendations for prevention of degenerative chronic diseases’. This has remained the research focus of the HSUHN under the leadership of Professors Christine Williams (1995–2005), Ian Rowland (2006–2013) and Julie Lovegrove (2014-present). Our mission is to improve population health and evaluate mechanisms of action for the effects of dietary components on health, which reflects Hugh Sinclair’s life ambition within nutritional science. Over the past 20 years, the HSUHN has developed an international reputation within the nutrition science community, and in recognition of the 20th anniversary, this paper highlights Hugh Sinclair’s contributions to the field of nutrition and key research achievements by members of the Unit.

Background: One strategy for improving population vitamin D status is consumption of fortified foods. However, the\ud effects of dairy products fortified with different vitamin D isoforms on postprandial vitamin D status and metabolic\ud outcomes have not been addressed.\ud Objective: We investigated whether consumption of dairy drinks fortified with either 25-hydroxycholecalciferol [25(OH)D3] or\ud cholecalciferol (vitamin D3) had differential effects on 24-h circulating plasma 25(OH)D3 concentration (a marker of vitamin\ud D status) and cardiometabolic risk markers.\ud Methods: A randomized, controlled, 3-way crossover, double-blind, postprandial study was conducted in 17 men with\ud suboptimal vitamin D status [mean 6 SEM age: 49 6 3 y; body mass index (in kg/m2): 26.4 6 0.6; and plasma 25(OH)D3\ud concentration: 31.7 6 3.4 nmol/L]. They were randomly assigned to consume 3 different test meals (4.54 MJ, 51 g fat, 125 g\ud carbohydrate, and 23 g protein),which contained either a nonfortified dairy drink (control), 20 mg 25(OH)D3-fortified (+HyD3) dairy\ud drink, or 20 mg vitamin D3–fortified (+D3) dairy drink with toasted bread and jam on different occasions, separated by a 2-wk\ud washout. Plasma 25(OH)D3 concentrations and cardiometabolic risk markers, including vascular stiffness, serum lipids, and\ud inflammatory markers, were measured frequently within 8 h postprandially and 24 h after the dairy drink was consumed.\ud Results: Plasma 25(OH)D3 concentrations (the primary outcome) were significantly higher after the +HyD3 dairy drink was\ud consumed compared with +D3 and control (P = 0.019), which was reflected in the 1.5-fold and 1.8-fold greater incremental\ud area under the curve for the 0–8 h response, respectively. The change in plasma 25(OH)D3 concentrations from baseline to\ud 24 h for the +HyD3 dairy drink was also 0.9-fold higher than the +D3 dairy drink and 4.4-fold higher than the control\ud (P < 0.0001), which were not significantly different from each other.\ud Conclusion: The dairy drink fortified with 25(OH)D3 was more effective at raising plasma 25(OH)D3 concentrations\ud postprandially than was the dairy drink fortified with vitamin D3 in men with suboptimal vitamin D status.

Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear.We investigated the substitution of 9.5-9.6%TE dietary SFAs with either monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on vascular function and other CVD risk factors.In a randomized, controlled, single-blind, parallel-group dietary intervention, 195 men and women aged 21-60 y from the United Kingdom with moderate CVD risk (≥50% above the population mean) followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA) that were rich in SFAs (36:17:11:4, n = 65), MUFAs (36:9:19:4, n = 64), or n-6 PUFAs (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation; secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation, and endothelial activation.Replacing SFAs with MUFAs or n-6 PUFAs did not affect the percentage of flow-mediated dilatation (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFAs with MUFAs attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFAs or n-6 PUFAs lowered fasting serum total cholesterol (-8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%), and total cholesterol to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality.Substitution of 9.5-9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure, and E-selectin offer a potential public health strategy for CVD risk reduction. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and gastrointestinal discomfort. It is thus pertinent to establish the efficacy of lower n-3 PUFA doses. Eight male adults with asthma and HIB and eight controls without asthma were randomly supplemented with two n-3 PUFA doses (6·2 g/d (3·7 g EPA and 2·5 g DHA) and 3·1 g/d (1·8 g EPA and 1·3 g DHA)) and a placebo, each for 21 d followed by 14 d washout. A eucapnic voluntary hyperpnoea (EVH) challenge was performed before and after treatments. Outcome measures remained unchanged in the control group. In the HIB group, the peak fall in forced expiratory volume in 1 s (FEV1) after EVH at day 0 (−1005 (sd 520) ml, −30 (sd 18) %) was unchanged after placebo. The peak fall in FEV1 was similarly reduced from day 0 to day 21 of 6·2 g/d n-3 PUFA (−1000 (sd 460) ml, −29 (sd 17) % v. −690 (sd 460) ml, −20 (sd 15) %) and 3·1 g/d n-3 PUFA (−970 (sd 480) ml, −28 (sd 18) % v. −700 (sd 420) ml, −21 (sd 15) %) (PP=0·020) and 31 % (P=0·018) after 6·2 and 3·1 g/d n-3 PUFA, respectively. Peak increases in 9α, 11β PGF2 after EVH were reduced by 65 % (P=0·009) and 56 % (P=0·041) after 6·2 and 3·1 g/d n-3 PUFA, respectively. In conclusion, 3·1 g/d n-3 PUFA supplementation attenuated HIB and markers of airway inflammation to a similar extent as a higher dose. Lower doses of n-3 PUFA thus represent a potentially beneficial adjunct treatment for adults with asthma and EIB.

At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4–6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism. Trial registration number NCT01522482.

Dietary fructose has been linked to an increased post-prandial triglyceride (TG) level; which is an established independent risk factor for cardiovascular disease. Although much research has focused on the effects of fructose consumption on liver-derived very-low density lipoprotein (VLDL); emerging evidence also suggests that fructose may raise post-prandial TG levels by affecting the metabolism of enterocytes of the small intestine. Enterocytes have become well recognised for their ability to transiently store lipids following a meal and to thus control post-prandial TG levels according to the rate of chylomicron (CM) lipoprotein synthesis and secretion. The influence of fructose consumption on several aspects of enterocyte lipid metabolism are discussed; including de novo lipogenesis; apolipoprotein B48 and CM-TG production; based on the findings of animal and human isotopic tracer studies. Methodological issues affecting the interpretation of fructose studies conducted to date are highlighted; including the accurate separation of CM and VLDL. Although the available evidence to date is limited; disruption of enterocyte lipid metabolism may make a meaningful contribution to the hypertriglyceridaemia often associated with fructose consumption.