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Body mass index (BMI) has been suggested to play an important role in the relationship between the APOLIPOPROTEIN (APO)E genotype and cardiovascular disease (CVD) risk. Using data from the BODYCON cross-sectional study (n = 360 adults) we assessed the association between\ud body composition and CVD risk markers according to APOE genotype, with examination of the role of BMI. In this study cohort, the APOE2/E3 group had lower fasting blood lipids than APOE4 carriers and APOE3/E3 group (p ≤ 0.01). After stratifying the group according to BMI, APOE4 carriers in the normal BMI subgroup had a higher lean mass compared with the APOE3/E3 group (p = 0.02) whereas in the overweight/obese subgroup, the android to gynoid percentage fat ratio was lower in APOE4 carriers than APOE3/E3 group (p = 0.04). Fasting lipid concentrations were only different between the APOE2/E3 and other genotype groups within the normal weight BMI subgroup (p ≤ 0.04). This finding was associated with a lower dietary fibre and a higher trans-fat intake compared with APOE4 carriers, and a lower carbohydrate intake relative to the APOE3/E3 group. Our results confirm previous reports that BMI modulates the effect of APOE on CVD risk markers and suggest novel\ud interactions on body composition, with diet a potential modulator of this relationship.

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

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. \ud 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. \ud DNL from [13C2]-acetate was detected following all treatments, with greater amounts in intracellular than secreted (media) samples (all P

Additional file 1: Table S1. Spearman���s correlation coefficients (rs) for the relationship between circulating cardiovascular disease risk markers and dietary macronutrient intakes in the whole group. Table S2. Spearman���s correlation coefficients (rs) for the relationship between circulating cardiovascular disease risk markers and dietary macronutrient intakes in men and women. Table S3. Spearman���s correlation coefficients (rs) for the relationship between DXA body composition measurements with CVD risk factors and dietary macronutrients in men and women.

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.

Plant proteins contain bioactive peptides with functional properties and physiological activities.\ud In the present work, the bioactive peptides produced during in vitro gastrointestinal digestion\ud of soya protein isolate were investigated. Protein samples were subjected to simulated gastrointestinal\ud digestion with a generation of permeate (3 kDa) fractions.\ud The permeate was analysed by nano-liquid chromatography electrospray ionisation tandem\ud mass spectrometry (LC-nano ESI MS/MS) using a shotgun peptidomic approach, and the retentate\ud was further digested with trypsin and analysed using a shotgun proteomic approach. Based\ud on protein profile observed, the retentate was further tested for its potential antimicrobial activity\ud by evaluating the inhibitory effect on E. coli growth. In the present study the peptidomic/\ud proteomic characterisation of permeate and retentate fractions revealed the presence of bioactive\ud peptides and proteins associated with antioxidant, ACE-inhibitory, anti-hypertensive and\ud antimicrobial activities. The presence of potentially antimicrobial proteins in the retentate fraction\ud is supported by a marked E. coli F18þ growth inhibitory activity of the same fraction. In\ud particular, the growth inhibitory effect was significant from one until six hours of incubation\ud with 0.65–2.6 mg/ml of in vitro digested soya. The obtained data confirmed that soya-based supplements\ud may have potential beneficial effects after human consumption, and they may be recycled\ud for animal nutrition in line with the circular economy concept.

Purpose The development of metabolic diseases such as type 2 diabetes (T2D) is closely linked to a complex interplay between genetic and dietary factors. The prevalence of abdominal obesity, hyperinsulinemia, dyslipidaemia, and high blood pressure among Brazilian adolescents is increasing and hence, early lifestyle interventions targeting these factors might be an efective strategy to prevent or slow the progression of T2D.\ud Methods We aimed to assess the interaction between dietary and genetic factors on metabolic disease-related traits in 200 healthy Brazilian young adults. Dietary intake was assessed using 3-day food records. Ten metabolic disease-related single nucleotide polymorphisms (SNPs) were used to construct a metabolic-genetic risk score (metabolic-GRS).\ud Results We found significant interactions between the metabolic-GRS and total fat intake on fasting insulin level (Pinteraction=0.017), insulin-glucose ratio (Pinteraction=0.010) and HOMA-B (Pinteraction=0.002), respectively, in addition to a borderline GRS-fat intake interaction on HOMA-IR (Pinteraction=0.051). Within the high-fat intake category [37.98±3.39% of total energy intake (TEI)], individuals with≥5 risk alleles had increased fasting insulin level (P=0.021), insulin-glucose ratio (P=0.010), HOMA-B (P=0.001) and HOMA-IR (P=0.053) than those with

Additional file 8. Effect of personalised nutrition intervention on proportion of participants who perceived that they reduced the amount of total fat, sugars and salt consumed over the 6 months intervention.

Additional file 4. Consort diagram. Consort diagram of participants included in the Food4Me study.

Additional file 1. CONSORT checklist.

Additional file 5. Baseline characteristics of participants according to control and intervention arms.

Additional file 6. Characteristics of participants according to baseline intake of discretionary foods and beverages according to the Food Standards Scotland (FSS) classification.

Additional file 2. TIDieR checklist.

Additional file 3. Classification of discretionary foods and beverages according to Food Standards Scotland (FSS) and the Australian Dietary Guidelines (ADG) used in the present analysis.

Additional file 7. Effect of personalised nutrition intervention on intake of discretionary foods and beverages at month 3.

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 and intra-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 n=9 in humans and n=3 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 cardiovascular diseases.

Appropriate dietary choices in later life may reduce the risk of chronic diseases and rate of functional decline, however there is little well-evidenced age-specific nutritional guidance in the UK for older adults, making it challenging to provide nutritional advice. Therefore, the aim of this critical review was to propose evidence-based nutritional recommendations for older adults (aged ≥65y). Nutrients with important physiological functions in older adults were selected for inclusion in the recommendations. For these nutrients: 1) Recommendations from the UK Scientific Advisory Committee for Nutrition (SACN) reports were reviewed and guidance retained if recent and age-specific, and 2) A literature search conducted where SACN guidance was not sufficient to set or confirm recommendations for older adults, searching Web of Science up to March 2020. Data extracted from a total of 190 selected publications provided evidence to support age-specific UK recommendations for protein (1.2gkg-1day-1), calcium (1000mgday-1), folate (400μgday-1), vitamin B-12 (2.4μgday-1) and fluid (1.6Lday-1 women, 2.0Lday-1 men) for those ≥65y. UK recommendations for carbohydrates, free sugars, dietary fibre, dietary fat and fatty acids, sodium and alcohol for the general population are likely appropriate for older adults. Insufficient evidence was identified to confirm or change recommendations for all other selected nutrients. In general, significant gaps in current nutritional research among older adults existed, which should be addressed to support delivery of tailored nutritional guidance to this age group to promote healthy ageing.

The aim of the study was to investigate whether lifestyle factors modify the association between fat mass and obesity-associated(FTO)gene single nucleotide polymorphisms (SNPs) and obesity in a Turkish population. The study included 400 unrelated individuals, aged 24-50 years recruited in a hospital setting. Dietary intake and physical activity were assessed using 24-hour dietary recall and self-report questionnaire, respectively. A genetic risk score (GRS) was developed usingFTOSNPs, rs9939609 and rs10163409. Body mass index and fat mass index were significantly associated withFTOSNP rs9939609 (p = 0.001 andp = 0.002, respectively) and GRS (p = 0.002 andp = 0.003, respectively). The interactions between SNP rs9939609 and physical activity on adiponectin concentrations, and SNP rs10163409 and dietary protein intake on increased waist circumference were statistically significant (P-interaction = 0.027 andP(interaction) = 0.044, respectively). Our study has demonstrated that the association betweenFTOSNPs and central obesity might be modified by lifestyle factors in this Turkish population.

Personalising nutrition advice using digital technologies, such as web-apps, offers great potential to improve users’ adherence to healthy eating guidelines. However, commercial offerings currently lack decision engines capable of delivering personalised nutrition advice. This article outlines the core concepts, content and features of the novel eNutri app, developed by researchers at the University of Reading. Uniquely, the app identifies and recommends food-based modifications that would be most beneficial for an individual taking into account both their current diet quality and their individual preferences.

Epidemiological studies show an inverse association between dairy consumption and blood pressure (BP) but there are few data on the postprandial effects of milk proteins. This study examined their effects, compared to maltodextrin, on postprandial BP and other CVD risk markers in volunteers with mild and pre-hypertension over an 8 h period. In this double-blinded, randomised, cross-over, controlled study 27 adults ingested a high-fat, isoenergetic breakfast and lunch with 28 g whey protein, 28 g Ca-caseinate or 27 g maltodextrin. Whey protein reduced systolic BP compared with Ca-caseinate (−15.2 ± 13.6 mmHg) and maltodextrin (−23.4 ± 10.5 mmHg) up to 5 h post-ingestion. There was an improvement in arterial stiffness after whey protein compared with maltodextrin (incremental Area Under the Curve- iAUC0–8h: +14.4 ± 6.2%). Despite similar glucose levels after both whey protein and Ca-caseinate, whey protein induced a higher insulin response than Ca-caseinate (iAUC0–8h: +219.5 ± 54.6 pmol/L). Ca-caseinate induced less suppression of non-esterified fatty acids than whey protein (iAUC0–5h: −58.9 ± 135.5 μmol/L) and maltodextrin (iAUC0–5h: −106.9 ± 89.4 μmol/L) and induced a smaller postprandial triacylglycerol response than whey protein (iAUC0–8h: −1.68 ± 0.6 mmol/L). Milk proteins co-ingestion with high-fat meals may have the potential to maintain or improve CVD risk factors.

Background Consumption of ≤10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; however there is no clear guidance on the optimum replacement nutrient. Lipid-associated single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid responses to dietary fat interventions. Hence, we performed a retrospective analysis in 120 participants from the Dietary Intervention and VAScular function (DIVAS) study to investigate whether lipoprotein lipase (LPL) and apolipoprotein E (APOE) SNPs modify the fasting lipid response to replacement of SFA with monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids. Methods The DIVAS study was a randomized, single-blinded, parallel dietary intervention study performed in adults with a moderate cardiovascular risk who received one of three isoenergetic diets rich in SFA, MUFA or n-6 PUFA for 16 weeks. Results After the 16-week intervention, a significant diet-gene interaction was observed for changes in fasting total cholesterol (P = 0.001). For the APOE SNP rs1064725, only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet (n = 33; −0.71 ± 1.88 mmol/l) compared to the SFA (n = 38; 0.34 ± 0.55 mmol/l) or n-6 PUFA diets (n = 37; −0.08 ± 0.73 mmol/l) (P = 0.004). None of the interactions were statistically significant for the other SNPs. Conclusions In summary, our findings have demonstrated a greater sensitivity of the APOE SNP rs1064725 to dietary fat composition, with a total cholesterol lowering effect observed following substitution of SFA with MUFA but not n-6 PUFA. Further large intervention studies incorporating prospective genotyping are required to confirm or refute our findings. Trial registration The trial was registered at www.clinicaltrials.gov as NCT01478958.

Over the past decades, several studies investigated the health-promoting functions of milk peptides. However, to date many hurdles still exist regarding the widespread use of milk-derived bioactive peptides, as they may be degraded during gastrointestinal digestion. Thus, the aim of our study was to in vitro digest intact whey protein isolate (WPI) and casein proteins (CNP), mimicking in vivo digestion, to investigate their bioactive effects and to identify the potential peptides involved. Whey protein isolate and CNP were digested using a pepsin-pancreatin protocol and ultra-filtered (3-kDa cutoff membrane). A permeate (3 kDa) were obtained. Soy protein was included as a control (CTR). Angiotensin-1-converting enzyme inhibitory (ACE1-I) and antioxidant activity (AOX) were assessed and compared with those observed in undigested proteins and CTR. Furthermore, the permeate was characterized by nano-liquid chromatography electrospray ionization tandem mass spectrometry (LC-nano ESI MS/MS) using a shotgun peptidomic approach, and retentate was further digested with trypsin and analyzed by MS using a shotgun proteomic approach to identify potentially bioactive peptides. Further, the effects of WPI, CNP, and CTR retentate on cell metabolic activity and on mucus production (MUC5AC and MUC2 gene expression) were assessed in intestinal goblet HT29-MTX-E12 cells. Results showed that WPI permeate induced a significant ACE1-I inhibitory effect [49.2 ± 0.64% (SEM)] compared with undigested WPI, CNP permeate, and retentate or CTR permeate (10.40 ± 1.07%). A significant increase in AOX (1.58 ± 0.04 and 1.61 ± 0.02 µmol of trolox AOX equivalents per mg of protein, respectively) upon digestion was found in WPI. Potentially bioactive peptides associated with ACE1-I and antihypertensive effects were identified in WPI permeate and CNP retentate. At specific concentrations, WPI, CNP, and CTR retentate were able to stimulate metabolic activity in HT29-MTX-E12 cells. Expression of MUC5AC was increased by CNP retentate and unaltered by WPI retentate; MUC2 expression was significantly increased by 0.33 mg/g of CNP and reduced by 1.33 mg/g of CNP. Our results confirm that milk proteins may be rich sources of bioactive compounds, with the greatest beneficial potential of CNP at the intestinal goblet cell level.

In recent years, vitamin D deficiency has attracted attention worldwide. Especially many\ud ethnic minority populations are considered at high-risk of vitamin D deficiency, owing to a lesser\ud ability to synthesis vitamin D from sunlight (ultraviolet B), due to the skin pigment melanin and/or\ud reduced skin exposure due to coverage required by religious and cultural restrictions. Therefore,\ud vitamin D intake from dietary sources has become increasingly important for many ethnic minority\ud populations to achieve adequate vitamin D status compared with the majority of the population.\ud The aim of the study was critically evaluate the vitamin D intake and vitamin D status of the\ud ethnic minority populations with darker skin, and also vitamin D absorption from supplements\ud and ultraviolet B. Pubmed, Embaase and Scopus were searched for articles published up to October\ud 2018. The available evidence showed ethnic minority populations generally have a lower vitamin\ud D status than the majority populations. The main contributory food sources for dietary vitamin D\ud intake were different for ethnic minority populations and majority populations, due to vary dietary\ud patterns. Future strategies to increase dietary vitamin D intake by food fortification or biofortification\ud needs to be explored, not only for the majority population but more specifically for ethnic minority\ud populations who are generally of lower vitamin D status.

Table S1. Baseline characteristics of the CURES study participants: Comparison of NGT, Pre-diabetics and T2D individuals. (PDF 108 kb)

Table S3. Interaction between the FTO-GRS and dietary factors on obesity. (PDF 33 kb)

Table S2. Interaction between the FTO-GRS and lifestyle factors on vitamin B12, folic acid, homocysteine and obesity traits. (PDF 96 kb)

Saturated fats have been implicated as one of the main dietary contributors to heart disease. These fats do not block our arteries directly, but can raise the concentration of blood cholesterol, which can form deposits inside arteries called 'plaques'. The plaques can then become unstable and rupture, causing blood clot formation and a heart attack or stroke. For this reason, dietary guidelines limit the amount of saturated fats we should eat. However, this recommendation has been challenged because of a seeming lack of evidence for a direct relationship between saturated fats and heart disease mortality, and the complexity of the relationship between saturated fats and blood cholesterol. When we eat less saturated fats, the effect on blood cholesterol and other risk factors often depends on what the fats are replaced with. This can be another type of fat (polyunsaturated or monounsaturated fat) or carbohydrate, all of which will lower blood cholesterol and heart disease risk, to variable extents, with greater benefits from unsaturated fats. Moreover, not all foods that contain saturated fats have the same effect on blood cholesterol, including dairy foods like butter and cheese. In comparison to butter, the saturated fats in cheese are absorbed in the gut to a lesser extent, which reduces the relative potential of cheese to raise blood cholesterol.

Dairy foods are not essential in our diet, but can contribute to over 40% of daily intake of calcium, iodine, phosphorus and some B-vitamins across Europe and in the USA. Dairy also provides a higher quality of protein than meat. All dairy foods are made from milk that comes from ruminant animals such as cows, sheep, goats and water buffalo and have been consumed for over 7500 years in some European populations. There is a popular misconception that milk is a high-fat food, yet whole milk contains only 3.6% fat, semi-skimmed 1.7% and skimmed 0%. Dairy foods are the main contributor to saturated fat intake in many European countries, but a high intake of dairy (excluding butter and cream) is not generally associated with heart disease risk. On the contrary, proteins, calcium, magnesium and probiotic bacteria in dairy foods have been linked to some beneficial effects on heart health, including blood pressure lowering. While some individuals develop an allergy to milk protein, others have lactose intolerance and are unable to digest dairy sugar (lactose). Interestingly, adult lactose intolerance is a normal condition in mammals. However, most humans have a genetic mutation that enables them to consume dairy products throughout adulthood, due to the persistence of lactase, required for lactose digestion.

Background\ud Endothelial progenitor cells (EPC) and microparticles (MP) are emerging novel markers of cardiovascular disease (CVD) risk, which could potentially be modified by dietary fat. We have previously shown that replacing dietary saturated fat (SFA) with monounsaturated (MUFA) or n-6 polyunsaturated fat (PUFA) improved lipid biomarkers, blood pressure and markers of endothelial activation, but their effects on circulating EPCs and MPs are unclear.\ud Objective\ud The Dietary Intervention and VAScular function (DIVAS) study investigated the replacement of 9.5-9.6% total energy (%TE) SFA with MUFA or n-6 PUFA for 16 weeks on EPC and MP numbers in UK adults with moderate CVD risk.\ud Design\ud 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 one of three 16-week isoenergetic diets. Target compositions for total fat, SFA, MUFA and n-6 PUFA (%TE) were: 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 MP (EMP) and platelet MP (PMP) numbers were analysed by flow cytometry. Dietary intake, vascular function and other cardio-metabolic risk factors were determined at baseline. \ud Results\ud Relative to the SFA-rich diet, MUFA and n-6 PUFA-rich diets decreased EMP (-47.3%, -44.9%) and PMP numbers (-36.8%, -39.1%) (overall diet effects P

Background Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. Methods The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. Results There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10− 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10− 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10− 6 and P = 3 × 10− 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10− 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. Conclusion In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts. Electronic supplementary material The online version of this article (10.1186/s12944-018-0744-2) contains supplementary material, which is available to authorized users.

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. \ud Objective: This study investigated the impact of sequential meals rich in saturated (SFAs), monounsaturated (MUFAs) or n-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. \ud Methods: A double-blind, randomized, cross-over, postprandial study was conducted with 32 postmenopausal women (58 ± 1 years, BMI 25.9 ± 0.7 kg/m2). 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.\ud Results: Postprandial FMD, laser Doppler imaging and digital volume pulse responses were not different after consuming the test fats. The incremental AUC (IAUC) for diastolic blood pressure was lower (-0.5-fold) after the MUFA than SFA-rich meals (P=0.009), with a similar trend for systolic blood pressure (-0.4-fold; P=0.012). This corresponded with a lower IAUC (-6.4-fold) for the plasma nitrite response after the SFA than MUFA-rich meals (P=0.010). The soluble intercellular adhesion molecule-1 (sICAM-1) time course profile, AUC and IAUC were lower after the n-6 PUFA than SFA and MUFA-rich meals (P≤0.001). Lipids, glucose and markers of insulin sensitivity did not differ between the test fats. \ud Conclusions: Our study revealed 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.

Table S1. Genotype distribution of SNPs at LPL and APOE genes and Hardy Weinberg Equilibrium P values. (DOCX 18 kb)

Table S1. Genotype distribution of SNPs at LPL and APOE genes and Hardy Weinberg Equilibrium P values. (DOCX 18 kb)

Background With widespread use of the internet, lifestyle and dietary data collection can now be facilitated using online questionnaires as opposed to paper versions. We have developed a graphical food frequency assessment app (eNutri), which is able to assess dietary intake using a validated food frequency questionnaire (FFQ) and provide personalised nutrition advice. FFQ user acceptance and evaluation have not been investigated extensively and only a few studies involving user acceptance of nutrition assessment and advice apps by older adults are published. Methods A formative study with 20 participants (including n = 10 ≥60 years) assessed the suitability of this app for adults and investigated improvements to its usability. The outcomes of this formative study were applied to the final version of the application, which was deployed in an online study (EatWellUK) with 324 participants (including n = 53 ≥60 years) in the UK, using different devices (smartphones, tablets and laptops/desktops). Completion times were based on browser timestamps and usability was measured using the System Usability Scale (SUS), scoring between 0 and 100. Products with a SUS score higher than 70 are considered to be good. Results In the EatWellUK study, SUS score median (n = 322) was 77.5 (IQR 15.0). Out of the 322 SUS questionnaire completions, 321 device screen sizes were detected by the app. Grouped by device screen size, small (n = 92), medium (n = 38) and large (n = 191) screens received median SUS scores of 77.5 (IQR 15.0), 75.0 (IQR 19.4) and 77.5 (IQR 16.25), respectively. The median SUS scores from younger (n = 268) and older participants (n = 53) were the same. The FFQ contained 157 food items, and the mean completion time was 13.1 minutes (95% CI 12.6–13.7 minutes). Small, medium and large screen devices resulted in completion times of 11.7 minutes (95% CI 10.9–12.6 minutes), 14.4 minutes (95% CI 12.9–15.9 minutes) and 13.6 minutes (95% CI 12.8–14.3 minutes), respectively. Conclusions The overall median SUS score of 77.5 and overall mean completion time of 13.3 minutes indicate good overall usability, and equally, comparable SUS scores and completion times across small, medium and large screen sizes indicates good usability across devices. This work is a step toward the promotion of wider uptake of online apps that can provide online dietary intake assessment at-scale, with the aim of addressing pressing epidemiological challenges.

Diet-quality scores (DQS), which are developed across the globe, are used to define adherence to specific eating patterns and have been associated with risk of coronary heart disease and type-II diabetes. We explored the association between five diet-quality scores (Healthy Eating Index, HEI; Alternate Healthy Eating Index, AHEI; MedDietScore, MDS; PREDIMED Mediterranean Diet Score, P-MDS; Dutch Healthy Diet-Index, DHDI) and markers of metabolic health (anthropometry, objective physical activity levels (PAL), and dried blood spot total cholesterol (TC), total carotenoids, and omega-3 index) in the Food4Me cohort, using regression analysis. Dietary intake was assessed using a validated Food Frequency Questionnaire. Participants (n = 1480) were adults recruited from seven European Union (EU) countries. Overall, women had higher HEI and AHEI than men (p < 0.05), and scores varied significantly between countries. For all DQS, higher scores were associated with lower body mass index, lower waist-to-height ratio and waist circumference, and higher total carotenoids and omega-3-index (p trends < 0.05). Higher HEI, AHEI, DHDI, and P-MDS scores were associated with increased daily PAL, moderate and vigorous activity, and reduced sedentary behaviour (p trend < 0.05). We observed no association between DQS and TC. To conclude, higher DQS, which reflect better dietary patterns, were associated with markers of better nutritional status and metabolic health.

Agriculture-based reformulation initiatives, including oleic acid-rich lipid supplementation of the dairy cow diet, provide a novel means for reducing intake of saturated fatty acids (SFA) at a population level. In a blinded manner, this study evaluated the consumer acceptance of SFA-reduced, monounsaturated fatty acid-enriched (modified) milk, Cheddar cheese, and butter when compared with control and commercially available comparative samples. The effect of providing nutritional information about the modified cheese was also evaluated. Consumers (n = 115) rated samples for overall liking (appearance, flavor, and texture) using 9-point hedonic scales. Although no significant differences were found between the milk samples, the modified cheese was liked significantly less than a regular-fat commercial alternative for overall liking and liking of specific modalities and had a lower liking of texture score compared with the control cheese. The provision of health information significantly increased the overall liking of the modified cheese compared with tasting the same sample in a blinded manner. Significant differences were evident between the butter samples for overall liking and modalities of liking; all of the samples were significantly more liked than the commercial butter and sunflower oil spread. In conclusion, this study illustrated that consumer acceptance of SFA-reduced, monounsaturated fatty acid-enriched dairy products was dependent on product type. Future research should consider how optimization of the textural properties of fatty acid-modified (and fat-reduced) cheese might enhance consumer acceptance of this product.

OBJECTIVE:\ud Prospective data on the associations between vitamin D intake and risk of CVD and all-cause mortality are limited and inconclusive. The aim of the present study was to investigate the associations between vitamin D intake and CVD risk and all-cause mortality in the Caerphilly Prospective Cohort Study.\ud DESIGN:\ud The associations of vitamin D intake with CVD risk markers were examined cross-sectionally at baseline and longitudinally at 5-year, 10-year and >20-year follow-ups. In addition, the predictive value of vitamin D intake for CVD events and all-cause mortality after >20 years of follow-up was examined. Logistic regression and general linear regression were used for data analysis.\ud SETTING:\ud Participants in the UK.\ud SUBJECTS:\ud Men (n 452) who were free from CVD and type 2 diabetes at recruitment.\ud RESULTS:\ud Higher vitamin D intake was associated with increased HDL cholesterol (P=0·003) and pulse pressure (P=0·04) and decreased total cholesterol:HDL cholesterol (P=0·008) cross-sectionally at baseline, but the associations were lost during follow-up. Furthermore, higher vitamin D intake was associated with decreased concentration of plasma TAG at baseline (P=0·01) and at the 5-year (P=0·01), but not the 10-year examination. After >20 years of follow-up, vitamin D was not associated with stroke (n 72), myocardial infarctions (n 142), heart failure (n 43) or all-cause mortality (n 281), but was positively associated with increased diastolic blood pressure (P=0·03).\ud CONCLUSIONS:\ud The study supports associations of higher vitamin D intake with lower fasting plasma TAG and higher diastolic blood pressure.

Background: Food frequency questionnaires (FFQs) are well established in the nutrition field, but there remain important questions around how to develop online tools in a way that can facilitate wider uptake. Also, FFQ user acceptance and evaluation have not been investigated extensively.\ud \ud Objective: This paper presents a Web-based graphical food frequency assessment system that addresses challenges of reproducibility, scalability, mobile friendliness,security, and usability and also presents the utilization metrics and user feedback from a deployment study.\ud \ud Methods: The application design employs a single-page application Web architecture with back-end services (database,authentication, and authorization) provided by Google Firebase’s free plan. Its design and responsiveness take advantage of the Bootstrap framework. The FFQ was deployed in Kuwait as part of the EatWellQ8 study during 2016. The EatWellQ8 FFQ contains 146 food items (including drinks). Participants were recruited in Kuwait without financial incentive. Completion time was based on browser timestamps and usability was measured using the System Usability Scale (SUS), scoring between 0 and 100. Products with a SUS higher than 70 are considered to be good.\ud \ud Results: A total of 235 participants created accounts in the system, and 163 completed the FFQ. Of those 163 participants, 142 reported their gender (93 female, 49 male) and 144 reported their date of birth (mean age of 35 years, range from 18-65 years). The mean completion time for all FFQs (n=163), excluding periods of interruption, was 14.2 minutes (95% CI 13.3-15.1 minutes). Female participants (n=93) completed in 14.1 minutes (95% CI 12.9-15.3 minutes) and male participants (n=49) completed in 14.3 minutes (95% CI 12.6-15.9 minutes). Participants using laptops or desktops (n=69) completed the FFQ in an average of 13.9 minutes (95% CI 12.6-15.1 minutes) and participants using smartphones or tablets (n=91) completed in an average of 14.5 minutes(95% CI 13.2-15.8 minutes). The median SUS score (n=141) was 75.0 (interquartile range [IQR] 12.5), and 84% of the participants who completed the SUS classified the system either “good” (n=50) or “excellent” (n=69). Considering only participants using\ud smartphones or tablets (n=80), the median score was 72.5(IQR 12.5), slightly below the SUS median for desktops and laptops(n=58), which was 75.0 (IQR 12.5). No significant differences were found between genders or age groups (below and above the median) for the SUS or completion time.\ud \ud Conclusions: Taking into account all the requirements, the deployment used professional cloud computing at no cost, and the resulting system had good user acceptance. The results for smartphones/tablets were comparable with desktops/laptops. This work has potential to promote wider uptake of online tools that can assess dietary intake at scale.

Background Food frequency questionnaires (FFQs) are well established in the nutrition field, but there remain important questions around how to develop online tools in a way that can facilitate wider uptake. Also, FFQ user acceptance and evaluation have not been investigated extensively. Objective This paper presents a Web-based graphical food frequency assessment system that addresses challenges of reproducibility, scalability, mobile friendliness, security, and usability and also presents the utilization metrics and user feedback from a deployment study. Methods The application design employs a single-page application Web architecture with back-end services (database, authentication, and authorization) provided by Google Firebase’s free plan. Its design and responsiveness take advantage of the Bootstrap framework. The FFQ was deployed in Kuwait as part of the EatWellQ8 study during 2016. The EatWellQ8 FFQ contains 146 food items (including drinks). Participants were recruited in Kuwait without financial incentive. Completion time was based on browser timestamps and usability was measured using the System Usability Scale (SUS), scoring between 0 and 100. Products with a SUS higher than 70 are considered to be good. Results A total of 235 participants created accounts in the system, and 163 completed the FFQ. Of those 163 participants, 142 reported their gender (93 female, 49 male) and 144 reported their date of birth (mean age of 35 years, range from 18-65 years). The mean completion time for all FFQs (n=163), excluding periods of interruption, was 14.2 minutes (95% CI 13.3-15.1 minutes). Female participants (n=93) completed in 14.1 minutes (95% CI 12.9-15.3 minutes) and male participants (n=49) completed in 14.3 minutes (95% CI 12.6-15.9 minutes). Participants using laptops or desktops (n=69) completed the FFQ in an average of 13.9 minutes (95% CI 12.6-15.1 minutes) and participants using smartphones or tablets (n=91) completed in an average of 14.5 minutes (95% CI 13.2-15.8 minutes). The median SUS score (n=141) was 75.0 (interquartile range [IQR] 12.5), and 84% of the participants who completed the SUS classified the system either “good” (n=50) or “excellent” (n=69). Considering only participants using smartphones or tablets (n=80), the median score was 72.5 (IQR 12.5), slightly below the SUS median for desktops and laptops (n=58), which was 75.0 (IQR 12.5). No significant differences were found between genders or age groups (below and above the median) for the SUS or completion time. Conclusions Taking into account all the requirements, the deployment used professional cloud computing at no cost, and the resulting system had good user acceptance. The results for smartphones/tablets were comparable with desktops/laptops. This work has potential to promote wider uptake of online tools that can assess dietary intake at scale.

SCOPE:\ud \ud To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation.\ud METHODS AND RESULTS:\ud \ud In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat (LF); high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed. Apolipoprotein (apo)B isoforms were determined in isolated TAG-rich lipoprotein fractions (Sf >400, Sf 60-400 and Sf 20-60) by specific ELISA. A genotype*meal/diet interaction for the Sf >400 fraction apoB-48 response (P400 particles. Fasting Sf 60-400 and 20-60 apoB-48 concentrations were also significantly higher in E4 carriers. No impact of genotype on the apoB-100 responses was evident.\ud CONCLUSION:\ud \ud Our study revealed marked effects of dietary fat composition on the Sf >400 apoB-48 response and particle TAG content in E4 carriers relative to the 'wild-type' E3/E3 genotype, which suggest APOE genotype is a potential modulator of chylomicron particle synthesis. This article is protected by copyright. All rights reserved.

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.

Factor loadings identified by orthogonal partial least squares discriminant analysis of plasma phospholipid fatty acid profiles at baseline (week 0) and following diets that incorporated the control and modified dairy products (week 12) in adults at moderate cardiovascular disease risk. (DOC 73Â kb)

Background: There has been limited evidence about whether genotype-tailored advice provides extra benefits in reducing obesityrelated traits compared with the benefits of conventional one-size-fitsall advice. Objective: We determined whether the disclosure of information on fat-mass and obesity-associated (FTO) genotype risk had a greater effect on a reduction of obesity-related traits in risk carriers than in nonrisk carriers across different levels of personalized nutrition. Design: A total of 683 participants (women: 51%; age range: 18'73 y) from the Food4Me randomized controlled trial were included in this analysis. Participants were randomly assigned to 4 intervention arms as follows: level 0, control group; level 1, dietary group; level 2, phenotype group; and level 3, genetic group. FTO (single nucleotide polymorphism rs9939609) was genotyped at baseline in all participants, but only subjects who were randomly assigned to level 3 were informed about their genotypes. Level 3 participants were stratified into risk carriers (AA/AT) and nonrisk carriers (TT) of the FTO gene for analyses. Height, weight, and waist circumference (WC) were self-measured and reported at baseline and months 3 and 6. Results: Changes in adiposity markers were greater in participants who were informed that they carried the FTO risk allele (level 3 AT/AA carriers) than in the nonpersonalized group (level 0) but not in the other personalized groups (level 1 and 2). Mean reductions in weight andWC at month 6 were greater for FTO risk carriers than for noncarriers in the level 3 group [-2.28 kg (95% CI: -3.06, -1.48 kg) compared with -1.99 kg (-2.19, -0.19 kg), respectively (P = 0.037); and -4.34 cm(-5.63, -3.08 cm) compared with -1.99 cm (-4.04, -0.05 cm), respectively, (P = 0.048)]. Conclusions: There are greater body weight and WC reductions in risk carriers than in nonrisk carriers of the FTO gene. This trial was registered at clinicaltrials.gov as NCT01530139. © 2017 American Society for Nutrition.

Baseline characteristics for participantsâ based on the order of allocation to the control and modified dietary exchange periods. (DOC 36Â kb)

Changes in lipid levels after intervention with one of three diets over 16Â weeks according to LPL rs328 genotypes. Table S2. Changes in lipid levels after intervention with one of three diets over 16Â weeks according to APOE rs405509 and rs1160985 genotypes. Table S3. Changes in lipid levels after intervention with one of three diets over 16Â weeks according to APOE rs769450, rs439401, rs445925 and rs405697 genotypes. (DOCX 26 kb)

Background: Cardiovascular diseases (CVDs) are the greatest cause of death globally, and their reduction is a key public-health target. High blood pressure (BP) affects 1 in 3 people in the United Kingdom, and previous studies have shown that milk consumption is associated with lower BP.\ud \ud Objective: We investigated whether intact milk proteins lower 24-h ambulatory blood pressure (AMBP) and other risk markers of CVD.\ud \ud Design: The trial was a double-blinded, randomized, 3-way–crossover, controlled intervention study. Forty-two participants were randomly assigned to consume 2 × 28 g whey protein/d, 2 × 28 g Ca caseinate/d, or 2 × 27 g maltodextrin (control)/d for 8 wk separated by a 4-wk washout. The effects of these interventions were examined with the use of a linear mixed-model ANOVA.\ud \ud Results: Thirty-eight participants completed the study. Significant reductions in 24-h BP [for systolic blood pressure (SBP): −3.9 mm Hg; for diastolic blood pressure (DBP): −2.5 mm Hg; P = 0.050 for both)] were observed after whey-protein consumption compared with control intake. After whey-protein supplementation compared with control intake, peripheral and central systolic pressures [−5.7 mm Hg (P = 0.007) and −5.4 mm Hg (P = 0.012), respectively] and mean pressures [−3.7 mm Hg (P = 0.025) and −4.0 mm Hg (P = 0.019), respectively] were also lowered. Flow-mediated dilation (FMD) increased significantly after both whey-protein and calcium-caseinate intakes compared with control intake [1.31% (P < 0.001) and 0.83% (P = 0.003), respectively]. Although both whey protein and calcium caseinate significantly lowered total cholesterol [−0.26 mmol/L (P = 0.013) and −0.20 mmol/L (P = 0.042), respectively], only whey protein decreased triacylglycerol (−0.23 mmol/L; P = 0.025) compared with the effect of the control. Soluble intercellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1 were reduced after whey protein consumption (P = 0.011) and after calcium-caseinate consumption (P = 0.039), respectively, compared with after control intake.\ud \ud Conclusions: The consumption of unhydrolyzed milk proteins (56 g/d) for 8 wk improved vascular reactivity, biomarkers of endothelial function, and lipid risk factors. Whey-protein supplementation also lowered 24-h ambulatory SBP and DBP. These results may have important implications for public health. This trial was registered at clinicaltrials.gov as NCT02090842.

Prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasingly and is a key risk for CVD development, now recognised as the leading\ud cause of death globally. Dietary strategies to reduce CVD development include reduction of saturated fat intake. Milk and dairy products are\ud the largest contributors to dietary saturated fats in the UK and reduced consumption is often recommended as a strategy for risk reduction.\ud However, overall evidence from prospective cohort studies does not confirm a detrimental association between dairy product consumption\ud and CVD risk. The present review critically evaluates the current evidence on the association between milk and dairy products and risk of\ud CVD, T2DM and the metabolic syndrome (collectively, cardiometabolic disease). The effects of total and individual dairy foods on\ud cardiometabolic risk factors and new information on the effects of the food matrix on reducing fat digestion are also reviewed. It is concluded\ud that a policy to lower SFA intake by reducing dairy food consumption to reduce cardiometabolic disease risk is likely to have limited or\ud possibly negative effects. There remain many uncertainties, including differential effects of different dairy products and those of differing fat\ud content. Focused and suitably designed and powered studies are needed to provide clearer evidence not only of the mechanisms involved,\ud but how they may be beneficially influenced during milk production and processing.

Background: It is hypothesised that individuals with knowledge of their genetic risk are more likely to make health-promoting dietary and lifestyle changes. The present study aims to test this hypothesis using data from the Food4Me study. This was a 6-month Internet-based randomised controlled trial conducted across seven centres in Europe where individuals received either general healthy eating advice or varying levels of personalised nutrition advice. Participants who received genotype-based personalised advice were informed whether they had the risk (CT/TT) (n = 178) or non-risk (CC) (n = 141) alleles of the methylenetetrahydrofolate reductase (MTHFR) gene in relation to cardiovascular health and the importance of a sufficient intake of folate. General linear model analysis was used to assess changes in folate intake between the MTHFR risk, MTHFR non-risk and control groups from baseline to month 6 of the intervention.Results: There were no differences between the groups for age, gender or BMI. However, there was a significant difference in country distribution between the groups (p = 0.010). Baseline folate intakes were 412 ± 172, 391 ± 190 and 410 ± 186 μg per 10 MJ for the risk, non-risk and control groups, respectively. There were no significant differences between the three groups in terms of changes in folate intakes from baseline to month 6. Similarly, there were no changes in reported intake of food groups high in folate.Conclusions: These results suggest that knowledge of MTHFR 677C → T genotype did not improve folate intake in participants with the risk variant compared with those with the non-risk variant.Trial registration: ClinicalTrials.gov NCT01530139