Professor Bruce Griffin

Human studies suggest that reducing dietary saturated fatty acids (SFAs) via replacing it with unsaturated fatty acids (UFAs) has a beneficial effect on fasting low-density lipoprotein cholesterol (LDL-C)(Reference Siri-Tarino, Sun and Hu1). However, significant variation in LDL-C concentration has been observed in response to change in dietary SFA intake(Reference Vafeiadou, Weech and Altowaijri2,Reference Jebb, Lovegrove and Griffin3) and there is considerable interest in potential determinants underlying the responsiveness of LDL-C to fat intake. Dietary fat composition affects body fat distribution with higher SFA intakes associated with abdominal obesity and greater cardiovascular disease (CVD) risk(Reference Rosqvist, Iggman and Kullberg4). However, it is not clear whether the variability in LDL-C response to dietary SFA is related to changes in body composition.

We have previously shown that replacement of dietary saturated fat (SFA) with unsaturated fat (UFA) lowers serum LDL-cholesterol and increases the gene expression of LDL-receptors (LDL-R) in peripheral blood mononuclear cells, in the RISSCI-1 (Reading Imperial Surrey Saturated fat Cholesterol Intervention) study(Reference Ozen, Koutsos and Antoni1). This dietary-induced upregulation of LDL-R gene expression has been reported to occur in response to a reduction in endogenous cholesterol synthesis and intra- cellular free cholesterol. The latter, in part, is regulated by a reciprocal ‘push-pull’ relationship between the endogenous synthesis and intestinal absorption of cholesterol(Reference Alphonse and Jones2). The aim of the present investigation was to evaluate the effects of exchanging SFA for UFA on markers of intestinal absorption and endogenous synthesis of cholesterol.RISSCI-1 was a non-randomised, sequential dietary intervention study, in which 109 healthy men (age 48, SD 11y, BMI 25.1 kg/m2 SD 3.3) followed two iso-energetic diets; a high SFA (18% total energy (TE)) - lower UFA (15% TE) diet, followed by a lower SFA (10% TE) - high UFA (24% TE) diet, for 4 weeks each. Plasma non- cholesterol sterols, standardised for total cholesterol and expressed as ratios of non-cholesterol sterol to total cholesterol, were used as validated biomarkers of intestinal cholesterol absorption (β- sitosterol, cholestanol, campesterol), and endogenous cholesterol synthesis (lathosterol, desmosterol)(Reference Mashnafi, Plat and Mensink3). Non-cholesterol sterols were measured in plasma samples collected at the end of each diet, using GC-MS and epicoprostanol (5b-cholestan-3a-ol) as an internal standard. Data was analysed by a linear mixed model, with age, BMI, baseline visit, diets (high SFA, low SFA), and study centre included as fixed effects, and participants as a random effect (R version 4.1.2). Replacement of dietary SFA with UFA produced increases of between 15 to 35% in all three plasma biomarkers of intestinal cholesterol absorption (high vs lower SFA diet). Mean cholesterol-standardised ratios (95% CI) were as follows: β-sitosterol 0.95 (0.94 −1.01) vs 1.31 (1.27–1.34); cholestanol 1.25 (1.22–1.28) vs 1.44 (1.41–1.47); campesterol 0.91 (0.87–0.94) vs 1.14 (1.11–1.18) all p < 0.0001. Plasma desmosterol increased (0.61 (0.59–0.63) vs 0.66 (0.65–0.68)) p < 0.0001, while plasma lathosterol showed no significant change. In conclusion, the consistent increase in biomarkers of intestinal cholesterol absorption is in accord with the replacement of dietary SFA with UFA reducing the endogenous synthesis of cholesterol. However, since there was no evidence of a consistent dietary effect on the biomarkers of endogenous cholesterol synthesis, this fails to support a reciprocal relationship between cholesterol synthesis and absorption. Further insight into these effects will be gained through the stable isotope trace-labelling of dietary saturated fat in a follow-up study (RISSCI-2).

The reproducibility of clinical trial results is of major importance in nutrition research. Variability in the results of apparently similar dietary studies has been previously reported(Reference Sorkin, Kuszak and Williamson1), due to differences in study design, assessment methods, participants’ background diet and inter-individual variability. However, comparisons of identical dietary interventions performed in the same participants, which will control for some of the mentioned variability, are rare. This study aims to assess the reproducibility of an identical dietary intervention (Reading, Imperial, Surrey Saturated fat Cholesterol Intervention study 1 and 2, RISSCI-1 and RISSCI-2) performed on two occasions, on the outcomes of fasted lipids.

Rationale for the dietary guideline to replace saturated (SFA) with unsaturated fatty acids (UFA) to reduce risk of atherosclerotic cardiovascular disease (ASCVD) rests heavily on the lowering of serum low density lipoprotein cholesterol (LDL-C)(Reference Mensink1). However, there is evidence to suggest that this dietary exchange may be associated with favourable effects on other cardiometabolic risk factors, including non-high-density lipoprotein-cholesterol (non-HDL-C), a measure of all atherogenic lipoproteins in serum(Reference Pinart, Jeran and Boeing2). The aim of this study was to determine the effects of dietary SFA on serum HDL-C, non-HDL-C, and remnant-cholesterol in the RISSCI-1 study.

It has been proposed that a high sugar intake was associated with cardiovascular disease (CVD) risk and metabolic syndrome depending on the amount of carbohydrate (CHO), other nutrients in foods, and underlying metabolic disturbances. This study aimed to investigate the effects of high (HS) and low sugar (LS) diets on metabolic profiles in 25 middle-aged men at increased CVD risk in a 12-week randomised cross-over intervention study. An isocaloric dietary exchanged model consisted of HS (24% energy from sugar) and LS (6% energy from sugar) with comparable total CHO, fat and fibre composition in normal foods was used. Anthropometric, blood pressure and plasma lipid profile were measured pre- and post-intervention. Body weight, waist circumference and fat mass increased and decreased significantly after HS (by 0.7±0.3 kg, 1.4±1.0 cm and 0.5±0.3 kg) and LS (by 2.1±0.5 kg, 2.0±0.8 cm and 1.4±0.3 kg) (p

To report patient activation, which is the knowledge, skills, and confidence in self-managing health conditions, and patient-reported outcomes of men after prostate cancer treatment from a community pharmacy lifestyle intervention. The 3-month lifestyle intervention was delivered to 116 men in nine community pharmacies in the UK. Patient Activation Measure (PAM) was assessed at baseline, 3 and 6 months. Prostate cancer-related function and quality of life were assessed using the European Prostate Cancer Index Composite (EPIC-26) and EuroQOL 5-dimension 5-level (EQ5D-5L) questionnaires at baseline and 6 months. Lifestyle assessments included Mediterranean Diet Adherence Screener (MEDAS) at baseline, 3 and 6 months and Godin Leisure Time Exercise Questionnaire (GLTEQ) at baseline and 3 months. PAM score increased from 62 [95% CI 59-65] at baseline to 66 [64-69] after the intervention (p = 0.001) and remained higher at 6 months (p = 0.008). Scores for all the EPIC-26 domains (urinary, bowel and hormonal) were high at both assessments, indicating good function (between 74 [70-78] and 89 [86-91]), except sexual domain, where scores were much lower (21 [17-25] at baseline, increasing to 24 [20-28] at 6 months (p = 0.012)). In EQ5D-5L, 3% of men [1-9] reported self-care problems, while 50% [41-60] reported pain and discomfort, and no significant changes over time. Men who received androgen deprivation therapy, compared with those who did not, reported higher (better) urinary incontinence scores (p 

Cardio-metabolic risk (CMR) embodies a clustering of metabolic abnormalities that increase the likelihood of developing CVD in the large arteries of the heart, peripheral tissues and brain. These abnormalities share a common origin of insulin resistance, which manifests typically as excess visceral adipose tissue in the abdominal cavity, and within cells of key metabolic tissues (ectopic fat), including the liver, pancreas, heart and skeletal muscle. As expected, the increased risk of CVD that can be attributed to CMR factors is alarmingly high in overweight and obese populations, but this risk can be reduced by reversing many of the inappropriate diet and lifestyle behaviours that underlie its development. The Nutrition Society's 2018 Winter Meeting at the Royal Society of Medicine addressed the topic of the 'Optimal diet and lifestyle for managing cardio-metabolic risk', with the aim of providing mechanistic insights into the impact of macronutrients, dietary patterns and meal timing in key metabolic tissues. The 2-d programme concluded with a summary of its main outcomes, and an overview of their implications for dietary policy in the UK.

Context: Maternal body mass index (BMI) is associated with increased birth weight but does not explain all the variance in fetal adiposity. Objective: To assess the contribution of maternal body fat distribution to offspring birth weight and adiposity. Design Longitudinal study throughout gestation and at delivery. Setting Women recruited at 12 weeks of gestation and followed up at 26 and 36 weeks. Cord blood was collected at delivery. Patients Pregnant women (n = 45) with BMI 18.0 to 46.3 kg/m2 and healthy pregnancy outcome. Methods: Maternal first trimester abdominal subcutaneous and visceral adipose tissue thickness (SAT and VAT) was assessed by ultrasound. Main Outcome Measures Maternal body fat distribution, maternal and cord plasma glucose and lipid concentrations, placental weight, birth weight, and fetal adiposity assessed by cord blood leptin. Results: VAT was the only anthropometric measure independently associated with birth weight centile (r2 adjusted 15.8%, P = .002). BMI was associated with trimester 2 and trimesters 1 through 3 area under the curve (AUC) glucose and insulin resistance (Homeostatic Model Assessment). SAT alone predicted trimester 2 lipoprotein lipase (LPL) mass (a marker of adipocyte insulin sensitivity) (11.3%, P = .017). VAT was associated with fetal triglyceride (9.3%, P = .047). Placental weight was the only independent predictor of fetal adiposity (48%, P < .001). Maternal trimester 2 and AUC LPL were inversely associated with fetal adiposity (r = -0.69, P = .001 and r = -0.58, P = .006, respectively). Conclusions: Maternal VAT provides additional information to BMI for prediction of birth weight. VAT may be a marker of reduced SAT expansion and increased availability of maternal fatty acids for placental transport.

Purpose: UK guidelines recommend dietary saturated fatty acids (SFAs) should not exceed 10% total energy (%TE) for cardiovascular disease prevention, with benefits observed when SFAs are replaced with unsaturated fatty acids (UFAs). This study aimed to assess the efficacy of a dietary exchange model using commercially available foods to replace SFAs with UFAs. Methods: Healthy men (n=109, age 48, SD 11y) recruited to the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-1 (RISSCI-1) study (ClinicalTrials.Gov n°NCT03270527) followed two sequential 4-week isoenergetic moderate-fat (34%TE) diets: high-SFA (18%TE SFAs, 16%TE UFAs) and low-SFA (10%TE SFAs, 24%TE UFAs). Dietary intakes were assessed using 4-day weighed diet diaries. Nutrient intakes were analysed using paired t-tests, fasting plasma phospholipid fatty acid (PL-FA) profiles and dietary patterns were analysed using orthogonal partial least square discriminant analyses. Results: Participants exchanged 10.2%TE (SD 4.1) SFAs for 9.7%TE (SD 3.9) UFAs between the high and low-SFA diets, reaching target intakes with minimal effect on other nutrients or energy intakes. Analyses of dietary patterns confirmed successful incorporation of recommended foods from commercially available sources (e.g. dairy products, snacks, oils, and fats), without affecting participants’ overall dietary intakes. Analyses of plasma PL-FAs indicated good compliance to the dietary intervention and foods of varying SFA content. Conclusions: RISSCI-1 dietary exchange model successfully replaced dietary SFAs with UFAs in free-living healthy men using commercially available foods, and without altering their dietary patterns. Further intervention studies are required to confirm utility and feasibility of such food-based dietary fat replacement models at a population level.

Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.

Controversy over fat quality and cardiovascular disease risk stems from a series of meta-analyses of prospective cohort and randomised intervention trials, which found little evidence for a significant relationship between the intake of saturated fat and disease endpoints. Possible explanations for these null findings include difficulties inherent in estimating true food intake, the confounding effects of macronutrient replacement and food composition, and marked inter-individual variation in the response of serum LDL-cholesterol. The aim of this narrative review was to present evidence for the existence and origins of variation in serum LDL-cholesterol response to the replacement of dietary saturated fat, and its potential to explain the controversy over the latter. The review provides evidence to suggest that variation in LDL-responsiveness may harbour significant potential to confound the relationship between saturated fat and atherosclerotic cardiovascular disease risk, thus undermining the effectiveness of the dietary guideline to replace saturated fat with unsaturated fat. It concludes that the identification and application of a simple biomarker of this phenomenon, would make it possible to tailor dietary guidelines to LDL responsive individuals, who stand to gain a greater benefit to their cardiovascular health. [Display omitted] •Variation in serum LDL-C response to dietary fat between individuals may attenuate strength of statistical associations.•Variance in the reciprocity between cholesterol synthesis and reabsorption contributes to LDL-C-responsive metabotypes.•Variation in serum LDL-C response to dietary SFA is influenced by bile acid production and reabsorption in the gut.•Genetic polymorphisms contribute to variance in serum LDL-C within populations and in response to changes in dietary fat.•A biomarker of LDL-C response to SFA would enable targeting of dietary advice to achieve a greater reduction in ASCVD risk.

The purpose of this study was to compare fitness parameters and cardiovascular disease risk of older and younger men with prostate cancer (PCa) and explore how men's fitness scores compared to normative age values. 83 men were recruited post-treatment and undertook a cardiopulmonary exercise test (CPET), sit-to-stand, step-and-grip strength tests and provided blood samples for serum lipids and HbA1c. We calculated waist-to-hip ratio, cardiovascular risk (QRISK2), Charlson comorbidity index (CCI) and Godin leisure-time exercise questionnaire [GLTEQ]. Age-group comparisons were made using normative data. Men > 75 years, had lower cardiopulmonary fitness, as measured by VO2 Peak (ml/kg/min) 15.8 + 3.8 p < 0.001, and lower grip strength(28.6+5.2 kg p < 0.001) than younger men. BMI ≥30kg/m2 and higher blood pressure all contributed to a QRisk2 score indicative of 20% chance of cardiovascular risk within 10 years (mean: 36.9–6.1) p < 0.001. Age, BMI and perceived physical activity were significantly associated with lower cardiopulmonary fitness. Men with PCa > 75 years had more cardiovascular risk factors compared to normative standards for men of their age. Although ADT was more frequent in older men, this was not found to be associated with cardiopulmonary fitness, but obesity and low levels of physical activity were. Secondary prevention should be addressed in men with PCa to improve men's overall health.

The Oxford English Dictionary defines the word myth as; 'a popular idea concerning natural or historical phenomena ... that has no foundation in fact'. The popular idea in this context is that eating dietary cholesterol, typically from eggs, increases the risk of developing coronary heart disease (CHD), because it increases blood cholesterol. This contentious idea prevails, despite a lack of scientific foundation to support its existence, and almost global re-vamping of dietary recommendations to lift restrictions on the intake of cholesterol-rich foods. In an attempt to dispel the mythical status of dietary cholesterol and CHD, the following chapter will examine the role of dietary cholesterol in relation to what has been well established in terms of the relationships between blood cholesterol, diet and CHD. © 2011 Woodhead Publishing Limited All rights reserved.

Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate- intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category , to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important ‘vital sign’ in clinical practice.

Background & Aims: Serum lipids and lipoproteins are established biomarkers of cardiovascular disease risk that could be influenced by impaired gut barrier function via effects on the absorption of dietary and biliary cholesterol. The aim of this study was to examine the potential relationship between gut barrier function (gut permeability) and concentration of serum lipids and lipoproteins, in an ancillary analysis of serum samples taken from a previous study. Methods and Results: Serum lipids, lipoproteins and functional gut permeability, as assessed by the percentage of the urinary recovery of 51-Cr-labelled EDTA absorbed within 24h, were measured in a group of 30 healthy men. Serum lipopolysaccharide, high sensitivity C-reactive protein and interleukin-6 were also measured as markers of low-grade inflammation. The group expressed a 5- fold variation in total gut permeability (1.11 - 5.03%). Gut permeability was unrelated to the concentration of both serum total and low density lipoprotein (LDL)-cholesterol, but was positively associated with serum high density lipoprotein (HDL)-cholesterol (r=0.434, P=0.015). Serum HDL cholesterol was also positively associated with serum endotoxaemia (r=0.415, p=0.023). Conclusion: The significant association between increased gut permeability and elevated serum HDL-cholesterol is consistent with the role of HDL as an acute phase reactant, and in this situation, potentially dysfunctional lipoprotein. This finding may have negative implications for the putative role of HDL as a cardio-protective lipoprotein.

The main lifestyle interventions to modify serum HDL cholesterol include physical exercise, weight loss with either caloric restriction or specific dietary approaches, and smoking cessation. Moderate alcohol consumption can be permitted in some cases. However, as these interventions exert multiple effects, it is often difficult to discern which is responsible for improvement in HDL outcomes. It is particularly noteworthy that recent data questions the use of HDL cholesterol as a risk factor and therapeutic target since randomised interventions and Mendelian randomisation studies failed to provide evidence for such an approach. Therefore, these current data should be considered when reading and interpreting this review. Further studies are needed to document the effect of lifestyle changes on HDL structure-function and health.

A cross-sectional analysis of ethnic differences in dietary intake, insulin sensitivity and beta-cell function, using the intravenous glucose tolerance test (IVGTT), was conducted on 497 healthy adult participants of the 'Reading, Imperial, Surrey, Cambridge, and Kings' (RISCK) study. Insulin sensitivity (Si) was significantly lower in African-Caribbean (AC) and South Asian (SA) participants [IVGTT-Si; AC: 2.13 vs SA: 2.25 vs white-European (WE): 2.84 (×10(-4) mL µU min)(2), p < 0.001]. AC participants had a higher prevalence of anti-hypertensive therapy (AC: 19.7% vs SA: 7.5%), the most cardioprotective lipid profile [total:high-density lipoprotein (HDL); AC: 3.52 vs SA: 4.08 vs WE: 3.83, p = 0.03] and more pronounced hyperinsulinaemia [IVGTT-acute insulin response (AIR)] [AC: 575 vs SA: 428 vs WE: 344 mL/µU/min)(2), p = 0.002], specifically in female participants. Intake of saturated fat and carbohydrate was lower and higher in AC (10.9% and 50.4%) and SA (11.1% and 52.3%), respectively, compared to WE (13.6% and 43.8%, p < 0.001). Insulin resistance in ACs is characterised by 'normal' lipid profiles but high rates of hypertension and pronounced hyperinsulinaemia.

Objective It is well established that exercise and lifestyle behaviours improve men's health outcomes from prostate cancer. With 3.8 million men living with the disease worldwide, the challenge is creating accessible intervention approaches that lead to sustainable lifestyle changes. We carried out a phase II feasibility study of a lifestyle intervention delivered by nine community pharmacies in the United Kingdom to inform a larger efficacy study. Qualitative interviews explored how men experienced the intervention, and these data are presented here. Methods Community pharmacies delivered a multicomponent lifestyle intervention to 116 men with prostate cancer. The intervention included a health, strength, and fitness assessment, immediate feedback, lifestyle prescription with telephone support, and reassessment 12 weeks later. Three months after receiving the intervention, 33 participants took part in semistructured telephone interviews. Results Our framework analysis identified how a teachable moment can be created by a community pharmacy intervention. There was evidence of this when men's self‐perception was challenged and coupled to a positive interaction with a pharmacist. Our findings highlight the social context of behaviour change with men identifying how their lifestyle choices were negotiated within their household. There was a ripple effect as lifestyle behaviours made a positive impact on friends and family. Conclusions The teachable moment is not a serendipitous opportunity but can be created by an intervention. Our study adds insight into how community pharmacists can support cancer survivors to make positive lifestyle behaviour changes and suggests a role for doing rather than just telling.

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n=11) and low liver fat ‘controls’ (n= 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling. There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P

PURPOSE OF REVIEW: Vascular function is recognized as an early and integrative marker of cardiovascular disease. While there is consistent evidence that the quantity of dietary fat has significant effects on vascular function, the differential effects of individual fatty acids is less clear. This review summarizes recent evidence from randomly controlled dietary studies on the impact of dietary fatty acids on vascular function, as determined by flow-mediated dilatation (FMD). RECENT FINDINGS: Critical appraisal is given to five intervention studies (one acute, four chronic) which examined the impact of long-chain n-3 polyunsaturated fatty acid [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] on FMD. In the acute setting, a high dose of long-chain n-3 polyunsaturated fatty acid (4.9 g per 70 kg man) improved postprandial FMD significantly, compared with a saturated fatty acid-rich meal in healthy individuals. In longer-term studies, there was limited evidence for a significant effect of EPA/DHA on FMD in diseased groups. SUMMARY: The strongest evidence for the benefits of EPA/DHA on vascular function is in the postprandial state. More evidence from randomly controlled intervention trials with foods will be required to substantiate the long-term effects of EPA/DHA, to inform public health and clinical recommendations.

Context:Maternal obesity is associated with high plasma triglyceride, poor vascular function, and an increased risk for pregnancy complications. In normal-weight pregnant women, higher triglyceride is associated with increased small, dense low-density lipoprotein (LDL).Hypothesis:In obese pregnancy, increased plasma triglyceride concentrations result in triglyceride enrichment of very low-density lipoprotein-1 particles and formation of small dense LDL via lipoprotein lipase.Design:Women (n = 55) of body mass index of 18-46 kg/m(2) were sampled longitudinally at 12, 26, and 35 weeks' gestation and 4 months postnatally.Setting:Women were recruited at hospital antenatal appointments, and study visits were in a clinical research suite.Outcome Measures:Plasma concentrations of lipids, triglyceride-rich lipoproteins, lipoprotein lipase mass, estradiol, steroid hormone binding globulin, insulin, glucose, leptin, and adiponectin were determined.Results:Obese women commenced pregnancy with higher plasma triglyceride, reached the same maximum, and then returned to higher postnatal levels than normal-weight women. Estradiol response to pregnancy (trimester 1-3 incremental area under the curve) was positively associated with plasma triglyceride response (r(2) adjusted 25%, P < .001). In the third trimester, the proportion of small, dense LDL was 2-fold higher in obese women than normal-weight women [mean (SD) 40.7 (18.8) vs 21.9 (10.9)%, P = .014], and 35% of obese, 14% of overweight, and none of the normal-weight women displayed an atherogenic LDL subfraction phenotype. The small, dense LDL mass response to pregnancy was inversely associated with adiponectin response (17%, P = .013).Conclusions:Maternal obesity is associated with an atherogenic LDL subfraction phenotype and may provide a mechanistic link to poor vascular function and adverse pregnancy outcome.

Nightshift work is associated with adverse health outcomes, which may be related to eating during the biological night, when circadian rhythms and food intake are misaligned. Nurses often undertake nightshift work, and we aimed to investigate patterns of energy distribution and dietary intake across 14 days in 20 UK National Health Service (NHS) nurses working rotational shifts. We hypothesised that the proportion of daily energy consumed during the nightshift would increase over consecutive nights. Primary and secondary outcome measures included intakes of energy and macronutrients. Our results show that nurses consumed the same total daily energy on nightshifts and non-nightshifts, but redistributed energy to the nightshift period in increasing proportions with a significant difference between Night 1 and 2 in the proportion of total daily energy consumed (26.0 ± 15.7% vs. 33.5 ± 20.2%, mean ± SD; p < 0.01). This finding indicates that, rather than increasing total energy intake, nurses redistribute energy consumed during nightshifts as a behavioural response to consecutive nightshifts. This finding informs our understanding of how the intake of energy during the biological night can influence adverse health outcomes of nightshift work.

Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic morbidity and mortality. Emerging evidence also suggests that ectopic fat deposition, including hepatic and epicardial fat, might contribute to increased atherosclerosis and cardiometabolic risk. This joint position statement from the International Atherosclerosis Society and the International Chair on Cardiometabolic Risk Working Group on Visceral Obesity summarises the evidence for visceral adiposity and ectopic fat as emerging risk factors for type 2 diabetes, atherosclerosis, and cardiovascular disease, with a focus on practical recommendations for health professionals and future directions for research and clinical practice. We discuss the measurement of visceral and ectopic fat, pathophysiology and contribution to adverse health outcomes, response to treatment, and lessons from a public health programme targeting visceral and ectopic fat. We identify knowledge gaps and note the need to develop simple, clinically applicable tools to be able to monitor changes in visceral and ectopic fat over time. Finally, we recognise the need for public health messaging to focus on visceral and ectopic fat in addition to excess bodyweight to better combat the growing epidemic of obesity worldwide.

Androgen deprivation therapy (ADT) is used widely as part of a combined modality for the treatment of prostate cancer. However, ADT has also been associated with the development of cardiometabolic complications that can increase mortality from cardiovascular events. There is emerging evidence to suggest that ADT-related cardiometabolic risk can be mitigated by diet and lifestyle modification. While the clinical focus for a nutritional approach for achieving this effect is unclear, it may depend upon the timely assessment and targeting of dietary changes to the specific risk phenotype of the patient. The present review aims to address the metabolic origins of ADT-related cardiometabolic risk, existing evidence for the effects of dietary intervention in modifying this risk, and the priorities for future dietary strategies.

Background Assessing fitness and promoting regular physical activity can improve health outcomes and early recovery in prostate cancer. This is however, underutilised in clinical practice. The cardiopulmonary exercise test (CPET) is increasingly being used pre-treatment to measure aerobic capacity and peak oxygen consumption (VO2peak - a gold standard in cardiopulmonary fitness assessment). However, CPET requires expensive equipment and may not always be appropriate. The Siconolfi step test (SST) is simpler and cheaper, and could provide an alternative. The aim of this study was to evaluate the validity and reliability of SST for predicting cardiopulmonary fitness in men with prostate cancer. Men were recruited to this two-centre study (Surrey and Newcastle, United Kingdom) after treatment for locally advanced prostate cancer. They had one or more of three risk factors: elevated blood pressure, overweight (BMI ˃ 25), or androgen deprivation therapy (ADT). Cardiopulmonary fitness was measured using SST and cycle ergometry CPET, at two visits three months apart. The validity of SST was assessed by comparing it to CPET. The VO2peak predicted from SST was compared to the VO2peak directly measured with CPET. The reliability of SST was assessed by comparing repeated measures. Bland-Altman analysis was used to derive limits of agreement in validity and reliability analysis. Results Sixty-six men provided data for both SST and CPET. These data were used for validity analysis. 56 men provided SST data on both visits. These data were used for reliability analysis. SST provided valid prediction of the cardiopulmonary fitness in men ˃ 60 years old. The average difference between CPET and SST was 0.64 ml/kg/min with non-significant positive bias towards CPET (P = 0.217). Bland-Altman 95% limits of agreement of SST with CPET were ± 7.62 ml/kg/min. SST was reliable across the whole age range. Predicted VO2peak was on average 0.53 ml/kg/min higher at Visit 2 than at Visit 1 (P = 0.181). Bland-Altman 95% limits of agreement between repeated SST measures were ± 5.84 ml/kg/min. Conclusions SST provides a valid and reliable alternative to CPET for the assessment of cardiopulmonary fitness in older men with prostate cancer. Caution is advised when assessing men 60 years old or younger because the VO2peak predicted with SST was significantly lower than that measured with CPET.

The replacement of saturated fatty acids (SFA) has been the mainstay of our dietary guidelines to help prevent cardiovascular disease (CVD) for over 30 years. However, the underlying evidence to support this guideline is now held in contentious disrepute on the grounds of an apparent lack of evidence, largely from meta-analyses, for a direct relationship between saturated fat and CVD mortality. This can be explained by the fact that the relationship between dietary SFA and CVD is not direct, but indirect and mediated through the low-density lipoprotein cholesterol (LDL-C) raising effects of certain SFA, in certain foods. There is over 100 years of evidence to link raised serum cholesterol with CVD and to support the current consensus that serum LDL is causally related to CVD morbidity and mortality. Nevertheless, the role of LDL as a biomarker of CVD risk, as measured by its cholesterol content (LDL-C), is often confused with its contribution to cardio-metabolic risk by its conversion into small and dense LDL particles with increased potential to cause CVD. The clinical utility of serum LDL is outstanding as a biomarker for CVD, albeit through an increase in its cholesterol mass (LDL-C), its small particle size or over-abundance of these particles. What is of overriding importance is to identify and modify these characteristics in LDL at the earliest stage of their development and to reduce the associated CVD risk through appropriate and sustained changes in diet and lifestyle.

Objectives: To assess the feasibility and acceptability of a community pharmacy lifestyle intervention to improve physical activity and cardiovascular health of men with prostate cancer. To refine the intervention. Design: Phase II feasibility study of a complex intervention. Setting: Nine community pharmacies in the UK. Intervention: Community pharmacy teams were trained to deliver a health assessment including fitness, strength and anthropometric measures. A computer algorithm generated a personalised lifestyle prescription for a homebased programme accompanied by supporting resources. The health assessment was repeated 12 weeks later and support phone calls were provided at weeks 1 and 6. Participants: 116 men who completed treatment for prostate cancer. Outcome measures: The feasibility and acceptability of the intervention and the delivery model were assessed by evaluating study processes (rate of participant recruitment, consent, retention and adverse events), by analysing delivery data and semi-structured interviews with participants and by focus groups with pharmacy teams. Physical activity (measured with accelerometry at baseline, 3 and 6 months) and patient reported outcomes (activation, dietary intake and quality of life) were evaluated. Change in physical activity was used to inform the sample size calculations for a future trial. Results: Out of 403 invited men, 172 (43%) responded and 116 (29%) participated. Of these, 99 (85%) completed the intervention and 88 (76%) completed the 6-month follow-up (attrition 24%). Certain components of the intervention were feasible and acceptable (eg, community pharmacy delivery), while others were more challenging (eg, fitness assessment) and will be refined for future studies. By 3 months, moderate to vigorous physical activity increased on average by 34 min (95% CI 6 to 62, p=0.018), but this was not sustained over 6 months. Conclusions: The community pharmacy intervention was feasible and acceptable. Results are encouraging and warrant a definitive trial to assess the effectiveness of the refined intervention.

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial (‘RISCK’ study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC −0.28 mmol/L p = 0.03; apo B −0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.

The idea that dietary cholesterol increases risk of coronary heart disease (CHD) by turning into blood cholesterol is compelling in much the same way that fish oil improves arthritis by lubricating our joints! Dietary cholesterol, chiefly in the form of eggs, has long been outlawed as a causative agent in CHD through its association with serum cholesterol. However, the scientific evidence to support a role for dietary cholesterol in CHD is relatively insubstantial in comparison with the incontrovertible link between its circulating blood relative in low density lipoprotein (LDL) cholesterol and CHD. Interpretation of the relationship between dietary cholesterol and CHD has been repeatedly confounded by an often inseparable relationship between dietary cholesterol and saturated fat. It has also been exaggerated by the feeding of unphysiologically high intakes of eggs. Nonetheless, numerous studies have shown that dietary cholesterol can increase serum LDL-cholesterol, but the size of this effect is highly variable between individuals and, according to over 30 years of prospective epidemiology, has no clinically significant impact on CHD risk. Variation in response to dietary cholesterol is a real phenomenon and we can now identify nutrient-gene interactions that give rise to this variation through differences in cholesterol homeostasis. More importantly, to view eggs solely in terms of the effects of their dietary cholesterol on serum cholesterol is to ignore the potential benefits of egg consumption on coronary risk factors, including obesity, diabetes and metabolic syndrome. Cardiovascular risk in these conditions is largely independent of LDL-cholesterol. These conditions are also relatively unresponsive to any LDL-cholesterol raising effects of dietary cholesterol. Treatment is focused primarily on weight loss, and it is in this respect that eggs may have a new and emerging role in facilitating weight loss through increased satiety. © 2006 British Nutrition Foundation.

Background: When advising patients on diet and health, the general practitioner (GP) makes judgements based on the evidence available. Since current evidence on diet and cardiovascular disease is conflicted and confusing, we surveyed the current consensus amongst GPs. The aim of this study was to determine the views of GPs on dietary saturated fat, carbohydrates and long chain omega-3 fatty acids in the management of cardiovascular disease. Method: An online questionnaire inviting participants to comment on seven contentious statements on diet and cardiovascular disease. Questionnaire circulated to the 1800 members of South West Thames Faculty of the Royal College of General Practitioners (RCGP). Participants were invited to tick “ Agree ” , “ Disagree ” or “ Not sure ” and were encouraged to add comments for each question. The results were analysed with a combination of statistical analysis and thematic analysis of comments. Results: There were 89 responses. Most GPs seem well aware that drug treatment alone is inadequate and that dietary advice is important. However, there was con siderable disagreement about the roles of saturated fats and carbohydrates in ca rdiovascular disease and “ Not sure ” responses ranged from 12 to 40.7%. The 40. 7% related to a statement on long chain omega-3 fatty acids. Analysis of comments revealed more opinions including an awareness of the need to warn patients about trans -fatty acids. Conclusions: Although the GP response rate was poor, responders do seem to see dietary advice as part of their role but do not consider themselves as experts. Education in this area should have a higher priority.

BACKGROUND: Dietary alpha-linolenic acid (ALA) has been associated with reduced risk of development of atherosclerosis. Adiponectin is a hormone specifically secreted by adipocytes and considered to have anti-atherogenic properties. AIM OF THE STUDY: We examined the effect of increased dietary intake of ALA on plasma concentration of adiponectin. METHODS: Thirty-five non-diabetic, dyslipidemic men, 38-71 years old, were randomly allocated to take either 15 ml of flaxseed oil rich in ALA (8.1 g/day; n = 18), or 15 ml of safflower oil per day, containing the equivalent n-6 fatty acid (11.2 g/day linoleic acid, LA; n = 17) (control group). The intervention period lasted for 12 weeks. RESULTS: Plasma levels of adiponectin did not change after the increase in dietary intake of ALA in the flaxseed oil supplementation group, compared to the control group. No changes in body mass index, serum lipid concentrations, LDL density, or plasma TNF-alpha were found in the flaxseed oil versus the control group. CONCLUSIONS: Dietary ALA has no effect on plasma adiponectin concentration in dyslipidemic men.

Objective SNPs identified from genome-wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. Methods Participants (n = 490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. Results The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total (P = 0.02) and LDL (P = 0.002) cholesterol, triglycerides (P = 0.001) and apolipoprotein B (P = 0.004), and with lower baseline concentrations of HDL cholesterol (P < 0.001) and apolipoprotein A-I (P < 0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Conclusion Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.

While the precise definition of hypertriglyceridaemia remains contentious, the condition is becoming more common in western populations as the prevalence of obesity and diabetes mellitus rise. Although there is strong epidemiological evidence that hypertriglyceridaemia is an independent risk factor for cardiovascular disease, it is has been difficult to demonstrate this by drug intervention studies, as drugs that reduce triglycerides also raise high density lipoprotein cholesterol. Precise target values have also been difficult to agree, although several of the new guidelines for coronary risk management now include triglycerides. The causes of hypertriglyceridaemia are numerous. The more severe forms have a genetic basis, and may lead to an increased risk of pancreatitis. Several types of hypertriglyceridaemia are familial and are associated with increased cardiovascular risk. Secondary causes of hypertriglyceridaemia are also numerous and it is important to exclude these before starting treatment with specific triglyceride-lowering agents. Lifestyle management is also very effective and includes weight reduction, restricted alcohol and fat intake and exercise.

Objective: The PPARG SNP rs1801282 (Pro12Ala C>G) has shown variable association with metabolic syndrome traits in healthy subjects. We investigated genotype association with plasma lipids and the influence of dietary polyunsaturated:saturated fat ratio (P:S) in subjects at increased cardiometabolic risk. Methods: Habitual dietary intake was recorded at recruitment to the RISCK Study. PPARG rs1801282 was genotyped in 466 subjects aged 30-70 y. Genotype associations with plasma lipids were assessed at recruitment, after a 4-wk high-SFA (HS) diet and a 24-wk intervention with reference (HS), high-MUFA (HM) and low-fat (LF) diets. The interaction of habitual P:S intake x genotype on plasma lipid concentrations was investigated. Results: PPARG rs1801282 G-allele frequency was 0.09. At recruitment, G-allele carriers had higher plasma total cholesterol concentration (n=415; P=0.05) after adjustment for BMI, gender, age and ethnicity. Dietary P:S ratio x genotype interaction influenced plasma LDLcholesterol (P=0.02) and triglyceride (P=0.03) concentrations. At P:S ratio 0.33, mean LDLcholesterol concentration in G-allele carriers was higher than in non-carriers, but fell between 0.34-0.65. Triglyceride concentration followed a similar pattern. After the 4-wk HS diet, Gallele carriers had higher concentrations of total cholesterol (P=0.03), LDL-cholesterol (P=0.04) and apo B (P=0.04) than non-carriers, after adjustments. After the 24-wk interventions, diet x genotype interaction did not significantly influence either LDLcholesterol (P=0.58) or triglyceride (P=0.57) concentrations. Conclusion: A high dietary P:S ratio would help to reduce plasma LDL-cholesterol and triglyceride concentrations in PPARG rs1801282 G-allele carriers at increased cardiometabolic risk.

Objective: To determine the effect of prolonged exposure to a submarine environment on biomarkers of cardiometabolic risk in Royal Navy (RN) submariners.

The link between dietary fat and coronary heart disease has attracted much attention since the effect of long-chain fatty acids on gene transcription has been established. The aim of this study was to investigate the effects of long-chain fatty acids and clofibrate on mRNA levels of specific lipid metabolism-related genes and to determine their effects on global transcriptome levels in a cardiovascular cell-line.

Re-examination of the evidence for the relationship between dietary cholesterol in eggs, blood cholesterol and heart disease has clarified that the effects of the dietary cholesterol on LDL do not translate into increased risk of developing coronary heart disease for the majority of the population. The resultant lifting of the restriction on the consumption of eggs should help to persuade healthy but limited egg-eaters to put aside their misconceptions and increase general access to the nutritional benefits of eggs. Unfortunately, food policy is not always driven by the weight of scientific evidence, but by the cost-effectiveness of a practice or behaviour. To this end, a recent study performed an analysis of the economic impact of eggs in terms of the risks and benefits of eating eggs as compared to the costs of developing disease from not eating eggs (17). The conclusion was that limiting egg consumption was not cost effective from a societal perspective and that removing the nutritional benefits of eggs could lead to other, less affordable, disease outcomes. Let's hope that we are all right.

In this Second Edition of the introductory text in the acclaimed Nutrition Society Textbook Series, "Introduction to Human Nutrition" has been revised and ...

A Nutrition Society member-led meeting was held on 9 January 2020 at The University of Surrey, UK. Sixty people registered for the event, and all were invited to participate, either through chairing a session, presenting a ‘3 min lightning talk’ or by presenting a poster. The meeting consisted of an introduction to the topic by Dr Barbara Fielding, with presentations from eight invited speakers. There were also eight lightning talks and a poster session. The meeting aimed to highlight recent research that has used stable isotope tracer techniques to understand human metabolism. Such studies have irrefutably shaped our current understanding of metabolism and yet remain a mystery to many. The meeting aimed to de-mystify their use in nutrition research.