Do high-protein diets have the potential to reduce gut barrier function in a sex-dependent manner?

PURPOSE: Impaired gut barrier function is associated with systemic inflammation and many chronic diseases. Undigested dietary proteins are fermented in the colon by the gut microbiota which produces nitrogenous metabolites shown to reduce barrier function in vitro. With growing evidence of sex-based differences in gut microbiotas, we determined whether there were sex by dietary protein interactions which could differentially impact barrier function via microbiota modification. METHODS: Fermentation systems were inoculated with faeces from healthy males (n = 5) and females (n = 5) and supplemented with 0.9 g of non-hydrolysed proteins sourced from whey, fish, milk, soya, egg, pea, or mycoprotein. Microbial populations were quantified using fluorescence in situ hybridisation with flow cytometry. Metabolite concentrations were analysed using gas chromatography, solid phase microextraction coupled with gas chromatography-mass spectrometry and ELISA. RESULTS: Increased protein availability resulted in increased proteolytic Bacteroides spp (p < 0.01) and Clostridium coccoides (p < 0.01), along with increased phenol (p < 0.01), p-cresol (p < 0.01), indole (p = 0.018) and ammonia (p < 0.01), varying by protein type. Counts of Clostridium cluster IX (p = 0.03) and concentration of p-cresol (p = 0.025) increased in males, while females produced more ammonia (p = 0.02), irrespective of protein type. Further, we observed significant sex-protein interactions affecting bacterial populations and metabolites (p < 0.005). CONCLUSIONS: Our findings suggest that protein fermentation by the gut microbiota in vitro is influenced by both protein source and the donor's sex. Should these results be confirmed through human studies, they could have major implications for developing dietary recommendations tailored by sex to prevent chronic illnesses.

Impact of a food-based dietary fat exchange model for replacing dietary saturated with unsaturated fatty acids in healthy men on plasma phospholipids fatty acid profiles and dietary patterns.

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 11 year) 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.

Patient activation and patient-reported outcomes of men from a community pharmacy lifestyle intervention after prostate cancer treatment.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.001), but lower (worse) scores in the urinary irritative/obstructive (p = 0.003), bowel (p < 0.001) and hormonal (p < 0.001) domains. Poor sexual function was common across all age groups irrespective of prostate cancer treatment. CONCLUSIONS: The intervention led to significant improvements in patient activation, exercise and diet. Community pharmacy could deliver effective services to address sexual dysfunction, pain and discomfort which are common after prostate cancer.

Obesity and low levels of physical activity impact on cardiopulmonary fitness in older men after treatment for prostate cancer.

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.

Musculoskeletal pain in lacrosse officials impacts function on the field.

This study determined the prevalence of joint pain among lacrosse officials and described the impact of pain thereof on current officiating duties on the field. Members of the US Lacrosse Officials Development Programme were provided with an electronic survey (a 15.7% response rate resulted in N = 1,441 of completed surveys). Pain sites and severity, previous injuries and current impact of musculoskeletal pain on officiating duties were captured. Pain was present in 18.1-40.1% of respondents at the foot, shoulder, back and knee. A total of 437 officials reported diagnoses of osteoarthritis ([OA]; knee 48.7%, hip 10.5%, spine 10.1%, shoulder 8.0%) and 247 reported OA in more than one joint (p < .05). Officials with OA or previous lacrosse-related injuries reported frequent difficulty with running the entire field distance (p < 0.0001), starting and stopping on the field (p < 0.0001), keeping pace (p < 0.0001), focusing on multiple actions of players at once (p < 0.0001), and enjoyment (all p < 0.0001). Musculoskeletal pain is a common, unrecognized issue in this population that interferes with sport officiating functions. Additional study is needed to objectively determine the impact of OA pain and musculoskeletal injuries on measurable performance outcomes on the field and subjective measures of focus, attention and enjoyment.

Impact of the occupational environment of a submerged submarine on cardiometabolic health of Royal Navy submariners.

OBJECTIVE: To determine the effect of prolonged exposure to a submarine environment on biomarkers of cardiometabolic risk in Royal Navy (RN) submariners. METHODS: Serum lipids (cholesterol (C), triglyceride (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C), glucose, insulin and anthropometrics were compared within three RN submarine crews before and after submerged patrols of 12 or 6 weeks, and with a crew that remained ashore (SUB-HOME). Dietary intake and activity patterns were self-reported during each patrol. Differences were assessed in crew characteristics using one-way analysis of variance and in serum lipids using paired t-tests. RESULTS: Postpatrol, the mean body weight of submerged crews decreased (-1.4±4.2 kg, p=0.0001), but increased in SUB-HOME (1.9±1.8 kg, p=0.0001). Modest improvements in serum lipids (mean individual change (mmol/L); C=-0.3±0.7, p=0.0001; TG=-0.3±0.7, p=0.0001; HDL-C=-0.1±0.3, p=0.0001; non-HDL-C=-0.2±0.6, p=0.012), glucose (-0.2±0.5, p=0.0001) and insulin (-1.5±4.6 mU/L, p=0.001) were observed in submerged crews. Changes in serum lipids were positively associated with changes in body weight within crews combined. Energy intake was maintained during submerged patrols but was lower compared with non-submerged (11 139±2792 vs. 9617±2466 kJ, p=0.001; 11 062±2775 vs. 9632±2682 kJ, p=0.003). CONCLUSIONS: The environment of a submerged submarine produced no adverse effects on serum biomarkers of cardiometabolic risk in crew. Conversely, modest improvements in these biomarkers were associated with a decrease in body weight.

Creating a teachable moment in community pharmacy for men with prostate cancer: A qualitative study of lifestyle changes.

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.

Responses to a GP survey: current controversies in diet and cardiovascular disease.

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 considerable disagreement about the roles of saturated fats and carbohydrates in cardiovascular 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.

Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets.

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<0.02) and low sugar (P<0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet (P<0.01), and a higher VLDL1-TAG production rate after the low sugar diet (P<0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG (P<0.02) in the controls, but in contrast, a higher production of VLDL2-TAG (P<0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.

Current and future strategies for the nutritional management of cardiometabolic complications of androgen deprivation therapy for prostate cancer.

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.

Randomised controlled trial of the effect of long-term selenium supplementation on plasma cholesterol in an elderly Danish population.

Although cross-sectional studies have shown a positive association between Se and cholesterol concentrations, a recent randomised controlled trial in 501 elderly UK individuals of relatively low-Se status found that Se supplementation for 6 months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were randomised to 100 (n 124), 200 (n 122) or 300 (n 119) µg Se-enriched yeast or matching placebo-yeast tablets (n 126) daily for 5 years. A total of 468 participants continued the study for 6 months and 361 participants, equally distributed across treatment groups, continued for 5 years. Plasma samples were analysed for total and HDL-cholesterol and for total Se concentrations at baseline, 6 months and 5 years. The effect of different doses of Se supplementation on plasma lipid and Se concentrations was estimated by using linear mixed models. Plasma Se concentration increased significantly and dose-dependently in the intervention groups after 6 months and 5 years. Total cholesterol decreased significantly both in the intervention groups and in the placebo group after 6 months and 5 years, with small and nonsignificant differences in changes in plasma concentration of total cholesterol, HDL-cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between intervention and placebo groups. The effect of long-term supplementation with Se on plasma cholesterol concentrations or its sub-fractions did not differ significantly from placebo in this elderly population.

HDL and lifestyle interventions.

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.

Nonpharmacological approaches for reducing serum low-density lipoprotein cholesterol.

PURPOSE OF REVIEW: To reinforce the key role of diet and lifestyle modification as the first-line treatment for the reduction of raised serum low-density lipoprotein cholesterol (LDL-C) and prevention of cardiovascular disease. Also, to counter recent claims that the current dietary guidelines for the treatment of cardiovascular disease have misplaced emphasis on the importance of removing dietary saturated fat instead of sugar. RECENT FINDINGS: This review provides new insight into the effects of diet and lifestyle factors with established efficacy in lowering serum LDL-C. This includes energy-restricted weight loss and new findings on the effects of alternative day fasting; novel metabolic and molecular effects of replacing palmitic acid with oleic acid; evidence for a dose-response relationship between the intake of dietary stanols and LDL-C; and identification of a unique metabolic pathway for the excretion of cholesterol. SUMMARY: The review reports new evidence for the efficacy of alternate day fasting, reassurance that the current dietary guidelines are not misguided by recommending removal of saturated fat, that a high intake of dietary stanols can achieve a reduction in LDL-C of up to 18%, and describes a pathway of cholesterol excretion that may help to explain variation in the response of serum LDL-C to dietary fat and cholesterol.

Saturated fat and CVD: importance of inter-individual variation in the response of serum low-density lipoprotein cholesterol.

The aim of this review is to provide an overview of the history in support of the role of dietary saturated fatty acids (SFA) in the development of cardiovascular disease (CVD), and the controversy and consensus for the evidence in support of guidelines to remove and replace SFA with unsaturated fatty acids. The review will also examine the existence, origins, and implications for CVD risk of variability in serum LDL-cholesterol in response to these guidelines. While the quality of supporting evidence for the efficacy of restricting SFA on CVD risk has attracted controversy, this has helped to increase understanding of the inter-relationships between SFA, LDL-cholesterol and CVD, and reinforce confidence in this dietary recommendation. Nevertheless, there is significant inter-individual variation in serum LDL-C in response to this dietary change. The origins of this variation are multi-factorial and involve both dietary and metabolic traits. If serum biomarkers of more complex metabolic traits underlying LDL-responsiveness can be identified, this would have major implications for the targeting of these dietary guidelines to LDL-responders, to maximise the benefit to their cardiovascular health.

Variation of LDL cholesterol in response to the replacement of saturated with unsaturated fatty acids: a nonrandomized, sequential dietary intervention; the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention ("RISSCI"-1) study.

BACKGROUND: Serum low density lipoprotein (LDL) cholesterol shows marked interindividual variation in response to the replacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs). OBJECTIVES: To demonstrate the efficacy of United Kingdom guidelines for exchanging dietary SFAs for UFAs, to reduce serum LDL cholesterol and other cardiovascular disease (CVD) risk factors, and to identify determinants of the variability in LDL cholesterol response. METHODS: Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2), consumed a higher-SFA/lower-UFA diet for 4 wk, followed by an isoenergetic, lower-SFA/higher-UFA diet for 4 wk (achieved intakes SFA:UFA as % total energy 19.1:14.8 and 8.9:24.5, respectively). Serum LDL cholesterol, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of each diet. RESULTS: Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids: LDL cholesterol (-0.50 mmol/L; 95% confidence interval [CI]: -0.58, -0.42), high-density lipoprotein (HDL) cholesterol (-0.11 mmol/L; 95% CI: -0.14, -0.08), and total cholesterol (TC) (-0.65 mmol/L; 95% CI:-0.75, -0.55). The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL cholesterol ratio, non-HDL cholesterol, E-selectin (P < 0.0001), and LDL subfraction composition (cholesterol [LDL-I and LDL-II], apoB100 [LDL-I and LDL-II], and TAG [LDL-II]) (P < 0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (ß-sitosterol, campesterol, cholestanol), and synthesis (desmosterol) (P < 0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P = 0.035). Marked interindividual variation in the change in serum LDL cholesterol response (-1.39 to +0.77 mmol/L) to this dietary exchange was observed, with 33.7% of this variation explained by serum LDL cholesterol before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and 6.7%, respectively). APOE genotype was unrelated to serum LDL cholesterol response to SFA. CONCLUSIONS: These findings support the efficacy of United Kingdom SFA dietary guidelines for the overall lowering of serum LDL cholesterol but showed marked variation in LDL cholesterol response. Further identification of the determinants of this variation will facilitate targeting and increasing the efficacy of these guidelines. The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).