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Chronic kidney disease (CKD) manifests with systemic inflammation, oxidative stress, and gut dysbiosis, resulting in metabolic disorders and elevated rates of cardiovascular disease–associated death. These all correlate with a high economic cost to healthcare systems. Growing evidence indicates that diet is an indispensable ally in the prevention and management of CKD and its complications. In this context, the root vegetable beetroot (Beta vulgaris rubra) deserves special attention because it is a source of several bioactive compounds, such as nitrate, betaine, and betalain, and has shown beneficial effects in CKD, including reduction of blood pressure, anti-inflammatory effects, and antioxidant actions by scavenging radical oxidative species, as observed in preclinical studies. Beetroot consumption as a possible therapeutic strategy to improve the clinical treatment of patients with CKD and future directions for clinical studies are addressed in this narrative review.

Aims/hypothesis Weight reduction is fundamental for type 2 diabetes management and remission, but uncertainty exists over which diet type is best to achieve and maintain weight loss. We evaluated dietary approaches for weight loss, and remission, in people with type 2 diabetes to inform practice and clinical guidelines. Methods First, we conducted a systematic review of published meta-analyses of RCTs of weight-loss diets. We searched MEDLINE (Ovid), PubMed, Web of Science and Cochrane Database of Systematic Reviews, up to 7 May 2021. We synthesised weight loss findings stratified by diet types and assessed meta-analyses quality with A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. We assessed certainty of pooled results of each meta-analysis using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (PROSPERO CRD42020169258). Second, we conducted a systematic review of any intervention studies reporting type 2 diabetes remission with weight-loss diets, in MEDLINE (via PubMed), Embase and Cochrane Central Register of Controlled Trials, up to 10 May 2021. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies – of Interventions [ROBINS-I]), with GRADE applied (PROSPERO CRD42020208878). Results We identified 19 meta-analyses of weight-loss diets, involving 2–23 primary trials (n = 100–1587), published 2013–2021. Twelve were ‘critically low’ or ‘low’ AMSTAR 2 quality, with seven ‘high’ quality. Greatest weight loss was reported with very low energy diets, 1.7–2.1 MJ/day (400–500 kcal) for 8–12 weeks (high-quality meta-analysis, GRADE low), achieving 6.6 kg (95% CI −9.5, −3.7) greater weight loss than low-energy diets (4.2–6.3 MJ/day [1000–1500 kcal]). Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI −3.3, −1.4) greater weight loss over 12–52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3–2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate). For type 2 diabetes remission, of 373 records, 16 met inclusion criteria. Remissions at 1 year were reported for a median 54% of participants in RCTs including initial low-energy total diet replacement (low-risk-of-bias study, GRADE high), and 11% and 15% for meal replacements and Mediterranean diets, respectively (some concerns for risk of bias in studies, GRADE moderate/low). For ketogenic/very low-carbohydrate and very low-energy food-based diets, the evidence for remission (20% and 22%, respectively) has serious and critical risk of bias, and GRADE certainty is very low. Conclusions/interpretation Published meta-analyses of hypocaloric diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets. Programmes including a hypocaloric formula ‘total diet replacement’ induction phase were most effective for type 2 diabetes remission. Most of the evidence is restricted to 1 year or less. Well-conducted research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications. Graphical abstract

Objectives: The Remote Diet Intervention to Reduce Long COVID Symptoms Trial (ReDIRECT) evaluates whether the digitally delivered, evidence-based, cost-effective Counterweight-Plus weight management programme improves symptoms of Long COVID in people with overweight/obesity. Methods: Baseline randomised, non-blinded design with 240 participants allocated in a 1:1 ratio either to continue usual care or to add the remotely delivered Counterweight-Plus weight management programme, which includes a Counterweight dietitian supported delivery of 12 weeks total diet replacement, food reintroduction, and long-term weight loss maintenance. Randomisation is achieved by accessing a web-based randomisation system incorporated into the study web portal developed by a registered Clinical Trials Unit. We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months. Participants in the control arm enter the weight management programme after six months. We are recruiting participants from social media and existing networks (e.g., Long COVID Scotland groups), through newspaper advertisements and from primary care. Main inclusion criteria: people with Long COVID symptoms persisting > three months, aged 18 years or above, body mass index (BMI) above 27kg/m2 (>25kg/m2 for South Asians). The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses). Anticipated results: The recruitment for this study started in December 2021 and ended in July 2022. Project results are not yet available and will be shared via peer-reviewed publication once the six-months outcomes have been analysed. Trial registration: Current Controlled Trials ISRCTN12595520

Although the relationship between colorectal neoplasia and inflammation is well described, the role of faecal calprotectin (FC) in clinical practice to diagnose or screen patients for colorectal neoplasia is less defined. This prospective study characterizes the relationship between FC and colorectal neoplasia in patients within the faecal occult blood testing (FOBT) positive patients in the Scottish Bowel Screening Programme.All FOBT positive patients attending for colonoscopy between February 2016 and July 2017 were invited to participate. Patients provided a stool sample for FC before commencing bowel preparation. All demographics and endoscopic findings were collected prospectively.In all, 352 patients were included. 210 patients had FC 50 µg. Colorectal cancer (CRC) patients had a higher median FC (138.5 μg/g, P 0.05), in comparison to those without CRC, and 13/14 had an FC 50 µg/g (93%). FC had a high sensitivity (92.8%) and negative predictive value (99.3%) for CRC, but with a low specificity (41.7%) and positive predictive value (6.2%). FC sensitivity increased sequentially as neoplasms progressed from non-advanced to malignant neoplasia (48.6% non-advanced adenoma vs. 92.9% CRC). However, no significant relationship was observed between FC and non-cancer neoplasia.In an FOBT positive screening population, FC was strongly associated with CRC (sensitivity 92.8%, specificity 41.7% for CRC, at 50 µg/g). However, although sensitive for the detection of CRC, FC failed to show sufficient sensitivity or specificity for the detection of non-cancer neoplasia. Based on these results we cannot recommend routine use of FC in a bowel screening population to detect cancer per se, but it is apparent that, with further optimization, faecal assessments including quantification of haemoglobin and inflammation could form part of a risk assessment tool aimed at refining the selection of patients for colonoscopy in both symptomatic and screening populations.

Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.

Low-carbohydrate diets (LCD) have been promoted for weight control and type 2 diabetes (T2D) management, based on an emerging body of evidence, including meta-analyses with an indication of publication bias. Proposed definitions vary between 50 and 130 g/d, or

Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.

This study investigated the efficacy of participation in culture-specific dancing to meet current physical activity recommendations and increase cardio-respiratory fitness in postmenopausal women. Sedentary postmenopausal women (n = 24), aged 63 &plusmn, 8 years and with BMI of 28 &plusmn, 3 kg/m2 completed a 4-week Scottish dancing study. The dancing sessions of approximately 75 min were performed twice a week and each session was based on five Scottish dances performed in 3 sets. Heart rate (HR) measurements were obtained during all dances to evaluate whether the intervention achieves the criteria of moderate to vigorous aerobic exercise intensity. Body composition, waist circumference, and HR during Chester Step test were measured before and after dancing intervention. HR achieved during individual dances ranged from 64 &plusmn, 5% to 80 &plusmn, 5% of HRmax and the mean HR of the five dances corresponded to 72 &plusmn, 7% of HRmax. Post-intervention mean HR was lower throughout Level 2 (Pre, 112 &plusmn, 13 bpm, Post, 106 &plusmn, p = 0.005) and Level 3 (Pre, 122 &plusmn, 14 bpm, Post, 115 &plusmn, p = 0.006) of the Chester test compared with baseline values. The intervention had no impact on body weight or body fat but reduced waist circumference (Pre, 94 &plusmn, 8 cm, Post, 91 &plusmn, 9 cm, p = 0.006). Thus, traditional Scottish dancing should be advocated to sedentary postmenopausal women, emphasising its potential in meeting current physical activity recommendations in relation of weekly duration and exercise intensity and improving cardiorespiratory fitness.

Chocolate is a widely appreciated foodstuff with historical appreciation as a food from the gods. In addition to its highly palatable taste, it is a rich source of (poly)phenolics, which have several proposed salutogenic effects, including neuroprotective anti-inflammatory, anti-oxidant and cardioprotective capabilities. Despite the known benefits of this ancient foodstuff, there is a paucity of information on the effects of chocolate on in the context of chronic kidney disease (CKD). This review focusses on the potential salutogenic contribution of chocolate intake, to mitigate inflammatory and oxidative burden in CKD, its potential, for cardiovascular protection and on the maintenance of diversity in gut microbiota, as well as clinical perspectives, on regular chocolate intake by CKD patients.

This narrative review aims to critically evaluate scientific evidence exploring the therapeutic role(s) of long-chain n-3 PUFA in the context of ageing, and specifically, sarcopenia. We highlight that beyond impairments in physical function and a lack of independence, the age-related decline in muscle mass has ramifications for cardio-metabolic health. Specifically, skeletal muscle is crucial in regulating blood glucose homeostasis (and by extension reducing type 2 diabetes mellitus risk) and providing gluconeogenic precursors that are critical for survival during muscle wasting conditions (i.e. AIDS). Recent interest in the potential anabolic action of n-3 PUFA is based on findings from experimental studies that measured acute changes in the stimulation of muscle protein synthesis (MPS) and/or chronic changes in muscle mass and strength in response to fish oil-derived n-3 PUFA supplementation. Key findings include a potentiated response of MPS to amino acid provision or resistance-based exercise with n-3 PUFA in healthy older adults that extrapolated to longer-term changes in muscle mass and strength. The key mechanism(s) underpinning this enhanced response of MPS remains to be fully elucidated, but is likely driven by the incorporation of exogenous n-3 PUFA into the muscle phospholipid membrane and subsequent up-regulation of cell signalling proteins known to control MPS. In conclusion, multiple lines of evidence suggest that dietary n-3 PUFA provide an essential link between musculoskeletal and cardio-metabolic health in older adults. Given that western diets are typically meagre in n-3 PUFA content, nutritional recommendations for maintaining muscle health with advancing age should place greater emphasis on dietary n-3 PUFA intake.

Flavanol intake positively influences several cardiometabolic risk factors in humans. However, the specific molecular mechanisms of action of flavanols, in terms of gene regulation, in the cell types relevant to cardiometabolic disease have never been systematically addressed. On this basis, we conducted a systematic literature review and a comprehensive bioinformatic analysis of genes whose expression is affected by flavanols in cells defining cardiometabolic health: hepatocytes, adipocytes, endothelial cells, smooth muscle cells and immune cells. A systematic literature search was performed using the following pre-defined criteria: treatment with pure compounds and metabolites (no extracts) at low concentrations that are close to their plasma concentrations. Differentially expressed genes were analyzed using bioinformatics tools to identify gene ontologies, networks, cellular pathways and interactions, as well as transcriptional and post-transcriptional regulators. The systematic literature search identified 54 differentially expressed genes at the mRNA level in in vitro models of cardiometabolic disease exposed to flavanols and their metabolites. Global bioinformatic analysis revealed that these genes are predominantly involved in inflammation, leukocyte adhesion and transendothelial migration, and lipid metabolism. We observed that, although the investigated cells responded differentially to flavanol exposure, the involvement of anti-inflammatory responses is a common mechanism of flavanol action. We also identified potential transcriptional regulators of gene expression: transcriptional factors, such as GATA2, NFKB1, FOXC1 or PPARG, and post-transcriptional regulators: miRNAs, such as mir-335-5p, let-7b-5p, mir-26b-5p or mir-16-5p. In parallel, we analyzed the nutrigenomic effects of flavanols in intestinal cells and demonstrated their predominant involvement in the metabolism of circulating lipoproteins. In conclusion, the results of this systematic analysis of the nutrigenomic effects of flavanols provide a more comprehensive picture of their molecular mechanisms of action and will support the future setup of genetic studies to pave the way for individualized dietary recommendations., COST (European Cooperation in Science and Technology) Action FA1403.

Introduction: Most consumers remain unaware of iodine sources in the diet. With no prophylaxis, iodine insufficiency remains a largely unappreciated issue in the UK. Including seaweed to the food supply represents a solution and opportunity but this supply needs to be carefully curated and calibrated, as excess iodine may be harmful for thyroid health. This project aimed to test the efficacy of a proof-of-concept reformulated food using seaweed as an ingredient source of iodine, to supplement women who have a habitual low iodine intake.Materials and Methods: Self-reported healthy women, pre-menopausal who avoid iodine-rich foods were randomised to: P1) reformulated food (pizza)with seaweed ingredient, or P2) a control food, similar to P1 but without supplemental iodine, or S1) control, empty capsules, or S2) PureSea Natural ascophyllum nodosum seaweed capsules, the ingredient used in P1. Capsules or food were to be consumed three times per week (providing 400μg iodine per intake). At least 10 spot urine samples were collected per person over at least 3 days preceding each study point. Urinary iodine was measured with a modified Sandell-Koltoff assay.Results: Participants (n = 96, median age 29, IQR 23–42) had a habitual iodine intake of 64μg/d (IQR 39–119, no detectable difference between groups). Dropout rates at 3-month were 41% (P1 &P2 each), 21% for S1, 11% for S2.Baseline urinary iodine concentration (UIC) was low/marginal, at 66μg/L (IQR 34-71), 64μg/L (IQR 40-96), 54μg/L (IQR 31-86) and 39μg/L (IQR 21-64) for P1, P2, S1 and S2 respectively (no difference between groups, p > 0.05).Change in UIC differed between groups at week-2 (p < 0.001), increasing in P1 & S2: by 45μg/L (IQR 2-69), and 35μg/L (IQR 13-48), respectively, decreasing in S1: -14μg/L (IQR –24-(–1)), with no change in group P2. This remained true for groups S1 & S2 when urinary iodine excretion was corrected for creatinine.After 3 months, differences in changes from baselines remained between groups (p < 0.01), with an increase in groups P1 and S2: 28μg/L (IQR 1-112), 43μg/L (IQR 23-93) but not groups P2 or S1. This remained true when UIC was corrected for creatinine.Changes in weight between and within groups were not detected at either time points, with group median changes within 2 kg of baseline weight.Discussion: Iodine-rich seaweed is effective in increasing the iodine status of women with a low habitual iodine intake, as a supplement, or as an ingredient in a cooked reformulated product. In term of feasibility, large attrition in the food groups P1 and P2 demands further attention, for interpretation of data and future translation of the findings.

IntroductionInteractions between polyphenols and non-digestible carbohydrates (NDC) can impact on polyphenolic metabolites bioavailability, including phenolic acids. The BLEND2 trial (NCT03840746) aims to study longer-term interactions of a flavonoid-rich food with/without NDC on microbiota metabolites and cardiometabolic markers. Trial feasibility using a bespoke food was tested.Material and MethodsThe soup was developed locally containing cherry tomatoes, tomato puree, red onion, fresh lovage, with/without the NDC inulin (10g), but improved and processed with Campden BRI, Chipping Campden, UK. The final product (~400g/ tin) was evaluated with VAS scales (0–10) for appearance, smell, taste and overall palatability, and flavonoid content evaluated using liquid chromatography-mass spectrometry. The 3-arm parallel randomised blinded design (control soup, soup + inulin, habitual diet control) recruited self-reported healthy participants (BMI > 25, 40–70y) with urine, blood, faecal samples collected at baseline, 3-week, 6-weeks.ResultsBoth soups scored similarly (n = 8 testers) for visual appeal (with inulin 5.1 ± 2.1; without 4.5 ± 2.0); smell (with 5.9 ± 1.7; without 5.4 ± 0.8); taste (with 6.6 ± 2.0; without 5.5 ± 2.3), aftertaste (with 6.3 ± 2.9; without 5.4 ± 2.3) and overall palatability (with 7.0 ± 1.9; without 6.1 ± 2.1).The soups (A&B), 1 tin/day, provide 68.5 ± 10.9 mg total flavonoids (soup A n = 3, quercetin equivalents) and 74.0 ± 16.1 mg (soup B, n = 3): quercetin (A 1.2 ± 0.1 mg; B 1.3 ± 0.6 mg), quercetin-4-glucoside (A 3.9 ± 1.0 mg; B 4.1 ± 1.9 mg), quercetin-3-rutinoside (A 23.0 ± 3.2 mg; B 20.5 ± 1.0 mg), quercetin 3,4-diglucosides (A 40.5 ± 6.9 mg; B 48.2 ± 14.9 mg).Following notes of interest (n = 415), n = 111 attended screening, n = 34 did not proceed (medications, opt-out; 31%). Participants (n = 77) are mostly British (79%), median age 56y (IQR 49-62) with a median BMI of 31 (IQR 28-35). Dropout was low (12%) and early in the study (personal issues, n = 2; gastrointestinal issues, n = 2; failure to comply with protocol, n = 2; acid reflux symptoms, n = 1; dislike of test food, n = 1). Adverse events included acid reflux/heartburn (n = 4), gastrointestinal distress (n = 3) accounting for 3 drop-outs.To date, urine, blood and faecal samples (study day or day + 1) were collected at all timepoints, for all participants. Participation (soup arms) has not led to body weight or blood lipids changes compared to control group.DiscussionThe protocol for this 6-week trial has proved feasible with lower dropout than expected. Soup flavonoid content representing ~16% of average European flavonoid intakes, with inulin (10g) half the UK daily fibre intake. The soup was well accepted with few reports of adverse issues. Recruitment in this population is challenging, due to high levels of medication and ill health.

Low-carbohydrate diets are being widely recommended, but with apparently conflicting evidence. We have conducted a formal systematic review of the published systematic reviews of RCTs between low-carbohydrate vs. control (low-fat/energy-restricted) diets in adults with overweight and obesity. In MEDLINE, Embase, Web of Knowledge and Cochrane Database of Systematic Reviews, searched from inception to September 2017, we identified 12 systematic reviews, 10 with meta-analyses. Differences in methods, study quality, weight change and citations of published systematic reviews were assessed by AMSTAR-2. Review methods varied in definitions of low-carbohydrate diet, databases searched and bias assessment. Overall review quality was high in two, moderate in three, critically low in seven. Among meta-analyses, 4/5 with critically low quality showed low-carbohydrate diet superiority for weight loss (0.7-4.0 kg), while high quality meta-analyses reported little or no difference between diets. Greater numbers of participants correlated with smaller differences in weight loss (r = 0.73, p = 0.03). More citations correlated with lower review quality (rho = -0.9, p = 0.037), with larger differences in weight loss (rho = -0.9, p = 0.037), and with journal impact factor (rho = 1.0, p = 0.01). In conclusion, publication acceptance and citations appear to favour apparently larger effect sizes above methodological quality. Better quality reviews and RCTs are needed, before recommending low-carbohydrate diets as preferred to other approaches for energy restriction.

Background Non-alcoholic fatty liver disease (NAFLD) is a serious health problem affecting ~25% of the global population. While NAFLD pathogenesis is still unclear, multiple NAFLD parameters, including reduced insulin sensitivity, impaired glucose metabolism and increased oxidative stress are hypothesised to foster the formation of advanced glycation end-products (AGEs). Given the link of AGEs with end organ damage, there is scope to examine the role of the AGE/RAGE axis activation in liver injury and NAFLD. Methods Age, sex and body mass index matched normo-glycemic NAFLD adults (n = 58) and healthy controls (n = 58) were enrolled in the study. AGEs were analysed by liquid chromatography-mass spectrometry (CML, CEL), fluorescence (pentosidine, AGE fluorescence), colorimetry (fructosamine) and ELISA (sRAGE). Their association with liver function, inflammation, fibrosis and stage of NAFLD was examined. Results Early and advanced glycation end-products, except Ne-carboxymethyl-L-lysine (CML), were 10–30% higher, sRAGE levels 1.7-fold lower, and glycation/sRAGE ratios 4-fold higher in the NAFLD cases compared to controls. While AGEs presented weak to moderate correlations with indices of liver function and damage (AST/ALT, HOMA-IR, TNF-α and TGF-β1), including sRAGE to characterize the AGEs/sRAGE axis strengthened the associations observed. High glycation/sRAGE ratios were associated with 1.3 to 14-fold likelihood of lower AST/ALT ratios. The sum of AGEs/sRAGE ratios accurately distinguished between healthy controls and NAFLD patients (area under the curve of 0.85). Elevated AGEs/sRAGE (>7.8 mmol/pmol) was associated with a 12-fold likelihood of the presence of NAFLD. Conclusion These findings strengthen the involvement of AGEs-RAGE axis in liver injury and the pathogenesis of NAFLD.

Iodine deficiency (ID) in women of childbearing age remains a global public health concern, mainly through its impact on fetal and infant neurodevelopment. While iodine status is improving globally, ID is still prevalent in pregnancy, when requirements increase. More than 120 countries have implemented salt iodisation and food fortification, strategies that have been partially successful. Supplementation during pregnancy is recommended in some countries and supported by the WHO when mandatory salt iodisation is not present. The UK is listed as one of the ten countries with the lowest iodine status globally, with approximately 60 % of pregnant women not meeting the WHO recommended intake. Without mandatory iodine fortification or recommendation for supplementation in pregnancy, the UK population depends on dietary sources of iodine. Both women and healthcare professionals have low knowledge and awareness of iodine, its sources or its role for health. Dairy and seafood products are the richest sources of iodine and their consumption is essential to support adequate iodine status. Increasing iodine through the diet might be possible if iodine-rich foods get repositioned in the diet, as they now contribute towards only about 13 % of the average energy intake of adult women. This review examines the use of iodine-rich foods in parallel with other public health strategies, to increase iodine intake and highlights the rare opportunity in the UK for randomised trials, due to the lack of mandatory fortification programmes.

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790., This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/).

This narrative review aims to critically evaluate scientific evidence exploring the therapeutic role(s) of long-chain n-3 PUFA in the context of ageing, and specifically, sarcopenia. We highlight that beyond impairments in physical function and a lack of independence, the age-related decline in muscle mass has ramifications for cardio-metabolic health. Specifically, skeletal muscle is crucial in regulating blood glucose homeostasis (and by extension reducing type 2 diabetes mellitus risk) and providing gluconeogenic precursors that are critical for survival during muscle wasting conditions (i.e. AIDS). Recent interest in the potential anabolic action of n-3 PUFA is based on findings from experimental studies that measured acute changes in the stimulation of muscle protein synthesis (MPS) and/or chronic changes in muscle mass and strength in response to fish oil-derived n-3 PUFA supplementation. Key findings include a potentiated response of MPS to amino acid provision or resistance-based exercise with n-3 PUFA in healthy older adults that extrapolated to longer-term changes in muscle mass and strength. The key mechanism(s) underpinning this enhanced response of MPS remains to be fully elucidated, but is likely driven by the incorporation of exogenous n-3 PUFA into the muscle phospholipid membrane and subsequent up-regulation of cell signalling proteins known to control MPS. In conclusion, multiple lines of evidence suggest that dietary n-3 PUFA provide an essential link between musculoskeletal and cardio-metabolic health in older adults. Given that western diets are typically meagre in n-3 PUFA content, nutritional recommendations for maintaining muscle health with advancing age should place greater emphasis on dietary n-3 PUFA intake.

A systematic review of published evidence on micronutrient intake/status with carbohydrate-restricted diets (CRD) was conducted in Web of Science, Medline, Embase, Scopus, CENTRAL, and ClinicalTrials.gov up to October 2018. We identified 10 studies: seven randomized controlled trials (RCTs) ("Atkins"-style, n = 5; "Paleolithic" diets, n = 2), two Atkins-style noncontrolled trials and one cross-sectional study. Prescribed carbohydrate varied 4% to 34% of energy intake. Only one noncontrolled trial prescribed multivitamin supplements. Dietary intakes/status were reported over 2 to 104 weeks, with weight losses from 2 to 9 kg. No diagnoses of deficiency were reported. Intakes of thiamine, folate, magnesium, calcium, iron, and iodine all decreased significantly (-10% to -70% from baseline) with any CRD types. Atkins diet trials (n = 6; 4%-34%E carbohydrate) showed inconsistent changes in vitamin A, E, and β-carotene intakes, while a single "Paleolithic" diet trial (28%E carbohydrate) reported increases in these micronutrients. One other "Paleolithic" diet (30%E carbohydrate) reported a rise in moderate iodine deficiency from 15% to 73% after 6 months. In conclusion, few studies have assessed the impacts of CRD on micronutrients. Studies with different designs point towards reductions in several vitamins and minerals, with potential risk of micronutrient inadequacies. Trial reporting standards are expected to include analysis of micronutrient intake/status. Micronutrients in foods and/or supplements should be considered when designing, prescribing or following CRDs.

&beta, Glucan and black tea are fermented by the colonic microbiota producing short chain fatty acids (SCFA) and phenolic acids (PA). We hypothesized that the addition of &beta, glucan, a dietary fiber, and tea polyphenols to a food matrix like bread will also affect starch digestion in the upper gut and thus further influence colonic fermentation and SCFA production. This study investigated SCFA and PA production from locally developed breads: white bread (WB), black tea bread (BT), &beta, glucan bread (&beta, G), &beta, glucan plus black tea bread (&beta, GBT). Each bread was incubated in an in vitro system mimicking human digestion and colonic fermentation. Digestion with &alpha, amylase significantly (p = 0.0001) increased total polyphenol and polyphenolic metabolites from BT bread compared with WB, &beta, G, and &beta, GBT. Total polyphenols in &beta, GBT remained higher (p = 0.016, 1.3-fold) after digestion with pepsin and pancreatin compared with WB. Fermentations containing &beta, G and &beta, GBT produced similar propionate concentrations ranging from 17.5 to 18.6 mmol/L and total SCFA from 46.0 to 48.9 mmol/L compared with control WB (14.0 and 37.4 mmol/L, respectively). This study suggests that combination of black tea with &beta, glucan in this functional bread did not impact on SCFA production. A higher dose of black tea and &beta, glucan or in combination with other fibers may be needed to increase SCFA production.

Purpose Evidence exists regarding the beneficial effects of diets rich in plant-based foods regarding the prevention of cardiometabolic diseases. These plant-based foods are an exclusive and abundant source of a variety of biologically active phytochemicals, including polyphenols, carotenoids, glucosinolates and phytosterols, with known health-promoting effects through a wide range of biological activities, such as improvements in endothelial function, platelet function, blood pressure, blood lipid profile and insulin sensitivity. We know that an individual’s physical/genetic makeup may influence their response to a dietary intervention, and thereby may influence the benefit/risk associated with consumption of a particular dietary constituent. This inter-individual variation in responsiveness has also been described for dietary plant bioactives but has not been explored in depth. To address this issue, the European scientific experts involved in the COST Action POSITIVe systematically analyzed data from published studies to assess the inter-individual variation in selected clinical biomarkers associated with cardiometabolic risk, in response to the consumption of plant-based bioactives (poly)phenols and phytosterols. The present review summarizes the main findings resulting from the meta-analyses already completed. Results Meta-analyses of randomized controlled trials conducted within POSITIVe suggest that age, sex, ethnicity, pathophysiological status and medication may be responsible for the heterogeneity in the biological responsiveness to (poly)phenol and phytosterol consumption and could lead to inconclusive results in some clinical trials aiming to demonstrate the health effects of specific dietary bioactive compounds. However, the contribution of these factors is not yet demonstrated consistently across all polyphenolic groups and cardiometabolic outcomes, partly due to the heterogeneity in trial designs, low granularity of data reporting, variety of food vectors and target populations, suggesting the need to implement more stringent reporting practices in the future studies. Studies investigating the effects of genetic background or gut microbiome on variability were limited and should be considered in future studies. Conclusion Understanding why some bioactive plant compounds work effectively in some individuals but not, or less, in others is crucial for a full consideration of these compounds in future strategies of personalized nutrition for a better prevention of cardiometabolic disease. However, there is also still a need for the development of a substantial evidence-base to develop health strategies, food products or lifestyle solutions that embrace this variability., Key messages A balanced diet, rich in plant-based foods is known for the prevention of obesity, diabetes, and cardiovascular disease risk.(Poly)phenols and phytosterols displayed a range of biological effects of relevance to contribute to the cardiometabolic health benefits of plant foodsHowever, inter-individual variability in response to plant food bioactive consumption exists, and there is a need to understand the causes of this variation.Analysis of published RCTs examining impact of consumption of (poly)phenols and phytosterols on cardiometabolic risk factors demonstrated that a number of factors including age, sex, adiposity and health status could contribute to the effect demonstrated within these studies.Genome and microbiome studies will help identify what may be causing this variation.More studies, specifically designed to investigate individual variation are needed to fully understand the factors responsible for and the impact of this variationOnce fully understood, such variation should be used in directing personalised nutrition advice.

Dietary fibre and polyphenols are both metabolised to short-chain fatty acids (SCFAs) and phenolic acids (PA) by the colonic microbiota. These may alter microbiota growth/diversity, but their interaction is not understood. Interactions between rutin and raftiline, ispaghula or pectin were investigated in human faecal batch cultures (healthy participants, 19&ndash, 33 years, 4 males, 6 females, BMI 18.4&ndash, 27.4) after a low (poly)phenol diet three days prior to study. Phenolic acids were measured by gas chromatography-mass spectrometry and SCFAs by gas chromatography-flame ionisation after 2, 4, 6, and 24 h. Rutin fermentation produced Phenyl acetic acid (PAA), 4-Hydroxy benzoic acid (4-OHBA), 3-Hydroxy phenyl acetic acid (3-OHPAA), 4-Hydroxy phenyl acetic acid (4-OHPAA), 3,4-Dihydroxy phenyl acetic acid (3,4-diOHPAA), 3-Hydroxy phenyl propionic acid (3-OHPPA), and 4-Hydroxy phenyl propionic acid (4-OHPPA). 3,4-DiOHPAA and 3-OHPAA were predominant at 6 h (1.9 &plusmn, 1.8 &micro, g/mL, 2.9 &plusmn, 2.5 &micro, g/mL, and 0.05 &plusmn, 0.0 &micro, g/mL, respectively) and 24 h (5.5 &plusmn, 3.3 &micro, g/mL, 3.1 &plusmn, 4.2 &micro, g/mL, and 1.2 &plusmn, 1.6 &micro, g/mL). Production of all PA except 3-OHPPA and 4-OHPPA was reduced by at least one fibre. Inhibition of PA was highest for rutin (8-fold, p &lt, 0.01), then pectin (5-fold, p &lt, 0.01), and ispaghula (2-fold, p = 0.03). Neither rutin nor quercetin had a detectable impact on SCFA production. These interactions should be considered when assessing dietary polyphenols and potential health benefits.

Raspberry pomace is a source of polyphenols, which nutritional and health promoting properties are not sufficiently known. The aim of this 8-weeks study was to scrutinize if raspberry extracts (REs) with different ellagitannins to flavan-3-ols ratios might favorably affect the caecal fermentation processes and blood lipid profile in rats. Forty male Wistar rats were fed with a standard diet or its modification with two types of REs (E1 and E2) characterized by different ratios of ellagitannins to flavan-3-ols (7.7 and 3.1 for E1 and E2, respectively) and added to a diet at two dosages of polyphenolic compounds (0.15 and 0.30% of a diet, L and H treatments, respectively). Irrespective of polyphenols dietary level, both REs reduced the activity of bacterial β-glucuronidase, increased production of butyric acid in the caecum and reduced triacylglycerols in blood plasma. The E1 treatment at both dosages caused more effective reduction in the concentration of ammonia and elevated acetate level in the caecal digesta than E2. On the other hand, only the E2 treatment lowered value of the atherogenic index when compared with control group. When comparing dosages of REs, a higher one was more potent to reduce the activity of bacterial β-glucosidase, β-, α-galactosidase and lowered value of the HDL profile in plasma. To conclude, REs may favorably modulate the activity of the caecal microbiota and blood lipid profile in rats, however, the intensity of these effects may be related to the dosages of dietary polyphenols and to their profile, e.g., ellagitannins to flavan-3-ols ratio.

A systematic review and meta-analysis of randomized controlled trials exploring the role of inter-individual variability on the effect of flavanols on insulin and HOMA-IR. 2018 Spring Conference on Nutrient-Nutrient Interaction

Iodine is essential for thyroid hormones synthesis and normal neurodevelopment; however, ~60% of pregnant women do not meet the WHO (World Health Organization) recommended intake. Using a qualitative design, we explored the perceptions, awareness, and experiences of pregnancy nutrition, focusing on iodine. Women in the perinatal period (n = 48) were interviewed and filled in a food frequency questionnaire for iodine. Almost all participants achieved the recommended 150 μg/day intake for non-pregnant adults (99%), but only 81% met the increased demands of pregnancy (250 μg/day). Most were unaware of the importance, sources of iodine, and recommendations for iodine intake. Attitudes toward dairy products consumption were positive (e.g., helps with heartburn; easy to increase). Increased fish consumption was considered less achievable, with barriers around taste, smell, heartburn, and morning sickness. Community midwives were the main recognised provider of dietary advice. The dietary advice received focused most often on multivitamin supplements rather than food sources. Analysis highlighted a clear theme of commitment to change behaviour, motivated by pregnancy, with a desired focus on user-friendly documentation and continued involvement of the health services. The study highlights the importance of redirecting advice on dietary requirements in pregnancy and offers practical suggestions from women in the perinatal period as the main stakeholder group.

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation., This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 “POSITIVe” to conduct a short-term scientific mission to K.C. at CEBAS-CSIC (A.G.-S. and M.T.G.-C.) during which the data analysis was performed.

Iodine is essential for thyroid hormones synthesis and normal neurodevelopment; however, ~60% of pregnant women do not meet the WHO (World Health Organization) recommended intake. Using a qualitative design, we explored the perceptions, awareness, and experiences of pregnancy nutrition, focusing on iodine. Women in the perinatal period (n = 48) were interviewed and filled in a food frequency questionnaire for iodine. Almost all participants achieved the recommended 150 μg/day intake for non-pregnant adults (99%), but only 81% met the increased demands of pregnancy (250 μg/day). Most were unaware of the importance, sources of iodine, and recommendations for iodine intake. Attitudes toward dairy products consumption were positive (e.g., helps with heartburn; easy to increase). Increased fish consumption was considered less achievable, with barriers around taste, smell, heartburn, and morning sickness. Community midwives were the main recognised provider of dietary advice. The dietary advice received focused most often on multivitamin supplements rather than food sources. Analysis highlighted a clear theme of commitment to change behaviour, motivated by pregnancy, with a desired focus on user-friendly documentation and continued involvement of the health services. The study highlights the importance of redirecting advice on dietary requirements in pregnancy and offers practical suggestions from women in the perinatal period as the main stakeholder group.

Current focus in colorectal cancer (CRC) management is on reducing overall mortality by increasing the number of early-stage cancers diagnosed and treated with curative intent. Despite the success of screening programs in down-staging CRC, interval cancer rates are substantial and other strategies are desirable. Sporadic CRC is largely associated with lifestyle factors including diet. Polyphenols are phytochemicals ingested as part of a normal diet, which are abundant in plant foods including fruits/berries and vegetables. These may exert their anti-carcinogenic effects via the modulation of inflammatory pathways. Key signal transduction pathways are fundamental to the association of inflammation and disease progression including those mediated by NF-κB and STAT, PI3K and COX. Our aim was to examine the evidence for the effect of dietary polyphenols intake on tumor and host inflammatory responses to determine if polyphenols may be effective as part of a dietary intervention. There is good epidemiological evidence of a reduction in CRC risk from case-control and cohort studies assessing polyphenol intake. It would be premature to suggest a major public health intervention to promote their consumption; however, dietary change is safe and feasible, emphasizing the need for further investigation of polyphenols and CRC risk.