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IMPORTANCE: The evidence that maintaining a healthy body weight in conjunction with healthier eating patterns, exercise training, and reduced stress can improve clinical outcomes in patients with atherosclerotic cardiovascular disease is substantial. However, little is known about the magnitude and temporal effects of a comprehensive lifestyle treatment on coronary artery anatomy, myocardial inflammation, and fibrosis in people affected by coronary heart disease. OBJECTIVE: To conduct a randomised clinical trial to determine the impact of a 12-month intense lifestyle intervention delivered via an mHealth platform (in the form of a mobile App) versus standard clinical care on low attenuation plaque volume and structure, stress myocardial perfusion, and diastolic function. DESIGN: A single centre, parallel-group, randomised controlled trial. The co-primary endpoints are: 1-Low Attenuation Plaque (LAP) volume (mm3) using coronary computed tomography angiography (CCTA) at 12 months, and 2-Adenosine stress myocardial blood flow (stress MBF, mL/min/g) using cardiovascular magnetic resonance imaging (MRI) at 12 months. Other key measurements include liver steatosis by MRI, subclinical abnormalities detected by advanced electrocardiography, arterial stiffness, endothelial function, genomic, metabolomic, and gut microbiome-related adaptations to these structural changes. An intention-to-treat principle will be used for all analyses. SETTING: Participants will be recruited from a large academic cardiology office practice (Central Sydney Cardiology) and Royal Prince Alfred Hospital (RPAH) Departments of Cardiology and Radiology. All clinical investigations will be undertaken within the Charles Perkins Centre-RPAH clinic. PARTICIPANTS: Individuals (n = 150) with stable coronary heart disease who have low attenuation plaque based on a CCTA within the past 3 months, will be randomised to a lifestyle intervention program comprising a 5:2 pesco-vegetarian diet, exercise training, and mindfulness-based stress reduction (n = 75) or usual care (n = 75). DISCUSSION: This trial will represent the single most detailed and integrated analysis of the effects of a comprehensive lifestyle intervention targeting multiple metabolic pathways, delivered via a customized mHealth App on smart devices, on coronary macro- and microcirculation, heart physiology, and cardiometabolic risk. It will provide a new framework for allowing clinicians and individuals to optimise metabolic health for the prevention and management of atherosclerotic cardiovascular diseases that is epidemic in modern society.

BackgroundNutritional intake could influence the development of frailty. The aim was to evaluate the associations between dietary iron intakes and changes in dietary iron intakes with frailty.MethodsCross-sectional analyses involved 785 men with Fried frailty phenotype (FP) and 758 men with Rockwood frailty index (FI) data aged 75 years and older at nutrition assessment from the Concord Health and Ageing in Men Project prospective cohort study. Of these, 563 men who were FP robust or prefrail, and 432 men who were FI nonfrail were included in the longitudinal analyses for more than 3 years. Dietary intake was assessed at both timepoints using a validated diet history questionnaire. The dietary calculation was used to derive heme iron and nonheme iron intakes from total iron intakes. The associations were evaluated through binary logistic regression.ResultsIncidence of FP frailty was 15.3% (n = 86). In longitudinal analyses, maintaining total iron intakes (medium tertile −2.61–0.81 mg/d), increases in total iron and nonheme iron intakes (high tertiles ≥0.82 mg/d and ≥0.80 mg/d), and changes in nonheme iron intake (1 mg increment) were associated with reduced risks of incident FP frailty (OR: 0.47 [95% confindence interval (CI): 0.24, 0.93, p = .031], OR 0.48 [95% CI: 0.23, 0.99, p = .048], OR 0.41 [95% CI: 0.20, 0.88, p = .022], and OR 0.89 [95% CI: 0.82, 0.98, p = .017]).ConclusionMaintaining or increases in total dietary iron and increases or changes in dietary nonheme iron intakes more than 3 years were associated with reduced incidence of FP frailty in older men.

Context Cardiometabolic diseases are leading causes of death and morbidity. Aging increases the risk of disease development. Diet has protective and causal effects on cardiometabolic health. Objective To consolidate the current evidence on the short- and long-term effects of dietary patterns on cardiometabolic health in adults aged ≥ 65 years. Data Sources The Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, Global Health, and Pre-Medline databases, along with ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched. Data Extraction A total of 40 042 records were identified. Quality assessment involved using the revised Cochrane risk-of-bias tool for randomized trials and Joanna Briggs Institute checklists. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. Results Thirteen articles were included (n = 5 cohort studies and n = 3 randomized controlled trials). The low-fat dietary pattern reduced adiposity; however, no effects were evident for hypertension incidence, composite coronary heart disease incidence (including myocardial infarction, coronary heart disease, and coronary revascularization), high-density lipoprotein cholesterol level, and increased blood pressure in the long term. The Mediterranean dietary pattern resulted in reduced triglyceride levels and systolic blood pressure, and had no effects on diastolic blood pressure and glucose in the short term. Other dietary patterns had inconclusive effects. Conclusions The Mediterranean dietary pattern showed the most benefits without harm on cardiometabolic health in older adults. The current body of evidence is small, indicating the need for more research to confirm these findings at a high certainty of evidence, and to include dietary patterns combined with other dietary components, subgroups with cardiometabolic disease or risk factors, longer follow-up, and outcomes that have not yet been investigated. Studies including these factors may help identify the most effective dietary pattern for cardiometabolic health benefits in older adults, to inform future guidelines. Systematic Review Registration PROSPERO registration no. CRD42020141400.

Background The association between dietary protein intake and the risk of mortality is still controversial. The present study aimed to examine the associations between dietary total, animal and plant protein intake and all-cause and cause-specific mortality. Methods Community-dwelling men aged ≥ 70 years were recruited from local government areas surrounding Concord Hospital in Sydney, New South Wales for the Concord Health and Ageing in Men Project (CHAMP). The research dietitian administered a standardised validated diet history questionnaire to capture baseline dietary intake. In total, 794 men participated in a detailed diet history interview at the third wave. Adequacy of protein intake was assessed by comparing participant intake with the Nutrient Reference Values. Total protein intake was categorised into quintiles. Sources of protein were also captured. Mortality was ascertained through the New South Wales death registry. Cox proportional hazard models were used to assess the association between dietary total, animal and plant protein intake and risk of mortality. Results The mean age of the CHAMP men was 81 years. In total, 162 men died during a median follow-up of 3.7 years. Of these, 54 (33.3%) and 49 (30.2%) men died due to cancer and cardiovascular disease, respectively. There were U-shaped associations between protein intake and all-cause and cancer mortality. In multiple adjusted analysis, the second (hazard ratio [HR] = 0.38; 95% confidence interval [CI] = 0.18-0.82) and third (HR = 0.36; 95% CI = 0.16-0.82) quintiles of protein intakes were significantly associated with reduced risk of all-cause and only second quintile (HR = 0.47; 95% CI = 0.10-0.93) of protein intake was significantly associated with cancer mortality. Each serve increase in animal protein was significantly associated with 12% (HR = 1.12; 95% CI = 1.00-1.26) and 23% (HR = 1.23; 95% CI = 1.02-1.49) increased risk of all-cause mortality and cancer mortality respectively. Conversely, each serve increase in plant protein intake was significantly associated with 25% (HR = 0.75; 95% CI 0.61-0.92) and 28% (HR = 0.72; 95% CI = 0.53-0.97) reduced risk of all-cause and cancer mortality, respectively. No such associations were observed for cardiovascular disease mortality. Conclusions Both second and third quintiles of total protein intake were associated with reduced all-cause and cancer mortality. Plant protein was inversely associated with all-cause and cancer mortality, whereas animal protein intake was positively associated with mortality.

Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure is associated with gut microbiota and their metabolites remains unclear. We characterized the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory blood pressure, fecal microbiome predicted from 16S rRNA gene sequencing, plasma and fecal metabolites called short-chain fatty acid, and expression of their receptors were analyzed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared with hypertensives (35%, P Acidaminococcus spp ., Eubacterium fissicatena, and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of short-chain fatty acid-activated GPR43 (G-protein coupled receptor 43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to blood pressure-lowering metabolites.

Reduced protein intake, through dilution with carbohydrate, extends lifespan and improves mid-life metabolic health in animal models. However, with transition to industrialised food systems, reduced dietary protein is associated with poor health outcomes in humans. Here we systematically interrogate the impact of carbohydrate quality in diets with varying carbohydrate and protein content. Studying 700 male mice on 33 isocaloric diets, we find that the type of carbohydrate and its digestibility profoundly shape the behavioural and physiological responses to protein dilution, modulate nutrient processing in the liver and alter the gut microbiota. Low (10%)-protein, high (70%)-carbohydrate diets promote the healthiest metabolic outcomes when carbohydrate comprises resistant starch (RS), yet the worst outcomes were with a 50:50 mixture of monosaccharides fructose and glucose. Our findings could explain the disparity between healthy, high-carbohydrate diets and the obesogenic impact of protein dilution by glucose-fructose mixtures associated with highly processed diets.

The role of antioxidant intake in cardiovascular disease remains inconclusive. This study evaluates the association between antioxidant intake and the risk of major adverse cardiovascular events (MACE) among older Australian men.794 men aged ≥75 years participated in the 3rd wave of the Concord Health and Ageing in Men Project. Dietary adequacy of antioxidant intake was assessed by comparing participants' intake of vitamins A, E, C and zinc to the Nutrient Reference Values (NRV) for Australia. Attainment of NRVs of antioxidants was categorised into a dichotomised variable 'inadequate' (meeting≤2 of 4 antioxidants) or 'adequate' (meeting≥3 of 4 antioxidants). The usage of antioxidant supplements was assessed. The outcome measure was MACE. The composite MACE endpoint was defined as having one of the following: death, myocardial infarction, ischemic stroke, congestive cardiac failure (CCF), and revascularization during the period of observation. There was no significant association between dietary (HR: 1.03, 95% CI: 0.71, 1.48) or supplemental antioxidant intake (HR: 1.10, 95% CI: 0.75, 1.63) and overall MACE. However, a significant association was observed between inadequate antioxidant intake and CCF (HR: 1.32; 95% CI: 1.16, 1.50). The lowest quartile of zinc intake (11.00 mg/d) was significantly associated with CCF (HR 2.36; 95% CI: 1.04, 5.34). None of the other antioxidants were significantly associated with CCF or other MACE components.Inadequate dietary antioxidant intake, particularly zinc, is associated with increased risk of CCF in older Australian men but not associated with overall MACE.

BACKGROUND/OBJECTIVES To compare the Australian Dietary Guideline Index (DGI-2013) and the Pyramid-based Mediterranean Diet Score (pyrMDS) as measures of diet quality in an ethnically diverse group of older men. SUBJECTS/METHODS Seven hundred and ninety-four older men aged ≥75 participated in wave 3 (2012-2013) of the Concord Health and Ageing in Men Project. Dietary intake was assessed using a validated diet history questionnaire. Ethnicity was based on self-reported country of birth and categorised as Australian-born (418 men), Italian or Greek migrants (188), and other migrants (188). Incident cardiovascular outcomes until March 2018 were measured using the composite of major adverse cardiovascular events (MACE), which comprises all-cause mortality, acute myocardial infarction, congestive cardiac failure, coronary revascularisation and/or ischaemic stroke. Ability to predict incident cardiovascular outcomes and all-cause mortality were compared between standardised DGI-2013 pyrMDS scores by comparison of hazard ratios, discrimination (Harrell's C-statistic) and calibration (calibration plots). RESULTS Italian and Greek migrant men had significantly lower DGI-2013 scores (91.7 vs. 93.9; p = 0.01) but significantly higher pyrMDS scores (8.8 vs. 8.2; p

Objective To assess the associations between nutrient intake and dietary patterns with different sarcopenia definitions in older men. Design Cross-sectional study. Setting Sarcopenia was defined using the Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP) and the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Dietary adequacy of fourteen nutrients was assessed by comparing participants' intakes with the Nutrient Reference Values (NRV). Attainment of NRV for nutrients was incorporated into a variable 'poor' (meeting ≤ 9) v. 'good' (meeting ≥ 10) using the cut-point method. Also, two different dietary patterns, monounsaturated:saturated fat and n-6:n-3 fatty acids ratio and individual nutrients were used as predictor variables. Participants A total of 794 men aged ≥75 years participated in this study. Results The prevalence of sarcopenia by the FNIH, EWGSOP and EWGSOP2 definitions was 12·9 %, 12·9 % and 19·6 %, respectively. With the adjustment, poor nutrient intake was significantly associated with FNIH-defined sarcopenia (OR: 2·07 (95 % CI 1·16, 3·67)), but not with EWGSOP and EWGSPOP2 definitions. The lowest and second-lowest quartiles of protein, Mg and Ca and the lowest quartiles of n-6 PUFA and n-3 PUFA intakes were significantly associated with FNIH-defined sarcopenia. Each unit decrease in n-6:n-3 ratio was significantly associated with a 9 % increased risk of FNIH-defined sarcopenia (OR: 1·09 (95 % CI 1·04, 1·16)). Conclusions Inadequate intakes of nutrients are associated with FNIH-defined sarcopenia in older men, but not with the other two sarcopenia definitions. Further studies are required to understand these relationships.

The objectives of the study were to evaluate the associations between antioxidant intake, dietary patterns and depressive symptoms among older men. 794 men participated in a detailed diet history interview at the Concord Health and Ageing in Men Project 3rd wave (considered baseline nutrition) and 781 men participated at the 4th wave (considered 3-year follow-up). Depressive symptoms were measured using the Geriatric Depression Scale (GDS ≥ 5). Dietary adequacy of antioxidant intake was assessed by comparing participants' median intake of vitamin A, E, C and zinc to the Nutrient Reference Values for Australia. Attainment of NRVs of antioxidant was categorised into a dichotomised variable 'poor' (meeting ≤ 2) or 'good' (meeting ≥ 3). Individual antioxidant nutrient was categorised into quartiles. The Australian and Mediterranean diet scores were assessed as predictor variables. The prevalence of GDS ≥ 5 was 12.8% at baseline nutrition and 13.2% of men developed GDS ≥ 5 at a 3-year follow-up. There was a significant cross-sectional association between poor antioxidant intake and GDS ≥ 5 in adjusted analyses [OR: 1.95 (95% CI 1.03, 3.70)]. Poor antioxidant intake at baseline nutrition remained prospectively associated with incident GDS ≥ 5 [OR: 2.46 (95% CI 1.24, 4.88)] in adjusted analyses. This association was also found for the lowest quartile of zinc [OR 2.72 (95% CI 1.37, 5.42)] and vitamin E intake [OR 2.18 (95% CI 1.05, 4.51)]. None of the other antioxidants and dietary patterns had a significant association with incident depressive symptoms. Inadequacy of antioxidant intake, particularly zinc and vitamin E, is associated with increased risk of clinically significant depressive symptoms in older men.

The aim was to assess two macronutrient interventions in a 2 × 2 factorial dietary design to determine their effects on oral health.Participants (65-75 years old) with a body mass index between 20 and 35 kg/mBetween baseline and follow up, the number of sites with a CAL5 mm (mean difference [MD] -5.11 ± 9.68, p = .039) increased and the GCF amount (MD -23.42 ± 39.42 Periotron Units [PU], p = .050) decreased for the semi-vegetarian high-fat diet. For the mean proportion of sites with PPD reduction of1 mm and CAL gain of1 mm, significant differences were calculated between the diets investigated. The clinical parameters were not associated with changes in the oral microbiota.The results of this study provided evidence that a semi-vegetarian high-fat diet provides benefits to clinical parameters of periodontal health. This study is registered in ClinicalTrials.gov (ACTRN12616001606471).

Sarcopenia is prevalent in middle-aged and older adults. A plant-based diet may be linked to changes in body composition and musculoskeletal health. This systematic review aimed to investigate the effects of plant-based dietary patterns on the body composition, muscle strength and function in middle-aged and older adults. PRISMA guidelines were followed. A systematic search was completed on databases including MEDLINE, Embase, Global Health, PREMEDLINE, Cochrane library, CINAHL and Scopus on articles published until 1st March 2019. Search terms included ‘middle-aged’, ‘older adult’, ‘plant-based diet’ and ‘muscle strength’. Title and abstract screening were conducted on 1,868 publications after deduplication. Sample size, subject characteristics, recruitment, inclusion and exclusion criteria, dietary measures, health outcome measures, statistical results and confounders were sorted by author, study type, year and country. The quality of evidence of extracted data was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools. 17 papers were included from 31 articles selected for full review. The majority of the studies were cross-sectional studies (n = 9) and RCTs (n = 6). The remaining studies were cohort studies. Positive associations were found between plant-based dietary patterns; negative association with body composition; and inconclusive association with muscle function. However, further studies are needed to improve the understanding.

Background The relations between diet, chronic inflammation, and musculoskeletal health are unclear, especially among older men. Objective This study aimed to determine associations of the Dietary Inflammatory Index (DII) with inflammatory biomarkers, musculoskeletal health, and falls risk in community-dwelling older men. Methods The cross-sectional analysis included 794 community-dwelling men, mean age 81.1 ± 4.5 y, who participated in the 5-y follow-up of the Concord Health and Aging in Men Project. Of these, 616 were seen again 3 y later for the longitudinal analysis. Energy-adjusted DII (E-DII) was calculated from a validated diet history questionnaire. Bone mineral density (BMD) was measured using DXA. Twenty-four inflammatory biomarkers were analyzed. Incident falls over 3 y were determined through telephone interviews every 4 mo. Multiple regression, linear mixed effects models, negative binomial regression, and mediation analysis were utilized in this study. Results A higher E-DII score (indicating a more proinflammatory diet) was associated with higher concentrations of IL-6 (β: 0.028 pg/mL; 95% CI: 0.003, 0.053), IL-7 (β: 0.020 pg/mL; 95% CI: 0.002, 0.037), and TNF-α (β: 0.027 pg/mL; 95% CI: 0.003, 0.051). A higher E-DII score was also associated with lower appendicular lean mass adjusted for BMI (ALMBMI) (β: -0.006 kg/m2; 95% CI: -0.010, -0.001). For every unit increase in E-DII (range: -4.91 to +3.66 units), incident falls rates increased by 13% (incidence rate ratio: 1.13; 95% CI: 1.05, 1.21) over 3 y. Mediation analysis showed that the association between E-DII and 3-y incident falls was influenced by the concentrations of IL-7 by 24%. There was no association between E-DII and BMD. Conclusions Consumption of a proinflammatory diet was associated with increased concentrations of IL-6, IL-7, and TNF-α; increased falls risk; and lower ALMBMI in community-dwelling older men. The association between incident falls and E-DII was partly mediated by concentrations of IL-7.

Background Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently contributes to each one of these risk factors, potentially mediated via gut microbial‐derived metabolites such as short‐chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α‐diversity (eg, number of microbes) and β‐diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF ( P =0.001). We did not find an association between β‐diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so ( P =0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short‐chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P =0.016). Conclusions We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.

OBJECTIVES: Mediterranean dietary patterns may exert favorable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men. METHODS: Seven hundred ninety-four (794) community-dwelling men with mean age 81.1 ± 4.5 years, who participated in the five-year follow-up of the Concord Health and Ageing in Men Project (CHAMP) were included in the cross-sectional analysis, and 616 attended follow-up three years later. Adherence to Mediterranean diet was assessed using MEDI-LITE (literature-derived Mediterranean diet) score which was derived using a validated diet history questionnaire. Twenty-four evaluable circulating cytokines were analyzed using Bio-Plex Pro Human Cytokine 27-plex Assay kit. Appendicular lean mass (ALM) and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA). Three-year changes in gait speed and hand grip strength were assessed by walking a 6-meter course and using a dynamometer respectively. Incident falls over three years were determined through telephone interviews every four months. RESULTS: A higher MEDI-LITE score, indicating greater adherence to Mediterranean diet, was associated with higher appendicular lean mass adjusted for body mass index (ALM(BMI)) (β: 0.004 kg/kg/m(2); 95% CI: 0.000, 0.008), and lower serum interleukin-7 (IL-7) (β: −0.017 pg/mL; 95% CI: −0.031, −0.003), and incident falls rates (IRR: 0.94; 95% CI: 0.89, 0.99). Higher consumption of monounsaturated fatty acids (IRR: 0.76; 95% CI: 0.59, 0.98) and monounsaturated fatty acids to saturated fatty acids ratio (IRR: 0.72; 95% CI: 0.57, 0.90) were associated with 24%, and 28% lower falls risk in older men respectively. MEDI-LITE scores were not associated with bone mineral density or physical function parameters. CONCLUSIONS: Adherence to a Mediterranean diet is associated with higher ALM(BMI), lower levels of serum IL-7, and fewer falls in community-dwelling older men. Monounsaturated and saturated fatty acids were the most important contributors to the association between Mediterranean diet and falls risk. FUNDING SOURCES: The CHAMP study is funded by the National Health and Medical Research Council of Australia, and the Ageing and Alzheimer's Institute.

Autoimmune diseases are characterized by a breakdown of immune tolerance partly due to environmental factors. The short-chain fatty acid acetate, derived mostly from gut microbial fermentation of dietary fiber, promotes antiinflammatory Tregs and protects mice from type 1 diabetes, colitis, and allergies. Here, we show that the effects of acetate extend to another important immune subset involved in tolerance, the IL-10–producing regulatory B cells (B10 cells). Acetate directly promoted B10 cell differentiation from mouse B1a cells both in vivo and in vitro. These effects were linked to metabolic changes through the increased production of acetyl-coenzyme A, which fueled the TCA cycle and promoted posttranslational lysine acetylation. Acetate also promoted B10 cells from human blood cells through similar mechanisms. Finally, we identified that dietary fiber supplementation in healthy individuals was associated with increased blood-derived B10 cells. Direct delivery of acetate or indirect delivery via diets or bacteria that produce acetate might be a promising approach to restore B10 cells in noncommunicable diseases.

Cell survival, proliferation and function are energy-demanding processes, fuelled by different metabolic pathways. Immune cells like any other cells will adapt their energy production to their function with specific metabolic pathways characteristic of resting, inflammatory or anti-inflammatory cells. This concept of immunometabolism is revolutionising the field of immunology, opening the gates for novel therapeutic approaches aimed at altering immune responses through immune metabolic manipulations. The first part of this review will give an extensive overview on the metabolic pathways used by immune cells. Diet is a major source of energy, providing substrates to fuel these different metabolic pathways. Protein, lipid and carbohydrate composition as well as food additives can thus shape the immune response particularly in the gut, the first immune point of contact with food antigens and gastrointestinal tract pathogens. How diet composition might affect gut immunometabolism and its impact on diseases will also be discussed. Finally, the food ingested by the host is also a source of energy for the micro-organisms inhabiting the gut lumen particularly in the colon. The by-products released through the processing of specific nutrients by gut bacteria also influence immune cell activity and differentiation. How bacterial metabolites influence gut immunometabolism will be covered in the third part of this review. This notion of immunometabolism and immune function is recent and a deeper understanding of how lifestyle might influence gut immunometabolism is key to prevent or treat diseases.

Objective:To assess the associations between nutrient intake and dietary patterns with different sarcopenia definitions in older men.Design:Cross-sectional study.Setting:Sarcopenia was defined using the Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP) and the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Dietary adequacy of fourteen nutrients was assessed by comparing participants’ intakes with the Nutrient Reference Values (NRV). Attainment of NRV for nutrients was incorporated into a variable ‘poor’ (meeting ≤ 9) v. ‘good’ (meeting ≥ 10) using the cut-point method. Also, two different dietary patterns, monounsaturated:saturated fat and n-6:n-3 fatty acids ratio and individual nutrients were used as predictor variables.Participants:A total of 794 men aged ≥75 years participated in this study.Results:The prevalence of sarcopenia by the FNIH, EWGSOP and EWGSOP2 definitions was 12·9 %, 12·9 % and 19·6 %, respectively. With the adjustment, poor nutrient intake was significantly associated with FNIH-defined sarcopenia (OR: 2·07 (95 % CI 1·16, 3·67)), but not with EWGSOP and EWGSPOP2 definitions. The lowest and second-lowest quartiles of protein, Mg and Ca and the lowest quartiles of n-6 PUFA and n-3 PUFA intakes were significantly associated with FNIH-defined sarcopenia. Each unit decrease in n-6:n-3 ratio was significantly associated with a 9 % increased risk of FNIH-defined sarcopenia (OR: 1·09 (95 % CI 1·04, 1·16)).Conclusions:Inadequate intakes of nutrients are associated with FNIH-defined sarcopenia in older men, but not with the other two sarcopenia definitions. Further studies are required to understand these relationships.

Objectives:To examine changes in micronutrient intake over 3 years and identify any associations between socio-economic, health, lifestyle and meal-related factors and these changes in micronutrient intakes among older men.Design:Prospective study.Setting:Dietary adequacy of individual micronutrient was compared to the estimated average requirement of the nutrient reference values (NRV). Attainment of the NRV for twelve micronutrients was incorporated into a dichotomised variable ‘not meeting’ (meeting ≤ 6) or ‘meeting’ (meeting ≥ 7) and categorised into four categories to assess change in micronutrient intake over 3 years. The multinomial logistic regression analyses were conducted to model predictors of changes in micronutrient intake.Participants:Seven hundred and ninety-four men participated in a detailed diet history interview at the third wave (baseline nutrition) and 718 men participated at the fourth wave (3-year follow-up).Results:The mean age was 81 years (range 75–99 years). Median intakes of the majority of micronutrients decreased significantly over a 3-year follow-up. Inadequacy of the NRV for thiamine, dietary folate, Zn, Mg, Ca and I were significantly increased at a 3-year follow-up than baseline nutrition. The incidence of inadequate micronutrient intake was 21 % and remained inadequate micronutrient intake was 16·4 % at 3-year follow-up. Changes in micronutrient intakes were significantly associated with participants born in the UK and Italy, low levels of physical activity, having ≥2 medical conditions and used meal services.Conclusions:Micronutrient intake decreases with age in older men. Our results suggest that strategies to improve some of the suboptimal micronutrient intakes might need to be developed and implemented for older men.

Branched chain amino acids (BCAA: leucine, valine, isoleucine) have key physiological roles in the regulation of protein synthesis, metabolism, food intake and aging. Many studies report apparently inconsistent conclusions about the relationships between blood levels of BCAAs or dietary manipulation of BCAAs with age-related changes in body composition, sarcopenia, obesity, insulin and glucose metabolism, and aging biology itself. These divergent results can be resolved by consideration of the role of BCAAs as signalling molecules and the bidirectional mechanistic relationship between BCAAs and some aging phenotypes. The effects of BCAAs are also influenced by the background nutritional composition such as macronutrient ratios and imbalance with other amino acids. Understanding the interaction between BCAAs and other components of the diet may provide new opportunities for influencing age-related outcomes through manipulation of dietary BCAAs together with titration of macronutrient ratios and other amino acids.

Background & aims Mediterranean dietary patterns may exert favourable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet as well as its components, with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men. Methods Seven hundred ninety-four (794) community-dwelling men with mean age 81.1 ± 4.5 years, who participated in the five-year follow-up of the Concord Health and Ageing in Men Project (CHAMP) were included in the cross-sectional analysis, and 616 attended follow-up three years later. Adherence to Mediterranean diet was assessed using MEDI-LITE (literature-derived Mediterranean diet) score which was obtained using a validated diet history questionnaire. Twenty-four evaluable circulating cytokines were analyzed using Bio-Plex Pro Human Cytokine 27-plex Assay kit. Appendicular lean mass (ALM) and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA). Three-year changes in gait speed and hand grip strength were assessed by walking a 6-m course and using a dynamometer respectively and analyzed using linear mixed-effects models. Incident falls over three years were determined through telephone interviews every four months. Multivariable linear regression was utilized to determine the cross-sectional associations between MEDI-LITE scores and circulating cytokines, bone mineral density, ALM, and ALMBMI. Linear mixed-effects models were performed to estimate associations between MEDI-LITE scores and three-year change in hand grip strength and gait speed while negative binomial regression was applied to estimate associations between MEDI-LITE scores and three-year incident falls as well as associations between each MEDI-LITE component and three-year incident falls. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing. Results A higher MEDI-LITE score, indicating greater adherence to Mediterranean diet, was associated with higher appendicular lean mass adjusted for body mass index (ALMBMI) (β: 0.004 kg; 95% CI: 0.000, 0.008), and lower incident falls rates (IRR: 0.94; 95% CI: 0.89, 0.99). Higher consumption of monounsaturated fatty acids (IRR: 0.76; 95% CI: 0.59, 0.98) and monounsaturated fatty acids to saturated fatty acids ratio (IRR: 0.72; 95% CI: 0.57, 0.90) were associated with 24%, and 28% lower falls risk in older men respectively. MEDI-LITE scores were not associated with BMD or physical function parameters. Conclusions Adherence to a Mediterranean diet is associated with higher ALMBMI, and fewer falls in community-dwelling older men. Monounsaturated and saturated fatty acids were the most important contributors to the association between Mediterranean diet and falls risk.

The revised Dietary Guideline Index (DGI-2013) scores individuals’ diets according to their compliance with the Australian Dietary Guideline (ADG). This cross-sectional study assesses the diet quality of 794 community-dwelling men aged 74 years and older, living in Sydney, Australia participating in the Concord Health and Ageing in Men Project; it also examines sociodemographic and lifestyle factors associated with DGI-2013 scores; it studies associations between DGI-2103 scores and the following measures: homoeostasis model assessment – insulin resistance, LDL-cholesterol, HDL-cholesterol, TAG, blood pressure, waist:hip ratio, BMI, number of co-morbidities and medications and frailty status while also accounting for the effect of ethnicity in these relationships. Median DGI-2013 score was 93·7 (54·4, 121·2); most individuals failed to meet recommendations for vegetables, dairy products and alternatives, added sugar, unsaturated fat and SFA, fluid and discretionary foods. Lower education, income, physical activity levels and smoking were associated with low scores. After adjustments for confounders, high DGI-2013 scores were associated with lower HDL-cholesterol, lower waist:hip ratios and lower probability of being frail. Proxies of good health (fewer co-morbidities and medications) were not associated with better compliance to the ADG. However, in participants with a Mediterranean background, low DGI-2013 scores were not generally associated with poorer health. Older men demonstrated poor diet quality as assessed by the DGI-2013, and the association between dietary guidelines and health measures and indices may be influenced by ethnic background.

Aging is the greatest risk factor for most diseases including cancer, cardiovascular disorders, and neurodegenerative disease. There is emerging evidence that interventions that improve metabolic health with aging may also be effective for brain health. The most robust interventions are non-pharmacological and include limiting calorie or protein intake, increasing aerobic exercise, or environmental enrichment. In humans, dietary patterns including the Mediterranean, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and Okinawan diets are associated with improved age-related health and may reduce neurodegenerative disease including dementia. Rapamycin, metformin and resveratrol act on nutrient sensing pathways that improve cardiometabolic health and decrease the risk for age-associated disease. There is some evidence that they may reduce the risk for dementia in rodents. There is a growing recognition that improving metabolic function may be an effective way to optimize brain health during aging.

The objectives of the study were to evaluate the associations between antioxidant intake, dietary patterns and depressive symptoms among older men.794 men participated in a detailed diet history interview at the Concord Health and Ageing in Men Project 3rd wave (considered baseline nutrition) and 781 men participated at the 4th wave (considered 3-year follow-up). Depressive symptoms were measured using the Geriatric Depression Scale (GDS ≥ 5). Dietary adequacy of antioxidant intake was assessed by comparing participants' median intake of vitamin A, E, C and zinc to the Nutrient Reference Values for Australia. Attainment of NRVs of antioxidant was categorised into a dichotomised variable 'poor' (meeting ≤ 2) or 'good' (meeting ≥ 3). Individual antioxidant nutrient was categorised into quartiles. The Australian and Mediterranean diet scores were assessed as predictor variables.The prevalence of GDS ≥ 5 was 12.8% at baseline nutrition and 13.2% of men developed GDS ≥ 5 at a 3-year follow-up. There was a significant cross-sectional association between poor antioxidant intake and GDS ≥ 5 in adjusted analyses [OR: 1.95 (95% CI 1.03, 3.70)]. Poor antioxidant intake at baseline nutrition remained prospectively associated with incident GDS ≥ 5 [OR: 2.46 (95% CI 1.24, 4.88)] in adjusted analyses. This association was also found for the lowest quartile of zinc [OR 2.72 (95% CI 1.37, 5.42)] and vitamin E intake [OR 2.18 (95% CI 1.05, 4.51)]. None of the other antioxidants and dietary patterns had a significant association with incident depressive symptoms.Inadequacy of antioxidant intake, particularly zinc and vitamin E, is associated with increased risk of clinically significant depressive symptoms in older men.

Increased blood levels of branched chain amino acids (BCAAs) have been associated with cardiometabolic risk factors. Here, we studied 918 community-dwelling older men to determine the relationship between BCAAs and other amino acids with cardiometabolic risk factors, major cardiovascular endpoints (MACE), and mortality. BCAAs had robust associations with many adverse metabolic risk factors (increased glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), triglycerides; decreased high-density lipoprotein cholesterol). However, paradoxically, participants with lower levels of BCAAs had greater mortality and MACE possibly because increasing age and frailty, both of which were associated with lower BCAA levels, are powerful risk factors for these outcomes in older people. Overall, amino acids that were lowest in frail subjects (BCAAs, α-aminobutyric acid [AABA], histidine, lysine, methionine, threonine, tyrosine) were inversely associated with mortality and MACE. In conclusion, BCAAs are biomarkers for important outcomes in older people including cardiometabolic risk factors, frailty, and mortality. In old age, frailty becomes a dominant risk factor for MACE and mortality.

Italian migrants are one of the largest groups of older migrants in Australia. Past research has found lower mortality rates in Italian migrants but it is unclear if this persists into older age. Data came from 334 Italian-born and 849 Australian-born men aged 70 years and over participating in a longitudinal study of men’s ageing. Male Italian migrants were more likely to smoke, be overweight, and have lower socio-economic status (SES). They also had higher morbidity from diabetes, chronic pain, dementia and depressive symptoms but lower morbidity from heart disease and cancer. There was no age-adjusted mortality difference. However, adjusting for SES, lifestyle and morbidity differences revealed a 25% lower mortality rate (adjusted HR = 0.75; 95% CI 0.57, 0.98) in Italian-born men. Compared to their Australian-born counterparts, older Italian-born men have a lower mortality than expected considering their lower SES, higher smoking and higher morbidity. NHMRC, Ageing and Alzheimer’s Research Foundation

Background: The objective of the study is to evaluate the prospective associations between antioxidant intake and incident frailty among older Australian men aged ≥75 years. Methods: Seven hundred and ninety-four men participated in a detailed diet history interview at the Concord Health and Ageing in Men Project (CHAMP) study third wave (considered baseline nutrition here) and 781 men participated at the fourth wave (considered 3-year follow-up here). The main outcome measurement was incident frailty at 3-year follow-up, using the Cardiovascular Health Study definition. Dietary adequacy of antioxidant intake was assessed by comparing participants' median intakes of four dietary antioxidants (vitamin A, E, C, and zinc) to the nutrient reference values (NRVs). Attainment of the NRVs was incorporated into a dichotomized variable "poor" (meeting ≤2 antioxidants) or "good" (meeting ≥3 antioxidants) as the independent variable using the cut-point method. Also, intakes of each individual dietary antioxidant at baseline nutrition were categorized into quartiles. Analyses were performed using multinomial logistic regression. Results: Incidence of pre-frailty was 53.0% and frailty was 6.4% at 3-year follow-up. Poor dietary antioxidant intake (meeting ≤2) at baseline nutrition was associated with incident frailty at 3-year follow-up in unadjusted (OR: 2.59 [95% CI: 1.47, 4.59, p = .001]) and adjusted (OR: 2.46 [95% CI: 1.10, 5.51, p = .03]) analyses. The lowest quartile of vitamin E intake (

Protein and branched-chain amino acid (BCAA) intake are associated with changes in circulating BCAAs and influence metabolic health in humans and rodents. However, the relationship between BCAAs and body composition in both species is unclear, with many studies questioning the translatability of preclinical findings to humans. Here, we assessed and directly compared the relationship between circulating BCAAs, body composition, and intake in older mice and men. Body weight and body fat were positively associated with circulating BCAA levels in both mouse and human, which remained significant after adjustments for age, physical activity, number of morbidities, smoking status, and source of income in the human cohort. Macronutrient intakes were similarly associated with circulating BCAA levels, however, the relationship between protein intake and BCAAs were more pronounced in the mice. These findings indicate that the relationship between circulating BCAAs, body composition, and intakes are comparable in both species, suggesting that the mouse is an effective model for examining the effects of BCAAs on body composition in older humans.