Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial.

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (ß = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (ß = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Alcohol Consumption and Measures of Sarcopenic Muscle Risk: Cross-Sectional and Prospective Associations Within the UK Biobank Study.

Alcohol intake is a major modifiable risk factor for many diseases. Alcohol can also damage skeletal muscle health during ageing which in turn increases risk of sarcopenia, frailty and falls but this relationship is understudied. The aim of this study was to model the relationship between a full range of alcohol consumption and components of sarcopenic risk, skeletal muscle mass and function, in middle-aged and younger older-aged men and women. A cross-sectional analyses was undertaken of 196,561 white participants from the UK Biobank with longitudinal analysis also in 12,298 of these participants, with outcome measures for the latter repeated after around four years. For the cross-sectional analysis fractional polynomial curves were fitted in models of measures of skeletal muscle mass, appendicular lean mass/body mass index (ALM/BMI), fat-free mass as a percentage of body weight (FFM%) and grip strength, all predicted from alcohol consumption with models fitted for men and women separately. Alcohol consumption at baseline was based on the mean of up to five dietary recalls, typically over 16 months. Linear regression was used for longitudinal analyses to model the effects of alcohol consumption groups on these measures. All models were adjusted for covariates. In the cross-sectional analysis, modelled values of the muscle mass measures all showed a peak at medium levels of alcohol consumption and a steep decline with increasing alcohol consumption. Modelled differences in muscle mass from zero consumption of alcohol to 160 g/d ranged from 3.6 to 4.9% for ALM/BMI for men and women, respectively, and 3.6 to 6.1% for FFM%. Grip strength consistently increased with alcohol consumption. No association between alcohol consumption and muscle measures were seen in the longitudinal results. Our results suggest that higher levels of alcohol consumption could have detrimental effects on muscle mass in middle- and older-aged men and women.

Higher dietary protein intake is associated with sarcopenia in older British twins.

BACKGROUND: Sarcopenia, characterised by an accelerated loss of skeletal muscle mass and function, is associated with negative outcomes. This study aimed to evaluate factors associated with skeletal muscle strength, mass and sarcopenia, particularly protein intake, and to assess whether shared twin characteristics are important. METHODS: This study utilised cross-sectional data from a study of community-dwelling twins aged ≥60 years. Multivariable logistic regression and between- and within-twin pair regression modelling were used. RESULTS: Participants (n = 3,302) were 89% female (n = 2,923), aged a mean of 72.1 (±7.3) years and composed of 858 (55%) monozygotic, 709 (45%) dizygotic twin pairs and 168 individual lone twins. Using optimal protein intake as the reference group (1.0-1.3 g/kg/day), there was no significant association between protein intake (neither high nor low) and low muscle strength, or between low protein intake and sarcopenia (odds ratio (OR) 0.7; 95% confidence interval (CI) 0.39-1.25; P = 0.229) in unadjusted models. High protein intake (>1.3 g/kg/day) was associated with low muscle mass (OR 1.76; 95% CI 1.39-2.24; P < 0.0001), while low protein intake was protective (OR 0.52; 95% CI 0.40-0.67; P < 0.0001). High protein intake was associated with sarcopenia (OR 2.04; 95% CI 1.21-3.44; P = 0.008), and this was robust to adjustment for demographic, anthropometric and dietary factors. The association between muscle strength and weight, body mass index, healthy eating index, protein intake and alpha diversity was not significantly influenced by shared twin factors, indicating greater amenability to interventions. CONCLUSIONS: High protein intake is associated with sarcopenia in a cohort of healthy older twins.

Evidence to Underpin Vitamin A Requirements and Upper Limits in Children Aged 0 to 48 Months: A Scoping Review.

Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

Effects of fluid and drinking on pneumonia mortality in older adults: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Advice to drink plenty of fluid is common in respiratory infections. We assessed whether low fluid intake (dehydration) altered outcomes in adults with pneumonia. METHODS: We systematically reviewed trials increasing fluid intake and well-adjusted, well-powered observational studies assessing associations between markers of low-intake dehydration (fluid intake, serum osmolality, urea or blood urea nitrogen, urinary output, signs of dehydration) and mortality in adult pneumonia patients (with any type of pneumonia, including community acquired, health-care acquired, aspiration, COVID-19 and mixed types). Medline, Embase, CENTRAL, references of reviews and included studies were searched to 30/10/2020. Studies were assessed for inclusion, risk of bias and data extracted independently in duplicate. We employed random-effects meta-analysis, sensitivity analyses, subgrouping and GRADE assessment. Prospero registration: CRD42020182599. RESULTS: We identified one trial, 20 well-adjusted cohort studies and one case-control study. None suggested that more fluid (hydration) was associated with harm. Ten of 13 well-powered observational studies found statistically significant positive associations in adjusted analyses between dehydration and medium-term mortality. The other three studies found no significant effect. Meta-analysis suggested doubled odds of medium-term mortality in dehydrated (compared to hydrated) pneumonia patients (GRADE moderate-quality evidence, OR 2.3, 95% CI 1.8 to 2.8, 8619 deaths in 128,319 participants). Heterogeneity was explained by a dose effect (greater dehydration increased risk of mortality further), and the effect was consistent across types of pneumonia (including community-acquired, hospital-acquired, aspiration, nursing and health-care associated, and mixed pneumonia), age and setting (community or hospital). The single trial found that educating pneumonia patients to drink ≥1.5 L fluid/d alongside lifestyle advice increased fluid intake and reduced subsequent healthcare use. No studies in COVID-19 pneumonia met the inclusion criteria, but 70% of those hospitalised with COVID-19 have pneumonia. Smaller COVID-19 studies suggested that hydration is as important in COVID-19 pneumonia mortality as in other pneumonias. CONCLUSIONS: We found consistent moderate-quality evidence mainly from observational studies that improving hydration reduces the risk of medium-term mortality in all types of pneumonia. It is remarkable that while many studies included dehydration as a potential confounder, and major pneumonia risk scores include measures of hydration, optimal fluid volume and the effect of supporting hydration have not been assessed in randomised controlled trials of people with pneumonia. Such trials, are needed as potential benefits may be large, rapid and implemented at low cost. Supporting hydration and reversing dehydration has the potential to have rapid positive impacts on pneumonia outcomes, and perhaps also COVID-19 pneumonia outcomes, in older adults.

Identifying Future Study Designs for Mental Health and Social Wellbeing Associated with Diets of a Cohort Living in Eco-Regions: Findings from the INSUM Expert Workshop.

Diets influence our mental health and social wellbeing (MHSW) in multiple ways. A rising community concept, Eco-Regions, has gained interest. The research project "Indicators for assessment of health effects of consumption of sustainable, organic school meals in Ecoregions" (INSUM) aims to develop future-oriented research approaches to measure the potential health effects of more sustainable and healthy diets. This first part of the project focuses on MHSW with the goal to identify suitable study designs and indicators. The methodology is based on a 2-day workshop with an interdisciplinary group of experts. This paper describes commonly applied research methods on the nexus between diet and MHSW as presented by the experts and summarises key points from the discussions. The results show that the dominating tool to investigate MSHW is questionnaires. Questionnaires vary largely depending on the research design, such as participants or distribution channels. Cohort studies addressing families and including in-depth interventional and/or experimental studies may be suitable for an Eco-Region investigation. Those MHSW studies can be conducted and combined with measurements of somatic health effects. We conclude that indicators should be seen as complementary rather than independent. Explorative research designs are required to investigate complex Eco-Regions.

Predicting Malnutrition Risk with Data from Routinely Measured Clinical Biochemical Diagnostic Tests in Free-Living Older Populations.

Malnutrition (undernutrition) in older adults is often not diagnosed before its adverse consequences have occurred, despite the existence of established screening tools. As a potential method of early detection, we examined whether readily available and routinely measured clinical biochemical diagnostic test data could predict poor nutritional status. We combined 2008-2017 data of 1518 free-living individuals ≥50 years from the United Kingdom National Diet and Nutrition Survey (NDNS) and used logistic regression to determine associations between routine biochemical diagnostic test data, micronutrient deficiency biomarkers, and established malnutrition indicators (components of screening tools) in a three-step validation process. A prediction model was created to determine how effectively routine biochemical diagnostic tests and established malnutrition indicators predicted poor nutritional status (defined by ≥1 micronutrient deficiency in blood of vitamins B6, B12 and C; selenium; or zinc). Significant predictors of poor nutritional status were low concentrations of total cholesterol, haemoglobin, HbA1c, ferritin and vitamin D status, and high concentrations of C-reactive protein; except for HbA1c, these were also associated with established malnutrition indicators. Additional validation was provided by the significant association of established malnutrition indicators (low protein, fruit/vegetable and fluid intake) with biochemically defined poor nutritional status. The prediction model (including biochemical tests, established malnutrition indicators and covariates) showed an AUC of 0.79 (95% CI: 0.76-0.81), sensitivity of 66.0% and specificity of 78.1%. Clinical routine biochemical diagnostic test data have the potential to facilitate early detection of malnutrition risk in free-living older populations. However, further validation in different settings and against established malnutrition screening tools is warranted.

Fracture Incidence and the Relevance of Dietary and Lifestyle Factors Differ in the United Kingdom and Hong Kong: An International Comparison of Longitudinal Cohort Study Data.

Geographic variation in fracture risk may be due to divergent profiles of dietary, lifestyle, and other risk factors between populations. We investigated differences in fracture rates between two older-population cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk cohort (n = 7732) in the United Kingdom (UK), and the Mr and Ms Os cohort (n = 3956) in Hong Kong (HK). Data were collected by questionnaires, laboratory assessments, and hospital records. Incidence of hip, spine, and wrist fractures in the two cohorts was calculated and multivariable regression was used to explore variables important to fracture risk. Total hip, spine, and wrist fracture incidence was higher in the UK vs HK for women (13.70 vs 8.76 per 1000 person-years; p < 0.001), but not men (5.95 vs 5.37 per 1000 person-years; p = 0.337), and the proportions of different fractures also varied between cohorts (p < 0.001). Hip fracture was the most common UK fracture (accounting for 56.8% fractures in men and 52.6% in women), while wrist fracture was most common in HK (42.9% in men and 57.9% in women). The major contributor to total fracture risk in multivariable regression models of both cohorts and sexes, was age; with BMI also an important contributor to fracture risk HK men and UK women. The distribution of factors relevant to fracture risk, and the rates of different fractures, varied significantly between UK and HK cohorts. However, the importance of each factor in contributing to fracture risk was similar between the cohorts. The differences in fracture rates suggest targeted approaches may be required when developing interventions and public health recommendations to reduce the burden of osteoporosis in these two countries.

REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.

Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE), and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Recently, the possibility of systemic features in CHM has been debated; therefore, in this study, whole metabolomic analysis of plasma samples from 25 CHM patients versus age- and sex-matched controls was performed. Results showed plasma alterations in oxidative stress-related metabolites, coupled with alterations in tryptophan metabolism, leading to significantly raised serotonin levels. Lipid metabolism was disrupted with decreased branched fatty acids and acylcarnitines, suggestive of dysfunctional lipid oxidation, as well as imbalances of several sphingolipids and glycerophospholipids. Targeted lipidomics of the chmru848 zebrafish provided further evidence for dysfunction, with the use of fenofibrate over simvastatin circumventing the prenylation pathway to improve the lipid profile and increase survival. This study provides strong evidence for systemic manifestations of CHM and proposes potentially novel pathomechanisms and targets for therapeutic consideration.

Positive Associations of Dietary Intake and Plasma Concentrations of Vitamin E with Skeletal Muscle Mass, Heel Bone Ultrasound Attenuation and Fracture Risk in the EPIC-Norfolk Cohort.

The prevalence of sarcopenia, frailty and fractures is increasing. Prevention options are limited, but dietary factors including vitamin E have the potential to confer some protection. This study investigated cross-sectional associations between dietary and plasma concentrations of vitamin E with indices of skeletal muscle mass (SMM) (n = 14,179 and 4283, respectively) and bone density (n = 14,694 and 4457, respectively) and longitudinal fracture risk (n = 25,223 and 7291, respectively) in European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk participants, aged 39-79 years at baseline. Participants completed a health and lifestyle questionnaire, a 7-day diet diary (7dDD) and had anthropometric measurements taken. Fat-free mass (as a SMM proxy) was measured using bioimpedance and bone density was measured using calcaneal broadband ultrasound attenuation (BUA) and incident fractures over 18.5 years of follow-up. Associations between indices of SMM, BUA and fracture risk were investigated by quintiles of dietary vitamin E intake or plasma concentrations. Positive trends in SMM indices and BUA were apparent across dietary quintiles for both sexes, with interquintile differences of 0.88%-1.91% (p < 0.001), and protective trends for total and hip fracture risk. Circulating plasma α- and γ-tocopherol results matched the overall dietary findings. Dietary vitamin E may be important for musculoskeletal health but further investigation is required to fully understand the relationships of plasma tocopherols.

Cross-sectional associations of schoolchildren's fruit and vegetable consumption, and meal choices, with their mental well-being: a cross-sectional study.

BACKGROUND: Poor mental well-being is a major issue for young people and is likely to have long-term negative consequences. The contribution of nutrition is underexplored. We, therefore, investigated the association between dietary choices and mental well-being among schoolchildren. METHODS: Data from 7570 secondary school and 1253 primary school children in the Norfolk Children and Young People Health and Well-being Survey, open to all Norfolk schools during October 2017, were analysed. Multivariable linear regression was used to measure the association between nutritional factors and mental well-being assessed by the Warwick-Edinburgh Mental Well-being Scale for secondary school pupils, or the Stirling Children's Well-being Scale for primary school pupils. We adjusted all analyses for important covariates including demographic, health variables, living/home situation and adverse experience variables. RESULTS: In secondary school analyses, a strong association between nutritional variables and well-being scores was apparent. Higher combined fruit and vegetable consumption was significantly associated with higher well-being: well-being scores were 3.73 (95% CI 2.94 to 4.53) units higher in those consuming five or more fruits and vegetables (p<0.001; n=1905) compared with none (n=739). The type of breakfast or lunch consumed was also associated with significant differences in well-being score. Compared with children consuming a conventional type of breakfast (n=5288), those not eating any breakfast had mean well-being scores 2.73 (95% CI 2.11 to 3.35) units lower (p<0.001; n=1129) and those consuming only an energy drink had well-being scores 3.14 (95% CI 1.20 to 5.09) units lower (p=0.002; n=91). Likewise, children not eating any lunch had well-being scores 2.95 (95% CI 2.22 to 3.68) units lower (p<0.001; 860) than those consuming a packed lunch (n=3744). In primary school analyses, the type of breakfast or lunch was associated with significant differences in well-being scores in a similar way to those seen in secondary school data, although no significant association with fruit and vegetable intake was evident. CONCLUSION: These findings suggest that public health strategies to optimise the mental well-being of children should include promotion of good nutrition.

Dietary acid-base load and its association with risk of osteoporotic fractures and low estimated skeletal muscle mass.

BACKGROUND/OBJECTIVES: Age-related decline in skeletal muscle mass and strength, loss of bone density, and increased risk of osteoporotic fractures are important public health issues. Systemic acid-base balance is affected by dietary intake and may be relevant to these conditions. We therefore investigated associations of dietary acid-base load with skeletal muscle mass, bone density status, and fracture risk. SUBJECTS/METHODS: We analysed the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of >25,000 individuals, 39-79 years at baseline. Potential renal acid load (PRAL) was calculated from 7-day food diary data. As a proxy for skeletal muscle mass, we estimated fat-free mass from bioelectrical impedance analysis and scaled this for BMI (FFMBMI). Bone density status was assessed by heel-bone broadband ultrasound attenuation (BUA), and fracture rates were obtained from health-care records. Multivariable regression was used to test musculoskeletal outcomes across sex-specific quintiles of PRAL. RESULTS: PRAL in quintiles was negatively associated with FFMBMI in men (n = 6350, p < 0.001) and women (n = 7989, p < 0.001), with quintile 5 vs 1 differences of -1.5% and -3.2% (both p < 0.001). PRAL was also negatively associated with BUA in women (n = 8312, p = 0.016; quintile 5 vs 1 difference -1.5%, p = 0.024). The combined hazard of hip, wrist and spine fractures (mean ± SD follow-up 17.9 ± 4.9 years) was higher with increasing quintiles of PRAL in men (610 fractures; n = 11,511; p = 0.013) and women (1583 fractures; n = 13,927; p = 0.009), with quintile 5 vs 1 hazard ratios of 1.33 (95% CI: 1.03-1.72, p = 0.029) and 1.21 (95% CI: 1.03-1.42, p = 0.022), but associations were not consistent for all fractures sites and age groups tested. CONCLUSIONS: This study provides strong evidence, albeit observational, for a negative association between PRAL and musculoskeletal health in middle to older age men and women, and thus supports the rationale for a less acidic dietary load.

High variability of food and nutrient intake exists across the Mediterranean Dietary Pattern-A systematic review.

A Mediterranean style dietary pattern (MDP) is considered beneficial for health. The MD Score (MDS) definition has evolved, resulting in considerable variability in the foods and nutrients associated with MDS adherence. We systematically investigated food and nutrient composition of the MD between studies, countries, and methods of classifying the MDS. We searched Embase for MD systematic reviews and selected observational studies reporting intakes of foods, macronutrients, or micronutrients by categories of MDS adherence. The percentage differences in food and nutrient intakes between categories of high and low adherence to the MDS were calculated for each study. A total of 369 full-text primary papers were reviewed from the included systematic reviews and 74 papers selected (66 adults, 8 children). We found considerable differences in MDS definitions and scoring criteria. Between-study variation in food intake between high- and low-adherence MDS adherence categories ranged from a mean of -23% for meat, to 119% for fruit, and 278% for fish. Greater variability was evident in non-Mediterranean than Mediterranean regions. We conclude that few studies report food and nutrient intakes across the range of the MDP in adults and even fewer in children. The considerable variability in the foods and nutrients reported makes comparison of results from studies and translation into dietary guidelines difficult. We recommend that future publications of MD studies include full details of the range of food and nutrient intakes across the distribution of MD adherence in order to facilitate translation into health policy and practice.

Lower Dietary and Circulating Vitamin C in Middle- and Older-Aged Men and Women Are Associated with Lower Estimated Skeletal Muscle Mass.

BACKGROUND: Age-related loss of skeletal muscle mass contributes to poor outcomes including sarcopenia, physical disability, frailty, type 2 diabetes, and mortality. Vitamin C has physiological relevance to skeletal muscle and may protect it during aging, but few studies have investigated its importance in older populations. OBJECTIVES: We aimed to investigate cross-sectional associations of dietary and plasma vitamin C with proxy measures of skeletal muscle mass in a large cohort of middle- and older-aged individuals. METHODS: We analyzed data from >13,000 men and women in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, aged 42-82 y. Fat-free mass (FFM), as a proxy for skeletal muscle mass, was estimated using bioelectrical impedance analysis and expressed as a percentage of total mass (FFM%) or standardized by BMI (FFMBMI). Dietary vitamin C intakes were calculated from 7-d food diary data, and plasma vitamin C was measured in peripheral blood. Multivariable regression models, including relevant lifestyle, dietary, and biological covariates, were used to determine associations between FFM measures and quintiles of dietary vitamin C or insufficient compared with sufficient plasma vitamin C (<50 µmol/L and ≥50 µmol/L). RESULTS: Positive trends were found across quintiles of dietary vitamin C and FFM measures for both sexes, with interquintile differences in FFM% and FFMBMI of 1.0% and 2.3% for men and 1.9% and 2.9% for women, respectively (all P < 0.001). Similarly, FFM% and FFMBMI measures were higher in participants with sufficient than with insufficient plasma vitamin C: by 1.6% and 2.0% in men, and 3.4% and 3.9% in women, respectively (all P < 0.001). Associations were also evident in analyses stratified into <65-y and ≥65-y age groups. CONCLUSIONS: Our findings of positive associations, of both dietary and circulating vitamin C with measures of skeletal muscle mass in middle- and older-aged men and women, suggest that dietary vitamin C intake may be useful for reducing age-related muscle loss.

A Mediterranean Diet Is Positively Associated with Bone and Muscle Health in a Non-Mediterranean Region in 25,450 Men and Women from EPIC-Norfolk.

Research on Mediterranean diet (MD) adherence and musculoskeletal health is limited. The current study determined if adherence to the alternative MD score (aMED) and MD score (MDS), quantified from 7-d food diaries, was associated with fracture incidence, bone density (calcaneal broadband ultrasound attenuation (BUA)) and fat free mass (expressed over BMI (FFMBMI) using bioelectrical impedance) in 25,450 men and women recruited to the European Prospective Investigation into Cancer study in Norfolk, UK. During 17.4 years of follow up (443,178 total person years) 2195 incident fractures occurred. Higher aMED adherence was associated with 23% reduced total (Q5-Q1 HR 0.77; 95% CI 0.67, 0.88; p-trend < 0.01) and 21% reduced hip (Q5-Q1 HR 0.79; 95% CI 0.65, 0.96; p-trend = 0.01) fracture incidence, and significantly higher BUA (Q5-Q1 1.0 dB/MHz 95% CI 0.2, 1.9; p-trend < 0.01) and FFMBMI (Q5-Q1 0.05 kg/(kg/m2) 95% CI 0.04, 0.06; p-trend < 0.01), comparing extreme adherence quintiles. Higher MDS was also associated with reduced total fractures (Q5-Q1 HR 0.83; 95% CI 0.71, 0.96; p-trend = 0.03) and significantly higher BUA (Q5-Q1 1.4 dB/MHz 95% CI 0.5, 2.3; p-trend < 0.01) and FFMBMI (Q5-Q1 0.03 kg/(kg/m2) 95% CI 0.01, 0.04; p-trend < 0.01). This evidence supports the need to develop interventions to enhance MD adherence, particularly in women, where evidence for associations was stronger.

The relationships between sarcopenic skeletal muscle loss during ageing and macronutrient metabolism, obesity and onset of diabetes.

Skeletal muscle is integral to the metabolism and utilisation of macronutrients; however, substantial muscle loss and morphological changes occur with ageing. These are associated with loss of muscle function and accelerate rapidly from the age of 60 years, leading to the conditions of sarcopenia and frailty. As the relationship between muscle ageing and macronutrient metabolism and utilisation has seen limited research to date, this review focuses on the interactions between skeletal muscle changes during ageing, metabolism and utilisation of fat, carbohydrates and overall energy expenditure.Skeletal muscle contributes less to resting energy expenditure during ageing, potentially contributing to onset of obesity from middle age. Age-related changes to skeletal muscle lead to glucose dysregulation, with consequent reduction in glycaemic control, increased insulin resistance and ultimately onset of type-2 diabetes. Recent studies indicate that high total fat and SFA intake are detrimental to skeletal muscle, while higher intakes of PUFA are protective. Age-associated changes in skeletal muscle may also reduce total fatty acid utilisation.In conclusion, further research is needed to understand the relationships between macronutrient metabolism and utilisation and age-related changes to skeletal muscle. No dietary recommendations exist specifically for skeletal muscle health during ageing, but we advise individuals to follow healthy eating guidelines, by consuming sufficient protein, fruit and vegetables, and limited SFA and to maintain physically active lifestyles. Clinicians responsible for managing type-2 diabetes need to be aware of growing evidence relating age-related skeletal muscle changes to diabetes onset and progression.

Age and Muscle Function Are More Closely Associated With Intracellular Magnesium, as Assessed by 31P Magnetic Resonance Spectroscopy, Than With Serum Magnesium.

Total serum magnesium is a common clinical measurement for assessing magnesium status; however, magnesium in blood represents less than 1% of the body's total magnesium content. We measured intramuscular ionized magnesium by phosphorus magnetic resonance spectroscopy (31P-MRS) and tested the hypothesis that this measure better correlates with skeletal muscle function and captures more closely the effect of aging than the traditional measure of total serum magnesium. Data were collected from 441 participants (age 24-98 years) in the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging that encompasses a broad age range. Results showed that intramuscular ionized magnesium was negatively associated with age (ß = -0.29, p < 0.001, R 2 = 0.08) and positively associated with knee-extension strength (ß = 0.31, p < 0.001, and R 2 = 0.1 in women; and ß = 0.2, p = 0.003, and R 2 = 0.04 in men), while total serum magnesium showed no association with age or strength (p = 0.27 and 0.1, respectively). Intramuscular ionized magnesium was significantly lower in women that in men (p < 0.001), perhaps due to chronic latent Mg deficiency in women that is not otherwise detected by serum magnesium levels. Based on these findings, we suggest that intramuscular ionized magnesium from 31P-MRS is a better clinical measure of magnesium status than total serum magnesium, and could be measured when muscle weakness of unidentified etiology is detected. It may also be used to monitor the effectiveness of oral magnesium interventions, including supplementation.

Best Practices for Conducting Observational Research to Assess the Relation between Nutrition and Bone: An International Working Group Summary.

Diet is a modifiable factor that can affect bone strength and integrity, and the risk of fractures. Currently, a hierarchy of scientific evidence contributes to our understanding of the role of diet on bone health and fracture risk. The strength of evidence is generally based on the type of study conducted, the quality of the methodology employed, the rigor and integrity of the data collected and analysis plan, and the transparency and completeness of the results. Randomized controlled trials (RCTs) are considered to be the gold standard from a clinical research paradigm, but there is a dearth of high-quality diet-related intervention trials with bone as the primary outcome, forcing the use of observational research to inform research and clinical practices. However, for observational research to be of the most utility, standardization and optimization of the study design, accurate and reliable measurement of key variables, and appropriate data analysis and data reporting are paramount. Although there have been recommendations made in relation to RCTs in the field of nutrition, no clear rubric exists for best practices in conducting observational research with regard to nutrition and bone health. Therefore, the purpose of this paper is to describe the best practices and considerations for designing, conducting, analyzing, interpreting, and reporting observational research specifically for understanding the role of nutrition in bone health, amassed by a global panel of scientific experts with strengths in bone, nutrition epidemiology, physical activity, public health, clinical and translational trials, and observational study methods. The global panel of scientific experts represents the leadership and selected participants from the 10th annual International Symposium for the Nutritional Aspects of Osteoporosis. The topics selected and best practices presented reflect expert opinion and areas of scientific expertise of the authors rather than a systematic or comprehensive literature review or professional reporting guidelines.

Nonsense-mediated mRNA decay efficiency varies in choroideremia providing a target to boost small molecule therapeutics.

Choroideremia (CHM) is an x-linked recessive chorioretinal dystrophy, with 30% caused by nonsense mutations in the CHM gene resulting in an in-frame premature termination codon (PTC). Nonsense-mediated mRNA decay (NMD) is the cell's natural surveillance mechanism that detects and destroys PTC-containing transcripts, with UPF1 being the central NMD modulator. NMD efficiency can be variable amongst individuals with some transcripts escaping destruction, leading to the production of a truncated non-functional or partially functional protein. Nonsense suppression drugs, such as ataluren, target these transcripts and read-through the PTC, leading to the production of a full length functional protein. Patients with higher transcript levels are considered to respond better to these drugs, as more substrate is available for read-through. Using Quantitative reverse transcription PCR (RT-qPCR), we show that CHM mRNA expression in blood from nonsense mutation CHM patients is 2.8-fold lower than controls, and varies widely amongst patients, with 40% variation between those carrying the same UGA mutation [c.715 C>T; p.(R239*)]. These results indicate that although NMD machinery is at work, efficiency is highly variable and not wholly dependent on mutation position. No significant difference in CHM mRNA levels was seen between two patients' fibroblasts and their induced pluripotent stem cell-derived retinal pigment epithelium. There was no correlation between CHM mRNA expression and genotype, phenotype or UPF1 transcript levels. NMD inhibition with caffeine was shown to restore CHM mRNA transcripts to near wild-type levels. Baseline mRNA levels may provide a prognostic indicator for response to nonsense suppression therapy, and caffeine may be a useful adjunct to enhance treatment efficacy where indicated.