Associations between branched chain amino acid intake and biomarkers of adiposity and cardiometabolic health independent of genetic factors: a twin study

Background: Conflicting data exist on the impact of dietary and circulating levels of branched chain amino acids (BCAA) on cardiometabolic health and it is unclear to what extent these relations are mediated by genetics.  Methods: In a cross-sectional study of 1997 female twins we examined associations between BCAA intake, measured using food frequency-questionnaires, and a range of markers of cardiometabolic health, including DXA-measured body fat, blood pressure, HOMA-IR, highsensitivity C-reactive protein (hs-CRP) and lipids. We also measured plasma concentrations of BCAA and known metabolites of amino acid metabolism using untargeted mass spectrometry. Using a within-twin design, multivariable analyses were used to compare the associations between BCAA intake and endpoints of cardiometabolic health, independently of genetic confounding.  Results: Higher BCAA intake was significantly associated with lower HOMA-IR (-0.1, Ptrend 0.02), insulin (-0.5 µU/mL, P-trend 0.03), hs-CRP -0.3 mg/L, P-trend 0.01), systolic blood pressure (-2.3 mm Hg, P-trend 0.01) and waist-to-height ratio (-0.01, P-trend 0.04), comparing extreme quintiles of intake. These associations persisted in within-pair analysis for monozygotic twins for insulin resistance (P<0.01), inflammation (P=0.03), and blood pressure (P=0.04) suggesting independence from genetic confounding. There were no association between BCAA intake and plasma concentrations, although two metabolitespreviously associated with obesity were inversely associated with BCAA intake (alphahydroxyisovalerate and trans-4-hydroxyproline).  Conclusions: Higher intakes of BCAA were associated, independently of genetics, with lower insulin resistance, inflammation, blood pressure and adiposity-related metabolites. The BCAA intake associated with our findings are easily achievable in the habitual diet.  Abbreviations: BCAA, branched chain amino acids; DBP, diastolic blood pressure; DZ, dizygotic; FFQ, food frequency questionnaire; HDL-C, high density lipoprotein cholesterol; hs-CRP, high sensitivity C-reactive protein; MZ, monozygotic; SBP, systolic blood pressure; T2DM, type 2 diabetes; SBP, systolic blood pressure; WHtR, waist to height rati

Amino acid intakes are inversely associated with arterial stiffness and central blood pressure in women

Background: Although data suggest that intake of total protein and specific amino acids (AAs) reduces blood pressure, data on other cardiovascular disease risk factors are limited. Objective: We examined associations between intake of AAs with known mechanistic links to cardiovascular health and direct measures of arterial stiffness, central blood pressure, and atherosclerosis. Methods: In a cross-sectional study of 1898 female twins aged 18–75 y from the TwinsUK registry, intake of 7 cardioprotective AAs (arginine, cysteine, glutamic acid, glycine, histidine, leucine, and tyrosine) was calculated from food-frequency questionnaires. Direct measures of arterial stiffness and atherosclerosis included central systolic blood pressure (cSBP), mean arterial pressure (MAP), augmentation index (AI), pulse wave velocity (PWV), and intima–media thickness (IMT). ANCOVA was used to assess the associations between endpoints of arterial stiffness and intake (per quintile), adjusting for potential confounders. Results: In multivariable analyses, higher intake of total protein and 7 potentially cardioprotective AAs was associated with lower cSBP, MAP, and PWV. Higher intake of glutamic acid, leucine, and tyrosine was most strongly associated with PWV, with respective differences of -0.4 ± 0.2 m/s (P-trend = 0.02),-0.4 ± 0.2 m/s (P-trend = 0.03), and -0.4 ± 0.2 m/s (P-trend = 0.03), comparing extreme quintiles. There was a significant interaction between AA intake and protein source, and higher intake of AAs from vegetable sources was associated with lower central blood pressure and AI. Higher intake of glutamic acid, leucine, and tyrosine from animal sources was associated with lower PWV. Conclusions: These data provide evidence to suggest that intake of several AAs is associated with cardiovascular benefits beyond blood pressure reduction in healthy women. The magnitude of the observed associations was similar to those previously reported for other lifestyle factors. Increasing intake of these AAs could be an important and readily achievable way to reduce cardiovascular disease risk

Improving mental health and reducing antipsychotic use in people with dementia in care homes: the WHELD research programme including two RCTs

BackgroundThe effective management of agitation and other neuropsychiatric and behavioural symptoms in people with dementia is a major challenge, particularly in care home settings, where dementia severity is higher and there is limited training and support for care staff. There is evidence for the value of staff training and the use of psychosocial approaches; however, no intervention currently exists that combines these elements into an intervention that is fit for purpose and effective in these settings based on evidence from a randomised controlled trial.ObjectiveThe objective was to develop and evaluate a complex intervention to improve well-being, reduce antipsychotic use and improve quality of life in people with dementia in care homes through person-centred care, management of agitation and non-drug approaches.DesignThis was a 5-year programme that consisted of six work packages. Work package 1 consisted of two systematic reviews of personalised psychosocial interventions for behavioural and psychological symptoms for people with dementia in care homes. Work package 2 consisted of a metasynthesis of studies examining implementation of psychosocial interventions, in addition to developing a draft Well-being and Health for people with Dementia (WHELD) programme. Work package 3 consisted of a factorial study of elements of the draft WHELD programme in 16 care homes. Work package 4 involved optimisation of the WHELD programme based on work package 3 data. Work package 5 involved a multicentre randomised controlled trial in 69 care homes, which evaluated the impact of the optimised WHELD programme on quality of life, agitation and overall neuropsychiatric symptoms in people with dementia. Work package 6 focused on dissemination of the programme.SettingThis programme was carried out in care homes in the UK.ParticipantsParticipants of this programme were people with dementia living in care homes, and the health and care professionals providing treatment and care in these settings.ResultsWork package 1: reviews identified randomised controlled trials and qualitative evidence supporting the use of psychosocial approaches to manage behavioural symptoms, but highlighted a concerning lack of evidence-based training manuals in current use. Work package 2: the meta-analysis identified key issues in promoting the use of interventions in care homes. The WHELD programme was developed through adaptation of published approaches. Work package 3: the factorial trial showed that antipsychotic review alone significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval 0.05 to 0.60). Antipsychotic review plus social interaction significantly reduced mortality (odds ratio 0.36, 95% confidence interval 0.23 to 0.57), but this group showed significantly worse outcomes in behavioural and psychological symptoms of dementia than the group receiving neither antipsychotic review nor social interaction (mean difference 7.37 symptoms, 95% confidence interval 1.53 to 13.22 symptoms). This detrimental impact was reduced when combined with social interaction (mean difference –0.44 points, 95% confidence interval –4.39 to 3.52 points), but with no significant benefits for agitation. The exercise intervention significantly improved neuropsychiatric symptoms (mean difference –3.58 symptoms, 95% confidence interval –7.08 to –0.09 symptoms) but not depression (mean difference –1.21 points, 95% confidence interval –4.35 to 1.93 points). Qualitative work with care staff provided additional insights into the acceptability and feasibility of the intervention. Work package 4: optimisation of the WHELD programme led to a final version that combined person-centred care training with social interaction and pleasant activities. The intervention was adapted for delivery through a ‘champion’ model. Work package 5: a large-scale, multicentre randomised controlled trial in 69 care homes showed significant benefit to quality of life, agitation and overall neuropsychiatric symptoms, at reduced overall cost compared with treatment as usual. The intervention conferred a statistically significant improvement in quality of life (Dementia Quality of Life Scale – Proxy z-score of 2.82, mean difference 2.54, standard error of measurement 0.88, 95% confidence interval 0.81 to 4.28, Cohen’s d effect size of 0.24; p = 0.0042). There were also statistically significant benefits in agitation (Cohen-Mansfield Agitation Inventory z-score of 2.68, mean difference –4.27, standard error of measurement 1.59, 95% confidence interval –7.39 to –1.15, Cohen’s d effect size of 0.23; p = 0.0076) and overall neuropsychiatric symptoms (Neuropsychiatric Inventory – Nursing Home version z-score of 3.52, mean difference –4.55, standard error of measurement 1.28, 95% confidence interval –7.07 to –2.02, Cohen’s d of 0.30; p

The relationship between perceived functional difficulties and the ability to live well with mild-to-moderate dementia: Findings from the IDEAL programme.

yesObjectives: The objectives of the study are to investigate how different levels of functional ability relate to quality of life, well‐being, and satisfaction with life, conceptualised as reflecting capability to “live well” in people with dementia. Methods/design: Participants were 1496 people with mild‐to‐moderate dementia and 1188 informants who completed baseline assessments in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort study. Total selfrated and informant‐rated scores on the Functional Activities Questionnaire were split into six ability levels to monitor how poorer functioning impacts the ability to live well. We also investigated the potential influence of sociodemographic and diagnostic variables, depression, cognition, and carer stress. Results: Multivariate multiple regression models found that people with dementia who had the greatest functional impairment according to self‐ratings and informant ratings had poorer living well scores than those with the least functional impairment. Sociodemographic and diagnostic factors and cognition had little impact on effect sizes. For self‐ratings, depression attenuated the relationship between functional ability and living well, whereas carer stress attenuated informant ratings. Conclusions: People with dementia with the least functional impairments had greater capability to live well than those with the most functional impairment. Even subtle perceived difficulties in functional ability had a detrimental effect on the ability of people with dementia to live well. Depression in people with dementia and carer stress in informants influenced these associations, and therefore, these factors should be routinely included in future research studies and clinical assessments

Systematic review processes and the management of opioid withdrawal

OBJECTIVE:To assess the diversity of research on the management of opioid withdrawal, identify sources of heterogeneity and provide a context for subsequent systematic reviews to establish evidence-based best practice. METHODS:References were identified through searches of multiple electronic databases and handsearching the reference lists of retrieved articles. The principal criterion for inclusion in the literature mapping process was that it be a study of an intervention intended to manage the process of opioid withdrawal. RESULTS:Of 218 references assessed, all participants were dependent on heroin in 41% and on methadone or l-alpha acetyl methadol (LAAM) in 24%. More than 17 different types of treatment approach were identified. Only 42% of references used a rating instrument to assess withdrawal severity and reported sufficient results to indicate the timing and magnitude of the peak and/or duration of withdrawal. The type of rating instrument used and the way in which results were reported varied enormously. A clear parameter for completion of detoxification was used for 37% of references. CONCLUSIONS:The capacity for rigorous systematic reviews of the management of opioid withdrawal is currently limited. There are multiple sources of heterogeneity that will need to be taken into account. IMPLICATIONS:The use of narrative reviews and observational studies are important complements to formal systematic reviews in the establishment of evidence-based practice in any area that combines aspects of psychology, behaviour, social context and medical treatment