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Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.

ABSTRACT: BACKGROUND:Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. METHODS:We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of <400 m and no contraindications to magnetic resonance imaging scanning. Outcomes were measured at baseline and 20 weeks. The primary outcome was post-exercise phosphocreatine (PCr) recovery rate measured using 31P magnetic resonance spectroscopy of the calf. Secondary outcomes included 6-min walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function and quality of life. RESULTS:In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, -0.07 to 0.27], P?=?0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4-46, P?=?0.02]). This was more pronounced in those with high baseline oxidative stress and urate. CONCLUSION:Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress.

SUBMITTER: Witham MD

PROVIDER: S-EPMC7583523 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.

Witham Miles D MD Clarke Clare L CL Hutcheon Anita A Gingles Christopher C Gandy Stephen S Priba Lukasz L Nicholas Richard S RS Cavin Ian I Sumukadas Deepa D Struthers Allan D AD George Jacob J

Age and ageing 20201001 6

<h4>Background</h4>Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance.<h4>Methods</h4>We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with b ...[more]

PMID: 32318695

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Project description:Background Selenium (Se) is a trace element with a narrow safety margin. Objectives To evaluate the cross-sectional and longitudinal dose-response association between Se exposure and measures of impaired physical function and disability in older adults. Design NHANES 2011–2014 cross-sectional (US, n = 1733, age ?60 years) and Seniors-ENRICA-2 2017–2019 cross-sectional and longitudinal (Spain, n = 2548 and 1741, respectively, age ?65 years) data were analyzed. Whole blood and serum Se levels were measured using inductively coupled plasma-mass spectrometry. Lower-extremity performance was assessed with the Short Physical Performance Battery, and muscle weakness with a dynamometer. Incident mobility and agility limitations, and disability in instrumental activities of daily living (IADL) were ascertained with standardized questionnaires. Analyses were adjusted for relevant confounders, including physical activity. Results across studies were pooled using random-effects meta-analysis. Results Meta-analyzed odds ratios (95% confidence interval) per log2 increase in whole blood Se were 0.54 (0.32; 0.76) for weakness, 0.59 (0.34; 0.83) for impaired lower-extremity performance, 0.48 (0.31; 0.68) for mobility limitations, 0.71 (0.45; 0.97) for agility limitations, and 0.34 (0.12; 0.56) for disability in at least one IADL. Analyses for serum Se in NHANES showed similar results. Findings suggest the inverse association with grip strength is progressive below 140 ?g/L (p-value for non-linear trend in the Seniors-ENRICA-2 study = 0.13), and above 140 ?g/L (p-value for non-linear trend in NHANES = 0.11). In the Seniors-ENRICA-2 cohort, with a 2.2 year follow-up period, a doubling in baseline Se levels were associated with a lower incidence of weakness [odds ratio (95% confidence interval): 0.45 (0.22; 0.91)], impaired lower-extremity performance [0.63 (0.32; 1.23)], mobility [0.43 (0.21; 0.91)] and agility [0.38 (0.18; 0.78)] limitations. Discussion In US and Spanish older adults, Se concentrations were inversely associated with physical function limitations. Further studies are needed to elucidate underlying mechanisms. Graphical abstract Image 1

Project description:BackgroundCurrently 21% of the German population is older than 65 years. Above this age, the risk of suffering from chronic disease and mental disorders increases rapidly. Therefore, physical inactivity is one of the most important public health concerns among older people. To address this issue, we have conceptualised and evaluated a simple and low-threshold intervention, which requires only minimal demand on the participants, targeting older people with inadequate activity levels. The aim of the POWER Study is to investigate whether volunteer-supported outdoor-walking improves physical function and quality of life in older people.Methods/designIn a randomised, controlled interventional superiority-trial, individuals older than 65 years of age living in the community or nursing homes will be randomised into two groups. The study will be conducted in two study centres with assessments at baseline, 6 and 12 months. The intervention group will participate in a supported physical activity intervention for 6 months. An assigned volunteer will visit them three times a week for an outdoor walk between 30 and 50 min, or equivalent indoor activity. Persons in the control group will be invited to two lectures covering topics related to health. Primary endpoint is the physical function measured by the Short Physical Performance Battery (SPPB) at baseline, after 6 and 12 months. Secondary and safety endpoints will be quality of life (EQ. 5D), fear of falling (Falls Efficacy Scale), physical activity (activity diary), cognitive executive function (clock drawing test), falls requiring medical attention, hospitalisation and death. Primary analysis will be carried out by intention to treat.DiscussionWe expect the intervention to improve the overall health status of the participants in a wide range of health-related outcomes. If effectiveness can be shown, the intervention will close an important gap in current services for older people. We will disseminate our experiences and results in the form of informational documents (training manual) to allow municipalities and health care organisations to implement a similar intervention.Trial registrationThe trial was registered on 31 Aug 2018; German Clinical Trials Register (www.germanctr.de), Deutsches Register Klinischer Studien: DRKS00015188 .

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Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.

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Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.

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