Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.
allopurinol
older people
oxidative stress
physical performance
skeletal muscle
Journal
Age and ageing
ISSN: 1468-2834
Titre abrégé: Age Ageing
Pays: England
ID NLM: 0375655
Informations de publication
Date de publication:
23 10 2020
23 10 2020
Historique:
received:
09
12
2019
revised:
19
02
2020
pubmed:
23
4
2020
medline:
29
7
2021
entrez:
23
4
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32318695
pii: 5823068
doi: 10.1093/ageing/afaa061
pmc: PMC7583523
doi:
Substances chimiques
Phosphocreatine
020IUV4N33
Allopurinol
63CZ7GJN5I
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1003-1010Subventions
Organisme : British Heart Foundation
ID : PG/13/67/30444
Pays : United Kingdom
Organisme : The Dunhill Medical Trust
ID : R315/1113
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society.
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