Effect of acipimox on skeletal muscle biochemistry, structure and function in older people with probable sarcopenia: an experimental medicine study

Abstract

Background: Skeletal muscle nicotinamide adenine dinucleotide (NAD) concentrations are low in people with sarcopenia. Increasing NAD concentrations may offer a novel therapy. This study tested if acipimox (a NAD precursor) improves skeletal muscle NAD concentration and function in people with probable sarcopenia. Participants aged 65 and over with low walk speed (< 0.8 m/s) and low muscle strength (by 2019 European Working Group criteria) were recruited to this before and after, proof-of-concept study. Participants received acipimox 250 mg orally (twice or thrice daily according to creatinine clearance) + aspirin 75 mg daily (to prevent facial flushing) for 4 weeks. Muscle biopsy of the vastus lateralis, ³¹P magnetic resonance spectroscopy and a 7-digital mobility assessment were performed before starting acipimox and after 3 weeks of treatment. The primary outcome was change in skeletal muscle NAD concentration. Secondary outcomes included change in phosphocreatine recovery rate and measures of physical performance. Eleven participants (8 women), mean age 78.9 years (SD 4.3), were recruited. Mean walk speed at baseline was 0.69 m/s (SD 0.07). All completed baseline and follow-up visits. Median medication adherence was 95% (range 91-104%). There was no statistically significant difference in the primary outcome of change in NAD concentrations in skeletal muscle between baseline and follow-up [median difference: - 0.003 umol/g (IQR - 0.058 to 0.210); P = 0.26] or secondary outcomes. Nineteen none-serious adverse events were reported. Although the study protocol was feasible and well tolerated, acipimox did not improve skeletal muscle NAD concentration, biochemical markers or physical function in people with probable sarcopenia.

Clinicaltrials: gov Identifier: ISRCTN (ISRCTN87404878).

Keywords: Acipimox; Clinical trial; Nicotinamide adenine dinucleotide; Sarcopenia.

Fig. 1

CONSORT diagram of participant flow through the trial

Fig. 2

Change in skeletal muscle NAD, NADH and NAD/NADH ratio between baseline and follow-up