Abstract
Introduction:
In vitro studies show that 1mmol/L nicotinamide (NAM) increases neutrophil-mediated killing of Staphylococcus aureus and Pseudomonas aeruginosa.
Aims:
To assess the dose of orally administered NAM required to achieve a serum level of 1mmol/L. To assess the effect of NAM in vivo on up-regulation of neutrophil function and bacterial killing.
Methods:
Participants were given oral NAM for two weeks at twice daily doses of 1.5g, 2g, 2.5g, or 3g, with one healthy and one bronchiectasis participant for each dose. The primary end point was peak serum NAM level. The secondary endpoints were levels of C/EBPε, lactoferrin and cathelicidin expression in neutrophils, and the number of surviving bacterial colony-forming units (CFUs) after incubation of four respiratory pathogens with blood from participants.
Results:
The highest peak concentration of NAM achieved was 0.3mmol/L in the 3g twice daily dosing. NAM significantly enhanced blood killing of Streptococcus pneumoniae, with the adjusted estimate of relative change in CFUs per 0.1mmol/L increase in serum NAM levels being 0.44 (95% CI 0.34 to 0.56). NAM increased the CFUs of P. aeruginosa (1.34, 95%CI 1.17 to 1.54), and did not significantly enhance blood killing against S. aureus or Haemophilus influenza. NAM did not augment the expression of the neutrophil transcription factor C/EBPe or downstream antimicrobial peptides cathelicidin and lactoferrin.
Conclusion:
Doses of oral NAM up to 3g twice daily did not achieve the serum concentration of 1mmol/L. At lower concentrations, NAM significantly enhanced bacterial killing against S. pneumoniae, but did not enhance the expression of neutrophil markers.
- © 2014 ERS