The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1β, IL-6 and TNFα responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4–40 mmol/l nicotinamide or 4–100 µmol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFα, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease.
Cytokines are small, cell-signaling proteins. It’s well-known that one of the effects of hard exercise, such as resistance training, is an increase in inflammatory cytokines. See, for example, here, in which the authors review the association of cytokines and exercise.
One problem with weight training as one gets older is recovery time, which get substantially longer as one ages. (I’m old.) Inflammatory cytokines rise precipitously in the days following a hard workout, then decline. The recovery period seems to be closely aligned with the rise and fall of cytokines. With that in mind, I decided to try supplementing with nicotinamide, 500 mg/d, to see if that would speed recovery time after a weight workout by suppressing pro-inflammatory cytokines. By God, it seems to work. My recovery times have been cut to 2 days from 3, at least so far. We’ll see how it plays out.