As many of you know, the Wikipedia page has a warning not to take more than 3g daily as it may elevate liver enzymes. I traced the warning to a few studies with high dose niacinamide using 4g - 6g daily for conditions like HIV and arthritis. However, they did not provide an explanation on why the effect was observed. I kept digging and found a few older references about niacinamide inhibiting respiration in the liver. These studies themselves pointed to a 1951 study which finally provided the answer. It was an in vitro study but it matches the results from other studies so I doubt it is a coincidence.
The 1951 study below shows that using a concentration of 0.5 mM/L niacinamide / nicotinamide or higher inhibited respiration in the liver (see attached image). That concentration of 0.5 mM/L just happens to be achievable in humans by a single dose of 3g niacinamide. Doses lower than that actually stimulated respiration, so niacinamide can have quite a beneficial effect on metabolism when used in the appropriate doses.
INHIBITION OF DIPHOSPHOPYRIDINE NUCLEOTIDE-REQUIRING ENZYMES BY NICOTINAMIDE
"...The presence of 0.5 mM of nicotinamide produced considerable inhibition which was reversed by supplements of DPN. Thus it appeared that nicotinamide at the level tested caused DPN to be rate limiting in the respiration scheme. When at a fixed level of DPN the amount of nicotinamide added was varied from 0 to 10V3 mole, the results presented in Fig. 2 were obtained. It will be noted that the highest level of nicotinamide tested caused considerable inhibition. However, at the low levels some stimulation occurred. This stimulatory effect is compatible with previous observations (2) and is probably due to protection of the DPN from destruction by the DPN nucleosidase. At an intermediary level of nicotinamide the oxygen uptake was almost identical to that with no nicotinamide. At this concentration of nicotinamide a balance between its stimulator-y effect (due to nucleosidase inhibition) and its inhibitory effect was obtained. At higher levels of nicotinamide its inhibitory activities exceeded its stimulatory action and resulted in a net decrease in respiratory rate."
The 1951 study below shows that using a concentration of 0.5 mM/L niacinamide / nicotinamide or higher inhibited respiration in the liver (see attached image). That concentration of 0.5 mM/L just happens to be achievable in humans by a single dose of 3g niacinamide. Doses lower than that actually stimulated respiration, so niacinamide can have quite a beneficial effect on metabolism when used in the appropriate doses.
INHIBITION OF DIPHOSPHOPYRIDINE NUCLEOTIDE-REQUIRING ENZYMES BY NICOTINAMIDE
"...The presence of 0.5 mM of nicotinamide produced considerable inhibition which was reversed by supplements of DPN. Thus it appeared that nicotinamide at the level tested caused DPN to be rate limiting in the respiration scheme. When at a fixed level of DPN the amount of nicotinamide added was varied from 0 to 10V3 mole, the results presented in Fig. 2 were obtained. It will be noted that the highest level of nicotinamide tested caused considerable inhibition. However, at the low levels some stimulation occurred. This stimulatory effect is compatible with previous observations (2) and is probably due to protection of the DPN from destruction by the DPN nucleosidase. At an intermediary level of nicotinamide the oxygen uptake was almost identical to that with no nicotinamide. At this concentration of nicotinamide a balance between its stimulator-y effect (due to nucleosidase inhibition) and its inhibitory effect was obtained. At higher levels of nicotinamide its inhibitory activities exceeded its stimulatory action and resulted in a net decrease in respiratory rate."