A new physiological biomarker for nitrate exposure in humans.

After toxicological studies with nitrate/nitrite in rats it was observed with nuclear magnetic resonance that N-methylnicotinamide (NMN), a metabolite of tryptophan was increased. The use of NMN as a biomarker for nitrate/nitrite exposure was investigated further in additional experiments with rats and in a human study with volunteers. Rats have been exposed to 36 mmol KCl, KNO2 or KNO3 per 1 tap water for 13 weeks. In general, the animals receiving KNO2 showed a statistically significant (P < 0.01) 2-fold increase in NMN compared with the KCl group. This increase was observed after a relatively high exposure (about 800 mg/kg body wt./day). It was also noticed that the initial increase in urinary NMN concentrations decreased after prolonged exposure for 12 weeks. To investigate the induction of urinary NMN in humans, an experiment has been performed in which 8 volunteers received a single oral dose of sodium nitrate, corresponding with 10 mg NaNO3/kg body wt./day (2 times the acceptable daily intake for nitrate). A rapid increase of urinary NMN (up to 6-fold) was observed in 4 volunteers. In the other 4 volunteers the urinary NMN concentration did hardly react. When the experiment was repeated with the same volunteers, it was remarkable to see that in this experiment all volunteers showed the same individual response on urinary NMN as in the first experiment. It is concluded that NMN can possibly be a good biomarker for the internal nitrite exposure of humans, but further studies are necessary to assess its value.