title: Excessive nicotinic acid increases methyl consumption and hydrogen peroxide generation in rats.
abstract: BACKGROUND
  Recent ecological evidence has showed a lag-correlation between the prevalence of diabetes and consumption of niacin (nicotinamide and nicotinic acid) in the US. Nicotinamide has been demonstrated to induce insulin resistance due to excess reactive oxygen species and methyl depletion, whereas the effect of nicotinic acid is poorly understood.
  
  
  OBJECTIVE
  To examine the mechanism of the effect of nicotinic acid on glucose metabolism.
  
  
  METHODS
  Rats were injected with different cumulative doses of nicotinic acid (0.5, 2, 4 g/kg) and nicotinamide (2 g/kg). A glucose tolerance test was given 2 h after the final injection. The role of methyl consumption and reactive oxygen species generation were evaluated by measuring N(1)-methylnicotinamide and hydrogen peroxide.
  
  
  RESULTS
  Cumulative doses of nicotinic acid produced a dose-dependent increase in the plasma levels of N(1)-methylnicotinamide and hydrogen peroxide, which was associated with a decrease in liver and skeletal muscle glycogen levels. At the same dosage (2 g/kg), in comparison with nicotinamide, nicotinic acid was weaker in raising plasma N(1)-methylnicotinamide levels (0.7 ± 0.11 µg/mL vs. 4.69 ± 0.24 µg/mL, P < 0.001), but stronger in increasing plasma hydrogen peroxide levels (1.88 ± 0.07 µmol/L vs. 1.55 ± 0.05 µmol/L, P < 0.001). Moreover, nicotinamide, unlike nicotinic acid, did not reduce liver glycogen levels.
  
  
  CONCLUSIONS
  This study suggested that excessive nicotinic acid, like nicotinamide, might induce methyl consumption, oxidative stress and insulin resistance. Long-term consumption high niacin may increase the risk of type 2 diabetes.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Da
authors.initials: D
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Luo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.forename: Shu-Zhuang
authors.initials: SZ
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shi
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Shi-Sheng
authors.initials: SS
authors.lastname: Zhou
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D009536:Niacinamide; D009525:Niacin; D006003:Glycogen; D006861:Hydrogen Peroxide; D005947:Glucose; C024058:N(1)-methylnicotinamide