Nicotinamide supplementation induces detrimental metabolic and epigenetic changes in developing rats

Br J Nutr. 2013 Dec;110(12):2156-64. doi: 10.1017/S0007114513001815. Epub 2013 Jun 17.


Ecological evidence suggests that niacin (nicotinamide and nicotinic acid) fortification may be involved in the increased prevalence of obesity and type 2 diabetes, both of which are associated with insulin resistance and epigenetic changes. The purpose of the present study was to investigate nicotinamide-induced metabolic changes and their relationship with possible epigenetic changes. Male rats (5 weeks old) were fed with a basal diet (control group) or diets supplemented with 1 or 4 g/kg of nicotinamide for 8 weeks. Low-dose nicotinamide exposure increased weight gain, but high-dose one did not. The nicotinamide-treated rats had higher hepatic and renal levels of 8-hydroxy-2'-deoxyguanosine, a marker of DNA damage, and impaired glucose tolerance and insulin sensitivity when compared with the control rats. Nicotinamide supplementation increased the plasma levels of nicotinamide, N1-methylnicotinamide and choline and decreased the levels of betaine, which is associated with a decrease in global hepatic DNA methylation and uracil content in DNA. Nicotinamide had gene-specific effects on the methylation of CpG sites within the promoters and the expression of hepatic genes tested that are responsible for methyl transfer reactions (nicotinamide N-methyltransferase and DNA methyltransferase 1), for homocysteine metabolism (betaine-homocysteine S-methyltransferase, methionine synthase and cystathionine β-synthase) and for oxidative defence (catalase and tumour protein p53). It is concluded that nicotinamide-induced oxidative tissue injury, insulin resistance and disturbed methyl metabolism can lead to epigenetic changes. The present study suggests that long-term high nicotinamide intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betaine / blood
  • Choline / blood
  • CpG Islands / drug effects
  • DNA / metabolism
  • DNA Damage
  • DNA Methylation / drug effects*
  • Dietary Supplements / adverse effects*
  • Epigenesis, Genetic / drug effects*
  • Glucose Intolerance / chemically induced
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Homocysteine / genetics
  • Homocysteine / metabolism
  • Insulin Resistance / genetics
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Metabolic Diseases / chemically induced*
  • Metabolic Diseases / genetics
  • Metabolic Diseases / metabolism
  • Niacin / adverse effects*
  • Niacinamide / adverse effects*
  • Niacinamide / analogs & derivatives
  • Niacinamide / blood
  • Oxidative Stress / genetics
  • Promoter Regions, Genetic / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Uracil / metabolism
  • Vitamin B Complex / adverse effects*
  • Weight Gain / drug effects


  • Homocysteine
  • Vitamin B Complex
  • Niacinamide
  • Niacin
  • Betaine
  • Uracil
  • DNA
  • Choline
  • N(1)-methylnicotinamide