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Aim: To investigate nicotinamide's action on glucose metabolism, and the association between niacin consumption and obesity prevalence., Methods: Dynamic nicotinamide's effect on plasma hydrogen peroxide and glucose metabolism was investigated using oral glucose tolerance tests with or without nicotinamide in the same five healthy subjects. Lag-regression analysis was used to examine the association between the niacin consumption and the obesity prevalence among US children using the data from the Economic Research Service of the US Department of Agriculture and from US Centers for Disease Control and Prevention, respectively., Results: Compared with the control oral glucose tolerance test, the 1-h plasma hydrogen peroxide (1.4 +/- 0.1 micromol/L vs 1.6 +/- 0.1 micromol/L, P = 0.016) and insulin levels (247.1 +/- 129.0 pmol/L vs 452.6 +/- 181.8 pmol/L, P = 0.028) were significantly higher, and the 3-h blood glucose was significantly lower (5.8 +/- 1.2 mmol/L vs 4.5 +/- 1.1 mmol/L, P = 0.002) after co-administration of glucose and 300 mg nicotinamide. The obesity prevalence among American children increased with the increasing per capita niacin consumption, the increasing grain contribution to niacin due to niacin-fortification, and the increasing niacin-fortified ready-to-eat cereal consumption, with a 10-year lag. The regression analyses showed that the obesity prevalence in the US children of all age groups was determined by niacin consumption (R(2) = 0.814, 0.961 and 0.94 for 2-5 years, 6-11 years and 12-19 years age groups, respectively)., Conclusion: The appetite-stimulating effect of nicotinamide appears to involve oxidative stress. Excess niacin consumption may be a major factor in the increased obesity prevalence in US children.

Aim: To investigate whether nicotinamide overload plays a role in type 2 diabetes., Methods: Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N(1)-methylnicotinamide on glucose metabolism, plasma H(2)O(2) levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively., Results: Diabetic subjects had significantly higher plasma N(1)-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 +/- 0.13 micromol/L vs 0.6 +/- 0.13 micromol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N(1)-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N(1)-methylnicotinamide. Moreover, cumulative exposure to N(1)-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/NADH ratio, and increased plasma H(2)O(2) levels. Decrease in NAD/NADH ratio and increase in H(2)O(2) generation were also observed in human erythrocytes after exposure to N(1)-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N(1)-methylnicotinamide clearance., Conclusion: These findings suggest that nicotinamide overload, which induced an increase in plasma N(1)-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.