Niacin (vitamin B3) occurs in two forms: nicotinic acid and nicotinamide. The active coenzyme forms (nicotinamide adenine dinucleotide [NAD] and NAD phosphate) are essential for the function of hundreds of enzymes and normal carbohydrate, lipid, and protein metabolism.
As a vitamin, the two compounds function similarly, but in pharmacological doses they have distinct effects. Nicotinic acid (1–3 g/day) is an effective treatment for dyslipidemia,4 although its use in people with diabetes has been limited because of its negative effect on glycemic control. Pharmacological doses of nicotinamide are being studied for their potential benefit in the prevention and treatment of diabetes.
The DRIs for niacin are reported in niacin equivalents (NE) because niacin can be synthesized by the body from tryptophan. The RDA is 14 mg NE for women and 16 mg NE for men. The UL is 35 mg NE/day for adults. Niacin deficiency (pellagra) is not common in the United States.
Mechanism of action.
Animal studies suggest that nicotinamide acts by protecting pancreatic β-cells from autoimmune destruction by maintaining intracellular NAD levels and inhibiting the enzyme poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair. Excessive PARP induction results in depletion of cytoplasmic NAD levels, induction of immunoregulatory genes, and cellular apoptosis (programmed cell death). Nicotinamide may additionally act as a weak antioxidant of nitric oxide radicals.
The effects of nicotinamide supplementation have been studied in several trials focusing on the developmentand progressionof type 1 diabetes; a meta-analysis; and one small trial in type 2 diabetes. Results have been mixed, and the largest clinical trial, the European Nicotinamide Diabetes Intervention Trial (ENDIT), is not yet complete.
Nicotinamide appears to be most effective in newly diagnosed diabetes and in subjects with positive islet cell antibodies but not diabetes. People who develop type 1 diabetes after puberty appear to be more responsive to nicotinamide treatment. Study results have offered more support for the idea that nicotinamide helps to preserve β-cell functionthan for its possible role in diabetes prevention. When evaluating these studies, one should pay particular attention to subjects’ age of diabetes onset, duration of diabetes, and form of diabetes; the dose and form of nicotinamide used; the clinical significance of effects; and effects on growth in pediatric populations.