Select Committee on GRAS Substances (SCOGS) Opinion: Niacinamide (nicotinamide)
- SCOGS-Report Number: 108*
- Type Of Conclusion: 1
- ID Code: 98-92-0
- Year: 1979
- 21 CFR Section: 184.1535
The term niacin as adopted by the American Institute of Nutrition, is a generic form including both nicotinic acid and its amide, nicotinamide (or niacinamide), to which it is readily converted in the body. However, niacin as employed by the Code of Federal Regulations refers only to nicotinic acid. Nicotinamide is a component of two essential coenzymes, nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate. The body is also able to form nicotinamide from tryptophan (60mf of tryptophan provide 1mg of niacin equivalent) and much of the total niacin equivalents of the diet are supplied in this manner.
Disappearance data suggest that per capita daily intakes of nicotinic acid and nicotinamide added to foods are less than 7.5 and 2.2mg, respectively. Thus the amount added to foods (about 0.15mg per kg body weight) is approximately one half the total dietary intake of these substances from both added and natural sources. The LD50 for various laboratory animals given the substances parenterally has generally been found to be more than 1g per kg per day. Limited data on oral ingestion by mice and rats suggest that the LD50 may be more than 4g per kg per day. Young laboratory animals fed diets containing 1 or 2 percent nicotinic acid or nicotinamide (1 to 2 g per kg body weight per day) have demonstrated growth depression in some but not all studies. At levels of 0.1 percent in the diet, fatty livers may occur, reflecting an induced choline deficiency.
Because large doses of nicotinic acid are known to reduce serum concentration of cholesterol, administration of nicotinic acid has been employed in management of patients with hypercholesterolemia. Dosage commonly employed is 3 to 9g daily (50 to 150 mg per kg). Initially experienced side effects, including cutaneous flushing, pruritis, and nausea, usually subside with continued therapy and the great majority of subjects then appear to experience no adverse effects. However, abnormal values in liver function test have been detected rather frequently and at least a few subjects have developed jaundice. These manifestations generally subside promptly after discontinuation of treatment. Pathologic changes in the liver, possibly irreversible, have been associated with treatment with large daily doses in a few instances.
Although there have been no short or long term animal studies defining the greatest no adverse effect level of intake of nicotinic and man have been associated with intakes at least a hundredfold greater than those likely to be achieved from fortification of foods.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on niacin (nicotinic acid) or niacinamide (nicotinamide) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.