NICOTINIC ACID & NICOTINAMIDE

 NICOTINIC ACID & NICOTINAMIDE
Niacin is used to describe two related compounds, nicotinic acid and nicotinamide, both having biological activity. Niacin is formed by the metabolism of tryptophan and is therefore not strictly named as a vitamin and is not in itself necessary for the body.

Niacin is the precursor for two cofactors, NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine phosphate dinucleotide), which are essential for the operation of a wide range of enzymes involved in redox reactions.

NAD and NADPH coenzymes are involved in a large number of redox reactions essential for the normal functioning of mammalian cells. In addition, NAD coenzyme is the source for ADP-ribose, which is used to repair DNA breakage caused by mutagenic and other toxins.

Niacin is largely present in food as a bound form requiring hydrolysis to release the free nicotinamide or nicotinic acid prior to absorption. In animal tissues niacin is predominantly co-enzyme NAD and NADP.

Nicotinamide can be obtained from the diet where it is predominantly NAD and NADP, which are hydrolyzed in the intestine and the resulting nicotinamide absorbed either as such or after hydrolysis into nicotinic acid. In addition, niacin in cereals is present as nicotinic acid glucoside, which is subject to limited hydrolysis in vivo and is essentially not absorbed by the gastrointestinal tract and is not bioavailable. Boiling releases most of the total niacin present in corn as nicotinamide and very little nicotinic acid. Niacin in cereals such as wheat, barley and oats do not give free nicotinic acid or nicotinamide during cooking. Coffee contains high concentrations of free nicotinic acid (160-400 mg / kg).

Nicotinic acid is rapidly absorbed by both the stomach and the upper small intestine, while the conversion of nicotinic acid to nicotinamide occurs after its formation as a pyridine nucleotide.

Due to the metabolic formation of niacin by tryptophan, the nutritional requirements for niacin are complex and related to the nutritional content of both tryptophan and niacin (overlooking niacin in cereals, which is largely unproductive). Total niacin in the diet is taken as the sum of preformed niacin plus 1/60 of the tryptophan content. There is no absolute requirement for the intake of preformed niacin in the diet, with between 9 and 18 mg / day of niacin equivalents. However, it was reported that there is likely to be no requirement for any preformed niacin in the diet under normal conditions and that the intrinsic synthesis by tryptophan will satisfy the requirements.

Data from studies in humans have shown toxicity risks have arisen due to the fact that high doses of nicotinic acid have been used for their therapeutic effects on cholesterol lowering and blood hyperlipidemias. The most comprehensive study was conducted by the Coronary Disease Research Group, where various dangers have been reported to be associated with high doses of nicotinic acid. Nicotinamide has been investigated to reduce the risk of developing diabetes with clinical trials being ongoing. Side effects that have been reported by high doses of nicotinic acid include vasodilatation, hot flashes, and gastrointestinal effects such as indigestion, diarrhea, constipation, hepatotoxicity, decreased glucose tolerance, edema, and blurred vision.

To reduce adverse reactions, safe upper levels of uptake for nicotinic acid and nicotinamide have been identified.

Nicotinic acid
Forms of toxicity of nicotinic acid occur mainly at doses greater than 500 mg / day, with hepatotoxicity to be the most serious and potentially life-threatening side effect.

Age (years) Tolerable upper recruitment level (UL)
for nicotinic acid (mg per day)
1-3 2
4-6 3
7-10 4
11-14 6
15-17 8
 
Nicotinamide
There was only one reported case of hepatotoxicity in a patient receiving a high dose of nicotinamide in use as a hypolipidemic drug. No significant side effects have been reported in cliical trials of the potential benefits of nicotinamide in patients with or at risk of diabetes who have used up to 3 g daily doses for periods of up to 3 years.

Age (years)
 
Tolerable upper recruitment level (UL) for nicotinamide (mg per day)
1-3 150
4-6 220
7-10 350
11-14 500
15-17 700
 
The form of niacin used generally in vitamin supplements and for addition to food is nicotinamide, which does not excite and appears to be of low toxicity compared to nicotinic acid.

There is insufficient data on the safety of nicotinic acid or nicotinamide during pregnancy or lactation and therefore the upper level for adults does not apply at these stages of life. Regarding nicotinamide, there is no indication that intakes within the range consumed in food, including fortified foods, in European countries are not associated with any risk during pregnancy or lactation and there are indications of at least one study, that an additional 15 mg had no adverse effect on the outcome of pregnancy.

Reference:
  • SCF (2002) Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Levels of Nicotinic Acid and Nicotinamide (Niacin) (expressed on 17 April 2002).
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