term niacin is the generic descriptor for nicotinic acid and nicotinamide, which are essential for formation of the coenzymes nicotinamide adenine dinucleotide (NAD)
and nicotinamide adenine dinucleotide phosphate (NADP).
Approximately 200 enzymes, primarily dehydrogenases, are dependent on the
coenzymes NAD and NADP, which both serve as a hydrogen donor or electron acceptor.
53 NAD functions as a coenzyme with enzymes involved in the oxidation of fuelmolecules such as glyceraldehyde 3-phosphate, lactate, alcohol, 3-hydroxybutyrate,
and a-ketoglutarate. NADP functions as a hydrogen donor in reductive biosynthesis
such as in fatty acid and steroid syntheses, and is involved in the pentose phosphate
pathways. In addition, NAD acts as donor of adenosine diphosphate ribose (ADPribose)
for the post-translational modification of proteins and for the formation of
cyclic ADP-ribose. Two enzymes, mono ADP-ribosyl transferase and poly ADPribose
polymerase, function to transfer ADP-ribose from NAD to an acceptor proteins
including histone and histone proteins. These proteins seem to function in DNA
replication and repair and in cell differentiation.
The niacin deficiency disease is known as pellagra, whose symptons include pigmented
rash developed by sunlight exposure, changes in the digestive tract causing
vomiting, constipation or diarrhea, a bright red tongue, and neurological symptoms
including apathy, depression, fatigue, headache, and loss of memory. The symptoms
of pellagra are often referred to as the four D’s: dermatitis, dementia, diarrhea,
and death. Niacin deficiency is rare in industrialized countires except in malnourished
alcoholics and in individuals having disorders of tryptophan pathways.
In that trypophan can be converted to niacin, niacin contents in foods and dietary
recommendations are commonly expressed as mg of niacin equivalents (NE). Sixty
milligrams of dietary tryptophan is considered equivalent to 1 mg of niacin. Thus, 1 mg
NE is equal to 1 mg of niacin or 60 mg of dietary tryptophan. The recommendations for
niacin intake as RDAs for adults are 16 mg NE/d for men and 14 mg NE/d for women.
Niacin is widely distributed in both animal foods and plant-derived foods. The dietary
sources of niacin are yeasts, meats, poultry, fish, nuts, and enriched products such as
cereals and grains. The dietary sources of the amino acid tryptophan include lean meats,
fish, poultry, and nuts. In supplements and in food fortification, niacin is generally found
as nicotinamide, while nicotinic acid is often used as a cholesterol-lowering agent.
The pharmacological doses have been shown to significantly lower total serum
cholesterol and low-density lipoproteins and increase high-density lipoproteins.
Despite the therapeutic effect of nicotinic acid, side effects are associated with these
large doses. The side effects are flushing of the skin with a concomitant itching and
feeling of heat, liver cell damage (hepatotoxicity) including elevated liver enzymes
and jaundice, and gastrointestinal problems such as heartburn, nausea, and vomiting.
Because flushing is the first observed adverse effects after large doses of nicotinic
acid, as this symptom is observed at lower doses than other adverse effects, the
IOM selected flushing as the most appropriate endpoint on which to base a UL.
Nicotinamide is generally better tolerated than nicotinic acid, and does not generally
cause flushing. However, a UL for niacin is considered protective against potential
adverse effects of nicotinamide. The UL for niacin is 35 mg NE/d for adults, and
is limited to niacin that is obtained from supplements or fortified foods. There is no
evidence of adverse effects from naturally occurring niacin from foods.
Niacin functions in energy metabolism like other B vitamins; therefore, exercise
performance could be affected by niacin status. However, there is no evidence of
inadequate niacin status in athletes or physically active individuals. Large doses of
nicotinic acid have been reported to decrease mobilization of free fatty acids (FFAs)
during exercise, which could affect exercise performance because circulating
FFAs provide energy in the muscle during exercise. A decrease in FFA availability
with large doses of niacin as nicotinic acid does not impact physical performance
unless carbohydrate sources are limited. Although experimental data are lacking,
the IOM has recommended at least 10% increase in the niacin requirement to allow
for increased energy utilization and the physical size of individuals who exercise
vigorously.
