Vitamin B3

(Niacin)

Synonyms: Food: Main functions:

Pellagra-Preventive factor (PP), nicotinic mg/100g • Coenzymes - Nicotinamide adenine
acid, nicotinamide. Veal og dinucleotide (NAD) and Nicotinamide
adenine dinucleotide phosphate
Liver 15
(NADP) - in redox reactions
Chemistry: Chicken 11
• NAD is a substrate for non-redox
Nicotinic acid (pyridine-3-carboxylic Beef 7.5 reactions
acid), nicotinamide (pyridine-3 Salmon 7.5
carboxamide). Almonds 4.2
Peas 2.4
Potatoes 1.2
Peaches 0.9
Molecular formula of nicotinic acid Tomatoes 0.5
Milk (whole) 0.1
(Souci, Fachmann, Kraut)

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Vitamin B3 (Niacin)
Within the human body, vitamin B3 helps to release energy from the foods
we eat, produce fatty acids and cholesterol, repair DNA and contribute to the
stress response. Commonly known as niacin or nicotinic acid, sufficient
levels of the water-soluble vitamin are typically met by eating a varied and
balanced diet.

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Functions Measurement
The coenzymes NAD and NADP are required for around 200 Determination of the urinary excretion of two niacin metabolites,
biological reduction-oxidation (redox) reactions. NAD is mainly N-methyl-nicotinamide and N-methyl-2-pyridone-5-
involved in reactions that generate energy in tissues through carboxamide, has been used to assess niacin status. Excretion
the biochemical degradation of carbohydrates, fats and of 5.8 ± 3.6 mg N-methyl-nicotinamide/24hrs and 20.0 ± 12.9
proteins. NAD is also required as a substrate for non-redox mg N-methyl-2-pyridone-5-carboxamide/24hrs are considered
reactions. It is the source of adenosine diphosphate (ADP)- normal. A ratio of the two metabolites is also used for status
ribose, which is transferred to proteins by different enzymes. assessment. An adequate niacin status is considered when the
These enzymes and their products seem to be involved in DNA ratio of N-methyl-2-pyridone-5-carboxamide to N-methyl-
replication, DNA repair, cell differentiation and cellular signal nicotinamide is between 1.3 and 4.0. Recent studies suggest
transduction. NADP is important for the reductive biosynthesis that the measurement of NAD and NADP concentrations and
of fatty acids and cholesterol. their ratio in red blood cells may be sensitive and reliable
indicators for the determination of niacin status. A ratio of
Dietary sources erythrocyte NAD to NADP <1.0 may identify subjects at risk of
developing niacin deficiency. Plasma tryptophan concentration
Nicotinamide and nicotinic acid occur widely in nature.
is also used for assessment of niacin status.
Nicotinic acid is more prevalent in plants, whereas in animals,
nicotinamide predominates. Most of the niacin obtained from
food comes from yeast, liver, poultry, lean meats, nuts and
Stability
legumes. Milk and green leafy vegetables contribute lesser Both nicotinamide and nicotinic acid are stable when exposed
amounts. Specific food processing techniques, such as the to heat, light, air and alkali. Little loss occurs during the cooking
treatment of corn with lime water involved in the traditional and storage of foods.
preparation of tortillas, increase the bioavailability of nicotinic
acid in these products. Tryptophan contributes as much as two
thirds of the niacin activity required by adults in typical diets.
Important food sources of tryptophan are meat, milk and eggs.
Physiological interactions
Absorption and body stores • Copper deficiency can inhibit the conversion of
tryptophan to niacin. The drug penicillamine has
Both the acid and amide forms of niacin are readily absorbed
been demonstrated to inhibit the tryptophan-to-
from the stomach and the small intestine. At low concentrations,
niacin pathway in humans. The pathway from
the two forms are absorbed by a sodium-dependent facilitated
tryptophan to niacin is sensitive to a variety of
diffusion and, at higher concentrations by passive diffusion.
nutritional alterations; inadequate iron, riboflavin,
Niacin is present in the diet mainly as NAD and NADP, and
or vitamin B6 status reduces the synthesis.
nicotinamide is released from the coenzyme forms by enzymes
in the intestine. The main storage organ, the liver, may contain • Long-term treatment of tuberculosis with isoniazid
a significant amount of the vitamin, which is stored as NAD. may cause niacin deficiency, because isoniazid is a
The niacin coenzymes NAD and NADP are synthesized in all niacin antagonist. Other drugs that interact with
tissues from nicotinic acid or nicotinamide. niacin metabolism may also lead to niacin deficiency,
e.g. tranquillizers (diazepam) and anticonvulsants
(phenytoin, phenobarbital).
Deficiency Reducing disease risk: therapeutic use
Symptoms of a marginal niacin deficiency include: insomnia, Niacin is specific in the treatment of glossitis, dermatitis and
loss of appetite, weight and strength loss, soreness of the the mental symptoms seen in pellagra. High doses of nicotinic
tongue and mouth, indigestion, abdominal pain, burning acid (1.5 - 4 g/day) can reduce total and low-density
sensations in various parts of the body, vertigo, headaches, lipoprotein cholesterol and triacylglycerols and increase
numbness, nervousness, poor concentration, apprehension, high-density lipoprotein cholesterol in patients at risk of
confusion and forgetfulness. cardiovascular disease (CVD).
Severe niacin deficiency leads to pellagra, a disease characterized There is a flush reaction to high doses of nicotinic acid, which
by dermatitis, diarrhea and dementia. A pigmented rash is seen primarily with a rising blood level and may wear off
develops symmetrically on the skin in areas exposed to once a plateau level has been reached. Nicotinic acid has also
sunlight. Symptoms affecting the digestive system include been used in doses of 100 mg as a vasodilator. Type 1 diabetes
a bright red tongue, stomatitis, vomiting, and diarrhea. mellitus results from the autoimmune destruction of
Headaches, fatigue, depression, apathy and loss of memory insulin-secreting β-cells in the pancreas. There is evidence
are neurological symptoms of pellagra. If left untreated, that nicotinamide may delay or prevent the development of
pellagra is fatal. Since the synthesis of NAD from tryptophan diabetes. Clinical trials are in progress to investigate this effect
requires an adequate supply of riboflavin and vitamin B6, of nicotinamide.
insufficiencies of these vitamins may also contribute to
Recent studies suggest that human immunodeficiency virus
niacin deficiency.
(HIV) increases the risk of niacin deficiency. Higher intakes of
Pellagra is rarely seen in industrialized countries, except for its niacin were associated with decreased progression rate to
occurrence in people with chronic alcoholism. In other parts of AIDS in an observational study of HIV-positive men.
the world where maize and jowar (barley) are the major
NAD is consumed as a substrate in ADP-ribose transfer
staples, pellagra persists. It also occurs in India and parts of
reactions to proteins which play a role in DNA repair. This has
China and Africa.
created interest in the relationship between niacin and cancer.
Patients with Hartnup disease, a genetic disorder, develop A large case-control study found increased consumption
pellagra because their absorption of tryptophan is defective. of niacin, along with antioxidant nutrients, to be associated
with decreased incidence of cancers of the mouth, throat
Carcinoid syndrome may also result in pellagra as NAD
and esophagus.
synthesis is restricted.

Groups at risk
• Patients with Hartnup disease
• Patients with carcinoid syndrome
• Alcoholics
• Those with long-term intake of certain drugs
Recommended Daily Intake (RDI) Safety
The actual daily requirement of niacin depends on the quantity There is no evidence that niacin from foods causes adverse
of tryptophan in the diet and the efficiency of the tryptophan effects. Pharmacological doses of nicotinic acid exceeding 300
to niacin conversion. The conversion factor is 60 mg of mg per day have been associated with a variety of side effects
tryptophan to 1 mg of niacin, which is referred to as 1 niacin including nausea, diarrhea and transient flushing of the skin.
equivalent (NE). This conversion factor is used for calculating Doses exceeding 2.5 g per day have been associated with
both dietary contributions from tryptophan and recommended hepatotoxicity, glucose intolerance, hyperglycemia, elevated
allowances of niacin. In the US, the RDI for adults is 16 mg NEs blood uric acid levels, heartburn, nausea and headaches.
for men and 14 mg NEs for women. RDI is estimated as 6.6 mg Severe jaundice may occur, even with doses as low as 750 mg
NE per 1,000 kcal. per day, and may eventually lead to irreversible liver damage.
Doses of 1.5 to 5 g/day of nicotinic acid have been associated
Recommended daily intakes (RDI) *
with blurred vision and other eye problems. Tablets with a
buffer and time release capsules are available to reduce
flushing and gastrointestinal irritation in individuals that are
Group Life stage Dose/day** sensitive to nicotinic acid.
Infants <6 months 2 mg (AI) These should be used with caution, however, because a high
Infants 7 – 12 months 4 mg (AI) intake of time-release niacin tablets has been linked to liver
Children 1 – 3 years 6 mg damage. The Food and Nutrition Board (1998) set the UL for
Children 4 – 8 years 8 mg niacin (nicotinic acid plus nicotinamide) at 35 mg/day. The EU
Scientific Committee on Food (2002) developed different ULs
Children 9 – 13 years 12 mg
for nicotinic acid and nicotinamide: the upper level (UL) for
Males >14 years 16 mg nicotinic acid has been set at 10 mg/day, for nicotinamide
Females >14 years 14 mg at 900 mg/day.
Pregnancy 14 – 50 years 18 mg
Supplements and food fortification
Breastfeeding 14 – 50 years 17 mg
Single supplements of nicotinic acid are available in tablets,
capsules and syrups. Multivitamin and B-complex vitamin
infusions, tablets and capsules also contain nicotinamide.
* Institute of Medicine (2001).
** As NE. 1 mg niacin = 60 mg of tryptophan;
Niacin is used to fortify grain, including corn and bran
0 - 6 months = preformed niacin (not NE). breakfast cereals and wheat flour.

If not otherwise specified, this table presents RDIs. Allowable levels of nutrients Production
vary depending on national regulations and the final application
Although other routes are known, most nicotinic acid is
produced by oxidation of 5-ethyl-2-methylpyridine.
Nicotinamide is produced via 3-methylpyridine. This
compound is derived from two carbon sources, acetaldehyde
and formaldehyde, or from acrolein plus ammonia.
3-methylpyridine is first oxidized to 3-cyanopyridine which, in
a second stage, converts to nicotinamide by hydrolysis.
History
The disease pellagra is Spies cures
first described by human pellagra using
1755 Thiery who calls the 1937 nicotinamide.
disease ‘mal de la rosa’.

Krehl discovers that

the essential amino
Huber provides acid tryptophan is 1945
the first description transformed into niacin
of nicotinic acid. 1867 by mammalian tissues.

The concept of niacin

Weidel describes the equivalents is proposed
elemental analysis and
1955 by Horwitt.
1873 crystalline structure of
the salts and other
derivatives of nicotinic
acid in some detail.
Altschul and colleagues
report that high doses
of nicotinic acid reduce 1955
serum cholesterol
in humans.
First preparation of
nicotinamide by Engler.
1894
Turner and Hughes
demonstrate that the
Funk isolates nicotinic 1961 main absorbed form of
acid from yeast. niacin is the amide.
1913

Shepperd and colleagues

Goldberger demonstrates report that high doses of
that pellagra is a dietary nicotinic acid lower 1978
deficiency disease. 1915 both serum cholesterol
and triglycerides.

Goldberger and Wheeler Bredehorst and

use the experimental colleagues show that
1928 model of black tongue 1980 niacin status affects
disease in dogs for the the extent of ADP-
human disease pellagra. ribosylation of proteins.

Elvehjem and team

show the effectiveness
of nicotinic acid and 1937
nicotinamide in curing
canine black tongue.