Nicotinamide (NAM), also known as niacinamide, is a form of vitamin B3 found in food and used

as a dietary supplement and medication.[3][4][5] As a supplement, it is used by mouth to

prevent and treat pellagra (niacin deficiency).[4] While nicotinic acid (niacin) may be used for
this purpose, nicotinamide has the benefit of not causing skin flushing.[4] As a cream, it is used
to treat acne.[5]

Side effects are minimal.[6][7] At high doses liver problems may occur.[6] Normal amounts are
safe for use during pregnancy.[1] Nicotinamide is in the vitamin B family of medications,
specifically the vitamin B3 complex.[8][9] It is an amide of nicotinic acid.[6] Foods that contain
nicotinamide include yeast, meat, milk, and green vegetables.[10]

Nicotinamide was discovered between 1935 and 1937.[11][12] It is on the World Health
Organization's List of Essential Medicines, the most effective and safe medicines needed in a
health system.[13] Nicotinamide is available as a generic medication and over the counter.[8] In
the United Kingdom a 60 g tube costs the NHS about £7.10.[5] Commercially, nicotinamide is
made from either nicotinic acid or nicotinonitrile.[12][14] In a number of countries grains have
nicotinamide added to them.[12]

Contents

1 Medical uses

1.1 Niacin deficiency

1.2 Acne

1.3 Skin cancer

2 Side effects

3 Chemistry

3.1 Industrial production

3.2 Biochemistry

3.3 Biological role

4 Food sources
5 Compendial status

6 Research

7 See also

8 References

9 External links

Medical uses

Niacin deficiency

Nicotinamide is the preferred treatment for pellagra, caused by niacin deficiency.[4] While niacin
may be used, nicotinamide has the benefit of not causing skin flushing.[4]

Acne

Nicotinamide cream is used as a treatment for acne.[5] It has anti-inflammatory actions, which
may benefit people with inflammatory skin conditions.[15]

Nicotinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and

improves the epidermal permeability barrier in vivo.[16] The application of 2% topical
nicotinamide for 2 and 4 weeks has been found to be effective in lowering the sebum excretion
rate.[17] Nicotinamide has been shown to prevent Cutibacterium acnes-induced activation of
toll-like receptor 2, which ultimately results in the down-regulation of pro-inflammatory
interleukin-8 production.[18]

Skin cancer

Nicotinamide decreases the risk of skin cancers, other than melanoma, in those at high risk.[19]

Side effects

Nicotinamide has minimal side effects.[6][7] At high doses liver problems may occur.[6] Normal
doses are safe during pregnancy.[1]

Chemistry
The structure of nicotinamide consists of a pyridine ring to which a primary amide group is
attached in the meta position. It is an amide of nicotinic acid.[6] As an aromatic compound, it
undergoes electrophilic substitution reactions and transformations of its two functional groups.
Examples of these reactions reported in Organic Syntheses include the preparation of 2-
chloronicotinonitrile by a two-step process via the N-oxide,[20][21]

Nicotinamide to 2-chloronicotinonitrile.png

from nicotinonitrile by reaction with phosphorus pentoxide,[22] and from 3-aminopyridine by

reaction with a solution of sodium hypobromite, prepared in situ from bromine and sodium
hydroxide.[23]

NAD+, the oxidised form of NADH, contains the nicotinamide moiety (circled in red)

Industrial production

The hydrolysis of nicotinonitrile is catalysed by the enzyme nitrile hydratase from Rhodococcus
rhodochrous J1,[24][25][14] producing 3500 tons per annum of nicotinamide for use in animal
feed.[26] The enzyme allows for a more selective synthesis as further hydrolysis of the amide to
nicotinic acid is avoided.[27][28] Nicotinamide can also be made from nicotinic acid. According
to Ullmann's Encyclopedia of Industrial Chemistry, worldwide 31,000 tons of nicotinamide were
sold in 2014.[12]

Biochemistry

The active Nicotinamide group on the molecule NAD+ undergoes oxidation in many metabolic
pathways.

Nicotinamide, as a part of the coenzyme nicotinamide adenine dinucleotide (NADH / NAD+) is

crucial to life. In cells, nicotinamide is incorporated into NAD+ and nicotinamide adenine
dinucleotide phosphate (NADP+). NAD+ and NADP+ are coenzymes in a wide variety of
enzymatic oxidation-reduction reactions, most notably glycolysis, the citric acid cycle, and the
electron transport chain.[29] If humans ingest nicotinamide, it will likely undergo a series of
reactions that transform it into NAD, which can then undergo a transformation to form NADP+.
This method of creation of NAD+ is called a salvage pathway. However, the human body can
produce NAD+ from the amino acid tryptophan and niacin without our ingestion of
nicotinamide.[30]

NAD+ acts as an electron carrier that helps with the interconversion of energy between nutrients
and the cell's energy currency, adenosine triphosphate (ATP). In oxidation-reduction reactions,
the active part of the coenzyme is the nicotinamide. In NAD+, the nitrogen in the aromatic
nicotinamide ring is covalently bonded to adenine dinucleotide. The formal charge on the
nitrogen is stabilized by the shared electrons of the other carbon atoms in the aromatic ring.
When a hydride atom is added onto NAD+ to form NADH, the molecule loses its aromaticity, and
therefore a good amount of stability. This higher energy product later releases its energy with
the release of a hydride, and in the case of the electron transport chain, it assists in forming
adenosine triphosphate.[31]

When one mole of NADH is oxidized, 158.2 kJ of energy will be released.[31]

Biological role

Nicotinamide occurs as a component of a variety of biological systems, including within the

vitamin B family and specifically the vitamin B3 complex.[8][9] It is also a critically important part
of the structures of NADH and NAD+, where the N-substituted aromatic ring in the oxidised
NAD+ form undergoes reduction with hydride attack to form NADH.[29] The NADPH/NADP+
structures have the same ring, and are involved in similar biochemical reactions.

Food sources

Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a
lesser extent in some vegetables.[32] It is commonly added to cereals and other foods. Many
multivitamins contain 20–30 mg of vitamin B3 and it is also available in higher doses.[33]

Compendial status

British Pharmacopoeia[34]

Japanese Pharmacopoeia[35]

Research

A 2015 trial found nicotinamide to reduce the rate of new nonmelanoma skin cancers and actinic
keratoses in a group of people at high risk for the conditions.[36]

Nicotinamide has been investigated for many additional disorders, including treatment of
bullous pemphigoid nonmelanoma skin cancers.[37]

Niacinamide may be beneficial in treating psoriasis.[38]

There is tentative evidence for a potential role of nicotinamide in treating acne, rosacea,
autoimmune blistering disorders, ageing skin, and atopic dermatitis.[37] Niacinamide also
inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand
breaks induced by radiation or chemotherapy.[39] ARCON (accelerated radiotherapy plus
carbogen inhalation and nicotinamide) has been studied in cancer.[40]