Nicotinic acid( CAS: 59-67-6)

Item	Index
Molecular   Formula	C6H5NO2
Molecular weight	123.11
Specification	CP/USP/EP
Appearance	White crystalline powder
Density	1.473
Melting point	236-239 °C(lit.)
Boiling point	260°C
Flash point	193°C
Solubility at 17 ºC	1-5 g/100   ml
Storage Condition	0-6°C

Niacin (also known as vitamin B3 and nicotinic acid) is an organic compound with the formula 

C6H5NO2 and, depending on the definition used, one of the 20 to 80 essential human nutrients.

Insufficient niacin in the diet can cause nausea, skin and mouth lesions, anemia, headaches, and

tiredness. Chronic Niacin deficiency leads to a disease called pellagra. The lack of niacin may also

be observed in pandemic deficiency disease which is caused by a lack of five crucial vitamins: niacin, 

vitamin C, thiamin, vitamin D and vitamin A, and is usually found in areas of widespread poverty and malnutrition.

Niacin has been used for over 50 years to increase levels of HDL in the blood and has been found to

decrease the risk of cardiovascular events modestly in a number of controlled human trials.

This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position.

Other forms of vitamin B3 include the corresponding amide, nicotinamide (“niacinamide”), where the carboxyl

group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of

esters. Nicotinic acid and niacinamide are convertible to each other with steady world demand rising from

8,500 tonnes per year in 1980s to 40,000 in recent years.

Niacin cannot be directly converted to nicotinamide, but both compounds are precursors of the coenzymes 

nicotinamide adenine dinucleotide (NAD) andnicotinamide adenine dinucleotide phosphate (NADP) in vivo.

NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. NADP and NAD

are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes. NAD is important

in catabolism of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP

mostly in anabolism reactions such as fatty acid and cholesterol synthesis. High energy requirements (brain)

or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency.

Insufficient niacin in the diet can cause nausea, skin and mouth lesions, anemia, headaches, and tiredness.

Chronic Niacin deficiency leads to a disease called pellagra. The lack of niacin may also be observed in

 pandemic deficiency disease which is caused by a lack of five crucial vitamins: niacin, vitamin C, thiamin,

 vitamin D and vitamin A, and is usually found in areas of widespread poverty and malnutrition.

Niacin has been used for over 50 years to increase levels of HDL in the blood and has been found to decrease

the risk of cardiovascular events modestly in a number of controlled human trials.

This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position.

Other forms of vitamin B3 include the corresponding amide, nicotinamide (“niacinamide”), where the carboxyl

group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of

esters. Nicotinic acid and niacinamide are convertible to each other with steady world demand rising from

8,500 tonnes per year in 1980s to 40,000 in recent years.

Niacin cannot be directly converted to nicotinamide, but both compounds are precursors of the coenzymes 

nicotinamide adenine dinucleotide (NAD) andnicotinamide adenine dinucleotide phosphate (NADP) in vivo.

NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. NADP and NAD

are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes. NAD is important

in catabolism of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP

mostly in anabolism reactions such as fatty acid and cholesterol synthesis. High energy requirements (brain)

or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency.

Therapeutic effects

In 1955, Altschul and colleagues described niacin as having a lipid lowering property for the first time. Niacin

is the oldest lipid lowering drug with unique anti atherosclerotic property. It reduces traditional parameters such

as low density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides

(TG), but effectively increases high density lipoprotein cholesterol (HDL).Despite the importance of other

cardiovascular risk factors, high HDL correlated to lower cardiovascular event independent of LDL reduction.Other

effects include anti-thrombotic and vascular inflammation, improving endothelial function, and plaque stability. Niacin

alone or in combination with other lipid lowering agents such as statin or ezetimibe significantly reduces risk of

cardiovascular disease and arthrosclerosis progression.

Niacin therapeutic effect is mostly through its binding to G protein coupled receptors, niacin receptor 1 (NIACR1) and

 niacin receptor 2 (NIACR2), that are highly expressed in adipose tissue, spleen, immune cells and keratinocytes but not

in other expected organs such as liver, kidney, heartor intestine. NIACR1 inhibits cyclic adenosine monophosphate

 (cAMP) production and thus fat breakdown in adipose tissue and free fatty acids available for liver to producetriglycerides

 and very-low-density lipoproteins (VLDL) and consequently low-density lipoprotein (LDL) or “bad” cholesterol.

Decrease in free fatty acids also suppress hepatic expression of apolipoprotein C3 (APOC3) and PPARg coactivator-1b

 (PGC-1b) thus increase VLDL turn over and reduce its production.It also inhibits diacylglycerol

acyltransferase-2(important hepatic TG synthesis).

The mechanism behind increasing HDL is not totally understood but it seems to be done in various ways. Niacin

increases apolipoprotein A1 levels due to anti catabolic effects resulting in higher reverse cholesterol transport.

It also inhibits HDL hepatic uptake, down-regulating production of the cholesterol ester transfer protein (CETP)

gene. Finally, it stimulatesABCA1 transporter in monocytes and macrophages and up-regulates peroxisome

proliferator-activated receptor γ results in reverse cholesterol transport.

Improving vascular endothelial function has been reported in few experiments using niacin. In an experiment on

type 2 diabetes, nicotinic acid improved endothelial function comparing with control. Daily dose of 1 g niacin

shows significant lipid modifying properties and reach the plateau using 2 grams. NIACR1 in immune cells such

as monocytes, macrophages, and dendritic cells is responsible for atherosclerosis effects of niacin by reducing the

immune cells’ infiltration of vessel wall It also down regulates endothelial adhesion molecules such as vascular cell

adhesion molecule 1 (VCAM-1) or of chemokines such as monocyte chemotactic protein 1 (MCP-1) and inflammatory

proteins which results in atherosclerotic stabilization and antithrombotic effects. The changes in adhesion molecules and

chemokines might be through activation of receptor NIACR1 on immune cells.

Adipokines are the adipocytes’ produced mediators. Some adipokines such as tumor necrosis factor (TNF)-a, interleukins

and chemokines, have pro-inflammatory effect and some others such as adiponectin have anti-inflammatory effect that

regulates inflammatory process, decrease vascular progression and atherosclerosis. Nicotinic acid increase adiponectin

plasma levels in humans and mice but inhibits pro-inflammatory chemokines such as MCP-1 and fractalkin. Other

recently explored therapeutic effect of nicotinic acid are neuroprotective and anti-inflammatory effects, beneficial in

animal models of arthritis, chronic renal failure, or sepsis; however, more work is needed in this area.

Following Coronary Drug Project (CDP), one of the first experiments done to study long term clinical lipid-lowering

effect of niacin in the 1960s to early 1970’s, many other experiments have been done. Their results, summarized in

two meta-analyses, concluded that therapeutic doses of niacin alone or in combination with other lipid-modifying agents

such asstatin reduce cardiovascular events and atherosclerosis progression significantly. This agrees with the current

National Cholesterol Education Program (NCEP) on high cholesterol treatment. NCEP recommends niacin alone for

cardiovascular and atherogenic dyslipidemia in mild or normal LDL levels or in combination for higher LDL levels

(NCEP, 2002). 1500 mg Immediate release niacin daily results in 13% LDL, 20% LP, 10% TG reduction and 19%

HDL increase comparing to placebo. Extended release niacin alone or with anti-flushing agent (laropiprant) shows similar effects.