Role of Vitamin B3 ( Niacin in human body)

 

 Vitamin B3(Niacin) 

History: 

•  The term Niacin(Vitamin B3) is considered as Generic term for nicotinic acid and nicotinamide( niacinamide).
•   Vitamin B3 was discovered through Pellagra in humans. 
• Vitamin B3 also known as Pellagra preventing factor.
•   The vitamin was once called the anti-black tongue factor because of its effects on dogs.
•   Pellagra was especially prevalent in the Southern United States where Corn(which contains a relatively unavailable form of niacin) was a main dietary staple in the early1900s.
•   In 1937 Elvehjem isolated the vitamin, which was shown then to cure both pellagra and black tongue.

Structure of VitaminB3: 

•  Structurally, Nicotinic acid is pyridine 3-Carboxylic acid, whereas nicotinamide is Nicotinic Acid amide.
•   Molecular formula of Niacin is C6H5NO2.

Sources: 

•  The best sources of niacin include Fish such as tuna and Halibut, and meat such as beef, and chicken. Enriched cereals, bread products, peanut butter, fruits, whole grains, fortified cereals, seeds, and legumes. 
•  Appreciable amount of Niacin in Coffee and Tea. 
•  Lesser amounts of Green vegetables and milk.
•   In Supplements, Niacin is generally found as Nicotinamide(niacinamide). 
• In animals, niacin occurs mainly as NAD(nicotinamide adenine dinucleotide) NADP(nicotinamide adenine dinucleotide phosphate).

Digestion, Absorption, Transport, and Storage. 

 Digestion of NAD and NADPH is needed to enable the absorption of niacin. A pyrophosphatase is required for the phosphate hydrolysis of NADP. The NAD is then hydrolyzed by glycohydrolase and releases free nicotinamide.

Absorption:

•  Nicotinamide and nicotinic acid can be absorbed in the stomach but they are readily absorbed in the small intestine. 
•  In the small intestine: If niacin concentration is low, it is absorbed by sodium-dependent, carrier-mediated diffusion.
•   At high concentrations niacin is absorbed by passive diffusion in the intestine. 
•  In the plasma, niacin is primarily found as nicotinamide with little nicotinic acid. Transport: 
•  From the blood, Nicotinamide and nicotinic acid move across cell membranes by simple diffusion.
•  Then nicotinic acid transport into kidney tubules and red blood cells requires a carrier, and uptake into the brain is energy dependent. 
•  Nicotinic acid may also be used to synthesize NAD, but this reaction occurs primarily in the liver. Phosphorylation of NAD by NAD kinase using ATP generates NADPH. These reactions may be reversed. In the liver, excess niacin and tryptophan are converted to NAD. It may be degraded to yield nicotinamide which is then available for transport to other tissues.

Storage: It is not stored in significant amounts in tissues. In tissues, it gets converted into coenzymes.

Excretion:

The little amount of nicotinic acid or nicotinamide is excreted, because both compounds may be absorbed from the glomerular filtrate. 

RDA (Recommended Dietary Allowance)

  14mg/day for women. 

 16mg/day for men. 

 17mg/day for lactation 

 18mg/day for pregnancy.

Deficiency:

Pellagra (pelle means skin, and agra means rough in Italian). It is a serious deficiency of niacin. 

 Pellagra can easily be remembered as the 4 Ds- dermatitis, dementia, diarrhea,  and death. 

•  Dermatitis is similar to Sunburn in areas exposed to the sun, such as the face, neck, hands, wrists, elbows, knees, and feet.
• Neurological manifestation includes Headache, loss of memory, dementia, peripheral neuritis, and paralysis of extremities. 
•  Gastrointestinal manifestation includes: Glossitis(redness and swelling of tongue), cheilosis(swelling of lips), stomatitis(inflamed and sore mouth), vomiting and diarrhea. 
• If untreated death occurs.

Treatment:

Treatment requires about 500 mg of nicotinamide daily for several weeks.

 Toxicity:

 Large doses of nicotinic acid (up to 6g/day) are used to treat Hypercholesterolemia. These pharmacological doses lower the cholesterol triglycerides, and LDL and increase HDLs.

These dose of vitamin has some undesirable side effects, especially a dose of 1g or more per day.

  Vasodilatory effects include uncomfortable flushing, redness, burning, itching, and headache. 

 GIT Problems such as heartburn, nausea and possibly vomiting.

  Liver injury (hepatic toxicity) elevated hepatic enzymes, jaundice, hepatitis, and liver failure.

  Hyperuricemia (raising serum uric acid level) 

 Elevation of plasma glucose concentration (i.e. glucose intolerance).