Vitamin B3
Niacin
History
• The term niacin (vitamin B3) is considered a generic
term for nicotinic acid and nicotinamide (also called
niacinamide).
• The vitamin was once called the anti–black tongue
factor because of its effect in 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 early 1900s.
• In 1937 Elvehjem isolated the vitamin, which was
shown then to cure both pellagra and black tongue.
Niacin (nicotinamide) Vitamin B3
• The vitamin activity of niacin is provided by
both nicotinic acid and nicotinamide.
• Structurally, nicotinic acid is pyridine 3carboxylic acid, whereas nicotinamide is
nicotinic acid amide.
Sources
• The best sources of niacin include: fish such as
tuna and halibut, and meats such as beef,
chicken, turkey, among others. Enriched cereals
and bread products, whole grains, fortified
cereals, seeds, and legumes.
• Contain appreciable amounts of niacin in coffee
and tea.
• lesser amounts in green vegetables and milk.
• In supplements, niacin is generally found as
nicotinamide (niacinamide).
Sources
• In animals, niacin occurs mainly as nicotinamide
adenine dinucleotide (NAD) and nicotinamide
adenine dinucleotide phosphate (NADP).
• But, after slighting of animals, NAD and NADP are
thought to undergo hydrolysis; thus, meats
provide niacin as free nicotinamide.
• In their oxidized forms, NAD and NADP possess a
positive charge and therefore may alternatively
be written NAD+ and NADP+.
Sources
DIGESTION, ABSORPTION, TRANSPORT,
AND STORAGE
• NAD and NADP may be hydrolyzed within the intestinal
tract or enterocyte by glycohydrolase to release free
nicotinamide.
Glycohydrolase
• NAD & NADP
Nicotinamide
• Nicotinamide and nicotinic acid can be absorbed in the
stomach, but they are more readily absorbed in the small
intestine
DIGESTION, ABSORPTION, TRANSPORT,
AND STORAGE
• In the small intestine, if niacin concentrations is low, its
absorbed by sodium-dependent, carrier-mediated
(facilitated) diffusion.
• At high concentrations (as with 3–4 g pharmacological
doses), niacin is absorbed almost completely by passive
diffusion.
• In the plasma, niacin is found primarily as nicotinamide,
with little nicotinic acid. Up to ~1/3 of plasma nicotinic acid
is bound to proteins.
• Nicotinamide and nicotinic acid move across cell
membranes by simple diffusion.
• Then, nicotinic acid transport into the kidney tubules and
red blood cells requires a carrier.
DIGESTION, ABSORPTION, TRANSPORT,
AND STORAGE
• Nicotinamide is primary precursor of NAD in
all tissues.
• Nicotinic acid may be used to synthesize NAD
in the liver which influenced by various
hormones.
• Vitamin is trapped within the cell as NAD or
NADP.
• Intracellular concentrations of NAD typically
predominate over those of NADP.
DIGESTION, ABSORPTION, TRANSPORT,
AND STORAGE
• In the liver, excess niacin and tryptophan are
converted to NAD and stored in small
amounts not bound to enzymes.
• NAD may be degraded to yield nicotinamide,
which then is available for transport to other
tissues.
• NAD is found primarily in its oxidized form
(NAD+), whereas NADP is found in cells mainly
in its reduced form (NADPH).
FUNCTIONS AND MECHANISMS OF ACTION
• Approximately 200 enzymes, primarily
dehydrogenases, require the coenzymes NAD
and NADP, which act as a hydrogen donor or
electron acceptor.
• Niacin functions as a substrate in nonredox
roles as a donor of adenosine diphosphate
ribose (ADP-ribose).
FUNCTIONS AND MECHANISMS OF ACTION
Coenzymes
• NAD and NADP are very similar and undergo
reversible reduction in the same way, their
functions in the cell are quite different.
• The major role of NADH is to transfer its electrons
from metabolic intermediates through the
electron transport chain thereby producing
adenosine triphosphate (ATP).
• NADPH: acts as a reducing agent in many
biosynthetic pathways such as (fatty acid,
cholesterol, and steroid hormone synthesis).
FUNCTIONS AND MECHANISMS OF ACTION
Coenzymes
• NAD and NADP are tightly bound to their
apoenzymes and can easily transport
hydrogen atoms from one part of the cell to
another.
• These reactions occur in the mitochondria and
in the cytoplasm.
FUNCTIONS AND MECHANISMS OF ACTION
Coenzymes
• Oxidative reactions in which NAD participates and is
reduced to NADH include:
• Glycolysis
• oxidative decarboxylation of pyruvate
• oxidation of acetyl CoA in the TCA cycle
• β-oxidation of fatty acids
• oxidation of ethanol
• NAD is required for catabolism of vitamin B6 as
pyridoxal to its excretory product, pyridoxic acid.
FUNCTIONS AND MECHANISMS OF ACTION
Coenzymes
• NADPH is generated from NADP by reduction which occurs as part of
the hexose monophosphate shunt by the mitochondrial.
• The NADPH producedin is used in some reductive biosynthesis:
• fatty acid synthesis
• cholesterol and steroid hormone synthesis
• oxidation of glutamate
• synthesis of deoxyribonucleotides (precursors of DNA)
• regeneration of glutathione, vitamin C, and thioredoxin
• conversion of folate to active forms, dihydrofolate (DHF) and
tetrahydrofolate (THF) and synthesis of 5-methyl THF and 5,10methylene THF.
METABOLISM AND EXCRETION
• NAD, generated from nicotinamide or produced
in the liver from tryptophan, and NADP can be
degraded by glycohydrolase into nicotinamide
and ADP-ribose.
• The released nicotinamide is methylated and is
then oxidized in the liver into a variety of
products that are excreted in the urine.
• Typically, little nicotinic acid or nicotinamide is
excreted, because both compounds may be
actively reabsorbed from glomerular filtrate.
METABOLISM AND EXCRETION
• The primary metabolites of nicotinamide are:
• N' methyl nicotinamide (~20% to 30% of niacin
metabolites).
• N' methyl 2-pyridone 5-carboxamide (~40% to
60%).
• N' methyl 4-pyridone carboxamide (4-pyridone)
in small amounts.
• Nicotinic acid is metabolized mainly to N‘
methylnicotinic acid.
RDA’s
• Recommendations for niacin intake include calculations of
niacin derived from the amino acid tryptophan (about 60
mg of tryptophan thought to generate 1 mg of niacin).
• Total niacin thus is provided to the body as nicotinic acid
and nicotinamide and from 1/60 mg of tryptophan.
• The term niacin equivalent (NE) is used to account for the
provision by tryptophan.
• Assuming that:
• 1 g of high- quality protein in diet = 10 mg of tryptophan.
• Intake 60 g complete protein = 600mg tryptophan.
• 60mg tryptophan /1mg of NE
• 60g protein = 10 NEs
RDA’s
•
•
•
•
•
The RDA’s for niacin (as niacin equivalents)
14 mg/day for women
16 mg/day for men
18 mg/day for pregnancy
17 mg/day for lactation
DEFICIENCY: PELLAGRA
• Pellagra is a serious deficiency of niacin.
• Pellagra can easily remembered as the four Ds—
dermatitis, dementia, diarrhea, and death—are often
used as a mnemonic device for remembering.
• The dermatitis sunburn in face and neck then in hands,
wrists, elbows, knees, and feet.
• Neurological: headache, loss of memory, peripheral
neuritis and dementia or delirium.
• Gastrointestinal: glossitis, stomatitis, nausea, vomiting,
and diarrhea or constipation.
• If untreated, death occurs.
Pellagra
TOXICITY
• Large doses of nicotinic acid (up to 6 g/day in divided
doses) are used to treat hypercholesterolemia (high
blood cholesterol).
• These pharmacological doses:
• significantly lower total serum cholesterol,
triglycerides, and low-density lipoproteins (LDLs) and
increase high-density lipoproteins (HDLs).
• Inhibits lipolysis in adipose tissue and decreases
hepatic VLDL secretion from the liver and LDL
production.
• Diminish triglyceride synthesis and increases HDL in
liver.
TOXICITY
• These dose of vitamin has some undesirable side effects,
especially in doses of 1 g or more per day.
• Vasodilatory effects: including uncomfortable flushing and
redness alongnwith burning, itching (pruritus), tingling, and
headaches
• gastrointestinal 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 levels).
• Elevation of plasma glucose concentrations (i.e., glucose
• intolerance).