VITAMIN B3: NIACIN

For every drug that benefits a patient, there is a natural substance that can achieve the same
effect. —CARL C. PFEIFFER, M.D., PH.D.

Niacin, or nicotinic acid, is a substituted pyridine derivative. It is not strictly a vitamin since it
can be synthesized in the body from the essential amino acid tryptophan. The biologically active
coenzyme forms are nicotinamide adenine dinucleotide (NAD+) and its phosphorylated
derivative, nicotinamide adenine dinucleotide phosphate (NADP+). Nicotinamide, a derivative of
nicotinic acid that contains an amide instead of a carboxyl group, also occurs in the diet.
Nicotinamide is readily deaminated in the body and, therefore, is nutritionally equivalent to
nicotinic acid. NAD+ and NADP+ serve as coenzymes in oxidation-reduction reactions in which
the coenzyme undergoes reduction of the pyridine ring by accepting a hydride ion (hydrogen
atom plus one electron. The reduced forms of NAD+ and NADP+ are NADH and NADPH,
respectively.

A. Pellagra (Vit. B3 Deficiency) and Schizophrenia (Vit. B3 Deficiency)

After Dr. Joseph Goldberger discovered the cause of pellagra, a deficiency disease, and
Dr. Conrad Elvehjem in Wisconsin discovered that niacin and niacinamide were the anti-
pellagra vitamins, pellagra was vanquished. The timely mandatory fortification of white flour in
1942 by the United States government during the Second World War saved humanity
incalculable numbers of lives and disability and trillions of dollars in costs. This brilliant decision
may have even influenced the outcome of the war.
The major difference is that pellagra is caused by total malnutrition generated by a diet
high in corn and non-nutritious food, while in schizophrenia, the major deficiency is vitamin B3 in
most cases where starvation is not endemic. The skin lesions in pellagra are responsive to
tryptophan. Like pellagrins, schizophrenic patients exposed to the sun suffered skin pigment
changes. The pellagrologists in the 1930s and 1940s were very good observers. How could
they miss this obvious similarity between schizophrenia and pellagra? They did not miss it. But
they were so indoctrinated by the vitamins-as-prevention paradigm that they were blinded by
theory rather than guided by what they observed. They knew pellagra was a deficiency disease
and that only small amounts were needed to cure and to prevent further relapses in most cases.
They knew schizophrenia was a major intractable chronic mental disease. Because they were
blinded by the old vitamin paradigm, they insisted the two were different conditions. When niacin
became available, they gave it to both pellagrins and schizophrenic patients. According to their
definition, they were pellagrins if they responded in a short period of time, even if it took 1,000
mg daily. They remained schizophrenic if they did not respond at these doses. The
pellagrinologists were unable to make the differential diagnosis on clinical grounds alone. And
because these experts were so certain the diseases were not the same, investigators thereafter
would no longer examine the issue.

B. Distribution of niacin
Niacin is found in unrefined and enriched grains and cereal, milk, and lean meats,
especially liver. [Note: Corn is low in both niacin and tryptophan. Corn-based diets can cause
pellagra]. Some 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content
of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 × mg tryptophan.
Since most of the niacin in cereals is biologically unavailable, this is discounted.

C. NAD Is the Source of ADP-Ribose

In addition to its coenzyme role, NAD is the source of ADP-ribose for the ADP
ribosylation of proteins and polyADP-ribosylation of nucleoproteins involved in the DNA repair
mechanism. Cyclic ADP-ribose and nicotinic acid adenine dinucleotide, formed from NAD, act
to increase intracellular calcium in response to neurotransmitters and hormones.

D. Clinical indications for niacin

1. Deficiency of niacin: A deficiency of niacin causes pellagra, a disease involving the

skin, gastrointestinal tract, and CNS. Pellagra is characterized by a photosensitive
dermatitis. As the condition progresses, there is dementia and possibly diarrhea.
Untreated pellagra is fatal. Although the nutritional etiology of pellagra is well
established, and either tryptophan or niacin prevents or cures the disease, additional
factors, including deficiency of riboflavin or vitamin B6, both of which are required for
synthesis of nicotinamide from tryptophan, may be important. In most outbreaks of
pellagra, twice as many women as men are affected, is probably the result of inhibition
of tryptophan metabolism by estrogen metabolites.

2. Treatment of hyperlipidemia: Niacin (at doses of 1.5 g/day or 100 times the
Recommended Dietary Allowance or RDA) strongly inhibits lipolysis in adipose tissue
the primary producer of circulating free fatty acids. The liver normally uses these
circulating fatty acids as a major precursor for triacylglycerol synthesis.
Thus, niacin causes a decrease in liver triacylglycerol synthesis, which is required for
very-low-density lipoprotein (VLDL) production. Low-density lipoprotein (LDL, the
cholesterolrich lipoprotein) is derived from VLDL in the plasma. Thus, both plasma tri
acylglycerol (in VLDL) and cholesterol (in VLDL and LDL) are lowered. Therefore, niacin
is particularly useful in the treatment of Type IIb hyperlipoproteinemia, in which both
VLDL and LDL are elevated. [Note: Niacin raises HDL levels.]

E. Pellagra Can Occur as a Result of Disease Despite an Adequate Intake of Tryptophan

& Niacin
A number of genetic diseases that result in defects of tryptophan metabolism are
associated with the development of pellagra, despite an apparently adequate intake of both
tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of
the membrane transport mechanism for tryptophan, resulting in large losses as a result of
intestinal malabsorption and failure of renal reabsorption. In carcinoid syndrome, there is
metastasis of a primary liver tumor of enterochromaffin cells, which synthesize 5-
hydroxytryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of
the body’s tryptophan metabolism, causing pellagra because of the diversion away from NAD
synthesis.
E. Niacin Is Toxic in Excess
Nicotinic acid has been used to treat hyperlipidemia when of the order of 1-6 g/d are
required, causing dilatation of blood vessels and flushing, along with skin irritation. Intakes of
both nicotinic acid and nicotinamide in excess of 500 mg/d also cause liver damage.
SOURCES:
1. NIACIN The Real Story
2. Lippincott’s
3. Harper’s