Niacin deficiency and toxicity, pharmacologic uses of niacin

1. Niacin deficiency and toxicity
Domina Petric, MD

2. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
2
Niacin deficiency
I.

3. Dermatitis Diarrhea
Delirium Death
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
3
General signs

4. • Niacin deficiency results in changes in the
skin, gastrointestinal tract and
nervous system.
• The dermatologic changes, which are
usually most prominent (pellagra), are
most pronounced in the parts of the skin
that are exposed to sunlight: face, neck,
backs of the hands and forearms.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
4
Deficiency signs

5. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
5

6. In some patients, lesions
resemble early sunburn.
In chronic cases the symmetric
lesions feature cracking,
desquamation, hyperkeratosis
and hyperpigmentation.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
6
Deficiency signs
Medfitbiological.com
Medicalpictures.info

7. Lesions of the gastrointestinal tract include:
• angular stomatitis
• cheilosis
• glossitis
• alterations of the buccal mucosa, tongue,
esophagus, stomach (resulting in
achlorhydria) and intestine (resulting in
diarrhea)
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
7
Deficiency signs
Sciencesource.com

8. Pellagra almost always involves anemia.
Early neurological symptoms associated with
pellagra include anxiety, depression and fatigue.
Later symptoms include depression, apathy,
headache, dizziness, irritability and tremors.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
8
Deficiency signs

9. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
9
Determinants of niacin status
II.

10. • Because a substantial amount of
niacin can be synthesized from
tryptophan, nutritional status with
respect to niacin involves not only
the level of intake of the preformed
vitamin, but also that of its potential
amino acid precursor.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
10
Determinants of niacin status

11. Clinical manifestation of niacin
deficiency includes evidence of
an unbalanced diet with respect
to both niacin and tryptophan,
and, frequently, pyridoxine
(vitamin B6).
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
11
Determinants of niacin status

12. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
12
Determinants of niacin status

13. • Zinc plays some role in the pyridoxine-
dependent metabolic interconversion of
tryptophan to niacin.
• Pellagra patients have been found to have
low-plasma zinc levels.
• Zinc supplementation increases their
urinary excretion of 1-methylnicotinamide
and 1-methyl-2-pyridone-5-carboxamide.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
13
Determinants of niacin status

14. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
14
Hereditary disorders of niacin
metabolism
III.

15. Two hereditary disorders
involve impaired niacin
function:
• schizophrenia
• Hartnup disease
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
15
Hereditary disorders of niacin
metabolism

16. • Schizophrenia appears to be an NAD-
deficiency disease involving a failure to
provide sufficient amounts of that pyridine
nucleotide to critical areas of the brain.
• Affected individuals apparently oxidize
nicotinamid (NAm) more readily than do
healthy people, as they excrete greater
amounts of 1-methyl-6-pyridone-3-
carboxamide than do healthy controls.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
16
Schizophrenia

17. • The excretion of this methylated product is
increased by treatment with methylated
hallucinogens (methylated indoles) and is
decreased by treatment with tranquilizers.
• The high endogenous production of methylated
hallucinogenic substances in schizophrenics
results in a depletion of NAm (via its
methylation and excretion), resulting in a
substrate limitation of NAD+ synthesis.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
17
Schizophrenia

18. Schizophrenics
respond to high oral
doses (1 g/day) of
nicotinic acid (NA).
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
18
Schizophrenia

19. • Patients with this rare familial disorder, which
involves malabsorption of tryptophan (and other
amino acids), also respond to treatment with NA.
• It is characterized by hyperaminoaciduria,
pellagra-like skin rash (precipitated by
psychological stress, sunlight or fever), and
neurological changes (attacks of ataxia and
psychiatric disorders ranging from emotional
instability to delirium).
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
19
Hartnup disease

20. Patients appear to have abnormally low
capacities to convert tryptophan to niacin,
which appears to result from reduced
enteric absorption and renal reabsorption
of monoamino monocarboxylic acids
(including tryptophan).
In these patients, nonreabsorbed
tryptophan appears to be degraded by
microbial tryptophanase to pyruvate and
indole, the latter of which is reabsorbed
from the intestine and is neurotoxic.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
20
Hartnup disease

21. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
21
Health benefits of niacin
IV.

22. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
22
Skin injury

23. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
23
Oxidant lung injury

24. • Epidemiological studies have
associated marginal niacin intake
with increased risk of esophageal
cancer, although no associations of
cancer risk and niacin status have
been reported.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
24
Cancer risk

25. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
25
Pharmacologic uses of nicotinic acid (NA)
V.

26. • Vasodilation: NA has been used as an
agent to stimulate tooth eruption, to
increase gastric juice flow and intestinal
motility.
• Skin flushing: High doses of NA can cause
skin flushing due to the release of
prostaglandin D2 in the skin followed by
the release of its metabolites.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
26
Effects of high NA doses

27. • Antihyperlipidemic effects: High doses
of NA have been used in the treatment
of hypercholesterolemia and for the
prevention of coronary disease.
• Results show reductions in all major
lipids and lipoproteins with increases
in HDL-cholesterol.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
27
Effects of high NA doses

28. Inhibition of lipolysis in adipose tissue
Reduced synthesis of very low-density lipoproteins
(VLDLs)
Reduced plasma cholesterol levels
Lowering the plasma concentrations of low-density
lipoproteins (LDLs) and VLDLs
Increasing plasma high-density lipoproteins (HDLs)
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
28
Antihyperlipidemic effects

29. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
29
Pharmacologic uses of nicotinamid (NAm)
VI.

30. Nicotinamide does not
show the
antihyperlipidemic
effects of NA!
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
30
Nicotinamide

31. • NAm enhances the effect of tryptophan in
supporting brain serotonin levels.
• NAm, which reduces the urinary excretion of
tryptophan metabolites in patients treated
with the amino acid, appears to block the
tryptophan-niacin pathway and increase the
availability of tryptophan for the synthesis of
serotonin.
• The effect of serotonin is antidepressive.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
31
Clinical depression

32. A high dose (1 g/day)
of NAm has been
reported to reduce
anxiety in some cases.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
32
Anxiety

33. • In clinical trials, NAm has been found to
protect high-risk children from developing
clinically apparent insulin-dependent
diabetes.
• These actions of NAm are thought to involve
support of pancreatic β-cell function through
the maintenance of both NAD+ and DNA-
protective enzyme poly(ADP-ribose)
polymerase activity.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
33
Diabetes

34. April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
34
Niacin toxicity
VII.

35. Short-term effects
High doses of NA have been reported
to cause skin flushing, itching
urticaria (hives) and gastrointestinal
discomfort (heartburn, nausea,
vomiting, rarely diarrhea).
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
35
Nicotinic acid

36. Chronic effects
• The longer term effects of high NA doses include
cases of altered glucose tolerance and
hyperuricemia.
• A few cases of transient elevations in the plasma
activities of liver enzymes without associated
hepatic dysfunction have been reported.
• Chronic doses of NA have been reported to cause
hepatic damage.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
36
Nicotinic acid

37. Short-term effects
• Acute adverse effects of NAm have not
been reported for doses used to treat
insulin-dependent diabetes (3 g/day).
• Larger doses (10 g/day) have been
found to cause hepatic damage.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
37
Nicotinamide

38. Chronic effects
• It is possible that chronic, high intakes of NAm
may deplete methyl groups due to the
increased demand for methylation to excrete
the vitamin.
• Such effects would be exacerbated by low
intakes of methyl donors, methionine and
choline.
• This could increase the risk of carcinogenesis.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
38
Nicotinamide

39. • Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
Literature
April 16, 2018 39