Niacin deficiency and toxicity

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. DermatitisDiarrhea
DeliriumDeath
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 inthe
skin, gastrointestinal tract and
nervous system.
•The dermatologic changes, which are
usually mostprominent (pellagra), are
most pronounced in the parts of the skin
that are exposedto sunlight: face, neck,
backs of the hands andforearms.
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 ofintake of the preformed
vitamin, but also that ofits 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. Clinicalmanifestation of niacin
deficiency includesevidence of
an unbalanced diet with respect
toboth 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 disordersof niacin
metabolism
III.

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

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

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

18. Schizophrenics
respond tohigh 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. •Patientswiththisrare familial disorder, which
involves malabsorption of tryptophan (and other
amino acids), also respond to treatment with NA.
•Itis characterized by hyperaminoaciduria,
pellagra-like skin rash (precipitated by
psychological stress, sunlight or fever), and
neurologicalchanges (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 toconvert tryptophan to niacin,
which appears to resultfrom reduced
enteric absorption and renal reabsorption
of monoaminomonocarboxylic acids
(including tryptophan).
In these patients, nonreabsorbed
tryptophan appears to be degraded by
microbial tryptophanaseto pyruvate and
indole, the latter of whichis 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 increasedriskof 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 tostimulate tooth eruption, to
increase gastric juiceflow and intestinal
motility.
•Skin flushing:High doses of NA can cause
skinflushing due to the release of
prostaglandin D2 inthe 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. •Antihyperlipidemiceffects:High doses
of NAhave been used in the treatment
of hypercholesterolemia andfor the
prevention of coronary disease.
•Results show reductions in all major
lipids and lipoproteins withincreases
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 plasmaconcentrations 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
Antihyperlipidemiceffects

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. •NAmenhances the effectof tryptophan in
supporting brain serotoninlevels.
•NAm, which reduces the urinaryexcretion of
tryptophan metabolites in patientstreated
with the amino acid, appears to blockthe
tryptophan-niacin pathway and increase the
availability of tryptophan for thesynthesis of
serotonin.
•The effect ofserotoninisantidepressive.
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 NAmhasbeen
reported to reduce
anxietyin some cases.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
32
Anxiety

33. •In clinical trials, NAmhas been foundto
protect high-risk children from developing
clinically apparent insulin-dependent
diabetes.
•These actions of NAmare thought to involve
support of pancreatic β-cell function through
themaintenance 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 beenreported
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 highNA doses include
cases of altered glucosetolerance and
hyperuricemia.
•A few casesof transient elevations in the plasma
activitiesof liver enzymes without associated
hepaticdysfunction have been reported.
•Chronicdoses 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 ofNAmhave not
been reported for doses used totreat
insulin-dependent diabetes (3 g/day).
•Largerdoses (10 g/day) have been
found to causehepatic 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, highintakes of NAm
may deplete methyl groupsdue to the
increased demand for methylationto excrete
the vitamin.
•Sucheffects would beexacerbated by low
intakes of methyl donors,methionine and
choline.
•This couldincrease 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