1. Niacin deficiency and toxicity
Domina Petric, MD

2. Niacin deficiency I.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

3. Death Diarrhea Delirium Dermatitis General signs
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

4. Deficiency signs
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

5. Wikipedia.org
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

6. Deficiency signs In some patients, lesions resemble early sunburn.
Medfitbiological.com
In some patients, lesions resemble early sunburn.
In chronic cases the symmetric lesions feature cracking, desquamation, hyperkeratosis and hyperpigmentation.
Medicalpictures.info
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

7. Deficiency signs angular stomatitis cheilosis glossitis
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)
Sciencesource.com
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

8. Deficiency signs 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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

9. Determinants of niacin status
II.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

10. Determinants of niacin status
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11. Determinants of niacin status
Clinical manifestation of niacin deficiency includes evidence of an unbalanced diet with respect to both niacin and tryptophan, and, frequently, pyridoxine (vitamin B6).
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

12. Determinants of niacin status
Excess intake of the branched-chain amino acid leucine may antagonize niacin synthesis and/or utilization and thus may also be a precipitating factor in the etiology of pellagra.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

13. Determinants of niacin status
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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

15. Hereditary disorders of niacin metabolism
Two hereditary disorders involve impaired niacin function:
schizophrenia
Hartnup disease
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

16. Schizophrenia
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

17. Schizophrenia
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

18. Schizophrenia
Schizophrenics respond to high oral doses (1 g/day) of nicotinic acid (NA).
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

19. Hartnup disease
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).
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

20. Hartnup disease
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

21. Health benefits of niacin
IV.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

22. Skin injury
Niacin deficiency produces photosensitivity of the skin, a sign common in pellagra.
This may relate to the function of niacin as a vasodilator in the skin.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

23. Oxidant lung injury
Hyperoxia has been shown to induce poly(ADP-ribose) synthesis in the lung.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

24. Cancer risk
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

25. Pharmacologic uses of nicotinic acid (NA)V.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

26. Effects of high NA doses
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

27. Effects of high NA doses
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

28. Antihyperlipidemic effects
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)
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

29. Pharmacologic uses of nicotinamid (NAm)
VI.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

30. Nicotinamide does not show the antihyperlipidemic effects of NA!
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

31. Clinical depression
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

32. Anxiety
A high dose (1 g/day) of NAm has been reported to reduce anxiety in some cases.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

33. Diabetes
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

34. Niacin toxicity
VII.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

35. Nicotinic acid
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).
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

36. Nicotinic acid 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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

37. Nicotinamide
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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

38. Nicotinamide 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.
November 14, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

39. Literature
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc
November 14, 2018