Pyridoxine deficiency and toxicity

Pyridoxine deficiency and toxicity, pharmacologic uses of pyridoxine

1. Pyridoxine deficiency and
toxicity
Domina Petric, MD

2. Pyridoxine deficiency
I.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2

3. Pyridoxine deficiency
Vitamin B6-deficient patientsexhibit symptoms
that can be quickly corrected by administration of
the vitamin:
•weakness
•sleeplessness
•nervous disorders (peripheral neuropathies)
•cheilosis, glossitis, stomatitis
•impaired cell-mediated immunity
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

4. Pyridoxine deficiency signs
Organ system/functionsSigns
Appetite Decreased
Growth Decreased
Dermatologic Acrodynia, cheilosis, stomatitis, glossitis
Muscular Weakness
Teeth Dental caries
Vital organs Hepatic steatosis
Vessels Arteriosclerosis
Erythrocytes Anemia
Reproductive Infertility, decreased fertility
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

5. Pyridoxine deficiency
Because plasma concentrations of
pyridoxal phosphate decrease
with age, it isexpected that
elderly people may be at greater
risk ofvitamin B6 deficiency than
younger people.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. Pyridoxine deficiency
Infants consuming less than 100 mg of
vitamin B6per day are at risk of
developing seizures, which arethought
to result from insufficient activities of
thepyridoxal phosphate-dependent
enzyme glutamatecarboxylase
required for the synthesis of GABA.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. Homocysteinuria
Hereditary deficiency of the cystathionine
β-synthaseoccurs at a rate of 3/1,000,000.
The resulting impairment in homocysteine
catabolism is manifestedas elevations in plasma
levels of homocysteine, methionineand cysteine.
Signs aredislocation of the optic lens,
osteoporosis and abnormalities of long bone
growth, mental retardation, thromboembolism.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. Homocysteinuria
The conditionis treated
with a low-methionine diet.
Half of casesrespond to
high doses of pyridoxine:
250-500 mg/day
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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9. Ectopia lentis
http://disorders.eyes.arizona.edu
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. Pyridoxine-responsive seizures
This is a rare, autosomal recessive disorder
involving impaired synthesis of the inhibitory
neurotransmitter, γ-aminobutyric acid (GABA).
Defectinvolves mutations in
pyridoxine/pyridoxamineoxidase.
The disorder is manifestedas intractable
seizures appearing within hours after birth.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

11. Pyridoxine-responsive seizures
•Patients show normal circulating levels of
pyridoxalphosphate, but their seizures stop
immediately uponadministration of high levels
(100-500 mg) of pyridoxine intravenously and
are controlled using dailyoral doses of
pyridoxine (0.2-3 mg/kg body weight).
•If untreated, progressive cerebral
atrophy ensues.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

12. Hyperoxaluria
Type 1 primary hyperoxaluriahas been found to
bedue to a mutant hepatic alanine glyoxylate
transferasewith abnormally low pyridoxal
phosphate-bindingcapacity.
In such cases high doses of vitamin B6
(400 mg/day) reduce hyperoxaluriaand
thus the risk offormation of oxalate
stones and renal injury.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

13. Pharmacologic uses of pyridoxine
II.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
13

14. Sideroblastic anemia
Dosages as great as 200 mg/day
(usually as pyridoxine HCl) have
been found effective in
stimulating hematopoesis
(δ-aminolevulinic acid synthase) in
sideroblastic anemia patients.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
14

15. Sickle cell anemia
•A small study found patientsto have
lower plasma pyridoxal phosphate levels
than controls, which responded to oral
supplementation (100 mg/day) of
pyridoxine within twomonths.
•Both pyridoxine and pyridoxal phosphate have
been found to protect sickle cells invitro.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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16. Iron storage disease
Complexes of pyridoxal,which
chelate iron (the isonicotinyland
benzoyl hydrazones), are effective
in stimulating the excretion of that
mineral in patients withiron
storage disease.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
16

17. Suppression of lactation
A few studies havereported vitamin
B6 as effective in suppressing
lactation, probably through the
stimulation ofdopaminergic activity
in the hypothalamus andthus the
suppression of prolactin.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
17

18. April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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Adverse drug effects

19. Hydrazines
•The antituberculin drug isonicotinic acid hydrazide
(isoniazid) produces a peripheral neuropathy
similar to that of vitamin B6 deficiency.
•It inhibits pyridoxal phosphate-dependent
glutamate-decarboxylase and γ-aminobutyrate
aminotransferase which produce and degrade
GABA in the nerve tissue.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
19

20. Antibiotics
•Two antibiotics have been foundto
antagonize vitamin B6 by reacting
withpyridoxal phosphate to form
inactive products.
•Cycloserinereacts with the coenzyme
to produce an oxime.
•Penicillamineproducesthiazolidine.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
20

21. L-DOPA
L-3,4-dihydroxyphenylalanine
antagonizes vitamin B6 by
reacting with pyridoxal
phosphate to form
tetrahydroquinolines.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
21

22. Ethanol
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
22

23. Oral contraceptives
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
23

24. April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
24

25. Schizophrenia
Vitamin B6 is recommended
(0.1-1 g/day alone or in combination
withtryptophan or magnesium) for
the treatment ofschizophrenia.
Vitamin B6 may be useful for
thereduction ofseizures in
alcoholics.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
25

26. Asthma
•Low circulating pyridoxal phosphatelevels
have been reported in patients withasthma.
•One small study found vitamin B6treatment
(100 mg/day) to reduce the severityand
frequency of attacks.
•These effects may besecondary to those of
theophylline, which inhibits pyridoxal
kinase.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
26

27. Herpes
Pyridoxine has been
used to treat herpes
gestationisat doses of
400-4000 mg/day.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
27

28. Carpal tunnel syndrome
•The syndrome, involving pain and paresthesia
of the hand, is caused byirritation and
compression of the medial nerve bythe
transverse ligaments of the wrist in ways that
are exacerbated by redundant motions.
•The condition has been associated with low
circulatinglevels of pyridoxal phosphate and
low erythrocyte glutamic-oxaloacetic
transaminase activities.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
28

29. Carpal tunnel syndrome
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
29
Highdoses of pyridoxine might
be effective as treatment:
50-300 mg/day for 12 weeks.

30. Chinese restaurant syndrome
•The syndrome,which involves
headache, sensation of heat,altered
heart beat, nausea, and tightness of
theneck induced by oral intake of
monosodiumglutamate, has been
reported to respond tovitamin B6
(50 mg/day).
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
30

31. Premenstrualsyndrome
•Occursin an estimated 40% of women 2-3
daysbefore their menstrual flow.
•It involves tensionof the breasts, pain in
the lumbar region, thirst,headache,
nervous irritability, pelvic congestion,
peripheral edema, and, usually, nausea
and vomiting.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
31

32. Premenstrualsyndrome
•Premenstrual syndrome has been
reported torespond to vitamin B6,
presumably by affectinglevels of the
neurotransmitters, serotoninand
γ-aminobutyric acid, which control
depression,pain perception and anxiety.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
32

33. Morning sickness
A randomized clinical trialshowed
that the use of pyridoxine (25 mg
everyeight hours for three days)
significantly reducedvomiting and
nausea in pregnant women.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
33

34. Pyridoxine toxicity
III.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
34

35. Pyridoxine toxicity
•The toxicity of vitamin B6 appears to
be relativelylow.
•Highdoses of the vitamin (several
grams per day) have been shown to
induce sensoryneuropathy marked
by changes in gait and peripheral
sensation.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
35

36. Pyridoxine toxicity
•In doses of 10-25 mg, vitamin B6 increases the
conversion of L-dopato dopamine, whichis
unable to cross the blood-brain barrier.
•The vitamincan therefore interfere withL-dopa
in the managementof Parkinson’s disease.
•It should not be administeredto individuals
taking L-dopawithout the concomitant
administration of a decarboxylase inhibitor.
April 18, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
36

37. Literature
•Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
April 18, 2018 37