Pyridoxine deficiency and toxicity

Pyridoxine deficiency and
toxicity
Domina Petric, MD

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

Vitamin B6-deficient patients exhibit 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
3

Pyridoxine deficiency signs
Organ system/functions Signs
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
4

Because plasma concentrations of
pyridoxal phosphate decrease
with age, it is expected that
elderly people may be at greater
risk of vitamin B6 deficiency than
younger people.
April 18, 2018
5

Infants consuming less than 100 mg of
vitamin B6 per day are at risk of
developing seizures, which are thought
to result from insufficient activities of
the pyridoxal phosphate-dependent
enzyme glutamate carboxylase
required for the synthesis of GABA.
April 18, 2018
6

Homocysteinuria
Hereditary deficiency of the cystathionine
β-synthase occurs at a rate of 3/1,000,000.
The resulting impairment in homocysteine
catabolism is manifested as elevations in plasma
levels of homocysteine, methionine and cysteine.
Signs are dislocation of the optic lens,
osteoporosis and abnormalities of long bone
growth, mental retardation, thromboembolism.
April 18, 2018
7

Homocysteinuria
The condition is treated
with a low-methionine diet.
Half of cases respond to
high doses of pyridoxine:
250-500 mg/day
April 18, 2018
8

Ectopia lentis
http://disorders.eyes.arizona.edu
April 18, 2018
9

Pyridoxine-responsive seizures
This is a rare, autosomal recessive disorder
involving impaired synthesis of the inhibitory
neurotransmitter, γ-aminobutyric acid (GABA).
Defect involves mutations in
pyridoxine/pyridoxamine oxidase.
The disorder is manifested as intractable
seizures appearing within hours after birth.
April 18, 2018
10

Pyridoxine-responsive seizures
• Patients show normal circulating levels of
pyridoxal phosphate, but their seizures stop
immediately upon administration of high levels
(100-500 mg) of pyridoxine intravenously and
are controlled using daily oral doses of
pyridoxine (0.2-3 mg/kg body weight).
• If untreated, progressive cerebral
atrophy ensues.
April 18, 2018
11

Hyperoxaluria
Type 1 primary hyperoxaluria has been found to
be due to a mutant hepatic alanine glyoxylate
transferase with abnormally low pyridoxal
phosphate-binding capacity.
In such cases high doses of vitamin B6
(400 mg/day) reduce hyperoxaluria and
thus the risk of formation of oxalate
stones and renal injury.
April 18, 2018
12

Pharmacologic uses of pyridoxine
II.
April 18, 2018
13

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
14

Sickle cell anemia
• A small study found patients to have
lower plasma pyridoxal phosphate levels
than controls, which responded to oral
supplementation (100 mg/day) of
pyridoxine within two months.
• Both pyridoxine and pyridoxal phosphate have
been found to protect sickle cells in vitro.
April 18, 2018
15

Iron storage disease
Complexes of pyridoxal, which
chelate iron (the isonicotinyl and
benzoyl hydrazones), are effective
in stimulating the excretion of that
mineral in patients with iron
storage disease.
April 18, 2018
16

Suppression of lactation
A few studies have reported vitamin
B6 as effective in suppressing
lactation, probably through the
stimulation of dopaminergic activity
in the hypothalamus and thus the
suppression of prolactin.
April 18, 2018
17

April 18, 2018
18
Adverse drug effects

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
19

Antibiotics
• Two antibiotics have been found to
antagonize vitamin B6 by reacting
with pyridoxal phosphate to form
inactive products.
• Cycloserine reacts with the coenzyme
to produce an oxime.
• Penicillamine produces thiazolidine.
April 18, 2018
20

L-DOPA
L-3,4-dihydroxyphenylalanine
antagonizes vitamin B6 by
reacting with pyridoxal
phosphate to form
tetrahydroquinolines.
April 18, 2018
21

Ethanol
April 18, 2018
22

Oral contraceptives
April 18, 2018
23

April 18, 2018
24

Schizophrenia
Vitamin B6 is recommended
(0.1-1 g/day alone or in combination
with tryptophan or magnesium) for
the treatment of schizophrenia.
Vitamin B6 may be useful for
the reduction of seizures in
alcoholics.
April 18, 2018
25

Asthma
• Low circulating pyridoxal phosphate levels
have been reported in patients with asthma.
• One small study found vitamin B6 treatment
(100 mg/day) to reduce the severity and
frequency of attacks.
• These effects may be secondary to those of
theophylline, which inhibits pyridoxal
kinase.
April 18, 2018
26

Herpes
Pyridoxine has been
used to treat herpes
gestationis at doses of
400-4000 mg/day.
April 18, 2018
27

Carpal tunnel syndrome
• The syndrome, involving pain and paresthesia
of the hand, is caused by irritation and
compression of the medial nerve by the
transverse ligaments of the wrist in ways that
are exacerbated by redundant motions.
• The condition has been associated with low
circulating levels of pyridoxal phosphate and
low erythrocyte glutamic-oxaloacetic
transaminase activities.
April 18, 2018
28

Carpal tunnel syndrome
April 18, 2018
29
High doses of pyridoxine might
be effective as treatment:
50-300 mg/day for 12 weeks.

Chinese restaurant syndrome
• The syndrome, which involves
headache, sensation of heat, altered
heart beat, nausea, and tightness of
the neck induced by oral intake of
monosodium glutamate, has been
reported to respond to vitamin B6
(50 mg/day).
April 18, 2018
30

Premenstrual syndrome
• Occurs in an estimated 40% of women 2-3
days before their menstrual flow.
• It involves tension of the breasts, pain in
the lumbar region, thirst, headache,
nervous irritability, pelvic congestion,
peripheral edema, and, usually, nausea
and vomiting.
April 18, 2018
31

Premenstrual syndrome
• Premenstrual syndrome has been
reported to respond to vitamin B6,
presumably by affecting levels of the
neurotransmitters, serotonin and
γ-aminobutyric acid, which control
depression, pain perception and anxiety.
April 18, 2018
32

Morning sickness
A randomized clinical trial showed
that the use of pyridoxine (25 mg
every eight hours for three days)
significantly reduced vomiting and
nausea in pregnant women.
April 18, 2018
33

Pyridoxine toxicity
III.
April 18, 2018
34

Pyridoxine toxicity
• The toxicity of vitamin B6 appears to
be relatively low.
• High doses of the vitamin (several
grams per day) have been shown to
induce sensory neuropathy marked
by changes in gait and peripheral
sensation.
April 18, 2018
35

Pyridoxine toxicity
• In doses of 10-25 mg, vitamin B6 increases the
conversion of L-dopa to dopamine, which is
unable to cross the blood-brain barrier.
• The vitamin can therefore interfere with L-dopa
in the management of Parkinson’s disease.
• It should not be administered to individuals
taking L-dopa without the concomitant
administration of a decarboxylase inhibitor.
April 18, 2018
36

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

Pyridoxine deficiency and toxicity

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