Vitamin A toxicity

Domina Petric, MD
Vitamin A toxicity

Introduction
• The hepatic storage of vitamin A tends to mitigate
against the development of intoxication due to
intakes in excess of physiological needs.
• Persistent large overdoses (more than 1000 times
the nutritionally required amount) can exceed the
capacity of the liver to store and catabolize and will
thus produce intoxication.
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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Four aspects of vitamin A metabolism tend
to protect against hypervitaminosis:
Relatively inefficient conversion of the provitamins A in the gut.
The unidirectional oxidation of the vitamin to a form (retinoic
acid) that is rapidly catabolized and excreted.
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Four aspects of vitamin A metabolism tend
to protect against hypervitaminosis:
The relative excess capacity of CRBP(II) to
bind retinol.
Accelerated vitamin A catabolism.
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Hypervitaminosis A
• Hypervitaminosis A requires high exposures.
• It is manifested after single large doses:
>660,000 IU for adults, >330,000 IU for
children, or after doses exceeding 100,000
IU/day have been taken for several months.
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Children experiencing hypervitaminosis A
develop transient (one to two days) signs:
• Nausea
• Vomiting
• Signs due to increased cerebrospinal fluid
pressure: headache, vertigo, blurred or
double vision
• Muscular incoordination
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Chronic hypervitaminosis A
Occurs with recurrent exposures exceeding
12,500 IU in infants to 33,000 IU in adults.
It is manifested mainly as changes in the
skin and mucous membranes.
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Chronic hypervitaminosis A
• Dry lips (cheilitis) is a common early sign, often followed
by dryness and fragility of the nasal mucosa, leading to dry
eyes and conjunctivitis.
• Skin lesions include dryness, pruritis, erythema, scaling,
peeling of the palms and soles, hair loss (alopecia)
and nail fragility.
• Headache, nausea and vomiting (signs of increased
intracranial pressure) have also been reported.
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Cheilitis
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Vitamin A and bones
Hypervitaminosis A
can affect bone and
may increase risk for
bone fracture.
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Signs of hypervitaminosis A
General: muscle and
joint pain, headache.
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Skin: erythema,
desquamation, alopecia.
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Mucous membranes:
cheilitis, stomatitis,
conjunctivitis.
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Sceletal: thinning and
fracture of long bones.
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Embryotoxic potential of high levels
of vitamin A
•Retinoids can be toxic to maternally
exposed embryos.
• 13-cis-retinoic acid is very effective in the treatment
of acne, but can cause severe disruption of cephalic
neural crest cell activity: birth defects characterized
by craniofacial, central nervous system,
cardiovascular and thymus malformations.
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of vitamin A
The critical period for fetal exposure
to maternally derived retinoids is the
time when organogenesis is occurring:
before many women suspect they are
pregnant.
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of vitamin A
•Fetal malformations of cranial–
neural crest origin have been
reported in cases of oral use of all
trans-retinoic acid in treating acne
vulgaris and of regular prenatal
vitamin A supplements.
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Carotenoid toxicity
β-carotene intakes of as much as
30 mg/day are without side effects other
than the accumulation of the carotenoid
in the skin, with consequent yellowing of
the skin (carotenodermia).
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• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
Literature
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Vitamin A toxicity

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