Vitamin A defi ciency and toxicity

7.11.1 Defi ciency
Animals
The fi rst sign of vitamin A defi ciency is loss of appetite.
In young animals, the decreased food intake results in lack of growth. Controlled experiments
using laboratory animals have shown that loss of appetite
is not due to poor palatability of the vitamin Adefi
cient diet, nor is it due to impaired taste function
(Anzano et al., 1979). Metabolic disturbances caused
by vitamin A defi ciency may be suffi ciently detrimental
to the animal that it reduces its food intake in order
to minimize these disturbances; however, the neurophysiological
control systems are unknown.
When rats are deprived of vitamin A, mucus-secreting
epithelia such as found in the trachea, certain
parts of the urinogenital tract and the conjunctiva
are replaced by a keratin-producing squamous epithelium
that is not secretory. This results in a drying
-up (xerosis) of the mucous membranes with loss
of function and a greater susceptibility to infection.
Goblet cells in the intestinal crypts are also reduced in
number. Reproductive changes in the male rat include
shrinkage of the testes and atrophy of the accessory
sex organs. The effects on the seminiferous tubules
include degeneration of the germinal epithelium, decrease
in tubule size and a halting of spermatogenesis.
These histological and reproductive changes can be
prevented or corrected by restoring vitamin A to the
animal’s diet. Female rats deprived of vitamin A fail
to maintain pregnancy and may resorb their fetuses.
This is more likely to be a direct effect on the fetus
than a reduction in placental transport of nutrients
(Anon, 1977).
In adult cattle, a mild defi ciency of vitamin A is associated
with roughened hair and scaly skin. Prolonged
defi ciency affects the cornea, which becomes dry, soft
and cloudy. Bulls continue to produce viable spermatozoa
even when blindness through xerophthalmia has
developed. Continued vitamin A deprivation leads to
degeneration of the seminiferous tubules, with a consequent
reduction in semen volume and sperm count,
and an increased production of abnormal spermatozoa.
The lack of protective mucus in the alimentary and
respiratory tracts of cattle leads to scours and pneumonia,
resulting often in death. In pigs, compression of the
brain, due to improper modelling of bone, gives rise to
nervous disorders such as uncoordinated movements
and convulsions. Vitamin A-defi cient poultry suffer a
high mortality rate. Early signs of defi ciency include
retarded growth, weakness, ruffl ed plumage and a staggering
gait (ataxia). The keratinization of intestinal epithelia
leads to parasitic infestations and the impaired
production of antibodies reduces the bird’s resistance
to infections such as coccidiosis. In mature birds suffering
from severe vitamin A defi ciency, egg production
and hatchability are reduced.
Humans
The clinical effects of vitamin A defi ciency in adults
are usually seen only in people whose diet has been defi
cient for a long time in both dairy produce and vegetables.
An early sign of vitamin A defi ciency is night
blindness, which is caused by an insuffi cient amount
of visual purple in the retina. In more advanced defi
ciency, the epithelial cells of the skin and mucous
membranes lining the respiratory, gastrointestinal
and urinogenital tracts cease to differentiate, and
lose their secretory function. The undifferentiated
cells are fl attened and multiply at an increased rate, so
that the cells pile up on one another and the surface
becomes keratinized. This condition promotes dry
skin and loss of hair sheen. The lack of protective
mucus in the affected mucosae leads to an increased
susceptibility to infections. Xerophthalmia, a disease
which mainly affects very young children, refers to
keratinization of the conjunctiva, which later spreads
to the cornea causing ulceration. The ultimate condition
is keratomalacia which, if not treated, leads to
permanent blindness.
7.11.2 Toxicity
An excessive intake of preformed vitamin A produces
symptoms of toxicity, either acute or chronic. In either
case, toxicity results from the indiscriminate use
of pharmaceutical supplements, and not from the
consumption of usual diets. The only naturally occurring
products that contain suffi cient vitamin A to
induce toxicity in humans are the livers of animals at
the top of long food chains, such as large marine fi sh
and carnivores (e.g. bear and dog).
Acute toxicity results from the ingestion of a single
or several closely spaced very large doses of vitamin
A, usually more than 100 times the recommended intake.
Such doses produce a variety of toxic signs that
include vomiting, severe headache, dizziness, blurred
vision, muscular incoordination and malaise. These
signs are usually transient and disappear within a few
days. In acute hypervitaminosis A, the excess retinol
circulating in the bloodstream is not subject to the
normal regulation of RBP binding, and the unbound
retinol disrupts the integrity of the cell membranes.
180 Vitamins: their role in the human body
Chronic toxicity results from the recurrent ingestion
over a period of weeks to years of excessive doses
of vitamin A that are usually more than 10 times the
recommended intake. Toxic signs commonly include
headache, bone and joint pain, hair loss, nose bleed,
bleeding lips, and cracking and peeling skin. After
terminating dosing, most patients recover fully from
toxicity. Prolonged dosing may eventually result in
cirrhosis of the liver.
The most serious consequences of an excessive
intake of vitamin A are its teratogenicity. Fetal resorption,
abortion, and malformed fetuses or infants are
the most serious teratogenic effects. The acidic retinoids,
both synthetic and natural, are more powerful
teratogens than are retinol and its esters.
Carotenoids in foods are not known to be toxic,
even when ingested in large amounts. Hypercarotenosis,
a benign condition characterized by a jaundice-
like yellowing of the skin, can result when large
amounts of carotene-rich foods (e.g. carrot juice) are
ingested regularly.