An unsaturated alcohol, is supplied in the diet as the preformed vitamin, which is found only in animal tissues (especially liver, egg yolk, butter and cream), and as the pro-vitamin, carotene, which is present in green and yellow vegetables and in fruits. Carotene is converted to vitamin A ester presumably in the intestinal wall. The availability of carotene in food varies widely, a factor which must be considered in estimating the potential vitamin A value of the diet. Since vitamin A is fat-soluble, absorption is facilitated by the simultaneous absorption of fat and deficiency may be en-countered when absorption of fat is decreased. The latter occurs when bile is absent from the intestinal tract, in infectious hepatitis, and in steatorrheas, i. e., sprue, celiac disease, pancreatic fibrosis and idiopathic steatorrhea. Administration of liquid petroleum with meals interferes with absorption of carotene and, to a lesser extent, of vitamin A. Vitamin A deficiency may be encountered in diabetes mellitus and hypothyroidism in which diseases conversion of carotene to vitamin A seems to be impaired. Since the liver is the chief site of storage of vitamin A, deficiency may be associated with chronic liver disease, particularly advanced cirrhosis.
The minimum daily requirement of vitamin A is 20 I.U. or 6 ,ug. per kilogram of body weight, if supplied by the preformed vitamin, and three to five times as much if furnished by dietary carotene. Quantities above mini-mum are needed to provide for significant storage and, in animals, for normal reproduction. The recommended allowance of the Food and Nutrition Board for vitamin A is 5000 I.U. daily for an adult receiving a mixed diet which supplies two-thirds of the vitamin as carotene. In using the dietary record for evaluating vitamin A nutrition, it should be remembered that large amounts of the vitamin may have been stored in the liver and that many months may be required for depletion of these reserves.
The two important metabolic functions of vitamin A in man are the maintenance of normal epithelium and the formation of the retinal pigment, rhodopsin, of which vitamin A is an integral part. Rhodopsin is necessary for vision in dim light. When the dark adapted retina is exposed to light, rhodopsin is changed to retinine, which is vitamin A aldehyde, plus a protein. Vita-min A is needed for regeneration of rhodopsin since a certain amount is lost in the process of breakdown.
In certain animal species, vitamin A has been shown to influence bone growth. Also, in animals, deficiency of this factor during pregnancy has resulted in congenital malformations in the offspring.
Vitamin A Deficiency
The principal signs of vitamin A deficiency in human subjects are night blindness and xerophthalmia. Mild degrees of vitamin A deficiency may be determined by measuring the rate of recovery of dark adaptation following exposure to bright light. This procedure re-quires special instrumentation and rigid techniques as there are many sources of error. Its usefulness is limited largely to research studies.
Xerophthalmia, which is encountered rarely in the United States, is manifested by decreased lacrimal secretion, keratinization of the corneal and conjunctival epithelium and Bitot’s spots, which are triangular conjunctival thickenings due to accumulations of white, foam-like epithelial cells lateral to the cornea. Bitot’s spots must be differentiated from pingueculae and pterygia which are unrelated to vitamin A deficiency. When vitamin A deficiency reaches an advanced stage, infection of the eye may occur with destruction of the cornea, panophthalmitis, and blindness.
Xerosis of the skin with hyperkeratinization, also called toad skin or phrynoderma, is probably another manifestation of vitamin A deficiency. The relationship of localized areas of keratosis of the hair follicles or of permanent “goose flesh” to vitamin A deficiency is less well documented. Follicular hyperkeratosis is observed in conditions unassociated with vitamin A deficiency and has not been produced in experimental deficiency in man.
In animals, cornification of the vaginal smear is noted in vitamin A deficiency and epithelial changes in the urinary tract have been associated with formation of calculi. In human subjects, administration of vitamin A has been reported to induce improvement in senile vaginitis but a role for vitamin A deficiency in formation of renal calculi remains to be demonstrated. In infants deficient in vitamin A, keratinization of the respiratory epithelium has resulted in blockage of small bronchioles, bronchiectasis and atelectasis. At one time, these findings were attributed erroneously to infection which led to the mistaken idea that vitamin A was an “anti-infective” vitamin.
Estimation of the level of carotene and vitamin A in blood serum are of assistance in the diagnosis of deficiency. The concentration of carotene reflects recent dietary intake in most instances and ranges from about 75 to 200 pg. per 100 ml. in well nourished subjects. Hypercarotenemia is associated with consumption of large amounts of carotene or with diseases in which conversion of vitamin A to carotene is impaired, such as diabetes mellitus and hypothyroidism. The concentration of vita-min A in the plasma ranges from 30 to 50 pg. per 100 ml. in well nourished children and adults. In vitamin A deficiency, the concentration is usually below 15-20 ,ug. per 100 ml. and, at times, no vitamin A may be detected.
Unfortunately from a diagnostic standpoint, a decrease in concentration of vitamin A in serum occurs in conditions unassociated with depletion of vitamin A stores of the body. Such decreases are observed in a number of febrile illnesses, the level returning to normal following recovery without administration of vitamin A. In the absence of such illness, a low plasma level of vitamin A is presumptive evidence of depletion of reserve stores in the liver.
The absorption of vitamin A may be tested by means of a tolerance test in which blood levels are determined at intervals after oral administration of large doses of the vitamin (p. 59). Comparison of absorption following ad-ministration of oily and aqueous preparations of vitamin A may also prove useful.
Vitamin A is not found in the urine of normal subiects but may be excreted in certain pathologic states, e. g., pneumonia, obstructive jaundice or chronic nephritis. In the nephrotic syndrome, high concentration of serum vitamin A has been noted following administration of the vitamin due, perhaps, to impaired metabolism.
Since vitamin A which has been absorbed is not excreted under normal conditions, it follows that repeated ingestion of large amounts may lead to excessive accumulation and toxicity. A number of instances of hypervitaminosis A have been reported, most of them in children (82) . Abnormal findings have included anorexia, loss of weight, irritability, low grade fever, pruriginous rash, sparseness of hair, changes in bone hyperostoses and periosteal elevations), hepatomegaly, splenomegaly and hypoplastic anemia. The concentration of vitamin A in serum is high, usually above 100 pg. per 100 ml. It has been postulated that the syndrome may be due to hepatic dysfunction. The minimal toxic dose reported is about 75,000 I.U. daily for a period of six months.