Vitamin A is an essential nutrient for man and other animals. Deficiency of vitamin A causes at least four physiologically distinct and clinically recognized states: loss of night vision; defects in bone growth; defects in reproduction; and defects in the growth and differentiation of epithelial tissues. The recommended dietary allowance of vitamin A for adults is about 3,300 international Units (IU) daily. A daily intake of 3,300 IU would amount to about 50 IU per kg for an adult.
Dietary vitamin A activity is supplied by animal products (preformed vitamin A), plant products (provitamin A, such as carotene), and by the addition of vitamin A (retinol) and/or its esters (retinyl acetate and retinyl palmitate) to fortify certain foods. Mean daily intake of vitamin A from all food sources (excluding vitamin preparations) was approximately 5,000 IU in 1971 to 1974. However, some 47 percent of young adults were found to consume no more than 3,500 IU daily. Nevertheless, there is no clear evidence that Vitamin A nutriture is a problem of public health significance in the United States. Per capita daily intake of vitamin A used for the fortification of foods is assumed to be about 800 IU (about 13 IU per kg body weight in adults). However, accurate data on the amounts actually added are not available. The Select Committee believes such data should be obtained.
Signs of hypervitaminosis A in laboratory animals include abnormal bone development and fractures, exophtalmos, intramuscular hemorrhages, alopecia, reduced rate of growth or weight loss, adrenal hypertrophy, and at highly toxic dose levels, death. The lowest reported adverse effect level in experimental animals appears to be in the range 25,000 to 60,000 IU per kg per day for periods of 3 to 5 weeks. In man, where expressed feelings of pain or illness on the part of the patient provide an early indication of adverse effects, the symptoms and signs of hypervitaminosis A vary in severity with the dose level, and include skin dryness, anorexia, headache, weakness, hair loss, joint pain, vomiting, irritability, enlarged liver and spleen, and bulging fontanel and increased intracranial pressure in babies. The lowest reported adverse effect level in man appears to lie in the range 700 to 1,000 IU per kg per day, if continued for periods of several months.
With excessive maternal doses of vitamin A, abortions, resorptions, and a large variety of teratogenic effects can be consistently produced in experimental animals, the effectiveness of vitamin A in this regard being greater when administered in the early stages of pregnancy. Administration of a range of doses of vitamin A at the stage of pregnancy when teratogenic effects are most likely to occur, indicate that the highest no effect level in mice, rats, and hamsters lies in the range 2,500 to 100,00 IU per kg per day. Species differ in sensitivity; the small amount of information available with respect to the relative sensitivity of man indicates that maternal doses of the order of 700 to 800 IU vitamin A per kg daily for most of gestation may lead to abnormalities of the urinary tract in offspring may lead to abnormalities of the urinary tract in offspring. It is to be noted that congenital malformations also occur in offspring of vitamin A deficient mothers.
Vitamin A has been found to exhibit no mutagenic activity in in vitro tests. There is no evidence that it is carcinogenic.
The lowest doses of vitamin A that produce toxic manifestations in animals and humans are manyfold greater than the daily doses human adults receive from food consumed, only a small portion of which represents from food consumed, only a small portion of which represents vitamin A or its esters that are added to food. Nevertheless, this margin of safety may be compromised by the total intake of vitamin A from all sources.
Based on the foregoing considerations, the Select Committee concludes that:
There is no evidence in the available information on vitamin A, vitamin A acetate, and vitamin A palmitate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.