Ascorbic Acid Deficiency
The primates, including man, and the guinea pig are the only animal species that require a dietary source of vitamin C. All other animal species studied need the vitamin for normal metabolic functions, to be sure, but they are able to synthesize all their requirement of this factor. The guinea pig has been the animal of choice in the bulk of the experimental work on the pathological and biochemical defects associated with ascorbic' acid deficiency. This animal is highly susceptible to a lack of vitamin C, and the alterations are known to be similar to those found in human scurvy. Vitamin C deficiency varies in degree from a mild condition scarcely recognizable to a profound state resulting in death.
In human beings the latter condition is not now seen except under extreme stress.
Outstanding among the pathological defects found in ascorbic acid deficiency is the failure to deposit intercellular cement substance. The presence of an abnormal collagen leads to a tendency to hemorrhage and to slow wound healing. Roe and others showed that ascorbic acid is essential for the production of connective tissue to insure postoperative healing as well as for maintenance of connective tissue in formed scar tissue. They demonstrated also that the vitamin accumulates in scar tissue quickly after a wound, and remains for a long time.
The connective tissue has the highest concentration of the vitamin. In the teeth there are changes as a result of scurvy in the very young, but they are not prominent features of the disease in: adult humans. The loss of teeth and the gum changes are more related to the deficiency effect on soft tissues.
In guinea pigs the poor dentine formation leads to poor tooth development. This was studied and described especially by Wolbach and co-workers. In the bones a deficiency results in the failure of the osteoblasts to form the intercellular substance osteoid. Without osteid, deposition of bone salts is arrested. The resulting scorbutic bone is weak and fractures easily. A detailed description of bone changes in guinea pigs and in man during ascorbic acid deficiency is available.
The advanced stage of scurvy in man is easily recognized. In infants the symptoms include Irritability and fretfulness, tenderness and swelling of joints, some degree of apathy and pallor, and a desire to remain quite motionless. In adults the advanced stage is attended by loosening r even loss of teeth, accompanied by sore, spongy gums, internal hemorrhage, subcutaneous emorrhage upon mild injury, painful joints, dyspnea, edema, and anemia. A loss of weight and a marked pallor are also noted. It is doubtful if all these symptoms are attributable to
corbic acid deficiency alone; more likely they represent the effects of a multiple deficiency.
In support of this view the important contribution of Crandon and others on experimental human deprivation of vitamin C is cited. Crandon remained on a diet totally deficient in vitamin C but supplemented with the other known vitamins for a period of six months. Some of the pertinent findings are listed herewith. After 41 days the blood plasma ascorbic acid level reached zero.
Since it was many weeks later before the first clinical signs were observed, the authors consider the plasma level of vitamin C as a poor index of the vitamin C status of an individual. They consider the ascorbic acid level in the white-ceil-platelet layer of blood a good index, since this remained elevated during most of the experimental period and fell to zero only shortly before the onset of clinical signs. The earliest symptoms noted were hyperkeratotic papules over the buttocks and calves. These began to develop after 132 days on the deficient diet.
According to these workers, this may be the earliest signs of deficiency. Perifollicular hemorrhages appeared after 161 days. Wound healing failed after the subject had remained on the diet for six months, although it was adequate at about the halfway mark in the experiment. At this time the plasma level of vitamin C had been zero for 44 days and the white-ceIl-platelet level was 4 mg per 100 ml (normal is 25 to 30 mg per 100 mI). No gross changes were seen in the gums or teeth although x-ray pictures showed interruptions in the lamina dura in the early acute phase of scurvy. This was considered likely to be a good diagnostic criteria in early scurvy. Correlation between capillary fragility and vitamin C deficiency was not good, and the authors doubt if the tests are as valuable as they were once thought to be, especially in a subclinical deficiency.
No anemia was found at any time during the experiment, nor was there any evidence of decreased resistance to infection. During the scorbutic state both the glucose and the insulin tolerance tests were found to be normal. Blood lactate disappeared abnormally slowly after exercise. Following the intravenous administration of ascorbic acid all the signs and symptoms of scurvy disappeard rapidly.
The tissue deficiency of this individual is shown by the fact that after the injection of 1 g of the vitamin the plasma level returned to zero after five hours. Even after 3 or 4 g of vitamin C the urinary excretion was subnormal, again demonstrating that the tissues were actively removing the vitamin from the blood stream. Another interesting experiment on experimental human ascorbic acid deprivation employing several volunteers was conducted in England. The findings were somewhat similar to those reported by Crandon and co-workers, although the English workers were attempting to establish requirements as well as to study the pathological and biochemical aspects of severe and moderate deficiency.
