Pantothenic Acid Deficiency
All species of animals investigated require pantothenic acid. The fox, mouse, monkey, rat, pig, dog, chick, and other species have been studied in this respect. Microorganisms also need the vitamin, although some are able to synthesize it and thus do not need an external supply. In the rat certain fairly well-defined symptoms of deficiency are observed. Retarded growth in young animals is seen.
Reproduction is seriously affected. It was demonstrated that institution of a pantothenic acid deficiency as late as the day of mating resulted in failure of inlplantation, resorption, or defective litters. Achromotrichia, or graying of hair, in black rats (and foxes) is related to but not due solely to a pantothenic acid deficiency. Other deficiencies, perhaps including inositol, are involved. The condition has not been produced in rats after adrenalectomy. Adrenal cortical necrosis results from continued deprivation of the vitamin. Rats suffering such a pathological condition exhibit serious abnormalities in salt and water metabolism. The cholesterol content of the adrenals is markedly lowered, indicating decreased ability on the part of the rat to synthesize this compound under the stress of pantothenic acid deficiency.
Cholesterol is the likely precursor of adrenal cortical hormones, and coenzyme A is known to participate in the utilization of acetate in cholesterol formation. Adrenal cortical secretion is decreased in pantothenic acid deficiency, and Langwell and co-workers demonstrated a reduced production of corticosterone in rat adrenals during deficiency. The porphyrin-caked or "bloody" whiskers in rats is another deficiency symptom, although a similar condition can be produced by restricting the water intake. There seems to be an important interrelation of the adrenals, pantothenic acid, and water and porphyrin metabolism. In chickens growth and appetite are retarded on a pantothenic acid-deficient diet. Also, a dermatitis and a fatty liver condition develop.
Egg hatchability is greatly reduced even before the hens demonstrate any visible symptoms. In dogs a pantothenic acid deficiency causes a loss of conditional reflex performance. Gantt and co-workers reported that this loss appears within four to ten days prior to other neurological symptoms, and without observable behaviour changes. Upon addition of the vitamin to the diet, the conditioned reflex function ret.urns to normal. In rats a pantothenic acid deficiency lessened the ability to form conditional reflexes.
The authors state that pantothenic acid is essential not only for physical health but apparently for normal conditional reflex performance, which is the basis of mental health. Gastrointestinal disturbances and duodenal ulcers appear in deficient rats, and in severe deficiency there is degeneration of testicular interstitial tissue. A reduction of 30 to 40 per cent in coenzyme A content was found in tissues of pantothenic acid-deficient rats.
The utilization of pyruvate by liver tissue was also decreased. In deficient ducks the injection of pantothenate markedly increased the coenzyme. A content of liver and the ability of liver slices to utilize pyruvate. Deficient rats also show a decreased ability to acetylate administered l3-amino-benzoic acid. However, it was reported that in such animals the ability to acetyl ate a test dose of an aromatic amine was restored in as short a time as three hours after injection of pantothenate. Pantothenyl alcohol (alcohol analogue) is growth promoting and prevents achromotrichia in rats. In man it is just as efficient as the vitamin in increasing pantothenic acid excretion in urine after a test dose. These facts indicate that the alcohol is converted to the acid (vitamin) in the body. The alcohol, however, does not support growth of Lactobacillus arabinosus, and so it seems that this organism cannot carry out the conversion.
Deficient rats respond to pantotheine, pantothine, pantothenylcysteine, and pantothenylcystine. Animal deficiency symptoms have been reviewed by Wagner and Folkers. Pantothenic acid deficiency in man is known only in the cases in which it has been produced experimentally. This undoubtedly results from the wide distribution of the vitamin in, plant and animal foods, and from the fact that some microorganisms, such as E. coli, synthesize quantities of the vitamin and excrete the excess above their needs. In man this organism is normally found in the gastro-intestinal tract. This is an important contributing factor in the absence of human pantothenic acid deficiency. The extravagant claims for pantothenic acid as an anti-gray hair factor for humans have been adequately disproved in carefully controlled experiments. Hodges and others restricted the pantothenic acid intake of two young men. Two others consumed the same deficient diet plus 1000 mg daily of the antagonist, comethylpantothenic acid. A third group of two men received the diet plus 20 mg of pantothenic acid daily. After a few weeks the antagonist group developed serious personality changes, including irritability and restlessness.
Alternate periods of somnolence and insomnia and excessive fatigue after mild exercise were experienced. A little later the men in the deficient group noted similar complaints, and soon the symptoms were indistinguishable in the two groups. They developed a. staggering gait and gastrointestinal symptoms became common. Biochemical changes reflected by laboratory tests were not prominent. The loss of eosinopenic response to adrenocorticotropic hormone (ACTH) was the most consistent. The men in the control group showed none of the foregoing symptoms. Massive doses of pantothenic acid to the four men who were deficient corrected the faulty eosinopenic response and alleviated most of the clinical symptoms.
