Administration of Ascorbic Acid to an Alkaptonuric Patient.

Abstract

Recently it has been reported from the senior author's laboratory that artificial alkaptonuria may be readily produced in the guinea pig by the supplementation of a vitamin C deficient diet with extra tyr0sine.l With the subsequent administration of the vitamin the homogentisic acid in the urine was promptly reduced in amount and within 48 to 72 hr was completely absent. These findings suggested that the relation of ascorbic acid to the excretion of homogentisic acid by the alkaptonuric patient should be investigated. However, in the course of the experiments with the guinea pigs, the results of two such investigations appeared. These reports by Monsonyi2 and by Diaz, Mendoza and Rodriquez3 indicate that ascorbic acid is without effect, but since, in our own mure recent studies* it has been apparent that in the guinea pig the effectiveness of the dose of ascorbic acid is dependent upon the state of vitamin saturation in the tissues, it was considered imperative to investigate the effect of doses of the vitamin greatly in excess of the normal human requirement, and also of the relatively small amounts used by the above investigators.Experimental. The individual who served as a subject for this study is an essentially normal 65-year-old white male who exhibited at the time of these experiments alkaptonuria and ochronosis-a deposition of pigment mainly in cartilage which is characteristic of these individuals in later years. Since the patient had previously been on an experiment in which he consumed a relatively high intake of protein, he was continued on this level, the diet being a mixed diet with considerable variety from day to day but so planned that it

A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria

“…1), and inhibits the generation of oxygen radicals in the development of ochronotic arthritis (Martin and Batkof 1987). The effect of ascorbic acid on the amount of HGA excreted by patients with alkaptonuria was inconclusive (Sealock et al 1940;Neuberger et al 1947, Wolff et al 1989Simoni et al 1994;Pradeep et al 1996). We presume that NTBC administered to alkaptonuric patients has a beneficial effect on ochronosis as well, by blocking the biosynthesis of HGA, the source of ochronotic pigments.…”

“…For either curative or preventive purposes, the use of NTBC together with ascorbic acid would be preferable, since, as pointed out by Sealock et al (1940), it is possible that adequate tissue concentrations of ascorbic acid may prevent the deposition of ochronotic pigment.…”

A Defect in the Metabolism of Tyrosine and Phenylalanine in Premature Infants. Ii. Spontaneous Occurrence and Eradication by Vitamin C 12

“…The persistent failure of hydroxyphenyl compounds to appear in significant amounts in the urine of one full term infant of 6% months (V. D.) who, according to his history, had been on a vitamin Cdeficient diet from birth and who presumably was in an extreme state of vitamin C desaturation (1lb), and the prompt eradication of these substances from the urine of another full term infant (G. T., Table V) by the administration of a vitamin C-free liver extract, suggest that full fetal maturity may bring with it a factor or factors, not solely dependent on vitamin C, capable of completing the degradation of aromatic amino acids. The failure of vitamin C to suppress the urinary excretion of the aromatic amino acid metabolites, homogentisic acid and phenylpyruvic acid in the inborn anomalies, alkaptonuria (15) and phenylpyruvic oligophrenia (16), has already been established.…”

Effects of Ascorbic Acid in Alkaptonuria: Alterations in Benzoquinone Acetic Acid and an Ontogenic Effect in Infancy

“…1) produces an accumulation of homogentisic acid and leads to debilitating ochronotic arthritis in adulthood (1, 2). In 1940 Sealock et al (3), studied the use of ascorbic acid for the treatment of a patient with alkaptonuria. Vitamin C therapy did not reduce the amount of homogentisic acid excreted in the urine.…”