M. Gross, S. Reiter and N. Zollner
Medizinische Poliklinik der Universitat Munchen
Summary. D-ribose was administered orally or intravenously over at least 5 h to eight healthy volunteers and five patients with myoadenylate deaminC~ se deficiency. Intravenous administration rates were 83, 167, and 222 mg/kg/h, which were well tolerated but oral administration of more than 200 mg/kg/h caused diarrhea. The average steady state serum ribose level ranged between 4.8 mg/100 ml (83 mg/kg/h, oral administration) and 81.7 mg/100 ml (222 mg/kg/h, intravenous administration). Serum glucose level decreased during ribose administration. The intestinal absorption rate of orally administered ribose was 87.8%-99.8% or the intake at doses up to 200 mg/kg/h without first pass effect. Urinary losses were 23% of the intravenously administered dose at 222 mg/kg/h. Ribose appeared to be excreted by glomerular filtration without active reabsorption; a renal threshold could not be demonstrated. The amount of ribose transported back from the tubular lumen depended on the serum ribose level. There was no difference in ribose turnover in healthy subjects and patients with MAD deficiency.
D-ribose and xylitol are the only substances known to prevent the symptoms of patients with myoadenylate deaminase (MAD) deficiency. An oral administration of 15-20 g ribose per hour can prevent pain and stiffness of the muscles [33, 34].
In experiments with rats, Zimmer [31] showed that after temporary ischemia the myocardium loses its purine nucleotides; their pool has to be recompleted by purine synthesis de novo. The initial cellular purine concentration is regained after 72 h. If ribose is administered, the restoration of cardiac ATP pool takes only 12 h. These results may become important in the therapy of human coronary infarction or chronic coronary heart disease.
The first experiment with ribose in man were done in 1946 [30] but up to today, no investigations were done with long-lasting administration of ribose in man. These early experiments did not show whether a steady state concentration of serum ribose concentration after administering ribose for several hours is obtained.
A hypoglycemic effect of ribose has repeatedly been described [1, 2, 6-8, 21, 22, 24, 25] after short-term administrations. It is not known whether the hypoglycemia induced by ribose will persist during a continuous administration over several hours -an important question for the therapy of patients with MAD deficiency.
Experiments with human lymphocyte cultures revealed cytotoxic effects of ribose after an incubation in concentrations of 20-50 mmol/1 after 24 h [15, 23, 28, 35]. It is important to know whether such concentrations may be reached during therapy with this sugar.
The aim of the study was the investigation of basic pharmacological data of D-ribose for the treatment of patients with MAD deficiency. The main topics were intestinal resorption and urinary excretion after oral administration, serum ribose concentration after long-term administration, disappearance of ribose from blood, and side-effects including the known hypoglycemic effect.