Effect of Low Caloric Diet on Endogenous Carbon Monoxide Production: Normal Adults and Gilbert's Syndrome

Abstract

In 1906 Gilbert (1) observed that caloric deprivation produced an elevation of serum bilirubin concentration. Recently this observation has been confirmed (2-4) and various mechanisms have been suggested for the indirect hyperbilirubinemia that occurs (2, 3). Studies by Bloomer et al. (3) showed that fasting-induced hyperbilirubinemia was secondary to impaired hepatic clearance.

Since the catabolism of heme yields carbon monoxide (CO) and bilirubin in equimolar amounts (5, 6), measurement of endogenous CO production therefore reflects heme turnover (7) and bilirubin production (5, 6). Because of the possibility that fasting itself produces an increase in heme turnover (and therefore CO and bilirubin production), we studied the effect of caloric deprivation on the endogenous production of CO.

Subjects and Methods. Five normal volunteers (two male and three female) and nine patients with Gilbert's syndrome (all male) were studied. All subjects were carefully screened to preclude intake of any drugs or diagnostic agents known to influence the metabolism of bilirubin or CO. Informed consent was obtained from all participants in this study. Serum bilirubin concentration (8) and endogenous CO production were determined before and after the subjects had consumed a 400 calorie diet/24 hr for 48 hr. The diet contained approximately 46 g of carbohydrate, 16.5 g of protein, and 14.5 g of fat/24 hr. In three of the patients with Gilbert's syndrome, additional studies were performed after 18 to 24 hr of caloric deprivation. Endogenous CO production was measured utilizing a closed rebreathing system (9). The CO content of venous blood was analyzed by the gas chromatographic technique of Collison, Rodkey and O'Neal (10). Standard hematologic and liver function studies were performed prior to the onset of the caloric restriction, and included serum lactic acid dehydrogenase, alkaline phosphatase, transaminase, and total and direct bilirubin (Table I).