1. The effect of total starvation for 4–5 days on the intestinal uptake and urinary excretion of markers from an orally administered mixture of mannitol (5 g), [14C]mannitol (0.5 μCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 μCi), was assessed in five lean (group 1) and four obese (group 2) subjects. The effect of a very low calorie diet for 1 week and of a subsequent 5 day period of total starvation on intestinal permeability was assessed in a similar way in another group of obese subjects (group 3). Transit time from mouth to caecum of the fastest component of the oral mixture was assessed by the appearance of hydrogen in breath (all subjects), and the configuration of the transit spectrum through various segments of the gastrointestinal tract, was assessed by a radionuclide scan method (group 2 subjects only). The effect of starvation on plasma/renal clearance of these markers in subjects of group 2 was assessed with the use of a bolus intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 μCi), lactulose (0.1 g) and 51Cr-EDTA (5 μCi).

2. The uptake and urinary excretion of orally administered mannitol was decreased by total starvation. The mean decrease was 47% in the lean subjects (P < 0.025), 33% in group 2 obese subjects (P < 0.05) and 41% in group 3 obese subjects P > 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose.

3. There was no significant effect of starvation on transit time, whether assessed by the increase in breath hydrogen concentration in expired air or by radionuclide scanning.

4. Starvation produced no significant change in the clearance of the intravenously administered markers from the plasma. Oxidation of intravenous mannitol was estimated to account for about 1% of the clearance both before and during starvation.

5. The data provide evidence of a selective decrease in the absorption and excretion of mannitol during short-term total starvation. The changes in the excretion of mannitol are not due to alterations in renal function or gastrointestinal transit time, or to changes in the oxidation and plasma clearance of mannitol. They are likely to reflect changes in the small intestinal mucosa during early starvation. In contrast, very low calorie diets taken for at least 1 week prevent changes in small intestinal permeability.

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