Sorbitol is a sugar alcohol widely used as a sucrose substitute in dietetic food and beverages because of its physicochemical properties and sweetening power. Sorbitol is absorbed in the human small intestine at a slow rate (Mehnert et al. 1959), resulting in osmotic diarrhea if ingested in excessive amounts (Corazza et al. 1988, Gryboski 1966, Hyams 1983, Ravry 1980). However, sorbitol is better absorbed and clinically tolerated when ingested with a meal (Beaugerie et al. 1990, Koisumi et al. 1983, Peters and Lock 1958, Steinke et al. 1961, Vaaler et al. 1987, Zeitoun et al. 1993). For example, diarrhea may occur in a few subjects ingesting 10 g sorbitol in the fasting state (Hyams 1983), whereas a 15- to 20-g single dose may be ingested in a meal without diarrhea (Koisumi et al. 1983, Vaaler et al. 1987). Because glucose is a constant and abundant component of meals, the rate of sorbitol absorption may be enhanced by the presence of glucose. Indeed, glucose has been shown to promote in vivo the intestinal absorption of small solutes such as urea or L-xylose (Fine et al. 1993 and 1994). Fine et al. (1994) showed that the increased absorption of these molecules is secondary to glucose-induced water absorption and can be attributed in similar proportions to solvent drag and passive absorption. Using the Ussing chamber, we have shown in vitro that the influx of sorbitol across the human jejunal mucosa is stimulated in the presence of glucose (Beaugerie et al. 1989).

The enhancement of sorbitol absorption by glucose could be related in vivo to a delay in the gastric emptying of sorbitol, which would lengthen the contact time between sorbitol and intestinal mucosa, and/or an interaction between the transport of sorbitol and glucose in the small intestine.

In the present study, we assessed the effect of glucose on the intestinal absorption of sorbitol in healthy volunteers, using the jejunal perfusion technique. Therefore, the effect of glucose on sorbitol absorption at the level of the intestine was tested, using an in situ method which prevents the influence of gastric emptying.

SUBJECTS AND METHODS

Table 1. Composition and osmolality of the three test solutions [View Table]

Data are expressed as means ± SEM. Variance analysis (ANOVA) was used to compare data among the three periods. Following a significant P value (0.05), the Newman-Keuls test (Games et al. 1983) was used to identify differences between individual means. Correlations were assessed by simple regression. A P value 0.05 was considered to be statistically significant.

RESULTS

Table 2. Osmolality, flow rate and concentration of sorbitol and glucose of the three sorbitol solutions differing in glucose concentrations perfused into the proximal jejunum of six human subjects and entering the test segment1 [View Table]

Table 3. The sorbitol load and the sorbitol and glucose concentrations in the test segment of the jejunum of six humans subjects perfused with three sorbitol solutions differing in glucose concentration [View Table]

Mean net sorbitol absorption in the test segment was 5.2 ± 1.3, 6.2 ± 0.5 and 5.8 ± 0.4 mmol/(h·30 cm) for the glucose-free solution, the 55 mmol/L glucose solution, and the 110 mmol/L glucose solution, respectively. These values did not differ significantly. When administered the solution without glucose, three of the six volunteers had sorbitol absorption values greater than those observed in the presence of glucose. There was no correlation between the absorption of glucose and the absorption of sorbitol (n = 12, r = 0.16, P = 0.62).

DISCUSSION

Some methodological points may be discussed. We used the triple lumen intestinal perfusion method developed by Fordtran's group, which utilizes a perfusion flow rate of 10 mL/min (Cooper et al. 1966, Fordtran 1966). This flow rate is not too high to impede sorbitol absorption because it corresponds to the postprandial flow rate in the duodenum (Fordtran and Locklear 1966, Sladen 1968). In addition, the facilitating effect of glucose on the absorption of other small solutes has been demonstrated by Fine et al. (1993 and 1994) using the perfusion method and similar flow rates.

The osmolality of the 110 mmol/L glucose solution was greater than that of the two other solutions. This difference persisted, although attenuated, when considering the solutions at the entry of the jejunal segments. It could have been assumed that the greater osmolality of the 110 mmol/L glucose solution should result in a limited net water absorption in the test segment, and thus, a limited passive sorbitol absorption, according to the hypothesis developed by Fine et al. (1994). As a matter of fact, the net absorption of water from the 110 mmol/L glucose solution was significantly greater than during the two other periods, suggesting that the glucose-induced water movement was predominant and not greatly affected by the higher osmolality of the solution.

Sorbitol was not absorbed to a greater extent when perfused concomitantly with glucose. This result does not confirm our in vitro findings with the Ussing chamber technique of a mild facilitating effect of glucose on sorbitol absorption (Beaugerie et al. 1989). In vivo, with the perfusion technique, Fine et al. (1993 and 1994) studied the effects of D-glucose on the passive absorption of others molecules in the human small intestine. They first demonstrated that D-glucose did not increase the permeability of jejunal mucosa (Fine et al. 1993), as had been shown in vivo in animal studies (Atisook et al. 1990, Pappenheimer and Reiss 1987). Then, they studied the mechanisms by which glucose stimulates the passive absorption of L-xylose (Fine et al. 1994), a smaller molecule than sorbitol. They demonstrated that 57% of the increase of L-xylose absorption could be attributed to solvent drag. Solvent drag is a mechanical water movement through or between the enterocytes induced by glucose absorption, and carrying hydrophilic solutes, such as L-xylose. Concurrently, 42% of the increase of L-xylose absorption could be attributed to passive diffusion of L-xylose, according to a chemical concentration gradient, created by the fact that the removal of water from the lumen, induced by glucose absorption, increased the luminal concentration of solutes. The experimental design of our study was close to that of Fine et al. (1994). In particular, we used the same perfusion rate as stated above. In agreement with Fine et al., we found that net water absorption increased significantly as the glucose concentration of the solution increased. If the factors affecting sorbitol absorption were similar to those described for small solutes such as urea or L-xylose, sorbitol absorption should have increased linearly with the increasing absorption of water induced by glucose. Our negative result with sorbitol cannot be attributed to the small number of subjects studied for the following reasons: 1) the effect of glucose on L-xylose absorption was demonstrated in the study of Fine et al. (1994), with a similar number of individuals; 2) in our study, water absorption increased linearly with the glucose concentration; and 3) because the absorption of sorbitol was better in the absence of glucose in half of the individuals, a similar proportion would have been expected in a study including a larger number of subjects.

The effect of glucose on intestinal absorption of diffusible molecules is different for L-xylose and sorbitol. The two driving forces of glucose-induced diffusion for small solutes, namely, simple diffusion and solvent drag, are both related to the size of molecules. Diffusion and solvent drag are greater for smaller molecules (Fine et al. 1994). Sorbitol has a molecular weight and a spatial structure similar to those of mannitol, whose molecular radius is 4.0 nm, whereas the molecular radii are 3.4 and 2.6 nm for L-xylose and urea, respectively (Fine et al. 1993). This difference may have represented a limiting factor for glucose-induced sorbitol absorption and thus a potential cause of our negative result.

Last, it could be argued that the perfusion technique in a 30-cm intestinal segment was not appropriate to demonstrate the facilitating effect of glucose on sorbitol absorption in the whole gut. Again, this length of intestine has been shown to be sufficient to demonstrate the effect of glucose on the absorption of other diffusible solutes (Fine et al. 1994). Moreover, the potential effect of glucose is maximal in the proximal jejunum, because the luminal contents of glucose decrease as they progress in the small intestine, and become almost nil in the terminal ileum (Beaugerie et al. 1990).

Using the hydrogen breath test, we have estimated that about 20% of a single 20-g dose of sorbitol, ingested in liquid form, is absorbed in the human small intestine (Beaugerie et al. 1991, 1992 and 1995). This value reaches 40% when the same dose of sorbitol is ingested with an equivalent amount of glucose (Beaugerie et al. 1991 and 1995) and represents a 100% increase in the amount of sorbitol absorbed in the small intestine. In a previous study, we have shown that the delay in the gastric emptying of sorbitol is significantly correlated to the better absorption of sorbitol (Beaugerie et al. 1996). Altogether, the results of these studies and the present study suggest that the delay of the gastric emptying of sorbitol is the main cause of the better absorption of sorbitol when ingested concomitantly with glucose.