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Steady-state extrarenal sorbitol clearance as a measure of hepatic plasma flow.

Hepatic plasma flow was assessed with sorbitol (hepatic extraction = 0.96) at steady state. After infusion of 50 mg/min for 3 h, total and renal sorbitol clearances were calculated, and the extrarenal clearance was obtained by taking the difference between the two. In normal volunteers, the mean (+/- SD) extrarenal sorbitol clearance was 10.6 +/- 2.1 ml/min.kg. In patients with various liver diseases, it was correlated more closely to the fractional clearance of indocyanine green (r = 0.83, n = 57) than the galactose elimination capacity (r = 0.66, n = 55). Hepatic vein catheterization showed that the hepatic extraction of sorbitol was always much higher than the extraction of indocyanine green; there was no evidence for extrahepatic, extrarenal sorbitol elimination. On the basis of these findings, sorbitol is kinetically superior to indocyanine green and, although the noninvasively determined extrarenal sorbitol clearance at steady state may not be equal to total hepatic plasma flow, it may at least be regarded as a measure of parenchymal liver plasma flow.

Adult↗

Effect of erythrocytes and prostacyclin production in the effect of fructose and sorbitol on platelet activation in human whole blood in vitro.

We analyzed the in vitro effects of sorbitol and fructose on platelet function. Sorbitol and fructose increased platelet aggregation induced with adenosine diphosphate (ADP) or collagen in whole blood, but had no effect in platelet-rich plasma. The concentration that increased basal aggregation by 50% with ADP as the inducer was 12.89 +/- 1.55 mmol/L for fructose, and 18.99 +/- 2.01 mmol/L for sorbitol. When collagen was the inducer, these concentrations were 15.02 +/- 0.98 mmol/L for fructose, and 12.94 +/- 1.57 mmol/L for sorbitol. Both sugars increased, in a concentration-dependent way, the proaggregatory effect of erythrocytes, and erythrocyte uptake of adenosine. Time to uptake of 50% adenosine was 2.1 +/- 0.3 min in control samples, 0.14 +/- 0.01 min in the presence of fructose, and 0.23 +/- 0.03 min with sorbitol. Both sugars reduced vascular prostacyclin synthesis, with 50% inhibitory concentrations of 26.48 +/- 1.97 mmol/L for fructose, and 39.53 +/- 2.81 mmol/L for sorbitol. Both sugars also increased arterial lipid peroxidation by 30% (sorbitol) and 23% (fructose). We conclude that these two sugars enhance platelet function and disrupt the thromboxane/prostacyclin ratio.

6-Ketoprostaglandin F1 alpha↗

Towards a molecular level understanding of protein stabilization: the interaction between lysozyme and sorbitol.

The paper is investigating the mechanism of stabilization of proteins by polyols at the molecular level. It is addressing the interactions of sorbitol, a polyol commonly used as a protein stabilizing agent, with hen egg white lysozyme, a well studied protein. Differential scanning calorimetry shows an increase in denaturation temperature of lysozyme upon addition of sorbitol at a concentration of 250 mM and above. Increasing sorbitol concentration also caused an increase in signal intensity of the CD spectrum of lysozyme in the wavelength region of 280-300 nm. Two-dimensional nuclear magnetic resonance spectroscopy was used to examine interactions between lysozyme and sorbitol. Most significant changes are manifest in the anomalous relaxation properties of Ala and Thr methyl groups indicating modifications of local motions and possibly compression of the entire structure. This is further corroborated by new intra-protein nuclear Overhauser effects in the presence of sorbitol. There is also evidence that water is displaced from the enzyme surface close to Ile-88 upon addition of sorbitol. In combination these results reveal a complex interplay of different interactions. Comparison to NMR-spectra of lysozyme with a bound inhibitor (tri-N-acetyl-glucosamine) shows that the interaction with sorbitol affects spatially disparate regions of the protein.

Calorimetry, Differential Scanning↗

Contribution of sorbitol combined with activated charcoal in prevention of salicylate absorption.

The use of cathartics and activated charcoal in treating toxic ingestions has become a standard treatment modality. Sorbitol has been shown to be the most rapidly acting cathartic, but its therapeutic significance has been debated. Using a previously described aspirin overdose model, ten healthy volunteers participated in a crossover design study that investigated the effect of activated charcoal alone versus that of activated charcoal and sorbitol in preventing salicylate absorption. In phase 1 of the study, subjects consumed 2.5 g aspirin followed by 25 g activated charcoal one hour later. Urine was collected for 48 hours and analyzed for quantitative salicylate metabolites. Phase 2 was identical except that 1.5 g/kg sorbitol was consumed with the activated charcoal. The mean amount of aspirin absorbed without the use of sorbitol was 1.26 +/- 0.15 g, whereas the mean absorption was 0.912 +/- 0.18 g with the addition of sorbitol. This is a 28% decrease in absorption of salicylates attributable to the use of sorbitol. The difference is significant at P less than .05 by the paired Student's t test. This study demonstrates that the addition of sorbitol significantly decreases drug absorption in a simulated drug overdose model. Effects on absorption in actual overdose situations and on patient outcome should be the subjects of further study.

Adult↗

Fructose and sorbitol malabsorption in ambulatory patients with functional dyspepsia: comparison with lactose maldigestion/malabsorption.

The aim of this study was to study sugar maldigestion/malabsorption in patients with functional dyspepsia using H2 breath testing. End-expiratory breath H2 after separate challenges with lactose (25 g), fructose (25 g), and sorbitol (5 g) were used to determine malabsorption, as well as small bowel transit time (SBTT). Five hundred twenty patients with functional dyspepsia received all three challenges. Smaller groups were also tested after lactulose (10 g, N = 36) and glucose (50 g, N = 90) challenges. Fructose and sorbitol were closely linked with respect to absorption and malabsorption status. Only in the case of lactose maldigestion/malabsorption was there a greater than random prevalence of malabsorption (P < 0.001) for fructose and sorbitol. In contrast to lactose, ethnic origin did not influence fructose or sorbitol malabsorption, and females predominated among fructose and sorbitol malabsorbers. In Jews, the prevalence of lactose maldigestion/malabsorption decreased in the age group of 25-55 and subsequently rose after 55, while fructose and sorbitol malabsorption decreased progressively with advancing age. With respect to small bowel transit time (SBTT), in the case of sorbitol and lactulose, it was significantly greater (P < 0.05) than those for fructose and lactose. Multiple sugar malabsorptions are common when lactose maldigestion/malabsorption is present.

Breath Tests↗

Addition of sorbitol to a milk substitute for veal calves. I. Effects on health, growth and feed conversion.

Two homologous groups of preruminant male calves (10 control and 9 sorbitol) of the Friesian X Holstein crossbreed were used to study the effects of sorbitol on appetite, health status and growth rate. Between 1 and 8 weeks of age they were given two milk replacers (IC and IS) that contained high levels of protein and fat (23% of DM), and then between 8 and 19 weeks two diets (FC and FS) containing lower levels of protein and fat (21% of DM). The IC and FC diets had no sorbitol, while in the IS and FS diets it accounted for 0.8% of DM. In each group 4 to 6 calves were used to measure milk digestibility at 3, 7 and 12 weeks of age. At slaughter (19 weeks), carcass quality and liver status were checked. The overall health status of the animals was satisfactory, but after accidental cold stress at week 7, the 10 calves of the control group had diarrhea for 2 to 5 days vs 4 calves in the sorbitol group. Sorbitol digestibility was about 95% at week 3 and almost 100% at weeks 7 and 12. Apparent energy and protein digestibilities increased in the two lots from 83.8 and 83.1, respectively, at week 3, to 89.8 and 90.7%, respectively, at week 7, but these digestibilities were not affected by sorbitol. Liveweight gain (+ 12% for the whole trial) and feed efficiency (+ 6.7% for the whole trial) were significantly (P less than 0.05) improved by the presence of sorbitol in the diet.

Animal Nutritional Physiological Phenomena↗

Addition of sorbitol to a milk substitute for veal calves. II. Effects on plasma, liver and muscle lipids.

Two homologous groups of preruminant male calves (10 control and 9 sorbitol) of the Friesian X Holstein crossbreed were used to study the effects of sorbitol on lipid metabolism. Between 1 and 8 weeks of age they received two diets (IC, IS) with high levels of protein and fat (23% of DM), and then between 8 and 19 weeks two diets (FC, FS) containing lower levels of protein and fat (21% of DM). Diets IC and FC contained no sorbitol, while in the IS and FS diets it accounted for 0.8% of DM. Blood samples were taken at 2, 3, 4, 7, 12 and 19 weeks of age and at the following times: 2 h before (T-2), and then 1/2 (T1/2), 2 (T2), 3 (T3), 5 (T5) and 7 (T7) hours after ingestion of the morning meal. At slaughter (19 weeks), samples of liver and of rectus abdominis muscle were taken from the carcasses. The addition of sorbitol to the replacer milks had no effect on plasma levels of nonesterified fatty acids or triglycerides. However at weeks 2, 7 and 12, the levels of free and esterified cholesterol decreased significantly by a mean of 60 and 15% respectively. Sorbitol intake significantly reduced muscle levels of triglycerides (6.8 mg/g of fresh tissue vs 18.6 mg/g), free cholesterol (0.41 mg/g vs 0.66) and total lipids (13.6 mg/g vs 26.1). Lipid composition of liver was not modified by sorbitol ingestion. An histological study confirmed that the diets caused no serious lesions. Generally, the results were more dispersed in the control group than in the sorbitol group.

Animal Nutritional Physiological Phenomena↗

Characteristics of sorbitol uptake in rat glial primary cultures.

Uptake of [U-14C]sorbitol was studied in astrogliarich rat primary cultures. Initial rate of sorbitol uptake is proportional to sorbitol concentration between 20 microM and 400 mM. Sorbitol transport is not inhibited by glucose, fructose, and a variety of structurally related polyols, or by cytochalasin B, an inhibitor of glucose transport. Phloretin, phlorizin, filipin, and n-hexanol, all compounds that alter the properties of biological membranes, and the sulfhydryl reagent p-chloromercuribenzoate inhibit sorbitol uptake to various degrees. Variation in the concentrations of extracellular Na+ and K+ does not affect transfer of sorbitol across the cell membrane. It is concluded that sorbitol is taken up into glial cells by a diffusion process, not involving a carrier and probably not through the lipid bilayer, but through a proteinaceous channel-like structure.

Animals↗

Temperature-dependent fermentation of D-sorbitol in Escherichia coli O157:H7.

The influence of growth temperature on the ability to ferment D-sorbitol was investigated in Escherichia coli O157:H7. It was found that O157:H7 strains have a temperature-sensitive sorbitol phenotype. D-Sorbitol transport and sorbitol-6-phosphate dehydrogenase activities were expressed in sorbitol-fermenting cells grown at 30 degrees C but only at a low level at 40 degrees C. Sorbitol-positive variants able to transport D-sorbitol were easily selected at 30 degrees C from culture of Sor(-) E. coli O157:H7 strains.

Anaerobiosis↗

Sorbitol promotes growth of Zymomonas mobilis in environments with high concentrations of sugar: evidence for a physiological function of glucose-fructose oxidoreductase in osmoprotection.

The gram-negative ethanologenic bacterium Zymomonas mobilis is able to grow in media containing high concentrations of glucose or other sugars. A novel compatible solute for bacteria, sorbitol, which enhances growth of Z. mobilis at glucose concentrations exceeding 0.83 M (15%), is described. Added sorbitol was accumulated intracellularly up to 1 M to counteract high external glucose concentrations (up to 1.66 M or 30%). Accumulation of sorbitol was triggered by a glucose upshift (e.g., from 0.33 to 1.27 M or 6 to 23%) and was prevented by the uncoupler CCCP (carbonyl cyanide m-chlorophenylhydrazone; 100 microM). The sorbitol transport system followed Michaelis-Menten kinetics, with an apparent Km of 34 mM and a Vmax of 11.2 nmol.min-1.mg-1 (dry mass). Sorbitol was produced by the cells themselves and was accumulated when growing on sucrose (1 M or 36%) by the action of the periplasmic enzyme glucose-fructose oxidoreductase, which converts glucose and fructose to gluconolactone and sorbitol. Thus, Z. mobilis can form and accumulate the compatible solute sorbitol from a natural carbon source, sucrose, in order to overcome osmotic stress in high-sugar media. No other major compatible solute (betaine, proline, glutamate, or trehalose) was detected.

Adaptation, Physiological↗

Effect of pH on acid production from sorbitol in washed cell suspensions of oral bacteria.

The acid production from sorbitol and glucose was studied under anaerobic conditions in resting cell suspensions of bacteria from the predominant sorbitol-fermenting human dental plaque flora, belonging to the genera Streptococcus, Lactobacillus and Actinomyces. The acid production activity of the bacterial cells was followed by titration with alkali, at environmental pH 7.0, 6.0 and 5.0 after addition of carbohydrate solution. The metabolic end products formed in the suspensions were analyzed thereafter by isotachophoretic and enzymatic methods. The results showed that sorbitol was fermented at a slower rate than glucose. Lowering the environmental pH decreased the acid production activity from the two carbohydrates. Compared with glucose, the catabolism of sorbitol was affected to greater extent by the pH conditions. The total amount of acids formed from sorbitol was considerably less than from glucose. Lactic acid, which was the major end product in glucose-challenged suspensions, was produced only in low concentrations from sorbitol by all strains tested. The ratio strong (formic + lactic)/weak acids was moreover lower for sorbitol than for glucose. The present results further illustrate some of the mechanisms behind the low cariogenic potential of this sugar substitute.

Acetates↗

Low blood-to-cerebrospinal fluid passage of sorbitol after intravenous infusion.

BACKGROUND AND PURPOSE: Compared with mannitol, the osmotherapeutic agent sorbitol is less prone to accumulate in the blood and the same quantity may be infused in a smaller volume. Because of these advantageous characteristics, we studied the pharmacokinetics of sorbitol in serum and cerebrospinal fluid. METHODS: Six patients (five women and one man; age range, 46-70 years) with an external ventriculostomy and suffering from brain edema due to cerebrovascular disease received sorbitol as part of their therapy. Before and after the first dose of 50 g infused over 20 minutes, sorbitol concentrations in serum and cerebrospinal fluid were determined repeatedly using an enzymatic procedure. RESULTS: Maximal sorbitol concentrations ranged from 2,705 to 5,821 (median, 3,227) mg/l in serum compared with 6.7-130.7 (median, 19.5) mg/l in cerebrospinal fluid. Cerebrospinal fluid maxima were observed 0.17-3 hours after the end of the infusion. Sorbitol elimination in serum was adequately described by a two-compartment pharmacokinetic model (distribution half-life, 0.05-0.14 hour; elimination half-life, 0.23-0.61 hour). Elimination in cerebrospinal fluid followed a single-exponential decay and was considerably slower than that in serum (half-life, 1.3-7.7 hours). CONCLUSIONS: The maximal cerebrospinal fluid concentration/maximal serum concentration ratio was low for sorbitol, thus suggesting a small potential risk of inducing an increase of intracranial pressure after osmotherapy (rebound effect).

Aged↗

Sorbitol content of selected oral liquids.

OBJECTIVE: Excipients in pharmaceuticals usually are considered inert, and may be overlooked in the differential diagnosis of diarrhea. Sorbitol-containing medicinal liquids are capable of inducing osmotic diarrhea. We reviewed the oral liquids in our formulary to determine their sorbitol content and to evaluate the availability of this information. DESIGN: The oral liquids stocked by our hospital were determined through a computer search and manual inspection of the pharmacy storeroom. Three common sources of drug information were consulted to determine each product's sorbitol content: manufacturers' product information, American Hospital Formulary Service (AHFS) Drug Information 91, and Facts and Comparisons Drug Information. We then contacted each manufacturer by mail or telephone to verify the information. SETTING: The study was conducted at the University of Cincinnati Hospital, a tertiary-care, teaching hospital. RESULTS: A total of 129 products (98 chemical entities) were reviewed. Fifty-four (42 percent) of the products examined contained sorbitol. The frequency of sorbitol presence by liquid type was: solutions (33 percent), suspensions (43 percent), syrups (59 percent), elixirs (43 percent), concentrates (67 percent), drops (33 percent), tinctures (0 percent), and emulsions (0 percent). The percentage of listings indicating the presence of sorbitol was: manufacturer's product information (79 percent), Facts and Comparisons (52 percent), and AHFS Drug Information 91 (13 percent). Only three of the 54 products had the exact sorbitol content stated in any source.

Administration, Oral↗

In vitro and in vivo reduction of erythrocyte sorbitol by ascorbic acid.

The in vitro accumulation of sorbitol by human erythrocytes incubated in a physiological glucose medium was found to be strongly reduced by the addition of ascorbic acid (AA). A maximal inhibition of sorbitol in the erythrocytes of 98.3% occurred when the concentration of AA was at its peak in the cells. After incubation, the erythrocyte sorbitol was found to be inversely correlated with the concentration of AA in the erythrocytes. A human supplementation study was conducted with 10 normoglycemic subjects. Each was given 500 mg/day AA alone or in a citrus fruit medium. Each supplementation lasted 2 wk and was followed by a 10-day washout. The citrus fruit medium produced a significantly greater increase in erythrocyte AA compared with AA alone. AA alone and in citrus fruit medium decreased erythrocyte sorbitol 12.6 and 27.2%, respectively, with the latter being significantly more effective. In a study with 4 subjects, 2000 mg/day AA resulted in a reduction in erythrocyte sorbitol of 56.1%. As in the in vitro study, there was an inverse relationship between erythrocyte AA and sorbitol. Two thousand milligrams of AA per day (AA or citrus fruit medium) was given to 8 diabetic subjects in a preliminary 3-wk supplementation trial in which erythrocyte sorbitol levels were decreased by 44.5%. These results suggest that AA supplementation for diabetic subjects may provide a simple means of preventing and ameliorating the complications of diabetes without the use of drugs.

Adolescent↗

Malabsorption of fructose-sorbitol mixtures. Interactions causing abdominal distress.

Hydrogen breath tests were performed on 10 healthy adults after they had ingested a mixture of sorbitol and fructose, in which these substances were present in amounts corresponding to the individual absorption capacities. A significant malabsorption of this mixture was evident in 7 of 10 subjects. The mixture caused mild to severe gastrointestinal distress in five subjects. When the carbohydrates were given separately, symptoms were absent. There was a significant correlation between the individual absorption capacities of fructose and of sorbitol. A mixture containing a similar amount of fructose, but given as sucrose, and a similar amount of sorbitol was further given to four of the seven subjects showing malabsorption of the fructose-sorbitol mixture. Malabsorption now failed to appear, and symptoms were absent. These findings are of potential importance for the understanding of the physiologic processes involved in fructose absorption and suggest that in healthy adults the presence of sorbitol interferes with fructose absorption and/or vice versa. An interaction between small amounts of fructose and sorbitol causing malabsorption and abdominal distress has not been demonstrated previously. Gastrointestinal discomfort must be suspected to occur in sensitive individuals at a rather limited daily intake of fructose- and sorbitol-containing foodstuffs.

Adult↗

Effect of activated charcoal in 70% sorbitol in healthy individuals.

Activated charcoal in 70% sorbitol enjoys wide use in the management of acute poisonings but the effects of the activated charcoal-sorbitol mixture in healthy individuals have not been characterized. We were concerned about the possibility of sorbitol causing changes in the routinely monitored serum chemistry and hematological parameters, either directly due to the absorbed polyol or due to the diarrhea induced by it, thus complicating the diagnosis and management in an overdose setting. We assessed the action of a single dose of 30g of activated charcoal in 150 ml of 70% sorbitol and its effects on serum osmolality, electrolytes, metabolic profile (SMAC), magnesium, hepatic enzymes, and complete blood count in healthy adult individuals. The only significant change in the laboratory parameters tested was the consistent rise in serum sodium and phosphorus concentrations four hours after drinking the charcoal-sorbitol mixture. However, a similarly consistent rise in the concentrations at the same hours on another day without ingestion of the charcoal-sorbitol mixture suggested the rise was due to circadian rhythm or other factors unrelated to the cathartic. The lack of effect on routinely monitored laboratory parameters, relative palatability and the rapid onset (40-225 minutes), and long duration (7 to 127 hours) of purgation, make charcoal-sorbitol an attractive combination for use as a gastrointestinal decontaminant. Possible effects of multiple dose regimens and the effects in pediatric and geriatric populations need further study.

Adult↗

Sorbitol accumulation in rats kept on diabetic condition for short and prolonged periods.

AIM: To study the influence of the course of diabetes, aging, and glycemia on the sorbitol accumulation in diabetic rats. METHODS: Streptozocin (Str) diabetic rats were obtained by Str i.v. (35 mg.kg-1). Glycemia and sorbitol levels from sciatic nerve and lens were measured after 1 d, 2, 5, and 8 months of diabetes. Sorbitol concentrations in serum, heart, diaphragm, small intestine, and kidney after 8 months of diabetes were measured. RESULTS: Diabetic rats after Str injection showed hyperglycemia (> 1.7 g.L-1), hyperphagia, polyuria, polydipsia, and loss of body weight. Sorbitol levels in lens and sciatic nerve increased in normal and diabetic rats; the increase was higher in diabetic rats. No relationship was shown between glycemia and sorbitol levels. An increased sorbitol level after 8 months of diabetes was found in small intestine and kidney. CONCLUSION: The sorbitol levels increased in lens and sciatic nerve with aging and this process was accelerated by diabetes.

Aging↗

Remineralizing potential, antiplaque and antigingivitis effects of xylitol and sorbitol sweetened chewing gum.

The objective of this study was to investigate the effects of xylitol and sorbitol sweetened chewing gums on plaque accumulation, gingival inflammation and remineralizing potential of plaque following six weeks of use. Twenty-eight consenting individuals were randomly assigned to each of three phases (six weeks in duration) consisting of chewing xylitol gum, chewing sorbitol gum and a non-chewing phase. Subjects chewed one stick after every meal and at two other times for a total of five sticks per day. At the completion of each treatment phase, plaque and gingival indexes were performed and plaque was later collected. Calcium concentration in plaque was determined by atomic absorption spectophotometry. Reductions in plaque indexes were significant for both xylitol gum (p < 0.001) and sorbitol gum (p < 0.05) when compared to the no chewing period. The gingival indexes reflected a decrement in gingival inflammation with both xylitol and sorbitol, though only sorbitol values were statistically significant (p < 0.05). Chewing xylitol and sorbitol gums reduced plaque accumulation and gingival inflammation. In addition, both gums enhanced the remineralization potential of plaque. Xylitol gum showed a superior effect with respect to remineralization potential and plaque reduction. Sorbitol gum had a superior effect on gingival health but not significantly so.

Calcium↗