XYLITOL RESEARCH

Annu Rev Nutr. 1981;1:437-75.

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Nutritional significance of fructose and sugar alcohols.

Wang YM, van Eys J.

Human metabolism of D-fructose, D-sorbitol, D-mannitol, and xylitol has been documented. In humans, sorbitol and xylitol at a single oral dose of 20 g or less and fructose at 70 g or less most likely can be fully absorbed. These there sugars can maintain, either independently or nearly independently, the integrity or the carbohydrate requirement for the growth of cells and animals. The absorption of D-mannitol is no more than 80% and is more laxative. In general, there is no adverse effect other than osmotic diarrhea after oral administration of these sugars. Transient hyperuricemia was seen in some humans. The chronic toxicity of life-long usage of these sugars in humans or other primates is not known. However, a 2-year Turku sugar studies suggested the safety of fructose and xylitol. Two-year feeding experiments in mice and rats indicated possible carcinogenicity of a high-percentage xylitol diet. Abnormalities of cellular growth were also documented in animals fed high percentages of sorbitol and sucrose. Long-term mannitol feeding experiments also revealed an increased incidence of benign thymic tumors in rats. Intravenous feeding of fructose, xylitol, and sorbitol causes major concern. The toxicity is total-dose and infusion-rate dependent. The physical toxicity induced by hyperosmolar effect of the concentrated infusion solutions can be lethal. The primary metabolic toxicities, mainly lactic acidosis and hypruricemia, are reversible. The suggested safe infusion rate of these sugars is 0.25 g/kg/h; sporadic toxic observations have been reported at this or lower doses (0.125 g/kg/h). The combination of glucose, fructose, xylitol, and sorbitol mixture intravenously is in use in Europe due to the critical threshold of each element. There are positive findings from the use of the combination in human illness (114). The beneficial effect of xylitol, mannitol, sorbitol, and fructose in decreasing order has been well documented in the prevention of dental caries in animals and in humans. Oral organisms do not appear to metabolically adapt to xylitol even after 4 years of in vivo exposure. This was based on the quantitation of xylitol dehydrogenase activity in saliva and oral organisms. In addition, a therapeutic and preventive effect for xylitol in human and animal dental caries has been demonstrated. There appears to be at least a theoretical edge in the dietary use of fructose, xylitol, and sorbitol in diabetics.

Metabolism. 1996 Nov;45(11):1354-9.

Effect of glucagon on the xylitol-induced increase in the plasma concentration and urinary excretion of purine bases.

Yamamoto T, Moriwaki Y, Takahashi S, Ohata H, Nakano T, Yamakita J, Higashino K.

Third Department of Internal Medicine, Hyogo College of Medicine, Japan.

To investigate whether glucagon affects the xylitol-induced increase in the production of purine bases (hypoxanthine, xanthine, and uric acid), the present study was performed with five healthy subjects. Intravenous administration of 300 mL 10% xylitol increased the plasma concentration and urinary excretion of purine bases, erythrocyte concentrations of adenosine monophosphate (AMP) and adenosine diphosphate (ADP), and blood concentrations of glyceraldehyde-3-phosphate (GA3P) + dihydroxyacetone phosphate (DHAP), fructose-1,6-bisphosphate (FBP), and lactic acid; it decreased the blood concentration of pyruvic acid and the plasma concentration and urinary excretion of inorganic phosphate. However, intravenous administration of 1 mg glucagon together with xylitol reduced the xylitol-induced changes in oxypurines, pyruvic acid, GABP + DHAP, and FBP, whereas it promoted the xylitol-induced increase in the urinary excretion of total purine bases and did not affect the xylitol-induced increase in the plasma concentration of total purine bases. In addition, in vitro study demonstrated that sodium pyruvate prevented the xylitol-induced degradation of adenine nucleotides in erythrocytes. These results suggested that gluconeogenesis due to glucagon increased the production of pyruvic acid, accelerated the conversion of NADH to NAD, and thereby prevented both the xylitol-induced degradation of adenine nucleotides in organs similar to erythrocytes and the inhibition of xanthine dehydrogenase in the liver and small intestine, resulting in decreases in the plasma concentration and urinary excretion of oxypurines. However, it was also suggested that in the liver storing glycogen, glucagon-induced glycogenolysis accumulated sugar phosphates, resulting in purine degradation, since the xylitol-induced increase in the NADH/NAD ratio partially blocked glycolysis at the level of GABP dehydrogenase. Therefore, administration of glucagon together with xylitol may synergistically increase purine degradation more than xylitol alone, despite decreases in the plasma concentration and urinary excretion of oxypurines.

J Clin Endocrinol Metab. 1993 Aug;77(2):388-92.

Carbohydrate metabolism and urinary excretion of calcium and oxalate after ingestion of polyol sweeteners.

Nguyen NU, Dumoulin G, Henriet MT, Berthelay S, Regnard J.

Explorations Fonctionnelles Renales Metaboliques et Endocriniennes, Centre Hospitalier Universitaire, Besancon, France.

Polyols are widely used instead of glucose and sucrose in sweets and dietary products because they are barely cariogenic, and their energy value is lower. In addition, it has been shown that calciuria and oxaluria increase after an oral glucose (Glu) load. We, therefore, investigated the effects of a single polyol ingestion on carbohydrate, calcium, phosphate, and oxalate metabolism in 10 healthy subjects. On 5 experimental days, subjects ingested 20 g Glu, Lycasin (Lyc), Maltisorb (Mal), sorbitol (Sor), or xylitol (Xyl). Glu, Lyc, and Mal intake caused an increase in glycemia [respectively, +34% (P < 0.001), +15% (P < 0.001), and +15% (P < 0.001)], insulinemia [respectively, +358% (P < 0.001), +88% (P < 0.05), and +94% (P < 0.01)], and C-peptide level [respectively, +170% (P < 0.001), +15% (P < 0.01), and +15% (P < 0.001)]. Conversely, no change occurred in glycemia, insulinemia, or C-peptide levels after ingestion of Sor or Xyl. Urinary calcium increased after Glu (+64%; P < 0.01) and Xyl (+74%; P < 0.01) intake, and urinary phosphate increased after Xyl (+27%; P < 0.05), but decreased after a Glu load (-68%; P < 0.01). Only Xyl increased urinary excretion of oxalate (+53%; P < 0.05). Our results suggest that ingestion of polyols causes a much lesser pancreatic stimulation than Glu intake. Also, Lyc, Mal, and Sor sweeteners have no effect on urinary excretion of calcium and oxalate, whereas calciuria and oxaluria increase after Xyl ingestion.

: J Nutr. 1994 Jun;124(6):874-81.

Bone repair in calcium-deficient rats: comparison of xylitol+calcium carbonate with calcium carbonate, calcium lactate and calcium citrate on the repletion of calcium.

Hamalainen MM.

Institute of Dentistry, University of Turku, Finland.

The potential value of xylitol in calcium therapy was evaluated by comparing the effect of dietary xylitol (50 g/kg diet) + calcium carbonate with the effects of calcium carbonate, calcium lactate and calcium citrate on bone repair of young male rats after the rats consumed for 3 wk a calcium-deficient diet (0.2 g Ca/kg diet). After this calcium-depletion period, the rats were fed for 2 wk one of four diets, each containing 5 g Ca/kg diet as one of the four dietary calcium sources. The diet of the control animals was supplemented with CaCO3 (5 g Ca/kg diet) throughout the study. The Ca-deficient rats showed low bone mass, low serum calcium and high serum 1,25-dihydroxycholecalciferol, parathyroid hormone (1-34 fraction) and osteocalcin concentrations. They also excreted magnesium, phosphate and hydroxyproline in the urine in high concentrations, and had high bone alkaline phosphatase and tartrate-resistant acid phosphatase activities. Most of these changes were reversed by the administered of the calcium salts. The highest recoveries of femoral dry weight, calcium, magnesium and phosphate were observed in the groups receiving xylitol+CaCO3 and calcium lactate. Calcium lactate and calcium citrate caused low serum phosphate concentration compared with rats receiving CaCO3 and with the age-matched Ca-replete controls. Xylitol-treated rats excreted more calcium and magnesium in urine than did the other rats, probably due to increased absorption of these minerals from the gut. These results suggest that dietary xylitol improves the bioavailability of calcium salts.

· Glucose, fructose, and xylitol in postoperative hypocaloric parenteral nutrition.

Behrendt W, Raumanns J, Hanse J, Giani G.

Clinic of Anaesthesiology, University of Technology Aachen, FRG.

The aim of the study was to use glucose, fructose and xylitol as alternative carbohydrates in hypocaloric parenteral nutrition (HPN) and to investigate their different nutritional effects. Twenty-four patients who had undergone elective gastrointestinal resection were examined in a prospective randomized study. Only metabolically normal patients between 30 and 65 years of age were admitted to the study. No patient with a body weight more than 20% above or below the normal weight of the patients was admitted. The study period extended from the operation day to the fifth postoperative day. The patients were given approximately 1.1 g amino acids and approximately 2.9 g carbohydrates per kg/B.W. and day using either glucose, fructose or xylitol as carbohydrates. The mean plasma glucose concentrations ranged between 6 and 8 mmol/l without insulin being supplied. There were no significant differences between the groups. However, the administration of glucose led to a somewhat larger dispersion range of the values. The labile plasma proteins (transferrin, prealbumin, retinol-binding protein) in the 3 groups revealed almost identical concentration courses. With N-losses between 51 and 57 g/4 days, only slightly negative cumulative N-balances were calculated (-4 to -13 g/4 days). No significant differences were observed between the 3 groups in the level of the urea-N production rates. Advantages which favor a general administration of fructose/sorbitol or xylitol in HPN could not be found in our investigation.

Biotechnol Bioeng. 2002 Jul 20;79(2):165-9.

Metabolic behavior of immobilized Candida guilliermondii cells during batch xylitol production from sugarcane bagasse acid hydrolyzate.

Carvalho W, Silva SS, Converti A, Vitolo M.

Department of Biotechnology, Faculty of Chemical Engineering of Lorena, Rodovia Itajuba-Lorena, km 74.5, Lorena, S.P., Brazil, 12600-000.

Candida guilliermondii cells, immobilized in Ca-alginate beads, were used for batch xylitol production from concentrated sugarcane bagasse hydrolyzate. Maximum xylitol concentration (20.6 g/L), volumetric productivity (0.43 g/L. h), and yield (0.47 g/g) obtained after 48 h of fermentation were higher than similar immobilized-cell systems but lower than free-cell cultivation systems. Substrates, products, and biomass concentrations were used in material balances to study the ways in which the different carbon sources were utilized by the yeast cells under microaerobic conditions. The fraction of xylose consumed to produce xylitol reached a maximum value (0.70) after glucose and oxygen depletion while alternative metabolic routes were favored by sub-optimal conditions.