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The effect of long-term consumption of refined xylitol on the natural populations of S. mutans in the human oral cavity has been investigated. Fifty-four S. mutans strains were isolated from adults and children who had been consuming commercial food products containing xylitol for a period of from 1 1/2 to 10 years. Twenty isolates were also obtained from control subjects who had never consumed xylitol-containing commercial food products. The inhibitory effect of xylitol on the isolated strains was determined by monitoring growth on glucose in the presence or absence of xylitol. This was used to define the sensitivity of each isolate to xylitol. Phosphoenolpyruvate:sugar phosphotransferase (PEP-PTS) activities were measured by means of the soluble and membrane fractions prepared from strains from both study populations. It was found that 87% of the fresh isolates from xylitol consumers were xylitol-resistant (XR), compared with only 10% of the strains isolated from the control subjects. The XR strains had low constitutive fructose PTS activity and very low xylitol-phosphorylating capacity. The xylitol-sensitive (XS) strains, however, had much higher levels of constitutive fructose PTS activity and phosphorylated xylitol 16 times more rapidly than did the XR strains. Evidence for the phosphorylation of xylitol by a fructose PEP-PTS in the XS strains was obtained. The growth inhibition by the intracellular accumulation of non-metabolizable toxic xylitol phosphate and its prevention by the presence of fructose are discussed.

The aim of parenteral nutrition should be to optimise fluid, energy and nitrogen balance. In the post-traumatic or post-operative phase a stress induced glucose intolerance may occur and it may become difficult to meet the patient's energy requirements with glucose alone. For these reasons the use of sugar substitutes (fructose, sorbitol and xylitol) in combination with glucose is recommended as an alternative. Patients receiving a mixed sugar solution of glucose, fructose and xylitol at a ratio of 1:2:1 require less exogenous insulin and yet maintain a lower blood glucose concentration. Used in limited quantities, we encountered no side effects either in patients undergoing elective surgery or requiring intensive care.

In a clinical study 12 healthy volunteers consumed a standardized basal diet consecutively supplemented with either sucrose (6 days, 80-100 g/day) or xylitol (18 days, 40-100 g/day). Pre- and post-periods with normal diet were also included in the study. With the exception of a few cases of diarrhoea at the start of the xylitol administration no other clinical signs indicated treatment-related side-effects. Whereas during the xylitol period plasma cholesterol values tended to be decreased, triglyceride levels remained unaffected. Other parameters (such as urinary calcium and oxalate as well as plasma uric acid) which have been suggested to be influenced by carbohydrate consumption were in fact not altered by the dietary regimen of the present study. A variety of other serum and urinary parameters revealed also no between-treatment differences. It may be concluded from these data under the present experimental conditions that subchronic consumption of considerable doses of sucrose and xylitol respectively reveals no relevant changes of a variety of clinical parameters which would indicate any kind of metabolic intolerance to these sweetening substances.

In 24 diabetic children treated with insulin xylitol was used as a sugar substitute for four weeks in an amount of 30 gms/day. In one case only the xylitol application was terminated before the end of the dietetic period because of diarrhoea. The other children tolerated xylitol fairly well, three of the children found the polyol too sweet. Because of incomplete data, the values of only 18 children were compiled. A significant increase of serum uric acid concentration measuring 1 mg/100 ml was the main side effect of xylitol usage. This effect was favoured by the fact that diabetic children do not use sucrose. As was shown earlier, a sucrose free period is the precondition for the possibility to find a xylitol induced hyperuricemia. In metabolically healthy children the existence of a sucrose induced hyperuricemia is also to be expected, this xylitol effect is, therefore, obviously without pathophysiological significance. Xylitol is suited for use as a sugar substitute in diabetic diet and in caries prophylaxis if the limited dose is observed.

The excretion of urinary acidic metabolites by 10 patients undergoing gastric or biliary tract surgery has been studied. Five patients were infused with xylitol and 5 with glucose. Four of the xylitol-infused patients had hyperglycollic aciduria and 3 of the glucose-infused patients had hyperlactic aciduria. There was no hyperoxaluria. Four of the xylitol-infused patients excreted more tetronic acids than any of the glucose-infused patients. Threonic acid was the predominant tetronic acid excreted by most (4/5) of the xylitol-infused subjects. Erythronic acid predominated in the glucose-infused as in control ambulant non-hospitalised subjects. It is suggested that these changes point to overloading of the transketolase pathway during xylitol infusion.

The effect of peroral administration of xylitol on the absorption of iron and the activities of xanthine oxidase (EC 1.2.3.2) and ferroxidase in rat duodenal wall was studied. Adult male rats were given the basal diet containing 200 g xylitol/kg or the same diet containing no added carbohydrates for 8 weeks. Both feeding groups comprised twelve animals. Xylitol significantly increased serum and liver Fe concentrations with a concomitant, significant increase in the duodenal xanthine oxidase activities, but caused a marginal increase in the duodenal ferroxidase activities. In vitro, sugar alcohols reduced the binding rate of Fe to transferrin. The xylitol-induced increase of Fe absorption may involve the following mechanism: the high intraluminal xylitol concentration of the xylitol-fed rats keeps Fe in the form of a soluble complex for a prolonged period of time, due to the slow absorption of xylitol. The polyol-Fe complex in turn induces xanthine oxidase and ferroxidase formation.

Previous rat caries experiments in our laboratory demonstrated an anti-cariogenic and most probably a remineralizing effect of xylitol. The purpose of the present study was to compare the caries-inhibiting property of xylitol and fluoride in drinking water. The study consisted of two experiments with Osborne-Mendel rats, superinfected with S. mutans. In the first experiment, the rats were fed ad libitum a cariogenic diet containing 20% sucrose and 5% glucose (diet SSP 20/5) and tap water containing 0%, 2%, or 4% xylitol. An additional control group was fed diet SSP 20/5 supplemented with 5% xylitol. In the second experiment, the rats were also fed diet SSP 20/5, but received tap water, demineralized water (both containing less than 0.1 ppm F-), or tap water containing 10 and 40 ppm fluoride. Some animals in the 4% xylitol drinking water group showed a mild osmotic diarrhea for the first four days and a retarded increase in body weight of limited duration. S. mutans colonized to a similar level in all groups of both experiments. Fluoride as well as xylitol in the drinking water reduced the fissure caries scores significantly. However, 10 and 40 ppm fluoride had a more pronounced inhibiting effect on the caries experience than did 4% xylitol in the drinking water or 5% xylitol in the diet.

In orderto find a new sweetner, different products such as xylitol, aspartame, saccharin, lactose and sucrose are tested by a panel of trained subjects. To determine sweetness intensity, we use the multiple paired comparison technique: each judge tested 9 pairs of samples, in each pair one sample is a sucrose solution at a fixed concentration (20 g/l or 60 g/l) and the other solution is made with a sweetner at a variable concentration, but near the reference. The results are in accordance with the data in the literature. The taste quality is determined with solutions or powders. Experiments are performed with either 10 solutions to identify or 2 unknown powders at the same granulometry. In each case sucrose is compared to a sweetner. The statistical analysis shows that xylitol, levulose and the aspartame-xylitol mixture (25.10(-3) g; 1 g) is tasted identical with sucrose. Studies about stability of the mixture are carried out in sealed ampoules with products at pH between 3 and 7 and temperatures between +4 and +120 degrees C. The results show that the aspartame-xylitol mixture with sweetness intensity equal to 5.0 is a good synthetic sweetner to substitute sucrose.

Nitrogen balance and other metabolic activity can be maintained by adequate calorie and protein supply during immediate postgastrectomy period. Despite high intake of protein, great loss of nitrogen seems to occur in urine during infusion with polyalcohol sugars as compared with natural sugars, e.g., glucose, fructose and maltose. The best utilization of amino acids resulting in positive nitrogen balance and energy utilization were shown to be achieved by combined use of Intralipid, glucose, maltose and essential as well as non-essential amino acids in the clinical and laboratory studies.

Field demonstration trials of preventive agents or methods are needed so that the effectiveness and acceptability of such methods can be evaluated when used as part of the prevailing system and life style in a particular community. Agents so tested should have already been shown in a clinical trial to have a positive effect. Field demonstration trials differ from clinical trials in having no traditional control group; the study is not 'blind'; there is no special supervision and there is no special selection of participants. Results of two field demonstration trials, one in a population in Thailand with moderate but increasing caries severity and the other in French Polynesia, where caries severity is very high, are reported. The trials compared the effectiveness of various chewing gum formulations with the effectiveness of a fortnightly supervised sodium fluoride rinse. One gum formulation contained fluoride and was sweetened with sucrose or xylitol and sorbitol, the other was fluoride free and was sweetened with xylitol and sorbitol. The important information from these field trials is that a fluoride-containing chewing gum sweetened with xylitol/sorbitol appears to be effective in controlling caries experience even in communities apparently experiencing an increase of the disease; and that the apparent effectiveness was achieved in a field situation subject to all the problems of a programme not under a rigid clinical trial type of control. The fluoride-containing chewing gum-sucrose regime, in both the trials, and the non-fluoride chewing gum-xylitol/sorbitol regime in the French Polynesia trial failed to exhibit any notable preventive effect.

Effects of complex therapy were examined in 76 patients with anastomositis following operations on the stomach. The intragastric administration of long chain alcohols was shown to improve the evacuation of food masses from the stomach. The volume of the congested gastric content was reduced from 1500 to 300 ml 6-7 days after the beginning of the treatment.

3 groups (6 control persons, 6 patients with liver cirrhosis, 6 patients with diabetes mellitus) were infused with 20% (w/v) carbohydrate mixture (glucose/fructose/xylitol, 1:2:1) for 48 hours. The metabolical status was controlled in defined intervals by means of 39 different laboratory parameters. The infusion rate was supposed to be 0.25 g carbohydrates/kg B. W. and hour. There were no significant changes in blood glucose levels in any of the 3 groups. However we could observe a slight but constant increase in lactate and triglyceride concentrations. Free fatty acids and keton bodies were suppressed on a low level. Only the diabetics showed a significant renal carbohydrate loss with up to 15% of the amount administered. No clinically relevant side effects were observed.

Xylitol has been suggested as a more advantageous calory source for intravenous administration than glucose in certain clinical situation, but the general suitability of intravenous xylitol infusion has not been confirmed. Thirty-middle-aged women were infused with 100 g of xylitol as postoperative fluid therapy after gynaecological laparotomy and general anaesthesia. Another 10 women received 50 g of glucose in a similar manner and served as a reference group. Infusion of xylitol both at the rate of 0.25 g/kg/h (1000 ml 10% xylitol in approx. 8 h) and 0.5 g/kg/h (1000 ml 10% xylitol in approx. 4 h) caused a distinct increase in the serum concentrations of lactic acid, pyruvic acid, and uric acid; such an increase was not seen with glucose infusion. The faster infusion of xylitol also distinctly increased serum bilirubin concentrations. Because of the possibility of lactic acidosis and urate deposits in kidneys, infusion of 100 g or more of xylitol at a rate of 0.25 g/kg/h or faster is not safe for postoperative fluid therapy in routine clinical work.

Due to the metabolic alterations following surgery, glucose is not completely oxidized but is converted into glycogen and lipids. Therefore we analysed 2 groups of 15 patients following surgery. They received parenteral nutrition with identical nitrogen (N = 0.28 g/kg/d) and lipid (1.5 g/kg/d) intake, whereby only the composition of carbohydrates was varied. Group I received exclusively glucose = 0.22 g/kg/h, and group II the combination fructose-glucose-xylitol in a proportion of 2:1:1 at the same infusion rate. The study lasted approximately 10 days. We found decreased exogenous insulin requirements and an increase in the NEFA levels with a maximum on the 3rd and 4th day in group II. There were no significant differences in the levels of either albumin, prealbumin or retinol-binding protein, nor were any hepatic or renal alterations related to the xylitol infusion observed. Xylituria was 6.13 +/- 3% of the amount infused. In our opinion, the partial substitution of glucose in group II led to a better utilisation of the infused energy supply, and to less insulin stimulation, which facilitated the mobilization of endogenous energy sources such as fatty acids, although we did not succeed in increasing the protein synthesis.

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.

After gastric operations, patients were fed completely by the parenteral route. Aminoacids, caloric nutrients and electrolytes were infused simultaneously and continuously 24 hours daily until the fourth postoperative day. The daily supply of aminoacids amounted to 80 g. Glucose, fructose and xylite in equal proportions were used to supply calories. The total daily amount was 605 g. The important electrolytes were contained in the infusion solutions in amounts corresponding to basic requirement. The results of the investigation confirmed that patients can be successfully nourished parenterally after extensive operations with the combined daily additives we have selected.

During parturition, there is an increase in the glucose, pyruvate and lactate levels in the maternal venous blood, as well as an increase in the concentrations of free fatty acids, d-(-)-3-hydroxybutyrate and acetoacetate. Peripartal acetonaemia in the mother can be reduced by infusing solutions which contain xylite. No essential increase in blood lactate levels was seen following in fusion of 0.4 g xylite/kg body weight. The acetone bodies reach the foetal blood via the placenta. It remains to be clarified as to how far they are an important source of energy during the newborn period.

Four groups of six volunteers were given continuous infusions of glucose, fructose, sorbitol and xylitol in a dosage of 0.25 g/kg body weight over 48 hours. All solutions were well tolerated provided that potassium was supplemented in sufficient amounts. During the first 12 hour period of xylitol infusion renal potassium loss was greater than during infusion of all other substrates. No substantial differences in the alterations of the other parameters were noted between glucose and glucose substitutes. The only exception was the rise in serum uric acid concentration during infusion of xylitol and of fructose, which was not noted during infusion of glucose or sorbitol. The concentration of serum bilirubin was elevated during infusion of all four substances. The decrease in serum free fatty acid concentration was equally caused by glucose, fructose, xylitol or sorbitol. The increase in serum triglyceride concentration was observed earlier during the infusion of glucose substitutes as compared to glucose. Blood glucose concentration was only elevated during infusion of glucose. In the post infusion period there was quick rise in fatty acid concentration after cessation of glucose infusion. This normalisation occurred more slowly after stopping fructose and particulary xylitol or sorbitol. These results have no indications for adverse effects of the continuous infusions of glucose or glucose substitutes.

The effects of four day periods of infusions of 600 gm/24 hours glucose and 600 gm/24 hours of a combination of glucose, fructose, and xylitol were compared. This study was performed during total parenteral nutrition of twelve postoperative patients with major complications. The mean plasma glucose level was significantly lower during the infusion of the combination of sugars (154.2+/-19.5 mg/100 ml versus 193.9+/-15.0 mg/100 ml[p is less than 0.005). Furthermore, the required dosage of exogenous insulin was significantly lower (18.9+/-12.3 units/day versus 43.7+/-19.7 units/day [p is less than 0.01). Mean renal carbohydrate losses were 0.85 per cent during glucose infusion and 1.7 per cent during infusion of the combination. The influence of both infusion regimes on values for pH, base excess, lactate, pyruvate, free fatty acids, insulin, sodium, potassium, chloride, magnesium, phosphorus, bilirubin, alkaline phosphatase, SGOT, and SGPT 0.85 has been investigated. No clinical side effects were observed. It is concluded that the administration of the investigated combination of glucose, fructose, and xylitol is justified in patients in whom hyperglycemia during infusion of glucose alone is difficult to control with insulin.

The aim was to assess caries increment as influenced by partial substitution of sucrose by xylitol (X group) over a 2-year period in comparison with systemic fluoride (F group) and restorative treatment only (C group). The study differed from the 3-year field study of the same series primarily in that existing base-line differences were eliminated because the protocol required that all the new subjects entering the institutions in the 1st year were to be included for a 2-year trial. During this period the number of dropouts was 243 (19.9% of all subjects), the final material consisting of 976 children (6-12 years old). The 2-year DMFS increment was 3.8 in the X group, 4.8 in the F group, and 6.0 in the C group. The corresponding ratio (RS) between caries incidence and the tooth surface population at risk was RSX, 4.5; RSF, 5.5; and RSC, 7.5. The xylitol regimen resulted in a lower increment of caries than measured in the F and C groups (p less than 0.001; convariance analysis, with base-line prevalence, number of permanent teeth, and visible plaque index as covariants.

By central venous catheterization, 6 control persons, 7 patients with liver cirrhosis and 6 patients with diabetes mellitus were infused for 48 h with a 20% (w/v) mixture of glucose/xylitol (1:1). The infusion 48 h with a 20% (w/v) mixture of glucose/xylitol (1:1). The infusion rate of 0.125 g monosaccharide/kg/h could be maintained with minor deviations. There were no significant changes in blood glucose levels using this infusion regimen. Lactate levels, however, did increase constantly during the whole infusion period. In the liver group as well as in the diabetic group we could measure values between 1.5 and 3.9 mmol/l. Triglycerides increased solely in the diabetic group. Uric acid concentrations were elevated in all 3 groups. Clinically significant side effects were not observed.

Xylitol, NaF and ZnCl2 in combination inhibited the growth of S. Sobrinus OMZ 176 when added to Brain Heart Infusion broth. Thin-layer chromatography, followed by autoradiography of cell extracts, was used to study the inhibiting mechanism. Glucose uptake was reduced, the glycolysis inhibited at the glucose 6-phosphate- and fructose- 1.6-diphosphate level and the accumulation of xylitol metabolites was increased. These effects in combination probably accounted for the inhibition of growth.

Postoperative hypocaloric peripheral-venous nutrition with the same content of amino acids (1 g/kg BW/d) and carbohydrates (2 g/kg BW/d) was performed in two groups of patients, one group receiving xylitol and sorbitol (1:1), the other pure glucose only. Regarding the behavior of different parameters of the protein metabolism it could be demonstrated, that glucose supply although improving the N-retention by 12% had no significant favourable effect on viscerally synthesized plasma proteins in contrast to the polyols. Because of the nearly identical endogenous insulin stimulation in both groups it can be assumed, that glucose supply inhibits lipolysis completely thus reducing free fatty acids levels in plasma and therefore increasing peripheral insulin sensitivity resulting in enhanced utilisation of the amino acids supplied mainly in muscle. Additionally the improvement in synthesis of visceral proteins supplying polyols can be also due to a specific effect of these substrates, because the known activation of pentose-phosphate-cycle, especially by xylitol, increases RNA-synthesis and therefore lately improving protein synthesis, too.

Basic caloric needs of patients with compensated liver cirrhosis and healthy controls were supplied for 48 h with mixtures of glucose, fructose, sorbite, and xylit. Mixed solutions (20% w/v) containing glucose + fructose (n = 6), glucose + sorbite (n = 36), glucose + xylit (n = 37) in a 1:1 ratio, and glucose + fructose + xylit (n = 6) in a 1:2:1 ratio as well as glucose alone (n = 6) were administered in a dosage of 0.25 g/kg/h each. Utilization of the monosubstances, corresponding blood levels, and the effects on parameters of carbohydrate and lipid metabolism were frequently controlled. In contrast to mixed solutions, infusion of glucose alone caused a pronounced increase of the insulin levels and hyperglycemia in some patients suffering from liver cirrhosis. In both groups infusion of glucose + xylit was accompanied by a rise of uric acid levels. In liver cirrhotics a permanent decrease of phosphate as well as an increase of xylit concentrations were observed. These changes were not seen with xylit lowered to 50%, in glucose + fructose + xylit infusion. Therefore, we recommend to restrict xylit in liver cirrhotics to 100/24 h. No significant changes of blood gas measurements, ph values, hyperlactatemia, or lactic acidosis were seen. There was no difference in the anticatabolic, antilipolytic, and antiketogenic effect of the solutions. The least changes of all controlled parameters were observed with glucose + fructose and glucose + fructose + xylit infusions.