Martti J. Svanberg

Dietary xylitol supplementation prevents osteoporotic changes in streptozotocin-diabetic rats

The effects of 10% and 20% dietary xylitol supplementation on the biomechanical properties, trabeculation, and mineral content of long bones were studied in streptozotocin-diabetic rats. Forty 3-month-old male Wistar rats were divided randomly into four groups of 10. Rats in three groups were administered a single injection of streptozotocin (50 mg/kg body weight) to induce type I diabetes, while animals in the fourth group were given a sham injection of physiological saline. The sham-injected group and one of the streptozotocin-diabetic groups were fed the basal diet, while the two diabetic groups were fed the same diet supplemented with 10% and 20% xylitol (wt/wt). After 3 months, the rats were killed and the long bones were prepared for analysis. The 10% and 20% dietary xylitol supplementation significantly prevented the type I diabetes-induced decrease in the mechanical stress resistance of the tibia in the three-point bending test, the shear stress of the femur in the torsion test, and the stress resistance of the femoral neck in the loading test. No statistically significant differences were found between any groups in the values for strain or Youngs modulus in the three-point bending test, or in the values for the shear modulus of elasticity in the torsion test. These findings indicate that dietary xylitol protects against the weakening of the bone strength properties of both cortical and trabecular bone without affecting the elastic-plastic properties. Supplementation with 10% and 20% dietary xylitol significantly prevented the type I diabetes-induced decrease of humeral ash weight and tibial density. Histomorphometric data for the secondary spongiosa of the proximal tibia showed that 10% and 20% dietary xylitol supplementation also significantly prevented the type I diabetes-induced loss of trabecular bone volume. In conclusion, dietary xylitol supplementation protects against the weakening of bone biomechanical properties in streptozotocin-diabetic rats. This is related to the preserved bone mineral content and preserved trabecular bone volume.

IMPROVED BONE BIOMECHANICAL PROPERTIES IN RATS AFTER ORAL XYLITOL ADMINISTRATION

Abstract. The effects of 5, 10, and 20% dietary xylitol supplementations on the biomechanical properties, histological architecture, and the contents of collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied. Tibiae were used for the three-point bending test, and femurs were used for the torsion and loading test of the femoral neck. The 10 and 20% oral xylitol administrations caused a significant increase of tibial stress, femoral shear stress, and stress of the femoral neck as compared with the controls. Parallel, but not significant, effects were also seen in the 5% xylitol supplementation group. No significant differences in strain or Youngs modulus of the tibiae were detected between the groups. An increased shear modulus of elasticity in femurs was detected in the 20% supplementation group as compared with the controls. The histomorphometrical data for the secondary spongiosa of the proximal tibia revealed that trabecular bone volume was significantly greater in all dietary xylitol supplementation groups as compared with the controls. The bone volume increased along with increasing xylitol content. No significant differences between the groups were detected concerning the amount of collagen per dry weight of organic matrix, the concentrations of pyridinoline or deoxypyridinoline in collagen, or the ratio of these crosslinks. This suggests no xylitol-dependent selective changes in these structures of bone collagen. In conclusion, dietary xylitol supplementation in rats improves the biomechanical properties of bone and increases the trabecular bone volume dose dependently.

Alterations in rat bone composition related to polyol supplementation of the diet

The effect of dietary supplements of xylitol, sorbitol and glucose on bone composition was studied in rats. The supplementation, expressed as a % of the dry diet, was gradually increased up to 20% over 3 weeks and continued for 5 weeks. The control group was fed a stock diet only. Each group consisted of nine rats aged 12 weeks at the beginning of the experiment. Ca, Mg, P, CO3 and citrate were analysed from the femur and Ca and citrate also from the serum and urine. The results showed that xylitol supplementation significantly increased the concentrations of Ca and citrate in bone (P less than 0.001) and sorbitol that of Ca only, whereas glucose slightly reduced both CO3 and citrate. The citrate concentration was found to correlate significantly with Ca and P (P less than 0.001), and also with Mg (P less than 0.002). Both xylitol and sorbitol increased serum Ca and the urinary excretion of Ca and citrate. In conclusion, high xylitol or sorbitol supplementation affects Ca and citrate metabolism. The results suggest a connection between citrate and Ca in bone.

Comparison of the effect of gluconate, lactose, and xylitol on bone recalcification in calcium-deficient rats

The therapeutic value of three calcium absorption promoting carbohydrates, lactose, gluconate and xylitol, in bone calcification was evaluated in 7-week-old male rats which were fed on a semisynthetic Ca-deficient diet for 3 weeks. Lactose + CaCO3, xylitol + CaCO3, Ca-gluconate, or CaCO3 alone were administered to the Ca-deficient rats for 2 weeks; the carbohydrate and Ca contents of the diets were 5% and 0.5%, respectively. The Ca-deficient rats showed a decrease in serum total Ca and ionized Ca2+ and in tibial Ca, Mg, P and density, with a concomitant increase in bone hydroxyproline concentration. Bone and serum tartrate-resistant acid phosphatase activities were increased 2-fold and the serum 1,25(OH)2D3 level 5-fold. Smaller increases were found in serum calcitonin, PTH, alkaline phosphatase and osteocalcin levels. These changes (except calcitonin) were reversed by the administration of Ca and the carbohydrates. It was observed that all three agents improved the recalcification of bones compared with the effect of CaCO3 alone. The effect of lactose and xylitol was superior to that of gluconate. These results suggest advantages in the use of xylitol in Ca-supplements.

Dietary xylitol prevents ovariectomy induced changes of bone inorganic fraction in rats

Thirty-six 3-month-old female Wistar rats were labelled with a single intraperitoneal tetracycline injection. Twenty-four animals were subsequently ovariectomized, while the control group of 12 animals underwent sham operations. All animals received the basal Ewos R3 diet and half of the ovariectomized animals (n = 12) were given an additional 5% dietary xylitol supplementation. Three months later, following the collection of blood and urine, the animals were killed by decapitation. The tibiae were detached and prepared for chemical and other studies. The weight and density of the tibiae were measured. The right tibiae were dried and pulverized for chemical analysis of calcium, phosphorus and citric acid. The total inorganic fraction was determined by ashing the powdered bone. The left tibiae were cross-sectioned at the tibio-fibular junctions for the measurement of the width of periosteally formed bone, which was identified by tetracycline fluorescence. The examination of mineral content of bone was performed by scanning electron microscopy, using an electron probe microanalytic technique. The results indicate that the supplementation of the diet with 5% xylitol had a protective effect against the loss of bone mineral after ovariectomy in the rat. This was clearly seen in tibial density and in the inorganic fraction of the bone, and in the concentrations of bone Ca and phosphorus. Ovariectomy caused a doubling in periosteal bone formation relative to the controls, whereas the growth of the periosteally formed bone was somewhat reduced following xylitol supplementation as compared with ovariectomy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Diminished bone resorption in rats after oral xylitol administration: A dose-response study

The effects of 5, 10, and 20% dietary xylitol supplementations on the resorption of bone were studied. The resorption was measured by the urinary excretion of [3H] radioactivity from [3H]tetracycline-prelabeled rats. The 10 and 20% oral xylitol administrations caused a significant decrease in the excretion of [3H] as compared with the control group with no xylitol supplementation. The effect was detected as early as 2 days after the beginning of xylitol-feeding and was maintained throughout the experimental period of 31 days. The retarding effect on bone resorption was about 25% in the 10% xylitol group, about 40% in the 20% xylitol group, and undetectable in the 5% xylitol group. The amount of preserved [3H] radioactivity in the tibiae of the 10 and 20% xylitol groups after the experiment clearly exceeded the valties of the control group. The mechanism of the retarded bone resorption caused by dietary xylitol still remains obscure, but an increased absorption of calcium may be involved. In conclusion, dietary xylitol supplementation in rats seems to retard the bone resorption in a dose-dependent way. The effect is achieved rapidly and is maintained at least over a period of 1 month xylitol feeding.

Dietary Xylitol Retards the Ovariectomy-Induced Increase of Bone Turnover in Rats

Abstract. The effects of 10% dietary xylitol supplementation in ovariectomized rats were studied on the degradation of bone organic and inorganic structures. The osseal concentrations of hydroxyproline, pyridinoline, and deoxypyridinoline were analyzed by high-performance liquid chromatography. Bone resorption was measured in [3H]tetracycline-prelabeled rats by urinary excretion of 3H, and by the amount of 3H preserved in bone. Bone trabeculation was measured by a computer image analyzer from sections stained by the method of von Kossa. The amount of collagen in bone organic fraction was lower in ovariectomized rats as compared with the sham-operated controls. This most likely is partly a consequence of an increased resorption, and partly a consequence of a higher proportion of immature periosteal bone in the ovariectomized animals, leading to a higher ratio of noncollagenous protein to collagen. The number of pyridinium crosslinks was lower in proportion, indicating no selective changes in the structure of collagen. Dietary xylitol significantly retarded the ovariectomy-associated decrease in the relative amount of collagen and the number of its mature crosslinks. Ovariectomy doubled the excretion of 3H and caused a significant decrease in the amount of 3H preserved in bone; both these changes were significantly retarded by the 10% dietary xylitol supplementation. Ovariectomy significantly decreased the volume of bone trabeculae, but this effect was also significantly inhibited by the xylitol supplementation in the diet. In conclusion, these findings suggest a dietary xylitol-induced normalizing effect on the rate of bone turnover in ovariectomized rats.

Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis

BackgroundXylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy.ResultsWe evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank test).ConclusionXylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis.

Increased Bone Volume and Bone Mineral Content in Xylitol-Fed Aged Rats

Background: Our previous studies have shown that dietary xylitol supplementation protects against the loss of bone mineral after ovariectomy. The ovariectomy-induced decrease in trabecular bone volume is significantly retarded by dietary xylitol. Objective: To study whether dietary xylitol can protect against bone loss also during aging, a long-term experimental study was performed with rats. Methods: Twenty-four male Sprague-Dawley rats were divided into two groups. The rats in the control group were fed a basal RM1 diet, while the rats in the experimental group were continuously fed the same diet supplemented with 10% (w/w) xylitol. The rats were killed after 20 months. Their tibiae were used for the analyses of bone density and trabecular bone volume, and their femurs were used for the scanning analyses with peripheral quantitative computed tomography (pQCT). Results: The tibial density of the xylitol-fed aged group (1.73 ± 0.14 g/mm3) was significantly greater than that of the aged group without xylitol (1.56 ± 0.14 g/ mm3). The trabecular bone volume of the xylitol-fed rats was 21.2 ± 4.0%. It was significantly greater than that of the rats not receiving xylitol (9.3 ± 4.3%). The pQCT-measured cortical bone mineral density and the pQTC-measured cortical bone mineral content of the femoral diaphysis were significantly greater in the xylitol-fed group than in the control group. The trabecular bone mineral density and the trabecular bone mineral content of the femoral distal metaphysis were also significantly greater in the xylitol-fed group than in the non-xylitol group. The total bone mineral density and the total bone mineral content of the femoral neck in the xylitol-fed aged group significantly exceeded those in the aged group without xylitol supplementation. Conclusions: A continuous moderate dietary xylitol supplementation leads to increased bone volume and increased bone mineral content in the long bones of aged rats. This indicates a xylitol-induced protection against aging-related osteoporotic changes.

Morphological analysis of dentine formation in young rat molars during the recovery phase with calcium alone or combined with xylitol following a low-calcium dietary regimen

The effects of dietary calcium deficiency and subsequent replenishment of the diet with calcium alone or with xylitol were studied. Thirty 3-week-old Wistar rats were labelled with an i.p. tetracycline injection. Twenty rats were fed a diet with 0.026% calcium (Ca-deficient); 10 received a 0.5% Ca diet (controls). After 3 weeks the tetracycline labelling was repeated. Replenishment of the diet was introduced for Ca-deficient rats, and 10 received additional 5% xylitol in the diet. After 4 weeks the labelling was repeated and the animals were decapitated. Dentine formation was measured by the tetracycline stripes in the lower first and second molars. Calcium deficiency during the first 3 weeks reduced dentine formation. In the control and xylitol groups, a much smaller amount of dentine was formed during the recovery period. With Ca alone, dentine formation was faster than in the controls or Ca-xylitol group and did not differ from the Ca-deficient period. These results indicate that in rat molars the odontoblasts can accelerate the rate of dentine formation when calcium is restored to the diet, at least during primary dentinogenesis. This effect was not seen when 5% xylitol was added to the replenishment diet.