Xylitol: an update. Recent studies, indications.
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Biomedical subjects
Publications and source records attributed to A Scheinin.
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Examination of several human studies shows the relationship between sugar intake and dental caries to be complex and partly independent of dosage. Under certain conditions frequent consumption, even in combination with surprisingly low dosage, may lead to high caries incidence. The potential use of sugar substitutes may be based on the concept of replacing sucrose particularly in foodstuffs proven to be highly cariogenic. So far, the evaluation of the cariogenicity of specific sugar substitutes has usually been carried out in comparison to sucrose. Glucose and fructose have thus been found somewhat less cariogenic than sucrose. Some polyols, however, may be considered virtually or completely noncariogenic in man. The low caries incidence observed in the clinical trials and most of the experimental studies have to be viewed as a natural consequence of the microbiological and biochemical behavior of these substances. As an entity, perorally administered polyols should be considered to stimulate a number of existing defense mechanisms to caries.
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This survey concerns the essential findings in two clinical trials. The first study involved almost complete substitution of sucrose (S) by fructose (F) or xylitol (X). After 2 years the mean DMFS-increment was 7.2 in the S-group, 3.8 in the F-group, and 0.0 in the X-group. The second study comprised partial substitution, the effects of a S- or X-containing chewing gum being compared during 1 year. The subjects consumed 4.0 chewing gums per day in the S-group and correspondingly 4.5 in the X-group. In the S-group the caries incidence assessed independently by clinical and radiographical means was significantly higher than in the X-group. It is concluded that the metabolic studies indicate the relative safety of perorally administered xylitol at the present dosage levels. In view on the findings in the chewing gum study it is suggested that the non- and anti-cariogenic properties of xylitol principally depend on its lack of suitability for microbial metabolism and the physico-chemical effects in plaque and saliva brought about through low and repeated dosage.
The aim of this study was to develop a planimetric, automatic method for evaluation of the extension and volume of plaque. Series of color macrophotographs of stained plaque were analyzed with a digitizer entering Cartesian coordinate data from the graphic records in a calculator. Estimations were carried out on the reproducibility, discriminatory power, and time required for the planimetric analysis. In addition, the ratios between values obtained before and after reproducible cleansing were interpreted as measurement of the adhesion of plaque in vivo.
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The purpose was to study differences in the caries increment rate as influenced by various sugars. The trial involved almost complete substitution of sucrose (S) by fructose (F) or xylitol (X) during a period of 2 years. There were no significant initial differences as to caries status between the prospective sugar groups; 35 subjects in the S-group, 38 in the F-group, and 52 in the X-group. During the entire study 10 subjects discontinued or were excluded. The clinical and radiographical observer error was reported and discussed. After 2 years the mean increment of decayed, missed and filled tooth surfaces was 7.2 in the S-group, 3.8 in the F-group, and 0.0 in the X-group. The weakness of the DMFS-index in not showing the development of new secondary caries and the increase in size of the lesions was overcome by expressing the caries activity in terms of indices showing the total quantitative and qualitative development. The results showed a massive reduction of the caries increment in relation to xylitol consumption. Fructose was found to be less cariogenic than sucrose. It was suggested that the non- and anticariogenic properties of xylitol principally depend on its lack of suitability for microbial metabolism and physico-chemical effects in plaque and saliva.
125 voluntary subjects, divided into three groups, were originally chosen to participate in a two-year trial in which the dental and general effects of the consumption of sucrose (S 35), fructose (F 38) and xylitol (X 52) were elucidated through an extensive clinico-chemical analysis plan. Additionally 2 edentulous subjects were included in the X-group for survey of the general metabolic effects only. The subjects were given free of charge a versatile assortment of foodstuffs sweetened with either S, F or X. Using special distribution and control systems, the subjects were handled and controlled so that an almost comparable consumption of the products was achieved throughout the trial. The mean individual monthly intake of S, F and X was 2.2, 2.1 and 1.5 kg, respectively. The highest daily amounts of S, F and X per person varied between 200--400 g. The cooperation of the subjects completing the study in the F- and X-groups was 97%, expressed as the intake frequency of the correct sugar. Ten persons discontinued or were otherwise excluded for a diversity of reasons. No health problems were observed, except for transient osmotic diarrhoea in the X-group. These symptoms gradually disappeared and occurred later in the trial in the X-group almost to the same extent as in the S- and F-groups.
Plaque and whole saliva samples of the subjects of the Turku sugar studies were analyzed for several enzymes and biochemical compounds. Strict xylitol diet maintained throughout the study a 50% lower quantity of plaque than the sucrose of fructose diets. Decreased plaque and whole saliva lactate concentration, diminished activity of salivary amylase, and reduced hydrolysis rate of sucrose in plaque and whole saliva were observed in relation to xylitol consumption. The xylitol diet also reduced the ratio of glucose to proteins in plaque. On the other hand, increased activity in plaque of alpha- and beta-glycosidases (against p- and o-nitrophenyl derivatives), fucosidase and aspartate transaminase, as well as increased activity of proteinases and lactoperoxidase in saliva were found in connection with xylitol consumption. The fructose diet caused less clear differences when compared to sucrose, but the experiments indicated a selectivity of the effects of dietary carbohydrates on the biochemistry of whole saliva, plaque and salivary glands. The results contribute in explaining the cariostatic effects of xylitol and the lower coriogenicity of fructose when compared to sucrose.
The possible qualitative and/or quantitative alterations in the proportions of cultivable groups of oral microorganisms were analysed during a clinical trial involving the consumption of fructose (F) or xylitol (X) in comparison to sucrose (S). Supragingival plaque samples and paraffin-stimulated saliva were collected from 115 subjects. The samples were dispersed by sonication, diluted stepwise, plated on blood sugar, Mac Leod agar, Mac Concey agar, Rogosa S.L. agar, and Sabouraud agar plates and incubated anerobically and/or aerobically. The number of the total colony forming units (CFU) on blood agar plates in anaerobic incubation was about 1-3 X 10(9)/ml saliva and 1-4 X 10(8)/mg plaque and in aerobic respectively 5-18 X 10(8)/ml saliva and 10(8)/mg plaque. The total CFU on Mac Leod agar was of a similar order of magnitude. The variation between subjects and consecutive determinations was of a similar order of magnitude. The variation between subjects and consecutive determinations was relatively large. The arithmetic mean of the total CFU on Mac Concey agar was about 1-5 X 10(5)/ml saliva, on Rogosa S.L. agar 6-130 X 10(3)/ml saliva and on Sabouraud about 1-2 X 10(3)ml saliva, all in aerobic incubations. Replacement of dietary sucrose with xylitol did not affect the proportion of major microbial categories in saliva or dental plaque. The percentage of typical streptococcal colonies on blood agar was of a similar order of magnitude (about 60-70%) during the diets. The arithmetic and geometric means of the total CFU values on Rogosa and Sabouraud agar plates were significantly lower in the X-group than in the S- or F-groups after a diet period of some months. It was thought that the reason for the reduction of acidogenic and aciduric oral flora in the X-group was partly due to the fact that xylitol is generally not metabolized by these microorganisms.
Dental plaque samples collected from the subjects during the last 20 months of the 2 year trial were subjected to quantitative and qualitative analysis of the occurrence of S. mutans, S. sanguis, S. salivarius and the total growth on phenol red agar. Lyophilized plaque samples were homogenized and incubated on a sucrose containing medium under anaerobic conditions. In addition, the pH-values were measured after incubation of the mixed plaque flora in media containing 1% respectively xylitol(X), sorbitol, sucrose (S), fructose (F) or no carbohydrates. The results show a significantly lower incidence of S. mutans in the X-group relative to the S- and F-groups. The corresponding difference could not be observed between the S- and F-groups. The logarithmic means and standard deviations of the colony counts of S. sanguis, S. salivarius and total bacteria yielded no significant differences between the 3 sugar groups during the test period. Repeated pH-measurements, carried out at the 4, 12, 18 and 24 month phases, showed that, except in the presence of X, the mean values all fell below the pH-limit of 5.5. In the course of the study, no evidence was obtained of adaption of mutation enabling acidogenic decomposition of X. These findings emphasize the importance of low acidogenic potential in dental plaque, generally paralleled by a low incidence of dental caries.
The effect of chronic consumption of sucrose, xylitol and fructose on lipid, carbohydrate and urate metabolism was studied in conjunction with a clinical trial on the effects of these sugars on dental caries. No consistent differences were found in serum triglycerides, glucose, insulin, urate, lactate, or pyruvate concentrations or in the urinary excretion of urate between the groups using sucrose, fructose or xylitol as the dietary sweetener. Serum cholesterol tended to be lower in the fructose than in the xylitol group, but the difference disappeared when subjects with initial high serum cholesterol in the baseline examination were excluded from the calculations. The results suggest that the effects of peroral fructose and xylitol on the metabolic parameters studied in this investigation do not differ from that of sucrose.
Detailed biochemical analyses of peroxidases in saliva, plaque and gingival exudate samples were carried out in view of the preliminary findings that the peroxidase activity of centrifuged oral fluid was considerably higher in the xylitol group than in the fructose or Sucrose groups. Chromatographic experiments revealed the activity which was increased due to the intake of xylitol, to be attributed to the involvement of the salivary lactoperoxidase, and not to enzymes formed in plaque or leucocytes. There were no significant differences between the sugar groups in the concentration of thiocyanate ions (mean 92 mg/l) and ionized iodine (mean 1.6 mug/l), but the concentration of ionized fluorine in saliva was lower in the xylitol group (0.128 mg/l) than in the other groups (0.150 mg/l). There were no clear differences in the salivary redox potential between the sugar groups. It is evident that various sugars selectively affect the enzyme and other production of the salivary glands. Xylitol-induced elevation of the salivary lactoperoxidase activity and the cariostatic properties of xylitol may partly be interrelated phenomena due to the antibacterial properties of lactoperoxidase.
Pooled and individual serum samples of subjects on long-term sucrose, xylitol and fructose diets were analyzed for Ca, Mg, K, Na inorganic phosphate, bilirubin, ascorbate, alkaline and acid phosphatase, amylase, transaminases, lactate dehydrogenase, and amino acids. Most serum samples were obtained from the last phases of the two-year dietary regimen. Significant differences between the three experimental groups were not found with regard to any of the compounds or enzymes studied. Almost significant differences were observed for amylase which was lower in the xylitol and the fructose groups than in the sucrose group, all these values being within the normal range. The results indicate that xylitol and fructose do not induce significant changes in liver function tests, nor in serum level of electrolytes, ascorbate or serum enzymes when their oral administration takes place in the same scale as that of sucrose.
The aim was to study possible alterations in the microbial flora of plaque and saliva in relation to partial substitution of dietary sucrose with xylitol. The development of plaque index values was observed simultaneously. These observations were carried out during a 1-year clinical trial, the effects of sucrose (S) and xylitol (X) chewing gum on the incidence of dental caries being observed in 100 young adults. Paraffin-stimulated saliva samples were diluted stepwise and cultivated on Rogosa S.L. agar and Sabouraud agar aerobically. Lyophilized dental plaque samples were cultivated on phenol red agar under anaerobic and aerobic conditions. The pH-values were measured after incubating the mixed plaque flora for 1 and 7 days in the presence of various sugars. Both the arithmetic and geometric means of the total CFU values on Rogosa S.L. agar decreased in the S-group at the 6-month phase but returned to the starting level after one year, whereas in the X-group they decreased or remained on the starting level. At the 6-month phase the difference between the groups was significant (U-test, p = 0.0013) and almost significant (U-test, p = 0.0569) at the end of the study. No significant differences or changes could be seen between or within the groups on Sabouraud agar. The geometric mean values of S. sanguis and S. mutans as well as the total CFU values on phenol red agar decreased considerably in both the S- and X-groups, but no significant differences could be detected in any of the streptococcal counts between the groups. The pH of the carbohydrate-containing culture media infected with mixed dental plaque significantly decreased, with the exception of the xylitol containing ones in which the pH values were not lowered even after 7 days' incubation. A significant decrease in plaque formation in relation of chewing per se was demonstrable. The difference in the plaque index values equalling or exceeding 2 was significant between the S- and X-groups. No bacterial adaptation to utilize xylitol occurred during the trial.
The aim was to study eventual physico-chemical changes occurring in whole saliva due to sweetened and unsweetened stimulators. The assay was carried out in 10 female subjects with regard to changes of pH, buffering capacity and electrolytes in saliva as influenced by chewing of fructose, sucrose, sorbitol and xylitol gum, gum base and paraffin. The flow rate of saliva was measured in relation to use of xylitol and sucrose chewing gum and unsweetened gum base. These sweeteners increased significantly the salivary flow rate in comparison to the unsweetened gum base. Generally, xylitol and sorbitol on one hand, and sucrose and fructose on the other, behaved in an almost similar way. Increased buffering capacity and elevation of pH saliva was found in the presence of the polyols tested.