Multigeneration Reproduction Study of Lactitol in Rats

Abstract

Lactitol is a disaccharide sugar alcohol (polyol) which holds promise as a reduced calorie, noncariogenic sugar substitute. In a multigeneration reproduction study, lactitol was fed to Wistar-derived Cpb:WU rats of both sexes throughout three successive generations at dietary concentrations of 0, 2, 5, and 10%. A comparison group receiving a diet with 20% lactose was included during the F., generation. The initial mating comprised 20 male and 40 female rats per group. For subsequent matings, 10 males and 20 females were used. In each generation, two litters were reared until they were at least 3 weeks old. Fertility was uniformly high in all treatment groups throughout the study and the feeding of lactitol was not associated with any adverse effects on fertility and reproductive performance. However, growth rates and survival were slightly decreased in pups of the 10% lactitol group, except in F3 litters where no effect of lactitol on survival was seen. In the 20% lactose group of the F, generation, a similar growth retardation and decreased survival was seen. The second litter of third-generation rats (F3b) was subjected to gross and histopathological examination 4 weeks after weaning. F3b rats fed 5 or 10% lactitol showed cecal enlargement which was not associated with any morphological alterations and which is commonly seen in rodents fed polyols or slowly digestible carbohydrates. In some F3b males of all dosage groups, an opaque appearance of the liver cell cytoplasm was noted. However, this effect was not dose related and was not accompanied by any other hepatic changes in the lactitol groups. Since this phenomenon was not seen in older rats or after chronic administration of lactitol, it was considered to be a transient manifestation of an altered metabolism in young rats. All other histopathological findings were equally distributed between control and test animals, or occurred in one or a few rats only. It is concluded that lactitol administered in the diet to three successive generations of rats at levels up to 10%, has no adverse effects on reproductive performance in either sex. The slight developmental delay which occurred in some generations, has been observed earlier with other polyols and may be attributed to the poor digestibility of these compounds.