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.(ABSTRACT TRUNCATED AT 400 WORDS)