2.1. Xylitol

Xylitol is a five-carbon polyalcohol, pentitol (Figure 2-1), which is widely distributed in nature. Most fruits, berries and plants contain xylitol, the richest natural sources being plums, strawberries, raspberries, cauliflower and endives (Washüttl et al. 1973). Xylitol is also an intermediate of mammalian carbohydrate metabolism. In human body, 5-15 grams of xylitol is formed daily (Hollman et al. 1964).

Endogenous xylitol is produced in the liver from L-xylulose by an NADP-linked dehydrogenase, as a metabolite of the glucuronate-xylulose pathway (Touster et al. 1956). The function of this cycle is obscure, but production of glucuronic acid for synthetic processes and detoxification reactions has been assumed (Touster 1974, Sochor et al. 1979).

Ingested xylitol is absorbed by passive or facilitated diffusion from the intestine (Bässler 1969, Lang 1971). The absorption rate is quite slow, which means that high oral doses may induce transient osmotic diarrhea. Unadapted persons can consume 30-60 grams oral xylitol per day without side effects (Mäkinen & Scheinin 1975). A unique feature of xylitol is the adaptive enhancement of intestinal absorption by continuous xylitol administration (Lang 1971). Proposed adaption mechanisms involve induction of polyol dehydrogenase activity in the liver (Bässler 1969), and selection of intestinal microflora (Krishnan et al. 1980). After adaptation up to 400 grams of xylitol have been taken daily without side effects (Mäkinen & Scheinin 1975).

Xylitol is apparently excreted by simple glomerular filtration (Wyngaarden et al. 1957). Although there is no reabsorptive mechanism for xylitol (Lang 1969), very little is excreted in the urine, probably due to the fast diffusion from the blood to the tissues (Demetrakopoulos & Amos 1978). The net xylitol utilization in humans is over 90 % after moderate xylitol administration (Lang 1969).

Most of the exogenous xylitol is metabolized in the liver (Jakob et al. 1971, Wang & vanEys 1981), although other tissues like kidney, testes, adipose tissue, adrenal cortex, muscles and erythrocytes are also able to metabolize it (Lang 1969, Wang & Meng 1971). Xylitol is oxidized mainly to D-xylulose by a non-specific NAD-linked polyol dehydrogenase (Smith 1962, for review see Froesch & Jakob 1974), which then enters the pentose phosphate shunt via D-xylulose-5-phosphatase. Another possible pathway of xylitol metabolism is oxidation to L-xylulose by a specific NADP-linked polyol dehydrogenase. In both these reactions a reduced redox state is produced (The ratios NADH/NAD and NADPH/NADP increased), which has been regarded as a primary metabolic effect of xylitol (Froesch & Jakob 1974). The final metabolic products of xylitol in the liver are glucose and glycogen. (Froesch & Jakob 1974).

Xylitol is used as a sugar substitute because of its anticariogenic properties (for review see Mäkinen 1994). Xylitol can also be used in the diet of diabetic subjects, because it is slowly absorbed, its initial metabolic steps are independent of insulin, and it does not cause rapid changes in blood glucose concentration (Lang 1971, Förster 1974). Furthermore, xylitol is used as a source of energy in intravenous nutrition, because tissues can use xylitol under postoperative and posttraumatic conditions, when considerable insulin resistance prevents the effective utilization of glucose (Georgieff et al. 1985). Recently, xylitol-containing chewing gum has been shown to reduce the occurence of acute otitis media in day-care children (Uhari et al. 1996).