2.2. Xylitol in mineral metabolism

Xylitol increases calcium absorption from the gut in rats (Hämäläinen et al. 1985). This effect is independent of vitamin D action, and it is suggested to proceed via passive diffusion (Hämäläinen et al. 1985). The exact mechanism behind this is not known, but increased osmotic pressure in the intestine (Pansu et al. 1976), the removal of an energy barrier to calcium movement (Hauschildt et al. 1981), and complex formation between xylitol and calcium (Angyal 1974) have been suggested. Complexed multivalent metal cations may remain soluble at the nearly neutral pH of the gut lumen, leading to a prolonged absorption process (Hämäläinen & Mäkinen 1989a). In addition, the chelators protect the cation from forming complexes with other ligands that may inhibit absorption (Schubert 1981). To be utilized, the metal cation must, however, also be assimilated from its complex. Thus, the chelators, which form complexes with cations with intermediate stabilities, seem to be the most suitable promoters of the absorption. This is also the case concerning comlexes with calcium and xylitol (Hämäläinen & Mäkinen 1989b). An additional explanation for the increased intestinal absorption of calcium may be better availability of calcium in the large intestine associated with decreased pH. This seems to be the case with lactitol (Ammann et al. 1988). However, no studies concerning xylitol in this aspect are available.

Dietary xylitol supplementation (20%) increases calcium and phosphorus levels of the bone in rats (Knuuttila et al. 1989). The xylitol-caused enhancement of calcium absorption is probably one of the main mechanisms behind this, but reduced intracellular redox state and changes in 1,25-dihydroxyvitamin D₃ concentration are also suggested to be involved (Svanberg & Knuuttila 1993). Bone and serum citrate concentrations elevate during xylitol administration (Knuuttila et al. 1989). This can be due to the xylitol metabolism-caused accumulation of NADH, enabling NADH to be used merely as an energy source in the respiratory chain. As a consequence, the rate of the citric acid cycle may retard, and lead to an accumulation of citric acid. Other suggested mechanisms of the elevated citrate levels include increased citrate synthesis, calcium-dependent inhibition of citrate decarboxylation, and increased rate of lipolysis (Knuuttila et al. 1989). Citrate can be considered a regulator of bone mineral metabolism, affecting mineralization, maturation and crystallization of bone inorganic fraction (Brecevic & Füredi-Milhofer 1979, Burnell et al. 1980, Johnsson et al. 1991).

Dietary xylitol addition (5%) in the rat diet during CaCO₃ rehabilitation promotes restoration of bone calcium content following dietary calcium deficiency as compared with CaCO₃ supplementation alone (Hämäläinen et al. 1990, Svanberg et al. 1993). This effect is most pronounced in the newly formed bone, indicating no major evidence of recalcification (Svanberg & Knuuttila 1993). The calcium deficiency-caused elevation in the serum 1,25-(OH)₂D₃ concentration fell as much as 65% below the control level after the xylitol supplementation period (Svanberg et al. 1993). The decrease in the 1,25-(OH)₂D₃ concentration may slow down the remodeling process by retarding the generation of osteoclasts (Bar-Shavit et al. 1983), and by retarding the maturation of organic matrix (Mechanic et al. 1975). The reduction in the 1,25-(OH)₂D₃ concentration may also be associated with the increased bone calcium content (Svanberg & Knuuttila 1994). The serum citrate level, as in the former study with normocalcemic diets, remained elevated in the xylitol-fed rats.

The supplementation of rat diet with xylitol (5%) has also been shown to protect against ovariectomy-induced decreases of bone calcium and phosphorus concentrations, of bone density, and of bone ash weight during experimental osteoporosis (Svanberg & Knuuttila 1994). While diminished absorption of calcium from the gut is suggested to be one of the major mechanisms in the pathogenesis of ovariectomy-induced osteoporosis (Nordin & Morris 1989), the enhanced calcium absorption associated with dietary xylitol administration could partly explain the preventive effect of xylitol on osteoporosis. The retarded remodeling rate associated with the decreased 1,25-(OH)₂D₃ concentration and the altered mineralization status associated with the increased citrate levels may also be involved.