Chronic High Fructose Intake Reduces Serum 1,25 (OH)(2)D(3) Levels in Calcium-Sufficient Rodents

Excessive fructose consumption inhibits adaptive increases in intestinal Ca(2+) transport in lactating and weanling rats with increased Ca(2+) requirements by preventing the increase in serum levels of 1,25(OH)(2)D(3). Here we tested the hypothesis that chronic fructose intake decreases 1,25(OH)(2)D(3) levels independent of increases in Ca(2+) requirements. Adult mice fed for five wk a high glucose-low Ca(2+) diet displayed expected compensatory increases in intestinal and renal Ca(2+) transporter expression and activity, in renal CYP27B1 (coding for 1α-hydroxylase) expression as well as in serum 1,25(OH)(2)D(3) levels, compared with mice fed isocaloric glucose- or fructose-normal Ca(2+) diets. Replacing glucose with fructose prevented these increases in Ca(2+) transporter, CYP27B1, and 1,25(OH)(2)D(3) levels induced by a low Ca(2+) diet. In adult mice fed for three mo a normal Ca(2+) diet, renal expression of CYP27B1 and of CYP24A1 (24-hydroxylase) decreased and increased, respectively, when the carbohydrate source was fructose instead of glucose or starch. Intestinal and renal Ca(2+) transporter activity and expression did not vary with dietary carbohydrate. To determine the time course of fructose effects, a high fructose or glucose diet with normal Ca(2+) levels was fed to adult rats for three mo. Serum levels of 1,25(OH)(2)D(3) decreased and of FGF23 increased significantly over time. Renal expression of CYP27B1 and serum levels of 1,25(OH)(2)D(3) still decreased in fructose- compared to those in glucose-fed rats after three mo. Serum parathyroid hormone, Ca(2+) and phosphate levels were normal and independent of dietary sugar as well as time of feeding. Thus, chronically high fructose intakes can decrease serum levels of 1,25(OH)(2)D(3) in adult rodents experiencing no Ca(2+) stress and fed sufficient levels of dietary Ca(2+). This finding is highly significant because fructose constitutes a substantial portion of the average diet of Americans already deficient in vitamin D.