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

Excessive fructose consumption inhibits adaptive increases in intestinal Ca2+ transport in lactating and weanling rats with increased Ca2+ 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 Ca2+ requirements. Adult mice fed for five wk a high glucose-low Ca2+ diet displayed expected compensatory increases in intestinal and renal Ca2+ transporter expression and activity, in renal CYP27B1 (coding for 1 alpha-hydroxylase) expression as well as in serum 1,25(OH)(2)D-3 levels, compared with mice fed isocaloric glucose- or fructose-normal Ca2+ diets. Replacing glucose with fructose prevented these increases in Ca2+ transporter, CYP27B1, and 1,25(OH)(2)D-3 levels induced by a low Ca2+ diet. In adult mice fed for three mo a normal Ca2+ 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 Ca2+ 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 Ca2+ 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, Ca2+ 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 Ca2+ stress and fed sufficient levels of dietary Ca2+. This finding is highly significant because fructose constitutes a substantial portion of the average diet of Americans already deficient in vitamin D.