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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.

Chronic High Fructose Intake Reduces Serum 1,25 (OH)2D3 Levels in Calcium-Sufficient Rodents