Chronic high fructose intake reduces serum 1,25 [(OH).sub.2][D.sub.3] levels in calcium-sufficient rodents

Excessive fructose consumption inhibits adaptive increases in intestinal [Ca.sup.2+] transport in lactating and weanling rats with increased [Ca.sup.2+] requirements by preventing the increase in serum levels of 1,25[(OH).sub.2][D.sub.3]. Here we tested the hypothesis that chronic fructose intake decreases 1,25[(OH).sub.2][D.sub.3] levels independent of increases in [Ca.sup.2+] requirements. Adult mice fed for five wk a high glucose-low [Ca.sup.2+] diet displayed expected compensatory increases in intestinal and renal [Ca.sup.2+] transporter expression and activity, in renal CYP27B1 (coding for 1a- hydroxylase) expression as well as in serum 1,25[(OH).sub.2][D.sub.3] levels, compared with mice fed isocaloric glucose- or fructose-normal [Ca.sup.2+] diets. Replacing glucose with fructose prevented these increases in [Ca.sup.2+] transporter, CYP27B1, and 1,25[(OH).sub.2][D.sub.3] levels induced by a low [Ca.sup.2+] diet. In adult mice fed for three mo a normal [Ca.sup.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.sup.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.sup.2+] levels was fed to adult rats for three mo. Serum levels of 1,25[(OH).sub.2][D.sub.3] decreased and of FGF23 increased significantly over time. Renal expression of CYP27B1 and serum levels of 1,25[(OH).sub.2][D.sub.3] still decreased in fructosecompared to those in glucose-fed rats after three mo. Serum parathyroid hormone, [Ca.sup.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).sub.2][D.sub.3] in adult rodents experiencing no [Ca.sup.2+] stress and fed sufficient levels of dietary [Ca.sup.2+]. This finding is highly significant because fructose constitutes a substantial portion of the average diet of Americans already deficient in vitamin D.