Chronic high fructose intake reduces serum 1,25 (OH)2D3 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)2D3. Here we tested the hypothesis that chronic fructose intake decreases 1,25(OH)2D3 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 1α-hydroxylase) expression as well as in serum 1,25(OH)2D3 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)2D3 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)2D3 decreased and of FGF23 increased significantly over time. Renal expression of CYP27B1 and serum levels of 1,25(OH)2D3 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)2D3 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.
Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Newark, New Jersey, United States of America.
Veronique
V
Douard
Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Newark, New Jersey, United States of America.
Chirag
C
Patel
Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Newark, New Jersey, United States of America.
Jacklyn
J
Lee
Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Newark, New Jersey, United States of America.
Phuntila
P
Tharabenjasin
Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America.
Edek
E
Williams
Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America; Department of Orthopaedics, New Jersey Medical School, RBHS, Newark, New Jersey, United States of America.
J Christopher
JC
Fritton
Tissue Protection and Repair, Sanofi-Genzyme R&D Center, Genzyme, a Sanofi Company, Framingham, Massachusetts, United States of America.
Yves
Y
Sabbagh
Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Newark, New Jersey, United States of America.
Ronaldo P
RP
Ferraris
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D000089703:Fibroblast Growth Factor-23; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D051381:Rats; D013997:Time Factors
D002136:Calcium, Dietary; C000717428:Fgf23 protein, mouse; D026901:Membrane Transport Proteins; D005632:Fructose; D000089703:Fibroblast Growth Factor-23; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D005947:Glucose; D002118:Calcium