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

Abstract

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.

Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK−/−and GLUT5−/−mice

“…This should not come as a surprise, since humans with fructosuria can readily tolerate dietary fructose (18,29). In studies III and IVB, the experimental diet had 40% free fructose with no other sugar (13). In study IVA, the experimental diet had 63% free fructose (13,21).…”

“…Because our 20% free fructose diets contained 10% sucrose, we made diets containing 40% fructose or glucose [without sucrose (13) to evaluate the effect of higher fructose concentrations (study III)]. Because preliminary work (data not shown) indicated that intake of 40% fructose tended to decrease in KHK Ϫ/Ϫ mice after a few days, KHK Ϫ/Ϫ and wild-type mice adapted to reversed light cycle were killed 7.5 h after initial intake (n ϭ 5 each diet).…”

“…In studies III and IVB, the experimental diet had 40% free fructose with no other sugar (13). In study IVA, the experimental diet had 63% free fructose (13,21). In all experiments, glucose isocalorically replaced fructose in control diets, with all other ingredients being exactly the same.…”

Two Cases of Mistaken Polyuria and Nephrocalcinosis in Infants with Glucose-Galactose Malabsorption: A Possible Role of 1,25(OH)₂D₃

“…In both patients, the 1,25(OH) 2 D 3 level normalized after the introduction of a fructose-based diet. Douard et al [30, 31] recently showed that an excessive fructose diet in rodents was associated with an inhibition of calcium absorption with a vitamin D-mediated decrease in TRPV5 and TRPV6 mRNA expression. In rats fed a high fructose diet, the 1α-hydroxylase activity was decreased while the 24-hydroxylase activity was increased leading to lower levels of 1,25(OH) 2 D 3 and higher levels of 24,25-dihydroxyvitamin D 3 , the inac tive vitamin D isoform.…”

An assessment of molecular pathways of obesity susceptible to nutrient, toxicant and genetically induced epigenetic perturbation

“…For example, Cytochrome p450 (Cyp450) enzymes have been shown to play critical roles in metabolizing POPs [35, 45]. Cyp450 enzyme levels are altered by many nutrients including dietary protein [46, 47], fat [48], sugar [49], vitamin C [50, 51], vitamin E [39], folate[40], betaine [52], iodine and selenium [53]. These findings highlight the potential for aggregate effects of diet-toxicant interactions and offer the promise of dietary intervention of diseases related to toxicant exposure.…”