Zhensheng Chen

Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty.

Few studies of the VDR polymorphisms have looked at calcium metabolism or long‐term effects. We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adolescents. We found a significant relationship between calcium absorption and skeletal calcium accretion and the Fok1, but not other VDR or related, genetic polymorphisms. It seems that the Fok1 polymorphism directly affects bone mineralization during pubertal growth through an effect on calcium absorption.

Perturbed Zinc Homeostasis in Rural 3-5-y-Old Malawian Children Is Associated With Abnormalities in Intestinal Permeability Attributed to Tropical Enteropathy

Tropical enteropathy and zinc deficiency are major public health problems worldwide. Tropical enteropathy is characterized by reduced mannitol absorption with normal or increased lactulose absorption when a dual sugar absorption test is administered, the results of which are reported as the lactulose:mannitol ratio (L:M). Zinc homeostasis is quantified with a dual stable isotope test. This study tested the hypothesis that endogenous fecal zinc (EFZ) was correlated with the L:M. A dual sugar absorption test and dual stable isotope test were performed on 25 asymptomatic Malawian children aged 3–5 y at risk for tropical enteropathy and zinc deficiency. EFZ and net zinc retention were estimated and correlated with the L:M. Twenty-two children (88%) had an abnormal L:M (L:M >0.10), and the L:M was 0.24 ± 0.10 (mean ± SD). EFZ was 1.68 ± 1.06 mg/d, a quantity greater than is seen in healthy populations from the developed world. EFZ was positively correlated with the L:M (r = 0.62, p < 0.001). Net zinc retention (0.67 ± 1.6 mg/d) was negatively correlated with the L:M (r = −0.47, p = 0.02). This suggests that perturbed zinc homeostasis is associated with subclinical enteropathy in these children.

Calcium Absorption, Kinetics, Bone Density, and Bone Structure in Patients with Hereditary Vitamin D-Resistant Rickets

BACKGROUND Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor gene. Children with HVDRR suffer from severe hypocalcemia and rickets that are treatable with extremely high-dose calcium supplements. Surprisingly, spontaneous recovery of calcium metabolism occurs after the end of puberty without the need for further calcium supplementation. OBJECTIVES To evaluate the role of vitamin D receptor in intestinal calcium absorption and bone, we investigated intestinal fractional calcium absorption (FCA), bone calcium accretion (Vo+), bone mineral density (BMD), and bone structure parameters in HVDRR patients from infancy into adulthood. PATIENTS AND METHODS Seventeen HVDRR patients aged 1.5-37 yr were investigated. FCA and Vo+ were determined by stable-calcium isotopes. BMD was determined by dual-energy x-ray absorptiometry and bone structure by high-resolution magnetic resonance imaging. RESULTS FCA in patients aged 1.5-17 yr was 34.9 ± 11.2% compared with 57.3 ± 2.0% in age-matched controls (P < 0.00004), whereas in patients aged 18-26 yr, it was 82.0 ± 7.8 and 53.6 ± 1.2% in controls (P < 0.001). FCA of patients older than 29 yr was comparable to controls. Patients aged 18-26 yr had higher Vo+ than controls (P < 0.02). Patients under 18 and over 29 yr of age had Vo+ comparable to controls. Femoral-neck BMD Z-score was -2.38 ± 0.3 in patients under 18 yr and 0.28 ± 0.87 in postpubertal patients (P < 0.0001). Bone structure by high-resolution magnetic resonance imaging and bone parameters of HVDRR patients and controls were similar. CONCLUSIONS Evidence from HVDRR patients reveals that calcium absorption is highly vitamin D dependent during infancy until the end of puberty, after which there is a period of about 10 yr in which mechanisms other than vitamin D-dependent ones are substantially involved in calcium absorption.

Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4–8-y-old children: a double-blind randomized controlled trial

BACKGROUND The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. OBJECTIVE The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. DESIGN In a double-blind, placebo-controlled trial, we randomly assigned 64 children to 1000 IU vitamin D(3)/d (n = 32) or placebo (n = 32) for 8 wk. Stable isotopes were used to assess calcium absorption. The main outcome measure was calcium absorption before and after supplementation. RESULTS All of the data are shown as means ± SDs. At baseline, vitamin D intake was 221 ± 79 IU/d and calcium intake was 830 ± 197 mg/d. Baseline serum 25-hydroxyvitamin D [25(OH)D] was not significantly correlated with fractional or total calcium absorption. After 8 wk, with baseline values used as a covariate, no differences were seen in fractional or total calcium absorption based on supplementation group (P = 0.75 and 0.36, respectively). Supplemented children had a significant increase in 25(OH)D concentrations (from 27.7 ± 7.4 to 36.0 ± 10.3 ng/mL; P < 0.0001) and a decrease in parathyroid hormone (from 21.4 ± 10.4 to 12.9 ± 7.1 pg/mL; P < 0.001); no significant changes in the placebo group were observed. No adverse side effects were noted in either group. CONCLUSIONS Vitamin D(3) supplementation at 1000 IU/d increases 25(OH)D and decreases parathyroid hormone in children with average vitamin D intakes below the dietary recommendations of the Institute of Medicine. However, no significant effects of this change on calcium absorption occurred. This trial was registered at clinicaltrials.gov as NCT 00868738.

Iron supplementation does not affect copper and zinc absorption in breastfed infants

BACKGROUND Iron supplements are commonly recommended for infants but were suggested to inhibit zinc and copper absorption. OBJECTIVE The objective of this study was to investigate potential effects of iron supplementation, infant age, and mineral status on zinc and copper absorption in infants at 6 and 9 mo of age. DESIGN Twenty-five healthy breastfed term infants were recruited from a larger randomized iron supplementation trial. Six of these infants received iron supplements (1 mg . kg(-1) . d(-1)) from 4 to 9 mo, 8 were supplemented from 6 to 9 mo, and 11 received placebo only. Zinc and copper absorption was measured at 6 and 9 mo of age, using orally administered (70)Zn and (65)Cu and fecal monitoring of recovered stable isotopes. RESULTS Mean (+/-SD) zinc absorption was 51.9 +/- 17.9%, and mean copper absorption was 79.0 +/- 13.5%. No significant difference was observed in zinc or copper absorption between 6 and 9 mo of age. When combining all measurements, no significant effect of prior iron supplementation was observed on zinc or copper absorption. No significant correlation was observed between plasma zinc and zinc absorption or between plasma copper and copper absorption. No significant correlation was observed between erythrocyte copper-zinc-dependent superoxide dismutase activity and copper absorption. CONCLUSIONS The study does not support the contention that iron supplements inhibit the absorption of zinc or copper in healthy breastfed infants at 6-9 mo of age. In addition, we did not find any age-related changes in zinc or copper absorption between 6 and 9 mo of age.

Effect of tannic acid on iron absorption in straw-colored fruit bats (Eidolon helvum).

Excessive absorption and subsequent storage of dietary iron has been found in a variety of captively held birds and mammals, including fruit bats. It is thought that feeding a diet that is low in iron can prevent the onset of this disease; however, manufacturing a diet with commonly available foodstuffs that contains a sufficiently low iron concentration is difficult. An alternative is to feed captive animals that may be susceptible to this disease potential iron chelators such as tannins that may bind to iron and block its absorption. Using stable isotope methods established in humans, we measured iron bioavailability in straw-colored fruit bats (Eidolon helvum) and tested whether tannic acid significantly reduced the extent of iron absorption. Regardless of dose, tannic acid significantly reduced iron absorption (by 40%) and in the absence of tannic acid, iron absorption was extensive in this species (up to 30%), more so than in humans. Species susceptible to iron storage disease may efficiently absorb iron in the gut regardless of iron status, and supplementing these species with tannic acid in captivity may provide an alternative or additional means of preventing the development of this disease.

Magnesium Metabolism in 4‐Year‐Old to 8‐Year‐Old Children

Magnesium (Mg) is a key factor in bone health, but few studies have evaluated Mg intake or absorption and their relationship with bone mineral content (BMC) or bone mineral density (BMD) in children. We measured Mg intake, absorption, and urinary excretion in a group of children 4 to 8 years of age. Mg absorption was determined using a dual‐tracer stable isotope technique, with 25Mg given intravenously and 26Mg given orally. We found a small, but significantly greater Mg absorption efficiency (percentage absorption) in males than females (67% ± 12% versus 60% ± 8%, p = 0.02) but no difference in estimated net Mg retention (average of 37 mg/d in both males and females). Relating dietary Mg intake to estimated Mg retention showed that an intake of 133 mg/d, slightly above the current estimated average requirement (EAR) of 110 mg/d, led to a net average retention of 10 mg/d, the likely minimum growth‐related need for this age group. Covariate analysis showed that Mg intake and total Mg absorption, but not calcium intake or total absorption were significantly associated with both total body BMC and BMD. These results suggest that usual Mg intakes in small children in the United States meet dietary requirements in most but not all children. Within the usual range of childrens diets in the United States, dietary Mg intake and absorption may be important, relatively unrecognized factors in bone health.

Inclusion of guava enhances non-heme iron bioavailability but not fractional zinc absorption from a rice-based meal in adolescents.

Assessing the bioavailability of non-heme iron and zinc is essential for recommending diets that meet the increased growth-related demand for these nutrients. We studied the bioavailability of iron and zinc from a rice-based meal in 16 adolescent boys and girls, 13-15 y of age, from 2 government-run residential schools. Participants were given a standardized rice meal (regular) and the same meal with 100 g of guava fruit (modified) with (57)Fe on 2 consecutive days. A single oral dose of (58)Fe in orange juice was given at a separate time as a reference dose. Zinc absorption was assessed by using (70)Zn, administered intravenously, and (67)Zn given orally with meals. The mean hemoglobin concentration was similar in girls (129 ± 7.8 g/L) and boys (126 ± 7.1 g/L). There were no sex differences in the indicators of iron and zinc status except for a higher hepcidin concentration in boys (P < 0.05). The regular and modified meals were similar in total iron (10-13 mg/meal) and zinc (2.7 mg/meal) content. The molar ratio of iron to phytic acid was >1:1, but the modified diet had 20 times greater ascorbic acid content. The absorption of (57)Fe from the modified meal, compared with regular meal, was significantly (P < 0.05) greater in both girls (23.9 ± 11.2 vs. 9.7 ± 6.5%) and boys (19.2 ± 8.4 vs. 8.6 ± 4.1%). Fractional zinc absorption was similar between the regular and modified meals in both sexes. Hepcidin was found to be a significant predictor of iron absorption (standardized β = -0.63, P = 0.001, R(2) = 0.40) from the reference dose. There was no significant effect of sex on iron and zinc bioavailability from meals. We conclude that simultaneous ingestion of guava fruit with a habitual rice-based meal enhances iron bioavailability in adolescents.

Calcium Absorption in Very Low Birth Weight Infants with and without Bronchopulmonary Dysplasia

OBJECTIVE To evaluate the effects of early bronchopulmonary dysplasia (BPD) on calcium (Ca) metabolism and growth in very low birth weight (VLBW) infants. STUDY DESIGN A dual-tracer, stable isotope method was used to assess Ca absorption in VLBW infants. Infants with early BPD received energy-dense feedings and mild fluid restriction. RESULTS Sixteen of 41 preterm infants were classified as having early BPD. Fractional Ca absorption (early BPD, 58.4 ± 4.6% versus no early BPD, 50.3 ± 4.0%, P = .2), total Ca absorption (early BPD, 127 ± 14 mg/kg/d versus no early BPD, 104 ± 9 mg/kg/d, P = .9), and Ca retention (early BPD, 99.6 ± 10.0 mg/kg/d versus no early BPD, 91.0 ± 9.8 mg/kg/d, P = .2) were similar among groups. There was no significant difference in weight gain, linear growth, or head circumference growth between groups. CONCLUSIONS The ability of VLBW infants with early BPD and fluid restriction to grow and accrete calcium is similar to those without early BPD. The use of high caloric density feedings in VLBW infants with early BPD can help achieve bone and overall growth outcomes close to those achievable in utero.

Orange but not apple juice enhances ferrous fumarate absorption in small children.

Objective: Ferrous fumarate is a common, inexpensive iron form increasingly used instead of ferrous sulfate as a food iron supplement. However, few data exist as to whether juices enhance iron absorption from ferrous fumarate. Subjects and Methods: We studied 21 children, ages 4.0 to 7.9 years using a randomized crossover design. Subjects consumed a small meal including a muffin containing 4 mg 57Fe as ferrous fumarate and either apple (no ascorbic acid) or orange juice (25 mg ascorbic acid). They were separately given a reference dose of 58Fe (ferrous sulfate) with ascorbic acid. Results: Iron absorption increased from 5.5% ± 0.7% to 8.2% ± 1.2%, P < 0.001 from the muffins given with orange juice compared with muffins given with apple juice. The absorption of ferrous fumarate given with orange juice and enhancement of absorption by the presence of juice were significantly positively related to height, weight, and age (P < 0.01 for each). Although iron absorption from ferrous fumarate given with apple juice was significantly inversely associated with the (log transformed) serum ferritin, the difference in absorption between juice types was not (P > 0.9). Conclusions: These data demonstrate an overall benefit to iron absorption from ferrous fumarate provided with orange juice. The effect was age related such that in children older than 6 years of age, there was a nearly 2-fold increase in iron absorption from ferrous fumarate given with orange juice.