Moderate consumption of freeze-dried blueberry powder increased net bone calcium retention compared with no treatment in healthy postmenopausal women: a randomized crossover trial.

BACKGROUND: Preclinical studies suggest that blueberry consumption is associated with improved bone health. OBJECTIVES: We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment. METHODS: OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries incorporated into food and beverage products. Urinary 41Ca:Ca ratio was measured by accelerator mass spectrometry. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures analysis of variance. RESULTS: In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions. CONCLUSIONS: Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02630797.

Skeletal Protection and Promotion of Microbiome Diversity by Dietary Boosting of the Endogenous Antioxidant Response.

There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling. Remarkably, Mont did not protect the male skeleton from androgen-induced bone loss. Moreover, Mont increased the variety of bacterial communities in the gut microbiome (α-diversity) more in female than in male mice; shifted the phylogenetic relatedness of bacterial communities (ß-diversity) further in females than males; and increased the prevalence of the taxon Ruminococcus1 in females but not males. Therefore, this nonpharmacologic intervention (i) protects from estrogen but not androgen deficiency; (ii) preserves bone, skeletal muscle, and body composition; (iii) elicits antioxidant defense responses independently of classical antioxidant/estrogenic signaling; and (iv) increases gut microbiome diversity toward a healthier signature. These findings highlight the impact of nutrition on musculoskeletal and gut microbiome homeostasis and support the precision medicine principle of tailoring dietary interventions to patient individualities, like sex. © 2020 American Society for Bone and Mineral Research (ASBMR).

Adiposity, Insulin Resistance, and Bone Mass in Children and Adolescents.

Context: Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship. Objective: To determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents. Design: Cross-sectional secondary analysis of baseline data from a previous randomized trial. Setting: University research facility. Participants: A total of 240 adolescents (68% female), aged 7 to 15 years. Main Outcome Measures: Using dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance. Results: Fat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, -5.893 to -0.956) and waist circumference (95% CI, -15.473 to -2.124) showed a negative relationship with LS BMC via HOMA-IR. Conclusions: These results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.

Mineral Intake Ratios Are a Weak but Significant Factor in Blood Pressure Variability in US Adults.

Background: Hypertension contributes substantially to chronic disease and mortality. Mineral intakes can modify blood pressure. Objective: Individual minerals and their intake ratios in US adults and their association with blood pressure were examined. Methods: Regression models were used to examine the associations of sodium, potassium, and calcium intakes and their ratios from food and supplements with blood pressure in 8777 US adults without impaired renal function from the 2011-2014 NHANES. We evaluated men (n = 4395) and women (n = 4382) separately. Models for predicting blood pressure were developed using age, blood pressure medication, race, body mass index (BMI), and smoking as explanatory variables. Results: Few adults met the recommended intake ratios for sodium:potassium (1.2% and 1.5%), sodium:calcium (12.8% and 17.67%), and sodium:magnesium (13.7% and 7.3%) for men and women, respectively. Approximately half of adults (55.2% of men and 54.8% of women) met calcium:magnesium intake ratio recommendations. In our regression models, the factors that explained the largest amount of variability in blood pressure were age, blood pressure medication, race/ethnicity, BMI, and smoking status. Together, these factors explained 31% and 15% of the variability in systolic blood pressure in women and men, respectively. The sodium:potassium (men and women), sodium:magnesium (women), and sodium:calcium (men) intake ratios were positively associated with systolic blood pressure, whereas calcium intake was inversely associated with systolic blood pressure in men only. When mineral intake ratios were added individually to our regression models, they improved the percentage of variability in blood pressure explained by the model by 0.13-0.21%. Conclusions: Strategies to lower blood pressure are needed. Lower sodium:potassium intake ratios provide a small benefit for protection against hypertension in US adults.

Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies, but its reliability and accuracy are unproven in health or CKD. This secondary analysis sought to determine the reliability and accuracy of 24-hour urine phosphorus as a biomarker of phosphorus intake and absorption in moderate CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eight patients with stage 3-4 CKD participated in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Thirteen 24-hour urine collections per patient were analyzed for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The accuracy of 24-hour urine phosphorus to predict phosphorus intake was determined using a published equation. The relationships of 24-hour urine phosphorus with phosphorus intake, net absorption, and retention were determined. RESULTS: There was wide day-to-day variation in 24-hour urine phosphorus within and among subjects (coefficient of variation of 30% and 37%, respectively). Two 24-hour urine measures were needed to achieve ≥75% reliability. Estimating dietary phosphorus intake from a single 24-hour urine resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. Twenty-four-hour urine phosphorus negatively correlated with whole-body retention but was not related to net absorption. CONCLUSIONS: From a sample of eight patients with moderate CKD on a tightly controlled dietary intake, 24-hour urine phosphorus was highly variable and did not relate to dietary phosphorus intake or absorption, rather it inversely related to phosphorus retention.

Behavioral Intervention in Adolescents Improves Bone Mass, Yet Lactose Maldigestion Is a Barrier.

Calcium intake during adolescence is important for attainment of peak bone mass. Lactose maldigestion is an autosomal recessive trait, leading to lower calcium intake. The Adequate Calcium Today study aimed to determine if a school-based targeted behavioral intervention over one year could improve calcium intake and bone mass in early adolescent girls. The school-randomized intervention was conducted at middle schools in six states over one school year. A total of 473 girls aged 10-13 years were recruited for outcome assessments. Bone mineral content (BMC) was determined by dual energy X-ray absorptiometry. Dietary calcium intake was assessed with a semi-quantitative food frequency questionnaire. Baseline calcium intake and BMC were not significantly different between groups. After the intervention period, there were no differences in changes in calcium intake and BMC at any site between groups. An unanticipated outcome was a greater increase in spinal BMC among lactose digesters than lactose maldigesters in the intervention schools only (12 months) (6.9 ± 0.3 g vs. 6.0 ± 0.4 g, p = 0.03) and considering the entire study period (18 months) (9.9 ± 0.4 vs. 8.7 ± 0.5 g, p < 0.01). Overall, no significant differences between the intervention and control schools were observed. However, lactose digesters who received the intervention program increased bone mass to a greater extent than lactose maldigesters.

Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States.

BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-ß after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-ß after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported. CLINICAL TRIAL REGISTRATION NUMBER: NCT00931580.

The effect of dairy intake on bone mass and body composition in early pubertal girls and boys: a randomized controlled trial.

Background: Calcium retention increases with increasing body mass index (BMI) on recommended calcium intakes. Dairy foods are an excellent source of essential nutrients that are needed to increase bone mineral content (BMC) and potentially decrease fracture.Objective: We compared children who were overweight with children who were healthy weight for the accrual of bone mass in response to an extra 3 servings dairy/d compared with usual intake.Design: Participants were 240 healthy boys and girls (64%), aged 8-15.9 y (mean ± SD age: 11.8 ± 1.5 y), who consumed low amounts of dairy (<800 mg Ca/d). A total of 181 subjects completed the trial-61% were black, 35% were white, and 4% were other; 50% of subjects were healthy weight [5th through 70th BMI percentiles for age (percentile)], and 50% of subjects were overweight (≥85th percentile). Participants were randomly assigned within BMI categories to receive an 18-mo dairy intervention (3 servings/d equivalent to ∼900 mg Ca/d) or control. Main outcome measures assessed every 6 mo included the total-body bone mineral content and density, cortical and trabecular bone mineral density (BMD), BMC, and bone area at the 4% tibia and anthropometric measures.Results: No significant differences in the change of BMD, BMC, or bone area for the total-body radius, lumbar spine, and total hip were observed between subjects who received the dairy intervention (achieved consumption of 1500 mg Ca/d) and subjects who did not (achieved 1000 mg Ca/d, which represented ∼2 cups milk or other dairy as part of the diet) with the exception of a tibial BMC gain, which was greater in the group who were given dairy (P = 0.02). Body fat was not influenced by the diet assignment.Conclusions: Dairy food interventions generally had no effect on bone mineral acquisition or body composition either within or between weight groups. This study suggests that 2 cups milk or the dairy equivalent is adequate for normal bone gain between ages 8 and 16 y. This trial was registered at clinicaltrials.gov as NCT00635583.

Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial.

BACKGROUND: The bioavailability of potassium should be considered in setting requirements, but to our knowledge, the bioavailability from individual foods has not been determined. Potatoes provide 19-20% of potassium in the American diet. OBJECTIVE: We compared the bioavailability and dose response of potassium from nonfried white potatoes with skin [targeted at 20, 40, and 60 milliequivalents (mEq) K] and French fries (40 mEq K) with potassium gluconate at the same doses when added to a basal diet that contained ∼60 mEq K. DESIGN: Thirty-five healthy, normotensive men and women with a mean ± SD age of 29.7 ± 11.2 y and body mass index (in kg/m(2)) of 24.3 ± 4.4 were enrolled in a single-blind, crossover, randomized controlled trial. Participants were partially randomly assigned to the order of testing for nine 5-d interventions of additional potassium as follows: 0 (control; repeated at phases 1 and 5), 20, 40, and 60 mEq K/d consumed as a potassium gluconate supplement or as unfried potato or 40 mEq K from French fries completed at phase 9. The bioavailability of potassium was determined from the area under the curve (AUC) of serial blood draws and cumulative urinary excretion during a 24-h period and from a kinetic analysis. The effects of the potassium source and dose on the change in blood pressure and augmentation index (AIx) were determined. RESULTS: The serum potassium AUC increased with the dose (P < 0.0001) and did not differ because of the source (P = 0.53). Cumulative 24-h urinary potassium also increased with the dose (P < 0.0001) and was greater with the potato than with the supplement (P < 0.0001). The kinetic analysis showed the absorption efficiency was high across all interventions (>94% ± 12%). There were no significant differences in the change in blood pressure or AIx with the treatment source or dose. CONCLUSIONS: The bioavailability of potassium is as high from potatoes as from potassium gluconate supplements. Future studies that measure the effect of dietary potassium on blood pressure will need to evaluate the effect of various dietary sources on potassium retention and in both normal and hypertensive populations. This trial was registered at clinicaltrials.gov as NCT01881295.

Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial.

BACKGROUND: Dietary soluble corn fiber (SCF) significantly improves calcium absorption in adolescents and the bone strength and architecture in rodent models. OBJECTIVE: In this study, we aimed to determine the skeletal benefits of SCF in postmenopausal women. DESIGN: We used our novel technology of determining bone calcium retention by following the urinary appearance of (41)Ca, a rare long-lived radioisotope, from prelabeled bone to rapidly and sensitively evaluate the effectiveness of SCF in reducing bone loss. A randomized-order, crossover, double-blinded trial was performed in 14 healthy postmenopausal women to compare doses of 0, 10, and 20 g fiber from SCF/d for 50 d. RESULTS: A dose-response effect was shown with 10 and 20 g fiber from SCF/d, whereby bone calcium retention was improved by 4.8% (P < 0.05) and 7% (P < 0.04), respectively. The bone turnover biomarkers N-terminal telopeptide and osteocalcin were not changed by the interventions; however, a significant increase in bone-specific alkaline phosphatase, which is a bone-formation marker, was detected between 0 and 20 g fiber from SCF/d (8%; P = 0.035). CONCLUSION: Daily SCF consumption significantly increased bone calcium retention in postmenopausal women, which improved the bone calcium balance by an estimated 50 mg/d. This study was registered at clinicaltrials.gov as NCT02416947.

Soluble Corn Fiber Increases Calcium Absorption Associated with Shifts in the Gut Microbiome: A Randomized Dose-Response Trial in Free-Living Pubertal Females.

BACKGROUND: Soluble corn fiber (SCF; 12 g fiber/d) is shown to increase calcium absorption efficiency, associated with shifts in the gut microbiota in adolescent males and females who participated in a controlled feeding study. OBJECTIVE: We evaluated the dose response of 0, 10, and 20 g fiber/d delivered by PROMITOR SCF 85 (85% fiber) on calcium absorption, biochemical bone properties, and the fecal microbiome in free-living adolescents. METHODS: Healthy adolescent females (n = 28; aged 11-14 y) randomly assigned into a 3-phase, double-blind, crossover study consumed SCF for 4 wk at each dose (0, 10, and 20 g fiber/d from SCF) alongside their habitual diet and were followed by 3-d clinical visits and 3-wk washout periods. Stable isotope ((44)Ca and (43)Ca) enrichment in pooled urine was measured by inductively coupled plasma mass spectrometry. Fecal microbial community composition was assessed by high-throughput sequencing (Illumina) of polymerase chain reaction-amplified 16S rRNA genes. Mixed model ANOVA and Friedman analysis were used to determine effects of SCF on calcium absorption and to compare mean microbial proportions, respectively. RESULTS: Calcium absorption increased significantly with 10 (13.3% ± 5.3%; P = 0.042) and 20 g fiber/d (12.9% ± 3.6%; P = 0.026) from SCF relative to control. Significant differences in fecal microbial community diversity were found after consuming SCF (operational taxonomic unit measures of 601.4 ± 83.5, 634.5 ± 83.8, and 649.6 ± 75.5 for 0, 10, and 20 g fiber/d, respectively; P < 0.05). Proportions of the genus Parabacteroides significantly increased with SCF dose (1.1% ± 0.8%, 2.1% ± 1.6%, and 3.0% ± 2.0% for 0, 10, and 20 g fiber/d from SCF, respectively; P < 0.05). Increases in calcium absorption positively correlated with increases in Clostridium (r = 0.44, P = 0.023) and unclassified Clostridiaceae (r = 0.40, P = 0.040). CONCLUSIONS: SCF, a nondigestible carbohydrate, increased calcium absorption in free-living adolescent females. Two groups of bacteria may be involved, one directly fermenting SCF and the second fermenting SCF metabolites further, thereby promoting increased calcium absorption. This trial was registered at clinicaltrials.gov as NCT01660503.

Individual variation in urinary sodium excretion among adolescent girls on a fixed intake.

BACKGROUND: According to traditional understanding of sodium homeostasis, nearly all of daily sodium intake is excreted in urine, with intraindividual variability attributed to variability in dietary sodium intake and urine collection errors. OBJECTIVE: To analyze the variability of urinary sodium in excretion from a balance study with fixed sodium intakes. METHODS: Daily 24-h urine collections were assessed for sodium, potassium, and creatinine in 22 black and 13 white adolescent girls (11-15 year, BMI 15-29 kg/m) in a randomized, crossover design with controlled diets containing either low (57 mmol/day) or high (167 mmol/day) sodium, each fed for 3 weeks. RESULTS: Coefficient of variation analysis indicated higher variation in urinary sodium excretion about the mean on low (vs high) sodium (40 vs 32%, P = 0.02) and in black (vs white) girls (42 vs 30%, P < 0.001). A mixed model showed no sodium intake × race interaction. Urinary sodium excretion was not correlated with urinary potassium or creatinine excretion. Excretion of 65 mmol/day (adequate intake) or less was documented on 16% on the days during the high-sodium diet. Reliability of the mean of several urine sodium samples varied from 23% for one sample to 75% for 10 samples for the high-sodium diet. CONCLUSION: The high intraindividual variability in urinary sodium excretion on a fixed diet highlights the potential for substantial error in (a) using a single 24-h urine collection to estimate an individual's usual sodium intake and (b) relating sodium excretion from a single 24-h collection with outcomes. Further research is warranted to understand the causes of such variation.

Soluble maize fibre affects short-term calcium absorption in adolescent boys and girls: a randomised controlled trial using dual stable isotopic tracers.

Soluble maize fibre (SCF) has been found to significantly improve bone mineral density and strength in growing rats compared with several other novel prebiotic fibres. The objective of the present study was to investigate the effect of SCF on Ca absorption and retention in pubertal children by studying the potential absorption mechanisms of the intestinal microbiota. A total of twenty-four adolescent boys and girls (12-15 years) participated in two 3-week metabolic balance studies testing 0 g/d SCF (control (CON) treatment) and 12 g/d SCF (SCF treatment) in a random order by inclusion in a low-Ca diet (600 mg/d). Fractional Ca absorption was measured at the end of the two intervention periods using a dual-stable isotope method. Diet composites and faecal and urine samples were collected daily and analysed for Ca content. Ca retention was calculated as dietary Ca intake minus Ca excretion in faeces and urine over the last 2 weeks. Microbial community composition in the faecal samples collected at the beginning and end of each session was determined by 454 pyrosequencing of the PCR-amplified 16S ribosomal RNA gene. Fractional Ca absorption was 12 % higher (41 mg/d) after the SCF treatment compared with that after the CON treatment (0·664 (sd 0·129) and 0·595 (sd 0·142), respectively; P= 0·02), but Ca retention was unaffected. The average proportion of bacteria of the phylum Bacteroidetes was significantly greater in the participants after the SCF treatment than after the CON treatment. These results suggest that moderate daily intake of SCF, a well-tolerated prebiotic fibre, increases short-term Ca absorption in adolescents consuming less than the recommended amounts of Ca.

Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial.

Adolescence is a time for rapid growth that represents an opportunity to influence peak bone mass. Prebiotic agents, such as galacto-oligosaccharides (GOS), increase Ca absorption in animal models and postmenopausal women. The objectives of the present study were to investigate the dose-response relationship of GOS supplementation on Ca absorption during growth and to assess changes in colonic microbiota to better understand the mechanism by which GOS is acting. A total of thirty-one healthy adolescent girls aged 10-13 years consumed smoothie drinks twice daily with 0, 2·5 or 5 g GOS for three 3-week periods in a random order. Fractional Ca absorption was determined from urinary Ca excretion over 48 h at the end of each 3-week period using a dual stable isotope method. Faecal microbiota and bifidobacteria were assessed by PCR-denaturing gradient gel electrophoresis and quantitative PCR. Fractional Ca absorption after the 48 h treatment with control, 5 and 10 g GOS/d was 0·393 (SD 0·092), 0·444 (SD 0·086) and 0·419 (SD 0·099), respectively. Significant improvements in Ca absorption were seen with both low and high doses of GOS compared with the control (P,0·02), but itwas not a dose-response relationship. The increase in absorption was greatest in the urine collected after 24 h, which is consistent with lower gut absorption. Faecal bifidobacteria increased (control 10·89 (SD 13·86), 5 g GOS 22·80 (SD 15·74) and 10 g GOS 11·54 (SD 14·20)) with the GOS treatment (P,0·03). The results suggest that daily consumption of 5 g GOS increases Ca absorption, which may be mediated by the gut microbiota, specifically bifidobacteria.

Galactooligosaccharides improve mineral absorption and bone properties in growing rats through gut fermentation.

Galactooligosaccharides (GOS), prebiotic nondigestible oligosaccharides derived from lactose, have the potential for improving mineral balance and bone properties. This study examined the dose-response effect of GOS supplementation on calcium and magnesium absorption, mineral retention, bone properties, and gut microbiota in growing rats. Seventy-five 4-week-old male Sprague-Dawley rats were randomized into one of five treatment groups (n = 15/group) and fed a diet containing 0, 2, 4, 6, or 8% GOS by weight for 8 weeks. Dietary GOS significantly decreased cecal pH and increased cecal wall weight and content weight in a dose-dependent manner (p < 0.0001). Fingerprint patterns of the 16S rRNA gene PCR-DGGE from fecal DNA indicated the variance of bacterial community structure, which was primarily explained by GOS treatments (p = 0.0001). Quantitative PCR of the samples revealed an increase in the relative proportion of bifidobacteria with GOS (p = 0.0001). Net calcium absorption was increased in a dose-response manner (p < 0.01) with GOS supplementation. Dietary GOS also increased (p < 0.02) net magnesium absorption, femur 45Ca uptake, calcium and magnesium retention, and femur and tibia breaking strength. Distal femur total and trabecular volumetric bone mineral density (vBMD) and area and proximal tibia vBMD increased (p < 0.02) with GOS supplementation. Trabecular-rich bones, that is, those that rapidly turn over, were most benefited. Regression modeling showed that GOS benefited calcium and magnesium utilization and vBMD through decreased cecal pH, increased cecal wall and content weight, and increased proportion of bifidobacteria.

Obesity augments calcium-induced increases in skeletal calcium retention in adolescents.

CONTEXT: Overweight adolescents have low bone mineral content for weight and are at increased risk for fractures. OBJECTIVE: The aim was to determine whether overweight and obesity influence the positive relationship between dietary calcium intake and skeletal calcium retention in adolescents. DESIGN: Analysis of pooled data from calcium balance studies in adolescents. SETTING: Participants each underwent a 3-wk calcium balance study in a controlled environment. PARTICIPANTS: Participants included 280 White, Black, and Asian boys (n = 73) and girls (n = 207) ages 10-16 yr. MAIN OUTCOME MEASURE: The relationship among body mass index (BMI), calcium intake, and calcium retention was modeled using linear regression. RESULTS: Calcium intake, BMI, sex, race, and age explained 27.9% of the variation in calcium retention. At low calcium intakes, there was no effect of BMI on skeletal calcium retention, but at higher calcium intakes, BMI increased skeletal calcium retention. CONCLUSIONS: Greater gains in calcium retention occur with increases in calcium intake in adolescents with higher BMI compared with those with lower BMI. Additional studies are needed to investigate whether increasing calcium intake reduces the increased risk of fracture associated with overweight and obesity in adolescents.

An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents.

In adults, maximal suppression of serum parathyroid hormone (PTH) has commonly been used to determine the sufficiency of serum 25-hydroxyvitamin D [25(OH)D]. In children and adolescents, the relationship between serum 25(OH)D and PTH is less clear and most studies reporting a relationship are derived from relatively small samples and homogeneous cohorts. Our objective was to determine the relationship between serum 25(OH)D and PTH in children and adolescents from a large and diverse U.S. cohort and to identify a point of inflection of serum 25(OH)D for maximal suppression of serum PTH. Data from 735 participants, ages 7-18 y, were pooled from 3 study sites located in Indiana, Texas, and Massachusetts. A two-phase linear spline was used to model the relationship between serum 25(OH)D and PTH. The value of serum 25(OH)D for maximal suppression of serum PTH was identified as the inflection point of the spline. Before adjustment for site, the inflection point of serum 25(OH)D for maximal suppression of serum PTH was 92.4 nmol/L (95% CI: 62.2, 130.7). After adjusting for site, the point of inflection was poorly defined and the relationship between serum 25(OH)D and PTH appeared to be linear. The lack of an inflection point of serum 25(OH)D for maximal suppression of PTH brings into question the value of using maximal suppression of serum PTH as a basis for determining optimal serum 25(OH)D for healthy children and adolescents.

Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis.

BACKGROUND: The World Health Organization recommends serum ferritin concentrations as the best indicator of iron deficiency (ID). Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated. OBJECTIVE: The objective was to estimate the increase in ferritin in 32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP), individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin concentrations. DESIGN: We estimated the increase in ferritin associated with inflammation (ie, CRP gt 5 mg/L and/or AGP gt 1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies), and women (16 studies) (n = 8796 subjects). In 2-group analyses (either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups: reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only). RESULTS: In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P lt 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P lt 0.001) higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ap 30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID. CONCLUSIONS: Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups.

Calcium requirements and metabolism in Chinese-American boys and girls.

Calcium requirements of North American adolescents were set at 1300 mg/day based on data from white girls. Calcium requirements for Asian-American adolescents have not been studied. Using metabolic balance protocols and a range in calcium intakes, skeletal calcium retention was determined in Chinese-American adolescents. A sample of 29 adolescents, 15 boys aged 12 to 15 years and 14 girls aged 11 to 15 years, was studied twice on paired calcium intakes ranging between 629 to 1835 mg/day using a randomized-order crossover design. Calcium absorption and bone turnover rates using double-stable calcium isotope kinetic analysis on two calcium intakes per subject were measured and compared in boys and girls. Girls and boys had low habitual mean calcium intakes of 648 and 666 mg/day, respectively, and low mean serum 25-hydroxyvitamin D concentrations of 19.1 and 22.2 ng/mL, respectively. True fractional calcium absorption varied inversely with calcium load. Boys had significantly higher bone turnover rate than girls at the same calcium intake. Calcium retention increased with calcium intake; calcium intakes to achieve maximal calcium retention were 1100 mg/day in boys and 970 mg/day in girls. Recommendations for calcium requirements should be lowered for Chinese-American adolescents.

Vitamin D status and calcium metabolism in adolescent black and white girls on a range of controlled calcium intakes.

BACKGROUND: There are limited data in adolescents on racial differences in relationships between dietary calcium intake, absorption, and retention and serum levels of calcium-regulating hormones. OBJECTIVES: The aim of this study was to investigate these relationships cross-sectionally in American White and Black adolescent girls. METHODS: Calcium balance studies were conducted in 105 girls, aged 11-15 yr, on daily calcium intakes ranging from 760-2195 mg for 3-wk controlled feeding periods; 158 observations from 52 Black and 53 White girls were analyzed. RESULTS: Black girls had lower serum 25-hydroxyvitamin D [25(OH)D], higher serum 1,25-dihydroxyvitamin D, and higher calcium absorption and retention than White girls. Calcium intake and race, but not serum 25(OH)D, predicted net calcium absorption and retention with Black girls absorbing calcium more efficiently at low calcium intakes than White girls. The relationship between serum 25(OH)D and serum PTH was negative only in White girls. Calcium intake, race, and postmenarcheal age explained 21% of the variation in calcium retention, and serum 25(OH)D did not contribute further to the variance. CONCLUSIONS: These results suggest that serum 25(OH)D does not contribute to the racial differences in calcium absorption and retention during puberty.