Linda D McCabe

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.

Dairy Calcium is Related to Changes in Body Composition during a Two-Year Exercise Intervention in Young Women

Objective: Relationships between micronutrients and dairy product intake and changes in body weight and composition over two years were investigated. Design: Two year prospective non-concurrent analysis of the effect of calcium intake on changes in body composition during a two year exercise intervention. Subjects: 54 normal weight young women, 18 to 31 years of age. Measures of Outcome: Mean intakes of nutrients of interest were determined from three-day diet records completed at baseline and every six months for two years. The change in total body weight and body composition (assessed by dual x-ray absorptiometry) from baseline to two years was also determined. Results: Total calcium/kilocalories and vitamin A together predicted (negatively and positively, respectively) changes in body weight (R2 = 0.19) and body fat (R2 = 0.27). Further, there was an interaction of calcium and energy intake in predicting changes in body weight, such that, only at lower energy intakes, calcium intake (not adjusted for energy) predicted changes in body weight. Conclusions: Regardless of exercise group assignment, calcium adjusted for energy intake had a negative relationship and vitamin A intake a positive relationship with two year changes in total body weight and body fat in young women aged 18 to 31 years. Thus, subjects with high calcium intake, corrected by total energy intake, and lower vitamin A intake gained less weight and body fat over two years in this randomized exercise intervention trial.

Peak spine and femoral neck bone mass in young women

Achievement of higher peak bone mass early in life may play a critical role against postmenopausal bone loss. Bone mineral density (BMD) of the spine, femoral neck, greater trochanter, Wards triangle, and spine bone mineral content (BMC) and bone surface area (BSA) were assessed by dual energy x-ray absorptiometry in 300 healthy females (age 6-32 years). Bone measurements were described by using nonlinear models with age, weight, height, or dietary calcium intake as the explanatory variables. At the spine, femoral neck, greater trochanter, and Wards triangle, the highest BMD level was observed at 23.0 +/- 1.4, 18.5 +/- 1.6, 14.2 +/- 2.0, and 15.8 +/- 2.1 years, respectively. The age of attaining peak spine BMC and BSA cannot be estimated, as significant increases in these two measures were observed through this age group. Age, weight, and height were all significant predictors of all these bone measurements. Weight was a stronger predictor than age for all sites. Dietary calcium intake was not a significant predictor for any of these bone measurements. We conclude that age of attaining peak bone mass at the hip is younger than at the spine, and BMC and BSA at the spine continue to increase through the early thirties in females.

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.

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.

Impact of exercise on bone health and contraindication of oral contraceptive use in young women.

PURPOSE The effect of quantified resistance and high impact exercise training on bone mass as modified by age and oral contraceptive (OCont) use in young women was studied. METHODS Women were categorized by age (18-23 vs 24-31 yr) and OCont use, and were then randomized into either three sessions of resistance exercise plus 60 min.wk-1 of jumping rope or a control group for 24 months. Total body, spine, femoral neck, greater trochanter, Wards area, and radial bone mineral density (BMD) and/or content (BMC), biochemical markers of bone turnover, dietary intake of calcium, lean body mass, maximal oxygen uptake, and strength were determined at baseline and every 6 months. RESULTS Total body (TB) BMC percent change from baseline was higher in exercisers compared with nonexercisers at 6 and 24 months. OCont users had lower bone turnover at baseline and a decrease in TBBMC from baseline compared with non-OCont users at 24 months. Spine BMC and BMD decreased in the exercise and OCont group at 6 months and remained significantly below nonexercisers who used oral contraceptives at 2 yr. Femoral neck BMD also decreased in the exercise and oral contraceptive group at 6 months. CONCLUSIONS Exercise prevented a decline in TBBMC seen in the nonexercisers. On the other hand, exercise in oral contraceptive users prevented the increase observed in the spine of the nonexercise plus OCont group.

Antiresorptive Effects of Phytoestrogen Supplements Compared with Estradiol or Risedronate in Postmenopausal Women Using 41Ca Methodology

INTRODUCTION Reduction of ovarian estrogen secretion at menopause increases net bone resorption and leads to bone loss. Isoflavones have been reported to protect bone from estrogen deficiency, but their modest effects on bone resorption have been difficult to measure with traditional analytical methods. METHODS In this randomized-order, crossover, blinded trial in 11 healthy postmenopausal women, we compared four commercial sources of isoflavones from soy cotyledon, soy germ, kudzu, and red clover and a positive control of oral 1 mg estradiol combined with 2.5 mg medroxyprogesterone or 5 mg/d oral risedronate (Actonel) for their antiresorptive effects on bone using novel (41)Ca methodology. RESULTS Risedronate and estrogen plus progesterone decreased net bone resorption measured by urinary (41)Ca by 22 and 24%, respectively (P < 0.0001). Despite serum isoflavone profiles indicating bioavailability of the phytoestrogens, only soy isoflavones from the cotyledon and germ significantly decreased net bone resorption by 9% (P = 0.0002) and 5% (P = 0.03), respectively. Calcium absorption and biochemical markers of bone turnover were not influenced by interventions. CONCLUSIONS Dietary supplements containing genistein-like isoflavones demonstrated a significant but modest ability to suppress net bone resorption in postmenopausal women at the doses supplied in this study over a 50-d intervention period.

Exercise and oral contraceptive use suppress the normal age-related increase in bone mass and strength of the femoral neck in women 18–31 years of age

Women who exercise during their second and third decades may increase their peak bone mass and lower their eventual risk for postmenopausal fracture. However, the effects of exercise in younger women can be modulated by the use of oral contraceptives, which may prevent the normal accretion of bone mass that would otherwise occur. We hypothesized that exercise intervention in young adult women would significantly increase both bone mass and the bending rigidity of the femoral neck. We further hypothesized that exercise intervention in the presence of oral contraceptive use would have a negative effect on bone mass and bending rigidity. Women 18-31 years of age (n = 123) were classified by oral contraceptive use (OC, NOC) and age (18-23, 24-31 years), and then randomized into exercise or nonexercise groups. The exercise protocol consisted of three sessions/week of aerobic and nonaerobic exercises, and continued for 2 years. Each 6 months, the femoral neck of each subject was scanned using a Lunar dual-energy X-ray absorptiometry (DEXA) scanner, and bone mineral content, density and geometric information were used to calculate estimated stresses and bending rigidity at the hip. Percent changes from baseline were analyzed using two-way analysis of variance (ANOVA) at 6, 12, 18, and 24 months. Women who neither exercised nor took oral contraceptives (NE/NOC) had the greatest percentage increases in cross-sectional area (4.98 +/- 2.29%), cross-sectional moment of inertia (9.45 +/- 2.37%), total bone mineral density (2.07 +/- 2.09%), fracture index (8.03 +/- 2.03%), and safety factor (20.03 +/- 5.79%) over the 24 month exercise program. Women who exercised and did not take oral contraceptives (E/NOC) declined on most variables related to femoral strength and bone mass, whereas those women who took oral contraceptives were usually intermediate between NE/NOC and E/NOC, whether they exercised or not. These data show that either exercise or OC use is associated with a suppression of the normal increase in bone mass and mechanical strength in the femoral neck in women 18-31 years old, but the combination of exercise and OC use appears to have a less suppressive effect.

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.