Mageda Mikhail

A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections.

Vitamin D has been shown to be an important immune system regulator. Vitamin D insufficiency during winter may cause increased susceptibility to upper respiratory tract infections (URIs). To determine whether vitamin D supplementation during the winter season prevents or decreases URI symptoms, 162 adults were randomized to receive 50 microg vitamin D3 (2000 IU) daily or matching placebo for 12 weeks. A bi-weekly questionnaire was used to record the incidence and severity of URI symptoms. There was no difference in the incidence of URIs between the vitamin D and placebo groups (48 URIs vs. 50 URIs, respectively, P=0.57). There was no difference in the duration or severity of URI symptoms between the vitamin D and placebo groups [5.4+/-4.8 days vs. 5.3+/-3.1 days, respectively, P=0.86 (95% CI for the difference in duration -1.8 to 2.1)]. The mean 25-hydroxyvitamin D level at baseline was similar in both groups (64.3+/-25.4 nmol/l in the vitamin D group; 63.0+/-25.8 nmol/l in the placebo group; n.s.). After 12 weeks, 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group, whereas there was no change in vitamin D levels in the placebo group. There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter. Further studies are needed to determine the role of vitamin D in infection.

Free 25(OH)D and the Vitamin D Paradox in African Americans

CONTEXT African Americans have a lower total serum 25-hydroxyvitamin D [25(OH)D] but superior bone health. This has been referred to as a paradox. A recent publication found that free serum 25(OH)D is the same in black and white individuals. However, the study was criticized because an indirect method was used to measure free 25(OH)D. A direct method has recently been developed. OBJECTIVE We hypothesized that although total serum 25(OH)D is lower in African Americans, free serum 25(OH)D measured directly would not differ between races. DESIGN White and black healthy postmenopausal women were matched for age and body mass index. Serum total 25(OH)D, PTH, 1,25-dihydroxyvitamin D, vitamin D binding protein (VDBP), and bone density were measured. Measurement of free 25(OH)D was carried out using an ELISA. SETTING The study was conducted at an ambulatory research unit in a teaching hospital. OUTCOME A cross-racial comparison of serum free 25(OH)D was performed. RESULTS A propensity match resulted in the selection of a total of 164 women. Total 25(OH)D was lower in black women (19.5 ± 4.7 vs 26.9 ± 6.4 ng/mL), but a direct measurement of free 25(OH)D revealed almost identical values (5.25 ± 1.2 vs 5.25 ± 1.3 ng/mL) between races. VDBP was significantly lower in blacks when using a monoclonal-based ELISA but higher with a polyclonal-based ELISA. Serum PTH, 1,25-dihydroxyvitamin D, and bone density were higher in African Americans. CONCLUSIONS Free serum 25(OH)D is the same across races despite the lower total serum 25(OH)D in black women. Results comparing VDBP between races using a monoclonal vs a polyclonal assay were discordant.

Racial differences in femoral dimensions and their relation to hip fracture

White women have a higher rate of age-specific hip fractures than black women. Recently, femoral dimensions have been implicated in osteoporotic fractures. To study racial differences in femoral dimensions, dual X-ray absorptiometry scans were obtained for two similar groups of 50 white women and 50 black women. We measured the hip axis length (the distance from below the lateral aspect of the greater trochanter to the inner pelvic brim), the neck width and the neck/shaft angle on the scan print-out. The observer was masked to the race of the subject. The results were analyzed using the independentt-test and showed that the hip axis length and the neck width were significantly longer in the white women than in the black women (p values <0.05 and <0.02 respectively) but that the neck/shaft angle was not statistically different in the two groups. We conclude that femoral geometry differs among races. Whether this contributes to the lower risk of hip fracture in black women will require prospectively based studies.

Biochemical and hormonal variables in black and white women matched for age and weight

Weight and age may influence the levels of indexes of bone remodeling and the calciotropic hormones. In a study of interracial differences in these women, our black population was heavier than our white population. We therefore matched a subset of 96 black and 96 white women from our larger population for age and weight to determine whether a racial difference exists independent of the effects of weight and age. In addition, we were able to measure other indexes of bone remodeling (N-telopeptide of cross-linked collagen and pyridinoline cross-links), as well as hormones that may influence calcium metabolism (insulin-like growth factor-1 (IGF-1), insulin, calcitonin, and gastrin) in this subset. All indexes of bone remodeling were lower in black women. Black postmenopausal women had lower serum levels of calcidiol and higher parathyroid hormone (PTH) levels. The higher bone mass of black women is associated with lower bone remodeling in the presence of skeletal resistance to PTH. Serum IGF- 1, insulin, and calcitonin levels did not differ significantly between races. Serum gastrin levels were higher in black women. The higher levels of gastrin in black women should be investigated further for its possible effect on the absorption of calcium salts.

Body Composition by Dual-Energy X-ray Absorptiometry in Black Compared with White Women

Abstract: Dual-energy X-ray absorptiometry (DXA) has recently been applied to the measurement of body composition using a three-compartment model consisting of fat, lean and bone mineral. The mass of skeletal muscle may be approximated by measurement of the lean tissue mass of the extremities. In addition, body fat distribution can be estimated by determining the ratio of fat in the trunk to the fat in the extremities. In the current study, DXA was used to compare body composition and fat distribution between black (n= 162) and white women (n= 203). Black women had a higher mineral mass and a higher skeletal muscle mass. The ratio of mineral to muscle mass was higher in black women, even when the data were adjusted for age, height and weight. Both total body bone mineral and muscle mass declined with age in both races, with evidence for an accelerated loss of bone mineral after menopause. Body size (height and weight) was generally a significant variable in developing regressions of each compartment against age. Their higher musculoskeletal mass may lead to misclassification of 12% of black women as obese if body mass index is used as an index of obesity. Body fat distribution (trunk/leg) did not differ between races in the raw data. However, for women of the same age, height and weight, white women have a significantly higher trunk/leg fat ratio. Body composition values for fat, lean and bone mineral obtained from DXA should be adjusted not only for gender but also for age, height, weight and ethnicity.

The relative influence of calcium intake and vitamin D status on serum parathyroid hormone and bone turnover biomarkers in a double-blind, placebo-controlled parallel group, longitudinal factorial design.

BACKGROUND Adequate calcium and vitamin D are needed to maintain calcium balance. OBJECTIVE Our objective was to examine the influence of calcium intake and vitamin D exposure separately and their interaction on biomarkers of calcium sufficiency. DESIGN Healthy men and women, age 20-80 yr, were randomly allocated to four groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D(3) (100 microg) plus placebo, and 4) vitamin D(3) and calcium. Fasting serum and urine as well as serum and urine 2 h after a calcium load (600 mg of calcium carbonate) were obtained at baseline and 3 months. RESULTS Ninety-nine participants were randomized; 78 completed the study. Baseline demographics, protein intake and laboratory studies did not differ among the four groups. Study medication compliance was 90%. Fasting bone turnover markers declined after 3 months only in the two groups given calcium supplements and increased in the vitamin D(3) plus placebo calcium group. The calcium load resulted in a decrease in PTH and in bone turnover markers that did not differ among groups. Urinary calcium excretion increased in the combined group. Mean serum 25-hydroxyvitamin D increased from a baseline of 67 (18 sd) nmol/liter to 111 (30 sd) nmol/liter after vitamin D supplementation. CONCLUSION Increased habitual calcium intake lowered markers of bone turnover. Acute ingestion of a calcium load lowered PTH and bone turnover markers. Additional intake of 100 microg/d vitamin D(3) did not lower PTH or markers of bone turnover.

Vitamin D and Serum Cytokines in a Randomized Clinical Trial

Background. The role of vitamin D in the bodys ability to fight influenza and URIs may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 μg/d (2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-γ, TNF-α) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group. Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (−62.9%, P < .0001), IFN-γ (−38.9%, P < .0001), IL-4 (−50.8%, P = .001), IL-8 (−48.4%, P < .0001), and IL-10 (−70.4%, P < .0001). In the placebo group, there were significant declines for GM-CSF (−53.2%, P = .0007) and IFN-γ (−34.4%, P = .0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 ± 25.4 nmol/L to 88.5 ± 23.2 nmol/L. Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.

Stiffness in Discrimination of Patients with Vertebral Fractures

Abstract: We measured the ultrasound parameters of the heels of 49 women with vertebral fractures and 87 age-matched controls using an Achilles ultrasound device. Average broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were significantly lower in fracture patients (p<0.0001). We also estimated the ultrasound parameters of patients compared with age-matched non-fracture controls and found the mean BUA to be −1.02 SD below control values. The mean SOS was −0.97 SD and the mean Stiffness was −1.12 SD below control values. Femoral bone mineral density (BMD) at the neck, Ward’s triangle and the trochanter, the total-body BMD and L2–4 BMD were measured with dual-energy X-ray absorptiometry (DXA) and found to be significantly lower in fracture patients (p<0.0001). All correlation coefficients between ultrasound parameters and DXA measurements were >0.5 and statistically significant (p<0.0001). A stepwise logistic regression with presence or absence of vertebral fracture as the response variable and all ultrasound – DXA parameters as the explanatory variables indicated that the best predictor of fracture was Stiffness, with additional predictive ability provided by spine BMD. Sensitivity and specificity of all measures were determined by the areas under the receiver operating characteristic (ROC) curve, which were 0.76 ± 0.04 for BUA, 0.77 ± 0.04 for SOS, 0.78 ± 0.04 for Stiffness and 0.78 ± 0.03 for spine BMD. The areas under the ROC curves of BUA, SOS, Stiffness and spine BMD were compared and it was found that Stiffness and spine BMD were significantly better predictors of fracture than BUA and SOS. These results support many recent studies showing that ultrasound measurements of the os-calcis have diagnostic sensitivity comparable to DXA, and also demonstrated that Stiffness was a better predictor of fracture than spine BMD.

Vitamin D supplementation increases calcium absorption without a threshold effect

BACKGROUND The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency. OBJECTIVE The objective was to determine whether there is a threshold beyond which increasing doses of vitamin D, or concentrations of serum 25-hydroxyvitamin D [25(OH)D], no longer increase calcium absorption. DESIGN This was a placebo-controlled, dose-response, randomized, double-blind study of the effect of vitamin D on calcium absorption in healthy postmenopausal women. Seventy-six healthy postmenopausal women were randomly assigned to placebo or 800 IU (20 μg), 2000 IU (50 μg), or 4000 IU (100 μg) vitamin D₃ for 8 wk. The technique of dual isotopes of stable calcium was used with a calcium carrier to measure calcium absorption at baseline and after 8 wk. RESULTS Seventy-one women with a mean ± SD age of 58.8 ± 4.9 y completed the study. The mean calcium intake was 1142 ± 509 mg/d and serum 25(OH)D was 63 ± 14 nmol/L at baseline. A statistically significant linear trend of an increase in calcium absorption adjusted for age and body mass index with increasing vitamin D₃ dose or serum 25(OH)D concentration was observed. A 6.7% absolute increase in calcium absorption was found in the highest vitamin D₃ group (100 μg). No evidence of nonlinearity was observed in the dose-response curve. CONCLUSIONS No evidence of a threshold of calcium absorption was found with a serum 25(OH)D range from 40 to 130 nmol/L. Calcium absorption in this range is not a useful biomarker to determine nutritional recommendations for vitamin D.

Free 25(OH)D and Calcium Absorption, PTH, and Markers of Bone Turnover

CONTEXT It has been proposed that serum free 25-hydroxyvitamin D [25(OH)D] may better reflect vitamin D action than total 25(OH)D. An ELISA for serum free 25(OH)D has recently become available, permitting direct assay. OBJECTIVE To determine whether serum free 25(OH)D provides additional information in relation to calcium absorption and other biomarkers of vitamin D action compared to total serum 25(OH)D. SETTING Ambulatory research setting in a teaching hospital. OUTCOME Serum free 25(OH)D measured in a previously performed study of varied doses of vitamin D3 (placebo and 800, 2000, and 4000 IU) on calcium absorption, PTH, procollagen type 1 N-terminal propeptide, and C-terminal telopeptides of type I collagen. Free 25(OH)D was measured by ELISA. Calcium absorption was measured at baseline and at 10 weeks using stable dual calcium isotopes. RESULTS Seventy-one subjects completed this randomized, placebo-controlled trial. Baseline group mean free and total 25(OH)D varied from 4.7 ± 1.8 to 5.4 ± 1.5 pg/mL, and from 23.7 ± 5.9 to 25.9 ± 6.1 ng/mL, respectively. Participants assigned to the 4000-IU dose arm achieved free 25(OH)D levels of 10.4 pg/mL and total 25(OH)D levels of 40.4 ng/mL. Total and free 25(OH)D were highly correlated at baseline and after increasing vitamin D dosing (r = 0.80 and 0.85, respectively). Free 25(OH)D closely reflected changes in total 25(OH)D. PTH was similarly correlated at baseline and follow-up with total and free 25(OH)D. Serum C-terminal telopeptides of type I collagen had a moderate positive correlation with total and free 25(OH)D at follow-up. The serum 1,25-dihydroxyvitamin D change increased significantly with the change in 25(OH)D but not with the change in free 25(OH)D. CONCLUSION There was no advantage from measuring free over total 25(OH)D in assessing the response of calcium absorption, PTH, and markers of bone turnover to vitamin D. Free 25(OH)D responded to increasing doses of vitamin D in a similar fashion to total 25(OH)D.