Vitamin D?supplementation in Batswana children and adults with HIV: a pilot double blind randomized controlled trial.
ABSTRACT: Since vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D?) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (?25D).Prospective randomized double-blind 12-week pilot trial of subjects ages 5.0-50.9 years.Sixty subjects randomized within five age groups to either 4000 or 7000 IU per day of D? and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ?32 ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores.Subjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log?? range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9 ng/ml to 56±18 ng/ml (p<0.0001) and 68% and 90% had 25D ?32 ng/ml, respectively (p = 0.02). ?25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000 IU/d group (p<0.04). Younger (5-13y) and older (30-50y) subjects had greater ?25D than those 14-29y (26±17 and 28±12 vs. 11±11 ng/ml, respectively, p?0.001). ?25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p?0.03).In a pilot study in Botswana, 12-week high dose D? supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.ClinicalTrials.gov NCT02189902.
Project description:We investigated intergenerational associations of adolescent mothers' and grandmothers' anthropometrics and schooling with adolescent mothers' offspring's anthropometrics in Ethiopia, India, Peru, and Vietnam. We examined birthweight (n = 283), birthweight Z-score (BWZ), conditional growth in weight-for-age Z-score (cWAZ, residuals from a regression of WAZ at last survey round on BWZ, sex, and age), and height-for-age Z-score (HAZ) of children born to older cohort adolescent girls in the Young Lives study. Our key independent variables were adolescent mothers' body size: HAZ and body-mass-index-for-age Z-score (BMIZ) at age 8, conditional HAZ (cHAZ, residuals from a regression of HAZ at the end of a growth period on prior HAZ, age, and sex), conditional BMIZ growth (cBMIZ, calculated analogously), and grandmaternal BMIZ, HAZ, and schooling. We adjusted for child, maternal, and household characteristics. Adolescent mothers' cHAZ (ages 8-15) predicted birthweight (? = 130 g, 95% confidence interval (CI) 31-228), BWZ (? = 0.31, CI 0.09-0.53), and cWAZ (? = 0.28, CI 0.04-0.51). Adolescent mothers' BMIZ at age 8 predicted birthweight (? = 79 g, CI 16-43) and BWZ (? = 0.22, CI 0.08-0.36). Adolescent mothers' cBMIZ (ages 12-15) predicted child cWAZ and HAZ. Grandmothers' schooling predicted grandchild birthweight (? = 22 g, CI 1-44) and BWZ (? = 0.05, CI 0.01-0.10).
Project description:<h4>Background</h4>Poor growth in early childhood has been associated with increased risk of mortality and morbidity, as well as long-term deficits in cognitive development and economic productivity.<h4>Objectives</h4>Data from the MAL-ED cohort study were used to identify factors in the first 2 y of life that are associated with height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, BMIZ) at 5 y of age.<h4>Methods</h4>A total of 1017 children were followed from near birth until 5 y of age at sites in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania. Data were collected on their growth, environmental enteric dysfunction (EED), micronutrient status, enteric pathogen burden, illness prevalence, dietary intake, and various other socio-economic and environmental factors.<h4>Results</h4>EED biomarkers were related to size at 5 y. Mean lactulose:mannitol z-scores during the first 2 y of life were negatively associated with all of the growth measures (HAZ: -0.11 [95% CI: -0.19, -0.03]; WAZ: -0.16 [95% CI: -0.26, -0.06]; BMIZ: -0.11 [95% CI: -0.23, 0.0]). Myeloperoxidase was negatively associated with weight (WAZ: -0.52 [95% CI: -0.78, -0.26] and BMIZ: -0.56 [95% CI: -0.86, -0.26]); whereas ?-1-antitrypsin had a negative association with HAZ (-0.28 [95% CI: -0.52, -0.04]). Transferrin receptor was positively related to HAZ (0.18 [95% CI: 0.06, 0.30]) and WAZ (0.21 [95% CI: 0.07, 0.35]). Hemoglobin was positively related to HAZ (0.06 [95% CI: 0.00, 0.12]), and ferritin was negatively related to HAZ (-0.08 [95% CI: -0.12, -0.04]). Bacterial density in stool was negatively associated with HAZ (-0.04 [95% CI: -0.08, 0.00]), but illness symptoms did not have any effect on size at 5 y.<h4>Conclusions</h4>EED markers, bacterial density, and iron markers are associated with growth at 5 y of age. Interventions to reduce bacterial burden and EED may improve long-term growth in low-income settings.
Project description:Context:Changes in vitamin D binding protein (DBP) concentrations and catabolism of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D (24,25D) after vitamin D2 supplementation may alter concentrations and bioavailability of circulating 25-hydroxyvitamin D (25D). Objective:Examine acute changes in vitamin D metabolism and bioavailability after vitamin D2 supplementation. Methods:Study design was secondary analysis of a single-arm interventional study. Thirty consenting volunteers were treated with five 50,000 IU oral doses of ergocalciferol over 2 weeks. Main outcome measures included concentrations of DBP, vitamin D metabolites, and bioavailable 25-hydroxyvitamin D (25D) in pre- and posttreatment serum samples. Results:After supplementation, 25D2 (mean ± standard deviation) increased from 1.4 ± 0.9 ng/mL to 45.3 ± 16.5 ng/mL (P < 0.0001), and 25D3 levels decreased from 26.8 ± 9.9 ng/mL to 19.7 ± 8.2 ng/mL (P < 0.0001). Total 25D (25D2 plus 25D3) increased from 28.2 ± 10.0 ng/mL to 65.0 ± 21.1 ng/mL (152.2% ± 102.5%; P < 0.0001). DBP and total 24,25D concentrations increased 39.1% ± 39.4% (165.6 ± 53.8 µg/mL to 222.0 ± 61.1 µg/mL; P < 0.0001) and 31.3% ± 48.9% (3.9 ± 2.0 ng/mL to 4.7 ± 2.1 ng/mL; P = 0.0147), respectively. In contrast to total 25D, bioavailable 25D increased by 104.4% ± 99.6% (from 5.0 ± 2.0 ng/mL to 8.7 ± 2.7 ng/mL; P < 0.001), and 1,25D increased by 32.3% ± 38.8% (from 45.5 ± 10.7 pg/mL to 58.1 ± 13.0 pg/mL; P = 0.0006). There were no changes in calcium or parathyroid hormone (P > 0.05 for both). Conclusion:Changes after vitamin D2 supplementation involve acute rise in serum DBP and 24,25D, both of which may attenuate the rise in bioavailable 25D and 1,25D.
Project description:Context:Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D status [total (protein bound plus free) vs free 25D]. Objective:To assess the effects of vitamin D3 (cholecalciferol, or D3) vs 25-hydroxyvitamin D3 (calcifediol, or 25D3) on total and free 25D in a multiethnic cohort of adults, and whether change in parathyroid hormone (PTH) is more strongly associated with total vs free 25D. Design:Sixteen-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks. Setting:Academic medical center. Participants:Thirty-five adults ?18 years of age with 25D levels <20 ng/mL. Intervention:Sixty micrograms (2400 IU)/d of D3 or 20 ?g/d of 25D3. Main Outcome Measures:Total and free 25D, and PTH. Results:Baseline total (16.2 ± 3.7 vs 17.0 ± 2.5 ng/mL; P = 0.4) and free (4.2 ± 0.8 vs 4.7 ± 1.0 pg/mL; P = 0.2) 25D were similar between D3 and 25D3 groups, respectively; 25D3 increased total (+25.5 vs +13.8 ng/mL; P = 0.001) and free (+6.6 vs +3.5 pg/mL; P = 0.03) 25D more than D3. By 4 weeks, 87.5% of 25D3 participants had total 25D levels ?30 ng/mL, compared with 23.1% of D3 participants (P = 0.001). Change in PTH was associated with both total (P = 0.01) and free 25D (P = 0.04). Conclusions:25D3 increased total and free 25D levels more rapidly than D3, regardless of race/ethnicity. Free and total 25D were similarly associated with change in PTH.
Project description:Controversy persists over: 1) how best to restore low serum 25-hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D.To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D.Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks.Thirty-eight adults (19 D2 and 19 D3) ?18 years of age with baseline 25D levels <30 ng/mL were recruited from an academic ambulatory osteoporosis clinic.Serum measures were total 25D, free 25D (directly measured), 1,25-dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio.Baseline total (22.2 ± 3.3 vs 23.3 ± 7.2 ng/mL; P = .5) and free (5.4 ± 0.8 vs 5.3 ± 1.7 pg/mL; P = .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P = .001) and free (+3.6 vs +6.2 pg/mL; P = .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium.D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity.
Project description:Calcifediol (25D) availability is crucial for calcitriol (1,25D) synthesis, but regulation of vitamin D hydroxylases is majorly responsible for 1,25D synthesis. The net efficiency of vitamin D hydroxylases might be informative. We assume that the ratio between calcitriol and calcifediol (25D/1,25D) serum concentrations could suggest the vitamin D hydroxylation efficiency.We evaluated 25D/1,25D in different patient populations: hemodialysis (HD, n = 76), CKD stage 2-5 (n = 111), renal transplant (TX, n = 135), patients with no renal disease (No-CKD, n = 290), and primary hyperparathyroidism (PHP, n = 20).The geometric mean of 1,25D/25D (pg/ng) averaged 1.11 (HD), 1.36 (CKD), 1.77 (TX), 2.22 (No-CKD), and 4.11 (PHP), with a progressive increment from HD to PHP (p-value for the trend <0.001). Each clinical condition elicited a significant effect on 25D/1,25D (p < 0.0001) and adjusted multivariate analysis indicated levels of Cas, Ps, PTH, and 25D as predictors of 25D/1,25D. Both in vitamin D deficient and replete subjects (25D< or ?20 ng/ml) 25D/1,25D associated with each clinical condition (p < 0.0001) and mean values increased progressively from HD to PHP (p-values for the trend <0.0001). Regression analysis between 25D (substrate) and 25D/1,25D (efficiency) revealed an exponential negative correlation in No-CKD (r(2)Exp = 0.53, p < 0.001) with sharp increments of 25D/1,25D when 25D values are <20 ng/ml. At variance, in CKD (r(2)lin = 0.19) and in TX (r(2)lin = 0.32) the regression was linear as if, in case of deficit, some inhibition of the system were operating.In conclusion 1,25D/25D can reflect the efficiency of vitamin D hydroxylases more than separate evaluation of 25D and 1,25D and can facilitate the therapeutic choices in different patient populations.
Project description:BACKGROUND:In the primary analysis of a 12-month double-blind randomized active placebo-controlled trial, treatment of children with cystic fibrosis (CF) and pancreatic insufficiency (PI) with a readily absorbable structured lipid (Encala™, Envara Health, Wayne, PA) was safe, well-tolerated and improved dietary fat absorption (stool coefficient of fat absorption [CFA]), growth, and plasma fatty acids (FA). OBJECTIVE:To determine if the Encala™ treatment effect varied by severity of baseline fat malabsorption. METHODS:Subjects (n = 66, 10.5±3.0 yrs, 39% female) with baseline CFA who completed a three-month treatment with Encala™ or a calorie and macronutrient-matched placebo were included in this subgroup analysis. Subjects were categorized by median baseline CFA: low CFA (<88%) and high CFA (?88%). At baseline and 3-month evaluations, CFA (72-hour stool, weighed food record) and height (HAZ), weight (WAZ) and BMI (BMIZ) Z-scores were calculated. Fasting plasma fatty acid (FA) concentrations were also measured. RESULTS:Subjects in the low CFA subgroup had significantly improved CFA (+7.5±7.2%, mean 86.3±6.7, p = 0.002), and reduced stool fat loss (-5.7±7.2 g/24 hours) following three months of EncalaTM treatment. These subjects also had increased plasma linoleic acid (+20%), ?-linolenic acid (+56%), and total FA (+20%) (p?0.005 for all) concentrations and improvements in HAZ (0.06±0.08), WAZ (0.17±0.16), and BMIZ (0.20±0.25) (p?0.002 for all). CFA and FA were unchanged with placebo in the low CFA group, with some WAZ increases (0.14±0.24, p = 0.02). High CFA subjects (both placebo and Encala™ groups) had improvements in WAZ and some FA. CONCLUSIONS:Subjects with CF, PI and more severe fat malabsorption experienced greater improvements in CFA, FA and growth after three months of Encala™ treatment. Encala™ was safe, well-tolerated and efficacious in patients with CF and PI with residual fat malabsorption and improved dietary energy absorption, weight gain and FA status in this at-risk group.
Project description:BACKGROUND:24,25-Dihydroxyvitamin D [24,25(OH)2D] is a metabolite of 25-hydroxyvitamin D (25D). Blacks frequently have low total 25D without manifestations of vitamin D deficiency, suggesting that total serum 25D may incorrectly reflect vitamin D status in different racial groups. The ratio of serum 24,25(OH)2D to 25D [vitamin D metabolite ratio (VMR)] represents a new candidate biomarker for vitamin D status. METHODS:We measured 24,25(OH)2D3 and 25D3 by mass spectrometry in a random community cohort of black (n = 212) and white (n = 164) Americans to evaluate VMR as a marker for vitamin D status. We measured parathyroid hormone concentrations by immunoassay to compare VMR and 25D3 against a physiological indicator of vitamin D deficiency. RESULTS:Serum 24,25(OH)2D3 strongly correlated with 25D3 in both black and white study participants (r = 0.90, P < 0.001 and r = 0.86, P < 0.001 respectively). Blacks had lower mean 25D3 than whites [17.0 (7.8) vs 27.5 (11.3) ng/mL; 42.4 (19.5) vs 68.6 (28.2) nmol/L, P < 0.001] and lower mean 24,25(OH)2D3 [2.1 (1.3) vs 3.6 (2.0) ng/mL; 5.1 (3.1) vs 8.7 (4.8) nmol/L, P < 0.001]. In contrast to total 25D3 concentrations, mean VMR values were similar in blacks and whites [11.9 (4.0) vs 12.5 (3.4), P = 0.16, respectively] and were negatively correlated with parathyroid hormone concentrations in both races (rs = -0.26, P < 0.001, and rs = -0.25, P < 0.001, respectively). CONCLUSIONS:Our results provide further evidence that measurement of total 25D for assessment of vitamin D status in patients of African descent deserves reevaluation and suggest that alternative measures such as VMR should be considered.
Project description:OBJECTIVE:To estimate the associations between measles vaccination and child anthropometry, cognition, and schooling outcomes in Ethiopia, India, and Vietnam. METHODS:Longitudinal survey data from Young Lives were used to compare outcomes at ages 7-8 and 11-12 years between children who reported receipt or non-receipt of measles vaccine at 6-18 months-of-life (n = ∼2000/country). Z-scores of height-for-age (HAZ), BMI-for-age (BMIZ), weight-for-age (WAZ), Peabody Picture Vocabulary Test (PPVT), early grade reading assessment (EGRA), language and mathematics tests, and attained schooling grade were examined. Propensity score matching was used to control for systematic differences between measles-vaccinated and measles-unvaccinated children. FINDINGS:Using age- and country-matched measles-unvaccinated children as comparisons, measles-vaccinated children had better anthropometrics, cognition, and schooling. Measles-vaccinated children had 0.1 higher HAZ in India and 0.2 higher BMIZ and WAZ in Vietnam at age 7-8 years, and 0.2 higher BMIZ at age 11-12 years in Vietnam. At ages 7-8 years, they scored 4.5 and 2.9 percentage points (pp) more on PPVT and mathematics, and 2.3 points more on EGRA in Ethiopia, 2.5 points more on EGRA in India, and 2.6 pp, 4 pp, and 2.7 points more respectively on PPVT, mathematics, and EGRA in Vietnam. At ages 11-12 years, they scored 3 pp more on English and PPVT in India, and 1.7 pp more on PPVT in Vietnam. They also attained 0.2-0.3 additional schooling grades across all ages and countries. CONCLUSION:Our findings suggest that measles vaccination may have benefits on cognitive gains and school-grade attainment that can have broad educational and economic consequences which extend beyond early childhood.
Project description:The study aim was to determine the effect of a dietary intervention on growth, body composition and resting energy expenditure (REE) in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in a randomized, double blind, placebo-controlled trial.Subjects (5 to 17 yrs) participated in a 12-month trial of the organized lipid matrix LYM-X-SORB™ (LXS) vs. placebo dietary supplements with similar calories, total fat and fatty acids. Dietary intake was assessed using 3-day weighed food records. Height (HAZ), weight (WAZ), BMI (BMIZ), mid-upper arm muscle (UAMAZ) and fat area (UAFAZ) Z-scores were calculated. Fat mass (FM) and fat-free mass (FFM) were obtained by whole body DXA. REE (kcal/d) was evaluated by indirect calorimetry at baseline, 3 and 12 months and %REE calculated using Schofield equations. No growth or REE differences were observed between LXS and placebo groups so data were pooled for analysis.63 children (57% males, age 10.6 ± 2.9 yr, 43% receiving LXS) completed REE measurements. Caloric intake increased from a median of 2502 [1478, 4909] to 2616 [1660, 4125] kcal/d at 12 months. HAZ, WAZ and UAMAZ increased (p < 0.05) over 12 months. Mean REE was 109 ± 8% predicted at baseline and 107 ± 9% at 12 months (p < 0.05). REE (kcal/d) adjusted for FFM and FM decreased over 12 months ([mean ± SE] -31 ± 12 kcals, p < 0.01), significant only in males (-49 ± 16 kcals, p < 0.01).Over a 12 month nutrition intervention with either LXS or placebo, the growth status, muscle stores and REE improved. Sustained increased energy intake improved energy metabolism, growth and nutritional status in school age children with CF, PI and mild lung disease.