Correction: Differential effects of growth hormone and alfa calcidol on trabecular and cortical bones in hypophysectomized rats.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction to: Effects of growth hormone on bone modeling and remodeling in hypophysectomised young female rats: a bone histomorphometric study.

The following corrections are found in the original publication of the article and corrected as below.

Safety of calcium and vitamin D supplements, a randomized controlled trial.

OBJECTIVE: It is anticipated that an intake of vitamin D found acceptable by Endocrine Society Guidelines (10 000 IU/day) with co-administered calcium supplements may result in frequent hypercalciuria and hypercalcaemia. This combination may be associated with kidney stones. The objective of this study was to compare the episodes of hypercalciuria and hypercalcaemia from calcium supplements co-administered with 10 000 IU or 600 IU vitamin D daily. This design allows a comparison of the Institute of Medicine recommendation for the RDA of vitamin D along with the upper limit of calcium intake with the high intake of vitamin D suggested by the Endocrine Society. CONTEXT: Harms of currently recommended high intake of vitamin D have not been studied. DESIGN: The design was a randomized controlled trial with 2 groups with evaluation every 3 months for one year: (a) CaCO3 1200 mg/day with 10 000 IU vitamin D3 /day or (b) CaCO3 1200 mg/day with 600 IU vitamin D3 /day. PATIENTS: This study was conducted in an ambulatory research centre in healthy, white postmenopausal women. MEASUREMENTS: Serum and 24-hour urine calcium were measured. RESULTS: Hypercalcaemia and hypercalciuria occurred in both groups. At the final visit, 19/48 in the high dose D group had hypercalciuria. The odds of developing hypercalciuria were 3.6 [OR = 3.6(1.39, 9.3)] times higher in the high dose D group. The odds of developing hypercalcaemia did not differ between groups. CONCLUSIONS: The safe upper level of vitamin D recommended by the Endocrine Society when accompanied by calcium supplements results in frequent hypercalciuria. The risk of kidney stones at these levels should be investigated.

The vitamin D metabolite ratio (VMR) as a predictor of functional biomarkers of bone health.

CONTEXT: The vitamin D metabolite ratio (VMR) (serum 24,25(OH)2 D3 /25(OH)D3 ) has been proposed as a biomarker of vitamin D sufficiency to replace serum 25(OH)D. OBJECTIVE: To examine the relationships of 24,25(OH)2 D3 and VMR to functional biomarkers of bone health following vitamin D supplementation. SETTING: An ambulatory research centre. DESIGN: Serum from a previous research study of dose response of PTH, calcium absorption and bone turnover to vitamin D supplementation was analysed for vitamin D metabolites (25(OH)D, 24,25(OH)2 D3 ). OUTCOME: The relationship of serum 24,25(OH)2 D3 and VMR to calcium absorption, PTH and bone turnover markers was examined. RESULTS: Although there were strong correlations of serum 25(OH)D with 24,25(OH)2 D3 and free 25(OH)D, its correlation with VMR was lower. After vitamin D supplementation, the change in 25(OH)D, 24,25(OH)2 D3 and VMR was associated with the change in calcium absorption, PTH and CTX. The correlation of the change in PTH with the change in metabolites was the lowest for VMR. Moreover, estimated dose response for standardized values of vitamin D metabolites showed a beta-coefficient for VMR that was significantly less in magnitude compared to other metabolites. CONCLUSION: Serum 24,25(OH)2 D3 is closely associated with the dose response of serum 25(OH)D to vitamin D supplementation. However, the VMR does not appear to be equivalent to either of these metabolites in its response to increasing vitamin D intake or its association with PTH. It is unlikely that VMR will replace 25(OH)D as a biomarker for vitamin D sufficiency.

ASSOCIATION BETWEEN 25-HYDROXYVITAMIN D AND INTACT PARATHYROID HORMONE LEVELS ACROSS LATITUDE AMONG ADULTS WITH AFRICAN ANCESTRY.

OBJECTIVE: To compare levels of 25-hydroxyvitamin D (25[OH]D) associated with a plateauing of intact parathyroid (iPTH) across latitudes among adults with African ancestry. METHODS: This study included approximately 500 adults of African ancestry ages 25 to 45 years living in 4 sites: Chicago, Illinois (41°N), Jamaica (17°N), Ghana (6°N), and South Africa (34°S). Multivariate linear regression models, a nonlinear logistic growth curve model, and piecewise linear models with a single knot were fitted to estimate the 25[OH]D level associated with a plateauing of iPTH with adjustment for covariates. Goodness of fit was compared using computer intensive permutation tests. RESULTS: Mean age was 34.7 (SD 6.2) years, and 46.5% were male. Within each site, the percentage of participants with an iPTH level ≥65 pg/mL was higher among females versus males and was most frequent among South African females (17.1%) and lowest among Jamaican males (0.6%). Goodness of fit tests supported linear regression as the preferred model for the association between iPTH and 25[OH]D in the 4 sites with no 25[OH]D level associated with iPTH plateauing in any site. The slope of the association between 25[OH]D and iPTH differed by latitude; it was strongest in the U.S. (ß = -0.81; 95% confidence interval [CI] = -1.03, -0.59), and weakest in Jamaica (ß = -0.45; 95% CI -0.71, -0.18) with covariate adjustment, but differences in slopes were small. CONCLUSION: The association between 25[OH]D and iPTH appears linear among adults with African ancestry regardless of latitude within a range of 25[OH]D levels between 10 and 60 ng/mL. ABBREVIATIONS: BMI = body mass index CI = confidence interval eGFR = estimated glomerular filtration rate iPTH = intact parathryoid hormone 25[OH]D = 25-hydroxyvitamin D.

Urinary calcium excretion in postmenopausal African American women.

AIM: The objective of this study was to develop a reference range for urine calcium excretion (both 24-hour and fasting) for African American women compared to White women. In addition, the variables that determine urine calcium excretion were identified. MATERIAL: Data were analyzed for baseline studies of healthy postmenopausal volunteers who participated in seven separate studies conducted at one site. METHODS: Some studies included fasting urine Ca/Cr and others 24-hour urine calcium excretion. 24-hour urine calcium was considered with and without correction for urinary creatinine excretion. Calcium was measured initially by atomic absorption spectrophotometry and more recently by an automated method (ADVIA 2400 Chemistry System). RESULTS: Participants were considered healthy based on history and physical and routine laboratory studies. Those screened who had a history of nephrolithiasis were excluded. A reference range for 24-hour urine calcium and fasting urine calcium/ creatinine was developed. Reference intervals of 11 - 197 mg/24-hour urine calcium excretion and of 0.007 - 0.222 of fasting Ca/Cr were found for African American women compared to 21 - 221 mg/24 hours and 0.019 - 0.264 in White women, respectively. Urine creatinine excretion was higher in African Americans consistent with their higher muscle mass. CONCLUSION: Urine calcium excretion is lower in postmenopausal African American than White women. The reference range developed should be considered in the diagnosis of hypocalciuric states and may also be useful in the diagnosis of hypercalciuria.

The vitamin d dose response in obesity.

OBJECTIVE: The prevalence of vitamin D inadequacy is high in obese individuals. Determining the response of serum 25-hydroxyvitamin D (25[OH]D) to vitamin D3 supplementation in obese and nonobese individuals may lead to concurrent recommendations for optimal vitamin D intake in these populations. The objective of this study was to determine the dose response of vitamin D3 in subjects with a body mass index ≥35 kg/m2. METHODS: Randomized, double-blind, placebo-controlled study. This study is an extension of our previous study of vitamin D dosing in healthy adults. After an assessment of baseline 25(OH)D levels, participants were randomized to a vitamin D supplementation arm (100 µg daily if baseline 25[OH]D was <50 nmol/L, or 50 µg daily if baseline 25[OH]D was ≥50 nmol/L) or placebo arm. Subjects with baseline 25(OH)D level ≥80 nmol/L were excluded from the study. Two months following randomization, a repeat 25(OH)D measurement was done. RESULTS: Final analysis included 25 subjects (14 placebo, 11 active). At 2 months, serum 25(OH)D concentration increased to a mean of 75 nmol/L in the active group. Mean slope (i.e., vitamin D3 response), defined as 25(OH) D change/baseline dose, was 0.398 nmol/L/µg/day. CONCLUSION: The dose response of vitamin D3 (slope) in obese subjects was significantly lower (P<.03) at 0.398 nmol/L/µg/day compared to the slope in the previous study of healthy subjects (0.66 nmol/L/µg/day). These results suggest that obese individuals may require 40% higher vitamin D intake than nonobese individuals to attain the same serum 25(OH)D concentration.

25-hydroxyvitamin D levels in African American and Nigerian women.

OBJECTIVES: African Americans (AA) have substantially lower levels of circulating 25-hydroxyvitamin D (25(OH)D) than whites. We compared population-based samples of 25(OH)D in women of African descent from Nigeria and metropolitan Chicago. METHODS: One hundred women of Yoruba ethnicity from southwest Nigeria and 94 African American women from metropolitan Chicago were recruited and compared using a standardized survey protocol and the same laboratory assay for 25(OH)D. RESULTS: Mean 25(OH)D levels were 64 nmol/l among the Nigerians and 29 nmol/l among the AA. Only 10% of the values were shared in common between the groups, and 76% of the Nigerians were above the currently defined threshold for adequate circulating 25(OH)D compared to 5% of the AA. Modest associations were seen between 25(OH)D and measures of obesity, although adjustment for these traits did not materially affect the group differences. CONCLUSION: These data support the presumption that skin color is an adaptive trait which has evolved in part to regulate 25(OH)D. It remains undetermined, however, whether lower values observed in AA have negative health consequences.

Effects of growth hormone on bone modeling and remodeling in hypophysectomized young female rats: a bone histomorphometric study.

Growth hormone (GH) deficiency causes decreased bone mineral density and osteoporosis, predisposing to fractures. We investigated the mechanism of action of GH on bone modeling and remodeling in hypophysectomized (HX) female rats. Thirty female Sprague-Dawley rats at age 2 months were divided into three groups with 10 rats each: control (CON) group, HX group, and HX + GH (3 mg/kg daily s.c.) group, for a 4-week study. Hypophysectomy resulted in cessation of bone growth and decrease in cancellous bone mass. Periosteal bone formation decreased and bone turnover rate of endocortical and trabecular surfaces increased as compared to the CON group. GH administration for 4 weeks restored weight gain and bone growth and mitigated decrease in bone density after hypophysectomy. However, trabecular bone mass in the proximal tibial metaphysis remained lower in group HX + GH than in group CON. Dynamic histomorphometric analysis showed that bone modeling of periosteal bone formation and growth plate elongation was significantly higher in group HX + GH than in group HX. New bone formed beneath the growth plate was predominately woven bone in group CON and group HX + GH. Bone remodeling and modeling-remodeling mixed modes in the endocortical and PTM sites were enhanced by GH administration; both bone formation and resorption activities were significantly higher than in group HX. In conclusion, GH administration to HX rats reactivated modeling activities in modeling predominant sites and increased new bone formation. GH administration also increases remodeling activities in remodeling predominant sites, giving limited net gain in the bone mass.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Vitamin D and Abdominal Aortic Calcification in Older African American Women, the PODA Clinical Trial.

Abdominal aortic calcification (AAC) detected on lateral vertebral fracture assessment is associated with increased cardiovascular risk. Vitamin D deficiency and toxicity have been linked with vascular calcification. The objective of this study was to determine the effect of high-dose vitamin D on the progression of AAC. The Physical Performance, Osteoporosis and vitamin D in African American Women (PODA) is a randomized, clinical trial examining the effect of vitamin D. There were 14.7% subjects with AAC in the vitamin D group, compared to 12.1% in the placebo group at baseline. The prevalence of extended AAC at baseline was 6.4% in the vitamin D group and 3.5% in the placebo group. The extended calcification scores over time were not different between groups. There was no association between AAC and serum 25(OH)D. However, PTH was associated with an increase in AAC in the placebo group.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed. METHODS: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633). FINDINGS: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test). INTERPRETATION: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. FUNDING: None.

Differential effects of growth hormone and alpha calcidol on trabecular and cortical bones in hypophysectomized rats.

Growth hormone (GH) deficiency in children causes severe growth retardation, vitamin D deficiency, and osteopenia. We investigated whether alfacalcidol (1OHD) alone or in combination with GH can improve bone formation. Forty hypophysectomized female rats (HX) at the age of 8 wk were divided into HX, HX + 1OHD (oral 0.25 microg/kg daily), HX+GH (0.666 mg/0.2 mL SC daily) and HX+GH + 1OHD groups for a 4-wk study. Results showed that GH increased body weight, bone area, bone mineral content (BMC), and bone mineral density (BMD), whereas 1OHD only increased BMC and BMD. In cortical bone, GH increased both periosteal and endocortical bone formation resulting in a significant increase in cortical size and area in percentage, whereas 1OHD suppressed endocortical erosion surface per bone surface (ES/BS) without a significant effect on bone formation rate per bone surface (BFR/BS). In trabecular bone, GH mitigated the bone loss by increasing BFR/BS, whereas the 1OHD effect was by suppression of trabecular bone turnover in the HX rats. The combination of GH and 1OHD had no additive effect on increasing trabecular bone mass. In conclusion, GH activates new bone formation and increases bone turnover whereas 1OHD suppresses bone turnover. The combination intervention does not seem to provide any additive benefit.

Vitamin D and Acute Respiratory Infections-The PODA Trial.

BACKGROUND: There is considerable heterogeneity in clinical trials examining the role of vitamin D in the prevention of acute respiratory infections (ARIs). METHODS: The primary aim of the Physical Performance, Osteoporosis, and Vitamin D in Older African-American Women (PODA) trial was the prevention of bone loss and decline in physical performance. A questionnaire about ARIs was administered every 3 months for 3 years to 260 black American women in a double-blind randomized clinical trial that had a placebo group and a vitamin D supplementation group. The serum 25(OH)D level was maintained >30 ng/mL in the vitamin D group. RESULTS: Serum 25(OH)D was maintained >30 ng/mL in 90% of the active group, whereas levels approximated those associated with the recommended dietary allowance (20 ng/mL) in the placebo group. There was no difference in occurrence of ARIs in the treatment group vs the placebo group. ARIs were not related to total or free 25(OH)D, which were measured at baseline and annually for 36 months. CONCLUSIONS: Vitamin D supplementation sufficient to maintain serum 25(OH)D >30 ng/mL does not prevent ARIs in older African American women. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT01153568.

Vitamin D and Falls in Older African American Women: The PODA Randomized Clinical Trial.

BACKGROUND: Limited information is available on the influence of vitamin D on falls in older high-functioning black American women. Endocrine Society guidelines propose serum 25(OH)D levels over 30 ng/mL. OBJECTIVE: To determine if maintenance of serum 25(OH)D above 30 ng/mL protects against falls. DESIGN: The Physical Performance, Osteoporosis and Vitamin D in African American Women (PODA) trial had a prospective, randomized, placebo-controlled, double-dummy design with two arms: one with placebo and one with vitamin D3 adjusted to maintain serum 25(OH)D above 30 ng/mL. The primary outcomes were the prevention of bone loss and the decline in physical performance. PATIENTS: The target population was healthy black women older than 60 years with serum 25(OH)D between 8 and 26 ng/mL. The trial was 3 years in duration with a falls questionnaire administered every 3 months. A total of 260 women entered the study, and 184 completed the 3 years. Mean age was 68.2 years. SETTING: Research center in an academic health center. MAIN OUTCOMES MEASURE: Prevention of falls. INTERVENTION: Participants were randomly assigned to placebo or active vitamin D. Vitamin D3 dose was adjusted to maintain serum 25(OH)D above 30 ng/mL in the active group using a double-dummy design. RESULTS: Baseline 25(OH)D was 22 ng/mL. Mean serum 25(OH)D reached 47 ng/mL in the active group compared with 21 ng/mL in the placebo group. There were 14.2% falls in the previous year recalled at baseline. During the study, 46% reported falling in the treatment group compared with 47% in the placebo group. There was no association of serum 25(OH)D or vitamin D dose with the risk of falling. CONCLUSIONS: There is no benefit of maintaining serum 25(OH)D above 30 ng/mL compared with the Institute of Medicine recommendation (20 ng/mL) in preventing falls in healthy older black American women. J Am Geriatr Soc 67:1043-1049, 2019.

Physical Performance and Vitamin D in Elderly Black Women-The PODA Randomized Clinical Trial.

CONTEXT: There is limited information on the influence of vitamin D on physical performance in black Americans. OBJECTIVE: To determine if maintenance of serum 25(OH)D >75 nmol/L prevents a decline in physical performance. DESIGN: The Physical Performance, Osteoporosis and Vitamin D in African American Women (PODA) trial had a prospective, randomized, placebo controlled, double-dummy design with two arms: one of which is placebo vitamin D3 adjusted to maintain serum 25(OH)D >75 nmol/L. PATIENTS: The target population was healthy elderly black women with serum 25(OH)D between 20 and 65 nmol/L. The trial was 3 years in duration with measurement of physical performance every 6 months: grip strength, Short Physical Performance Battery (SPPB), 10 chair rises, and 6-minute walk distance. A total of 260 women entered the study and 184 completed 3 years. Mean age was 68.2 years. Baseline 25(OH)D was 53 nmol/L; total SPPB was 11 (10 to 12). SETTING: Research center in an academic health center. MAIN OUTCOMES MEASURE: Prevention of decline in physical performance measures. INTERVENTION: Participants were randomly assigned to placebo or active vitamin D. Vitamin D3 dose was adjusted to maintain serum 25(OH)D >75 nmol/L. RESULTS: There was a decline with time in grip strength and the 6-minute walk test. The SPBB increased with time. There were no substantial differences between the placebo and active vitamin D3 groups with respect to the temporal patterns observed for any of the performance measures. CONCLUSION: There is no benefit of maintaining serum 25(OH)D >75 nmol/L in preventing the decline in physical performance in healthy black American women.

Cognition and Vitamin D in Older African-American Women- Physical performance and Osteoporosis prevention with vitamin D in older African Americans Trial and Dementia.

OBJECTIVES: To examine the effect of 25-hydroxyvitamin D (25(OH)D) levels recommended by Endocrine Society guidelines (>30 ng/mL) on cognition in healthy older African-American women over 3 years. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Bone Mineral Research Center at New York University Winthrop Hospital. PARTICIPANTS: Healthy postmenopausal African American women aged 65 and older (N=260; mean age 68.2 ± 4.9; 46% college education or higher). INTERVENTION: Half of the women were randomized to receive vitamin D (adjusted to achieve a serum level > 30 ng/mL) with calcium (diet and supplement total of 1,200 mg), and half were randomized to receive placebo with calcium (1,200 mg). MEASUREMENTS: Cognitive assessments every 6 months using the Mini-Mental State Examination (MMSE) to detect cognitive decline. Mean MMSE scores were calculated over time for both groups. Those with MMSE scores less than 21 at baseline were excluded. RESULTS: The average dose of vitamin D3 was 3,490 ± 1,465 IU per day, and average serum 25(OH)D at 3 years was 46.8 ± 1.2 ng/mL in the active group and 20.7 ± 1.1 ng/mL in the placebo group. Serum 25(OH)D concentration was maintained at greater than 30 ng/mL in 90% of the active group. Over the 3-year period, MMSE scores increased in both groups (p < .001), although change over time was not significantly different between the groups. No adverse events associated with vitamin D were observed. CONCLUSION: There was no difference in cognition over time between older African-American women with serum concentrations of 25(OH)D of 30 ng/mL and greater than those taking placebo. There is no evidence to support vitamin D intake greater than the recommended daily allowance in this population for preventing cognitive decline. J Am Geriatr Soc 67:81-86, 2019.

Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis.

BACKGROUND: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. OBJECTIVES: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. STUDY SELECTION: Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. STUDY APPRAISAL: Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. RESULTS: We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. LIMITATIONS: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. CONCLUSIONS: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013953. FUNDING: The National Institute for Health Research Health Technology Assessment programme.