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 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.

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.

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.

Vitamin D Supplementation in Elderly Black Women Does Not Prevent Bone Loss: A Randomized Controlled Trial.

Black Americans have lower levels of serum 25(OH)D but superior bone health compared to white Americans. There is controversy over whether they should be screened for vitamin D deficiency and have higher vitamin D requirements than recommended by the Institute of Medicine (IOM). The purpose of this trial was to determine whether Vitamin D supplementation in elderly black women prevents bone loss. A total of 260 healthy black American women, 60 years of age and older were recruited to take part in a two-arm, double-dummy 3-year randomized controlled trial (RCT) of vitamin D3 versus placebo. The study was conducted in an ambulatory clinical research center. Vitamin D3 dose was adjusted to maintain serum 25(OH)D above 75 nmol/L. Bone mineral density (BMD) and serum were measured for parathyroid hormone (PTH), C-terminal crosslink telopeptide (CTX), and bone-specific alkaline phosphatase (BSAP) every 6 months. Baseline serum 25(OH)D3 was 54.8 ± 16.8 nmol/L. There was no group × time interaction effect for any BMD measurement. For all BMD measurements, except for total body and spine, there was a statistically significant negative effect of time (p < 0.001). An equivalency analysis showed that the treatment group was equivalent to the control group. Serum PTH and BSAP declined, with a greater decline of PTH in the treatment group. The rate of bone loss with serum 25(OH)D above 75 nmol/L is comparable to the rate of loss with serum 25(OH)D at the Recommended Dietary Allowance (RDA) of 50 nmol/L. Black Americans should have the same exposure to vitamin D as white Americans. © 2018 American Society for Bone and Mineral Research.

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.

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.

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.

Calcium and vitamin d supplementation in postmenopausal women.

CONTEXT: Bone health is influenced by the intake of both calcium and vitamin D. OBJECTIVE: Our objective was to evaluate the influence of calcium and vitamin D supplementation on PTH and bone turnover. SETTING, PATIENTS, AND DESIGN: At an ambulatory research center, 159 postmenopausal healthy white women participated in this double-blind, placebo-controlled parallel, longitudinal factorial study that was 6 months in duration. INTERVENTIONS: Subjects were randomly allocated to 4 groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D3 (100 µg) plus placebo, and 4) vitamin D3 and calcium. Serum and urine were collected fasting and 2 hours after a calcium load at baseline and at 3 and 6 months. MAIN OUTCOME MEASURES: Serum PTH, cross-linked C-telopeptide (CTX), and procollagen type I N-terminal propeptide (P1NP) were measured. RESULTS: Before study medication, a calcium load resulted in a decline in PTH and CTX and an increase in urinary calcium excretion. Serum CTX and P1NP declined over time with calcium supplementation but did not change with increased vitamin D intake. There was a decline in PTH in the vitamin D groups in the fasting state compared with placebo. Suppression of PTH was greater after a calcium load in the vitamin D groups. A calcium load decreased PTH and CTX and raised urinary calcium. CONCLUSIONS: Fasting PTH declines with vitamin D supplementation. PTH declines after calcium intake. Supplementation of the diet with 1200 mg calcium/d reduces bone turnover markers, whereas supplementation with up to100 µg vitamin D3/d does not.

Vitamin d and serum cytokines in a randomized clinical trial.

Background. The role of vitamin D in the body's ability to fight influenza and URI's 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.

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 intake to attain a desired serum 25-hydroxyvitamin D concentration.

BACKGROUND: Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [25(OH)D] concentration >75 nmol/L. OBJECTIVE: We aimed to determine the intake of vitamin D(3) needed to raise serum 25(OH)D to >75 nmol/L. DESIGN: The design was a 6-mo, prospective, randomized, double-blinded, double-dummy, placebo-controlled study of vitamin D(3) supplementation. Serum 25(OH)D was measured by radioimmunoassay. Vitamin D(3) intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration. RESULTS: A total of 138 subjects entered the study. After 2 dose adjustments, almost all active subjects attained concentrations of 25(OH)D >75 nmol/L, and no subjects exceeded 220 nmol/L. The mean (+/-SD) slope at 9 wk [defined as 25(OH)D change/baseline dose] was 0.66 +/- 0.35 (nmol/L)/(microg/d) and did not differ statistically between blacks and whites. The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.