Jamil B. Scott

Effect of Vitamin D Supplementation on Blood Pressure in Blacks

Blacks have significantly higher rates of hypertension than whites, and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on blood pressure in blacks. During 2 winters from 2008 to 2010, 283 blacks (median age, 51 years) were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 international units of cholecalciferol per day. At baseline, 3 months, and 6 months, systolic and diastolic pressure and 25-hydroxyvitamin D were measured. The 3-month follow-up was completed in 250 (88%) participants. The difference in systolic pressure between baseline and 3 months was +1.7 mm Hg for those receiving placebo, −0.66 mm Hg for 1000 U/d, −3.4 mm Hg for 2000 U/d, and −4.0 mm Hg for 4000 U/d of cholecalciferol (−1.4 mm Hg for each additional 1000 U/d of cholecalciferol; P=0.04). For each 1-ng/mL increase in plasma 25-hydroxyvitamin D, there was a significant 0.2-mm Hg reduction in systolic pressure (P=0.02). There was no effect of cholecalciferol supplementation on diastolic pressure (P=0.37). Within an unselected population of blacks, 3 months of oral vitamin D3 supplementation significantly, yet modestly, lowered systolic pressure. Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results, particularly among blacks, a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension.

Effect of Vitamin D Supplementation on Blood Pressure in BlacksNovelty and Significance

Blacks have significantly higher rates of hypertension than whites, and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on blood pressure in blacks. During 2 winters from 2008 to 2010, 283 blacks (median age, 51 years) were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 international units of cholecalciferol per day. At baseline, 3 months, and 6 months, systolic and diastolic pressure and 25-hydroxyvitamin D were measured. The 3-month follow-up was completed in 250 (88%) participants. The difference in systolic pressure between baseline and 3 months was +1.7 mm Hg for those receiving placebo, −0.66 mm Hg for 1000 U/d, −3.4 mm Hg for 2000 U/d, and −4.0 mm Hg for 4000 U/d of cholecalciferol (−1.4 mm Hg for each additional 1000 U/d of cholecalciferol; P=0.04). For each 1-ng/mL increase in plasma 25-hydroxyvitamin D, there was a significant 0.2-mm Hg reduction in systolic pressure (P=0.02). There was no effect of cholecalciferol supplementation on diastolic pressure (P=0.37). Within an unselected population of blacks, 3 months of oral vitamin D3 supplementation significantly, yet modestly, lowered systolic pressure. Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results, particularly among blacks, a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension.

Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial

BACKGROUND Association studies have suggested that lower circulating 25-hydroxyvitamin D [25(OH)D] in African Americans may partially underlie higher rates of cardiovascular disease and cancer in this population. Nonetheless, the relation between vitamin D supplementation and 25(OH)D concentrations in African Americans remains undefined. OBJECTIVE Our primary objective was to determine the dose-response relation between vitamin D and plasma 25(OH)D. DESIGN A total of 328 African Americans in Boston, MA, were enrolled over 3 winters from 2007 to 2010 and randomly assigned to receive a placebo or 1000, 2000, or 4000 IU vitamin D₃/d for 3 mo. Subjects completed sociodemographic and dietary questionnaires, and plasma samples were drawn at baseline and 3 and 6 mo. RESULTS Median plasma 25(OH)D concentrations at baseline were 15.1, 16.2, 13.9, and 15.7 ng/mL for subjects randomly assigned to receive the placebo or 1000, 2000, or 4000 IU/d, respectively (P = 0.63). The median plasma 25(OH)D concentration at 3 mo differed significantly between supplementation arms at 13.7, 29.7, 34.8, and 45.9 ng/mL, respectively (P < 0.001). An estimated 1640 IU vitamin D₃/d was needed to raise the plasma 25(OH)D concentration to ≥ 20 ng/mL in ≥ 97.5% of participants, whereas a dose of 4000 IU/d was needed to achieve concentrations ≥ 33 ng/mL in ≥ 80% of subjects. No significant hypercalcemia was seen in a subset of participants. CONCLUSIONS Within African Americans, an estimated 1640 IU vitamin D₃/d was required to achieve concentrations of plasma 25(OH)D recommended by the Institute of Medicine, whereas 4000 IU/d was needed to reach concentrations predicted to reduce cancer and cardiovascular disease risk in prospective observational studies. These results may be helpful for informing future trials of disease prevention.

Impact of Vitamin D Supplementation on Inflammatory Markers in African Americans: Results of a Four-Arm, Randomized, Placebo-Controlled Trial

African Americans have a disproportionate burden of inflammation-associated chronic diseases such as cancer and lower circulating levels of 25-hydroxyvitamin D [25(OH)D]. The effect of vitamin D3 (cholecalciferol) supplementation on inflammatory markers is uncertain. We conducted a randomized, double-blind, placebo-controlled trial of supplemental oral vitamin D (placebo, 1,000, 2,000, or 4,000 IU/day of vitamin D3 orally for 3 months) in 328 African Americans (median age, 51 years) of public housing communities in Boston, MA, who were enrolled over three consecutive winter periods (2007–2010). Change from 0 to 3 months of plasma levels of 25(OH)D, high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-10, and soluble TNF-α receptor type 2 (sTNF-R2) in 292 (89%) participants were measured. Overall, no statistically significant changes in CRP, IL-6, IL-10, and sTNF-R2 were observed after the vitamin D supplementation period. Baseline CRP was significantly inversely associated with the baseline 25(OH)D level (P < 0.001) in unadjusted and adjusted models. An interaction between baseline 25(OH)D and vitamin D supplementation was observed for outcome change in log CRP (month 3–month 0; P for interaction = 0.04). Within an unselected population of African Americans, short-term exposure to vitamin D supplementation produced no change in circulating inflammatory markers. This study confirms the strong independent association of CRP with 25(OH)D status even after adjusting for body mass index. Future studies of longer supplemental vitamin D3 duration are necessary to examine the complex influence of vitamin D3 on CRP and other chronic inflammatory cytokines for possible reduction of cancer health disparities in African Americans. Cancer Prev Res; 7(2); 218–25. ©2013 AACR.

Null Association Between Vitamin D and PSA Levels Among Black Men in a Vitamin D Supplementation Trial

Background: Black men exhibit a high prevalence of vitamin D deficiency as well as a higher incidence of prostate cancer and higher mortality rates from prostate cancer than Whites. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on prostate-specific antigen (PSA) in healthy Black men. Methods: During three winters from 2007 to 2010, 105 Black men (median age, 48.9 years) of Boston, MA were randomized into a four-arm, double-blind trial for 3 months of placebo, 1,000, 2,000, or 4,000 U of vitamin D3. At baseline and 3 months, free and total PSA was measured. Results: With vitamin D supplementation, no significant differences in free and total PSA were observed; free PSA, −0.0004 ng/mL (P = 0.94) and total PSA, −0.004 ng/mL (P = 0.92) for each additional 1,000 U/d of vitamin D3. Conclusion: Within an unselected population of healthy Black men without a cancer diagnosis, we found no effect of vitamin D supplementation on free or total PSA. Impact: These findings support prior findings of no change in PSA with vitamin D supplementation and emphasize the need for new methods to assess the influence of vitamin D supplementation on prostate cancer prevention. Cancer Epidemiol Biomarkers Prev; 23(9); 1944–7. ©2014 AACR.

Risk of Hypercalcemia in Blacks Taking Hydrochlorothiazide and Vitamin D

INTRODUCTION Hydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined. METHODS We assessed the frequency of hypercalcemia in hydrochlorothiazide users in a post hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age 51 years) assigned to either placebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010). RESULTS Of the 328 participants, 84 reported hydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not taking hydrochlorothiazide had serum calcium measurements at 3 months, but not at baseline. At 3 months, hydrochlorothiazide participants had higher calcium levels (0.2 mg/dL, P <.001) than nonhydrochlorothiazide participants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the nonhydrochlorothiazide participants had hypercalcemia. In a linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3 months, and other covariates, only hydrochlorothiazide use (Estimate [SE]: 0.05 [0.01], P = .01) predicted serum calcium at 3 months. CONCLUSION In summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with an increase in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use hydrochlorothiazide with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.

Effects of Vitamin D Supplementation on C-peptide and 25-hydroxyvitamin D Concentrations at 3 and 6 Months

The link between African-Americans’ disproportionate rates of diabetes, obesity and vitamin D deficiency may be marked by C-peptide as an indicator of insulin secretion. We hypothesize that vitamin D supplementation will increase C-peptide, a marker of insulin secretion. During 3 winters from 2007-2010, 328 healthy African-Americans (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. The differences in non-fasting C-peptide between baseline and 3 months were −0.44 ng/mL for those receiving placebo, −0.10 ng/mL for those receiving 1000 IU/d, 0 ng/mL for those receiving 2000 IU/d, 1.24 ng/mL for those receiving 4000 IU/d (C-peptide increased 0.42 ng/mL for each additional 1000 IU/d of vitamin D3, p < 0.001). Vitamin D supplementation increased C-peptide in overweight African-Americans and may be compatible with other recommendations for diabetes prevention and management including weight loss and increased physical activity.

Impact of vitamin D supplementation on adiposity in African-Americans

Background:African-Americans have higher rates of obesity-associated chronic diseases. Serum 25-hydroxyvitamin D (25(OH)D) shows an inverse association with obesity status. We investigated whether vitamin D supplementation changes body mass index (BMI).Subjects:In total, 328 overweight African-Americans were enrolled over three consecutive winter periods (2007–2010) into a randomized, double-blind, placebo-controlled trial to receive cholecalciferol supplementation (0, 1000 international units (IU), 2000 IU or 4000 IU per day) for 3 months. Plasma concentrations of 25(OH)D and anthropometric measurements were done at baseline, 3 and 6 months.Results:At 3 months, vitamin D supplementation in three dose groups (1000 IU, 2000 IU or 4000 IU per day) did not cause any significant changes in BMI as compared with placebo group 3-month change in BMI per 1000 IU per day estimate (SE): 0.01 (0.039); P=0.78.Conclusions:In overweight African-Americans, short-term high-dose vitamin D supplementation did not alter BMI.

Effect of Vitamin D Supplementation on Blood Pressure in African-Americans

Blacks have significantly higher rates of hypertension than whites, and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on blood pressure in blacks. During 2 winters from 2008 to 2010, 283 blacks (median age, 51 years) were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 international units of cholecalciferol per day. At baseline, 3 months, and 6 months, systolic and diastolic pressure and 25-hydroxyvitamin D were measured. The 3-month follow-up was completed in 250 (88%) participants. The difference in systolic pressure between baseline and 3 months was +1.7 mm Hg for those receiving placebo, −0.66 mm Hg for 1000 U/d, −3.4 mm Hg for 2000 U/d, and −4.0 mm Hg for 4000 U/d of cholecalciferol (−1.4 mm Hg for each additional 1000 U/d of cholecalciferol; P=0.04). For each 1-ng/mL increase in plasma 25-hydroxyvitamin D, there was a significant 0.2-mm Hg reduction in systolic pressure (P=0.02). There was no effect of cholecalciferol supplementation on diastolic pressure (P=0.37). Within an unselected population of blacks, 3 months of oral vitamin D3 supplementation significantly, yet modestly, lowered systolic pressure. Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results, particularly among blacks, a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension.

Abstract A43: Recruitment and retention success of African Americans in a vitamin D supplementation trial

Purpose: The purpose of this abstract is to describe the recruitment and retention success of a double-blind, randomized-controlled vitamin D supplementation trial enrolling African American (AA), English-speaking participants between the ages of 30 and 80 in the Boston area. Background: This study addresses the critical areas of cancer prevention and racial disparities by defining the optimal dose of vitamin D supplementation in AAs needed for future large intervention efforts in the prevention of colorectal cancer. AAs are at higher risk of colorectal and other gastrointestinal cancers, and compelling evidence suggests that the high rates of hypovitaminosis D in AAs may possibly account for this disparity in cancer incidence. Although the optimal dose of supplemental vitamin D needed to achieve adequate levels of plasma 25(OH)D is unknown in virtually all populations, there is a critical need to define doses of oral vitamin D supplementation in AAs that will achieve a sufficient level of plasma 25(OH)D before vitamin D chemoprevention studies are initiated. Study subjects were randomized to placebo, 1000 IU, 2000 IU, or 4000 IU of vitamin D3 per day to determine the minimum dose of vitamin D needed to achieve an optimal level. Supplementation occurred during the winter months, to reduce sun exposure. After 3 months of supplementation, plasma levels of 25(OH)D are determined and compared to baseline levels. We also assessed vitamin D levels 3 months post supplementation. Methods: The recruitment goal was to enroll 320 participants, including100 men, into the study. A 3-phase eligibility and consent process was used to reach this goal. 1) Only people who were AA, English-speaking, and 30-80 years old were approached to participate in the study. 2) Among these individuals, basic nonclinical eligibility criteria were assessed. 3) Primary care physicians of the remaining individuals were contacted to assess clinical eligibility. Targeted recruitment efforts focused on obtaining individuals who met the first-phase eligibility criteria. Potential participants were identified at public housing sites, faith-based organizations, community organizations, and through participant referrals. To encourage retention, a case-manager approach was implemented and research assistants made biweekly phone calls and monthly pill bottle exchange visits with participants. Results: Through our recruitment efforts, we consented 572 individuals and exceeded our recruitment goals with 329 participants enrolled in the study, including 107 men. During year 1, with 2.5 months of recruitment, we enrolled 46 participants. During years 2 and 3 with 6 months of recruitment each year, we enrolled 166, and 117 participants, respectively. Retention for the 3-and 6-month assessment was 90.1 % and 87.4%, respectively. Conclusions: The number of individuals needed to be approached was about twice the desired amount of participants to be enrolled in the study. The design of this study posed many challenges for recruitment and retention; however, through collaborations with community-based organizations and biweekly contact with study participants, we were able to surpass our goals. Our strategies and lessons learned are relevant to other researchers conducting research in a population, such as this one, that has historically been challenging to recruit and retain into clinical studies. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A43.