Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data

Louise A Beveridge, Allan D Struthers, Faisel Khan, Rolf Jorde, Robert Scragg, Helen M Macdonald, Jessica A Alvarez, Rebecca S Boxer, Andrea Dalbeni, Adam D Gepner, Nicole M Isbel, Thomas Larsen, Jitender Nagpal, William G Petchey, Hans Stricker, Franziska Strobel, Vin Tangpricha, Laura Toxqui, M Pilar Vaquero, Louise WambergArmin Zittermann, Miles D Witham, D-PRESSURE Collaboration

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Importance: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.

Objective: To systematically review whether supplementation with vitamin D or its analogues reduce BP.

Data Sources: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.

Study Selection: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.

Data Extraction and Synthesis: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.

Main Outcomes and Measures: Difference in SBP and DBP measured in an office setting.

Results: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.

Conclusions and Relevance: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

Original languageEnglish
Pages (from-to)745-754
Number of pages10
JournalJAMA Internal Medicine
Volume175
Issue number5
Early online date16 Mar 2015
DOIs
Publication statusPublished - May 2015

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Vitamin D
Meta-Analysis
Blood Pressure
Information Storage and Retrieval
MEDLINE
Antihypertensive Agents
Diabetes Mellitus
Language
Randomized Controlled Trials
Placebos
Demography
Outcome Assessment (Health Care)

Keywords

  • Vitamin D
  • Supplement
  • Blood Pressure

Cite this

Effect of Vitamin D Supplementation on Blood Pressure : A Systematic Review and Meta-analysis Incorporating Individual Patient Data. / Beveridge, Louise A; Struthers, Allan D; Khan, Faisel; Jorde, Rolf; Scragg, Robert; Macdonald, Helen M; Alvarez, Jessica A; Boxer, Rebecca S; Dalbeni, Andrea; Gepner, Adam D; Isbel, Nicole M; Larsen, Thomas; Nagpal, Jitender; Petchey, William G; Stricker, Hans; Strobel, Franziska; Tangpricha, Vin; Toxqui, Laura; Vaquero, M Pilar; Wamberg, Louise; Zittermann, Armin; Witham, Miles D; D-PRESSURE Collaboration.

In: JAMA Internal Medicine, Vol. 175, No. 5, 05.2015, p. 745-754.

Research output: Contribution to journalArticle

Beveridge, LA, Struthers, AD, Khan, F, Jorde, R, Scragg, R, Macdonald, HM, Alvarez, JA, Boxer, RS, Dalbeni, A, Gepner, AD, Isbel, NM, Larsen, T, Nagpal, J, Petchey, WG, Stricker, H, Strobel, F, Tangpricha, V, Toxqui, L, Vaquero, MP, Wamberg, L, Zittermann, A, Witham, MD & D-PRESSURE Collaboration 2015, 'Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data', JAMA Internal Medicine, vol. 175, no. 5, pp. 745-754. https://doi.org/10.1001/jamainternmed.2015.0237
Beveridge, Louise A ; Struthers, Allan D ; Khan, Faisel ; Jorde, Rolf ; Scragg, Robert ; Macdonald, Helen M ; Alvarez, Jessica A ; Boxer, Rebecca S ; Dalbeni, Andrea ; Gepner, Adam D ; Isbel, Nicole M ; Larsen, Thomas ; Nagpal, Jitender ; Petchey, William G ; Stricker, Hans ; Strobel, Franziska ; Tangpricha, Vin ; Toxqui, Laura ; Vaquero, M Pilar ; Wamberg, Louise ; Zittermann, Armin ; Witham, Miles D ; D-PRESSURE Collaboration. / Effect of Vitamin D Supplementation on Blood Pressure : A Systematic Review and Meta-analysis Incorporating Individual Patient Data. In: JAMA Internal Medicine. 2015 ; Vol. 175, No. 5. pp. 745-754.
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T1 - Effect of Vitamin D Supplementation on Blood Pressure

T2 - A Systematic Review and Meta-analysis Incorporating Individual Patient Data

AU - Beveridge, Louise A

AU - Struthers, Allan D

AU - Khan, Faisel

AU - Jorde, Rolf

AU - Scragg, Robert

AU - Macdonald, Helen M

AU - Alvarez, Jessica A

AU - Boxer, Rebecca S

AU - Dalbeni, Andrea

AU - Gepner, Adam D

AU - Isbel, Nicole M

AU - Larsen, Thomas

AU - Nagpal, Jitender

AU - Petchey, William G

AU - Stricker, Hans

AU - Strobel, Franziska

AU - Tangpricha, Vin

AU - Toxqui, Laura

AU - Vaquero, M Pilar

AU - Wamberg, Louise

AU - Zittermann, Armin

AU - Witham, Miles D

AU - D-PRESSURE Collaboration

PY - 2015/5

Y1 - 2015/5

N2 - Importance: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.Objective: To systematically review whether supplementation with vitamin D or its analogues reduce BP.Data Sources: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.Study Selection: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.Data Extraction and Synthesis: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.Main Outcomes and Measures: Difference in SBP and DBP measured in an office setting.Results: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.Conclusions and Relevance: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

AB - Importance: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.Objective: To systematically review whether supplementation with vitamin D or its analogues reduce BP.Data Sources: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.Study Selection: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.Data Extraction and Synthesis: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.Main Outcomes and Measures: Difference in SBP and DBP measured in an office setting.Results: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.Conclusions and Relevance: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

KW - Vitamin D

KW - Supplement

KW - Blood Pressure

U2 - 10.1001/jamainternmed.2015.0237

DO - 10.1001/jamainternmed.2015.0237

M3 - Article

C2 - 25775274

VL - 175

SP - 745

EP - 754

JO - JAMA Internal Medicine

JF - JAMA Internal Medicine

SN - 2168-6106

IS - 5

ER -