Cancer and vitamin D supplementation: a systematic review and meta-analysis

Beatriz Goulao, Fiona Stewart, John A. Ford, Graeme MacLennan, Alison Avenell

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Low 25-hydroxyvitamin D status has been associated with a higher risk of cancer in epidemiologic studies.

Objective: The aim of this study was to undertake a systematic review and meta-analysis of randomized clinical trials (RCTs) investigating the effect of vitamin D supplementation alone on cancer incidence and mortality.

Design: A systematic review was undertaken. MEDLINE, Embase, CENTRAL, conference abstracts, and clinical trial registries were searched (last search March 2017) for RCTs investigating vitamin D supplementation alone. RCTs with ≥12 mo of follow-up and in participants with a mean or median age ≥60 y were eligible. During-study events were used as the main analysis, but after-study events were included in a secondary analysis. Subgroup analyses concerning different forms of vitamin D supplementation, 25-hydroxyvitamin D status at baseline, vitamin D dose, and exclusion of open-label trials were undertaken.

Results: Thirty studies in 18,808 participants were included in the systematic review, with a median follow-up ranging from 1 to 6.2 y. The results of the meta-analysis for during-study events showed no evidence of an effect of vitamin D supplementation for cancer incidence (RR: 1.03; 95% CI: 0.91, 1.15) and cancer-related deaths (RR: 0.85; 95% CI: 0.70, 1.04). Including after-study events, the RRs were 1.02 (95% CI: 0.92, 1.13) and 0.85 (95% CI: 0.72, 1.00), respectively. These results did not appear to be affected by baseline 25-hydroxyvitamin D status, vitamin D dose, or the exclusion of open-label trials.

Conclusion: We did not find evidence to suggest that vitamin D supplementation alone reduces the incidence of cancer or cancer mortality, even after including long-term follow-up results.
Original languageEnglish
Pages (from-to)652-663
Number of pages12
JournalThe American Journal of Clinical Nutrition
Volume107
Issue number4
Early online date9 Apr 2018
DOIs
Publication statusPublished - Apr 2018

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Vitamin D
Meta-Analysis
Neoplasms
Randomized Controlled Trials
Incidence
Mortality
MEDLINE
Registries
Epidemiologic Studies
Clinical Trials
25-hydroxyvitamin D

Keywords

  • vitamin D
  • cancer
  • mortality
  • systematic review
  • meta-analysis

Cite this

Cancer and vitamin D supplementation : a systematic review and meta-analysis . / Goulao, Beatriz; Stewart, Fiona; Ford, John A.; MacLennan, Graeme; Avenell, Alison.

In: The American Journal of Clinical Nutrition, Vol. 107, No. 4, 04.2018, p. 652-663.

Research output: Contribution to journalArticle

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title = "Cancer and vitamin D supplementation: a systematic review and meta-analysis",
abstract = "Background: Low 25-hydroxyvitamin D status has been associated with a higher risk of cancer in epidemiologic studies.Objective: The aim of this study was to undertake a systematic review and meta-analysis of randomized clinical trials (RCTs) investigating the effect of vitamin D supplementation alone on cancer incidence and mortality.Design: A systematic review was undertaken. MEDLINE, Embase, CENTRAL, conference abstracts, and clinical trial registries were searched (last search March 2017) for RCTs investigating vitamin D supplementation alone. RCTs with ≥12 mo of follow-up and in participants with a mean or median age ≥60 y were eligible. During-study events were used as the main analysis, but after-study events were included in a secondary analysis. Subgroup analyses concerning different forms of vitamin D supplementation, 25-hydroxyvitamin D status at baseline, vitamin D dose, and exclusion of open-label trials were undertaken.Results: Thirty studies in 18,808 participants were included in the systematic review, with a median follow-up ranging from 1 to 6.2 y. The results of the meta-analysis for during-study events showed no evidence of an effect of vitamin D supplementation for cancer incidence (RR: 1.03; 95{\%} CI: 0.91, 1.15) and cancer-related deaths (RR: 0.85; 95{\%} CI: 0.70, 1.04). Including after-study events, the RRs were 1.02 (95{\%} CI: 0.92, 1.13) and 0.85 (95{\%} CI: 0.72, 1.00), respectively. These results did not appear to be affected by baseline 25-hydroxyvitamin D status, vitamin D dose, or the exclusion of open-label trials.Conclusion: We did not find evidence to suggest that vitamin D supplementation alone reduces the incidence of cancer or cancer mortality, even after including long-term follow-up results.",
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author = "Beatriz Goulao and Fiona Stewart and Ford, {John A.} and Graeme MacLennan and Alison Avenell",
note = "We thank the following study authors for supplying additional information, data, and clarifications: John Baron, Wendy Bedale, Cyrus Cooper, Chang-Hai Ding, Itsuo Gorai, Karen Hansen, Hazel Inskip, Wim Janssens, Xingzhong Jin, Rolfe Jord, Glenn Liu, Helen Macdonald, Per Magnusson, JoAnn Manson, Adrian Martineau, Toshio Matsumoto, Lee Mott, Rachel Neale, Susan Ott, Kerrie Sanders, Kirsti Uus-Raasi, Miles Witham, Klaus Witte, Weino Xia, and Kun Zhu. We also thank Daryll Archibald for his help in extracting data. The authors’ responsibilities were as follows— BG, FS, JAF, GM, and AA: participated equally in the development, writing, and review of the manuscript and accept full responsibility for this publication; and all authors: read and approved the final manuscript. AA and GM were investigators in the RECORD trial, one of the trials included in this systematic review. Quality assessment of this trial was not undertaken by these authors. The remaining authors had no conflicts to declare. Notes No funding was provided for this systematic review. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. No funding source had any role in design, data collection, interpretation, or reporting of the trial or these analyses. Supplemental Material and Supplemental Figures 1–5 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/ajcn/.",
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T1 - Cancer and vitamin D supplementation

T2 - a systematic review and meta-analysis

AU - Goulao, Beatriz

AU - Stewart, Fiona

AU - Ford, John A.

AU - MacLennan, Graeme

AU - Avenell, Alison

N1 - We thank the following study authors for supplying additional information, data, and clarifications: John Baron, Wendy Bedale, Cyrus Cooper, Chang-Hai Ding, Itsuo Gorai, Karen Hansen, Hazel Inskip, Wim Janssens, Xingzhong Jin, Rolfe Jord, Glenn Liu, Helen Macdonald, Per Magnusson, JoAnn Manson, Adrian Martineau, Toshio Matsumoto, Lee Mott, Rachel Neale, Susan Ott, Kerrie Sanders, Kirsti Uus-Raasi, Miles Witham, Klaus Witte, Weino Xia, and Kun Zhu. We also thank Daryll Archibald for his help in extracting data. The authors’ responsibilities were as follows— BG, FS, JAF, GM, and AA: participated equally in the development, writing, and review of the manuscript and accept full responsibility for this publication; and all authors: read and approved the final manuscript. AA and GM were investigators in the RECORD trial, one of the trials included in this systematic review. Quality assessment of this trial was not undertaken by these authors. The remaining authors had no conflicts to declare. Notes No funding was provided for this systematic review. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. No funding source had any role in design, data collection, interpretation, or reporting of the trial or these analyses. Supplemental Material and Supplemental Figures 1–5 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/ajcn/.

PY - 2018/4

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N2 - Background: Low 25-hydroxyvitamin D status has been associated with a higher risk of cancer in epidemiologic studies.Objective: The aim of this study was to undertake a systematic review and meta-analysis of randomized clinical trials (RCTs) investigating the effect of vitamin D supplementation alone on cancer incidence and mortality.Design: A systematic review was undertaken. MEDLINE, Embase, CENTRAL, conference abstracts, and clinical trial registries were searched (last search March 2017) for RCTs investigating vitamin D supplementation alone. RCTs with ≥12 mo of follow-up and in participants with a mean or median age ≥60 y were eligible. During-study events were used as the main analysis, but after-study events were included in a secondary analysis. Subgroup analyses concerning different forms of vitamin D supplementation, 25-hydroxyvitamin D status at baseline, vitamin D dose, and exclusion of open-label trials were undertaken.Results: Thirty studies in 18,808 participants were included in the systematic review, with a median follow-up ranging from 1 to 6.2 y. The results of the meta-analysis for during-study events showed no evidence of an effect of vitamin D supplementation for cancer incidence (RR: 1.03; 95% CI: 0.91, 1.15) and cancer-related deaths (RR: 0.85; 95% CI: 0.70, 1.04). Including after-study events, the RRs were 1.02 (95% CI: 0.92, 1.13) and 0.85 (95% CI: 0.72, 1.00), respectively. These results did not appear to be affected by baseline 25-hydroxyvitamin D status, vitamin D dose, or the exclusion of open-label trials.Conclusion: We did not find evidence to suggest that vitamin D supplementation alone reduces the incidence of cancer or cancer mortality, even after including long-term follow-up results.

AB - Background: Low 25-hydroxyvitamin D status has been associated with a higher risk of cancer in epidemiologic studies.Objective: The aim of this study was to undertake a systematic review and meta-analysis of randomized clinical trials (RCTs) investigating the effect of vitamin D supplementation alone on cancer incidence and mortality.Design: A systematic review was undertaken. MEDLINE, Embase, CENTRAL, conference abstracts, and clinical trial registries were searched (last search March 2017) for RCTs investigating vitamin D supplementation alone. RCTs with ≥12 mo of follow-up and in participants with a mean or median age ≥60 y were eligible. During-study events were used as the main analysis, but after-study events were included in a secondary analysis. Subgroup analyses concerning different forms of vitamin D supplementation, 25-hydroxyvitamin D status at baseline, vitamin D dose, and exclusion of open-label trials were undertaken.Results: Thirty studies in 18,808 participants were included in the systematic review, with a median follow-up ranging from 1 to 6.2 y. The results of the meta-analysis for during-study events showed no evidence of an effect of vitamin D supplementation for cancer incidence (RR: 1.03; 95% CI: 0.91, 1.15) and cancer-related deaths (RR: 0.85; 95% CI: 0.70, 1.04). Including after-study events, the RRs were 1.02 (95% CI: 0.92, 1.13) and 0.85 (95% CI: 0.72, 1.00), respectively. These results did not appear to be affected by baseline 25-hydroxyvitamin D status, vitamin D dose, or the exclusion of open-label trials.Conclusion: We did not find evidence to suggest that vitamin D supplementation alone reduces the incidence of cancer or cancer mortality, even after including long-term follow-up results.

KW - vitamin D

KW - cancer

KW - mortality

KW - systematic review

KW - meta-analysis

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DO - 10.1093/ajcn/nqx047

M3 - Article

VL - 107

SP - 652

EP - 663

JO - The American Journal of Clinical Nutrition

JF - The American Journal of Clinical Nutrition

SN - 0002-9165

IS - 4

ER -