The role of vitamin D supplementation for primary prevention of cancer: meta-analysis of randomized controlled trials

Haykal, Tarek; Samji, Varun; Zayed, Yazan; Gakhal, Inderdeep; Dhillon, Harsukh; Kheiri, Babikir; Kerbage, Josiane; Veerapaneni, Vijaysai; Obeid, Michele; Danish, Rizwan; Bachuwa, Ghassan

doi:10.1080/20009666.2019.1701839

Cited by 34 publications

(43 citation statements)

References 24 publications

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“…follow-up (<1 year (19,20)) or intervention (<3 years (22), age (<18 (21) or <60 (19) years), number of outcomes (<10 (20)) and pregnancy (15,16,21).…”

Section: Meta-analyses Of Randomized Clinical Trialsmentioning

confidence: 99%

“…Five meta-analyses had shortcomings in critical domains (17)(18)(19)(20)22): all 5 did not cite a pre-defined, registered protocol, 4 did not cite excluded primary studies (18)(19)(20)22), 3 did not use a satisfactory technique to assess risk of bias (17,18,20) and 2 used a literature search that was not fully comprehensive (17,18). All studies had deficiencies in non-critical domains, with the most common being reporting funding sources of primary studies (absent in 7 meta-analyses (15,(17)(18)(19)(20)(21)(22)) and explaining selection of study designs for inclusion in the review (absent in 6 meta-analyses (15-17, 19, 21, 22)). Based on weaknesses in the critical and non-critical domains, the overall confidence in the 8 meta-analyses was deemed critically low or moderate for 7 of these (15,(17)(18)(19)(20)(21)(22).…”

Section: Quality Of Meta-analysesmentioning

confidence: 99%

“…All studies had deficiencies in non-critical domains, with the most common being reporting funding sources of primary studies (absent in 7 meta-analyses (15,(17)(18)(19)(20)(21)(22)) and explaining selection of study designs for inclusion in the review (absent in 6 meta-analyses (15-17, 19, 21, 22)). Based on weaknesses in the critical and non-critical domains, the overall confidence in the 8 meta-analyses was deemed critically low or moderate for 7 of these (15,(17)(18)(19)(20)(21)(22).…”

Section: Quality Of Meta-analysesmentioning

confidence: 99%

“…Six of these meta-analyses had total cancer incidence as an outcome (16)(17)(18)(19)(20)22). These reports were published between 2014 and 2019 -with each comprising 4-18 studies, 18,440-83,353 participants and 1061-6537 cancer incident events.…”

Section: Cancer Incidencementioning

confidence: 99%

“…Meta-analyses provide an opportunity to make decisions on accurate, succinct, credible and comprehensive summaries of the best available evidence, and act as a key tool for healthcare professionals to achieve evidence-based decisions (9). Several meta-analyses have synthesized data on the association of vitamin D status with cancer outcomes from observational studies (5)(6)(7)(10)(11)(12)(13)(14) and the effect of vitamin D supplementation on cancer outcomes in randomized clinical trials (15)(16)(17)(18)(19)(20)(21)(22). However, the evidence base is inconsistent and fragmented into various meta-analyses that combine different study populations and outcomes, making assessment of the evidence using a similar methodological framework difficult.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

2020

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The relationship between vitamin D status or supplementation and cancer outcomes has been examined in several meta-analyses. To address remaining knowledge gaps, we conducted a systematic overview and critical appraisal of pertinent meta-analyses. For meta-analyses of trials, we assessed their quality using AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews), strength of associations using umbrella review methodology and credibility of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Meta-analyses of observational studies reported inverse associations of 25-hydroxyvitamin D with risk of cancer incidence and cancer mortality and, particularly for colorectal cancer, fulfilled some of Bradford-Hill's causation criteria. In meta-analyses of trials, vitamin D supplementation did not affect cancer incidence. However, we found credible evidence that vitamin D supplementation reduced total cancer mortality risk, with 5 out of 6 meta-analyses reporting a relative risk (RR) reduction of up to 16%: RR=0.84 (95% confidence interval: 0.74-0.95). The strength of the association, however, was classified as weak. This was true among meta-analyses of high, moderate and lower quality (AMSTAR-2-rated). Trials did not include large numbers of vitamin D-deficient participants, many tested relatively low doses and lacked sufficiently powered data on sitespecific cancers. In conclusion, meta-analyses show that, while observational evidence indicates that low vitamin D status is associated with a higher risk of cancer outcomes, randomized trials demonstrate that vitamin D supplementation reduces total cancer mortality but not cancer incidence. However, trials with larger proportions of vitamin D-insufficient This article is protected by copyright. All rights reserved. participants and longer durations of follow-up, plus adequately powered data on site-specific common cancers, would provide further insight into the evidence base.

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“…follow-up (<1 year (19,20)) or intervention (<3 years (22), age (<18 (21) or <60 (19) years), number of outcomes (<10 (20)) and pregnancy (15,16,21).…”

Section: Meta-analyses Of Randomized Clinical Trialsmentioning

confidence: 99%

Section: Quality Of Meta-analysesmentioning

confidence: 99%

Section: Quality Of Meta-analysesmentioning

confidence: 99%

Section: Cancer Incidencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

2020

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Vitamin D supplementation to the older adult population in Germany has the cost‐saving potential of preventing almost 30 000 cancer deaths per year

et al. 2021

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Recent meta-analyses of randomized controlled trials (RCTs) have demonstrated significant reduction in cancer mortality by vitamin D supplementation. We estimated costs and savings for preventing cancer deaths by vitamin D supplementation of the population aged 50+ years in Germany. Our analysis is based on national data on cancer mortality in 2016. The number of preventable cancer deaths was estimated by multiplying cancer deaths above age 50 with the estimated proportionate reduction in cancer mortality derived by vitamin D supplementation according to meta-analyses of RCTs (13%). Saved costs were estimated by multiplying this number by estimated end-of-life cancer care costs (€40 000). Annual costs of vitamin D supplementation were estimated at 25€ per person above age 50. Comprehensive sensitivity analyses were conducted. In the main analysis, vitamin D supplementation was estimated to prevent almost 30 000 cancer deaths per year at approximate costs of €900 million and savings of €1.154 billion, suggesting net savings of €254 million. Our results support promotion of supplementation of vitamin D among older adults as a costsaving approach to substantially reduce cancer mortality.

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Vitamin D: Bolus Is Bogus—A Narrative Review

2021

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In this review we summarize the impact of bolus versus daily dosing of vitamin D on 25(OH)D and 1,25(OH) 2 D levels, as well as on key countervailing factors that block vitamin D functions at the cellular level. Further, we discuss the role of bolus versus daily dosing of vitamin D for several health outcomes, including respiratory infections and coronavirus disease 2019 (COVID-19), rickets, falls and fractures, any cancer, and cancer-related mortality. This discussion appears timely because bolus doses continue to be tested for various disease outcomes despite a growing amount of evidence suggesting lack of efficacy or even detrimental effects of bolus dosing of vitamin D for outcomes where daily dosing at modest levels was effective in the vitamin D deficient. As a result, these discordant results may bias health recommendations for vitamin D if the recommendations are based on meta-analyses combining both daily and bolus dosing trials.

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The role of vitamin D supplementation for primary prevention of cancer: meta-analysis of randomized controlled trials

Cited by 34 publications

References 24 publications

Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

Vitamin D supplementation to the older adult population in Germany has the cost‐saving potential of preventing almost 30 000 cancer deaths per year

Vitamin D: Bolus Is Bogus—A Narrative Review

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