Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials

Keum, NaNa; Lee, Dong Hoon; Greenwood, Darren C.; Manson, JoAnn E.; Giovannucci, Edward

doi:10.1093/annonc/mdz059

Cited by 296 publications

(301 citation statements)

References 55 publications

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“…(45,46) Nevertheless, the protective benefit of vitamin D supplementation against cancer mortality became pronounced when pooling the large RCTs together. (9) In addition, two recent RCTs suggest that patients with digestive tract cancers, especially colorectal cancer, may benefit from vitamin D supplementation. (47,48) Our findings indicate that the assessment of vitamin D status using bioavailable instead of total 25OHD levels would aid in the identification of individuals who are most likely to benefit from vitamin D supplementation.…”

Section: Discussionmentioning

confidence: 99%

“…(6)(7)(8) However, a recent meta-analysis of randomized controlled trials (RCTs) has demonstrated a divergent effect of vitamin D supplementation, which reduces total cancer mortality but does not lower total cancer incidence in the general population, supporting a broad benefit of vitamin D in cancer prognosis. (9) Consistent with this hypothesis, observational cohort studies have shown improved survival in cancer patients with higher circulating vitamin D concentrations, measured before or shortly after diagnosis of cancer. (10) However, evidence linking vitamin D status to organ-specific cancer survival is sparse and has produced conflicting results between and within types of cancers.…”

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confidence: 83%

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Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Fang

Long²,

Zhang

et al. 2020

Hepatology

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BaCKgRoUND aND aIMS:Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. appRoaCH aND ReSUltS: We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum-free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable-adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CoNClUSIoNS:Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis. (Hepatology 2020;0:1-14).

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 83%

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Fang

Long²,

Zhang

et al. 2020

Hepatology

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“…Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates [61]. A more recent 2019 study of higher dose random control trials showed that while vitamin D supplementation did not reduce total cancer incidence, it significantly reduced total cancer mortality [62]. There is evidence that critically ill patients with very low 25(OH)D concentrations have blunted responses to vitamin D replacement which may also explain the apparently negative results of earlier trials and meta-analyses [63].…”

Section: Causal Evidence For Vitamin Dmentioning

confidence: 99%

Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes

Davies

Garami

Byers

2020

Preprint

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We analyse global data for COVID-19 deaths and recoveries and show that outbreak severity displays a striking latitude relationship with a northern hemisphere bias. Transmission rates can be explained by seasonal weather conditions, but this does not account for observed variations in fatality rates. Many factors point to Vitamin D as a candidate explanation but historical controversy surrounding Vitamin D studies and the lack of a coherent framework for causal inference has hampered acceptance of this explanation despite a wealth of evidence in its favour.We analyse global COVID-19 data using Causal Inference, constructing two contrasting directed acyclic graph (DAG) models, one causal and one acausal, and set out clearly multiple predictions made by each model. We show that observed data strongly match predictions made by the causal model but largely contradict those of the acausal model. We explore historic evidence further supporting the causal model.We review biochemical mechanisms that may explain the various ways in which vitamin D acts. We detail the mechanisms by which the SARS-Cov-2 virus causes the disease and known pathways that involve Vitamin D and show how these both protect against viral infection, as well as ameliorating disease symptoms in COVID-19 and other respiratory diseases.We examine the factors that govern confidence in causal inference models and conclude that a high level of confidence in a causal beneficial role for Vitamin D is justified.

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“…Vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence. 60 Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D3 supplementation at 4000 IU/d. 61 Among patients with metastatic colorectal cancer, the addition of high-dose Vitamin D3, vs standard-dose Vitamin D3, to standard chemotherapy resulted in a difference in median progression-free survival that was not statistically significant, but with a significantly improved supportive effect.…”

Section: Discussionmentioning

confidence: 99%

Association Between Blood Circulating Vitamin D and Colorectal Cancer Risk in Asian Countries: A Systematic Review and Dose-Response Meta-analysis

Zhang

Zou

Zhao

et al. 2019

Preprint

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ObjectivesTo assess the association between blood circulating Vitamin D levels and colorectal cancer risk in the Asian population. DesignThis is a systematic review and dose-response meta-analysis of observational studies that investigated the relationship between blood circulating Vitamin D levels and colorectal cancer risk in the Asian population. Data SourcesRelevant studies were identified through a literature search in MEDLINE, EMBASE, studies published in peer-reviewed journals investigating the association between blood circulating Vitamin D levels and the risk of colorectal cancer and/or adenoma in Asian countries. Data extraction and synthesis:Two authors independently extracted data and assessed the quality of included studies. Studyspecific ORs were pooled using a random-effects model. A dose-response meta-analysis was performed with generalized least squares regression. We applied the Newcastle-Ottawa Scale quality assessment to evaluate the quality of the selected studies. ResultsThe eight included studies encompassed a total of 2,916 cases and 6,678 controls. The pooled ORs of colorectal cancer for the highest versus lowest categories of blood circulating Vitamin D levels was 0.75 [95% CI, 0.58-0.97] up to 36.5 ng/mL in the Asian population. There was heterogeneity among the studies (I 2 =53.9%, P heterogeneity =0.034). The dose-response metaanalysis indicated a significant linear relationship (P non-linearity =0.11). An increment of 16 ng/mL in blood circulating Vitamin D level corresponded to an OR of 0.79 [95% CI, 0.64-0.97]. ConclusionsThe results of this meta analysis indicate that blood circulating Vitamin D level is associated with decreased risk of colorectal cancer in Asian countries. The dose-response meta-analysis shows that the strength of this association among the Asian population is similar to that among the Western population. Our study suggests that the Asian population should improve nutritional status and maintain a higher level of blood circulating Vitamin D.

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Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials

Cited by 296 publications

References 55 publications

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes

Association Between Blood Circulating Vitamin D and Colorectal Cancer Risk in Asian Countries: A Systematic Review and Dose-Response Meta-analysis

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