Funded in part by Pharmavite, Quest Diagnostics
Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial
Chandler PD, Chen WY, Ajala ON, Hazra A, Cook N, Bubes V, Lee IM, Giovannucci EL, Willett W, Buring JE, Manson JE, VITAL Research Group
JAMA network open · 194 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Industry funded
- Nonprofit
- American Cancer Society
- Government
- Office of Dietary Supplements
- Company
- Pharmavite
- Company
- Quest Diagnostics
- Government
- National Institutes of Health
- Government
- National Institute on Aging
- Government
- National Heart, Lung, and Blood Institute
- Government
- National Institute of Mental Health
- Government
- National Cancer Institute
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Government
- National Center for Complementary and Integrative Health
- Government
- NCI NIH HHS
- Grants
- American Cancer Society (127524-MRSG-15-012-01-CNE); National Heart, Lung, and Blood Institute (U01CA138962); National Cancer Institute (R01 CA138962); National Cancer Institute (U01CA138962); National Cancer Institute (CA138962); National Heart, Lung, and Blood Institute (R01 CA138962); National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 CA138962); National Center for Complementary and Integrative Health (U01 CA138962); National Institute of Diabetes and Digestive and Kidney Diseases (U01 CA138962); National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01 CA138962); National Center for Complementary and Integrative Health (R01 CA138962); National Cancer Institute (127524-MRSG-15-012-01-CNE); National Institute of Mental Health (R01 CA138962); National Institute of Mental Health (U01 CA138962); National Institute of Diabetes and Digestive and Kidney Diseases (R01 CA138962); National Institutes of Health (U01 CA138962); National Institutes of Health (R01 CA138962); National Institutes of Health (CA-138962)
Based on 13 listed funder(s).
Publication
- Published
- 2020-11-18 · JAMA Netw Open · vol. 3 · issue 11 · p. e2025850
- Publisher
- American Medical Association
- Cited
- 257 citations · more than 100% of similar papers · 22.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 38 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Vitamin D Research Studies · Cancer Research and Treatments · Vitamin C and Antioxidants Research
- Keywords
- Medicine, Vitamin D and neurology, Cholecalciferol, Cancer, Internal medicine, Body mass index, Vitamin, Placebo, Clinical trial, vitamin D deficiency, Randomized controlled trial, Omega 3 fatty acid, Fatty acid, Pathology
- MeSH
- humans, neoplasms, neoplasm metastasis, obesity, disease progression, cholecalciferol, vitamins, proportional hazards models, double-blind method, comorbidity, dietary supplements, aged, middle aged, female, male, overweight
11 authors
From US
- Paulette D. Chandler · correspondingBrigham and Women's Hospital; Harvard University
- Wendy Y. ChenBrigham and Women's Hospital; Harvard University; Dana-Farber Cancer Institute
- Oluremi N AjalaBrigham and Women's Hospital; Harvard University
- Aditi HazraBrigham and Women's Hospital; Harvard University
- Nancy R. CookBrigham and Women's Hospital; Harvard University
- Vadim Y. BubesBrigham and Women's Hospital; Harvard University
Abstract
Importance
Epidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways.
Objective
To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index.
Design, setting, and participants
VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017.
Interventions
Vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements.
Main outcomes and measures
For the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations.
Results
Among 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI).
Conclusions and relevance
In this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight.
Trial registration
ClinicalTrials.gov Identifier: NCT01169259.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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