Dataset Information

Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial.

ABSTRACT:

Importance

Previous randomized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence.

Objective

To examine whether high-dose vitamin D supplementation received monthly, without calcium, is associated with a reduction in cancer incidence and cancer mortality in the general population.

Design, setting, and participants

This is a post hoc analysis of data from the Vitamin D Assessment (ViDA) study, a randomized, double-blind, placebo-controlled trial that recruited participants from family practices and community groups in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up completed December 31, 2015. Participants were adult community residents aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants withdrew consent, and all others (n = 5108) were included in the primary analysis. Data analysis was by intention to treat.

Interventions

Oral vitamin D3, in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years).

Main outcomes and measures

Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms (excluding nonmelanoma skin cancers) diagnosed from randomization until the study medication was discontinued on July 31, 2015.

Results

Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 58.1% were male, and 4253 (83.3%) were of European or another race/ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 (9.0) ng/mL. In a random sample of 438 participants, the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of cancer comprised 328 total cases of cancer (259 invasive and 69 in situ malignant neoplasms) and occurred in 165 of 2558 participants (6.5%) in the vitamin D group and 163 of 2550 (6.4%) in the placebo group, yielding an adjusted hazard ratio of 1.01 (95% CI, 0.81-1.25; P = .95).

Conclusions and relevance

High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer. This study suggests that daily or weekly dosing for a longer period may require further study.

Trial registration

anzctr.org.au Identifier: ACTRN12611000402943.

SUBMITTER: Scragg R

PROVIDER: S-EPMC6248079 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial.

Scragg Robert R Khaw Kay-Tee KT Toop Les L Sluyter John J Lawes Carlene M M CMM Waayer Debbie D Giovannucci Edward E Camargo Carlos A CA

JAMA oncology 20181108 11

<h4>Importance</h4>Previous randomized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence.<h4>Objective</h4>To examine whether high-dose vitamin D supplementation received monthly, without calcium, is associated with a reduction in cancer incidence and cancer mortality in the general population.<h4>Design, setting, and participants</h4>This is a post hoc analysis of data from the Vitamin D Assessment (ViDA) study, a randomized, doubl ...[more]

PMID: 30027269

Similar Datasets

Project description:ImportanceCohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D.ObjectiveTo examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population.Design, setting, and participantsThe Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis.InterventionsOral vitamin D3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years).Main outcomes and measuresThe primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis.ResultsOf the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes.Conclusions and relevanceMonthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study.Trial registrationclinicaltrials.gov Identifier: ACTRN12611000402943.

Project description:ContextBlood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.ObjectiveTo determine the efficacy and safety of B vitamin supplementation in the treatment of AD.Design, setting, and patientsA multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States.InterventionParticipants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months.Main outcome measureChange in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog).ResultsA total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements.ConclusionThis regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD.Trial registrationclinicaltrials.gov Identifier: NCT00056225.

Project description:BackgroundA critical need exists to better understand the physiological sequel of vitamin D supplementation in obese individuals and African Americans. The aim was to comprehensively evaluate dose- and time-responses of a panel of vitamin D biomarkers to vitamin D supplements in this population.MethodsWe conducted a 16-week randomized, double-blinded, and placebo-controlled clinical trial. Seventy overweight/obese African Americans (age 13-45 years, 84 % females) with 25-hydroxyvitamin D [25(OH)D] concentrations ≤20 ng/mL were randomly assigned to receive a supervised monthly oral vitamin D3 of 18,000 IU (~600 IU/day, n = 17), 60,000 IU (~2000 IU/day, n = 18), 120,000 IU (~4000 IU/day, n = 18), or placebo (n = 17).ResultsThere were significant dose- and time-responses of circulating 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2D], and intact parathyroid hormone (iPTH), but not fibroblast growth factor-23 (FGF-23), phosphorus and urine calcium to the vitamin D supplements. The mean 25(OH)D concentrations in the 2000 IU and 4000 IU groups reached ≥30 ng/mL as early as 8-weeks and remained at similar level at 16-weeks. The increase of 25(OH)D was significantly higher in the 4000 IU group than all the other groups at 8-weeks. The increase of 1,25(OH)2D was significantly higher in the 2000 IU and 4000 IU groups than the placebo at 8-weeks. Only the 4000 IU compared to the placebo significantly reduced iPTH at 8- and 16-weeks.ConclusionsOur RCT, for the first time, comprehensively evaluated time- and dose- responses of vitamin D supplementation in overweight/obese African Americans with suboptimal vitamin D status. Circulating 25(OH)D, 1,25(OH)2D, and iPTH, but not FGF-23, phosphorus and urine calcium, respond to vitamin D supplementation in a time- and dose-response manner. By monthly dosing, 2000 IU appears to be sufficient in achieving a 25(OH)D level of 30 ng/mL in this population. However, importantly, 4000 IU, rather than 2000 IU, seems to suppress iPTH. If replicated, these data might be informative in optimizing vitamin D status and providing individualized dosing recommendation in overweight/obese African Americans.Trial registrationClinicalTrials.gov number: NCT01583621, Registered on April 3, 2012.

Dataset Information

Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial.

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