July 24, 2018
The latest results come from New Zealand and are based on a post hoc analysis of the Vitamin D Assessment (ViDA) study, which involved 5108 community participants. The primary purpose of the ViDA study was to investigate cardiovascular outcomes.
The cumulative incidence of cancer during a median follow-up of 3.3 years was 6.5% for those who received 100,000 IU of vitamin D3 each month. By comparison, the cumulative incidence of cancer during the same period was 6.4% among participants who received placebo (adjusted hazard ratio [HR], 1.01; P = .95).
"Monthly high-dose vitamin D supplementation may not be associated with cancer prevention and should not be used for this purpose," say Robert Scragg, MBBS, PhD, of the University of Auckland, and colleagues.
The report was published online July 19 in JAMA Oncology.
Scragg and colleagues note that other randomized clinical trials of vitamin D supplementation have provided inconsistent results. They point out that these latest results on cancer incidence are consistent with findings from previous randomized clinical trials of community samples from the United States and the United Kingdom, and they are also consistent with the results from a recent meta-analysis of vitamin D supplementation trials.
Approached for comment, Carolyn Y. Fang, PhD, coleader of Cancer Prevention and Control at Fox Chase Cancer Center in Philadelphia, Pennsylvania, said that in spite of the current study's null findings, "there is still considerable interest in the possible connection between vitamin D and cancer."
Clinicians should talk to patients who have vitamin D deficiency about how they can make healthy dietary or behavioral changes and whether taking a vitamin D supplement is warranted, Fang told Medscape Medical News.
"However," she added, "from a population health perspective, key questions regarding the appropriate 'dosage' of vitamin D for cancer prevention and how long one might need to take this dose in order to positively impact health remain to be addressed."
Results of previous studies on whether vitamin D can reduce cancer risk are conflicting.
In the largest and most comprehensive observational study to date, an international research group concluded that vitamin D was unlikely to provide primary prevention of lung cancer, even in nonsmokers.
Prior to that, the SUNSHINE study showed that high-dose vitamin D supplementation significantly improved progression-free survival in patients with advanced colorectal cancer who were receiving chemotherapy.
Last month, results from an international collaborative meta-analysis indicated that higher vitamin D levels in the blood may protect against colorectal cancer, especially in women.
In 2016, a literature review that included 28 new meta-analyses and 100 trials published between 2013 and 2017 revealed evidence that 10 to 20 μg daily of vitamin D can reduce death from any cause and death from cancer in middle-aged and older adults.
The ViDA trial was a randomized, double-blind, placebo-controlled clinical trial that was conducted from March 1, 2011, to July 31, 2015. The primary outcome was the effect of vitamin D supplementation on the incidence of cardiovascular disease, but it also assessed possible effects related to acute respiratory infection, falls, and nonvertebral fractures.
Scragg and colleagues comment that findings from an earlier meta-analysis suggested that vitamin D supplements were "associated with a reduction in cancer mortality, but not cancer incidence."
The ViDA study participants were recruited from 55 family practices in Auckland. The mean age of the participants was 66 years, 58% were male, and 83% were of European or other race/ethnicity. The rest of the participants were of Polynesian or South Asian descent.
Of the participants, 320 (6.3%) used tobacco, and 2173 (42.5%) reported that they had formerly been smokers.
Some 1214 (23.8%) participants said they had been previously diagnosed with cancer. Cancer cases were evenly distributed between the two arms — of 2558 participants in the vitamin D group, 622 (24.3%) had been previously diagnosed with cancer, compared to 592 of 2550 (23.3%) patients in the placebo group.
Participants in the vitamin D group received an initial bolus of 200,000 IU of oral vitamin D3 followed by monthly doses of 100,000 IU. All participants were followed for up to 4.2 years.
At baseline, the mean concentration of deseasonalized 25-hydroxyvitamin D (25[OH]D) was 26.5 ng/mL. At follow-up, the mean concentration in a random sample of 438 participants was consistently higher than 20 ng/mL in participants taking vitamin D compared to those taking placebo.
The study showed that in 375 participants who were diagnosed with cancer after randomization, there were no differences in the percentage taking vitamin D vs placebo. The most common cancers included melanoma in situ, which was diagnosed in 71 participants, and malignant melanoma, which was diagnosed in 55 participants. Prostate cancer was diagnosed in 64 participants, colorectal cancer in 38, breast cancer in 36, and lymphoid and hematopoietic cancers in 36.
There were no significant differences between men and women, between participants with serum concentrations of 25(OH)D higher than 20 ng/mL vs lower than 20 ng/mL, or in the time to diagnosis after randomization. Similar results were seen for all secondary outcomes. These were defined as all malignant neoplasms reported from more than 12 months after randomization until the study medication was discontinued on July 31, 2015.
The fact that 25% of study participants had vitamin D deficiency may have limited the statistical power in that subgroup, the researchers indicate.
Funding for the study was provided by the Health Research Council of New Zealand. Dr Scragg and study coauthors have disclosed no relevant financial relationships.