Researchers have conducted both observational studies and randomized controlled trials to look at possible links between someone’s vitamin D level or use of vitamin D supplements and their risk of developing or dying from cancer. Randomized trials are considered a stronger design because they control for the possibility that other differences between people, rather than their vitamin D status, explain associations seen in observational studies. However, vitamin supplementation trials are typically limited to testing one daily dosage, as compared with the measurement of a range of blood levels in observational studies.
Evidence from observational studies
Cancer risk. Observational studies have examined a number of individual cancer sites for possible associations of risk with vitamin D level. Higher vitamin D levels have been consistently associated with reduced risks of colorectal cancer and, to a lesser extent, bladder cancer. Studies have consistently shown no association between vitamin D levels and risk of breast, lung, and several other, less common cancers. By contrast, opposite (i.e., harmful) associations of risk with higher blood vitamin D levels have been suggested for prostate cancer and possibly pancreatic cancer.
Cancer mortality. Possible associations between vitamin D status and cancer mortality have generally been studied for all cancers combined. Most meta-analyses (i.e., studies that combine multiple individual studies) of observational studies have found that lower serum vitamin D levels are associated with higher overall cancer mortality. For example, a meta-analysis of 12 cohort studies found a 14% higher cancer mortality among people with the lowest 25-hydroxyvitamin D levels than among those with the highest levels. Similarly, an analysis of approximately 4,000 cancer cases within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial found a 17% lower cancer mortality among men and women in the highest category of vitamin D than in the lowest category.
Evidence from randomized controlled trials
Cancer risk. Most randomized controlled trials have found that vitamin D supplements, with or without calcium, do not reduce the risk of developing cancer overall or of developing specific cancers. An evidence report prepared for the United States Preventive Serves Task Force (USPSTF) in its assessment of nutrient supplements to prevent cardiovascular disease or cancer found little or no benefit for vitamin D in preventing cancer, cardiovascular disease, and death.
For example, the early large randomized Women’s Health Initiative trial found that supplementation with 400 IU vitamin D plus 1000 mg calcium had no effect on the incidence of breast or colorectal cancer among postmenopausal women.
More recently, the largest trial of vitamin D supplementation, VITAL, assigned more than 25,000 participants aged 50 and over (men) or 55 and over (women) to receive a daily dose of 2000 IU vitamin D plus fish oil omega-3 fatty acids or of placebo. After 5 years of follow-up, the vitamin D/omega-3 group had the same overall cancer incidence as the placebo group. The incidence of breast, prostate, and colorectal cancer was also the same in both groups. Another large trial of vitamin D supplementation, ViDA, conducted among New Zealanders aged 50–84, also found no association between supplementation and the risk of cancer overall.
In addition, findings from several trials cast doubt on the idea that taking vitamin D supplements prevents the development of colorectal adenomas, which can become colorectal cancer. In the VITAL trial, people who took vitamin D supplements did not have a lower risk of colorectal adenomas or serrated polyps at 5 years of follow-up. An ancillary study of a randomized trial in US adults with prediabetes and overweight or obesity found that vitamin D supplementation was not associated with incident cancer or colorectal polyps. And in the Vitamin D/Calcium Polyp Prevention Study, which studied people who had had at least one adenoma removed during colonoscopy at the start of the study, taking a daily vitamin D supplement did not reduce the risk that adenomas would recur during the following 10 years.
Cancer mortality. Several randomized controlled trials have studied whether vitamin D supplements lowers the risk of death from cancer, with varying results. For example, in the VITAL trial, vitamin D did not reduce cancer deaths overall, although a mortality reduction was seen in analyses that excluded deaths in the first few years of follow-up. In the D-Health trial, which included Australians 60 years and older, a monthly dose of 60,000 IU vitamin D for 5 years also did not reduce cancer mortality.
However, a meta-analysis of 10 randomized controlled trials through 2018 (including the VITAL trial) found that vitamin D supplementation was associated with a slight (13%) reduction in cancer mortality over 3–10 years of follow-up. A meta-analysis of 21 randomized trials found no evidence that vitamin D supplementation was associated with reduced mortality from all causes combined or from cardiovascular disease.
Many participants in these trials had blood levels of vitamin D that are considered adequate for overall health. This has led to speculation that any effects of vitamin D supplementation on cancer mortality might be more evident in people with low vitamin D levels, and researchers are pursuing this question.