Can vitamin D protect against cancer?

Liz Meszaros, MDLinx | March 04, 2019

Researchers of several observational studies have previously suggested that taking vitamin D supplements could lower the risk of many diseases. But observational studies can fail to include confounding factors or biases that may skew results. In other epidemiologic research, investigators suggested that higher serum vitamin D levels may lower the risks of developing cancer. But such studies highlight associations only, while cause and effect remain unproven.

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Taking vitamin D supplements does not lower cancer risk, according to results of the largest-ever clinical trial to assess vitamin D for cancer prevention, the Vitamin D and Omega-3 Trial (VITAL).

However, taking vitamin D supplements does not lower cancer risk, according to results of the largest-ever clinical trial to assess vitamin D for cancer prevention, the Vitamin D and Omega-3 Trial (VITAL). Researchers published their results in the New England Journal of Medicine.

For the researchers of this large, randomized, clinical trial, the goal was to determine whether taking more than the recommended dietary allowance of vitamin D—in amounts that are above what is considered necessary for bone health—was beneficial.

Primary endpoints of the study included the impact of vitamin D supplements on the risk of developing invasive cancer of any kind and major cardiovascular events (including myocardial infarction, stroke, or death due to cardiovascular causes). Secondary endpoints were comprised of site-specific cancers, cancer mortality, and any additional cardiovascular events.

Led by JoAnn E. Manson, MD, DrPH, chief, Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, the VITAL Research Group included a nationally representative sample of 25,871 subjects (50.6% women; 20.2% African American) with no history of invasive cancer or cardiovascular disease. To enroll, men had to 50 years or older, and women, 55 years or older.

Subjects were randomized to one of four groups: daily vitamin D plus placebo (2,000 IU/d), omega-3 supplements (1 g/d) plus placebo, vitamin D plus omega-3 supplements, or two placebos. They were followed for a median of 5.3 years.

Mean baseline serum total 25-hydroxyvitamin D was 30.8 ng/mL. Notably, 12.7% of 15,787 subjects who provided analyzable blood samples had levels under 20 ng/mL, and 32.2% had levels even lower, from 20 ng/mL to less than 30 ng/mL. Among those 1,644 subjects with repeat measurements at 1 year who were taking vitamin D, these levels increased by 40% compared with minimal changes in the placebo group.

Despite this, the incidence of invasive cancer did not differ between the groups receiving vitamin D supplementation and those that did not. In the vitamin D group, 6.1% had a diagnosis of cancer compared with 6.4% of subjects who received placebo (HR: 0.96; 95% CI: 0.88-1.06; P=0.47).

During follow-up, 341 cancer-related deaths occurred: 1.2% in those taking vitamin D compared with 1.4% in the placebo group. While this was not a statistically significant difference, the difference between groups became larger over time, according to the researchers.

Researchers did not find a statistically significant reduction in either the risk of cancer or cancer mortality in subjects taking omega-3 fatty acids, and presented their results in a separate paper.

The incidence of cardiovascular events was also similar between the groups (HR: 0.97; 95% CI: 0.85-1.12; P=0.69).

Finally, researchers found no significant differences between the groups in the incidence of adverse events such as hypercalcemia, kidney stones, or gastrointestinal symptoms.

In an accompanying editorial, John F. Keaney, Jr, MD, professor, University of Massachusetts Medical School, Worcester, MA, and Clifford J. Rosen, MD, director, Clinical and Translational Research, and senior scientist, Maine Medical Center Research Institute, Scarborough, ME, reviewed the VITAL study, as well as previous studies in which researchers analyzed the effects of vitamin D supplementation. These prior studies included the Vitamin D Assessment Study (VIDA), in which researchers found no effect of vitamin D supplementation on the incidence of major cardiovascular events, or on cancer outcomes.

They stressed that the number of subjects included by Manson et al, as well as the number of African American subjects, made this cohort a nationally representative sample. In addition, they noted that even in subjects with a median serum 25-hydroxyvitamin D level of less than 20 ng/mL at baseline, vitamin D had no effects.

“Even in that subgroup, vitamin D supplementation had no effect on the number of cases of invasive cancer of any type. Hence, across a wide range of serum vitamin D levels there was no health benefit from vitamin D supplementation,” wrote Drs. Keaney and Rosen.

“Thus, in the absence of additional compelling data, it is prudent to conclude that the strategy of dietary supplementation with either n−3 fatty acids or vitamin D as protection against cardiovascular events or cancer suffers from deteriorating VITAL signs,” they concluded.

This study was funded by the National Cancer Institute, the National Heart, Lung, and Blood Institute, the Office of Dietary Supplements, the National Institute of Neurological Disorders and Stroke, and the National Center for Complementary and Integrative Health.

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