Vitamin D3 Supplements Tied to Reduced Risk of Advanced Cancer, Death

By Linda Carroll

November 20, 2020

(Reuters Health) - Normal-weight individuals taking vitamin D3 supplements have a reduced risk of diagnosis with advanced cancer, a new study finds.

In a secondary analysis of data from a randomized clinical trial that included nearly 26,000 participants, researchers found a reduced risk of metastatic or fatal cancers over a mean follow-up period of 5.3 years among participants taking D3 supplements, according to the report published in JAMA Network Open.

"We found in this secondary analysis of a diverse cohort that vitamin D at 2,000 IU a day in people who had no cancer at baseline reduced the risk of developing advanced cancer by 17% overall and by 38% in those with a BMI less than 25," said the study's lead author, Dr. Paulette Chandler, an epidemiologist in the division of preventive medicine at Brigham and Women's Hospital and an assistant professor of medicine at the Harvard Medical School in Boston. "There was no significant reduction in those who were overweight or obese."

This paper does not provide definitive insight into mechanisms of how vitamin D might reduce cancer risk, Dr. Chandler said. "But we saw the reduction across 17 different cancers," she added. "And it was not just by vitamin D levels. Most of the study participants had normal levels at baseline and the effect was independent of vitamin D levels."

It's possible, Dr. Chandler said, that vitamin D may modulate immune function by improving natural killer cell function, which is something that other studies have suggested.

With regard to the lack of effect in those with BMI above 25, Dr. Chandler suggested this might be related to obesity's impact on cancer risk. "There are 13 cancers with an increased risk in the setting of obesity," she said. "This highlights the importance of addressing the obesity epidemic."

To take a look at whether vitamin D3 supplementation might impact the risk of advanced cancers, Dr. Chandler and her colleagues analyzed data collected for the Vitamin D and Omega 3 Trial (VITAL), a randomized, double-blind, placebo-controlled, 2 x 2 factorial trial.

The VITAL study, which was originally designed to explore the value of the two supplements in staving off cancer and cardiovascular disease, included 25,871 adults, including men aged 50 and older and women aged 55 and older at baseline. Participants were randomly assigned to receive vitamin D3, marine omega-3 fatty acids, both supplements, or both placebos.

Eligible participants had no history of cancer (except melanoma) or cardiovascular disease at the outset. Other exclusion criteria included kidney failure or dialysis, cirrhosis, history of hypercalcemia or other serious conditions that would preclude participation.

All participants completed a three-month run-in phase before randomization. The median intervention period was 5.3 years (range: 3.8 to 6.1 years). Baseline blood samples were collected during the run-in period.

Although there were no significant differences in cancer incidence between the groups, there was a significant reduction in advanced cancers (metastatic or fatal) found for those randomized to vitamin D compared with placebo: 226 of the 12,927 participants (1.7%) assigned to vitamin D versus 274 of the 12,944 assigned to placebo (2.1%) developed advanced cancers for a hazard ratio (HR) of 0.83.

When the researchers stratified the results by BMI, they found an even larger risk reduction in those who received vitamin D with BMI<25 (HR: 0.62), but no significant risk reduction in those with BMI above 25.

"The 'Holy Grail' of cancer prevention trials is a drug or supplement that is well-tolerated, lacks long and late-effects, and reduces cancer deaths," said Dr. Charles Shapiro, a professor of medicine and director of translational breast cancer research and director of cancer survivorship at the Icahn School of Medicine at Mount Sinai in New York City. "Is vitamin D3 such a supplement? (This study) suggests that it may be."

Still, Dr. Shapiro said, there are caveats. First, the original trial did not find an impact on incident cancers, although that could be because vitamin D3 affects only cancer progression rather than initiating events, he added.

"Furthermore, the reductions in cancer metastases or deaths were only in individuals that had normal body mass index," Dr. Shapiro said in an email. "Those individuals that were overweight or obese did not experience any significant declines in cancer metastases or deaths."

Once again, "there is plausible explanation for this too - namely that higher BMIs are proinflammatory and serve as sink for the fat-soluble vitamin D3," said Dr. Shapiro, who was not involved in the new study.

"Is vitamin D3 supplementation ready for prime time?" Dr. Shapiro said. "On the basis of this secondary analysis, I think not. However, repleting and maintaining vitamin D3 levels is essential for bone health and decreasing bone loss."

SOURCE: and JAMA Network Open, online November 18, 2020.