Dietary supplementation with vitamin D and/or calcium after removal of precancerous colorectal adenomas (polyps) does not reduce risk of developing future adenomas. Despite promising findings in models of the disease and in previous, smaller trials, the study offers strong evidence against the usefulness of these supplements in the prevention of future polyps. This 2259-person study was conducted at 11 academic medical centers and published in the New England Journal of Medicine (2015; doi:10.1056/NEJMoa1500409).

“After a patient has colonic polyps removed, it would be great to be able to offer a way for that patient to reduce his or her risk of developing future polyps or colorectal cancer. Unfortunately, this trial shows that taking vitamin D or calcium is probably not very useful in this setting,” said coauthor Dennis J. Ahnen, MD, investigator at the University of Colorado Cancer Center and professor of gastroenterology at the Denver VA Medical Center in Denver.

The study included patients 45 to 75 years old who had colonic polyps removed and no remaining polyps at the time of trial enrollment. Participants agreed to take daily dietary supplements of vitamin D, calcium, or both. According to standard of care in these cases, participants had follow-up colonoscopy 3 to 5 years after the initial examination.

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In all, 43% of patients showed additional polyps at the time of the second screening. No significant difference occurred in the frequency of new polyps over the next 5 years between patients in a control group and patients who had taken one or both supplements.

“In addition to knowing what works, it’s important to discover what doesn’t work,” Ahnen said. “This way we can both move on to researching additional, promising strategies and also avoid prescribing treatments that have no effect.”

In laboratory studies, vitamin D has been shown to slow the growth of cancer cells by inhibiting the growth of new blood vessels required to feed a cancer’s growth, and also by directly causing the death of cancer cells. In addition, vitamin D supplementation lowered the risk of the disease developing in mouse models of cancer.

“This shows that what works in a dish and even what works in animal models doesn’t always work in humans,” Ahnen said.

Similar is true of calcium supplementation: In population studies, people with higher calcium intake have lower incidence of colorectal cancer, and previous, smaller human trials have shown promise for calcium in the prevention of colorectal cancer.

“This was particularly surprising,” Ahnen said, “since one of our own previous trials showed that calcium supplementation could modestly reduce the risk of new polyp formation.”

Ahnen pointed out that this study specifically examined the possible effects of these supplements against the formation of new precancerous polyps and that, “it could be that vitamin D and/or calcium work later in the process of carcinogenesis to prevent dangerous cancers, but not their precancerous predecessors.”

Overall, though, the authors wrote that they have “no ready explanation” for these negative findings that seem to controvert the promise of many previously published studies.

“More work is required,” said Ahnen. “But at least in this setting, at this dose, with this population and measuring these outcomes, vitamin D and calcium supplementation did not appear useful.”