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Possible risks must be weighed against the benefits of supplements, a study led by Seth Crockett, MD, MPH, finds.

Calcium supplements, taken with or without vitamin D, may increase the risk of small growths in the bowel called polyps, suggest results from a large U.S. trial published online in the journal Gut.

The researchers say further studies are recommended to confirm these results – and any possible risks must be weighed against the benefits of supplementation. But given that calcium supplements are taken by millions of people around the world, the findings may have important implications for bowel cancer screening and prevention.

Lead author of the study is Seth D. Crockett, MD, MPH, assistant professor of gastroenterology and hepatology in the UNC School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center.

“This study examines the risk of a really interesting class of colon polyps called serrated polyps,” Crockett said. “Specifically, we were interested in ‘sessile serrated polyps’, which have only recently been recognized as important colon cancer precursors that give rise to 20-30 percent of sporadic colon cancer cases. Sessile serrated polyps are therefore an important target of colon cancer screening, but they are more difficult to detect on colonoscopy compared to adenomatous polyps due to their flat shape and subtle appearance.

“The findings from this study were somewhat unexpected,” Crockett said. “There is some evidence from epidemiologic studies that people who have calcium rich diets are at lower risk of colon polyps, including serrated polyps. So it stands to reason that calcium supplementation might have beneficial effects in terms of preventing colon cancer or polyps. In fact, some studies have shown beneficial effects of calcium for preventing adenomatous polyps. In contrast, we found evidence that calcium supplementation (with or without vitamin D supplementation) appeared to be associated with an increased risk of precancerous serrated polyps.

“It’s important to put these findings in perspective and to not cause alarm. Calcium and vitamin D supplementation are taken by lots of people, and do have some beneficial effects on bone health. Many people take low doses of calcium in multivitamins (lower than what was used in our study) that are unlikely to be harmful. This possible association does not necessarily negate the other benefits of these supplements. But for some patients, including those with a history of serrated polyps and/or smoking, data from this study could alter the balance of risks and benefits of calcium supplementation,” Crockett said.

Polyps are small growths in the lower part of the large bowel (colon). They are non-cancerous, but some could eventually turn into cancer if they are not removed.

Polyps come in different shapes and sizes, with serrated polyps more likely to turn into cancer than conventional polyps. Some studies have suggested that calcium and vitamin D may protect against serrated polyps, but results have been mixed.

So to investigate further, a team of U.S.-based researchers set out to determine whether taking daily calcium and vitamin D supplements reduce the risk of serrated polyps.

They analyzed findings from a large U.S. trial involving over 2,000 patients aged between 45 and 75 who had had at least one serrated polyp detected and removed – and were due to have a follow-up test (colonoscopsy) in 3 to 5 years.

Patients were excluded if they had a family history of bowel cancer, inflammatory bowel disease, or other serious health conditions – and several factors were taken into account at the start of the study, including sex, diet, body mass index (BMI), and use of anti-inflammatory drugs.

The remaining patients were randomly split into groups to receive either daily calcium supplements, daily vitamin D supplements, both or neither for 3 or 5 years (treatment phase) until their colonoscopsy.

Effects 3 to 5 years after treatment ended (observational phase) were also recorded.

During the treatment phase, there was no effect of either calcium or vitamin D on cases of serrated polyps. However, during the later observational phase (6-10 years after treatment began), the researchers found increased risks of serrated polyps among patients taking calcium alone and among those taking a combination of calcium and vitamin D.

There was evidence that women and smokers were at higher risk when exposed to calcium supplements, but no association was found between vitamin D alone and the risk of serrated polyps. The results also suggest an association with calcium supplements only, not dietary calcium.

Strengths of the study include its randomised design and large sample size, say the authors. However, they point out that findings are derived from a secondary analysis of a trial and it is possible that some results from these analyses were due to chance.

Further studies are recommended to confirm these results, say the authors, but if calcium and its combination with vitamin D are truly associated with an increased risk of serrated polyps, “this has important public health implications,” they conclude.

In the meantime, they suggest that patients with a history of pre-cancerous serrated polyps, especially women and smokers, may wish to avoid vitamin D and calcium supplementation.