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Calcium supplements linked to precancerous colon polyps
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Calcium supplements with or without vitamin D appeared to increase the risk for premalignant serrated polyps — specifically, sessile serrated adenomas and polyps — in patients with a history of colorectal adenomas, according to data from a recently completed chemoprevention trial.
Women and current smokers who took calcium supplements were especially at risk for developing serrated polyps, and the effects appeared to begin 6 to 10 years after supplementation began, Seth D. Crockett, MD, MPH, assistant professor of gastroenterology at University of North Carolina, and colleagues noted.
While further study is needed to confirm these findings, they concluded that patients with a history of premalignant serrated polyps should weigh these possible risks against the benefits of calcium and vitamin D supplementation.
“The findings from this study were somewhat unexpected,” Crockett told Healio Gastroenterology and Liver Disease. “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.”
Crockett and colleagues reviewed data from the “treatment phase” of a double-blind randomized controlled trial, in which 2,058 participants with at least one adenoma at baseline were randomly assigned to receive daily supplementation with calcium, vitamin D, both or neither for 3 to 5 years, after which they underwent a colonoscopy. The investigators also reviewed data on the 1,108 patients with additional follow-up from the “observational phase” of the study.
“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% to 30% 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.”
Investigators detected serrated polyps in 27.5% of participants in the treatment phase and in 29.7% in the observational phase, and a total of 211 sessile serrated adenomas or polyps during follow-up.
Crockett and colleagues found calcium or vitamin D supplementation had no effect on the incidence of sessile serrated adenomas or polyps during the treatment phase, but during the observational phase, the risk for developing these lesions significantly correlated with calcium supplementation (adjusted RR = 2.65; 95% CI, 1.43-4.91) and a combination of calcium and vitamin D supplementation (aRR = 3.81; 95% CI, 1.25-11.64). Vitamin D alone did not appear associated with an increased risk for these lesions.
Subgroup analyses showed that, compared with non-smokers, current smokers showed a significantly higher risk for any serrated polyp when taking calcium supplements (aRR = 2.16; 95% CI, 1.32-3.51). Additionally, calcium supplementation correlated with a significantly higher risk of serrated polyps overall among women (aRR = 2.62; 95% CI, 1.39-4.95).
“It's important to put these findings in perspective and to not cause alarm,” Crockett said. “Calcium and vitamin D supplementation are taken by lots of people, and do have some beneficial effects on bone health, etc. Many people take low doses of calcium in multivitamins (ie, 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 smokers, data from this study could alter the balance of risks and benefits of calcium supplementation.” – by Adam Leitenberger
Disclosures: The authors report no relevant financial disclosures.
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