Calcium supplementation tied to increased risk of serrated polyps

Reuters Health Information: Calcium supplementation tied to increased risk of serrated polyps

Calcium supplementation tied to increased risk of serrated polyps

Last Updated: 2018-03-06

By Marilynn Larkin

NEW YORK (Reuters Health) - Calcium supplements taken with or without vitamin D may increase the risk of sessile serrated adenomas/polyps (SSA/Ps), known precursors to colorectal cancer, researchers suggest.

Dr. Seth Crockett of the University of North Carolina in Chapel Hill told Reuters Health, "Sessile serrated polyps have only recently been recognized as important (colorectal) cancer precursors that give rise to 20-30% of sporadic colon cancer cases."

"They are therefore an important target of colon cancer screening," he said by email, "but are more difficult to detect on colonoscopy compared to adenomatous polyps due to their flat shape and subtle appearance."

Dr. Crockett and colleagues analyzed data on 2,058 subjects in the Vitamin D/Calcium Polyp Prevention Study, a multicenter randomized controlled trial that took place at 11 US hospitals.

Participants (median age 58; 63% men; 88% white) had at least one adenomatous polyp removed within the preceding four months and were scheduled for surveillance colonoscopy three or five years later. Eighteen percent had advanced adenomas, 8% had three or more conventional adenomas, 23% had hyperplastic polyps, 1% had SSA/Ps and one had a TSA.

Participants were randomized to receive 1200 mg/day of elemental calcium; 1,000 IU/day of vitamin D3; both calcium and vitamin D; or placebo. Treatment continued for three or five years, when the risk of polyps was assessed from the surveillance colonoscopy (treatment phase).

Outcomes also were assessed after an "observational phase," i.e., at the first colonoscopy at least three years after the "end of treatment" colonoscopy.

As reported online March 1 in Gut, serrated polyps were diagnosed in 27.5% participants after the treatment phase and 29.7% after the observational phase.

A total of 211 SSA/Ps were identified. No effect of calcium or vitamin D supplementation on SSA/P incidence was seen in the treatment phase. By contrast, six to 10 years after supplementation began, elevated risks of SSA/Ps were associated with calcium alone (adjusted relative risk, 2.65) and calcium plus vitamin D (aRR, 3.81).

Observational phase analyses also showed higher risks of serrated polyps in women (aRR, 2.62) and current smokers who took calcium supplements. Among current smokers, the aRR was 2.16 compared to 1.04 for non-smokers.

Dr. Crockett called the findings "somewhat unexpected," but cautioned that they should be "put in perspective and not cause alarm."

"Calcium and vitamin D supplementation are taken by lots of people, and do have some beneficial effects on bone health, etc.," he said. "Many people take low doses of calcium in multivitamins (i.e., 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," he noted. "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."

Dr. Steven Itzkowitz, Director of the GI Fellowship program at the Icahn School of Medicine at Mount Sinai in New York City said, "The study is well done, and although the conclusions drawn are a reasonable interpretation of the data, the implications have to be taken with a grain of salt."

All patients started out with at least one colonic adenoma, he said. "Since only about 30% of the US population will develop an adenoma, the findings may not be representative of the 70% without adenomas."

While SSA/Ps are known to be precursors of colon cancer, the SSA/Ps that are most likely to progress to cancer either have dysplasia in the polyp, or have a traditional serrated polyp (TSA).

"Of the study subjects, only 12/544 (2%) had a dysplastic SSA/P or TSA at baseline, 12/565 (2%) during treatment, and 9/329 (2.7%) during the observational phase . . . Thus, the more 'ominous' types of SSA/Ps affected only a handful of subjects," Dr. Itzkowitz said.

"SSA/Ps are notoriously hard to detect," he continued, "so one cannot exclude the possibility that if you look often enough into someone's colon - each patient had three colonoscopies over time - you might find more of them."

"Alternatively," he suggested, "the doctors doing the exams might have gotten better at recognizing them over the several years of the study."

"Even if overall SSA/P incidence was higher in those who took calcium," he said, "we know that non-dysplastic SSA/Ps are small, benign lesions akin to adenomas that are not as ominous in their biology as we once thought."

"This study provides some food for thought," he concluded, "but should not yet be a reason to alter what primary care physicians are now recommending to their patients."


Gut 2018.

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