Calcium supplements linked to premalignant bowel polyp growth
Intake of calcium supplements may up the risk of developing sessile serrated adenomas or polyps (SSA/Ps) in the colon, according to a new study.
“Chemoprevention with various agents has been frequently studied as a means of reducing the incidence of colorectal cancer (CRC) and its precursors, though results have been mixed,” wrote the authors. “Given the biological differences between serrated polyps and conventional adenomas, it is plausible that they respond differently to chemopreventive agents. Thus, it is important to understand the effects of such agents on both types of premalignant lesions.”
In a secondary analysis of a large multicenter chemoprevention trial conducted across 11 centres in the US, 2,058 participants with previously diagnosed adenomatous polyps were identified and randomly assigned to receive 1,200 mg/day of elemental calcium, 1,000 IU/day of vitamin D3, both, or neither as supplementation.
While the supplements appeared to have no significant effect during a 3 to 5-year follow up period, researchers observed a higher incidence of SSA/Ps in the groups taking calcium alone and calcium with vitamin D (adjusted risk ratio, aRR (95% CI): 2.65 (1.43–4.91) and 3.81 (1.25–11.64), respectively) during later observation and follow-up. [Gut 2018; doi:10.1136/gutjnl-2017-315242]
“This appeared to be a late effect: 6 to 10 years after supplementation began,” said Dr Seth Crockett, corresponding author and assistant professor at the University of Carolina’s Division of Gastroenterology and Hepatology. “These possible risks must be weighed against the benefits of calcium and vitamin D supplementation.”
SSA/Ps are the most common premalignant form of serrated polyps (SPs), which are known to be precursor lesions to colorectal cancer; they account for an estimated 20 to 30 percent of sporadic cases thereof. [Gastroenterology 2010;138(6):2088–2100] Importantly, SPs are distinct from conventional adenomas and differ in their biology, appearance during endoscopy, typical location, histopathology and natural history.
Data from the study also showed that women and smokers were at higher risk for SPs overall (aRR (95% CI) 2.62 (1.39–4.95) and 2.16 (1.32–3.51), respectively). However, the researchers also highlighted that there appeared to be no association between dietary calcium intake and SP incidence in their study.
The researchers noted that their study was derived from a trial originally intended to assess the occurrence of conventional adenomas, and their data did not account for SP development in patients without such indications. Nevertheless, they advised that patients with a history of pre-cancerous SPs—particularly women and smokers—might wish to avoid vitamin D and calcium supplements.
Patients in the study were between 45 and 75 years old, had at least one adenomatous polyp detected and removed in the 4 months preceding the study, and were scheduled for surveillance colonoscopy after 3 or 5 years. Exclusion criteria included a family history of bowel cancer, inflammatory bowel disease, or other serious health conditions.
Enrolment for the study was conducted between July 2004 to July 2008, and outcomes were collected up to June 2016. Participants were contacted every 6 months to verify adherence, health status and adverse events, concomitant medications and supplement use, and performance of colonoscopy or other colorectal imaging during the period.