Calcium and vitamin D supplements were associated with increased risk of developing sessile serrated adenomas or polyps, according to a recent study of patients with a history of adenoma.
The trial included 2,058 patients between the ages of 45 and 75 years with a history of at least one adenoma at baseline. They were randomized to receive 1,200 mg of elemental calcium per day, 1,000 IU of vitamin D3 per day, both supplements, or placebo for a treatment period of three to five years. Patients underwent colonoscopy at the end of treatment and again at least three years after treatment was discontinued. Results were published online March 1 by Gut.
Overall, serrated polyps were diagnosed in 27.5% of the participants during treatment and in 29.7% of the 1,108 participants who completed post-treatment observation. During the treatment phase, no association was found between use of calcium or vitamin D and sessile serrated adenomas or polyps. However, during the observation phase, calcium alone or in combination with vitamin D was associated with significantly elevated risk (adjusted risk ratios, 2.65 [95% CI, 1.43 to 4.91] and 3.81 [95% CI, 1.25 to 11.64], respectively).
Given that the trial was intended to test the potential value of the supplements for chemoprevention, the finding of increased sessile serrated adenomas or polyps with calcium supplementation was surprising, the authors said. Previous research had found inverse associations between dietary calcium intake and hyperplastic polyps, leading the study authors to speculate that only calcium supplementation, not dietary calcium, appears to be associated with serrated neoplasia.
The mechanisms for this association are uncertain, they said. The study did find some modifiers of the effects. Women and current smokers showed a stronger association between calcium supplementation and sessile serrated adenomas or polyps. The study was limited by a number of factors, including that it was derived from a secondary analysis of a trial designed to evaluate occurrence of conventional adenomas, so it had limited statistical power. If the findings are confirmed by future research, however, they could have significant public health implications, given the large number of people who take calcium and vitamin D supplements, the authors said.