Vitamin D, Calcium a Bust for Preventing Colorectal Polyps – MedPage Today
Taking vitamin D, calcium, or a combination of the two supplements, failed to prevent the recurrence of precancerous colorectal polyps in a large, randomized, placebo-controlled trial that followed patients for up to 5 years.
The negative findings came as a surprise because they contradict years of previous observational and animal studies suggesting a protective role for the supplements in preventing precancerous polyps, researcher John Baron, MD, of the University of North Carolina, Chapel Hill, and colleagues wrote in the Oct. 15 issue of New England Journal of Medicine.
They also contradict findings from several smaller randomized trials, including one by Baron and colleagues published in 1999, which showed calcium supplementation significantly lowered recurrent colorectal polyp risk.
‘Calcium Data Especially Surprising’
The newly published study is among the first randomized trials to examine vitamin D’s role in the prevention of polyp recurrence and the largest to examine calcium’s role, Baron said.
“We were especially surprised by the calcium data,” Baron told MedPage Today. “We plan to look at this trial and our previous trial to see if we can explain the difference in findings.”
The study included 2,259 people between the ages of 45 and 75 with at least one colorectal adenoma removed within 120 days of enrollment who also had no evidence of polyps on follow-up colonoscopy.
Participants were assigned to one of four regimens daily: 1,000 IU of vitamin D3, 1,200 mg of calcium as carbonate, both agents, or placebo. Women could elect to be randomly assigned to receive either calcium or calcium plus vitamin D or placebo.
Follow-up colonoscopy was performed 3 to 5 years after baseline examination and randomization, according to the endoscopist’s recommendation.
Participants randomized to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to those in the placebo arm of the study.
A total of 43% of participants had one or more adenomas identified during follow-up colonoscopy. The adjusted risk ratios for recurrent adenomas were 0.99 (95% CI 0.85-1.09) for vitamin D versus no vitamin D, 0.95 (95% CI 0.85-1.06) for calcium versus no calcium, and 0.93 (95% CI 0.80-1.08) for both supplements versus neither.
Similar findings were shown in a subanalysis of patients with advanced adenomas and in those with low baseline serum 25-hydroxyvitamin D levels.
1,000 IU of Vitamin D Isn’t Protective
Study strengths included its large size, rigorous design, and a high adherence rate among participants.
“We can say with some confidence that at this (1,000 IU) dose, which is a very commonly used dose now, vitamin D does not affect colorectal carcinogenesis,” Baron said. “The calcium story is somewhat more complicated given the strength of the previous evidence.”
Baron added that it is not clear if larger doses of vitamin D or increasing the duration of supplementation would protect against colorectal polyp recurrence and colorectal cancer.
“We started designing this trial around 15 years ago, and at the time there was some concern about toxicity at the dose we used,” he said. “Today 1,000 IU is considered a relatively moderate dose of vitamin D.”
A 2014 meta-analysis of randomized controlled trials examining the impact of vitamin D supplementation on various outcomes including ischemic heart disease, stroke, cancer, and hip fracture showed no evidence of protection with supplementation, with or without calcium, against any of these outcomes.
In an email exchange with MedPage Today, the meta-analysis’ lead author Mark J. Bolland, PhD, of the University of Auckland, Auckland, New Zealand, noted that earlier trials have failed to show vitamin D supplementation to protect against cancer.
“This (latest trial) was a large, well-conducted, randomized, placebo-controlled study carried out by experienced researchers that was specifically designed to test whether calcium or vitamin D supplements can prevent colorectal adenomas,” he said.
The research was funded by the National Institutes of Health.
Researcher John Baron reported receiving nonfinancial support related to this research from Lederle/Pfizer. He also reported a patent related to the chemopreventive use of calcium.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
last updated 10.16.2015