A large, randomized study led by a UNC Lineberger Comprehensive Cancer Center researcher found that vitamin D and calcium supplements do not reduce the risk of colorectal adenomas, which are benign tumors that can evolve into colorectal cancer.
The results, which were published today in the New England Journal of Medicine, came as a disappointment to the researchers. Previous observational studies have pointed to an association between lower colorectal cancer risk with higher vitamin D blood levels, and to lower colorectal cancer risk alongside increased calcium intake.
“There’s a lot of interest in vitamin D these days because of many positive findings in non-randomized studies.”
“There’s a lot of interest in vitamin D these days because of many positive findings in non-randomized studies. In particular, vitamin D has been investigated for its protective benefits against a range of diseases, including colorectal cancer,” said the study’s lead author John Baron, MD, MS, MSc, a UNC Lineberger member and research professor in the UNC School of Medicine Division of Gastroenterology and Hepatology and UNC Gillings School of Global Public Health. “We found that vitamin D and calcium supplements did not affect the occurrence of colon polyps, which are benign precursors to colorectal cancer. So our results came as a disappointment.”
Colorectal cancer is the fourth most common cancer in the United States, with an estimated 132,700 new cases and 49,700 deaths from the disease this year, according to NCI Surveillance, Epidemiology and End Results Program data. Colorectal cancers can develop from precancerous growths called adenomas.
The UNC Lineberger-led study included 2,259 people at 11 academic medical centers or affiliated medical practices. Patients recently diagnosed with precancerous adenomas, but who had no colorectal polyps remaining after a colonoscopy, were included.
Patients were randomly assigned to take either daily doses of 1,000 International Units of vitamin D3, 1,200 milligrams of calcium, both, or neither. Women could opt to receive calcium and be randomized to vitamin D or placebo.
The study found that 42.8 percent of patients developed one or more adenomas after taking the higher vitamin D doses, compared to 42.7 percent of patients who were not given vitamin D. Even after adjustment for variables such as age, gender and study center, there was essentially no difference between the two groups in the risk of adenomas.
Of patients taking the higher calcium doses, 45.3 percent developed adenomas compared to 47.6 of patients who did not take calcium. And 45.7 percent of patients taking both vitamin D and calcium developed one or more adenomas, compared to 48.2 percent taking neither. The relative risks were also not statistically significant for those comparisons.
While the study did not find that higher daily doses of calcium and vitamin D reduced the risk of recurrent colorectal adenomas across three to five years, Baron said the study paves the way for longer-term trials testing the effect of higher doses of vitamin D and calcium.
The doses of vitamin D used in the UNC Lineberger-led study were above daily recommendations from the Institute of Medicine. This 2010 report recommended that most Americans and Canadians up to age 70 need no more than 600 international units of vitamin D per day to maintain their health, and that people aged 71 and older may need as much as 800 international units. The daily dose of supplemental calcium used in the UNC Lineberger-led study, when considered alongside dietary calcium, would raise the subjects’ total intake above the IOM’s recommended range of 700 to 1,300 milligrams per day.
“Vitamin D did not reduce risk of adenomas, suggesting that it does not interfere with colorectal carcinogenesis, as thought,” Baron said of the study findings. “However, the data are consistent with a modest effect and there were suggestions that with longer treatment there might be some benefit.”
This work was supported by a grant from the National Institutes of Health, National Cancer
Institute (CA098286 to JAB). Pfizer Consumer Healthcare provided the study agents.
In addition to Baron, other authors includes: Elizabeth L. Barry, Ph.D., Leila A. Mott, M.S., Judy R. Rees, B.M., B.Ch., of the Geisel School of Medicine at Dartmouth; Robert S. Sandler, M.D., division chief emeritus of the UNC School of Medicine Division of Gastroenterology and Hepatology and a professor in the UNC School of Medicine and UNC Gillings School of Global Public Health Department of Epidemiology; Dale C. Snover, M.D., of the Department of Pathology, Fairview Southdale Hospital; Roberd M. Bostick, M.D., M.P.H., of the Department of Epidemiology, Rollins School of Public Health, Emory University and Winship Cancer Institute, Emory University; Anastasia Ivanova, Ph.D., of the Department of Biostatistics, University of North Carolina at Chapel Hill; Bernard F. Cole, Ph.D., of the Department of Mathematics and Statistics, University of Vermont; Dennis J. Ahnen, M.D., the Department of Medicine, University of Colorado School of Medicine; Gerald J. Beck, Ph.D., of Department of Quantitative Health Sciences, Cleveland Clinic; Robert S. Bresalier, M.D., Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center; Carol A. Burke, M.D., Department of Gastroenterology and Hepatology, Cleveland Clinic; Timothy R. Church, Ph.D., of the Division of Environmental Health Sciences, University of Minnesota School of Public Health Minneapolis; Marcia Cruz-Correa, M.D., Ph.D., of the Puerto Rico Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan; Jane C. Figueiredo, Ph.D., of the Department of Preventive Medicine, Keck School of Medicine, University of Southern California (JCF) Los Angeles; Michael Goodman, M.D., M.P.H., of the Department of Epidemiology, Rollins School of Public Health, Emory University and Winship Cancer Institute, Emory University; Adam S. Kim, M.D., of the Minnesota Gastroenterology, P.A. Minneapolis; Douglas J. Robertson, M.D., of the VA Outcomes Group, White River Junction VT and Department of Medicine, Dartmouth Hitchcock Medical Center; Richard Rothstein, M.D., of the Department of Medicine, Dartmouth Hitchcock Medical Center; Aasma Shaukat, M.D., M.P.H., of the Department of Medicine, Minneapolis Veterans Affairs Medical Center, University of Minnesota, Minneapolis; March E. Seabrook, M.D., of the Consultants in Gastroenterology, West Columbia, SC; Robert W. Summers, M.D., of the Department of Internal Medicine, University of Iowa Carver College of Medicine.