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Calcium Supplementation Shown To Reduce Colon Cancer In Large National Cancer Institute Trial
James Meschino D.C., M.S. R.O.H.P.
Abundant evidence suggests that colorectal cancer is a multistage process characterized by successive accumulation of cancer-related gene mutations that are associated morphologically with the development of adenomatous polyps of increasing degree of dysplasia, culminating in malignant invasion. Factors that encourage this multi-step process have been identified, many of which include common dietary constituents. At the same time, a number of protective dietary factors have also been identified, which are associated with reduced risk of colon cancer. The mechanism through which these factors may reduce risk of cancer is the subject of intensive study at this time.
One dietary constituent that has received attention in this regard is calcium. In recent years a significant body of evidence has emerged which indicates that a high level of calcium intake can significantly reduce risk of colon cancer and reduce risk of colon cancer recurrence. Calcium has been shown to reduce the risk of colorectal tumors by binding to bile acids and fatty acids in the intestinal tract, converting them into insoluble calcium soaps. This prevents bile acids and fatty acids from being converted into secondary sterols by bacteria that inhabit the large bowel. Secondary sterols such as deoxycholic acid and lithocholic acid are known to encourage cancer development in the large bowel by initiating DNA mutations and increasing the rate of proliferation of colon epithelial cells. Calcium has been shown to reduce the build up of cancer causing secondary sterols, producing an antiproliferative effect on colonic epithelium. Calcium also promotes apoptosis (programmed cell death of old cells and precancerous cells), and with Vitamin D, encourages cellular differentiation of colonic epithelial cells. All three of these physiological effects are associated with reduced risk of cancer development.
Numerous animal studies have demonstrated these protective effects and a significant number of human studies demonstrate that the calcium that does not get absorbed from the intestinal tract into the bloodstream (approximately 60-70% of ingested calcium from food and supplements) exerts important chemopreventinve effects on the colonic epithelium.
Approximately, twenty recent human studies, including 8 cohort studies of colorectal cancer and 2 case-control studies of almost 2000 colon cancer cases reported an inverse association between calcium intake and overall risk of colorectal tumors. In addition, three recent randomized clinical trials showed that calcium supplementation reduced recurrence of colon cancer. Baron et al found a significant 15% reduction in adenoma recurrence after 4 years of calcium supplementation at 1200/d. Bonithon-Kopp et al found a 34% reduction in adenoma recurrence after 3 years of supplementation at 2000 mg/d. Hofstad et al found a significant reduction in new adenoma formation in polyp-bearing patients after 3 years of supplementation with a combination of antioxidants and calcium at 1600 mg/d.
In the largest study published to date, Peters et al showed that individuals who ingested calcium supplements at more than 1200 mg per day had a 27% reduction in risk of developing colon ademoma, compared to nonusers of calcium supplements. After adjusting for known risk factors, they also showed that adenoma risk was 12% lower in individuals consuming more than 1767 mg per day of calcium (from food and supplementation), compared to individuals with a total daily consumption of calcium below 731 mg.
The study by peters et al compared the supplemental and dietary calcium intakes of 3696 participants with histologically verified adenoma of the distal colon with calcium intakes of 34,817 sigmoidoscopy-negative control participants, as one arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, sponsored by The National Cancer Institute. The researchers noted that the large study size and detailed questions about calcium use enabled them to investigate theses associations in detail, including specific attention to risks by diet compared with supplemental sources and risk by site, ademoma number and histological characteristics.
The surprising result is that this study suggests that throughout adult life individuals should consider consuming at least 1200 mg per day of calcium from a calcium supplement, in order to reduce risk of colon cancer development (primary prevention).
The National Health and Nutrition Examination Survey III conducted in 1988-1994 suggests that median intake for calcium from food among the American adult population is an additional 631 mg per day.
Thus health care practitioners should consider advising patients to include calcium supplementation, at appropriate doses, as a means to potentially help reduce risk of colon cancer, in addition to their known benefits in regards to preventing osteoporosis.
Colorectal cancer is the second leading cause of cancer death in the United States and Canada. The National Cancer Institute suggests that between 70-90% of colon cancer cases could be prevented via more prudent dietary and lifestyle practices. Consuming less animal fat (thereby encouraging the production and secretion of fewer bile acids), ingesting calcium at levels discussed in this review, eating more fruits and vegetables as well as dietary fiber, and regular involvement in physical activity, are lifestyle behaviors that are strongly associated with decreased risk of colon cancer. Evidence is also building for the daily use of certain antioxidant supplements (selenium, Vitamin E, Vitamin C) and Vitamin D supplementation (600-1,000 IU per day).
- Peters U, Chatterjee N, McGlynn A, et al. Calcium intake and colorectal adenoma in a US colorectal early detection program. Am J Clin Nutr. 2004;80:1358-65
- Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med 1999;340:101-7
- Bonithon-Kopp C, Kronborg O, Giacosa A, et al. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomized intervention trial. European Cancer Preventiionon Organisation Study Group. Lancet 2000;356:1300-6
- Hofstad B, Almendingen K, Vatn M, et al. Growth and recurrence of colorectal polyps: a double-blind 3-year intervention with calcium and antioxidants. Digestion 1998;59:148-56