Calcium Supplements Linked to Reduced Risk of Colorectal Cancer:

Are your patients achieving optimal intake?

James Meschino DC, MS, ROHP
Over the past 25 to 30 years studies have suggested that calcium may confer protection against colorectal cancer. Animal studies have shown this effect, and many epidemiological studies have shown a strong correlation between higher calcium intake and lower incidence of colorectal cancer. (1-5)

A meta-analysis published in 2014 in the International Journal of Cancer has provided additional evidence that higher calcium intake, including calcium supplements, is associated with a significant reduction in risk of colorectal cancer.  In this study Boston-based scientists conducted a dose-response meta-analyses of 15 studies involving 12,305 cases of colorectal cancer and calcium intakes, ranging from 250-1,900 mg/day. They included studies that varied in duration from 3.3 to 16 years. The data indicated that both total and supplemental calcium were associated with a reduction in the risk of colorectal cancer. More specifically, the data showed that for every 300 mg increase in calcium from supplements there was an associated 9% reduction in risk of colorectal cancer, and that for every 300 mg increase in total calcium there was an associated reduction in risk of 8%. Thus, whether the individual relied on food or supplements as their source of calcium, both showed a similar reduction in risk of colorectal cancer, such that for every 300 mg of calcium consumed there was a corresponding colorectal cancer risk reduction of 8-9%. Accordingly, ingesting 1200 mg of calcium per day from food and/or supplements (typical for someone striving to maintain optimal bone density) would confer a 32-36% reduction in colorectal cancer risk.

This has important clinical application, as the 2003 to 2006 U.S. National Health and Nutrition Examination Survey showed that the median total calcium intake of adults aged over 50 years was only about 650 mg/day for non-calcium-supplement users and 1,000 mg/day for calcium-supplement users. The National Health and Nutrition Examination Survey is a nationally representative cross-section survey in the United States. The 2014 meta-analysis suggests that benefit of calcium intake in preventing colorectal cancer would be expected to increase with continued calcium intake beyond 1,000 mg/day, not only for non-supplement users, but that supplement users may further reduce their risk of colorectal cancer through additional calcium intake (e.g. additional supplementation). The researchers conclude that both dietary and supplementary calcium intake may continue to decrease colorectal cancer risk beyond 1,000 mg/day. (6)

Calcium Supplements Have Prevented Colon Cancer Recurrence
These observations are further supported by the published results in 2004 of the Calcium Poly Prevention Study, which was a randomized, double-blind, placebo-controlled chemoprevention trial among patients with a recent colorectal adenoma. Nine hundred thirty (930) patients were randomly assigned to calcium carbonate (1200 mg/day) or placebo. Follow-up colonoscopies were conducted approximately 1 and 4 years after the qualifying examination. The results showed that group receiving the calcium supplementation (1200 mg per day) had showed pronounced anticancer effects on advanced colorectal lesions compared to the placebo group. (7) Other studies, including randomized clinical trials, have also shown that supplementation with calcium is associated with a decreased risk of colorectal adenoma recurrence and colorectal cancer. (8, 9)

How Does Calcium Reduce Risk of Colon Cancer
Calcium has been shown to exhibit protection against colorectal cancer through various biological mechanisms.  Animal studies suggest that calcium binds to secondary bile acids and fatty acids in the colonic lumen, thereby diminishing the potential proliferative stimulus of these compounds on the colonic mucosa. Calcium may also reduce the risk of colorectal cancer by direct effects on cells that line the colon (epithelial cells) by slowing the rate of cell division, promoting cellular differentiation and inducing apoptosis (programmed cell death) of cells with genetic damage. All of the mechanisms are shown to be important in cancer prevention. Animal studies and some, although not all, clinical trials have shown that increased calcium and dairy food intakes can decrease colonic epithelial cell proliferation. (8)

Concluding Remarks
From a practitioner standpoint it is reassuring to see that the same level of calcium intake that has been shown to prevent and manage osteoporosis, is consistent with the same range of calcium intake associated with reduced risk of colorectal cancer (1000-1500 mg per day). Although a number of epidemiological studies have shown that dairy products are linked to decreased risk of colon cancer, researchers on the meta-analysis team of the 2014 study suggest that calcium supplements and non-dairy sources of calcium may be better choices to increase calcium intake, including non-dairy, calcium-fortified foods and beverages.  Their concerns are that many dairy products are high in fat, hormones and calories, and contain casein protein, which is linked to increased cancer risk in some studies.

As for an increased risk for cardiovascular disease from higher calcium intakes, this has largely been dismissed by recent research investigations. (10) Although it is important in my view to ensure that the patient is also receiving adequate magnesium, as calcium intakes increase and that blood levels of vitamin D remain at or above 30 ng/ml (75 nmol/L) throughout the course of the entire year.

Note also that a recent Medscape review highlighted the fact that vitamin D blood levels above 30 ng/ml are highly correlated with a decreased risk of colon cancer, breast cancer, leukemia and melanoma, as well as diabetes (http://www.medscape.com/viewarticle/829677 ).

In order to provide patients with personalized recommendations about calcium and vitamin D, I suggest that you get your patients to complete a 7-day diet history to determine their present calcium intake, along with undergoing a simple blood test for 25-hydroxycholecalciferol (vitamin D).  Once you have this data, you can advise them, if necessary, about how to increase their calcium intake and vitamin D blood levels into the optimal range.

References

1. Lipkin M. Preclinical and early human studies of calcium and colon cancer prevention. Ann N Y AcadSci1999;889:120–7.
2. Vinas-Salas J, Biendicho-Palau P, Pinol-Felis C, Miguelsanz-Garcia S, Perez-Holanda S. Calcium inhibits colon carcinogenesis in an experimental model in the rat. Eur J Cancer1998;34:1941–5.
3. Pence BC, Buddingh F. Inhibition of dietary fat-promoted colon carcinogenesis in rats by supplemental calcium or vitamin D3. Carcinogenesis1988;9:187–90.
4. Pence BC. Role of calcium in colon cancer prevention: experimental and clinical studies. Mutat Res1993;290:87–95.
5. Pence BC, Dunn DM, Zhao C, Patel V, Hunter S, Landers M. Protective effects of calcium from nonfat dried milk against colon carcinogenesis in rats. Nutr Cancer1996;25:35–45.
6. Keum N, Aune D, Greenwood D.C., Ju W, Giovannucci E.L. Calcium intake and colorectal cancer risk: Dose-response meta-analysis of prospective observational studies. International J Cancer (2014) 135 (8): 1940-1948)
7. Wallace K, Baron J.A., Cole B.F., Sandler R.S., Karagas M.R. Effect of Calcium Supplementation on the Risk of Large Bowel Polyps JNCI J Natl Cancer Inst (2004) 96 (12): 921-925.
8. Larsson S.C., Bergkvist L, Rutegard J, Giovannucci E., Wolk A. Calcium and dairy food intakes are inversely associated with colorectal cancer risk in the Cohort of Swedish Men. Am J ClinNutr(2006): 83 (3):  667-673
9. Shaukat A, Scouras N, Schunemann HJ. Role of supplemental calcium in the recurrence of colorectal adenomas: a meta-analysis of randomized controlled trials. Am J Gastroenterol2005;100:390–4.
10. The effects of calcium supplementation on coronary heart disease hospitalisation and death in postmenopausal women: a collaborative meta-analysis of randomised controlled trials. J. R. Lewis, K. L. Ivey, S. Radavelli-Bagatini, L. Rejnmark, J. S. Chen, J. M. Simpson, J. M. Lappe, L. Mosekilde, R. L. Prentice, R. L. Prince. Osteoporos Int. Vol 25, Suppl. 2, 2014