Calcium and Prevention of Colorectal Cancer

Clinical Question

Do calcium supplements prevent colorectal cancer and adenomatous polyps?

Evidence-Based Answer

Combined evidence from two clinical trials of calcium supplementation lasting for several years revealed a reduced rate of recurrent colorectal adenoma. However, evidence is insufficient to recommend supplementation with dietary calcium for patients who have never had an adenoma.

Practice Pointers

A recent review¹ of epidemiologic evidence did not show that calcium supplementation prevents colon cancer. However, epidemiologic studies of dietary interventions for cancer prevention are vulnerable to survivor bias, confounding factors,and inaccurate dietary recall.

Weingarten and colleagues reviewed the literature to find randomized controlled trials (RCTs) of calcium supplementation used for prevention of colon cancer. Such studies are difficult because they require a large number of patients for a long time. Weingarten found two studies that included a total of 1,346 patients with a previous diagnosis of colon adenoma. In one study, patients took 1,200 mg of calcium daily for four years. Patients in the other study took 2,000 mg per day for three years. When data from the studies were combined, there was a 26 percent relative reduction in recurrent adenomas (odds ratio, 0.74; 95 percent confidence interval, 0.58 to 0.95). However, there were not enough new diagnoses of colon cancer to support conclusions about calcium supplementation’s effect on cancer prevention. No RCTs were found that studied calcium supplementation for primary cancer prevention in patients who had never had a polyp or tumor.

Dietary calcium supplementation promises to reduce the risk of colon cancer moderately. Although it would be appealing to find a simple, inexpensive, and safe dietary supplement to prevent colon cancer, comprehensive programs for healthy living are more likely to be effective. For prevention of colon cancer, the American Cancer Society recommends increasing the intensity and duration of physical activity; eating more vegetables and fruits; limiting intake of red meat; avoiding obesity; and avoiding excess alcohol consumption.²

Link Between Metformin and Lactic Acidosis?

Clinical Question

Does metformin cause lactic acidosis?

Evidence-Based Answer

There is no evidence that metformin causes lactic acidosis, even in patients with renal insufficiency or other comorbidities. Although caution is still indicated in patients with multiple or severe comorbidities, it appears that the initial concern about lactic acidosis with this drug was misplaced.

Practice Pointers

Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients.¹ It is therefore being used increasingly often for the treatment of type 2 diabetes. However, many physicians are concerned about a possible increase in the risk of lactic acidosis, particularly in patients who have cardiovascular disease, renal disease, liver problems, chronic respiratory disease, or advanced age. Phenformin, another biguanide, was withdrawn from the market after a rate of 40 to 64 cases of lactic acidosis per 100,000 patient-years was reported.

Salpeter and colleagues found 176 studies that met their inclusion criteria, of which 118 were prospective clinical trials. The 176 studies followed 26,099 patients who took metformin for a total of 65,621 patient-years, and 8,943 control patients who did not take metformin for 30,002 patient-years.

Although many studies excluded patients with comorbidities, a significant number did not. For example, 81 did not exclude patients with renal insufficiency. Remarkably, there was not a single case of fatal or nonfatal lactic acidosis in any of the patients, whether or not they took metformin. Therefore, the upper limit of a 95 percent confidence interval with zero at the lower end is 8.4 cases per 100,000 patient-years in patients taking metformin and 9.0 cases per 100,000 patient-years in patients not taking it. There was no difference in intermediate physiologic outcomes, such as change in lactate levels, and no evidence of publication bias. The authors cite data showing that contraindications to the use of metformin are largely ignored in clinical practice. It appears that, in this case, physicians are correct.