SAN DIEGO — Calcium and vitamin D supplementation may protect against colorectal cancer by creating an environment in the colon that is less conducive to the formation of polyps and adenomas.
In a pilot study presented in a poster at the annual meeting of the American Association for Cancer Research, subjects who took 800 IU of vitamin D3 per day for 6 months increased the expression of Bax—a protein that promotes the killing of damaged cells—in their colons by 56%, compared with subjects who took placebo.
When calcium was added to the vitamin D, Bax expression also increased, but to a lesser extent (33%), reported Veronika Fedirko, a PhD candidate at Emory University's Rollins School of Public Health, Atlanta.
“We were interested in how calcium and vitamin D prevent colorectal adenomas and colorectal cancers. There is pretty good evidence for calcium, but not as much for vitamin D,” Ms. Fedirko said in an interview.
Ms. Fedirko and her colleagues randomized 92 patients aged 40–75 years with a history of at least one adenomatous colonic or rectal polyp within the past 36 months to receive one of the following treatments for 6 months: 2,000 mg calcium a day (23 patients); 2,000 mg calcium plus 800 IU vitamin D a day (23); 800 IU vitamin D a day (23); or placebo (23).
Patients underwent a colorectal biopsy at study entry and another biopsy at the end of the study period. The tissue samples were examined for expressions of Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter.
After 6 months, Bax expression along the full lengths of the colorectal crypts rose by 56% in the vitamin D-alone group, and by 33% in both the calcium alone and calcium-plus-vitamin D groups, relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40% of the crypts.
There were no statistically significant treatment effects on Bcl-2 expression, although data indicated a potential decrease in Bcl-2 expression after supplementation with calcium alone and with calcium plus vitamin D, said the researchers. They also looked at the ratio of Bax to Bcl-2 density as an indicator of the balance of pro-apoptotic versus anti-apoptotic stimuli in the colorectal crypts. They found that the ratio of Bax to Bcl-2 increased 62% in the calcium group, 47% in the vitamin D group, and 71% in the calcium-plus-vitamin D group.
For the vitamin D group, the proportional increase in the Bax to Bcl-2 ratio in the upper 20% as opposed to the lower 20% of the crypts was 352%, compared with placebo. “It appears that the strongest treatment effect was due to vitamin D and that this occurred in the upper sections of the colon crypts,” Ms. Fedirko said.
Cells that reach the top of the colon crypt are more likely to be diseased or to have mutations, and are therefore prime candidates to be killed off, Ms. Fedirko explained. The fact that vitamin D enhanced Bax production is therefore encouraging, she said.
“Our patients already had adenomas; they have something in their colon that is not right, so supposedly they have a low rate of apoptosis to start with. If we give them vitamin D, and if this increases the level of apoptosis, they will have fewer cells that will ever get to the top of the crypt, so they will be less likely to develop adenomas,” said the researchers.