According to Dr. Li Li, a researcher at the Case Western Reserve, if two isolated compounds are promising in colon cancer prevention, the odds are they should become more effective together.
Investigators found that this combination significantly improved outcomes in animal models using only very discrete amounts of Vitamin D3 and metformin, which erased concerns about dosage toxicity.
“In the two animal models, we showed that metformin and vitamin D3 did indeed work together. Clearly, if we put the two together, they are much more potent in preventing colon neoplasia than by taking just either one of them alone. The medium dose also tells us that it is not necessary to take huge doses of the drugs to have a cancer-prevention effect. If the results in the animal models translate to humans, that will be a highly significant finding in colorectal cancer prevention,” explained Dr. Li in a press release.
Vitamin D3 is important in cancer mechanisms such as cell differentiation, proliferation and apoptosis and it inhibits the activation of the Wnt/β-catenin pathway, a process linked to colon cancer cells’ proliferation. Metformin plays a key role in the suppression of proliferation of colon epithelial cells and aberrant crypt foci (ACF), frequent precursors to colorectal cancer.
Laboratory studies in both rats and mice were based in chemical induction of colitis. While some groups of animals received varying doses of both metformin and vitamin D3 combined, others received either metformin alone or vitamin D3 alone. Further, control groups received Celebrex (celecoxib), a positive control, or no drug at all.
“Few colon neoplasias developed in the animals receiving moderate doses of metformin-vitamin D combination. On average, there was also a 40 percent decrease in the development of polyps in all animals receiving both drugs in combination compared to the control groups,” said Dr. Li, the lead researcher.
The studies in rats revealed that moderate doses of metformin-vitamin D3 had the best outcomes against tumors when compared to other doses of the combination and single doses of both metformin and vitamin D3 isolated. The combination treatment significantly reduced the number of tumors in both rats and mice.
When it comes to clinical testing in humans, current options include:
- testing the combination of metformin-vitamin D3 to address treatment for colorectal cancer as a neo-adjuvant therapy;
- testing the combination to prevent colon cancer in those with familial adenomatous polyposis (FAP);
- assessing the outcomes of administering the combination in those with colon cancer before their surgery.
Dr. Li added: “Persons with a 10 millimeter or larger adenoma polyp or high-grade neoplasia have a 50 percent chance for recurrence within four years. We can screen them for colon cancer with colonoscopy every few years, but we don’t have much to offer them in terms of prevention. This metformin-vitamin D3 combo may provide an opportunity to prevent recurrence.”
Li believes that this study emphasizes the importance of rethinking ways of addressing treatment with well-proven medicines that might be more effective together. He added: “Millions of individuals with diabetes, even those who are pregnant, are taking metformin, and individuals with vitamin D deficiency are taking vitamin D3 medications. So metformin and vitamin D3 may already be providing a colorectal cancer prevention benefit to a significant number of people.”