Vitamin D3 and metformin have individually shown promise in reducing the risk of colorectal cancer, but a new study in the journal Cancer Prevention Research indicates that combined use may be significantly more effective than either vitamin D or metformin alone.

Researchers at Case Western University and Lanzhou University sought to investigate the potential chemopreventive effects of vitamin D3 and metformin against the development of early colon neoplasia in two animal models. In the first model, 110 rats were chemically induced for a predisposition to develop neoplasia of the colon (1,2-dimethylhydrazine dihydrochloride-induced colon cancer); in the second model, 125 mice were chemically induced to develop colitis (DMH-dextran sodium sulfate-induced colitis-associated colon neoplasia). Varying doses of both vitamin D3 and metformin, vitamin D3 alone, metformin alone, celecoxib (positive control), or no drugs (control) were administered in both models. The rats received one of the treatments for 18 weeks and the mice for 20 weeks.

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Combined use of vitamin D3 and metformin was associated with a decrease in the number of tumors vs. singular use of the compounds in the rats, with the moderate metformin-vitamin D3 dose exhibiting the more significant tumor-inhibiting effect. The number of colorectal tumors was also significantly less in the metformin-vitamin D3 mice arm and noticeably fewer in the vitamin D3 alone group. There was a 40% decrease in the development of polyps in all animals receiving both drugs in combination compared to the control groups on average.

Future clinical trial options in humans include:

  • Testing dual metformin-vitamin D3 as an ongoing therapy for individuals who have had colorectal cancer as neoadjuvant therapy
  • Testing the metformin-vitamin D3 combination as a prevention measure in individuals with familial adenomatous polyposis (FAP)
  • Administering both compounds in individuals diagnosed with colorectal cancer one to four weeks before their surgery to reveal mechanisms for the progression of the disease, and therapeutics that could be developed to interrupt those mechanisms

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