Vitamin D metformin combo shows promise for colorectal cancer prevention

Vitamin D/metformin combo shows promise for colorectal cancer prevention

Life Extension Update

Tuesday, April 7, 2015. The February 2015 issue of Cancer Prevention Research published the finding of researchers from China's Lanzhou University and Case Comprehensive Cancer Center in Ohio of an additive benefit for vitamin D and the antidiabetic drug metformin in the prevention of colorectal cancer in rodent models of the disease.

Vitamin D helps regulate cell proliferation, differentiation and apoptosis, while inhibiting the activation of a pathway (Wnt/β-catenin) that triggers genes responsible for colon cancer cell proliferation. In addition to suppressing the proliferation of colon epithelial cells and aberrant crypt foci (a precursor of colorectal polyps), metformin stimulates the AMP-activated protein kinase (AMPK) pathway, which reduces signaling and protein synthesis necessary for cancer cell growth.

Li Li, MD, PhD, of Case Western Reserve and colleagues administered varying doses of vitamin D3, metformin, both compounds, or an anti-inflammatory control drug for 18 weeks to rats given a compound that renders the colon susceptible to the development of neoplasia (precancerous cells). In another experiment involving mice that received a substance that causes colitis (which can lead to neoplasia), the animals were given the same treatments for 20 weeks.

In comparison with vitamin D or metformin alone, the combination of a moderate dose of vitamin D and metformin resulted in the formation of fewer aberrant crypt foci and tumors in both experiments. "Few colon neoplasias developed in the animals receiving moderate doses of metformin-vitamin D combination," reported Dr Li, who is the Case Comprehensive Cancer Center's associate director for prevention research. "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."

"In the two animal models, we showed that metformin and vitamin D3 did indeed work together," he observed. "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."

"Persons with a 10 millimeter or larger adenoma polyp or high-grade neoplasia have a 50 percent chance for recurrence within four years," Dr Li noted. "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."

"There is a lot of talk now about drug repurposing today where one drug developed for one condition can be used for an entirely different one," he added. "Here we have two well-proven medicines that if you put them together, they appear to prevent cancer, and they are safe."

"Millions of individuals with diabetes, even those who are pregnant, are taking metformin, and individuals with vitamin D deficiency are taking vitamin D3 medications," commented Case Comprehensive Cancer Center director Stanton Gerson, MD. "So metformin and vitamin D3 may already be providing a colorectal cancer prevention benefit to a significant number of people."

What's Hot
Higher vitamin D levels predict improved colorectal cancer survival
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The 2015 American Society of Cancer Oncology (ASCO) Gastrointestinal Cancers Symposium held in San Francisco was the site of a presentation on January 12, 2015 concerning the finding of longer average survival among colorectal cancer patients with higher vitamin D levels in comparison with those whose levels were low.

Researchers at Dana-Farber Cancer Institute analyzed data from 1,043 patients with colorectal cancer enrolled in a clinical trial that evaluated the effects of chemotherapy plus the biologic therapies bevacizumab and/or cetuximab. Plasma 25-hydroxyvitamin D levels were measured at the beginning of the study and dietary questionnaire responses were analyzed for vitamin D intake from food and supplements.

Being older or African-American, having a low intake of dietary or supplemental vitamin D, participating in a reduced amount of physical activity, having a high body mass index, and other factors were associated with significantly lower vitamin D levels. Patients whose plasma vitamin D levels were among the top 20% of subjects at an average of 27.5 nanograms per milliliter (ng/mL) survived a median of 32.6 months in comparison with 24.5 months among those whose levels were among the lowest at an average of 8 ng/mL. Higher vitamin D levels were also associated with improved progression-free survival. Exclusion of subjects who died within three to six months of vitamin D measurement failed to modify the results.

"This is the largest study that has been undertaken of metastatic colorectal cancer patients and vitamin D," stated lead author, Kimmie Ng, MD, MPH, who is a medical oncologist in the Gastrointestinal Cancer Treatment Center at Dana-Farber Cancer Institute. "It's further supportive of the potential benefits of maintaining sufficient levels of vitamin D in improving patient survival times."

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Life Extension Magazine® April 2015 Issue Now Online

Life Extension Magazine® April 2015 Issue Now Online

On the cover

Blueberries boost longevity beyond calorie restriction, by Walter Deriggio


Olive oil offers unique cardiovascular protection, by Marsha McCulloch, RD

The silent epidemic of liver disease, by Michael Campbell

Snow algae and novel peptides revive aging skin, by Robert Goldfaden and Gary Goldfaden, MD

CoQ10 combats congestive heart failure, by Martin Stein

The beginning of the end of the war on medicine, by Charles K. Bens, PhD


As we see it: CoQ10 wars, by William Faloon

In the News

Wellness Profile: Debbie Sherrick, holistic health care practitioner, by Donna Caruso

Author interview: Rick Rosner, by Michael Downey

Journal abstracts: blueberry, olive oil, liver disease and CoQ10


Health Concern

Colorectal cancer

More akin to a hormone than a vitamin, vitamin D broadly influences the genome by activating the vitamin D receptor in the cell nucleus. Activation of the vitamin D receptor is estimated to modulate as many as 2,000 genes, many of which are related to inflammation and cellular mutation – initial drivers in all cancers (Smith 2010).

A review of nine studies found that for every 10 ng/mL increase in serum vitamin D, the relative risk of colorectal cancer decreases 15% (Gandini 2011). These findings are consistent with the conclusion of a large, case-control study across 10 European countries, which also found that as vitamin D blood levels rose, the risk for colorectal cancer declined considerably. Compared with those in the lowest quintile (1/5th) (<10 ng/ml),="" those="" in="" the="" highest="" (="">40 ng/ml) had a 40% lower risk of developing colorectal cancer (Jenab 2010).

Individuals with colon cancer appear to have lower levels of vitamin D at the time of diagnosis as well. Serum vitamin D levels were insufficient (less than 29 ng/mL) in 82% of patients with stage IV colon cancer at the time of diagnosis (Ng 2011).

Low levels of vitamin D may also adversely impact prognosis. One large study found an inverse association between serum 25-hydroxyvitamin D at the time of diagnosis and colon cancer mortality (Freedman 2007).

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