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Vitamin D and Calcium Boost Colorectal Health in New Trial
12/3/2009
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Clinical trial finds that calcium and vitamin D supplements enhance the health of the cells in the colon and rectum in ways that should deter tumor development
by Craig Weatherby


Colorectal cancer is the second greatest cause of cancer deaths in the US, but it's also one of the most treatable if caught early.

Katie Couric, shown here in an American Cancer Society ad, deserves credit for publicizing the problem and encouraging people to get colonoscopies.

Key Points
  • Clinical trial finds that calcium and vitamin D pills enhance the health of colorectal cells.
  • Vitamin D produced the largest effect, increasing markers of cell health by 242 percent, compared with placebo pills.
  • The results overturn negative, widely doubted findings from the Women's Health Initiative (WHI) study.
  • Findings from this clinical trial also support a new hypothesis that vitamin D3 and calcium help prevent development of cancer by reducing oxidative damage to DNA in colorectal cells.
  • (Oxidative damage is caused by the unstable oxygen molecules called free radicals, which proliferate beyond the body's ability to control them when diets are high in sugars and processed, damaged fats.)
  • The new results support prior indications that vitamin D3 and calcium reduce “biomarkers” of risk for colorectal tumors and that higher circulating vitamin D levels yield a reduced risk for colorectal cancers (Bostick RM et al. 1995; Holt PR et al. 2006).
But, despite advances in treatment, screening, and prevention, mortality rates have declined only modestly in recent years… so the search for preventive dietary and lifestyle factors goes on.

Some evidence links risk of colon cancer to red meats and chemically cured meats, while fish-rich diets are associated with reduced risk.

And a preponderance of the available evidence indicates that calcium and vitamin D can deter development of tumors in the colon and rectum.

This evidence comes from several small clinical trials and from epidemiological studies, in which researchers compare people’s diets and supplement use with their rates of cancer. (One major exception has been criticized as unreliable… see “Findings reverse dubious results”, below.)

Biomarkers... a new approach to early detection
A biomarker is any measurement that correlates with disease risk. For example, insulin resistance and chronic high blood sugar are biomarkers for development of diabetes.

Biomarkers also point to treatments that can lower the likelihood of a disease developing or worsening. To be effective and widely used for screening, biomarker measures must be fast, inexpensive, simple to use, and
unlike sigmoidoscopy and colonoscopy testseasy on the patient.

In 2008, Emory University researchers discovered a number of differences in colon tissuethat is, biomarkers for canceramong people who later developed the disease, compared with those who remained cancer-free.

Thesebiomarkers included differences include early alterations in the genes involved in the normal structure and function of the colon; subtle aberrations in the normal growth, repair, and death cycles of cells; inflammation; and an increase in hormones that stimulate proliferation and differentiation of cells.

The biomarkers influenced positively by calcium and vitamin D in the new trial were cell differentiation, cell proliferation, and the process called apoptosis, in which cells commit “suicide” when they begin to undergo cancerous changes.

New clinical trial focused on biomarkers for colorectal cell health
Researchers from Emory University, the University of Minnesota, the National Cancer Institute, and the National Institutes of Health conducted the randomized, double-blind, placebo-controlled, clinical trial in 92 men and women with a history of benign colorectal tumors (Fedirko V et al. Oct. 2009).

Led by Veronika Fedirko, the researchers randomly assigned the participants to receive daily calcium (2 grams) and/or vitamin D3 supplements (800 IU), or placebo pills for six months.

Markers of the health of cells were found to increase by 201, 242, and 25 percent in the calcium, vitamin D, and calcium-plus-vitamin D groups relative to the placebo group.

“These results indicate that calcium and vitamin D promote colorectal epithelial cell differentiation and may ‘normalize’ the colorectal crypt proliferative zone in sporadic adenoma patients, and support further investigation of calcium and vitamin D as chemopreventive agents against colorectal neoplasms [tumors],” wrote Fedirko and her co-workers.

And earlier this year, a similar trial conducted by the same group found that calcium and vitamin Dindividually or togetherpromoted apoptosis.

As they wrote then, “…the strongest treatment effects may be vitamin D related...” (Fedirko V et al. March 2009).

Findings refute dubious results from Women's Health Initiative
The potential benefits of calcium and vitamin D supplements in relation to colorectal cancer came into question in 2006, when an analysis of data from the large Women's Health Initiative (WHI) study seemed to show that daily supplements of vitamin D and calcium had no preventive effect (Wactawski-Wende J et al. 2006).

However, those results were questioned by many cancer experts, who said that those findings should be taken with a big grain of salt in the light of the complexities of the studywhich produced many “confounding factors” that muddied the waters badlyand the positive indications of most other trials.

For example, Michele Forman and Bernard Levin from the MD Anderson Cancer Center at the University of Texas noted that the WHI trial had three overlapping components, which as they wrote, “created a complex approach with potential confounders...” (Forman MR, Levin B 2006).

Stay tuned… we’ll keep following this important story.


Sources
  • Bostick RM, Fosdick L, Wood JR, Grambsch P, Grandits GA, Lillemoe TJ, Louis TA, Potter JD. Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: a randomized, double-blinded, placebo-controlled clinical trial. J Natl Cancer Inst. 1995 Sep 6;87(17):1307-15.
  • Fedirko V, Bostick RM, Flanders WD, Long Q, Shaukat A, Rutherford RE, Daniel CR, Cohen V, Dash C. Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial. Cancer Prev Res (Phila Pa). 2009 Mar;2(3):213-23. Epub 2009 Mar 3.
  • Fedirko V, Bostick RM, Flanders WD, Long Q, Sidelnikov E, Shaukat A, Daniel CR, Rutherford RE, Woodard JJ . Effects of vitamin d and calcium on proliferation and differentiation in normal colon mucosa: a randomized clinical trial. Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):2933-41. Epub 2009 Oct 27.
  • Forman MR, Levin B. Calcium plus vitamin D3 supplementation and colorectal cancer in women. N Engl J Med. 2006 Feb 16;354(7):752-4. No abstract available. Erratum in: N Engl J Med. 2006 Mar 9;354(10):1102.
  • Holt PR, Bresalier RS, Ma CK, Liu KF, Lipkin M, Byrd JC, Yang K. Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa. Cancer. 2006 Jan 15;106(2):287-96.
  • Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE; Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006 Feb 16;354(7):684-96. Erratum in: N Engl J Med. 2006 Mar 9;354(10):1102.

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