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Open Access Article

Optimizing Vitamin D Status to Reduce Colorectal Cancer Risk: An Evidentiary Review

Guiyun Zhou
Jill Stoltzfus
Beth Ann Swan
CJON 2009, 13(4), E3-E17 DOI: 10.1188/09.CJON.E3-E17

Vitamin D deficiency is common in the general public and in patients with cancer. Optimizing vitamin D intake is increasingly recognized in cancer risk reduction, particularly in decreasing colorectal cancer risk. Therefore, summarizing the current evidence to promote best practices related to vitamin D intake and colorectal cancer risk reduction is important. The objectives of this article are to examine the current evidence regarding the impact of vitamin D on colorectal cancer risk reduction and provide practice recommendations for clinicians. Relevant research articles from 2002-2008 were retrieved from multiple electronic databases. Reference lists of relevant articles also were searched manually. Twenty-five research reports were selected for this article: 4 randomized, controlled trials; 11 cohort or case-control studies measuring serum 25-OH-D levels; and 10 cohort studies reporting vitamin D intake. This review generated three themes: raising 25-OH-D levels to a vitamin D sufficient state (32-100 ng/ml) achieved colorectal cancer risk reduction, increasing the intake of vitamin D reduced colorectal cancer risk, and increasing vitamin D intake to 1,000 IU daily is safe and likely sufficient to raise serum 25-OH-D levels above 32 ng/ml to achieve colorectal cancer risk reduction. Several practice recommendations are suggested.

References 

Adams, J.S., Kantorovich, V., Wu, C., Javanbakht, M., & Hollis, B.W. (1999). Resolution of vitamin D insufficiency in osteopenic patients results in rapid recovery of bone mineral density. <i>Journal of Clinical Endocrinology and Metabolism</i>, 84(8), 2729-2730.

American Cancer Society. (2008). <i>Cancer facts and figures, 2008.</i> Retrieved March 28, 2008, from <a target="_blank" href='http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf'>http://www...

Autier, P., & Gandini, S. (2007). Vitamin D supplementation and total mortality: A meta-analysis of randomized controlled trials. <i>Archives of Internal Medicine</i>, 167(16), 1730-1737.

Beres, S. (2008). Vitamin D: Cancer prevention's sunny future? <i>Journal of the National Cancer Institute</i>, 100(5), 292-293, 297.

Bischoff-Ferrari, H.A., Giovannucci, E., Willett, W.C., Dietrich, T., & Dawson-Hughes, B. (2006). Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. <i>American Journal of Clinical Nutrition</i>, 84(1), 18-28.

Bischoff-Ferrari, H.A., Willett, W.C., Wong, J.B., Giovannucci, E., Dietrich, T., & Dawson-Hughes, B. (2005). Fracture prevention with vitamin D supplementation: A meta-analysis of randomized controlled trials. <i>JAMA</i>, 293(18), 2257-2264.

Boscoe, F.P., & Schymura, M.J. (2006). Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993-2002. <i>BMC Cancer</i>, 6, 264.

Canadian Cancer Society. (2007). Canadian Cancer Society announces vitamin D recommendation. Retrieved on March 10, 2008, from <a target="_blank" href='http://www.cancer.ca/ccs/internet/mediareleaselist/0,3172_1613121606_199...

Cannell, J.J., & Hollis, B.W. (2008). Use of vitamin D in clinical practice. <i>Alternative Medicine Review</i>, 13(1), 6-20.

Cherniack, E.P., Levis, S., & Troen, B.R. (2008). Hypovitaminosis D: A widespread epidemic. <i>Geriatrics</i>, 63(4), 24-30.

Conron, M., Young, C., & Beynon, H.L. (2000). Calcium metabolism in sarcoidosis and its clinical implications. <i>Rheumatology (Oxford)</i>, 39(7), 707-713.

Diaz, G.D., Paraskeva, C., Thomas, M.G., Binderup, L., & Hague, A. (2000). Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: Possible implications for prevention and therapy. <i>Cancer Research</i>, 60(8), 2304-2312.

Ding, E.L., Mehta, S., Fawzi, W.W., & Giovannucci, E.L. (2008). Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: Reanalysis of Women's Health Initiative randomized trial. <i>International Journal of Cancer</i>, 122(8), 1690-1694.

Everett, P.C. (2008). The prevalence of vitamin D deficiency and insufficiency in a hematology-oncology clinic. <i>Clinical Journal of Oncology Nursing</i>, 12(1), 33-35.

Fakih, M., & Sunga, A. (2006). Prevention of colorectal cancer: An emerging role for high-dose vitamin D supplementation. <i>Oncology (Williston Park)</i>, 20(13), 1707-1710.

Feskanich, D., Ma, J., Fuchs, C.S., Kirkner, G.J., Hankinson, S.E., Hollis, B.W., et al. (2004). Plasma vitamin D metabolites and risk of colorectal cancer in women. <i>Cancer Epidemiology, Biomarkers, and Prevention</i>, 13(9), 1502-1508.

Freedman, D.M., Looker, A.C., Chang, S.C., & Graubard, B.I. (2007). Prospective study of serum vitamin D and cancer mortality in the United States. <i>Journal of the National Cancer Institute</i>, 99(21), 1594-1602.

Garland, C.F., Garland, F.C., Gorham, E.D., Lipkin, M., Newmark, H., Mohr, S.B., et al. (2006). The role of vitamin D in cancer prevention. <i>American Journal of Public Health</i>, 96(2), 252-261.

Garland, C.F., Gorham, E.D., Mohr, S.B., Grant, W.B., Giovannucci, E.L., Lipkin, M., et al. (2007). Vitamin D and prevention of breast cancer: Pooled analysis. <i>Journal of Steroid Biochemistry and Molecular Biology</i>, 103(3-5), 708-711.

Giovannucci, E. (2006). The epidemiology of vitamin D and colorectal cancer: Recent findings. <i>Current Opinions in Gastroenterology</i>, 22(1), 24-29.

Giovannucci, E., Liu, Y., Rimm, E.B., Hollis, B.W., Fuchs, C.S., Stampfer, M.J., et al. (2006). Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. <i>Journal of the National Cancer Institute</i>, 98(7), 451-459.

Goodwin, P.J., Ennis, M., Pritchard, K.I., Koo, J., & Hood, N. (2008). Frequency of vitamin D (Vit D) deficiency at breast cancer (BC) diagnosis and association with risk of distant recurrence and death in a prospective cohort study of T1-3, N0-1, M0 B [Abstract 511]. <i>Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition)</i>, 26(May 20 Suppl.), 15S.

Gorham, E.D., Garland, C.F., Garland, F.C., Grant, W.B., Mohr, S.B., Lipkin, M., et al. (2007). Optimal vitamin D status for colorectal cancer prevention: A quantitative meta analysis. <i>American Journal of Preventive Medicine</i>, 32(3), 210-216.

Grant, W.B. (2007). A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: Additional evidence that solar ultraviolet-B irradiance cancers. <i>Journal of Steroid Biochemistry and Molecular Biology</i>, 103(3-5), 668-674.

Grant, W.B., & Garland, C.F. (2008). The health benefits of vitamin D greatly outweigh the health risks. <i>Bioassays</i>, 30(5), 506-507.

Grant, W.B., Garland, C.F., & Gorham, E.D. (2007). An estimate of cancer mortality rate reductions with 1,000 IU of oral vitamin D per day. <i>Recent Results Cancer Research</i>, 174, 225-234.

Grau, M.V., Baron, J.A., Sandler, R.S., Haile, R.W., Beach, M.L., Church, T.R., et al. (2003). Vitamin D, calcium supplementation, and colorectal adenomas: Results of a randomized trial. <i>Journal of the National Cancer Institute</i>, 95(23), 1765-1771.

Hartman, T.J., Albert, P.S., Snyder, K., Slattery, M.L., Caan, B., Paskett, E., et al. (2005). The association of calcium and vitamin D with risk of colorectal adenomas. <i>Journal of Nutrition</i>, 135(2), 252-259.

Hathcock, J.N., Shao, A., Vieth, R., & Heaney, R. (2007). Risk assessment for vitamin D. <i>American Journal of Clinical Nutrition</i>, 85(1), 6-18.

Heaney, R.P., Davies, K.M., Chen, T.C., Holick, M.F., & Barger-Lux, M.J. (2003). Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. <i>American Journal of Clinical Nutrition</i>, 77(1), 204-210.

Hershman, D.L., McMahon, D., Irani, D., Cucchiara, G., Crew, K., Raptis, G., et al. (2006). High prevalence of vitamin D deficiency in premenopausal women with early-stage breast cancer [Abstract 8568]. <i>Journal of Clinical Oncology, 2006 ASCO Annual Meeting</i>, 24(18s), 485s.

Holick, M.F. (2007). Vitamin D deficiency. <i>New England Journal of Medicine</i>, 357(3), 266-281.

Holick, M.F., & Giovannucci, E. (2006). Comment on: Calcium plus vitamin D and the risk of colorectal cancer. <i>New England Journal of Medicine</i>, 354(21), 2287-2288.

Holt, P.R., Arber, N., Halmos, B., Forde, K., Kissileff, H., McGlynn, K.A., et al. (2002). Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. <i>Cancer Epidemiology, Biomarkers, and Prevention</i>, 11(1), 113-119.

Holt, P.R., Bresalier, R.S., Ma, C.K., Liu, K.F., Lipkin, M., Byrd, J.C., et al. (2006). Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa. <i>Cancer</i>, 106(2), 287-296.

Jackson, R.D., LaCroix, A.Z., Gass, M., Wallace, R.B., Robbins, J., Lewis, C.E., et al. (2006). Calcium plus vitamin D supplementation and the risk of fractures. <i>New England Journal of Medicine</i>, 354(7), 669-683.

Jacobs, E.T., Alberts, D.S., Benuzillo, J., Hollis, B.W., Thompson, P.A., & Martinez, M.E. (2006). Serum 25(OH)D levels, dietary intake of vitamin D, and colorectal adenoma recurrence. <i>Journal of Steroid Biochemistry and Molecular Biology</i>, 103(3-5), 752-756.

Kesse, E., Boutron-Ruault, M.C., Norat, T., Riboli, E., & Clavel-Chapelon, F. (2005). Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3N-EPIC prospective study. <i>International Journal of Cancer</i>, 117(1), 137-144.

Lappe, J.M., Travers-Gustafson, D., Davies, K.M., Recker, R.R., & Heaney, R.P. (2007). Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. <i>American Journal of Clinical Nutrition</i>, 85(6), 1586-1591.

Li, H., Stampfer, M.J., Hollis, J.B., Mucci, L.A., Gaziano, J.M., Hunter, D., et al. (2007). A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. <i>PLoS Medicine</i>, 4(3), E103.

Lin, J., Manson, J.E., Lee, I.M., Cook, N.R., Buring, J.E., & Zhang, S.M. (2007). Intakes of calcium and vitamin D and breast cancer risk in women. <i>Archives of Internal Medicine</i>, 167(10), 1050-1059.

Lin, J., Zhang, S.M., Cook, N.R., Manson, J.E., Lee, I.M., & Buring, J.E. (2005). Intakes of calcium and vitamin D and risk of colorectal cancer in women. <i>American Journal of Epidemiology</i>, 61(8), 755-764.

Lips, P., Hosking, D., Lippuner, K., Norquist, J.M., Wehren, L., Maalouf, G., et al. (2006). The prevalence of vitamin D inadequacy amongst women with osteoporosis: An international epidemiological investigation. <i>Journal of Internal Medicine</i>, 260(3), 245-254.

Looker, A.C., Dawson-Hughes, B., Calvo, M.S., Gunter, E.W., & Sahyoun, N.R. (2002). Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. <i>Bone</i>, 30(5), 771-777.

Lyman, D. (2005). Undiagnosed vitamin D deficiency in the hospitalized patient. <i>American Family Physician</i>, 71(2), 299-304.

Maddipatla, S., Tan, W., Wilding, G.E., Trump, D., Sunga, A., Johnson, C. et al. (2007). Vitamin D status in patients with colorectal cancer [Abstract 260]. <i>2007 Gastrointestinal Cancers Symposium.</i>

Martinez, M.E., Marshall, J.R., Sampliner, R., Wilkinson, J., & Alberts, D.S. (2002). Calcium, vitamin D, and risk of adenoma recurrence (United States). <i>Cancer Causes Control</i>, 13(3), 213-220.

McCullough M.L., Robertson A.S., Rodriguez C., Jacobs E.J., Chao A., Carolyn J., et al. (2003). Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). <i>American Journal of Epidemiology</i>, 165(10), 1178-1186.

MedlinePlus Medical Encyclopedia. (2007a). 25-hydroxy vitamin D test. Retrieved December 25, 2008, from <a target="_blank" href='http://www.nlm.nih.gov/medlineplus/ency/article/003569.htm#Definition'>h...

MedlinePlus Medical Encyclopedia. (2007b). Parathyroid hormone. Retrieved December 25, 2008, from <a target="_blank" href='http://www.nlm.nih.gov/medlineplus/ency/article/003690.htm'>http://www.n...

Melamed, M.L., Michos, E.D., Post, W., & Astor, B. (2008). 25-hydroxyvitamin D levels and the risk of mortality in the general population. <i>Archives of Internal Medicine</i>, 168(15), 1629-1637.

Melnyk, B., & Fineout-Overholt, E. (2005). <i>Evidence-based practice in nursing and healthcare.</i> Philadelphia: Lippincott Williams and Wilkins.

Miller, E.A., Keku, T.O., Satia, J.A., Martin, C.F., Galanko, J.A., & Sandler, R.S. (2005). Calcium, vitamin D, and apoptosis in the rectal epithelium. <i>Cancer Epidemiology, Biomarkers, and Prevention</i>, 14(2), 525-528.

Miller, P., Demark-Wahnefried, W., Snyder, D.C., Sloane, R., Morey, M.C., Cohen, H., et al. (2008). Dietary supplement use among elderly, long-term cancer survivors. <i>Journal of Cancer Survivorship</i>, 2(3), 138-148.

Mizoue, T., Kimura, Y., Toyomura, K., Nagano, J., Kono, S., Mibu, R., et al. (2008). Calcium, dairy foods, vitamin D, and colorectal cancer risk: The Fukuoka Colorectal Cancer Study. <i>Cancer Epidemiology, Biomarkers, and Prevention</i>, 17(10), 2800-2807.

Munro, B.H. (2005). <i>Statistical methods for health care research</i> (5th ed.). Philadelphia: Lippincott Williams and Wilkins.

Murillo, G., Matusiak, D., Benya, R.V., & Mehta, R.G. (2007). Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancer. <i>Journal of Steroid Biochemistry and Molecular Biology</i>, 103(3-5), 763-767.

National Cancer Institute. (2008). <i>Dictionary of cancer terms: Hazard ratio.</i> Retrieved December 25, 2008, from <a target="_blank" href='http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=618612'>http://www.c...

Ng, K., Meyerhardt, J.A., Wu, K., Feskanich, D., Hollis, B.W., Giovannucci, E.L., et al. (2008). Circulating 25-hydroxyvitamin d levels and survival in patients with colorectal cancer. <i>Journal of Clinical Oncology</i>, 26(18), 2984-2991.

Oh, K., Willett, W.C., Wu, K., Fuchs, C.S., & Giovannucci, E.L. (2007). Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women. <i>American Journal of Epidemiology</i>, 165(10), 1178-1186.

Otani, T., Iwasaki, M., Sasazuki, S., Inoue, M., & Tsugane, S. (2007). Plasma vitamin D and risk of colorectal cancer: The Japan Public Health Center-Based Prospective Study. <i>British Journal of Cancer</i>, 97(3), 446-451.

Palmieri, C., MacGregor, T., Girgis, S., & Vigushin, D. (2006). Serum 25-hydroxyvitamin D levels in early and advanced breast cancer. <i>Journal of Clinical Pathology</i>, 59(12), 1334-1336.

Park, S.Y., Murphy, S.P., Wilkens, L.R., Nomura, A.M., Henderson, B.E., & Konlonel, L.N. (2007). Calcium and vitamin D intake and risk of colorectal cancer: The Multiethnic Cohort Study. <i>American Journal of Epidemiology</i>, 165(7), 784-793.

Peters, U., Hayes, R.B., Chatterjee, N., Shao, W., Schoen, R.E., Pinsky, P., et al. (2004). Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk. <i>Cancer Epidemiology, Biomarkers, and Prevention</i>, 13(4), 546-552.

Quest Diagnostics. (2008). Vitamin D, 25-hydroxy, LC/MS/MS: Test summary. Retrieved December 25, 2008, from <a target="_blank" href='http://www.questdiagnostics.com/hcp/topics/endo/vitamin_d.html'>http://w...

Robien, K., Cutler, G.J., & Lazovich, D. (2007). Vitamin D intake and breast cancer risk in postmenopausal women: The Iowa Women's Health Study. <i>Cancer Causes Control</i>, 18(7), 775-782.

Schumann, S.A., & Ewigman, B. (2007). Double-dose vitamin D lowers cancer risk in women over 55. <i>Journal of Family Practice</i>, 56(11), 907-910.

Sharma, O.P. (2000). Hypercalcemia in granulomatous disorders: A clinical review. <i>Current Opinion in Pulmonary Medicine</i>, 6(5), 442-447.

Sieg, J., Sieg, A., Dreyhaup, J., & Schmidt-Gayk, H. (2006). Insufficient vitamin D supply as a possible co-factor in colorectal carcinogenesis. <i>Anticancer Research</i>, 26(4A), 2729-2733.

Slattery, M.L., Neuhausen, S.L., Hoffman, M., Caan, B., Curtin, K., Ma, K.N., et al. (2004). Calcium, vitamin D, VDR genotypes and colorectal cancer. <i>International Journal of Cancer</i>, 111(5), 750-756.

Theodoratou, E., Farrington, S.M., Tenesa, A., McNeill, G., Cetnarskyj, R., Barnetson, R.A., et al. (2008). Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding. <i>International Journal of Cancer</i>, 123(9), 2170-2179.

Tuohimaa, P., Pukkala, E., Scelo, G., Olsen, J.H., Brewster, D.H., Hemminki, K., et al. (2007). Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: Vitamin D as a possible explanation. <i>European Journal of Cancer</i>, 43(11), 1701-1712.

Velicer, C.M., & Ulrich, C.M. (2008). Vitamin and mineral supplement use among US adults after cancer diagnosis: A systematic review. <i>Journal of Clinical Oncology</i>, 26(4), 665-673.

Vieth, R. (1999). Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. <i>American Journal of Clinical Nutrition</i>, 69(5), 842-856.

Vieth, R., Bischoff-Ferrari, H., Boucher, B.J., Dawson-Hughes, B., Garland, C.F., Heaney, R.P., et al. (2007). The urgent need to recommend an intake of vitamin D that is effective. <i>American Journal of Clinical Nutrition</i>, 85(3), 649-650.

Wactawski-Wende, J., Kotchen, J.M., Anderson, G.L., Assaf, A.R., Brunner, R.L., O'Sullivan, M.J., et al. (2006). Calcium plus vitamin D supplementation and the risk of colorectal cancer. <i>New England Journal of Medicine</i>, 354(7), 684-696.

Wang-Gillan, A., Miles D.A., & Hutchins, L.F. (2006). Evaluation of vitamin D deficiency in breast cancer patients on bisphophonate therapy [Abstract 6098]. <i>San Antonio Breast Cancer Symposium 2006.</i>

Wu K., Feskanich, D., Fuchs, C.S., Willett, W.C., Hollis, B.W., & Giovannucci, E.L. (2007). A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. <i>Journal of the National Cancer Institute</i>, 99(14), 1120-1129.

Yazbeck, C.F., Gonzalez-Angulo, A.M., Shaw, S.A., Waguespack, S.G., Vassilopoulou-Sellin, R., & Busaidy, N.L. (2007). Hypocalcemia induced by bisphophonates in cancer patients with vitamin D deficiency [Abstract 19644]. <i>Journal of Clinical Oncology, 2007 ASCO Annual Meeting</i>, 25(18s), 718s.