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Quick Facts
- Vitamin D deficiency is a widespread health issue in the general population; in the cancer population the prevalence is upwards of 90%
- Vitamin D has been shown to increase cell death in the colorectal epithelium thus reducing the risk of the development of CRC
- Maintain vitamin D at the sufficient state with 25-OH-D levels in the range of 32–100 ng/ml; levels of 50–100 ng/ml are optimal for most patient populations
- Randomized clinical trials reveal vitamin D at higher doses of 700–1,100 IU/day resulted in subsequent reductions of cancer risks and fractures
Vitamin D Status and Risk of Colorectal Cancer: A Review

The effect of lifestyle factors including dietary habits, exercise patterns, stress levels, work environment, smoking and alcohol behaviors and their impact on cancer risk have been broadly researched. The plethora of media reports about the dos and don’ts regarding dietary patterns and supplement ingestion, to decrease cancer risk, continue to evolve.

Vitamin D is a supplement of interest which is increasingly being recognized as a component of cancer risk reduction. Vitamin D deficiency is a public health problem in the general population however, in the cancer population the prevalence is upwards of 90%.1 The impact of vitamin D on cancer has been researched in ecological studies revealing that increased sun exposure decreases internal solid organ cancers2 while a meta-analysis of 18 randomized, controlled trials (RCTs) concluded that vitamin D supplementation is associated with decreased mortality from conditions such as cancer, cardiovascular disease and diabetes mellitus.3 In colorectal cancer (CRC) vitamin D has been shown to increase cell death in the colorectal epithelium thus reducing the risk of development of CRC.4 Additionally colorectal epithelial cells contain vitamin D receptors (VDRs) and express 1-a-hydroxylase. This enables the cells to convert circulating 25-OH-D (25 hydroxyvitamin D) into active 1-25-OH-D metabolite resulting in binding to the cells’ VDRs which produces an autocrine effect inhibiting the metastatic potential.5

Vitamin D has been studied in relation to various cancers, however its effects on CRC has been most widely researched. Zhou and colleagues6 recently reported on a summary of the current evidence of vitamin D to promote best practices on CRC risk reduction. The authors examined relevant research articles form 2002–2008 and selected 25 research publications based on strength of evidence for this report including:  

  • 4 randomized, controlled trials
  • 11 cohort or case-control studies measuring serum 25-OH-D levels
  • 10 cohort studies reporting vitamin D intake

Results of the review are grouped into 3 categories:  

  • Vitamin D as a research intervention in RCTs
  • Dose Response between 25-OH-D level and CRC risk
  • Vitamin D intake and CRC risk

Vitamin D as a Research Intervention

Randomized controlled trials and the role of vitamin D supplementation reveal some conflicting results in decreasing cancer risk.

  1. A breakthrough RCT reported by Lappe and colleagues7 (N=1,179) demonstrated that postmenopausal women who took vitamin D supplementation of 1,100 IU in conjunction with calcium 1,400–1,500 mg daily for four years had a 60% to 77% overall reduction in cancer risk.
  2. Contrasting results came from the Women’s Health Initiative (WHI) study with 36,282 postmenopausal women where no protective effects against CRC were found following7 years of daily vitamin D at 400 IU with 1,000mg of calcium.8
  3. Authors concluded that this may be related to the lower daily dose of vitamin D supplementation whereby impact on raising 25-OH-D levels was insufficient for CRC risk reduction.
  4. Adherence and overlapping use of estrogen therapy in this study were also confounding factors in outcomes.8

Two smaller RCTs found the effects of calcium 1,500mg with vitamin D 400 IU daily for 6 months decreased epithelial cell proliferation from colorectal mucosa and polyps. Additionally the combination appeared to inhibit polyp formation.4

Dose Response Between 25-OH-D Level and CRC Risk
Of the 11 studies examining the relationship between 25-OH-D levels and CRC risk, varying degrees of CRC risk reduction were identified in 7 studies and 4 studies for colorectal adenoma at higher serum 25-OH-D levels respectively. Limitations of the studies were that evaluation of 25-OH-D levels was mostly one-time measurements which may be inaccurate due to the fluctuating nature of these levels with seasonal changes. However, an inverse relationship is realized between 25-OH-D levels (vitamin D status) and CRC and colorectal adenoma risks. What is known is that the lower the level of vitamin D the higher the risk.6

Vitamin D Intake and CRC Risk
Ten studies examining the effect of vitamin D intake from diet and supplementation were reviewed. Seven of them revealed favorable findings regarding higher vitamin D intake and CRC risk reduction while 3 studies did not detect an inverse relationship. Zhou and colleagues 6 suggest that these inconsistent results may be attributed to the fact that  vitamin D intake may represent only one piece of overall vitamin D resource availability thus not reflecting real vitamin D status. Additional factors to explain the variance of results include: different food survey questionnaires were utilized in the studies and the use of questionnaires are subject to measurement errors and report bias.

The Role of Healthcare Providers (HCPs)
As stated earlier, vitamin D deficiency is a widespread health issue in the general population linked to cancer and other health risks. HCPs have a responsibility to intervene in this easily correctable condition. In 1997 the FDA recommendations for vitamin D established. The WHI results suggest these recommendations may be inadequate in preventing vitamin D deficiency. As revealed in the cited RCTs higher doses of 700–1,100 IU/day resulted in subsequent reductions of cancer risks and fractures. Zhou and colleagues6 have identified the following as treatment recommendations for vitamin D deficiency:  

  • Encourage patients to take 1,000 IU per day of vitamin D plus 1,200–1,500 mg of daily calcium if 25-OH-D levels are not available 

  • Screen 25-OH-D levels twice a year (near the end of summer and near the end of winter) for high-risk individuals

  • Correct vitamin D deficiency through vitamin D repletion
  • Maintain vitamin D at the sufficient state with 25-OH-D levels in the range of 32–100 ng/ml however, levels of 50–100 ng/ml are optimal for most patient populations
  • Advise calcium intake of 1,200 mg daily for men and premenopausal women and 1,500 mg daily for postmenopausal women and individuals with osteoporosis or osteopenia

References

  1. Everett C. The prevalence of vitamin D deficiency and insufficiency in a hematology-oncology clinic. Clin J Oncol Nurs. 2008;12:33-35.
  2. Tuohimaa P, Pukkala E, Scélo G, et al. Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: Vitamin D as a possible explanation. Eur J Cancer. 2007;43:1701–1712.
  3. Autier P, Gandini S. Vitamin D supplementation and total mortality: A meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167:1730–1737.
  4. Holt PR, Bresalier RS, et al. Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa. Cancer. 2006;106:287-296.
  5. Giovannucci E. The epidemiology of vitamin D and colorectal cancer: Recent findings. Curr Opin Gastroenterol. 2006;22:24-29.
  6. Zhou G, Stoitzfus J, Swan BA. Optimizing vitamin D status to reduce colorectal cancer risk: An evidentiary review. Clin J Oncol Nurs. 2009;13:E3-E17. Link to abstract: http://ons.metapress.com/content/m085797k71101304/?p=66d27cdc6d6e45ce8a27b51657cc96a0&pi=0. Accessed April 6, 2010. 
  7. Lappe JM, Travers-Gustafson D, et al. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized Trial. Am J Clin Nutr. 2007;85:1586-1591.
  8. Holick MF, Giovannucci E. Comment on calcium plus vitamin D and the risk of colorectal cancer. N Eng J Med. 2006;354:2287-2288.

 



Article Created On : 9/10/2009 3:36:19 PM             Article Updated On : 4/6/2010 10:52:07 AM