Page 321 - Vitamin D and Cancer

308 M. Fakih et al.

13.4 Vitamin D Status and Colorectal Cancer Outcome

At least two reports have recently associated vitamin D status and patient outcome
after a diagnosis of colorectal cancer. The first study is an ecological study from
Norway [84]. Norway was divided into three geographical regions based on solar
exposure and vitamin D intake based on regional differences in fish consumption.
Diagnosis of colorectal cancer was stratified per season (Winter: December–
February; Spring: March–May; Summer: June–August; Autumn: September–
November). Collected samples from various outpatient clinics on more than 14,000
individuals showed that 25-D levels were lowest in winter and spring. Data regard-
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ing colorectal cancer diagnosis and mortality were obtained from the cancer regis-
try for the period of 1964–1992. Data on 12,823 men and 14,922 women with
colorectal cancer were analyzed. Colorectal cancer mortality was higher when the
diagnosis of colon cancer was made during winter or spring (low 25-D ) compared
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to summer and autumn (higher 25-D ) [84].
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The second study analyzed the outcome of colorectal cancer patients who had a
baseline vitamin D level (RIA) at least 2 years prior to cancer diagnosis through a
retrospective analysis of the NHS and HPFS studies [85]. Three hundred and four
colorectal cancer cases were identified. Stages I–IV of colorectal cancer were
equally distributed among all four quartiles of 25-D . Yet, the mortality rate was the
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lowest in the highest quartile of 25-D . Compared to the lowest quartile, the highest
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quartile had an adjusted HR for overall mortality of 0.52 (95% CI: 0.29–0.94). The
HR for colorectal cancer mortality was 0.61 (95% CI: 0.31–1.19) for the highest
25-D quartile compared to the lowest [85]. This study strongly suggests a correla-
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tion between vitamin D status and the risk of death from colorectal cancer. Whether
this association is a cause – effect association or signifies a common association
between a more replete vitamin D status and other factors that positively impact
colorectal cancer outcome remains to be determined.

13.5 Vitamin D Replacement Strategies and Recommended
Dosing in Colorectal Cancer

The recommended daily dose of cholecalciferol in the general population is a subject
of debate, as is the dosing for the purpose of colorectal cancer prevention. The
Institute of Medicine recommends 400 IU of cholecalciferol/day for the population
older than 50 years [86]. However, this dose has been regarded by many experts in
this field to be inadequate, especially in a vitamin D insufficient population. Indeed,
a dose of 400 IU of cholecalciferol/day is estimated to raise 25-D levels by a modest
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2.8 ng/mL [87]. It is thus no surprise that clinical trials evaluating doses of 400 IU
of cholecalciferol/day failed to show any benefit against osteoporotic fractures while
higher doses did [88]. In a review of randomized studies of cholecalciferol vs.
placebo and fracture prevention, only the study treatment arms achieving a 25-D
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