Page 336 - Vitamin D and Cancer

14 Unique Features of the Enzyme Kinetics for the Vitamin D System 323

for a drug is an interval at about the half-life of the drug [57]. For vitamin D, the
effective half-life for the decline in 25(OH)D after a dose of vitamin D is approxi-
3
mately 2 months [58]. However, during the first month after a dose of vitamin D,
serum 25(OH)D concentrations are relatively stable [37, 59]. In contrast, with vita-
min D the total serum 25(OH)D concentration after the subsequent month ends up
even lower than the baseline level before the first dose was given [59]. The phenom-
enon of a total serum 25(OH)D falling to below its initial level a month after a dose
of vitamin D is clinical support for the present contention that the rate of adaptation
2
of metabolic clearance is too slow to respond to fluctuations in vitamin D supply. A
key implication of the theory described here is that clinical trials using vitamin D at
intermittent doses should avoid vitamin D and they should avoid dosing intervals of
2
any form of vitamin D that go beyond 1 or 2 months. Vitamin D given on a once
3
weekly or once monthly may be an optimal, because less frequent dosing improves
adherence compared to daily dosing [60, 61] while minimizing fluctuations in serum
25(OH)D concentration that would occur with semi-annual or annual doses.
An inherent benefit to moderately higher 25(OH)D concentrations makes a lot
of sense in many respects [62–64], but it has not been the purpose of this chapter
to deal with those aspects. The perspective presented here provides an explanation
that can account for many of the things that led to the reservations IARC has
expressed against broad advice to increase vitamin D as a way to prevent cancer [7].
The present perspective helps to justify vitamin D supplementation for situations in
which latitude appears to increase the risk of cancer even if the population 25(OH)
D concentrations might average higher than for populations at lower latitudes.
Supplementation raises overall serum 25(OH)D concentrations, and it will lessen
the role of seasonal fluctuations in serum 25(OH)D.

References

1. Kricker A, Armstrong B (2006) Does sunlight have a beneficial influence on certain cancers?
Prog Biophys Mol Biol 92(1):132–139
2. Knight JA, Lesosky M, Barnett H, Raboud JM, Vieth R (2007) Vitamin D and reduced risk of
breast cancer: a population-based case-control study. Cancer Epidemiol Biomarkers Prev
16(3):422–429
3. Grant WB (2002) An estimate of premature cancer mortality in the US due to inadequate
doses of solar ultraviolet-B radiation. Cancer 94(6):1867–1875
4. John EM, Schwartz GG, Koo J, Van Den BD, Ingles SA (2005) Sun exposure, vitamin D
receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res
65(12):5470–5479
5. Rukin NJ, Zeegers MP, Ramachandran S, Luscombe CJ, Liu S, Saxby M et al (2007) A com-
parison of sunlight exposure in men with prostate cancer and basal cell carcinoma. Br
J Cancer 96(3):523–528
6. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N et al (2008) Serum vitamin
D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst
100(11):796–804
7. IARC Working Group on Vitamin D (2008) Vitamin D and cancer. WHO Press, Geneva,
Switzerland, Report No.: 5