Page 328 - Vitamin D and Cancer

Chapter 14
Unique Features of the Enzyme Kinetics
for the Vitamin D System, and the Implications

for Cancer Prevention and Therapeutics

Reinhold Vieth

Abstract An inadequate vitamin D supply per se does not fully explain the role
of vitamin D in the prevention of cancer. The paradigm for the vitamin D sys-
tem differs from the rest of endocrinology because the enzymes that metabolize
25-hydroxyvitamin D [25(OH)D] behave according to first-order reaction kinetics in
vivo. Perpetually fluctuating 25(OH)D in the circulation forces perpetually adaptive
adjustments to the enzymes, CYP27B1 and CYP24, that respectively synthesize and
catabolize 1,25-dihydroxyvitamin D [1,25(OH)2D] in various tissues. Low levels
of 1,25(OH)2D within tissues such as breast and prostate are thought to increase
propensity toward cancer. This chapter details the hypothesis that during the times
when 25(OH)D levels are declining, such as during fall and winter, concentrations of
1,25(OH)2D within tissues cannot be maintained at any cellular set point for optimal
cellular biology. If higher latitude increases the risk of cancer, then vitamin D supple-
mentation will raise and stabilize serum 25(OH)D concentrations, and this will lessen
the adverse effects of seasonal fluctuations in serum 25(OH)D.

Keywords Latitude • Seasonality • Enzyme kinetics • Pharmacokinetics
• Feedback control • Regulation • Dosage interval • Cholecalciferol • Paracrine

14.1 Introduction

Although environmental ultraviolet light (UVB) is associated with fewer internal
cancers, there is no direct experimental evidence that exposure of a person or an
animal to light prevents or moderates an internal cancer. The vitamin D system is
regarded as one mechanism by which lower latitude and/or higher UVB exposure
lower cancer risk or improve prognosis. But aside from colorectal cancer,

R. Vieth (*)
Departments of Nutritional Sciences, and Laboratory Medicine and Pathobiology,
University of Toronto, 600 University Ave,
Toronto, Ontario, M5G 1X5, Canada
e-mail: rvieth@mtsinai.on.ca

D.L. Trump and C.S. Johnson (eds.), Vitamin D and Cancer, 315
DOI 10.1007/978-1-4419-7188-3_14, © Springer Science+Business Media, LLC 2011