Page 334 - Vitamin D and Cancer

14 Unique Features of the Enzyme Kinetics for the Vitamin D System 321

Humans were “designed” through evolution
for steady, “normal” levels around 150 nmol/L

Serum 25(OH)D nmol/L Annual cycles
150
of 25(OH)D
fluctuation not
accommodated
for by evolution.

50

Sun-deprived
humans rarely have
25(OH)D levels
Years Æ over 50 nmol/L

Fig. 14.2 Long-term patterns of 25(OH)D levels in modern populations, showing two patterns for
modern humans that would have been unlikely to have existed during our evolution. Populations
at temperate latitudes who avoid exposing skin to sunshine exhibit perpetually low serum 25(OH)
D concentrations. Populations that sunbathe during summer will exhibit annual cycles of rising
and falling serum 25(OH)D concentrations. The prevalent view is that low 25(OH)D may not be
ideal, but cyclic patterns in serum 25(OH)D may also have adverse consequences even though
average levels may appear to be comparatively high. Cycles of rising and falling 25(OH)D would
force the system of enzymes represented in Fig. 14.1 to adapt, and during the declining phase
CYP24 would be in relative excess, causing insufficient tissue levels of 1,25(OH) D
2

latitude. At latitudes distant from the equator, persons who exhibit the highest
serum 25(OH)D concentrations during the summer should as a consequence suffer
the largest absolute and relative declines in 25(OH)D through the “vitamin D win-
ter,” when at high latitudes, the sun does not reach high enough in the sky to
deliver vitamin D-forming UVB to the earth’s surface [48, 49]. Those who avoid
exposing skin to summer sunlight will exhibit the smallest amplitude fluctuations
in serum 25(OH)D. In other words, at the level of tissues like the prostate, serum
25(OH)D levels that are actively declining may be just as bad as very low levels
of 25(OH)D, because the tissue level of the catabolic enzyme, 1,25(OH) D-24-
2
Ohase are relatively excessive during declining phases in serum 25(OH)D. Near
the equator there seasonal variability in UVB radiation is minimal, but with
increasing latitude, the variability in environmental UVB increases dramatically
[50]. Serum 25(OH)D concentrations cycle in a pattern and amplitude that lags by
about 3 months the fluctuations in UVB light throughout the seasons. We humans
are the hairless primates, with a biology suited for an environment where the der-
mal vitamin D factory is exposed throughout the year. We have been designed
through evolution to be optimized for tropical latitudes where serum 25(OH)D
concentrations do remain high and stable all year. Consequently, it is reasonable
to infer that perpetually fluctuating inputs of vitamin D may pose a risk to certain
aspects of our biology.