Before I begin I'm going to put a few simplifications in place. I'm going to talk about 25(OH)D as Vitamin D because this is the substance in the blood produced from vitamin D3 in rough approximation to intake and/or available body stores. I will leave 1,25(OH)2D, the tissue active form, as exactly that.
Ted Hutchinson posted a link to Dr Reinhold Vieth's discussion of vitamin D. Dr Vieth is extremely knowledgeable about vitamin D and is looking for an hypothesis to explain the prostate/pancreatic cancer paradox.
Figure 1 sets out the paradox, which is observational in nature.
Under year round UV exposure conditions (low latitudes, broken line, "High UV") there is no association between 25(OH)D and either prostate or pancreatic cancer. At high latitudes (Solid line, "Low UV") there is a positive association between blood levels of 25(OH)D and these cancers. The average year round levels of 25(OH)D actually tend to be higher in northern latitudes, higher than those where there is year-round solar UVB.
Vieth explains that we know almost nothing about the enzymes controlling tissue 1,25(OH)2D levels and much of his discussion is extrapolated from renal enzyme activity.
Formation of 1,25(OH)2D is under the direct control of blood Vitamin D, the more Vitamin D, the more 1,25(OH)2D is formed. An increase in Vitamin D will immediately produce an increase in 1,25(OH)2D as the enzyme is just there and waiting for substrate. Eventually the production of the enzyme down regulates but by then there is plenty of 1,25(OH)2D. The degradation of 1,25(OH)2D is also under the control of blood Vitamin D. There is a lag in response of this enzyme so as blood Vitamin D rises there will eventually be increased breakdown of 1,25(OH)2D and all will be hunky dory with optimal tissue levels.
So there is no problem dealing with rising or steady state Vitamin D levels.
The bug bear is during periods of falling blood Vitamin D levels. Falling substrate produces falling production of 1,25(OH)2D but the degradation enzyme is still active and takes time to shut down in response to low blood Vitamin D levels.
The result is graph A in Figure 5.
I'll put the whole figure up with legend after the individual graphs. In northern latitudes (in my hemisphere!) there is sub optimal 1,25(OH)2D from just after the summer solstice until the UVB comes back in March. The fall is relatively slow and the rise is rapid due to the enzyme kinetic reasons detailed above. Grey hatching suggests sub optimal or pro-neoplasic levels of 1,25(OH)2D in tissues.
Vieth points out in graph C that the situation can be largely ameliorated by constantly supplementing the mean level of northern people from graph A's 40nmol/l to fluctuations around the mean level of 130nmol/l:
There are several implications from this hypothesis.
Short term studies at constant dose rates will mimic the up-swing of Spring in the northern hemisphere. They should produce optimal tissue 1,25(OH)2D concentrations. The supplementation would need to be sustained and long term benefits need long term supplementation.
Anything which produces a falling Vitamin D level will put you in to the unpleasant grey zone. Large intermittent doses are the worst case scenario and are illustrated in graph D.
Stopping your supplements or reducing your dose rate will also put you in to the grey zone.
The very simple message is, if you are going to supplement, supplement consistently and don't take more than a week off at any given time.
But life is never quite that simple. It's time to look at graph B.
Graph B is the pattern of those southerners who get a bit of all year round sun but never go over the top or under the bar for sun exposure and Vitamin D levels. The grey zones in graph B look as small as those in "supplemented" graph C to me. Ultimately it is variations in vitamin D levels which produce the grey zones.
Because the synthetic and degradation enzymes for 1,25(OH)2D adapt to blood Vitamin D levels, provided there is a basic minimum of Vitamin D, tissue levels should be OK.
I'll take a break here and come back to the implications, especially for us Glaswegians, of diet in addition to sunlight and supplementation.
Oh, here are the four graphs and legend all together: