Do vitamin D levels affect PCa survival?
Malmö, Sweden, is probably one of the worst places in the world to do a D study, since most men will be deficient for a good part of the year, without supplementation. Nevertheless [1]:
"We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years .., and the mean time from inclusion until end of follow-up was 16.6 years ..."
"We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85-102 nmol/L) compared to the first (<68 nmol/L), HR 0.54 (0.34-0.85) when adjusting for age, time of inclusion, and BMI. The association was further strengthened when adjusted for age at diagnosis, Gleason score, and {tumor characteristics} classification with a HR in Q3 0.36 (0.22-0.60)."
"85-102 nmol/L" is 34-41 ng/mL {<68 nmol/L = <27 ng/mL}
(Many view 32 ng/mL the minimum for sufficiency. Others prefer 30 ng/mL.)
Some here will associate Nordic D studies with a U-shaped or J-shaped risk of PCa occurrence. It's odd to see fairly low values of D (<32 ng mL) being riskier than outright deficiency (<20 ng/mL), but does the apparent risk continue after diagnosis?
"In this study population, s-25(OH)D was inversely associated with total mortality during more than two decades of follow-up, despite, as previous reported, high s-25(OH)D was associated with increased risk of prostate cancer." [2] i.e. in the same population.
Similarly [3]"
"We examined prediagnostic serum 25-hydroxy-vitamin D (25(OH)D) and prostate cancer survival in a cohort of 1,000 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. During 23 years of follow-up, 363 men died from their disease."
"Men with higher serum 25(OH)D were less likely to die from their prostate cancer (Q5 vs. Q1 HR, 0.72 ...)"
Once again: "higher serum 25(OH)D years prior to diagnosis was associated with longer prostate cancer survival".
One thing I have never seen discussed is the effect of PCa studies on the behavior of men without PCa.
A PubMed search on <prostate "vitamin d"> returns 1,242 hits.
Men who consider themselves at higher risk for PCa might well turn to vitamin D. If a man with familial risk takes vitamin D, do we blame the D if he later develops PCa?
Another aspect of this problem is that D users may be more inclined to screen for PCa. This would lead to greater detection among users.
In the Robert Scragg ViDA paper cited elsewhere [4], there are some obvious issues:
A monthy dose of 200,000 IU or 100,000 IU vitamin D is highly unnatural. I think it was Holick who warned against erratic doses. Circulating 1,25-D (the hormonal form) depends on low circulating calcium levels. Consequently, peripheral tissue such as that of the prostate produce the enzyme that converts 25,D (from circulation) to 1,25-D within cells. When 25-D levels are low, calcium homeostasis trumps the needs of peripheral tissue. The body seems to protect the 25-D reservoir when supplies are erratic.
We are told that "Mean ... baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 ... ng/mL." & that "the mean follow-up 25-hydroxyvitamin D concentration {in a sample} consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group". We don't see from the abstract how many men (or women) started off with deficiency. Obviously, one would expect such a study to be particularly interested in that group.
And we read nothing about those who started as D-sufficient yet received these massive doses.
This is a gripe that I also have with the SELECT study that seems to impress so many. Why give a supplement to men who already have a sufficiency of the nutrient?
The population was followed "for a median of 3.3 years (range, 2.5-4.2 years)". Perhaps too short to notice an effect on PCa?
One of the cases for vitamin D that I find compelling, is that PCa down-regulates the enzyme that converts 25-D to 1,25-D, while up-regulating the enzyme that clears 1,25-D. Seems that the cancer does not want 1,25-D in its cells.
Note that the 25-D reservoir is not active. It is the hormonal form, 1,25-D, that is PCa-protective. Calcium supplements can suppress the conversion. Same for excessive phosphorus/phosphate intake. Pointless to have a D study that does not control for this.
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/270...
[2] journals.plos.org/plosone/a...
vitamin D3 or Vitamin D 
