New review below [1].
The details are not free, but the Abstract has something I'd like to address:
"There has been substantial enthusiasm recently regarding the potential role of vitamin D in the primary and secondary prevention of cancer. Laboratory studies demonstrate a range of anticarcinogenic effects for vitamin D compounds, but human studies have yielded little consistent evidence supporting a protective association. Higher circulating levels of vitamin D ... appear to be associated with reduced risk of colorectal and bladder malignancies, but higher risk of prostate and possibly pancreatic cancers".
[1] Studies that reported risk at higher levels.
These are mainly Scandanivian studies. It simply isn't possible to be D-sufficient via Stockholm's winter sun. Those with 25-D > 32 ng/mL are likely to be supplementing. Even in summer it can be tough to build up values in the high 30's. So it is puzzling to read of U-shaped PCa risk, where the mid 20's might be the best place to be. i.e. the midpoint of insufficiency [4]:
We "found that both low (</=19 nmol/l {<8 ng/mL}) and high (>/=80 {>32 ng/mL} nmol/l) 25(OH)-vitamin D serum concentrations are associated with higher prostate cancer risk."
"The normal average serum concentration of 25(OH)-vitamin D (40-60 nmol/l) {16-24 ng/mL} comprises the lowest risk of prostate cancer."
In Finland, the high-end of deficiency & the low-end of insufficiency apparently passes for normal. And who knows - perhaps Finns are well-adapted to such levels.
[2] "High" vitamin D levels in men with PCa.
Men at risk for PCa might be inclined to use supplemental D. e.g. those with PSA close to 4.0, or steadily rising, as well as those with familial cancer. After diagnosis, D use is likely to climb. This could explain why PCa is associated with higher levels.
[3] Hypervitaminosis D.
I feel that hypervitaminosis D is badly named. Supplementation can cause serum calcium levels to rise. Many men with PCa know the importance of vitamin K2 to bone health, & K2 has anti-PCa properties. We regularly hear of men who have attained D levels above 70 ng/mL without ill effect. Vitamin K is needed if calcium is to be transported from blood to bone.
Masterjohn published his hypothesis [2] a decade ago:
"Although the toxicity of vitamin D has conventionally been attributed to its induction of hypercalcemia, animal studies show that the toxic endpoints observed in response to hypervitaminosis D such as anorexia, lethargy, growth retardation, bone resorption, soft tissue calcification, and death can be dissociated from the hypercalcemia that usually accompanies them, demanding that an alternative explanation for the mechanism of vitamin D toxicity be developed. The hypothesis presented in this paper proposes the novel understanding that vitamin D exerts toxicity by inducing a deficiency of vitamin K. According to this model, vitamin D increases the expression of proteins whose activation depends on vitamin K-mediated carboxylation; as the demand for carboxylation increases, the pool of vitamin K is depleted. Since vitamin K is essential to the nervous system and plays important roles in protecting against bone loss and calcification of the peripheral soft tissues, its deficiency results in the symptoms associated with hypervitaminosis D."
Men with PCa often shun dairy products, due to the association od calcium intake with aggressive PCa. Here is Giovannucci with a Health Professionals Follow-up Study paper [3]:
"We hypothesized that high calcium intake, possibly by lowering 1,25(OH)2 vitamin D levels, is associated with poorer differentiation in prostate cancer and thereby with fatal prostate cancer."
"In a sample of this cohort, higher calcium intake was associated with lower circulating 1,25(OH)2 vitamin D levels. Our findings suggest that calcium intakes exceeding 1,500 mg/d may be associated with a decrease in differentiation in prostate cancer and ultimately with a higher risk of advanced and fatal prostate cancer ..."
The body tightly controls circulating calcium. If levels dip, calcium will be drawn from bone, but calcium will also be taken up from the gut to restore bone levels. This requires hormonal vitamin D - calcitriol (1,25-D). Normal prostatic cells have a need for calcitriol & can produce it from circulating calcidiol (25-D). PCa cells inhibit the enzyme that does this, which means that circulating calcidiol is of no use in fighting PCa while blood calcium levels are elevated.
There is an irony here: men taking D without K, thereby increasing calcium levels & PCa progression risk. One must be wary of quick fixes with single agents - the more we understand the context, the better the results IMO.
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/284...
[2] ncbi.nlm.nih.gov/pubmed/171...