(Latitudes shown below are for the center of each country - more or less.)
It seems well-accepted that multiple sclerosis [MS] is a 'latitude disease'. The idea has been around for at least sixty years & there are currently 257 PubMed hits for <"multiple sclerosis" "latitude">. In Europe, the UK (Manchester is latitude 53.4808°) leads in terms of annual MS mortality per 100,000 lives - 1.47 - whereas Spain (Madrid 40.4168°) has only 0.32.
For PCa, the respective mortality rates are 20.23 & 13.84.
Countries with a PCa mortality rate >20 per 100,000: Norway (25.45) (Trondheim latitude 63.4305°), Sweden (24.17) (Uppsala 59.8586°), Denmark (24.16) (Silkeborg 56.1764°), Iceland (22.46) (Reykjavik 64.1466°). All northern latitudes where very low levels of vitamin D are common during the winter months.
In contrast, Italy is 12.19 (Rome 41.9028°).
I don't think there is much point in comparing incidence rates, since they are a function of screening, which varies by country. Low-risk countries presumably have less screening & therefore a greater rate of advanced disease at diagnosis. The latitude mortality differences might be even wider if screening & standard of care were uniform across countries.
Gary Schwartz suggested the PCa lattitude connection in 1990 [3]. He says he was ridiculed at the time, but there are now 1,210 PubMed hits for <prostate cancer "vitamin d">. I can't imagine that interest will die following the recent Mendelian randomization study.
***
The aim of vitamin D supplementation is to maintain a reservoir of inactive calcidiol [25-D]. We measure 25-D, rather than the active 1,25-D (calcitriol) because the latter fluctuates throughout the day.
If we were to measure 1,25-D we would be measuring kidney production. When circulating calcium dips, the kidneys convert a little of the calcidiol to calcitriol. Calcitriol has two functions, in this context. The first is to increase osteoclast activity to break down bone & release calcium into the blood. The second is to trigger increased calcium uptake from the gut, so that the loan from the bones can ultimately be repaid.
There are a number of tissues in the body, including prostatic, that have a need for calcitriol. They have evolved the ability to convert calcidiol to calcitriol. This indicates how important calcitriol is to the tissue & how unreliable the kidney supply is.
PCa cells inhibit production of the enzyme that converts calcidiol to calcitriol, & up-regulates the enzyme that breaks down calcitriol. If the cancer doesn't want calcitriol around, one must suppose that it has an anti-cancer role.
Someone asked how a vitamin that seems to be ineffective for prevention, could have any value after diagnosis? I would ask why PCa needs the eradication of the active form - calcitriol - in order to progress?
After diagnosis, we become dependent on kidney production of calcitriol. 25-D levels may be a poor estimate of calcitriol access.
Many older men take calcium to ward off osteopenia/osteoporosis. In some cases, calcium is used to treat osteopenia/osteoporosis - perhaps caused by PCa treatment. I find it odd, that if there was no bone issue before treatment (indicative of calcium sufficiency), why increasing calcium intake would solve the problem.
In any case, calcium supplementation has the effect of stopping the kidneys from making calcitriol. It is pointless for a study to measure 25-D & not control for calcium supplementation & milk intake.
The other thing that will interfere with kidney production is excess phosphorus. Large portions of meat or fish should be avoided, as should phosphates from deli meats & soft drinks.
I doubt that many men try to increase kidney production, but this can be done with fructose. Yes, even high-fructose corn syrup can be useful.
PCa researchers have realized that if vitamin D is going to be useful as part of therapy, it should be given as calcitriol. But calcitriol can be dangerous, because the immediate effect is to raise blood levels of calcium.
BigPharma has investigated hundreds of analogs of calcitriol, looking for one that is far less calcemic & with greater therapeutic value.
But it seems that calcitriol may have its uses - from a 2009 Stanford study [4]:
"Patients with biochemical relapse after local therapy for prostate cancer were treated with high dose calcitriol (DN101, Novacea) (45 μg once per week) and naproxen (375 mg twice daily) for one year and followed with serum PSA levels as well as imaging studies. Results: Twenty-one patients were enrolled in the trial. Four patients met criteria for progression, with a PSA doubling time (PSADT) that decreased while on therapy. Fourteen patients had a prolongation of PSADT compared to baseline. Conclusion: Combination therapy with weekly calcitriol and daily naproxen is well tolerated by most patients and prolongation of PSADT was achieved in 75% of patients."
Naproxen is Aleve.
-Patrick
[1] worldlifeexpectancy.com/cau...
[2] worldlifeexpectancy.com/cau...
