New study below.
This is a horrible paper. It takes as a given that vitamin D increases PCa risk (see yesterday's post on vitamin D & mortality). & then piggybacks on the discredited belief that testosterone [T] causes PCa, to ask: Does D increase T? Indeed, there is an association, & thus we have the smoking gun.
{I was puzzled to see Elizabeth Platz (Hopkins) as co-author - she has written a number of important papers in the past. But her name is on a lot of papers these days.}
"higher testosterone ... and SHBG ... were observed with increasing 25(OH)D." Note that about half of total T is bound to the SHBG protein. As such, it is not bioavailable. The paper makes no mention of the net effect on free T.
"PSA concentration was not associated with serum 25(OH)D ..." But seemingly, that doesn't let D off the hook. It does, however, eliminate detection bias.
"... a positive association between serum 25(OH)D and testosterone and SHBG. The findings support an indirect mechanism through which vitamin D may increase prostate cancer risk ..." Ugh!
It's really ironic that in the past two years we have seen a number of studies that have found that T replacement does not increase the risk for PCa. Which is impressive given how the T replacement age range overlaps the PCa incidence age range.
The new paper doesn't claim that the rise in T caused by D can take T outside of its normal range. My reading is that higher normal D is associated with higher normal T. The problem with the study is the assumption that T is intrinsically dangerous at normal levels.
Given that vitamin D insufficiency is common in the U.S., it might be more appropriate to claim that sub-optimal D will lead to sub-optimal T.
It has been noted in chronic spinal cord injury, where men "exhibit a high prevalence of both androgen and vitamin D deficiency", that lower D was associated with lower T & free T. [2]
In another 2015 paper, vitamin D was proposed as a performance enhancer for athletes, because it might increase T production & "large portions of athletic populations are vitamin D deficient". [3] I suppose it will be a banned substance soon. LOL
& a Chinese study, also from 2015 [4], found that: "A lower vitamin D level was associated with a higher prevalence of hypogonadism"
It is well-established that vitamin D & T, through their receptors (VDR & AR) work together to regulate prostatic growth. Gary Schwartz, the guy who first proposed that vitamin D was essential to prostate health, was involved in a 1996 rat study [5] that found that:
"A greater degree of cellular differentiation was observed in the rats treated with testosterone and vitamin D compared to rats that received testosterone supplementation alone." i.e. the cells were more normal-looking.
In a 1999 study [6] of human prostatic epithelial cells:
"Incubation of primary cultures of prostate epithelial cells with 1,25-D at a concentration of 10(-8) M reduced cell proliferation by 40% of controls. The inhibition of growth by 1,25-D was maintained in the presence of DHT."
{1,25-D (calcitriol) is the active hormonal form of D, whereas 25-D (aka calcidiol & 25(OH)D)) is the inactive form of D used in blood tests.}
In a 2003 rat study [7]:
"Administration of 1,25 D in the intact animals decreased the prostatic size by 40%, compared to control animals, whereas 1,25 D did not influence the size of the prostate in castrated rats."
The preamble to a 2013 paper [8]:
"Previous studies from our laboratory have shown that testosterone (T) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) co-operate to inhibit cell proliferation and induce significant changes in gene expression and differentiation in LNCaP cells."
& so on. The interaction between VDR & AR is such that I doubt that vitamin D can do much against PCa in the absence of T.
Elizabeth Platz was also involved in a 2012 study [9] of the relationship between D & T:
"The shape of the dose-response curves indicate that associations between 25(OH)D and testosterone are strongest in lower ranges of 25(OH)D."
That adds a little balance, for those who fear an out-of-control linear relationship. LOL
Why might vitamin D & PCa be associated in populations that do not see a lot of strong sunlight?
1] men at high risk for PCa might use supplements. In the Scandinavian studies, one would have to use supplements to have adequate D throughout the winter. Life Extension did an interesting study using member data. They looked at those who ordered cholecalciferol (D) & also D blood tests. To their chagrin, many of their members who were taking 5,000 IU D could not get their calcidiol (25-D) levels above 32. This prompted them to introduce a 7,000 IU dose. It takes diligence to have adequate D in Uppsala during March, & one must question the motivation.
2] Sweden (& many other countries) did not react to the introduction of the PSA test with the enthusiasm that Americans did. If the men who take D supplements are more inclined to have PSA tests, we have detection bias. The higher rate of cases with D adequacy, might be an artifact of the concern that led the men to supplementation in the first place.
There is, however, a situation where men who supplement can shoot themselves in the foot. It is common knowledge that calcium supplementation is associated with PCa progression. This may be a major reason why dairy products are also associated with advanced disease. The problem with calcium is that vitamin D is not activated until serum calcium dips. One can have a large reservoir of calcidiol, but excess calcium in the blood will prevent any of it converting to calcitriol.
Many people concerned about osteoporosis know to take vitamin D along with their calcium. Supplementation with D helps get the calcium into the blood. But without vitamin K (specifically, K2) to help transport the calcium into bones, it will linger & inhibit D activation. This form of calcium elevation is called hypervitaminosis D. Without K2, D supplementation might actually prevent active D getting to the PCa cells. The cure for hypervitiminosis D? Vitamin K2!
-Patrick
[1]
[2] ncbi.nlm.nih.gov/pubmed/263...
[3] ncbi.nlm.nih.gov/pubmed/262...
[4] ncbi.nlm.nih.gov/pubmed/261...
[5] ncbi.nlm.nih.gov/pubmed/893...
[6] ncbi.nlm.nih.gov/pubmed/104...
[7] ncbi.nlm.nih.gov/pubmed/129...
Xgeva & Calcium/vitamin D
Sunlight and vitamin d
Role of Vitamin D in Prostrate Cancer
