Advanced Prostate Cancer
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Vitamin D

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!











7 Replies


Missing link:


Clin Endocrinol (Oxf). 2016 Mar 17. doi: 10.1111/cen.13062. [Epub ahead of print]

Association between serum 25-hydroxyvitamin D and serum sex steroid hormones among men in NHANES.

Anic GM1,2, Albanes D2, Rohrmann S3, Kanarek N4,5, Nelson WG4,5,6, Bradwin G7, Rifai N7, McGlynn KA2, Platz EA4,6,8,9, Mondul AM8,9.

Author information

1Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.

2Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

3Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.

4Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.

5Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

6Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

7Department of Laboratory Medicine, Harvard Medical School and Children's Hospital, Boston, MA.

8Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

9Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI.



Recent literature suggests that high circulating vitamin D may increase prostate cancer risk. Although the mechanism through which vitamin D may increase risk is unknown, vitamin D concentration could influence circulating sex steroid hormones that may be associated with prostate cancer; an alternate explanation is that it could be associated with prostate-specific antigen (PSA) concentration causing detection bias.


We examined whether serum vitamin D concentration was associated with sex steroid hormone and PSA concentrations in a cross-sectional analysis of men in the National Health and Nutrition Examination Surveys (NHANES).


Testosterone, oestradiol, sex hormone binding globulin (SHBG), androstanediol glucuronide, and 25-hydroxyvitamin D (25(OH)D) were measured in serum from men ages 20 and older participating in NHANES III (n=1,315) and NHANES 2001-2004 (n=318). Hormone concentrations were compared across 25(OH)D quintiles, adjusting for age, race/ethnicity, body fat percentage, and smoking. PSA concentration was estimated by 25(OH)D quintile in 4,013 men from NHANES 2001-2006.


In NHANES III higher testosterone (quintile (Q) 1=17.2, 95% confidence interval (CI)=16.1-18.6; Q5=19.6, 95% CI=18.7-20.6 nmol/L, p-trend=0.0002) and SHBG (Q1=33.8, 95% CI=30.8-37.0; Q5=38.4, 95% CI=35.8-41.2 nmol/L, p-trend=0.0005) were observed with increasing 25(OH)D. Similar results were observed in NHANES 2001-2004. PSA concentration was not associated with serum 25(OH)D (p-trend=0.34).


Results from these nationally representative studies support 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, and suggest the link to prostate cancer is not due to PSA-detection bias. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.


NHANES ; men; testosterone; vitamin D

PMID: 26991691 [PubMed - as supplied by publisher]


Results from these nationally representative studies support a positive association between serum 25(OH)D and testosterone and SHBG. When SHBG is increased, Testosterone binds to the SHBG; therefore, it is not available to the prostate cancer cell. Then Vitamin D increasing testosterone should not be a problem. I take a supplement of 1000 UI, daily. What do you take?

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I use LEF's 7,000 IU softgel. It keeps my 25(OH)D above 55 ng/dL.

Life Extension sells blood tests too, so they looked at customers who were buying D & also testing D levels. The shocking result was that many who were supposedly taking the max - 5,000 IU - were failing to achieve significant levels - hence the 7,000 IU option.

LEF later realized that there was better uptake if taken with a meal containing fat. They switched from powder to a softgel that contains oil, but I take it with breakfast, which is usually my fattiest meal of the day.


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SO what is the bottom line does d3 and T feed PC ? I read where high T can kill PC



The recent studies that show a U-shaped risk curve for vitamin D are largely from Nordic countries, where most men are deficient in the winter & insufficient in the summer. Not enough men with sufficiency all year long. I don't take them seriously.

I agree with the Vitamin D Council that we should aim for >50pg/mL. Mine is 70-75pg/mL.

A low T at diagnosis is associated with poorer prognosis.

Morgentaler says that PCa has all the T it can use in the upper region of hypogonadism. Thus, some extra T isn't going to hurt.

My own feeling is that at lower T levels, there might be estrogen dominance, & estradiol might drive proliferation. So, unless on ADT, I think high-normal T is desirable.

Some CRPC men respond to T supplementation.

There are threads here on BAT, where T is injected into castrate men once a momth, so that the blood cycles from high T to none. Results look promising, but not everyone responds.



Are you going to be at the PCRI conference in LA in September. I would like to see what you look like.


No - too far. -Patrick


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