Vitamin D & PCa Survival.: Do vitamin D... - Advanced Prostate...

Advanced Prostate Cancer

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Vitamin D & PCa Survival.

pjoshea13 profile image

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...

[3] cebp.aacrjournals.org/conte...

[4] ncbi.nlm.nih.gov/pubmed/300...

10 Replies

Patrick, so what in your opinion is the actionable take away?

1] Don't move to Sweden.

2] Avoid deficiency / Insufficiency. Which means using a supplement for many of us.

3] Try to take the same dose every day.

4] Avoid calcium supplement doses associated with worse survival.

5] Avoiod phosphates from soft drinks & deli meats. & large portions of meat that contains phosphorus.

6] There are no studies showing poorer survival with better D status.

j-o-h-n profile image
j-o-h-n in reply to pjoshea13

"Don't move to Sweden."

Geez and I was all packed and ready to go, well I guess Newark, New Jersey is it.

Good Luck and Good Health.

j-o-h-n Tuesday 07/24/2018 11:23 AM EDT

Hello Patrick,

very interested in your item #4

4] Avoid calcium supplement doses associated with worse survival.

I am on Estrogen patches which are working very well for me.

However to compensate for bone loss as with other ADT therapies I was recommended to take Calcium with Magnesium (2:1).

I hadn't heard that Calcium as a supplements can compromise PC Survival.

I would greatly appreciate further information on this risk factor.

Thanks

Peter

Hi Peter,

I'm afraid that I am limited to observational data - LOL - but it is compelling IMO.

The earliest study involves the large Health Professionals Follow-Up Study.

At some point, Giovannucci et al formed a hypothesis that 1,25-D might be important to PCa survival [3]. This is the hormonal form of vitamin D. Excess calcium in the diet causes the kidneys to ditch it, & there is no need to convert 25-D to 1,25-D. In normal situations, the conversion occurs when calcium levels in the blood dip. In that case:

- 1,25-D causes calcium to be drawn from bone ...

- ... & calcium to be taken up from the gut ...

- ... & put back into the bones.

(note that vitamin K is required for the final step.)

Fructose, whether from fruit or a sweetener, has a different effect to excess calcium. It can cause 1,25-D levels to be elevated.

So in 1998, we have a study [1] that reported:

"Higher consumption of calcium was related to advanced prostate cancer ... for intakes > or = 2000 mg/day versus < 500 mg/day" Triple risk. Jumps to 4.5 times the risk for mets.

"High fructose intake was related to a lower risk of advanced prostate cancer ... for intakes > 70 versus < or = 40 g/day ..." Half the risk.

"Fruit intake was inversely associated with risk of advanced prostate cancer ... for > 5 versus < or = 1 serving per day), and this association was accounted for by fructose intake." One-third less risk. "Non-fruit sources of fructose similarly predicted lower risk of advanced prostate cancer."

Also in 1998, Giovannucci (& Chan) looked at Swedish data for "526 cases and 536 controls" [2]:

"Calcium intake was an independent predictor of prostate cancer (relative risk (RR) = 1.91 ... for intake > or = 1183 vs. < 825 mg/day), especially for metastatic tumors (RR = 2.64 ...), controlling for age, family history of prostate cancer, smoking, and total energy and phosphorous intakes. High consumption of dairy products was associated with a 50 percent increased risk of prostate cancer."

In 2001, Giovannucci & Chan are back, but with data from the Physicians' Health Study [4]:

"At baseline, men who consumed >600 mg Ca/d from skim milk had lower plasma 1,25(OH)(2)D(3) concentrations than did those consuming < or =150 mg Ca/d [71 compared with 85 pmol/L (30.06 compared with 35.64 pg/mL) ...]. Compared with men consuming < or =0.5 daily servings of dairy products, those consuming >2.5 servings had a multivariate relative risk of prostate cancer of 1.34 ... after adjustment for baseline age, body mass index, smoking, exercise, and randomized treatment assignment in the original placebo-controlled trial. Compared with men consuming < or =150 mg Ca/d from dairy products, men consuming >600 mg/d had a 32% higher risk of prostate cancer ..."

In 2003, Giovannuci was co-author in a Cancer Prevention Study II Nutrition Cohort study [5]:

"Total calcium intake (from diet and supplements) was associated with modestly increased risk of prostate cancer [RR = 1.2 ... for >or=2000 versus <700 mg/day ...). High dietary calcium intake (>or=2000 versus <700 mg/day) was also associated with increased risk of prostate cancer (RR = 1.6 ...)"

(2006) [6]:

"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 but not with well-differentiated, organ-confined cancers."

I'm glad to hear that you were told to take magnesium with calcium. The two are usually out of synch & that can be a PCa issue too.

I feel that we need very little calcium. Before dairy farming, hunter-gatherers somehow got by.

If one had strong bones before ADT, later problems are unlikely to be due to calcium deficiency. Low estradiol is the obvious thing to correct (& you have a patch). A good vitamin K2 product can improve transport of calcium to bone. Taking a look at your status for other minerals associated with bone health is worthwhile: magnesium, boron, zinc, etc.

Best, -Patrick

[1] cancerres.aacrjournals.org/...

[2] ncbi.nlm.nih.gov/pubmed/101...

[3] ncbi.nlm.nih.gov/pubmed/101...

[4] ncbi.nlm.nih.gov/pubmed/115...

[5] ncbi.nlm.nih.gov/pubmed/128...

[6] ncbi.nlm.nih.gov/pubmed/164...

Fortunately, we don't have to rely on observational studies like this anymore. Once we have a higher level of evidence, we can discard studies like these.

pcnrv.blogspot.com/2018/07/...

I thought the recent New Zealand research study put this issue behind us. level 1 evidence.

Rich

Once again, damned if you do...damned if you don’t. I’ve been taking Theralogix Prosteon , which among other things has 500 iu of D3, for 3+ years. The urologist who diagnosed my PCa recommended it. My family physician is ok with it, but recommended I take it bid rather than tid, and my Mayo oncologist is aware that I am taking it, but hasn’t recommended either for it, nor has he told me to stop taking it. I honestly have no idea what, if any, effect it has on my overall bone health, but since starting my ADT, with a few supplements including Prosteon, 3 years ago I have had no bone pain whatsoever, and bone scans 2 years ago and 10 days ago both showed interval resolution of my one bone mets, and no new bone tumors. So, I guess I will continue taking it until my oncologist instructs me to stop.

ITCandy profile image
ITCandy in reply to Litlerny

500 iu of D3 is a pretty small amount. Are you just taking one pill a day? I think you would do more harm worrying about it than the supplement could do.

From the scans you mentioned, I would say that you're doing quite well.

Keep smiling...

Litlerny profile image
Litlerny in reply to ITCandy

I totally agree with you, IT! I take it twice a day, one with breakfast and one with supper. My Mayo oncologist is a pretty straight forward, no nonesense guy. I’m sure he would have told me if he thought it would either be harmful or even just peeing away money.

Thanks for the encouraging words! I wish the same good health for a long time for you. Golfed 🏌️⛳️ today and shot an 86, so life is good. 😎

Smiling here. Hope you are doing the same. 😃

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