Vitamin D - Latitude / Calcitriol - Advanced Prostate...

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Vitamin D - Latitude / Calcitriol

pjoshea13 profile image
22 Replies

(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...

[3] ncbi.nlm.nih.gov/pubmed/224...

[4] ar.iiarjournals.org/content...

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22 Replies
cesanon profile image
cesanon

Really nice article Patrick. Thanks

NPfisherman profile image
NPfisherman

Patrick....thank you...the question that arises for me is whether the naproxen plus calcitriol vs naproxen alone would show a statistical difference on PSADT....larger cohort is needed...I am guessing that what you are saying is that it is better to supplement with rocaltrol than CaCO3, but there are issues with watching out for kidnety stones, etc..

pjoshea13 profile image
pjoshea13 in reply toNPfisherman

Well, since Naproxen is simply the NSAID Aleve, an over-the-counter drug, my inclination is to give calcitriol the credit. Of course, it always helps to inhibit inflammation - & perhaps there is synergy.

-Patrick

NPfisherman profile image
NPfisherman in reply topjoshea13

That is what I would want to see...large cohort--naproxen alone vs naproxen plus calcitriol---is there a statistical difference??-- My question to you is whether it is better to use rocaltrol ie: calcitriol for calcium rather than calcium carbonate??--not sure if this has been studied in prostate cancer....anyone know??

pjoshea13 profile image
pjoshea13 in reply toNPfisherman

Calcitriol has no calcium - it is pure hormonal vitamin D. It gets its name because it increases calcium uptake from the gut.

-Patrick

pjoshea13 profile image
pjoshea13 in reply topjoshea13

Some might be wondering what Rocaltrol is:

"Calcitriol is marketed as a pharmaceutical for medical use under various trade names including Rocaltrol (Roche), Calcijex (Abbott), Decostriol (Mibe, Jesalis), Vectical (Galderma), and Rolsical (Sun Pharma)."

en.wikipedia.org/wiki/Calci...

As I mentioned in my post, calcitriol's primary job is to release calcium from bone & then to replace the loss from calcium in the gut - i.e. from diet or supplements.

In the prostate, calcitriol, via the vitamin D receptor [VDR], acts with the androgen receptor [AR] to regulate growth.

-Patrick

NPfisherman profile image
NPfisherman in reply topjoshea13

Thanks

p3d1 profile image
p3d1

Hi Patrick,

Thank you for the information.

Could the following tablet meet the criteria of the trials as indicated by your post.

Not looking for a prescribed answer just a general opinion.

1. Name of the medicinal product

Calcichew-D3 Forte 500 mg/400 IU Chewable Tablets

2. Qualitative and quantitative composition

Per tablet:

Calcium carbonate

1250 mg

(equivalent to 500 mg of elemental calcium)

Cholecalciferol

400 IU

(equivalent to 10 micrograms vitamin D3)

Contains isomalt (E953) and sucrose.

pjoshea13 profile image
pjoshea13

Hi P3D1,

A lot of calcium & not much vitamin D. Perhaps a good product for someone who has no calcium in his diet - & doesn't have PCa!

500 mg calcium will stop the production of calcitriol until its effect on the blood has cleared.

Is Calcichew-D3 Forte a good product? Calcium should be balanced by magnesium. And any product that aims to build up bone must have vitamin K2 IMO. K2 is needed for transport to the bone.

-Patrick

p3d1 profile image
p3d1 in reply topjoshea13

Hi Patrick,

These tablets are what the MO has give me since Dx 14 months ago.

I supplement the D3 with an oral spray. (One shot is 3000 IU each morning)

I also take K2 (from Natto) to get the the D3 into the bone and away from the blood vessels

I will look into Magnesium, but may have sufficient from "Natures Plus source of life Gold" which I take. total D3 from al sources estimated at 5000IU per day.

Thank you for the advice.

ITCandy profile image
ITCandy

Fascinating work.

In your opinion, if one needed pain relief, would Aleve be a better choice than Advil when Pca is involved?

pjoshea13 profile image
pjoshea13 in reply toITCandy

Very few references to naproxen in the PCa literature.

"Any use of propionates (e.g., ibuprofen, naproxen) was associated with a modest reduction in prostate cancer risk" [1]

In the VITAL study:

"Low-dose aspirin, regular-strength aspirin, ibuprofen, and any nonaspirin NSAID (ibuprofen, naproxen, and COX-2 inhibitors) were not associated with prostate cancer risk." [2]

See the back story as to why naproxen was chosen: [3]

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/212...

[2] ncbi.nlm.nih.gov/pubmed/209...

[3] ncbi.nlm.nih.gov/pubmed/200...

jimbob99999 profile image
jimbob99999

Thanks Patrick. Am I correct in concluding that Vitamin D dietary supplements, even high unit levels of 1,000 to 5,000 IU, are not converted into calcitriol? So to get Calcitriol directly we will need a script for something like Rocaltrol?

pjoshea13 profile image
pjoshea13 in reply tojimbob99999

Yes, cholecalciferol supplements are converted to calcidiol (25-D) and only converted to calcitriol (1,25-D) as needed. I expect that most men think that a good level of calcidiol guarantees a good supply of calcitriol. It doesn't. One must coax the kidneys to make it by limiting calcium & phosphorus, & by using fructose.

"Calcitriol is prescribed for:

- Treatment of hypocalcaemia – hypoparathyroidism, osteomalacia ... renal osteodystrophy, chronic kidney disease

- Treatment of osteoporosis

- Prevention of corticosteroid-induced osteoporosis" [1]

None of the 18 clinical trials of calcitriol for PCa are active. I doubt that most oncologists would want to use it at this stage.

-Patrick

[1] en.wikipedia.org/wiki/Calci...

LeeLiam profile image
LeeLiam

Thanks Patrick. But I have an "out of the box" thought. What if we get more from sunlight than just one nutrient, Vitamin D. What if we get one or more additional nutrients that haven't been discovered yet. I ask because I have been using a tanning bed for over thirty years. I feel good when I use it consistently. If I get away from it for a while, I supplement with Vitamin D but it's not the same feeling. I'm convinced there is something else in the ultraviolet light.

pjoshea13 profile image
pjoshea13 in reply toLeeLiam

The missing steps, when we use a cholecalciferol supplement:

a) the skin contains 7-Dehydrocholesterol, which is a cholesterol precursor.

b) UV light bombards 7-Dehydrocholesterol to produce pre-vitamin D3.

c) pre-vitamin D3 spontaneously converts to cholecalciferol.

So if something else is going on, it might involve pre-vitamin D3.

Perhaps more likely is a therapeutic benefit of being exposed to UV light?

Sitting in the sun for 20 minutes, would be more enjoyable than anything I have planned today.

But here's a thought - I was forgetting the pineal gland:

philmaffetone.com/sun-and-b...

-Patrick

teamkv profile image
teamkv

And what about transdermal Vit D? Then it doesn’t have to go through the liver?

pjoshea13 profile image
pjoshea13 in reply toteamkv

Cholecalciferol is converted in the liver to calcidiol (25-D).

Transdermal D that does not enter the liver cannot produce 25-D.

However, transdermal D mimics natural production.

-Patrick

JimVanHorn profile image
JimVanHorn

Correct me if I am wrong but isn't Vit D3 stored in the kidneys and some in the liver? So if someone is on Lupron with kidney failure the storage could be wiped out. I have that problem and I am given 50,000 units of Vit D3 (on prescription) once a week for 13 weeks rebuild my storage of Vit D3.

pjoshea13 profile image
pjoshea13 in reply toJimVanHorn

Hi Jim,

There is a two-step conversion:

1] the liver converts cholecalciferol to calcidiol, & that circulates in the blood as an inactive reservoir.

2] the kidneys convert a little of the calcidiol to calcitriol as needed, & that circulates in the blood too - because the destination is bone & gut.

The liver & kidneys do not store vitamin D.

Incidentally, you can buy bioidentical vitamin D3 quite cheaply. I take 7,000 IU daily from LEF:

lifeextension.com/Vitamins-...

-Patrick

JimVanHorn profile image
JimVanHorn in reply topjoshea13

Thank you Patrick that explains a lot to me.

j-o-h-n profile image
j-o-h-n

As I've stated before and which nobody shives a git....I get my vitamin D from my two scoops of chocolate chip ice cream while sitting in the sun. Only problem I have is I have to eat it fast before it melts.

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 01/ 04/2019 5:04 PM EST

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