Vitamin D & PCa in Kuopio, Finland

[pjoshea13]

New study below [1].

Preamble.

An interesting phenomenon of some Nordic vitamin D PCa studies is the U-shaped risk curve. Both, low & high levels of vitamin D are associated with increased PCa incidence.

One has to admire the audacity of the Nordic researcher who believes that the local population is ideal for vitamin D studies.

Who are the Nordic men with high levels of vitamin D?

At Nordic latitudes almost everyone has some degree of deficiency by the time that winter is over. Unless they supplement.

I used to know a man in Toronto who supplemented with 5,000 IUs & couldn't get out of the 'insufficiency' range during winter. Back then, most brands did not have high doses. Dr Myers reported that the only patients who were able to increase vitamin D levels, were those using the Life Extension high-dose product.

I always thought that Myers was slow to endorse supplements, but vitamin D was an early enthusiasm. And even 15+ years ago, vitamin D was a popular supplement among men with PCa.

So, who are the Nordic men with high D levels in the winter? I contend that they include some men with familal PCa. And also men with higher PSA levels. Generally, men who are concerned that they have a higher risk for PCa.

What we have is detetion bias, imo. Future PCa studies should exclude those who are supplementing because of a perceived PCa risk.

An important Swedish study that reported a U-shaped risk for PCa incidence, later reported lower PCa mortality at higher D levels.

An esteemed member of this group once said that if something does not help prevent PCa, it can't help you to survive it.

The Kuopio study.

Where the heck is Kuopio?

... Toronto is at latitude 43.6532°.

,,, Edinburgh is at latitude 55.9533°.

... Kuopio is at latitude 62.8980°.

"2578 middle-aged men belonging to the Kuopio Ischaemic Heart Disease Risk Factor Study" " were free of cancer at baseline, and the mean ... follow-up time was 23.3 ... years. During this period, 296 men had a PCA diagnosis, and 1448 men died without the PCA diagnosis. The absolute risk of developing PCA was highest in the highest 25(OH)D tertile (15%), whereas that of death was highest in the lowest 25(OH)D tertile (67%).

Here were the winter vitamin D levels in the Kuopio men (ng/mL):

... 1st tertile: 3.21 to 12.02 (average 9.62)

... 2nd tertile: to 17.23 (average 14,02)

... 3rd tertile: to 54.49 (average 30.45)

This looks pretty grim to those of us used to:

... deficiency: <20

... insufficiency: 20 to <32

... sufficiency: 32 & up

Anyway, for those of us with active PCa, I have yet to see a vitamin D survival curve that dips or even plateaus. There are usually not enough men at the higher levels to verify that & certainly not at latitude 63° N.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/352...

{Full: onlinelibrary.wiley.com/doi...

Andrologia

. 2022 Feb 28;e14410. doi: 10.1111/and.14410. Online ahead of print.

How competing risks affect the epidemiological relationship between vitamin D and prostate cancer incidence? A population-based study

Ari Voutilainen 1 , Jyrki K Virtanen 1 , Sari Hantunen 1 , Tarja Nurmi 1 , Petra Kokko 1 , Tomi-Pekka Tuomainen 1

Affiliations collapse

Affiliation

1 Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

PMID: 35229338 DOI: 10.1111/and.14410

Abstract

We hypothesized that controversial results regarding the epidemiological relationship between circulating 25-hydroxyvitamin D, 25(OH)D, and risk of prostate cancer (PCA) incidence are partly due to competing risks. To test the hypothesis, we studied associations across 25(OH)D, PCA and death in 2578 middle-aged men belonging to the Kuopio Ischaemic Heart Disease Risk Factor Study. The men were free of cancer at baseline, and the mean (SD) follow-up time was 23.3 (9.1) years. During this period, 296 men had a PCA diagnosis, and 1448 men died without the PCA diagnosis. The absolute risk of developing PCA was highest in the highest 25(OH)D tertile (15%), whereas that of death was highest in the lowest 25(OH)D tertile (67%). A competing risk analysis showed that belonging to the highest 25(OH)D tertile increased the risk of PCA incidence and improved survival with the respective hazard ratios (HR) of 1.35 (95% CI = 1.07-1.70) and 0.79 (95% CI = 0.71-0.89). Adjusting for 10 covariates together with 25(OH)D did not significantly change the results, but the respective adjusted HRs for PCA and death were 1.20 and 0.87. To conclude, the competing risk analysis did not eliminate the direct relationship between 25(OH)D and PCA but rather strengthened it.

Keywords: cohort study; competing risk; incidence; prostate cancer; vitamin D.

© 2022 The Authors. Andrologia published by Wiley-VCH GmbH.

[Scout4answers]

Confused, What does it all mean?

[pjoshea13 in reply to Scout4answers]

The powerful message is that there is better survival with higher D.

Some will ask: but doesn't this show that vitamin D does not prevent PCa onset in high-risk men? You would need to do an intervention study on men from PCa families to prove that.

I can't imagine that a megadose of vitamin D is going to reliably inhibit PCa in BRCA2 men. How many high-dosing BRCA2 men would it take to create the U-shaped curve? Perhaps not a lot.

-Patrick

[Ralph1966]

The absolute risk of developing PCA was highest in the highest 25(OH)D tertile (15%), whereas that of death was highest in the lowest 25(OH)D tertile (67%).? So having high Vitamin D is associated with increased risk of PCa?

[pjoshea13 in reply to Ralph1966]

Ralph,

Notice that in the highest third, the average D was 30.45 ng/mL But there was a guy at 54.49 ng/mL. How much D was he taking? 10,000 IUs daily? What was he so worried about to get so high in that population? If PCa, he should have been excluded. If familial PCa, say, & he subsequently had a PCa diagnosis, he skewed the incidence statistic.

But, paradoxically, that higher D was associated with better survival.

You say: "So having high Vitamin D is associated with increased risk of PCa?"

I say that the association is due to bad design. The researchers were expected the D numbers to be random. i.e. that men were supplementing for reasons unrelated to the thing being studied.

-Patrick

[Ralph1966 in reply to pjoshea13]

Thank you Patrick for posting this.

For all or most of us here, we already got this PCa, so we will aim to keep our vitamin D3 level at least above 50 ng/mL. I am taking 10,000 IU one day and 5,000 IU the next day alternately. My last vitamin D blood level test was 69 ng/mL. When I was diagnosed in 2017 it was 29 ng/mL.

[Captain_Dave]

My Vitamin D was low when I was diagnosed. I keep it high now as my PSA slowly creeps up. Doc told me he wants it high.

[LearnAll]

Most men have low Vit D level at the time of diagnosis as two members above noticed. I had Vit D level of 22 at diagnosis and by using SunLight and Vit D3+K2 (4000 IU) a day, the level has increased to 65. The ideal range seems to be between 50 and 70.

[Hidden]

If you know what your serum level is and you know how much supplementation you use, this calculator will estimate what you need to reach a target level. grassrootshealth.net/projec...

Some curves:

3. UPDATE: How Much Vitamin D Should You Take? | HuffPost Life huffpost.com/entry/update-h...

4. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium journals.plos.org/plosone/a...

10. 25-hydroxyl Vitamin D Levels and the Risk of Mortality in the General Population ncbi.nlm.nih.gov/pmc/articl...

11. Meta-analysis of All-Cause Mortality According to Serum 25-Hydroxyvitamin D ncbi.nlm.nih.gov/pmc/articl...

A year or so ago I dug into it a bit and calculated an optimal range (I don't recall the exact number but I think it was based on over a dozen medical recommendations, observational studies, and RCTs). My best guess at a target range is 30-52 ng/ml. My MO thinks that 30-40 is the best range and thinks that supplementation might be needed to get to that range. My NMD thinks 40-75 is the best range but the higher numbers are not borne out by most of the data I have seen. And studies indicate that the lower limit should be moved down and could be set even a little lower than 30.

Other references:

5. Effects of Vitamin D and Omega-3 Fatty Acids Co-Supplementation on Inflammatory Factors and Tumor Marker CEA in Colorectal Cancer Patients Undergoing Chemotherapy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial – PubMed pubmed.ncbi.nlm.nih.gov/324...

13. Vitamin D May Reduce Prostate Cancer Metastasis by Several Mechanisms Including Blocking Stat3 ncbi.nlm.nih.gov/pmc/articl...

15. Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients – PubMed pubmed.ncbi.nlm.nih.gov/307...

17. Apoptosis Induction by 1α,25-Dihydroxyvitamin D3 in Prostate Cancer 1 Supported by the International Union Against Cancer [International Cancer Technology Transfer (ICRETT) and American Cancer Society Beginning Investigator (ACSBI) awards], Molecular Cancer Therapeutics mct.aacrjournals.org/conten...

[Cooolone]

Much Ado about this Vit D...

I was low when originally diagnosed, and even thereafter with supplementing, was and is still hard to elevate my D levels... So I take it, but not to go above recommended levels, I would be happy to achieve the upper range 45-50. Don't know why that is, but we are who we are.

Maybe a better study, would be looking at those mechanism(s) of action and inter-relation between low D or high D and PCa. Results are great to see, but absent identifying what is actually taking place, what do we really understand?

Funny thing is I every time I read about Vit D, I remember reading that it was or is used as a Rat poison because in mega doses, it causes calcification of organs, or something like that... Lol. But I still take it (& Vit K2) lolz

[homer13]

Nal, I would like to hear what you learn

[Jalbom49]

Interesting post. Vitamin D levels are open to debate. But adding Calcium has had problems. An excellent discussion of this is the book VitaminK2 and the Calcium Paradox.Chris Masterjohn phd has an excellent article on how Vitamin K2 was discovered to be Weston A Price’s Activator X. Dr Price discovered that Actvator X, and Vitamins A and D all worked synergisticly.

On a personal note, nine years ago I started on D supplement with 5000u daily.

Before that I has 3-4=upper respiratory infections per year, which is typical.

Since then I had a mild flu and two sore throats in nine years.

[lewicki]

Perhaps the suggested range of vit D is two low. Think about how much Vit D a roofer on the roof all day without a shirt on as to how much does he get. His amount would be off the suggested chart. Just thinking.

[pjoshea13 in reply to lewicki]

Something I recall from long long ago is that a young white guy at the Jersey shore in summer will get 20,000 IUs in 30 minutes.

That jibes with something I just found:

"... 30 minutes of midday summer sun exposure in Oslo, Norway was equivalent to consuming 10,000–20,000 IU of vitamin D" (Yes, but a month later in Oslo it will be winter. LOL)

ar.iiarjournals.org/content...

However, this does not continue all day.

Vitamin D3 is a hormone. As with steroidogenesis, the starting point is cholesterol, or rather, a precursor of cholesterol: 7-Dehydrocholesterol, in the skin. When this form of cholesterol is bombarded by UV light, we get previtamin D3. The extent of production is limited by the availability of 7-Dehydrocholesterol in the skin. I have no idea how that is controled.

More mysterious to me is how the 25-D3 reservoir is able to affect the process - at 20,000+ IU each day, the reservoir will soon fill, but I never heard of a case of hypervitaminosis D3 in a roofer.

-Patrick

[j-o-h-n]

D for 2 and 2 for D.... and etc.

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 04/05/2022 10:50 PM DST