Vitamin D metabolism in cancer: potential feasibility of vitamin D metabolism blocking therapy

[pjoshea13]

New paper below [1].

Vitamin D circulates in the blood as inactive 25-D.  The kidneys will convert 25-D to the active hormone 1,25-D, as needed, to maintain circulating calcium levels.

Elsewhere, cells that need 1,25-D first produce the enzyme that performs the conversion of 25-D.

It is normal for hormones created in a cell to be given a short window in which to operate.  As soon as 1,25-D is created, the enzyme CYP24A1 will be produced to destroy it [2].

The situation is altered in PCa.  The enzyme to create 1,25-D is downregulated and the enzyme to destroy it is upregulated.  Cells produce less 1,25-D and clear it faster.

The Japanese authors:

"... propose the potential feasibility of vitamin D metabolism-blocking therapy in various types of human malignancies that express constitutive CYP24A1."

***

I have the impression that many men with PCa are aware of the importance of 25-D, but ignore 1,25-D.  We can do little to make PCa cells produce more 1,25-D, or to keep it around longer.  But we can do something to improve access to 1,25-D in the blood.

Briefly, high intake of calcium will reduce access; fructose will increase access.  In my case, I do not use calcium supplements & I sweeten my coffee with fructose.

-Patrick

[1]  pubmed.ncbi.nlm.nih.gov/367...

[2]  en.wikipedia.org/wiki/CYP24A1

[No_stone_unturned]

Sorry for being so dumb, but can you translate this into what the practical application would be for us?

[cesces in reply to No_stone_unturned]

Take lots of vitamin D.Error on the side of too much as opposed to two little.

[No_stone_unturned in reply to cesces]

that’s interesting, because when I was taking 4000mcg a day my OC said that was overkill even for someone with a Vit D deficiency. Also made it sound like I could be doing more harm than good. Just posting what I was told.

[cesces in reply to No_stone_unturned]

Both propositions can be right.

Depends on whether Patrick's conjecture is right.

If it is, then the vitamin D is like any medication. When used at the necessary dosages, it can generate adverse side effects elsewhere.

Though vitamin D, is still relatively tame, even at high levels. There are way more nastier medications and treatments out there.

[MrG68 in reply to No_stone_unturned]

Most people are deficient. It's not a good idea to look at oral intake quantities. You need to look at the blood concentration. I believe that here is a lot of scaremongering with D3. The issue is with calcium intake resulting from the D3. To much calcium could cause issues. I have taken 10KIUs (and LOTS more on occasions) and never had any issues. IMO, If you aim for around 50ng/ml you should be roughly where you need to be. I've also had a lot of conversations with practitioners about this since they regard my level as high. But usually it ends the same way, they just read the 'recommended' number from a chart and get alarmed if your figure is higher. Most (not all) don't know why they want you to have any specific level - it's just what the chart says.

That being said, you should still consult with your medical team on any levels or issues.

[No_stone_unturned in reply to No_stone_unturned]

this is what I’m taking

Life extension

[cesces]

Peter

Are you aware of any supplement that might theoretically help vitamin D get through and do it's job?

[MrG68 in reply to cesces]

From what I've read, D3 is a fat soluble vitamin. So it's probably a good idea to take it with meals or some fat. K2 is a vitamin that you should also consider taking with D3. There may be some fat included with the supplement you take.

It depends on the individual, but I take 10K IUs a day and have never had any issues. I don't take it with calcium because it increases calcium absorption and I don't want that.

You need to get your blood work done though because the blood concentration is the thing to measure. The response curve isn't linear for how much you intake wrt your blood. If you are deficient you need to take a lot initially to overcome the bottom (flat) part of the curve.

Also, from what I've researched, taking it at a higher frequency is more beneficial. For example: taking it twice a day, is better than the weekly/monthly loaded equivalent dose.

This is because it doesn't last long in your system and you need to replenish it.

[cesces in reply to MrG68]

"K2 is a vitamin that you should also consider taking with D3."

Why?

[MrG68 in reply to cesces]

Oh, I forgot to mention, you should also take have some form of magnesium along with D3. If I remember right this is due to magnesium being required to effectively convert it to calcitriol - where a deficiency will hinder that somewhat. I actually take magnesium bicarbonate as a drink.

As for K2, you should take that because D3 will increase your calcium a LOT. D3 is required to enable your body to direct the calcium to the right places.

For what it's worth, I prefer to use food than supplements where possible. There is a tendency for people to take to tempted to take too many supplements because of the mindset that more is better. This could cause an imbalance and lead to a deficiency of something else.

So for example, in the summer I suggest that you don't take D3 and get it from sunshine. K2 is available in grass-fed (eg butter) and fermented products (eg sauerkraut).

[GreenStreet in reply to MrG68]

Interesting. I take K2 but I don’t take it with D3. I take D3 morning and evening and I take K2 separately at lunch time. I can’t remember why but I read somewhere that taking the two at the same time may not be a good idea?

[MrG68 in reply to GreenStreet]

Hhhmmm, I’ve never came across anything to suggest that. This is why you will see a lot of D3 supplements with K2 added.

[Medline]

Dietary influences of 1,25(OH)2 vitamin D in relation to prostate cancer: a hypothesis

Diets high in dairy products and meats are related to higher risk of prostate cancer incidence or mortality in most ecologic, case-control, and prospective studies. Recent laboratory and epidemiologic evidence indicates that a high circulating level of 1,25(OH)2 vitamin D [1,25(OH)2D], the biologically active form of vitamin D, inhibits prostate carcinogenesis. This paper will examine the hypothesis that these observations may be linked, specifically that high dairy and meat consumption increase risk of prostate cancer by lowering 1,25(OH)2D. High intakes of calcium and phosphorus, largely from dairy products, lower circulating 1,25(OH)2D level, and sulfur-containing amino acids from animal protein lower blood pH, which also suppresses 1,25(OH)2D production. Additionally, high fructose consumption produces a transitory hypophosphatemia, and may adversely affect calcium and phosphate balance, all of which may stimulate 1,25(OH)2D production. The evidence that 1,25(OH)2D inhibits prostate carcinogenesis, and that diets that are high in calcium, phosphorus, and sulfur-containing amino acids from animal protein, as well as low in fructose, tend to decrease circulating 1,25(OH)2D will be presented. The studies examining these dietary factors in relation to prostate cancer risk will be reviewed.

pubmed.ncbi.nlm.nih.gov/101...

[pjoshea13 in reply to Medline]

Giovannucci wrote that 25 years ago.  Made sense to me 18 years ago & still does.

-Patrick

[GreenStreet]

Patrick thanks. I take D3 and also K2 separately. But looks like some fructose is in order!

[KocoPr]

Patrick, great sibject but im really wanting to read this 2023 article. Any way to get around that paywall?