Folate consumption & ADT mortality.

[pjoshea13]

A curious new study [1].

"We identified 56 men with prostate cancer {the South Texas Veterans Healthcare System} undergoing androgen deprivation in which folate levels had been determined. 15 out of 16 (94%) men initiating ADT had increases in their folate, which is substantially more than 67% in {the ADT} maintenance group"

"We identified more rapid time to death from prostate cancer if folate levels increased to levels >200 ng/ml above their baseline ..."

Folate is a vitamin [B9] & can only come from the diet, or via synthetic folic acid.

In the U.S. folic acid is added to grains (including rice), as mandated by the FDA, so a high-carb diet might account for a high intake.

I have written about folate as a methyl donor & its role in the hypermethylation (silencing) of tumor suppressor genes in PCa cells,

There are mice studies going back 50 years that show that castration affects folate co-enzymes, resulting in a reduction of folate clearance [2].

56 men seems like a small study. However, we have control over dietary folate/folic acid. Why wait for the definitive study?

Would be interesting to see this study replicated in a country that has resisted folic acid fortification of food.

-Patrick

[1] sciencedirect.com/science/a...

Rise in serum folate after androgen deprivation associated with worse prostate cancer-specific survival

Author links open overlay panelMichael A.LissM.D.KeithAshcraftPh.D.ArpanSatsangiM.D., Ph.D.DeanBacichPh.D.

Show more

doi.org/10.1016/j.urolonc.2... rights and content

Highlights

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Folate may rise after suppression of testosterone.

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Folate rises in mice after castration.

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Folate rise of >200 ng/ml from baseline is associated with prostate cancer death.

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Folate rise after initiating androgen deprivation.

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This study is not causal but does provide plausibility and proof of concept.

Abstract

Introduction

High folate has an association with advanced prostate cancer and levels of testosterone. Herein, we perform a translational study to investigate the inverse response of serum folate in prostate cancer patients initiating androgen deprivation therapy (ADT) and a mirrored animal model.

Methods

A retrospective study was performed using the South Texas Veterans Healthcare System to identify patients with prostate cancer on ADT. We documented testosterone and folate levels before and after ADT initiation (defined by a reduction in testosterone by 50 ng/ml) as compared to those already on ADT (maintenance). Our primary outcome was overall mortality with secondary outcome of prostate cancer-specific mortality. In parallel, we tested castration of C57BL/6J mice on folate-defined diet to determine if folate levels change with response to androgen deprivation. Students’ t test on continuous variables and Chi-squared test on dichotomous variables was performed along with Kaplan-Meier for time to event analysis.

Results

We identified 56 men with prostate cancer undergoing androgen deprivation in which folate levels had been determined. 15 out of 16 (94%) men initiating ADT had increases in their folate, which is substantially more than 67% in maintenance group (P = 0.04). We identified more rapid time to death from prostate cancer if folate levels increased to levels >200 ng/ml above their baseline (P = 0.03). Mice models demonstrated a significant rise in serum red blood cell folate after mice were castrated (P = 0.03) by an average of 1.5x over pre-castrated baseline level. By contrast, sham-castrated mice showed no increase in serum folate levels over baseline.

Conclusion

Our study suggests that men with substantial rises in folate after initiating ADT may be associated with worse prostate cancer-specific and overall survival. Our translational experiments in mice confirmed correlation between rising in folate levels post-castration. Given this study, further investigation is warranted on the role of dietary folate consumption during initiation of ADT and progression to castrate-resistant prostate cancer.

Keywords

Castrate resistant prostate cancerAndrogen deprivation therapyFolate

***

[2] ncbi.nlm.nih.gov/pmc/articl...

[rnewman751]

Hello Patrick, thank you for the folate article. Have you seen anything in the literature about B12. I believe methylation nutrients may not be beneficial for those with prostate cancer. Thank you and best wishes. Rob

[pjoshea13 in reply to rnewman751]

healthunlocked.com/advanced....

-Patrick

[henukit]

Thanks for posting. Due to my AS I've been on strict no-starch diet for many years before cancer diagnosis, Hopefully this will contribute to a better PCa outcome.

[cigafred]

The increase number "200 ng/ml" seems a typo (in the original article--I checked). Seems high since the reference range on my last test was ">5.8 ng/ml" and my reading was "21.8 ng/ml" and I was fully on ADT at the time.

[pjoshea13 in reply to cigafred]

"If the test is done on your blood plasma, a normal range for folate is 2 to 10 ng/mL. If the test is done on red blood cells, a normal range is 140 to 960 ng/mL."

urmc.rochester.edu/encyclop...

-Patrick

[cigafred in reply to pjoshea13]

Once again proving I am way out of my league here. Yes, my test was "serum." Thanks Patrick

[pjoshea13 in reply to cigafred]

Your post turned out to be very helpful. Don't hesitate. -Patrick

[Hidden]

So what's a guy supposed to eat? Potatoes and rice are both trouble now!

But wait....

endocrineweb.com/news/diabe...

[timotur]

Thanks for posting and bringing awareness to foliate in our diet.

[Graham49]

Unfortunately some foods considered to have anti cancer properties such as leafy vegetables including cruciferous vegetables are high in folate. However cooking, tea and coffee are known to reduce folate levels so apart from avoiding cereals where folic acid is supplemented I don't think I need to take any special measures.

Any comments Patrick?

[pjoshea13 in reply to Graham49]

Graham,

Eat sparingly of chicken liver & peanuts - see:

en.wikipedia.org/wiki/Folate

-Patrick

[Graham49 in reply to pjoshea13]

Thanks Patrick

[Seebs9]

Thanks pjoshea3, I will stop my 5000mcg 'high potency optimized' folate. Another example of how this group can help people. Right when I thought I knew everything...

[j-o-h-n]

Folate, Toolate.....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 05/28/2020 5:40 PM DST

[GeorgeGlass]

Hi Patrick, I'm having trouble absorbing B12. Doctors recommend supplementing 400mcg of 5 Methyl Folate, which is supposed to be a "better" form of folate. What do you think about men with APCx taking 400mcg daily and if that is a bad idea for those with APCancer?

FYI - my most recent folic acid test result was 15, which I think is pretty decent.

[pjoshea13 in reply to GeorgeGlass]

Hi George,

A folate/folic acid of 15 ng/mL looks good to me. So why does your doc want you to supplement?

You say that you are "having trouble absorbing B12". How do you know - was B12 tested too? Or is your homocysteine elevated?

If your B12 is very low, i.e. close to deficiency, you could inject into belly fat - but I would not inject much & would do so infrequently.

With normal levels of folate but insufficient B12, homocysteine cannot be recycled back to methionine & on to SAM. If you correct that, PCa cells will have greater access to the methyl in folate (not a good thing.) It's tricky to figure out what to do. Need more info.

-Patrick

[GeorgeGlass in reply to pjoshea13]

Hey Patrick, sorry that I didn't include my B12 level. My B12 test showed a level >2000 pg/ml which is way above the normal levels but I dont take any B12 supplements so I dont know why it would be that high. The doc theorized that the b12 might be going into my body but not getting absorbed, so the levels are high but my energy is low. Thus, he thought methyl folate might help get the B12 into my system. Maybe the B12 absorption was affected by the Levaquin I took in March which has effected my ATP and mitochondria since then. I dont know. I don't even know for sure if the B12 is not getting absorbed or if eating salad, broccoli, almonds and peanuts a lot led to high levels of B12. Maybe I should test the B12 again. those tests were on 30 April.

Additionally, after reading this article - medicalxpress.com/news/2018... I'm not sure that I want the B12 to be absorbed into my cells more efficiently. I can't figure out whether it's worse to have the B12 sitting in the blood stream or going into the cells (which could feed the cancer cells?) I posted this question earlier today. I'm not sure if you saw it or not.

Lastly, I went back to Valencia peanut butter earlier this year and couldn't remember why I had switched from PB to almond butter but a comment by you reminded me why I had switched, which was due to the folate levels in peanut butter. They are five times higher than almond butter, so I'm going to switch back to almond butter.

Thanks for your thoughts,

George

[pjoshea13 in reply to GeorgeGlass]

Hi George,

I seem to remember your B12 issue. I'm not so good at retaining individual details.

Here is my take. You are not supplementing or loading up on B12 via diet, so I can only conclude that your body is releasing B12 supplies into the blood.

Have you ruled out liver issues?

I think a second opinion from a hematologist might be called for.

Best, -Patrick

[GeorgeGlass]

Thanks Patrick. I think I'm going to get the B12 retested first. My liver tests looked good previously. If the new B12 test is lousy also then I'll go see a hematologist. Thanks for your insights!

Have a good Saturday.

George