Folate & Vitamin B12; SAMe & Methyl. - Advanced Prostate...

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Folate & Vitamin B12; SAMe & Methyl.

pjoshea13 profile image
20 Replies

This is prompted by a post from BBruce:

"Stay away from Vitamin B12"

I reviewed the folate-PCa literature 2 years ago. B12 is covered in that post. What seemed lacking in the new thread was context, IMO.

A number of the B vitamins feed into 'one-carbon metabolism' (a term that is usually found in PCa papers that looked at the issue.) I prefer to narrow that down to the SAM cycle, which I simplify as:

... Methionine--->SAM (SAMe)--->Homocysteine--->Methionine ...

Cells have a need for methyl. SAM is the universal methyl donor in the body. SAM obtains its methyl from Methionine. When SAM drops off its methyl load, we are left with homocysteine.

Although there will be some methionine in the diet, there will generally be a need for other dietary methyl donors. Folate (vitamin B9) is the most important. Folic acid is a synthetic form.

With adequate folate and cofactors that include vitamins B6 & B12, homocysteine can be converted back to methionine.

When the supply of methyl is low, cells can become hypomethylated, leading to genetic instability & an increased risk of cancer.

When the supply of methyl is adequate, PCa cells take up way more than normal prostate cells. They become hypermethylated. Most damaging is the silencing of tumor suppressor genes. This occurs by methylation of suppressor gene promotor regions (see CpG island hypermethylation [1]). In normal cells, promoter regions of tumor suppressor genes are never methylated.

So we have a situation where hypomethylation increases cancer risk, but hypermethylation increases the risk of aggressive cancer.

We don't often get to see a poorly thought out experiment conducted on an entire population, but the fortification of flour with folic acid in Chile had terrible consequences for some.

Comparing the periods 1992-1996 with 2001-2004, colon cancer rates increased by a factor of 2.6 in those aged 45-64 years, and 2.9 in those aged 65-79. [2]

And, "a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada." [3]

The health damage done in a country that adopted folic acid fortification depends on the baseline degree of folate insufficiency. In the Chilean population, folate insufficiency was no doubt responsible for many colon cancer cases, but also prevented them from developing. With sufficiency, these cancers were suddenly unmasked.

...

The Chilean experience shows how hypomethylation might work as a strategy when cancer already exists.

For men in North America & in those countries that adopted the FDA mandate of grain fortification, it is difficult to be folate-insufficient. (European & Scandinavian countries have been more cautious.)

One could however target one of the cofactors. Vitamin B12 is easiest. Many aging men have poor uptake of B12. Their stomachs do not produce enough intrinsic factor.

Vegans will find it easy to be B12 deficient [5]. In fact, vegans are often found to be deficient in a number of nutrients. While many respond to a cancer diagnosis by eating a 'healthy' diet, selective insufficiency is a more promising strategy IMO.

To return to the recent thread: vitamin B12 will not cause PCa. It will not even cause aggressive PCa. But insufficiency might lower the risk of aggressive disease.

I forget how many pinheads a lifetime of vitamin B12 will fit on, but we don't need much in the diet. The body also recycles it. One could become vegan today & still not be deficient a year from now, depending on our stores. Deficiency "may not appear for decades." [4]

One must be careful when flirting with B12 deficiency. Some of the potential damage cannot be reversed. What do we fear more than PCa? Dementia, perhaps? B12 is protective. But if PCa mortality is the immediate concern, increased risk might be acceptable.

-Patrick

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

[2] ncbi.nlm.nih.gov/pubmed/191...

[3] ncbi.nlm.nih.gov/pubmed/280...

[4] en.wikipedia.org/wiki/Vitam...

[5] ncbi.nlm.nih.gov/pubmed/233...

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20 Replies
cesanon profile image
cesanon

Dr. Myers had me on B12: 1000 mcg 4 x week (to counteract depletion of B12 by metformin)

rnewman751 profile image
rnewman751

Hi Patrick, do you feel or know whether TMG, trimethylglycine may also cause hypermethylation. I am still psa undetectable and do supplement TMG. I do so for overall liver support. Hope your well.

Rob

pjoshea13 profile image
pjoshea13 in reply tornewman751

Hi Rob,

Yes, I stay away from beets, which have betaine - an important methyl donor for those who eat them. TMG was the first betaine discovered.

-Patrick

spinosa profile image
spinosa

This makes sense -as Sloan (as in Sloan-Kettering) was desperately seeking a "cure" for cancer, he tried numerous compounds, elements, etc. He reasoned that folate might be the answer... but, this caused cancer to grow - he then tried ANTI-folates...and, this set him on the path to a treatment for leukemia in children.

pjoshea13 profile image
pjoshea13 in reply tospinosa

Speaking of which (from Dec.) [1]:

"Herein we report a dramatic response to continuous-infusion 5-fluorouracil (5-FU) at a dose of 200 mg/m2 in a patient with rapidly progressive, heavily pretreated, metastatic castrate-resistant prostate cancer. Baseline prostate-specific antigen values declined from 1,890 ng/mL to <1 ng/mL after 5-FU therapy."

!!!

"We hypothesized that prostate-specific membrane antigen overexpression may result in cancer cells uniquely susceptible to antifolate therapies."

But no antifolate is mentioned. Just the fluorouracil, which is used with antifolates.

In any case, add this to the "when all else has failed" list.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/292...

snoraste profile image
snoraste in reply topjoshea13

I’d be curious what antifolate they used and at what dosage.

With Metformin’s effect in B12, would that be considered an antifolate as well?

pjoshea13 profile image
pjoshea13 in reply tosnoraste

From 2012:

"Our current findings suggest for the first time that metformin can function as an antifolate chemotherapeutic agent that induces the ATM/AMPK tumor suppressor axis secondarily following the alteration of the carbon flow through the folate-related one-carbon metabolic pathways."

ncbi.nlm.nih.gov/pmc/articl...

-Patrick

snoraste profile image
snoraste in reply topjoshea13

Thanks Patrick. The article is a little too technical for me, but I did get the gist of it. Is there an introductory online/book that comes to your mind to get me up to speed on cell biology?

pjoshea13 profile image
pjoshea13 in reply tosnoraste

My basic PCa education, such as it is, has come mostly from countless study Abstracts. They are usually well-written. Seems to me that the authors want to be understood.

& thankfully, Wikipedia is usually able to add clarification to new terms & concepts.

-Patrick

Dan59 profile image
Dan59 in reply topjoshea13

Thank You for this one, will add 5FU to file “when all else fails “along with cytozan. 5fu flouracil was a part of the Servadio Protocol used in Isreal in the 80s that had such a great OS that Strum often talked about.

in reply toDan59

Dan, if you do ever use 5FU, make sure you don't have a dpd enzyme deficiency. If you do, this chemo will definitely FU over.

Dan59 profile image
Dan59 in reply to

I see that Gregg, though it is fairly rare, good to check. 5 fu is still used , I have seen it given to people in the chemo room several times, It is a portable take home unit they wear. Here is a link on dpd deficiency and 5fu. cancerresearchuk.org/about-...

in reply toDan59

I'm trying to find some trials to show the efficacy of 5FU for prostate cancer, but haven't seen anything.

Dan59 profile image
Dan59 in reply to

This is a paper from 1980 descibing the servadio protocol. sciencedirect.com/science/a... of those in the study all presented with d2 or widespread metastatic disease, and 40% were alive at 15 year followup. goldjournal.net/article/009...

in reply toDan59

Thanks, I'll check it out.

snoraste profile image
snoraste in reply toDan59

Dan,

I read it as these guys were way ahead of CHAARTED and STAMPEDE trials with their aggressive combination therapies. I cannot see how the role of 5FU can be determined here.

Dan59 profile image
Dan59 in reply tosnoraste

I agree, and after looking at some old studies an papers patient Bill Aishman (2001) had posted years ago 5fu itself had less than a 20% response in CRPCA, I would be more interested in cytozan on the “ when all else fails”list there are some studies with Glode et al. showing benefit in salvage3 therapy after chemo.

People like me who take acid reducers for reflux / hiatal hernia are at risk for B12 deficiency. B12 is liberated from meat when stomach acid is sufficient. That also explains why vegans are at risk. Yes I've heard that B12 deficiency can cause irreversible brain impairment. I'll keep taking my B12 supplements and take my chances with the PC that I am already dealing with.

Dan59 profile image
Dan59

Patrick, Thank You for clearing up this issue on b12

Bluebird11 profile image
Bluebird11

It’s such a mine field. My husband’s B12 keeps dropping. I never realized a connection to brain function. We are concerned about PCa aggressiveness. And yet he’s pretty low 159. We are trying to get a number of things in balance right now and really don’t want to add to aggressiveness. Is there a way to figure out any different forms or reasons for PCa that would allow us to bring his B12 up.

His blood work RBC and HCT continue to drop.

Also you say you don’t eat beets. Would there be a good source you would use if you were dealing with these low numbers?

It’s just such a depressing situation when it gets this complex. We do need to address this. It’s been going on for a while now.

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