Methionine restriction

[pjoshea13]

New (anecdotal) paper below [1].

Chronic Treatment of an Advanced Prostate-cancer Patient With Oral Methioninase Resulted in Long-term Stabilization of Rapidly Rising PSA Levels

I wrote about methionine restriction 2 years ago. [2]

"Our laboratory discovered methionine addiction, presumably a characteristic of all cancer types, including prostate cancer, which can be targeted by methionine restriction (MR), through treatment with oral recombinant methioninase (o-rMETase)."

"Before treatment, the patient had a rapid rise in PSA levels, from 39 to 56 ng/ml, within 6 weeks. At the 15th week of o-rMETase administration, the PSA levels stabilized at 62 ng/ml. No overt side effects were observed."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/341...

In Vivo

. Jul-Aug 2021;35(4):2171-2176. doi: 10.21873/invivo.12488.

Chronic Treatment of an Advanced Prostate-cancer Patient With Oral Methioninase Resulted in Long-term Stabilization of Rapidly Rising PSA Levels

Qinghong Han 1 , Robert M Hoffman 2

Affiliations collapse

Affiliations

1 AntiCancer, Inc, San Diego, CA, U.S.A.

2 AntiCancer, Inc, San Diego, CA, U.S.A. [e-mail].

PMID: 34182494 DOI: 10.21873/invivo.12488

Abstract

Background/aim: Advanced prostate cancer is a recalcitrant disease with very limited treatment options. Our laboratory discovered methionine addiction, presumably a characteristic of all cancer types, including prostate cancer, which can be targeted by methionine restriction (MR), through treatment with oral recombinant methioninase (o-rMETase).

Patients and methods: o-rMETase was produced by fermentation of recombinant E. coli containing the Pseudomonas putida methioninase gene, and purified by column chromatography. An advanced prostate cancer patient received o-rMETase as a supplement, 500 units per day, divided into two oral doses of 250 units each.

Results: Before treatment, the patient had a rapid rise in PSA levels, from 39 to 56 ng/ml, within 6 weeks. At the 15th week of o-rMETase administration, the PSA levels stabilized at 62 ng/ml. No overt side effects were observed.

Conclusion: o-rMETase single treatment can be beneficial for advanced prostate cancer patients.

Keywords: Methioninase; PSA; advanced prostate-cancer patient; methionine addiction; oral.

Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[2] healthunlocked.com/advanced....

[noahware]

"presumably a characteristic of all cancer types, including prostate cancer"

Of all types, but perhaps not of all individual cancers? I of course have not tried o-rMETase, but did try an extremely low-met diet for nearly a month (mostly fruit and low-met veg, with a small amount of grains -- otherwise vegan with NO beans, seeds or nuts). That month unfortunately saw one of my largest PSA spikes ever!

Even so, I have not dismissed its potential. But I wonder, how low do you have to go, and for how long? You don't want zero met for too long. One proposal is that you could cycle your diet (sort of like the dietary version of BAT).

Daniel Epner filed for a patent some years ago to use cyclic met-restriction as a therapy, but apparently he abandoned the project. The closest thing to it I have seen actively promoted (by Mark Simon) is the NORI protocol.

Regarding the study above: if PC is truly "addicted" to methionine, why did the patient's PSA merely stabilize rather than drop?

[pjoshea13 in reply to noahware]

SAM is the universal methyl donor in the body & methionine is the source. However, we appear not to get enough fully formed methionine from dietary sources - hence the SAM cycle, which typically obtains methyl from folate and recycles homocysteine back to methionine. The SAM cycle:

Methionine >>> SAM >>> Homocysteine >>> Methionine

requires a methyl donor (usually folate/ folic acid) and cofactors - notably B12.

In 1996 the FDA mandated the fortification of grains with folic acid, so most Americans are unlikely to be deficient in methyl. But B12 restriction, which is not uncommon with age, will upset the SAM cycle.

B12 deficiency is dangerous & may take a long time to achieve, but those who do not secrete the intrinsic factor (in the stomach) have an advantage - as do vegans.

In countries that did not follow the U.S. lead, methyl restriction is easier, and safter than playing around with B12.

-Patrick

[noahware in reply to pjoshea13]

Yes, and thanks to you posting that info prior, I did have some clue about the SAM cycle. So I did try to restrict my intake of folate-rich foods, as well, limiting grains to low amounts of unfortified types (a bit of bulger wheat) and low-folate veg. So low met, low folate, and no B12 in the diet... but of course the months prior to that I had a diet extremely high in all those! Perhaps a longer and more severe B12 deficiency is needed?

Interestingly, a lot of the veggies (and beans) that are higher in folate are also higher in methionine, I discovered. I ate a lot of apples, tomatoes, onions, carrots and cabbage. No avocado, no dark leafy greens, etc. Maybe too much dark chocolate, lol?

[Spyder54]

One more piece of the puzzle. Man it is a complex puzzle, but we are finding many good pieces on this site. We need to find that exact combo and timing that put most of us into the 20+ year Club !Thanks Patrick,

Mike

[Ramp7]

ar.iiarjournals.org/content...

[Currumpaw]

Hey pjoshea13!

Stabilization! Dr. Laurence Klotz's patient who dosed himself with hot sauce 3X a day had very similar results. The patient who had castration resistant prostate cancer stabilized his PSA until he "went off the sauce"! Dr. Klotz graphed the patient's PSA. When the patient stopped dosing himself with hot sauce his PSA resumed it's same trajectory on the graph it had been on.

I believe you posted the study that Dr. Klotz was involved in which was funded by a US agency showing that capsaicin killed prostate cancer stem cells. From memory -- those in the study were given 40,000 heat unit, capsaicin capsules 2X a day. One can increase that amount.

You have acquired much knowledge. Perhaps it is time for a book?

Thanks for the post and your time.

Currumpaw

[TheTopBanana]

Is this possible to achieve through supplements? Or mostly diet?

[pjoshea13 in reply to TheTopBanana]

Some might be abe to do it with diet by restricting methyl donors - e.g. folate sources (leafy vegetables), betain sources (beets, etc.) Or by restricting vitamin B12, an essential co-factor - e.g. meats.

Regarding supplements: (i) avoid folic acid (synthetic folate source) &/or (ii) super-high levels of genistein, which is a demethylation agent.

Here in America, grains are fortified with folic acid, so all baked goods would be out. You don't have that constraint in Sweden.

Otherwise, a drug.

Best, -Patrick