Foods/Supplements-Vitamins: Amino Acids - Selective Restriction.

[pjoshea13]

There are 20+ amino acids needed for building protein. All it takes is for one to be in short supply to cause a reduction in the growth factor IGF-I. Omnivores might be able to reduce their intake of whole protein, I suppose, but vegans would find it easier to selectively restrict a single amino acid. IGF-I is an important PCa growth factor.

[1] Gary Meadows, at Washington State U, has spent a number of years looking at the feasibility of selective restriction. I will limit quotes from his papers, since his account of the effects on cells gets very technical.

[1a] (2001) "Specific Amino Acid Deficiency Alters the Expression of Genes in Human Melanoma and Other Tumor Cell Lines".

"Studies in humans and rodents suggest that restriction of tyrosine (Tyr) and phenylalanine (Phe) could become a very important addition to antineoplastic therapies. Dietary restriction of these amino acids is not toxic to healthy humans and it enhances natural killer cell cytolytic activity, increases T-lymphocyte numbers and decreases the activation of platelets, which could retard metastasis (1). In fact, dietary Tyr and Phe restriction specifically inhibits metastasis of melanoma, leukemia, hepatocarcinoma and lung carcinoma in rodents ..."

"Recently, a number of metastasis suppressor genes have been identified. One of these ... (MKK4/SEK1), is a gene that suppresses metastasis of prostate cancer ..."

"... data indicate clearly that deprivation of Tyr and Phe regulates MKK4/SEK1 protein expression ... and that the regulation is cell-type specific. Although it is not clear whether MKK4/SEK1 protein is a target for cancer therapy, the fact that amino acid deficiency modulates MKK4/SEK1 protein expression ... suggests that nutrients play an important role in regulation of cancer progression."

[1b] (2003)

"Here we studied the effect of deprivation of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), ... on human DU145 and PC3 androgen-independent prostate cancer cells ..."

"Deprivation of the amino acids similarly inhibited growth of DU145 and PC3 cells, arresting the cell cycle ..."

"Met and Tyr/Phe deprivation induces {cell death} in DU145, but only Met deprivation induces {cell death} in PC3 cells."

"Tyr/Phe and Met deprivation inhibits invasion of DU145 and PC3, but Gln deprivation only inhibits invasion of DU145 cells."

"This study shows the potential for specific amino acid restriction to treat prostate cancer."

[1c] (2006) "Selective amino acid restriction targets mitochondria to induce {cell death} of androgen-independent prostate cancer cells."

"Relative specific amino acid dependency is one of the metabolic abnormalities of cancer cells, and restriction of specific amino acids induces {cell death} of prostate cancer cells."

"This study shows that restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), ... affects the function of mitochondria in DU145 and PC3" cells. These changes induce cell death in the PCa cells.

[1d] (2008) "Selective Amino Acid Restriction Differentially Affects the Motility and Directionality of DU145 and PC3 Prostate Cancer Cells"

[1e] (2011) "Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells."

"In DU145 cells, Gln and Met restriction increased glucose consumption and decreased lactate production, but Tyr/Phe restriction did not."

"In PC3 cells, all amino acid restrictions reduced glucose consumption and lactate production."

[2] Methionine Restriction.

Amino acids have activity apart from building protein. Methionine, for instance, is a methyl donor in one-carbon metabolism. PCa cells like to be hypermethylated. This is how tumor suppressor genes are silenced.

Some years ago my integrative medicine doctor advised me to inject vitamin B12. My homocysteine was high & I had zero cobalt in a hair sample. I was taking B12 orally, but seemingly lacked enough intrinsic factor for uptake.

For 4 straight months, my PSA, which had been constant for 6 straight months, rose. That's when I learned of the SAM cycle & the protective effect of low B12. Which is actually the protective effect of methionine restriction. B12 is needed to convert homocysteine back to methionine.

In 1974, a paper was published that described the effect of replacing methionine with homocysteine in cell growing medium. Normal cells thrived but cancer cells did not. [2a] It seems that PCa cells might want methionine itself - not just the methyl it carries.

It is important, I feel, to realize that, while methionine is found in food, most of the methionine in the body at any point in time, has come from recycled homocysteine.

The conversion of homocysteine to methionine is associated with the B vitamins. Folate (B9) generally acts as the methyl donor. B12, as mentioned, is an essential cofactor. In countries where grains are fortified with folic acid, methyl deficiency is rare. In other countries, diets may have an insufficiency of folate - or can be made so.

[2b] Some here may be familiar with Michael Greger. He is in charge of propaganda for veganism. LOL. I say this because, for him, it's a cause rather than a lifestyle option. And, although he uses published studies, he cherry-picks. & it seems that none of us would ever have ever become ill (any disease) if we had been vegans.

Anyway, veganism is a not uncommon response to a cancer diagnosis, & Greger does have a number of videos (2c) that might help those who are interested. There is spin, sometimes outrageously so, but I respect him for using published studies which one can take the trouble to read.

It was natural for him to make a video [2b] on methionine restriction for cancer, because the main dietary sources are chicken & fish. Plants have low levels. He doesn't mention egg whites, which are high.

He makes no mention of restricting the regeneration of methionine from homocysteine. Presumably because no animals are sacrificed in that process.

-Patrick

[1a] jn.nutrition.org/content/13...

[1b] ncbi.nlm.nih.gov/pubmed/127...

[1c] ncbi.nlm.nih.gov/pubmed/168...

[1d] ncbi.nlm.nih.gov/pmc/articl...

[1e] ncbi.nlm.nih.gov/pmc/articl...

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

[2b] nutritionfacts.org/video/st...

[2c] nutritionfacts.org/videos/

[Burnett1948]

+Burnett 1948. Can advise me which one of these foods reduced my PSA from .9 to .87. Broccoli, Walnuts, Pomegranate Juice, Curcumin phospholipid complex 500 mg containing curcuma 90mg tablets and about 4 to 5 cups of green a day?

[Neal-Snyder]

Patrick, would you say that all of us who are interested in attempting to extend our lives via integrative medicine, complementing what our MedOnc's prescribe, need to find an integrative medicine doctor? I'm beginning to think this is especially important for those of us whose minds tend to get boggled by scientific reports.

In the meantime, am I making a big mistake in eating fish, & sometimes seafood, daily? When I read that I should give up meat, poultry & dairy shortly after I was diagnosed in 2003 with what proved to be metastatic PCa, I was relieved to find that fish seemed to be allowable or even desirable. I do eat wild Alaskan salmon frequently, & all the fish I eat at home is wild-caught.

I also eat eggs sometimes, & you have me worried about them too. (I do often eat them with avocados--hopefully an antidote!)

Have you read Donald Abrams & Andrew Weil's Integrative Oncology, 2nd ed. (Oxford University Press, 2014)? Did you find it helpful in terms of what we should be consuming?

I must say figuring out the food & supplement intricacies for advanced PCa patients is quite a challenge. Could you write a document for us, presenting what we should all know, but for dummies? Seriously. I do realize you probably have your hands full providing us valuable information constantly. & I'm very grateful to you for it.

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

Thanks for your reply.

I went to my integrative medicine doctor 8-9 years ago, because I needed someone who was sympathetic to what I was doing - some of which worried my regular doctor. I was able to get various prescriptions from him, e.g. metformin & arimidex. Many men with high estradiol who have asked for arimidex have been laughed at. "That's a drug for women." & so on.

What I found with my IM guy was that he usually had a couple of good discussion topics whenever we met. & that he looked at my blood test results more carefully than my regular doctor.

Fin & shell seafood is actually a significant part of my diet. I had mussels for breakfast on Monday & Norwegian smoked salmon yesterday morning (OK, smoke may not be a good idea) & canned Alaskan sockeye this morming. I always have some King Oscar sardines on hand - they contain 2.5 grams of omega-3 (a perfect basic dose), & tiny fish have no great accumulation of bad things.

There is a guy in Asheville who brings fresh fish from the NC coast on Thursdays - my favorite being redfish.

I'm not concerned about the methionine in a fish portion, in spite of Greger. I'll be doing an analysis of studies that looked at PCa & fish soon.

I don't worry about eggs. I might have a morning egg every day for a couple of weeks & it doesn't make me nervous. I wouldn't eat a 3-egg omelet, though. I haven't had many eggs this month, but that doesn't signify much.

I haven't read the book. I try to come at the subject of PCa & diet with a willingness to go where the research leads. & that sometimes means having to knock down some basic beliefs.

Perhaps when I get to the letter Z in my posts, I'll summarize all of the food conclusions. Hopefully, there will be some things left that we can safely eat.

-Patrick

[Neal-Snyder in reply to pjoshea13]

Patrick,

Thank you so much for your reply. It was prompt & funny, & it's a relief that I don't need to give up certain foods that help keep me happy. (I wrote very late at night in California, & you replied quite early in NC.)

I would love it if you'd summarize your food conclusions when you get to Z, & I'm sure many others would, too!

I was pretty sure my MedOnc wouldn't prescribe metformin, so I asked my PCP & he said yes. He's wonderful. Which reminds me: How did you decide on 500 mg THREE times a day? I assume they're time-release, right?

The Abrams & Weil book has chapters by scientists who are experts in each chapter topic. They all refer to & cite the research supporting their conclusions. It's very much an evidence-based book. Donald Abrams is the oncologist at UCSF's Osher Center for Integrative Medicine. He studied integrative medicine under Andrew Weil.

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

Regarding Metformin: Dr Myers can be frustrating to observe. Men with PCa want to know of things they can do now that have "probable benefit". After all, many men can't afford to wait. Whatever Myers' thinks privately, or does for himself, he is not going on the record until the perfect study is published.

So he was a late adopter of Metformin, but he now recommends 2,000 mg /day. I see my integrative guy in 2 weeks & will ask for my dose to be increased. I don't use a time-release version.

Here is the "perfect" study:

ncbi.nlm.nih.gov/pubmed/244...

I think Metformin should be offered to all after a PCa diagnosis, regardless of Gleason or stage.

I feel the same way about statins. Normally, I wouldn't use one. Dr Myers offers statins to patients who can't control their cholesterol. But it has been known for a century that cancer cells accumulate cholesterol. & Myers has spoken about PCa (under ADT) making androgens - & even making cholesterol. Eventually, the perfect study will be done ...

Thanks for the book info.

-Patrick

[Neal-Snyder in reply to pjoshea13]

Once again, Patrick, thank you for a most helpful response. I will email my PCP & make the same request.

I agree with you about metformin & statins. I was already on a statin when I was diagnosed.

You're welcome re Abrams & Weil. If you do check it out, I hope you find it worthwhile.

Neal

[paulofaus]

Hi Patrick,

I've been taking B12 tablets (1,000mg/day) as I'm now effectively a vegan (I do eat some fish and shellfish). This post and others seem to indicate that B12 is not good for PCa sufferers, but it's not all that clear. You mentioned that you stopped injecting it. I started with the B12 supplements after reading what Dr Greger had to say about vegans and CVD. I also understand B12 is good for bone strength (and I have many mets, in my spine etc.). You mentioned that you would do a B12 only post one day, but just wondering about your thoughts of continuing with B12 tablets?

[pjoshea13 in reply to paulofaus]

Paul,

In my own situation, B12 shots turned out to be a big mistake.

I never thought to check out the PCa-B12 literature - I assumed there was none.

Once I read it, I realized that my inability to absorb B12 from food was a good thing.

But there is a downside to B12 deficiency that is very significant. I accept a higher risk of cognitive issues, etc, because PCa is my immediate problem.

One cannot immediately create deficiency. An extraordinarilly small amount is enough for life, & the body does store it. So if you turned from meat to vegan, it could take a couple of years before outright deficiency set in.

My clues were: (1) no cobalt found in a hair mineral test, & (2) high homocysteine.

One option you have is to reduce the dose so that you flirt with insufficiency. Perhaps one tablet / week.

Or, you might not want to mess with insufficiency.

You mention Dr. Greger. I admire him for what he is - a superb propagandist for veganism. He knows his science, but he does cherry pick. A clever man. Watch out! LOL

Best, -Patrick