Nitric Oxide

[pjoshea13]

New study [1].

I have used a nitroglycerine patch for several years. The idea is to help improve blood flow to tumors. When the oxygen supply is poor, PCa cells will respond with Hypoxia-inducible factor 1-alpha [HIF1alpha]. HIF1alpha is implicated in treatment resistance & it makes cells more aggressive. The patch releases nitric oxide [NO] which dilates blood vessels. In spite of those who believe that "cancer hates oxygen", tumors want to have a good supply. A key role of HIF1alpha is to stimulate creation of blood vessels via VEGF (vascular endothelial growth factor).

For some reason, Arora & Ramasamy figured that NO might be useful in CRPC control. They used GSNO (S-nitrosoglutathione) [2] to increase NO levels & used human tumor xenografts containing ARV-7 cells in an animal model.

"The study found the compound suppressed these tumors and continued to suppress them with no signs of resistance. The increased NO helped neutralize the tumor microenvironment — the complex, inflammatory shell around which tumors grow. Specifically, GSNO reduced levels of tumor-associated macrophages, immune cells that cancers co-opt into their microenvironment."

-Patrick

{I was unable to locate the paper on the Proceedings of the National Academy of Sciences [PNAS] site.}

[1] med.miami.edu/news/sylveste...

[2] en.wikipedia.org/wiki/S-Nit...

[pjoshea13]

IT,

When I had salvage radiation 14 years ago, I followed a LEF recommendation to swallow a ton of arginine just before each session. The dilation effect is brief.

The NO patch is generally prescribed for angina, etc. It delivers a constant NO dose. My integrative medicine guy had no problem giving it to me.

-Patrick

[SuppWife in reply to pjoshea13]

Hello, I've been reading and lurking for months but this is my first post. Would you mind elaborating on this; "I followed a LEF recommendation to swallow a ton of arginine just before each session." We are consulting with an RO tomorrow for my husband who is 65 years old with zero comorbidities except borderline high triglycerides. He's just had his second Firmagon shot after failed RP (April 2018). PSA history Jan 2016 psa 24 (denial and symptoms waxed and waned), Mar 2018 psa 34, gleason 8 after biopsy (all cores were 7s, but one was 8), upgraded to 9 after surgery, extensive positive margins and EPE, 88 gram prostate, 80% tumor, SVI +, PNI +, PT3bNOMO (negative bone scan, negative LNs). After 30 days on Firmagon PSA from 22 to 0.66 and testosterone from 630 to 22.5. I have him taking 15 grams of MCP (since late June), 8 grams of IP6 (since August), daily, plus D3, K, B-complex, CoQ10, and a high quality mushroom supplement. I have bought L-citrulline, L-arginine, and milk thistle, but haven't worked them into the protocol yet as I'm unsure of the doses. I would be very interested to hear more about how you dosed arginine before radiation and how you use it daily if you'd be willing to share. If you have shared this information elsewhere, please share a link. I follow you, Nalakrats, and CalBear74 and appreciate all your insights and experience. Thank you in advance.

[pjoshea13 in reply to SuppWife]

I don't use arginine. It's good for generating NO but the effect is short-lived.

The Life Extension protocol called for so much arginine that I bought a big jar of the powder & empty capsules (the largest size) & packed my own. I sat in the car with my wife & forced myself to swallow handfuls of caps before going in for the next session.

-Patrick

[SuppWife in reply to pjoshea13]

Thanks so much for your reply. I corrected my post, btw. He was staged pT3bNoMo. I will look for the LE protocol. Thanks again!

[adlerman]

The L-Argenine is harder to absorb if you're over 40. I found tablets that dissolve making absorption more likely. It contains 420mg of a Proprietary Nitric oxide blend. Beet Root powder, Hawthorn berry, L-Citrulline plus small amounts of C (100mg) and B12(50mcg).

More info at HumanN.com. I have no connection with this company other than as a user of this product.

[dave2]

Thanks, Patrick, for this intriguing research!

Your post caused me to search for more info about the effect of NO on cancer. Turns out that it's been known for nearly 20 years that NO (via various NO donors/drugs) can potentially have an anti-oncogenic effect, although there have also been some reports that NO can have a pro-oncogenic effect. Intracellular concentration, duration of exposure, and other factors are hypothesized as the explanation for the variable reports on its effectiveness. This 2008 paper discusses the potential role of NO in cancer therapy at that time: spandidos-publications.com/...

The research you cited included the comment that "the tumors did not develop further resistance that commonly occurs with most therapies currently available for prostate cancer." It would be so wonderful if that also occurs with human PCa patients! Hoping that human trials of GSNO (and possibly other NO-donor drugs) will be started soon!

[herb1]

Hi Pat, I too looked at nitroglycerine for pca benefit. At the time I was using an NG spray intermittently. Did it help my PSA? I thought so, but hard to prove. In fact, at the time I suggested an easy test might be to check psa values or pca occurrence in guys working in US explosives plants manufacturing NG (yup, same), TNT,etc. Never got encouragement from my urologist or oncologist; cardiologist just shrugged.