Note the articles title and published date on NIH.gov:
"Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics"
Published online 2021 Jan 27
ncbi.nlm.nih.gov/pmc/articl...
Also see malecare article below about NO and PCa: A clinical trial that showed NO slows PSA doubling time.
Nitric Oxide -- slows prostate cancer progression and PSA doubling time.
malecare.org/phase-ii-study...
The following link is one source of Nitric Oxide formulated @ the University of Texas Medical center
"This rational for this trial using low-dose nitric oxide (NO) is supported by preclinical in vitro and in vivo evidence which confirmed the absence of cytotoxic activity against neoplastic cells, but revealed that its use decreased the emergence of a more malignant phenotype, including invasion and metastases induced by a hostile tumor micro-environment.
Seventeen of the 29 men enrolled in the study (58%) completed the 24 months of the study treatment. Results suggest a significant inhibition of disease progression, with the mean PSADT increasing to 31.8 months from 13.2 months before starting the investigational treatment. For the 17 men who completed the study, there was no evidence of asymptomatic metastases on the end-of-study bone scans.
When the treatment group was compared with the matched group of men a similar significant difference in PSADT was observed between the two groups.
The data is supported by results of another retrospective study using data from the HealthFacts™ database, which compared the time to “Nadir PSA + 2 ng/mL” and the time to “2X Baseline PSA” between prostate cancer patients who had had radical prostatectomy and GTN exposure (n=29) and attribute-matched control patients who had had radical prostatectomy and no GTN exposure (n=29). Results of this study were suggestive of GTN efficacy in delaying disease progression in post-radical prostatectomy prostate cancer patients (data on file, Nometics Inc, Ottawa ON; available at: nometicsinc.com).
This Phase II study is the first report of the clinical use of NO donors for the treatment of prostate cancer. Recently, Yasuda et al. (2006) published a Phase II trial demonstrating the benefit of GTN as an adjuvant to chemotherapy for nonsmall cell lung cancer.
Despite the seemingly significant effects on the PSADT as well as the lack of any adverse events suffered by any of the men in the study with the low-dose GTN patch in men with recurrent prostate cancer, these results must be interpreted with great caution. Remember, there has not been any evidence that slowing PSADT necessarily result in long-term clinical benefit or survival benefit with men who have recurrent prostate cancer."
here is a paper that describes how low levels of NO promotes PCa friendly environment and high levels of NO slows PCa progression and causes apoptosis.
ncbi.nlm.nih.gov/pmc/articl...
"Thus maintaining low/transient levels of NO and ensuring that apoptotic pathways are effectively inhibited is one potential mechanism by which tumors are able to increase their proliferation capacity."
George, how effective do you think it is to do Exercise with Oxygen Therapy (EWOT) once a day, and/ or take a daily dose of Arginine and Citrulline prior to exercising? I know these helps increase NO, but the big question is whether this once a day NO increase in the body is sustained long enough to make a big difference compared to the ~12 hour use of the NO patches. I have the low dose NO patches in my closet (prescribed for stable angina that occurs at higher levels of exercise, such as jogging). I have not used the patches yet though, because I read that it can cause damage to the endothelial lining in the arteries, which might cause more plaque buildup and heart attack risk. What are your thoughts on this and risk vs. reward?
Have you found any recent data as this is quite old? I compared the HumanN product in your link to organic beet juice that I take now. HumanN gives you 420mg NO for $1.20/day. 1/2 cup beet juice gives you 1300mg NO for $0.91/day. Or take 1/4 cup and still almost double the mg of the HumanN product. And the sweetness of the beet juice helps when I mix it with my daily cup of pomegranate juice (which can be a little tart) as supported by clinical studies. Reaffirms my use of beet juice as I had no idea it helped with PSADT. Thanks for posting.
why did you start using beet juice?
NO for blood pressure. I also take L-Citrulline, Pennogenyl, Fish Peptides and Celery Seed Extract. NO also good for other parts of the anatomy 
I’m not sure I’d be looking to increase my NO. Actually from what I’ve read, I’m more inclined to look at reducing it. NO is in high concentrations in city smog, just so you’re aware.
Lady M, my wife, grows our own fresh beets and makes a wonderful salad with grated beets, walnuts, home grown garlic with some olive oil mayo. I have been doing beets for the mild anemia from abiraterone. I'll have to ask about making juice. Probably good with vodka.
Fish
Your source of beet juice sounds like it is much better for NO than the HumanN .. Yours is 3 times stronger -- I just found HumanN listed as having been researched and developed by UT Medical staff. HumanN does contain other ingredients but they are all available in supplement form also ...
I think I will buy the beet juice like you -- plus buy the other stuff included with the UT concoction as supplements. What brand (source) of beet juice do you use ?
ncbi.nlm.nih.gov/pmc/articl...
Published online 2021 Jan 27
"At high concentrations, NO is able to induce death, while at low concentrations it may actually protect cells from death. At 50–100 nM, NO is able to phosphorylate extracellular signal regulated kinase (ERK) activate the AKT pathway, and stabilize HIF1a, while at the 300 nM–1 μM range, NO induces DNA damage, p53 activation, and causes nitrosative stress [56]."
The very current article was published on NIH.gov in 2021 --
it confirms other long established trial results as far back as 2006.
Some may be bothered by the fact that one of the RCTs that proved NOs efficacy was done as far back as 2006 !
Even though it was 600 years ago when the world was proven to be round and the earth circled around the sun instead the sun orbiting the earth ... or the law of gravity -- once proven true then it is an established fact -- these articles cite 5 or 6 other RC trials than confirm NO in high amounts have shown to be able to kill several types of cancers, microbes and fungi -- lower PSA doubling time and even lower blood pressure in people. Those facts are not going to change.
great post! Thanks
George et al, This paper on NO from my files might also interest you.
The Yin Yang Role of Nitric Oxide in Prostate Cancer - American Journal of Men's Health, 2020 Jan-Feb;14
ncbi.nlm.nih.gov/pmc/articl...
Note the attached graphic.
What is Tall_Allen's position on the use of Nitric Oxide?
why don't you ask HIM?
Way too angry of a guy.
If you feel that way about him, then I get why you did not PM him and asked here what his position might be on the subject. There is no need for any of us to undergo unnecessary stress.
Stay calm and happy,
Fish
"If you feel that way about him, then I get why you did not PM him and asked here what his position might be on the subject. There is no need for any of us to undergo unnecessary stress.
Stay calm and happy
Fish"
That is no less mean spirited than Tall_Allen often is.
The only difference is I think you have a higher EQ and you know better.
So what is your excuse for the gratuitous and intentionally offensive message?
To make yourself feel good at the expense of another? Even Tall_Allen doesn't do that. Does he.
My intent was to provide understanding and support. Personally, I do not care what mean spirited people's opinions are on subjects. Perhaps, you should consider doing the same for peace of mind. If you took offense at my response, then apologies...
Have a nice day,
Fish
There is the PM option under HU... I'm interested in Nalakrat's take on this issue, but that is not available...
NPfish -- check your PM from me
Got it... right back to you... Is it a triumvirate of one ?? Who knows?
I would like to hear both plus poshea as well.
Hey George,
I believe that pjoshea13 uses a nitro patch as part of his regimen. I am considering it now for an add on to my vacation regimen. Thanks for posting this information.
Fish
where do you get the patchs?
Rx from an MD... NP... or PA...
George thanks for posting 👍
great find George
Great article, George, thank you. It will keep me busy reading this deep dive review today. 119 pages. NO is certainly complex roles in so many processes and is carefully regulated, as is ROS. Perhaps high dosing of beet juice best for those with currently rising PSAs So one can watch the PSADT trend for themselves .
Have to consider the protective actions of low to moderate NO activity in protecting and modulating so many physiologic processes. We are not just composed of the cancer. Don’t want to harm the long term health of the body (65 Kg) while my 10-20 grams of PC burden is otherwise behaving. For me I think moderation in supplementation currently best (Even though I certainly supplement many phytochemicals! Reflecting my uncertainty). 🤷🏼♂️
also watch the BP drops if taking a PDE5 inhibitor (Viagra or Cialis)
El desesperado desarrollar de las mulas (The desperate mule skinner) MB
Senor Mulas - I got interested in NO several years back, but the following from the paper I linked in the above reply caused me to put it on hold. (It seems similar to the possible yin/yang action of synolytics?)
* * *
Conclusion
In conclusion, while low-dose NO is thought to be cancer promoting and high-dose NO cancer inhibiting, this is a generalization as substantial research contradicts this assumption. In prostate cancer there is evolving research, which demonstrates that NO is upregulated from hormonal stimulation and inflammation, both of which are precursors to prostatic neoplasia. NO has also been reported to downregulate the AR, which may implicate it in the proliferation of AR-independent cancers. Further studies should explore this area of prostate cancer to analyze this cancer type. NO can impact DNA binding of the AR intracellularly, which has been a therapeutic target in CRPC. Research on the genetic polymorphisms in the NOS genes as well as case-controlled studies to link them to cancer are well underway. Finally, there are in vitro and in vivo cellular and animal studies that show promise for NO production as well as inhibition as therapeutic targets. These studies are a starting point for the next step, early-phase human trials, which will ultimately decide the role of NO production or inhibition in the fight against prostate cancer. The new bottom line is that NO action and its consequences on cancer are cell and context specific and cannot be explained or predicted with simple dogma. Understanding the tumor type and its dependence on NO for growth may aid in suggesting whether NO can be useful to cancer therapy. (Emphasis added.)
K-9, thanks for that comparison. Both potentially two edged swords. Thought occurs to me that a near term approach (due to limited present knowledge of complex highly-regulated systems in both senolytics as well as NO (and ROS for that matter), may be the intermittent strike approach (Hit and run). As I do with senolytics every 2 or 3 months, just a 3 day senolytics regimen. So too, could do episodic cycles of NO supplementing with beet juice (several days) to hit the cancer. Then Longer off times to restore homeostasis. The middle path, The Way of the Tao, my wise fanged friend.
Beetlejuice, Betelgeuse, Beetjuice!
Pablo,
So cujoe starts out with Clint Eastwood in "The Mule" and you keep up this mulish pattern of conversation. I guess if you can't beat them...
youtube.com/watch?v=OiAYi9x...
Another fine Clint Eastwood picture with the lovely Shirley McClaine... and let's not forget a classic scene about a mule insulted .... skip the ads....
youtube.com/watch?v=D8Qgmo1...
Twenty Mule Team Borax
The yin/yang article is saying the same thing as the RTCs ..
ie. low NO facilitates mutation, spread and growth -- where as high NO stops mutation, spread, growth and kills PCa.
Continuous high NO is what would be most desirable in my opinion.
as cited from the earlier RTC:
"At high concentrations, NO is able to induce death, while at low concentrations it may actually protect cells from death. At 50–100 nM, NO is able to phosphorylate extracellular signal regulated kinase (ERK) activate the AKT pathway, and stabilize HIF1a, while at the 300 nM–1 μM range, NO induces DNA damage, p53 activation, and causes nitrosative stress [56]."
With NO having a half-life of 2-5 seconds, seems like keeping a "high level" might well be a challenge regardless of dosing strategy?
K9 Enemy of the State,
That may be why Patrick would choose a NTG patch... continuous release. I am unsure what level that might get one to achieve. MB...feel free to chime in here...
Dangerous 1.
Good point, NP. (We need to get pjoshea13 back online! His 19 years of knowledge is sorely missed.)
K9 Terror,
Calling... pjoshea13, and... Nalakrats.... come Up on the Roof at FPC !!!
youtube.com/watch?v=puM1k-S...
Love the song and the lyrics... and while Nalakrats will need to start a new profile... his opinions will be most welcome ... miss that guy ...
Dangerous1
As you wish, Fish. I think Beetroot deserves a broader consideration. Perhaps a separate post. For it offers more than nitrate as precursors for NO. Fortunately the mechanisms of regulation for production and actions are very tightly modulated. Very complex regulation intertwined with ROS regulation. But this perhaps keeps us from screwing them up too badly.
There are several other drug molecules that act as NO donors or promotors. These include the "Statins" via non-cholesterol mechanisms; Non-steroidal NO donating anti-oxidants including aspirin, ibuprofen, indomethacin and others; and Melatonin. So besides nitroglycerin patches there are other sources. (Bacon? 😜)
I am particularly intrigued with beetroot. The whole dehydrated root as powder or tablets would be my preference as they have the full potency of other phytochemicals, especially betalain pigments. Also good fiber content not as present in juice or juice extracts. And I try to avoid juices for their rapid sugar absorption.
Here is a good comprehensive review of Beetroot: (Not cancer/PCa specific)
The Potential Benefits of Red Beetroot Supplementation in Health and Disease
ncbi.nlm.nih.gov/pmc/articl...
"In recent years there has been a growing interest in the biological activity of red beetroot (Beta vulgaris rubra) and its potential utility as a health promoting and disease preventing functional food. As a source of nitrate, beetroot ingestion provides a natural means of increasing in vivo nitric oxide (NO) availability and has emerged as a potential strategy to prevent and manage pathologies associated with diminished NO bioavailability, notably hypertension and endothelial function. Beetroot is also being considered as a promising therapeutic treatment in a range of clinical pathologies associated with oxidative stress and inflammation. Its constituents, most notably the betalain pigments, display potent antioxidant, anti-inflammatory and chemo-preventive activity in vitro and in vivo. The purpose of this review is to discuss beetroot’s biological activity and to evaluate evidence from studies that specifically investigated the effect of beetroot supplementation on inflammation, oxidative stress, cognition and endothelial function."
Pablo. Another happy Mule wandering the deserts of Baja.
Pablo,
Bacon 🥓... I love Bacon !! Rushing to the grocery store for a quadruple helping. Forget NTG patches...headaches, etc... Bacon...LOL... As for the beets, we have beet salad regularly, and the Lady M, my favorite MD, grows them in her garden for us. Have I mentioned borscht?? Enjoy the wandering, but stay safe...
DD
The results of the nitric oxide RTC s supports several other research papers --- as was noted earlier by Mateobeach about benefits seen in Viagra / Cialis and blood pressure meds (both dilate blood vessels and allow oxygen and nitric oxide in. Observational studies have shown slowing of progression with some blood pressure meds. Also the prostate gland is a dense organ and over years enlarges and has poor circulation -- this may be the main reason over time we develop PCa in the first place.
High testosterone plus Cialis, nice combination!
What is SPA?
Nitric Oxide seems like it's potentially tricky to get right. Maybe best done with patches.
Dosing with beet juice doesn't seem reliable.
Does anyone know of any Docs out there who are on the program and who are willing to supervise?
I checked out Tall_Allens blog. He has nothing on NO, pro or con.
I take that as not a good indicator.
The Science is Coming and so fast... when I took my first round of treatment, the MO told me to stay on lupron and abi for almost 2 years...on this time around, he says 1 year..I haven't seen any clinical trials verifying doing that tx plan... The treatment paradigm is evolving faster than trials...
Everyone is who they are.
And they see what they see.
I remember being simultaneously accused by pjoshea and Tall Allen of being of being a stooge for the other.
Over the long term in alphabetical order, my opinion is that pjoshea, smurtaw and TA have been the most prolific contributors here.
Though Patrick fell off the wagon for a while for a while.
It seems to me smurtaw is the currently the largest, though pretty on BAT.
TA seems to have pulled back a bit. Interestingly smurtaw seems to have altered TAs once virulent anti bat bias.
Everyone contributes in their own way. TA seems to have stopped speaking to me. For some undisclosed offense.
That doesn't mean he isn't contributing.
And who knows maybe he will start talking to me again.
Still no reason to hold any grudges here.
This is still the best place on the internet for a new patient to educate themselves about prostate cancer.
Actually, if I remember, if your priority is to communicate information to people, I made the right decision in my opinion.
I notice that TA is trying to do a better job at that.
He seems to be spending some extra effort in the titling of his posts.
As I understand it, he doesn't believe in reading between the lines with analysis.
That's his whole schtick: logic, intuition, and belief will lead you to places that are not supported by data.
He just doesn't believe in operating in that grey area.
Risk Management (Taleb-style) meets Adaptive Theory (Moffitt-style)Update on Prostate Cancer Vaccines from Previous Posts done over the last few years... and a new one...Study Solves Testosterone’s Paradoxical Effects in Prostate Cancer, Duke Health, Published September 04, 2024 
Seminal Vesicle Invasion & Senescent tumor cells.Arnab Basu, MD, on Breaking the Barriers to Genetic Counseling in Prostate Cancer - ASCO Reading Room - MedPage Today - 04.07.2021
