Foods/Supplements-Vitamins: Arginine - Nitric Oxide

Nalakrats wrote a number of things that I disagree with. Here is one of them:

"Cancer cells hate oxygen"

Such statements are usually followed by a reference to Otto Warburg who won a Nobel in 1931. i.e. it must be true. (Poor Otto is usually misquoted, but his view that hypoxia is the cause of cancer has been discredited.)

Cancer cells can survive in a low-oxygen setting, but oxygen will not kill them.

When a tumor outgrows its blood supply, cells that cannot get the oxygen they need, respond with Hypoxia-Inducible Factor 1-alpha [HIF1a]. [1]

I used to think that hypoxia would make tumors more vulnerable. In fact, HIF1a is responsible for a number of survival actions that make it extremely difficult to treat the cancer. HIF-1a is responsible for radioresistance & drug resistance. The cancer becomes very aggressive & invasive.

One of the most important activities of HIF1a is the generation of VEGF [Vascular endothelial growth factor] - a growth factor that stimulates the creation of new blood vessels (angiogenesis). Turns out that the tumor wants oxygen after all.

As an aside, the internet talk of "cancer hates oxygen" is often paired with "cancer loves sugar". Many cancers turn to glycolysis - the use of glucose for energy by a process that does not use oxygen. This is given as proof that cancer cells prefer a hypoxic condition. But PCa cells do not favor glucose for energy. They prefer fatty acids, particularly palmitic acid. In fact, other cancer types will often turn to glycolysis even in the presence of oxygen.

If one can improve the oxygen supply to a tumor, the status quo is maintained. We avoid hypoxia, the creation of new blood vessels, increased aggressiveness & invasiveness. Drugs will continue to work as well (or poorly) as before. It is the lesser of two evils.

The way this can be achieved is by dilating blood vessels with nitric oxide (not nitrous oxide). There is medication that can do that. Niroglycerine!

D. Robert Siemens [2] had the bright idea to use "low-dose glyceryl trinitrate (GTN) on men with biochemical recurrence of prostate cancer after primary therapy" - "nitric oxide signaling plays a significant role in the hypoxia-induced progression of prostate cancer."

"The calculated PSADT {PSA doubling time} of the treatment group before initiating GTN was 13.3 months ... In an intention-to-treat analysis, the end-of-study PSADT for the treatment group was significantly different at 31.8 months"

Now that is a really big deal.

There hasn't been a trial on men with advanced PCa.

Arginine is a precursor of nitric oxide. The effect is short-lived. There is great interest in bodybuilding circles for improving performance via arginine-generated nitric oxide. Regular arginine supplements will not do the job. High doses upset the stomach.

Another aside: When I first needed to get an understanding of androgens & estrogens in the male body, I kept coming up with Google hits for bodybuilding sites. I fould that there was a serious depth of understanding of the science at those sites. There always seemed to be someone heading the group who could describe the metabolic fate of hormones & supplements, and their effect on performance. These guys are very intense. For some, it takes over their lives. The references to scientific papers is not at all academic - these men apply what they know & reject what doesn't work.

Anyway, I came across a product that seemed to increase vascular dilation:


I am not recommending it. If interested in the concept of increasing nitric oxide, find a bodybuilder site & ask questions. There might be something better.

If I had a cardio problem & could get a nitro patch ... I would certainly give it a trial & monitor my PSADT.


SELECTIVE Amino Acid Restriction.

One of the most studied growth factors in the PCa literature is IGF-I (Insulin-Like Growth Factor 1). One of the reason to avoid milk & its products is that bovine IGF-I is bio-identical to human IGF-I. Milk is the only food that contains not only the elements for growth, but also the hormone to stimulate growth. Why would an adult entering the cancer years feel that milk was a good idea?

Anyway - what to do when PCa elevates free IGF-I? The body will not commit to growth when the building blocks from diet are sparse. The building blocks for protein are amino acids. One could restrict whole protein intake. If vegetarian (i.e. no whole protein in the diet) one could selectively limit one of the least important amino acids. In this post, I am only concerned with arginine.

The body can make arginine from citruline, using the enzyme argininosuccinate synthetase [ASS]. Arginine is therefore only conditionally essential. Restricting intake would have limited value if citruline levels were adequate.

A 2004 study [4] set out to identify cancers that are deficient in the enzyme:

"Melanoma, hepatocellular carcinoma, and prostate carcinoma were most frequently deficient in ASS"

In fact, "Dillon and colleagues demonstrated that 100% of examined prostate cancer cells lines were deficient in ASS". [5]

In a 2015 "Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors" [5]:

"Arginine was variably suppressed with 10 patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including 2 patients with PSA response) were documented, and 7 patients had stable disease."

"Conclusions: ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted, and expansion cohorts are now accruing for ... castrate-resistant prostate cancer ... at a recommended phase II dose of 36 mg/m2."


The two sides of arginine: (a) a potential means, in some form, of increasing nitric oxide, or (b) a potential contender for selective amino acid restriction.






[5] clincancerres.aacrjournals....

2 Replies

  • Enjoyed your retort, pjoshea. I am on very high levels of Arginine, by splitting up does into 4 segments a day. Taking 6 grams a day. On days of weight lifting, before lifting, I use 3 grams plus 1 gram of citruline, and 1 gram of Ornithine--which has synergies with Arginine. At 73 years of age and with almost no testosterone, and a PSA of 0.03. I am bench pressing 400 pounds and curling 150 pounds. This is the same as pre-surgical removal of the prostate and the ADT drugs. I give credit to the NO. And to God!

    As to your rail about oxygen. I was being simplistic, without wanting to get into the chemistry of the Prostate Cell innards'. But what the goal is relative to the creation of lactic acid in the metabolism of the cancer cell is to change its PH, by raising it from a typical 6.5 to something over 7.45 . Oxygen containing chemicals that can release oxygen is only about PH alteration of cancer cells and not about whether cancer cells hate or like oxygen. One thing prostate cancer cells try to do is maintain a certain PH, and that appears to be 6.5 as determined by dozens of publications.

    As to angiogenesis and to stop or slow, the best material today is Pectasol-C or modified citrus pectin. Now in Phase 3 Trial testing in the USA and Phase 2 Testing in Israel. Results so far have been outstanding as the Pectasol-C has an infinity to grab on to Galectin-3, considered the main protagonist to angiogenesis, when is expresses itself.

    Anyway have a nice day! Regards:


  • I was taking arginine to increase nitric oxide then came across an article that said if you're over 40 it's difficult to absorb arginine. I switched to L-citrulline and that seems to be doing the job. I found some Nitric oxide Indicator strips online and I'm in the optimal range.

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