Plasma Levels of Nitrate & PCa

[pjoshea13]

5 months ago, I posted:

"Non-PCa Prescription Drugs: Nitroglycerin"

I use a nitroglycerine patch to improve the oxygen supply to the tumor(s). Contrary to the predominant view on the internet, cancer doesn't "hate" oxygen. My patch generates nitric oxide [NO], which dilates blood vessels & thus improves the blood supply to the cancer & keeps it happy. Why would anyone want to do that? Because prostate cancer becomes really mean & nasty under hypoxic conditions.

I bring this up because I now recall a 2013 Giovannucci study that has a direct bearing on the NO issue [1] - & the full text is available, which wasn't free when I first read the paper.

"Nitrate and nitrite supplements have recently been shown to improve cardiovascular health, but there is concern that these supplements could contribute to the development of cancer."

"We conducted a nested case–control study within the Health Professionals Follow-up Study. Baseline blood samples were collected in 1994, and incident cases of prostate cancer were identified from 1997 to 2005. Baseline plasma levels of nitrate were measured in the 630 cases and 630 matched controls."

"We have found that baseline levels of plasma nitrate were not associated with risk of prostate cancer."

However:

"... plasma nitrate seemed to be inversely associated with advanced-stage prostate cancer. The relative risk across extreme quartiles was 0.44 ... for the whole dataset ..."

"... and 0.30 ... for the fasting dataset.

So, as an indication of protection, fasting blood levels of nitrate are more significant.

Giovannucci seems surprised by the finding.

"Plasma nitrate comes from 2 sources. Nitrate can form endogenously from nitric oxide produced through the NOS pathway (as shown in Fig. 1) or from dietary intake, mainly vegetables. Approximately 80% of nitrate intake derives from vegetable consumption (6). A plate of green leafy vegetables such as spinach contains more nitrate than is formed endogenously from all NOS pathways in a day (30). Our study shows that vegetable intake seems to have a stronger association with plasma nitrate than total nitrate intake."

"Nitrate can be converted to nitrite and, subsequently, nitrite converted to nitric oxide "

"The conversion of nitrate to nitrite to nitric oxide occurs under hypoxic and/or acidic conditions when the NOS pathway is dysfunctional"

"... nitrate may affect prostate cancer tissues where a low pH/hypoxic condition exist, and the major NOS system does not function properly."

-Patrick

[1] cebp.aacrjournals.org/conte...

[BigRich]

Patrick,

A very interesting read, but I fear in enhancing the blood supply to the tumors.

Rich

[pjoshea13 in reply to BigRich]

Rich,

I felt the same way until I discovered that hypoxia inducible factor 1alpha (HIF1alpha) causes treatment resistance & the formation of new blood vessels.

-Patrick

[BigRich in reply to pjoshea13]

Patrick,

"I discovered that hypoxia inducible factor 1alpha (HIF1alpha) causes treatment resistance & the formation of new blood vessels." Could you provide a link to that article; so that, I may learn about it?

Rich

[pjoshea13 in reply to BigRich]

Rich,

There are hundreds of PCa-hypoxia inducible factor papers.

I'll just give you one human study [1]. Note that HIF causes vascular endothelial growth factor (VEGF) to be induced. VEGF is the growth factor for blood vessels.

"To our knowledge, this is the largest study of intrinsic markers of hypoxia and angiogenesis in relation to the outcome of radical treatment of localised prostate cancer. Increased expression of VEGF, HIF-1 alpha, and, for patients treated with surgery, osteopontin, identifies patients at high risk of biochemical failure who would be suitable for enrolment into trials of treatment intensification."

If we can inhibit HIF, PCa becomes more amenable to treatment.

-Patrick

[1] thelancet.com/pdfs/journals...

[BigRich in reply to pjoshea13]

Patrick,

I will read the paper tomorrow, thank you.

Rich

PS: We had our usual snowfall, I am lucky, I only have to shovel a half foot of snow this time.

Rich

[Neal-Snyder]

Is eating leafy dark green veggies daily an adequate substitute for wearing a nitroglycerin patch, do you think, Patrick?

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

I don't know.

Information on nitric oxide production is likely to found on fitness performance sites.

Here is a list of 18 foods:

amrapnutrition.com/interest...

but how to quantify the effect?

-Patrick