The Nitric Oxide (NO) Theory Of Aging

visionofstrength · Sep 3, 2014

Milklove said:
I don't think of the effect of red light as "activating" the cells. It restores healthy functioning of the mitochondria and can put the cell in a relaxed state. It also has anti-excitatory and anti-imflammatory actions.

Then there is this very interesting quote by Ray Peat:
The older the person is, the more emphasis should be put on protective inhibition, rather than immediately increasing energy production. Magnesium, carbon dioxide, sleep, red light, and naloxone might be appropriate at the beginning of therapy."

Yes, completely agree. The interesting question (if only for me) is whether Peat will feel dosing is needed, as the paper you cited above, for example, seems to conclude, proposing a "biphasic" dose response that limits the irradiance and the time, and concluding that the controversy over redlight therapy is a misapprehension of "biphasic" dose response.

[Idealized biphasic dose response curve (often termed Arndt-Schulz curve) typically reported in LLLT studies.]

In contrast, it would seem Peat feels that the first three therapies are evidently self-limiting, magnesium from coffee, carbon dioxide and sleep.

Very glad you asked Peat the question!

Mittir · Sep 3, 2014

dd99 said:
I just stumbled across this comment by Mittir in the Red light, infrared, DPL thread:

Mittir said:

He did mention in interview that any source of red light including LED, LASER, Sun light, Incandescent bulb,
will activate Cytochrome oxidase, the respiratory enzyme. Most red light experiments used either laser or led.
But he did not recommend any specific LED product. Incandescent light has both orange and red, and LED has only
one red light frequency. There are lots of studies on red LED.

Click to expand...

.

RP has talked about a study that showed bright light suppressing cortisol after
sunset. RP always insist on using at least several hundred watts of incandescent
to get benefit of light Therapy. You will definitely get benefit of red light from
using red LED. It is not clear to me if those LED board has enough bright light
to suppress cortisol after dark. I remember reading a study that sounded similar
to the one RP talked about. IIRC they used 10,000 lux. You can use LED for
red light therapy and bright incandescent for regular lighting.

Such_Saturation · Sep 3, 2014

I think the various parts of the respiratory chain have different bands of resonance. Just buying "any red LED" will not cut it. An incandescent or halogen will always cover more less all of them however.

dd99 · Sep 5, 2014

Thank you all for your comments. I use the LED board during the day whenever I'm sitting at my desk. I have halogens everywhere else in the house. There's a big campaign here in the UK to get people to switch from halogen to LEDs for energy efficiency. If I were to get warm white LEDS (with colour temperature of 3000 Kelvin, similar to a 200-watt incandescent, apparently), would that be good for regular lighting?

Mittir · Sep 5, 2014

dd99 said:
Thank you all for your comments. I use the LED board during the day whenever I'm sitting at my desk. I have halogens everywhere else in the house. There's a big campaign here in the UK to get people to switch from halogen to LEDs for energy efficiency. If I were to get warm white LEDS (with colour temperature pf 3000 Kelvin, similar to a 200-watt incandescent, apparently), would that be good for regular lighting?

I was considering regular LED lighting. I think there are regular LED bulb with
much less Kelvin, 2400-2600 kelvin seems more preferable to me.
You want yellowish light like incandescent. My understanding is that
cortisol suppression required higher luminosity, studies usually use 10,000 lux
for depression treatment. Day light ( not direct sun light) has between
10,000 to 25,000 lux. I think Idea is to mimic luminosity of day light.
LED bulbs have much higher lumen per watt than incandescent.
You can experiment with different watts of LED to figure out the
similar effect you are getting from halogen.

dd99 · Jun 21, 2016

Bumping this thread because I think it's full of interesting info.

ecstatichamster · Jun 21, 2016

And I miss VoS...sigh...a bit before my time here but a wonderful poster.

Stryker · Jun 22, 2016

Effects of γ-Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide-Treated Rats - Sjakste - 2008 - Basic & Clinical Pharmacology & Toxicology - Wiley Online Library
Effects of γ-Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide-Treated Rats

"Administration of the antiischaemic drug, mildronate (120 mg/kg) caused a significant twofold decrease of the nitric oxide level in brain cortex and cerebellum 1 hr after drug administration. Its natural analogue gamma-butyrobetaine (30 mg/kg) triggered a twofold decrease of the nitric oxide concentration in all studied tissues 30 min. after the administration. Nitric oxide reached the initial level 2 hr later. Neither mildronate nor gamma-butyrobetaine could inhibit the inducible nitric oxide synthase in vitro. Analogues of gamma-butyrobetaine appear to be prospective drugs for the treatment of circulatory complications of sepsis."

Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease
Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

"The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS."

http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2005.tb00267.x/epdf
Mildronate: An Antiischemic Drug for Neurological Indications

"Our recent findings suggest that CNS effects of mildronate could be mediated by stimulation of the
nitric oxide production in the vascular endothelium by modification of the y-butyrobetaine
and its esters pools. It is hypothesized that mildronate may increase the formation of the
y-butyrobetaine esters. The latter are potent cholinomimetics and may activate eNOS via
acetylcholine receptors or specific y-butyrobetaine ester receptors."

"It has been also reported that mildronate and y-butyrobetaine (GBB) combined eliminated physiological effects of nitric oxide synthase (NOS) inhibitors"

"Changes in the NO content in different rat tissues (brain cortex, cerebellum, liver, heart,
kidneys) were evaluated after mildronate administration by the electron paramagnetic resonance method (EPR). Mildronate (50 mg/kg, i.p.) triggered a slight but reproducible
wave-like increase in NO level in the brain cortex and cerebellum at 30 min after drug administration"

Interesting that mildronate can protect against excessive NO levels caused by endotoxin , carnitine ingestion and the activation iNOS but at the same time maintain normal activity of eNOS

dookie · Jun 22, 2016

Stryker said:
Effects of γ-Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide-Treated Rats - Sjakste - 2008 - Basic & Clinical Pharmacology & Toxicology - Wiley Online Library
Effects of γ-Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide-Treated Rats

"Administration of the antiischaemic drug, mildronate (120 mg/kg) caused a significant twofold decrease of the nitric oxide level in brain cortex and cerebellum 1 hr after drug administration. Its natural analogue gamma-butyrobetaine (30 mg/kg) triggered a twofold decrease of the nitric oxide concentration in all studied tissues 30 min. after the administration. Nitric oxide reached the initial level 2 hr later. Neither mildronate nor gamma-butyrobetaine could inhibit the inducible nitric oxide synthase in vitro. Analogues of gamma-butyrobetaine appear to be prospective drugs for the treatment of circulatory complications of sepsis."

Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease
Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

"The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS."

http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2005.tb00267.x/epdf
Mildronate: An Antiischemic Drug for Neurological Indications

"Our recent findings suggest that CNS effects of mildronate could be mediated by stimulation of the
nitric oxide production in the vascular endothelium by modification of the y-butyrobetaine
and its esters pools. It is hypothesized that mildronate may increase the formation of the
y-butyrobetaine esters. The latter are potent cholinomimetics and may activate eNOS via
acetylcholine receptors or specific y-butyrobetaine ester receptors."

"It has been also reported that mildronate and y-butyrobetaine (GBB) combined eliminated physiological effects of nitric oxide synthase (NOS) inhibitors"

"Changes in the NO content in different rat tissues (brain cortex, cerebellum, liver, heart,
kidneys) were evaluated after mildronate administration by the electron paramagnetic resonance method (EPR). Mildronate (50 mg/kg, i.p.) triggered a slight but reproducible
wave-like increase in NO level in the brain cortex and cerebellum at 30 min after drug administration"

Interesting that mildronate can protect against excessive NO levels caused by endotoxin , carnitine ingestion and the activation iNOS but at the same time maintain normal activity of eNOS

Agmatine seems to do the same - lower all forms of NO, but in a few studies, does seem to enhance the eNOS

Anyone else confused about the various isoforms of NO?

Stryker · Jun 22, 2016

http://cardiovascres.oxfordjournals.org/content/43/3/521

this helped me alot , i argue about nitric oxide and its roles in health or disease alot with my father so i want to ready for the next one

ecstatichamster · Jun 22, 2016

Methylene blue reduces nitric oxide. How does it compare to mildronate

Such_Saturation · Jun 22, 2016

So making nitric oxide makes NADP+?

Jac · Jul 6, 2016

ecstatichamster said:
Methylene blue reduces nitric oxide. How does it compare to mildronate

Would that be considered a good or bad thing in your opinion?

nograde · Nov 3, 2016

Activated charcoal binds Nitric Oxide, it's actually used in filters for that. Could this be the mechanism behind it's anti-aging effects observed in rats? Ray also wonders what AC actually scavenges that leads to longevity. I doubt it's endotoxin, according to a study (which I can't find anymore) AC's endotoxin reducing effects are very weak compared e.g. to bentonite (which is bad because of aluminum).

haidut · Nov 3, 2016

nograde said:
Activated charcoal binds Nitric Oxide, it's actually used in filters for that. Could this be the mechanism behind it's anti-aging effects observed in rats? Ray also wonders what AC actually scavenges that leads to longevity. I doubt it's endotoxin, according to a study (which I can't find anymore) AC's endotoxin reducing effects are very weak compared e.g. to bentonite (which is bad because of aluminum).

It binds serotonin as well as NO. Plasma serotonin levels have been shown to drop after charcoal usage. Given the study on serotonin antagonists greatly extending lifespan, I'd guess that the serotonin and NO are primary candidates for the lifespan extension effects.
Good point, thanks for bringing it up.

Luann · Nov 8, 2016

So, if it's okay to look for an "easy" answer, what would be the most important diet factors in bringing NO lower? Low PUFA & endotoxin?

Wagner83 · Nov 9, 2016

Aragula, beets (among other things) and if I'm not wrong vit C + garlic boost NO .

haidut · Nov 9, 2016

Liubo said:
So, if it's okay to look for an "easy" answer, what would be the most important diet factors in bringing NO lower? Low PUFA & endotoxin?

Yes, these are two major factors. And avoiding stress in general. As soon as a cell is stressed beyond the point where metabolism can meet the energetic demands of the stressor it starts synthesizing NO. There is an enzyme called inducible NO synthase (iNOS) and it gets activated by everything from arachidonic acid (PUFA) to infections, to endotoxin, to mental stress, etc.

ecstatichamster · Nov 9, 2016

Wagner83 said:
Aragula, beets (among other things) and if I'm not wrong vit C + garlic boost NO .

avoid pde5 inhibitors such as Viagra.

Luann · Nov 13, 2016

@Wagner83 Awesome

@haidut nice to hear from you thanks.

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The Nitric Oxide (NO) Theory Of Aging

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