Erection Biochemistry Lesson: NAC — N-Acetyl-Cysteine — Potentiates PDE5-inhibitors and Works Synergistically with NO-donors and Citrulline
This blog post was from Karl Wikman's PE blog. He is a moderator on the subreddit TSoPE
His blog can be found here.
And his reddit can be found here.
Sometimes I write replies to people two or three levels down a comment thread, which when I later reflect on the matter, are worthy of being rewritten as a post. This post originated like that, in a thread where someone asked what they could do to make sure their erection quality was maxed out later that day. I listed the most obvious things, such as good hydration, taking a Viagra or Cialis (PDE5-inhibitor), taking some Citrulline (5–8g) and Arginine (3–4g), and eating a fuckton of beetroot (400g). As an afterthought, I added that he could take 1200–1800mg of NAC, which is one of my favourite supplements because of its beneficial effects in so many parts of the body.
Here is why NAC works in synergy with PDE5i, NO-donors and Citrulline, adapted from my comment:
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What does NAC do?
It’s a little complicated to explain easily, but I will try.
Tl;dr (shortest possible explanation)
NAC increases NO availability, and that means you get better EQ.
Longer explanation:
Nitric Oxide (NO) is responsible for causing and maintaining the smooth muscle relaxation in an erection. NO activates soluble guanylate cyclase sGC in smooth muscle cells, increasing cGMP levels (cyclic guanosine monophosphate, a messenger molecule). Elevated cGMP leads to smooth muscle relaxation, vasodilation, increased blood flow, and erection. Think of NO as a “trigger signal” for smooth muscle relaxation. Pathway:
Nitric Oxide (NO) Production → Guanylate Cyclase Activation → Increased cGMP → Smooth Muscle Relaxation → Vasodilation → Erection.
Footnote: When people with heart disease get “nitroglycerin” pills to put on their tongue in case they get angina, the job of the nitro is to supply a quick peak of NO, causing a rapid vasodilation in the blood vessels around the heart (and elsewhere, of course).
Reactive Oxygen Species (ROS) are chemically reactive molecules containing oxygen — produced mainly by the metabolism in mitochondria, especially faulty mitochondria (common in metabolic syndrome, diabetes, etc). ROS can react with NO to form peroxynitrite, reducing NO bioavailability, which of course impairs vasodilation. (They also generally fuck up endothelial tissue and also cause cancer etc, but that’s not the central point I’m making.)
NO + ROS → Peroxynitrite → less NO to go into the previously described pathway.
NAC is a precursor to Glutathione, one of the body’s most potent antioxidants, whose job it is to take care of ROS before they cause damage. Lower ROS levels mean less NO is converted to peroxynitrite, preserving NO availability for vasodilation.
NAC is similar in this respect to a PDE5-inhibitor, whose job it is to turn off the break-down of cGMP. By lowering ROS, you maintain NO levels higher, resulting in better production of cGMP and therefore better EQ.
NAC increases NO availability by reducing oxidative degradation, whereas PDE5 inhibitors work downstream by preventing cGMP breakdown. They act at different points in the NO-cGMP pathway but have complementary -synergistic effects.
It works best if taken together with NO-donors, PDE5i, and Citrulline. They are all synergistic.
Let’s look at Arginine and Citrulline next:
Arginine is a direct precursor for nitric oxide (NO). The enzyme nitric oxide synthase (NOS) converts L-arginine into NO and citrulline as a byproduct.
L-Arginine + NOS → Nitric Oxide (NO) + L-Citrulline.
L-Citrulline is basically a better delivery vehicle of L-Arginine: L-Citrulline → (converted in the kidneys) → L-Arginine. It’s better because it does not get metabolized as fast.
Arg + Cit → More NO → More cGMP production → Greater smooth muscle relaxation → Improved blood flow → Better erection quality.
A PDE5i such as Viagra or Cialis works by inhibiting the enzyme that breaks down cGMP.
So, basically, by taking the cocktail of a direct NO donor such as beets + NO precursors such as Cit & Arg + a PDE5i + NAC, you make sure there is an ample supply of NO to stimulate cGMP production, and you also prevent cGMP break-down. Thereby, you max out your EQ.
Drawbacks, you ask? Well, beets will make your pee purple. No, but seriously, the most important drawback is that all of these taken together will tend to decrease your blood pressure significantly. I’m currently starving myself by fasting every other day, resulting in low BP, so if I take this cocktail I can get a little tired and dizzy. If your BP is low to begin with, proceed with caution and start with low doses and work your way up. You don’t want to pass out — that’s not a good way to end a date.
Sorry for the biochem, but it’s the only way I know to explain what NAC does with respect to erections.
A long footnote singing the praise of NAC as a supplement in general:
I haven’t mentioned it other than as a side note, but NAC is one of those supplements that have a broad scope of beneficial effects in the body. In the brain, which is densely populated with mitochondria, NAC’s neuroprotective properties are nothing to sneeze at. Individuals with metabolic syndrome (which I have, or at least used to have before I got myself together) often experience mitochondrial dysfunction, resulting in elevated oxidative stress. This oxidative stress, driven by an overproduction of reactive oxygen species, contributes to low-grade neuroinflammation. Research increasingly supports the hypothesis that this neuroinflammatory state plays a key role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s, as well as mood disorders like depression and anxiety (both of which I suffer from, btw). NAC, by boosting glutathione levels and reducing ROS, helps protect astrocytes (the immune system of the brain) and other neural cells from oxidative damage, thus mitigating some of the detrimental effects associated with metabolic syndrome in the brain. I have taken NAC for this reason for a few years now, and it’s made a very significant improvement to my symptoms of depression. It has similarly protective effects in the liver, which is also densely packed with mitochondria and intimately involved in the metabolic syndrome.
/Karl — over and out.
ps. Thanks u/Semtex7 for having a look at my comment to check that I remembered the biochem correctly. (Semtex is the dude I go to whenever I feel the slightest bit insecure about biochemistry. He is a walking encyclopedia of erection-related biochem, as you might have noticed if you read his posts.)