N-Acetylcysteine: Beyond Paracetamol Overdose
May 5, 2016
I asked David Aiello, President BioAdvantex Pharma Inc.: of all the molecules, why study and productise N-acetylcysteine?
“That makes me think of another question, why did you marry that woman? You become fascinated with something, and your mind sees forward. I saw this as a huge business and scientific project with such a broad scope to help people. We didn't even understand the scope way back then.”
Paracetamol-induced acute liver failure.
In the US and UK, paracetamol (acetaminophen) toxicity is the most common cause of acute liver failure. When taken in normal therapeutic doses, paracetamol is safe.
The cytochrome P450 enzymes convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione. In cases of overdose, the pathways become saturated, leading to more NAPQI. Liver supplies of glutathione become depleted, and NAPQI remains in its toxic form in the liver, reacting with cellular membrane molecules, resulting in widespread damage and death of liver cells.
Beyond Paracetamol Overdose.
Paracetamol is not the only thing that can cause oxidative stress and cell death. Inflammation and oxidative stress are almost synonymous, and we measure both in the testing we do. Urinary P-Hydroxyphenyllactate on an organic acids test is a marker of cell turnover, and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) is a marker of oxidative damage to the guanine of DNA.
Enter N-acetylcysteine.
The availability of the sulfur-containing amino acid cysteine is known to be the rate-limiting substrate for glutathione resynthesis. L-cysteine is not safe to take as a supplement in high doses, what you want is the N-acetylcysteine (NAC) form. NAC doesn’t encapsulate well because the minimum effective dose is too big to fit into a capsule, and even if it did fit, the molecule would oxidise and fall apart. David's team at BioAdvantex have solved these problems by creating PharmaNAC, a large effervescent tablet sealed into a nitrogen filled blister pack.
It's important to understand that exercise is itself an antioxidant and athletes should proceed with caution before supplementing with antioxidants without testing. Context matters.
Here’s the outline of this interview with David Aiello
0:00:35 David was trained in immunology at the Stanford Herzenberg Lab.
0:01:03 He wanted to create a product that was relevant, made the right way and given at the right dose.
0:01:34 BioAdvantex have done 12 or 13 clinical trials in breathing, immunity, oxidative stress and mental health.
0:02:46 NAC is the standard of care of acetaminophen toxicity.
0:03:19 80,000 people every year are affected.
0:03:54 NAPQI.
0:04:13 Making glutathione requires glycine, glutamate and cysteine.
0:04:28 Almost every protein is less than 2% cysteine by weight.
0:05:56 You don't want L-cysteine.
0:07:30 NAC is easily oxidised.
0:08:55 Hydrogen sulfide is one of the degradation products of NAC.
0:09:20 Humans can detect H2S at 6 ppb.
0:09:31 There are 7 other degradation pathways.
0:11:43 NAC placebo pills.
0:15:51 Taking NAC is NOT like pouring water on the fire.
0:18:56 There's about a three-hour gap between when you take cysteine, and when it shows up in your blood, then there's about another three-hour gap until an increase in glutathione.
0:20:07 The liver is main store of cysteine, and also there’s cysteinylglycine in the blood.
0:28:30 Logging food and supplement intake.
0:29:05 Grace Liu.
0:29:10 GAD1 mutation.
0:29:47 The cystine-glutamate antiporter (xCT).
0:35:18 Depression, ruminations and PTSD.
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