Mitochondrial antioxidants and Annonaceous acetogenins (re: pawpaws)

Does anyone here have thoughts or experience with taking mitochondrial antioxidants (e.g. NAC or CoQ10) when consuming pawpaws or other Annona fruit?

The research seems pretty clear that the reason why annonaceous acetogenins cause progressive supranuclear palsy (atypical parkinson’s) is that they’re a mitochondrial complex I inhibitor. My non-scientific understanding is that they kill your brain cells by inhibiting their mitochondria and starving them of ATP.

But interestingly, the research also shows that ROS buildup within the mitochondria is a key part of the inhibition process, and that mitochondrial antioxidants might be able restore mitochondrial function enough to prevent cell death.

There are a lot of mitochondrial antioxidants, but I’ve personally been looking the most into NAC and CoQ10 – not because they’re the most powerful, but because their safety profiles are well understood. (See also: SkQ1.)

Articles about NAC

“Increased ROS concentrations caused by depletion of mitochondrial proteins led to activation of cell death signaling […] Importantly, elevated ROS levels were necessary to mediate AA005-induced cell death, in that N-acetyl-L-cysteine (NAC), an efficient antioxidant, largely suppressed the number of dead cells.”

A general overview of the pharmacology of NAC

Articles about CoQ10

“This model for sporadic tauopathies can also be used to screen potential drugs
that might interfere with the mechanism of action of energy depleting neurotoxins (e.g. Coenzyme Q10), or that affect microtubule dynamics.”

Here is another paper on CoQ10, in relation to preventing propofol toxicity. Apparently propofol is another mitochondrial complex 1 inhibitor, although I’m unclear on whether or not it’s inhibiting the mitochondria through the same mechanism of action:

Role of mitochondrial complex I and protective effect of CoQ10 supplementation in propofol induced cytotoxicity

There is also at least one paper claiming that soursop actually contains CoQ10, which is interesting.

So in short I have no idea whether or not either NAC or CoQ10 would be useful in trying to ameliorate any harm caused by Annonaceous acetogenins – either or both may actually be harmful! But Just trying to start a discussion on this and hopefully get some thoughts on folks who have either tried this or understand the science better, because I’ve never seen this discussed on the web (or Facebook) before.

I do think this is an important issue, since there was a recent fatal case of progressive supranuclear palsy (atypical parkinson’s) linked to someone who consuming only 30 pounds of these fruit per year:

Now before everyone spams this thread, I’ll just pre-emptively point out that this may not be a huge problem due to:

  • Annonaceous acetogenins having low bioavailability
  • The fruit containing antioxidants, which may ameliorate any mitochondria damage
  • The fruit containing a very high sugar content, which may ameliorate any mitochondria damage

That said, there is clearly still a lot that’s unknown here, and having a death linked to someone consuming only 30 pounds of fruit per year is somewhat alarming.

So if there were some sort of supplement that one could take during pawpaw season as an additional harm reduction strategy then that would be super interesting to me, and surely to others as well!


Annonacins are neurotoxins. They kill cells on contact.

1 Like

I don’t have a lot to add to this specific case, but there are plenty of cases in nutrition where a study shows a specific nutrient/chemical is dangerous when separated by itself, yet when combined with the other nutrients naturally present in said food its negative effects are, to some extent, counterbalanced.

The pawpaw has evolved in many ways to protect itself. The leaves taste bad and can be toxic. The flowers taste bad. And the fruit has some of these chemicals as well. However, at ripening they become sweet, edible, and tasty. It’s been theorized that megafauna ate the fruit and helped spread the seeds in their excrement. Usually over time these things evolve together and benefit from one another. It would make sense that at ripening the fruit becomes somewhat beneficial to the animal eating it.

Maybe pawpaws are the exception, but it’s an interesting question.