"Pawpaw fruit contains high concentrations of annonacin, which is toxic to nerve cells. In addition there have been case reports of possibly related nerve toxicity. Therefore, chronic use should be avoided."
Probably not a huge issue as long as you only eat it every so often. But I wonder about the possibility of producing varieties of pawpaw (or soursop or other related Annonas) that don't produce annonacin. Probably could be done with genetic engineering, or much more slowly with selective breeding.
Given that there are places where people consume Annonas very often, and that this may lead to alarmingly high rates of parkinsonism [1], this could be considered an effective public health intervention.
"The paucity of adequate studies, particularly related to long‐term use of A. muricata supplements, currently does not allow the establishment of a safe intake level."
"Cognitive performance assessed with the MDRS worsens above a cumulative consumption threshold of 0.2 fruit‐years of Annonaceae fruit/juice (ie, one fruit every 5 days for 1 year) or with consumption of any quantity of Annonaceae herbal tea."
"one fruit every 5 days for 1 year" is far above what I would consider occasional consumption.
Pawpaws are not in season for very long, and do not keep well. Unless you are canning or otherwise preserving them, a dozen per year is probably a high estimate for people who live in areas where they grow.
Relatives such as the soursop are available year-round in tropical areas, but if you limit your intake to the pawpaw only, eating a handful when they are ripe each year probably won't hurt you.
I lived in Maryland near a forest with a large number of wild pawpaw trees that produced an enormous amount of fruit, and was very into foraging as a hobby, and I don't think I ever ate more than six or seven in a single season.
I don't know about Parkinson's, but acetogenins[1] work by down regulating ATP production in mitochondria. This mechanism has been studied for potential applications from cancer treatment to pesticides.[2]
In addition to what other commenters have noted about difficulty eating enough quantity, this is not a commercial fruit and thus no standards for what you'll get. There are a variety of on-going breeding programs for commercial pawpaws. This is just one more item on the checklist to successfully selectively breed out. If you see pawpaws in the supermarket its unlikely current studies will apply to it. Breeders understanding how to breed for and against the annonacin content is actually very high on their list of priorities, not for eating, but the high annonacin makes pawpaws an excellent deer and mosquito repellent, and is being studied as a source for chemo-therapy and other drugs. https://pubmed.ncbi.nlm.nih.gov/18598079/ I suspect these will be the first commercial use cases for the pawpaw as they use the trees bark, leaves, and skins of the fruit and not the fragile flesh.
Fortunately you’ve gotta work pretty hard for chronic use, since it’s only available for a couple months out of the year. This is definitely a concern if they ever do develop a pawpaw industry, though.
The person you’re replying to probably assumed (as I did) that the article was about papaya, which is called pawpaw in some parts of the world. They will probably be relieved (as am I) to find out it’s about an unrelated fruit.
Given that there are places where people consume Annonas very often, and that this may lead to alarmingly high rates of parkinsonism [1], this could be considered an effective public health intervention.
[1] https://pubmed.ncbi.nlm.nih.gov/10440304/