As a new homeowner and a newbie starting my subtropical fruit collection, I am eagerly awaiting all of the fruits I will finally get try try. I'm particularly eager to try the annona fruits, and am happy to have 4 sapling pawpaws of good varietals in my collection. Then, browsing the forum, I found a post warning of pawpaw neurotoxicity. As a scientist, I then spent the next 5 hours of my life fervorously searches in google scholar learning everything I could learn about the subject. There is a good synthesis of all the data available, but it definitely takes a LOT of time digging up this information from obscure places, and some knowledge of pharmacy and bioavailability. I would like to share my findings here for anyone who would like to know. For those who do not wish to read: Cherimoya, Atemoya, Sugar Apple, and Biriba *flesh* is rather benign, consuming soursop leaf tea from *dry* leaves is probably benign, annonacins will not give you Parkinsons (but if you have parkinsons, it may make your symptoms MUCH worse), and think critically about how much risk you're willing to take to eat this fruit.
All plants have some mechanism for preventing themselves from being eaten by undesirable things, and bugs are particularly pestilent. Natural pesticides are found in nearly all plants. Annona plants have evolved annonacins and similar groups of chemicals as their chosen pesticides. Pawpaw extract was a hot topic for a little while for being the next natural & organic pesticide, with patents granted
http://www.pawpawresearch.com/botanical-2002.html. However, these plants generally also want us mammals to eat their fruits, and us mammals have managed to be quite tolerant of natural pesticides in reasonable doses.
Simon put together an EXCELLENT review of the literature on his parkinson’s blog:
https://scienceofparkinsons.com/2017/12/16/paq/comment-page-1/?unapproved=24905&moderation-hash=e85986022f83b02e21abe8bad7b2ffa3#comment-24905. He provides links to all of the scientific literature, and I encourage you all to read it (he is a fun writer!). You can also see my reply to Simon at the bottom of that page. I’ll be summarizing some of his blog and my response here.
The dilemma with annonacins and human health was first conceived in the 1999 paper by Caparros-Lefebvre, where they found that 80% of people in their study with Parkinsons in Guatemala had a very bad form of it, which doesn’t respond to treatment. Compared to USA and Europe, these bad form of Parkinsons were relatively unlikely among those with Parkinsons (only ~30% of people). They hypothesized a reason for this was due to consumption of Soursop fruit and tea. It was then found that these toxins are surprisingly good at killing neurons when directly applied to nervous tissue compared to common lab standard toxins.
Simon continues on with his article about positive effects of other Annona chemicals for parkinsons. However, there is more to the annonacin story.
Pomper et al. looked at the toxicity of soursop, cherimoya, pawpaw varietals, peach, and banana:
https://pubs.acs.org/doi/abs/10.1021/jf9018239. They measured toxicity by finding the amount of extract needed to kill 50% of a brine shrimp population. Among many things, they found:
1) that cherimoya flesh was 100x less toxic than soursop, and is almost as benign as peaches (yay!).
2) that some pawpaws were 100x more toxic than soursop, and that some pawpaws were about as toxic as soursop.
3) Drying the pawpaw fruit reduced the toxicity by ~100x. They did not comment on why (nor did they interpret their results correctly…ugh). If it is real that this toxicity reduction occurs, a *guess* at this mechanism are that the toxins crystallized and became significantly less bioavailable (a routine scenario in pharmacology).
Thanks to Nullzero for finding this awesome science poster by Smith et al. on Annona neurotoxin concentrations!
https://www.scribd.com/document/314499988/FDA-Annona. There is indeed ~100x more total ug/g concentration of annonacin+squamocin in soursop compared to Atemoya and Sugar apple (presumably, cherimoya has a similar concetration to atemoya and sugar apple). They used overlese pawpaws in this study (
https://pubs.acs.org/doi/full/10.1021/jf504500g?src=recsys), which was found to have ~10x more annonacin in this case. So, Pomper’s methodology, measurements, and conclusions seem to generally agree to the measured annonacin by Smith et al.
The amount of annonacin in some pawpaws is truly staggering! But, it’s this dramatic figure which likely proves the point that this is rather well tolerated by much of the population. A homeowner binge-eating fruit from their pawpaw tree could end up eating ~3lbs of pawpaw in a day (or 3~5 pawpaw fruits). Assuming a typical soursop weighs 6lbs, that’s roughly like eating 50 soursop fruits in a single day! A single tree could yield 30~80 pounds of fruit, so that could amass to eating the equivalent of 500~1300 soursops per tree. That’s a dose higher than eating a full 6lbs of soursop every day *and* drinking the soursop leaf tea every day for a year, but administered all in 1~2 months! If that’s the case, fruit fanatics and pawpaw lovers in the american midwest should be suffering just as much or more than the people of french west indies due to the Indiana banana!
One of the concluding points of that paper was that there have not yet been any links between consumption of pawpaw and the incidence rates of Parkinsons vs. Parkinsonisms. They point to another paper in the concluding remarks, and suggest that people who seem to be affected by this toxin are likely genetically predisposed. This is perhaps backed up during a presentation by the same authors with an acknowledgement of Caparros-Lefebvre et al, who estimated in 2005 that there are approximately 640 cases of parkinsons and parkinsonisms combined in Guadeloupe out of a population of 420,000, which is an incidence rate that is identical to the united states and europe.
http://www.pawpaw.kysu.edu/PDF/AcetoUpdate3.pdf. That is, there weren’t more people with Parkinson’s in the countries of concern, simply those that had Parkinson’s were worse. That paper amazingly also found that younger folks who had parkinsonism symptoms managed to reverse symptoms (presumably down to regular parkinsons) when they stopped annona products. It seems that this toxin doesn’t cause parkinsons, but it seems like there is clear evidence that it could make existing parkinsons worse.
It is extremely concerning that Champy found in 2004 that *injecting* rats for 1 month with annonacin induced neurodegeneration of basal ganglia and mesencephalon. However, it is again pointed out by the authors that this does not investigate bioavailability upon digestion
http://www.pawpaw.kysu.edu/PDF/AcetoUpdate3.pdf; 1 month is really dramatic, and I would imagine that people would have quite a bad reaction if it damaged their nervous system that hard every month.
As for Soursop tea, the concentration of annonacin is ~300ug/g:
https://www.sciencedirect.com/science/article/pii/S0102695X15002331. A typical serving of dry leaf tea is ~2g, providing a dose of 600ug. If this is dried tea, and assuming that the dried tea is 100x less toxic than fresh tea due to the relationship seen in Pomper’s data remaining true, that’s roughly equivalent to consuming 6ug. That’s a trivial dose.
For getting sick from an acute dose (ingesting seeds), I note that the fruit flesh of soursop and pawpaws seem to have more ug/g of annonacin than an atemoya seed, but atemoya seeds have a MASSIVE concentration of squamocin (14,200ug/g), whereas squamocin concentrations are low in the flesh (<200ug/mg)
https://www.scribd.com/document/314499988/FDA-Annona. All that said, I believe that there is enough evidence to say that this can make certain people with parkinsons develop worse symptoms. Further, it is not known if there are other neurological conditions that this could negatively affect. How about people who have a genetic predisposition to alzheimers or dementia? What about just simple anxiety? Fibromyalgia? Schizophrenia?
Unlike twilight plea on the Parkinson’s blog, I’ve decided for myself that I have enough health problems, and pawpaw is unfortunately too risky to grow and consume.

This may be a conservative approach, and I suspect that most could tolerate annonacin without any problem. I may partake on occasion, but I’ll be giving my trees away. However, I will be enjoying cherimoya, atemoya, sugar apple, and biriba without worry

. I’ll just have to figure out how in the world I’ll GROW those things…