[ex3xu]

The preservative in question is propionic acid (PPA):

> In the current study, Saleh Naser, PhD and her team at UCF found that when neural stem cells were exposed to high levels of PPA, the neurons incurred multiple changes resulting in cellular damage and inflammation. One of the major effects of PPA they noted was the overproduction of glial cells, the protective outer cells making up the sheath covering neurons, with a corresponding reduction in the number of neurons themselves.

Here's another article covering some more of the etiological history behind this finding: https://www.foundationalmedicinereview.com/blog/the-link-bet...

On a side note: at the risk of both being slightly off topic and/or spreading bad science, there was that controversial assessment of Einstein's brain which noted that he had a higher proportion of glial cells than other brains studied (see Wikipedia for potential issues with the findings): https://en.wikipedia.org/wiki/Albert_Einstein%27s_brain#Glia...

I'm noting this only as a layman's speculation about glial cell concentration as a potential mechanism behind the phenomenon of higher intelligence and occasionally savant-like abilities in some of the high-functioning ASD population.

[gowld]

Were the "high levels" of PPA food level, or 100x total human lifetime exposure?

This is very preliminary speculative science that shouldn't be oversold.

[ex3xu]

The elevated levels of PPA are linked to a dysbiotic gut bacteria imbalance, with ASD children exhibiting more bacteria that produce PPA. I'd imagine if you're not eating PPA in excess of your body's ability to metabolize it you're fine.

Regarding the second half of your comment, I'll cite from the etiology article I linked:

> In the concluding sentences of their analysis, Witters and Debold make their strongest argument for the connection between propionic acid and ASD by observing that, given the rates of PA [proprionic acidemia] and of ASD occurrence in the general population, the probability of there being no link between the two pathologies is 4.34 in 10 trillion. Put differently, comorbid incidences of PA and ASD are far more common than should be expected between two unrelated diseases, meaning that there is most likely a link between the two.

[gus_massa]

How did they make the calculation? From the same article:

> Research produced in 2016 by Drs Peter Witters and Eric Debold corroborates the link between the two conditions in a longitudinal study of 12 patients investigating blood metabolite balance in patients with PA and behavioral disruptions.

From https://en.wikipedia.org/wiki/Propionic_acidemia the incidence of PA is 1/3500 and from https://en.wikipedia.org/wiki/Autism_spectrum the incidence of ASD is 1/100, so assuming independence it's expected that you can find in the word 7000000000/3500/100 = 20000 person with both illness, and they are analyzing a group of 12 patients with PA and only 5 have clear ASD and other 3 have only some symptoms of ASD.

[ex3xu]

You're right that it's a low sample size, and the authors themselves do warn that diagnostic rates of ASD in children may be inflated:

> With the increasing reported frequency of ASD in the pedi-atric population one cannot rule out a possible coincidence of the diagnosis of ASD in patients with propionic acidemia.

Regarding the calculation, Wikipedia says 1 in 35000 for PA the US, rather than 3500, and the researchers use an incidence rate of .5% for autism rather than 1%. So the number of people is 1000, not 20000. The researchers say they're calculating off a 5/8 ASD/PA incidence rate, so the calculation is something like (1000/7 billion)^5*(some negligible amount)^3.

[gus_massa]

* 1000 cases in the word instead of 20000

OK. I'm fine with that. My idea was to show that if we assume independence, it is not difficult that someone can find 12 cases with both illness.

* About the calculation:

Is that in the paper? [I assume that "some negligible amount" means "close to 1".]

This calculation is the probability that if you pick 12 persons at random from the whole word population you find a group with 5 person with PA+ASD and 3 PA+dubiousASD and 4 with PA+noASD. There is a missing (1-epsilon)^4 that doesn't matter. And you need to add some combinatorial number, like (12! / 5! 3! 4!) ~= 30000.

Even assuming that "1-epsilon" and "some negligible amount" are equal to 1, the result of your calculation is 6E-35 that is much much much smaller than the reported result 4E-13 (after using the combinatorial number you get or 2E-30 that is still smaller). So they clearly used another calculation.

Anyway, your calculation is wrong because you can't use the probabilities of the general population in a calculation of a group that you cherrypicked.

[ex3xu]

They mention the 5 ASD out of 8 PA sample size, and they explicitly cite the .005 rate of ASD, but I think their PA incidence number is different than the one available on Wikipedia, and I couldn't find it in the paper so that may be where the discrepancy is from. I may be wrong but I don't think we need the combinatorics for this particular calculation since their calculation is trying to disprove that these events are independent rather than calculate the joint conditional probability. Obviously I can't comment on whether any cherry picking was done, or if these just happen to be the available sample of available children with this rare metabolic disorder. I'd agree and I think the authors of the study would agree that the sample size is too small for any definitive conclusions, but I think the body of evidence when considering the rest of the available PPA studies make a reasonable case for it to be a finding of interest.

[nickpsecurity]

I was wondering about that, too. Inspired in part by articles like this:

https://www.scientificamerican.com/article/the-root-of-thoug...

[ex3xu]

Thanks for sharing, I'll have to look into that book sometime. Also a real throwback to see Jonah Lehrer's name on a piece of scientific journalism.

Looks like in 2018 there's a few [0] interesting [1] papers [2] on the link between senescent glial cells and neurodegeneration, which I think would support a theory of glial cells playing some role in cognition. Seems to be a fairly active area of research.

[0]: https://www.nature.com/articles/s41586-018-0543-y

[1]: https://www.researchgate.net/profile/Jay_Penney/publication/...

[2]: https://www.sciencedirect.com/science/article/pii/S089662731...