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Spike in Autism May Be Linked to Preservative in Processed Foods, Study Suggests (forbes.com)
71 points by jhalt 2552 days ago
7 comments

Or maybe the "rise" in autism rates is due to the fact that our diagnostic tools have become more advanced in the past 20 years which has resulted in more people getting their diagnoses.

In particular older people (i.e. 30+) are getting diagnosed just now because doctors previously didn't know what they were looking for.

Do you not think that the highly competent researchers didn't account for this very well know the rise in the data. Their findings here are novel, critically important and are related to a host of other works revealing the intricate links between the gut biome and neurobiology previously unknown. Parkinsons is another disease that recently has been shown to potentially be related to changes in the gut biome.
The highly competent researchers have to answer the question:

“why have the number of children diagnosed with ASD increased?”

They can’t “control” for changing diagnostic rules: that would literally mean “controlling” the exact thing they’re trying to analyze.

What they are doing (as medicinal chemists?) is identify a compound(s) that correlate with the increased diagnoses.

Another study might investigate the method by which ASD is diagnosed - eg applying modern diagnoses to old diagnoses, and vice versa.

There are also definitely sociological factors that could contribute - in the US specialized educational support for kids diagnosed with ASD is much better funded per-capita than most other learning difficulties, so there is a clear advantage to pushing for (or shopping around for) a dr that will give an ASD diagnosis - eg If you can get FAS diagnoses as ASD you’ll get much more financial and educational support.

Personally I expect there to be a parental age component (which would explain the increased prevalence, relative to overall average, of ASD in middle and upper class Caucasian families, at least in the US).

I suspect however it’s going to be a combination of all those factors, and probably a few more for good measure.

I've seen brilliant people make mistakes and not recognize it for decades. Consider the Intel processor Spectre vulnerabilities. Being smart doesn't make the logic correct
Or if we want to keep guessing instead of doing thorough long-term research, a more likely answer is that it's a mixture of many things.
I'm no doctor or biochemist but propionic acid seems way too natural and common a chemical to be a likely cause. It's not the first preservative I'd investigate either. For example, why not investigate benzoic acid?
I can't speak about benzoic acid, but the article notes that propionic acid is the most common compound produced by bacteria unique to the gut microbiomes of ASD children:

>Previous studies have demonstrated increased levels of PPA, a short chain fatty acid (SCFA), in the feces of children with ASD; we also know that the gut microbiome in these children is also quite distinct in terms of the type of bacteria that inhabit their intestines.

>Clostridia, Bacteriodetes, and Desulfovibrio bacteria are unique to patients with ASD. What’s interesting is that these bacteria are also known to be fermenters of carbohydrates that produce PPA, and other SCFAs as well. Ironically, while PPA is the most common compound produced by bacteria in ASD patients, it is also widely used in the food industry as a preservative due to its ability to inhibit grown of fungi (mold).

So following up I found an article on the etiological history of the PPA link [0]. From that article, there was a 2008 study of PPA injections in rats (spoiler, observed to cause ASD-like symptoms)[1], and a case study in 2012 of an ASD child with propionic acidemia, a rare metabolic condition that affects PPA metabolism [2], which led to more recent studies establishing a connection between behavioral disruptions and propionic acidemia, even in children who did not meet the diagnostic criteria for ASD [3].

ASD can also exhibit GI tract issues like constipation and IBS as symptoms, which would have supported some kind of gut microbiome hypothesis. Regarding what you're saying about how common PPA is, one research group speculates a "two-hit" mechanism behind ASD:

>Al-Owain’s group suggests that PA may thus act as one of the drivers of developing ASD under the two-hit model of ASD pathology, which posits that two separate factors must be present before ASD is developed. Under this model, one problem—such as PA in isolation—is insufficient to cause ASD, but when paired with another problem—such as another metabolic disorder affecting the gut-brain axis, like biotinidase deficiency—the combined detrimental effects of the two pathologies can cause ASD.

[0]: https://www.foundationalmedicinereview.com/blog/the-link-bet...

[1]: https://www.ncbi.nlm.nih.gov/pubmed/18395759

[2]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573175/pdf/978...

[3]: https://www.sciencedirect.com/science/article/pii/S109671921...

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.

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.

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.

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.

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.

* 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.

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

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

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...

Should change the link to the actual, open access paper: https://www.nature.com/articles/s41598-019-45348-z

The Forbes summary contains some things that appear to be misunderstandings at best.

Interesting how it’s not listed for food use in EU: https://echa.europa.eu/substance-information/-/substanceinfo...
Never mind, it’s classifies separately in additives: https://www.efsa.europa.eu/en/efsajournal/pub/3779
How and if people got autism before processed foods?
You don't directly say it, so maybe I'm reading you wrong, but you seem to be suggesting that this hypothesis is nonsense because autism existed before this preservative was used.

The article isn't saying that the only cause of autism is the preservative. It is suggesting maybe part of the increase is due to this preservative.

Although people died before cars existed, it doesn't mean that cars aren't the cause of some deaths today.

While propionic acid is used artificially as a preservative, it is a naturally occuring byproduct of fermentation of certain kinds of carbohydrates.

The article notes the link between certain kinds of bacteria in ASD children that overproduce PPA as a byproduct.

Even if this isn't rock-solid I'd rather see a backlash against processed foods than against vaccines.
Thinking about this a lot lately. Biggest thing is getting people ready to put in the time needed to process food themselves. Reducing packaging and eating better food takes A LOT of time, and I don't think anyone except the portion of us that like to hunt recipes and cook are ready for that.
Basic cooking taking a lot of time is a myth. Sure, if you don't have a kitchen and a fridge at all, that is a problem.

And I suppose if you don't know how to turn on the oven then the whole endeavor looks like marathon running (and winning) looks to a bed-ridden person. But your goal is not to be a professional chief in 5 star restaurant, it is to cook some soup from whatever is in the fridge, boil some pasta, fry some eggs and chop up some greens. Cook enough to last a week and you are set.

Ask your first generation immigrant coworker to teach you what they cook (or ask them to introduce you to their parents :)).

It is absolutely not a myth. Every convenience you see represents time and "value" added by the food industry making it easier to put food into yourself. Of course it comes at the cost of health and the health of the environment.

Compare a fresh head of broccoli to a package frozen; with fresh, you've got to clean it, trim it, clean up after your trimming, and finally cook it. With frozen, snip a bag open and you're on your way. Much simpler, but of course now you're using something that was shipped from afar, wrapped in plastic, and held in a freezer and it won't even taste as good when you're done!

Now compare ordering delivery from your phone. Compare shopping, storing, chopping, wiping up etc. to building a Blue Apron dinner. In terms of convenience, it's not even close. This is coming form someone who prepares 2-3 meals per day for my family.

That's the problem -- you are preparing 2-3 meals a day instead of two big pots once a week and simply reheating them for your meals. At this point time and effort investment starts being significant (you get to eat different freshly cooked food each day so it might be worth it, if that's your preference).

For example it took me 1-2h (including cleanup, but not counting shopping) to prepare 7 liter pot of stew from random veggies and some meat. It will last us whole week in lunches to take to work. Another day we'll make a pot of soup (our old one wasn't done yet) and that would be all dinners for a week. Takes 3 minutes to reheat each day, no delivery can beat that, unless you live above fast food place or something.

This is why I quit diet soda. I don't really want to drink some science experiment.
"The Radium Water Worked Fine Until His Jaw Came Off"

http://lateralscience.blogspot.com/2017/12/the-radium-water-...