
Spike in Autism May Be Linked to Preservative in Processed Foods, Study Suggests - jhalt
https://www.forbes.com/sites/robertglatter/2019/06/28/spike-in-autism-may-be-linked-to-preservative-in-processed-foods-study-suggests/
======
nilsb
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.

~~~
typeformer
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.

~~~
olliej
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.

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etaioinshrdlu
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?

~~~
ex3xu
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...](https://www.foundationalmedicinereview.com/blog/the-link-between-
propionic-acidemia-and-autism-spectrum-disorder-may-offer-etiological-clues/)

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

[2]:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573175/pdf/978...](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573175/pdf/978-3-642-32442-0_Chapter_143.pdf)

[3]:
[https://www.sciencedirect.com/science/article/pii/S109671921...](https://www.sciencedirect.com/science/article/pii/S1096719216301779)

------
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...](https://www.foundationalmedicinereview.com/blog/the-link-between-
propionic-acidemia-and-autism-spectrum-disorder-may-offer-etiological-clues/)

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...](https://en.wikipedia.org/wiki/Albert_Einstein%27s_brain#Glial_cells)

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](https://en.wikipedia.org/wiki/Propionic_acidemia)
the incidence of PA is 1/3500 and from
[https://en.wikipedia.org/wiki/Autism_spectrum](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.

------
ac29
Should change the link to the actual, open access paper:
[https://www.nature.com/articles/s41598-019-45348-z](https://www.nature.com/articles/s41598-019-45348-z)

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

------
sologoub
Interesting how it’s not listed for food use in EU:
[https://echa.europa.eu/substance-
information/-/substanceinfo...](https://echa.europa.eu/substance-
information/-/substanceinfo/100.001.070)

~~~
sologoub
Never mind, it’s classifies separately in additives:
[https://www.efsa.europa.eu/en/efsajournal/pub/3779](https://www.efsa.europa.eu/en/efsajournal/pub/3779)

------
pointillistic
How and if people got autism before processed foods?

~~~
tasty_freeze
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.

------
rralian
Even if this isn't rock-solid I'd rather see a backlash against processed
foods than against vaccines.

~~~
aklemm
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.

~~~
UnFleshedOne
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 :)).

~~~
aklemm
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.

~~~
UnFleshedOne
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.

