Is There Any Doubt Left that Propionic Acid is a Cause of Autism? Apparently not

I first started to write about autism and propionic acid (PPA) not long after creating this blog, back in the fall of 2016.  In January 2017, I described to you some of the work of Dr. Derrick MacFabe, which as particularly fascinated me for well over a decade.  For many years now, Dr. MacFabe has been publishing research showing that abnormally high levels of this ordinarily beneficial short-chain fatty acid adversely affect the developing brain, resulting in autistic –like behavior (in rodents).  Dr. M has many times injected PPA directly into the blood stream in rats and found that doing so induces cognitive deficits, repetitive behaviors, impaired social interactions, abnormal motor movements, ASD-like neurochemical changes and abnormal levels of inflammation.

Then, just a couple of months ago, I described to you research out of the University of  Central Florida, wherein scientists introduced, in vitro, PPA to human neural stem cells  and found that PPA caused the stem cells to become glial cells (the immune cells of the brain – as opposed to neurons) at a greatly increased rate.[i]  They propose a hypothesis that PPA exposure during fetal gestation – during the earliest stages of brain development – leads to abnormal brain connectivity and increased brain inflammation.

It’s important to remember that proprionic acid is commonly used as a food preservative.  Thus, maternal exposure  – between diet and bacterial dysbiosis – has increased over the years, and yes, PPA can pass into both the brain (through the blood-brain barrier) and the placental barrier.

At this point, the evidence that PPA plays a role in the pathogenesis of at least some cases of autism is so overwhelming that it appears to be considered accepted fact…which was news to me.  In a newly published paper, the authors state emphatically:  “…we evaluated the consequences of PPA (one of the factors which provokes autism) on social and anxiety-related behavior…”[ii]   There is no “may provoke” in that sentence.

These authors state that it has been proven that individuals with autism have “…increased levels of toxin-generating enteric bacteria and short-chain fatty acids, produced by these bacteria…Excessive levels of PPA can produce adverse effects, including developmental delay, mitochondrial dysfunction, oxidative stress, and other metabolic and immune reactions.”  Also, it is accepted as fact that “PPA readily crosses the gut-brain barrier, and affects functional brain networks, provoking the changes in neurotransmitter synthesis, neuro-transmission, brain signaling and mitochondrial function.”

Previous research has also shown that in rodents, chronic exposure to high levels of PPA affects social skills, cognitive flexibility (i.e. rigidity) and other alterations observed in autism.

In this study, the scientists were looking to discover whether or not a one-off, acute dose of only a small amount of PPA would be enough to affect the brain and behavior of the rodents and if so, how.  Specifically, re: the brain, they were looking in detail at the effects on the amygdala, which plays a key role in social behavior, social communication, eye gaze, attachment behavior, emotional memory and emotional processing…so obviously important in determining autistic behaviors.  Their findings were remarkable – and depressing:  “Our experiments revealed that not only chronic treatment, but also acute…injection of low dose of PPA is sufficient to provide the decrease of social motivation…”

Even worse, one dose of PPA led to mild neurobehavioral changes plus significant changes to the amygdala, including alterations to the populations of neurons (mildly) and glial cells (greatly).  Postmortem examinations of the brains of those with autism have shown similar changes, including excessive glial cell proliferation and subsequent high levels of proinflammatory cytokines. That is – the immune system of the brain is activated leading to inflammation of that organ.

To sum up, their data supports the findings of other researchers, including Dr. MacFabe, and indicates that “…even acute administration of low dose of PPA produces significant decrease of social motivation.  Behavioral changes are associated with significant modifications in amygdala’s structure/ultrastructure…”

The authors point out that difficulty metabolizing PPA is more common than previously recognized, and many of these people have cognitive impairments, movement disorders, and seizures.

What causes this potentially disastrous rise in PPA?  As I mentioned in my last post on the subject (and earlier in this one), maternal dysbiosis and food intake may play a part.  Early-life microbiome alterations, must be considered: antibiotics?  Lack of breast feeding?  C-sections?  I don’t think we know all the answers as yet.  But certainly, it seems to me that the evidence is solid enough now to confirm, as these authors state, that this is one of the causes of autism.

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[i] Abdelli, LS, Samsam, A, Naser, SA. Propionic acid induces gliosis and neuro-inflammation through  modulation of PTEN/AKT pathway in autism spectrum disorders.  Scientific Reports. 2019. 9(8824).  doi.org/10.1038/s41598-019-45348-z

[ii] Lobzhanidze, G, Lordkipanidze, T, Zhvania, M, Japaridze, N, Pochkidze, N, Gasimov, E. Rzaev, F. Effect of propionic acid on the morphology of the amygdala in adolexcent male rats and their behavior. Micron. 2019;125.

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