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Friday, 17 April 2015

Butyric Acid– my choice of short-chained fatty acid (SCFA), as a potential anti-inflammatory autism therapy


Stockholm in spring


Hot on the heels of the last post that showed that regulatory T cells (Tregs) may indeed be a useful target to treat inflammation in autism, today’s post is about the particular short chained fatty acid (SCFA) that I have chosen to treat it.


Based on my homework, I have chosen Butyric Acid.

Some of my posts do not lead to therapeutic interventions, but the posts on Treg and SCFA are going to lead to some good options, particularly for those with GI problems.

As usual with effective interventions, there are multiple possible modes of action. 

Since I have introduced epigenetics to this blog, I will also highlight a paper showing the epigenetic effects of Butyric Acid.  My real objective is to increase Tregs, as a means of shifting the balance between the proinflammatory IL-6 and the anti-inflammatory IL-10.

Monty, aged 11 with ASD, does not have GI problems and has a very mixed and healthy diet, so I have not really looked at the myriad of possible GI therapies.  However, in this blog we have seen that the integrity of the Blood Brain Barrier (BBB) is critical in autism and that, in fact, it has variable permeability (it can self-repair).  I suggest that increased permeability might lead to worsening behaviour and observed flare-ups/regressions.

We have also seen that the mechanisms controlling the BBB overlap with those governing the Intestinal Epithelial Barrier (the gut-blood barrier).

The SCFAs that appear to be able to repair the Intestinal Epithelial Barrier have been shown to be able to circulate throughout the body, reach, and then cross the Blood Brain Barrier.  As a result it is certainly plausible that increasing SCFAs and Tregs will benefit those both with, and without, GI problems.  What is clear from the research and anecdotal evidence is that those with ulcerative colitis (UC) do very much benefit.  People with UC will have a compromised Intestinal Epithelial Barrier.  Some people with autism may have both a slightly permeable Blood Brain Barrier and a compromised Intestinal Epithelial Barrier (leaky gut).

I have also established from the research that a moderate increase in Butyric Acid has many measurable good effects and for this reason it is already widely used as an additive in animal feed.  It results in more healthy chickens, with less inflammatory disease and measurably lower levels of e-coli and salmonella.  I expect there is also more meat and less fat.


First, Why Bother?

About 20% into my current autism investigation, one of Monty’s grandmothers suggested that I had now done enough and should stop.   Clearly I did not.  She also told me “just make sure he does not get violent, when he is older”.  As a retired doctor, she is aware of what the end result would be.

At the time I thought “easier said than done”.

A year or so later, I am able to control my son’s mood, anxiety and indeed occasional aggression.  It is not perfect, but it is about 80% perfect.

This makes a huge difference to daily life. 

We just returned from a week in Stockholm, Sweden.  We were on buses, trains, trams, boats, taxis and planes.  We were in museums, shops, cafes and restaurants.  Behaviour was “almost” perfect and with some “fine tuning”, it was actually big brother who was the troublesome one.

Grandma number two has just been reading the well-known book, "The Reason I Jump".

“Written by Naoki Higashida when he was only thirteen, this remarkable book explains the often baffling behaviour of autistic children and shows the way they think and feel - such as about the people around them, time and beauty, noise, and themselves. Naoki abundantly proves that autistic people do possess imagination, humour and empathy, but also makes clear, with great poignancy, how badly they need our compassion, patience and understanding.”

Yesterday, she told me all about why some people with autism self-injure.  It is just something they have to do and you just leave them to it; just make sure they do not do any serious damage.

As you might imagine, I will not be waiting in line to read such a book.

As I explained to Grandma, people with autism self-injure for mostly biological reasons and you can figure out many of them.  Then they will not self-injure.  They will then be happier and higher functioning. 

It also means that when they are full grown adults they will not pose a threat to their carers and develop such “complex needs” that they have to be institutionalized, at great emotional and financial cost.  I suppose Grandma number one had this in mind.

So why bother? because I can.



The epigenetic effects of butyrate

The following paper looks at the positive therapeutic effects of butyrate in terms of epigenetics.  In the paper on Tregs in the last post, the Harvard researchers were attributing some of these effects to the increase in Tregs.  I do not mind who is right, and quite possibly both groups are right.


Butyrate is a short chain fatty acid derived from the microbial fermentation of dietary fibers in the colon. In the last decade, multiple beneficial effects of butyrate at intestinal and extraintestinal level have been demonstrated. The mechanisms of action of butyrate are different and many of these involve an epigenetic regulation of gene expression through the inhibition of histone deacetylase. There is a growing interest in butyrate because its impact on epigenetic mechanisms will lead to more specific and efficacious therapeutic strategies for the prevention and treatment of different diseases ranging from genetic/metabolic conditions to neurological degenerative disorders. This review is focused on recent data regarding the epigenetic effects of butyrate with potential clinical implications in human medicine.









In later posts I will give more of the research evidence in favour of butyrate and you will see how chickens currently get better intestinal care than humans.

As suggested in the original post on Tregs and SCFAs, there will be different methods to raise Butyrate levels.  It can be achieved directly via supplementation, with sodium butyrate, and indirectly by adding a butyrate-producing bacteria, such as Clostridium Butyricum.  This is widely used in Asia as a probiotic, but is available elsewhere.








9 comments:

  1. Hi,
    Why sodium butyrate and not calcium magnesium butyrate (cal-mag butyrate)?
    Best regards,
    João Santos

    ReplyDelete
    Replies
    1. Hi João,

      Good question, and the same one appears on some Ulcerative Colitis forums. The answer is that the successful research was done using sodium butyrate, as is the large scale commercialization of this science (for animals).

      Here is a link to the promo website of one animal feed additive:-

      http://www.novyrate-gut-integrity.com/

      One issue is taste and smell. Butyrate compounds do not smell good. This has been solved by the animal feed people, buy making tiny granules that are coated and some are even extended release.

      It may be that calcium magnesium butyrate is equally effective, but it seems wise to start with the compound that was tested.

      The cleverest solution is probably the bacteria, so that you make your own butyrate. I suppose the animal feed people choose the most effective solution, for the least cost.

      Delete
  2. Sodium butyrate is a salt in which the cation is sodium. As for calcium-magnesium butyrate (they call it a "complex", but it appears to be a mixture of calcium butyrate and magnesium butyrate), you get both calcium and magnesium as cations.
    We want Butyric Acid and it only uses the anion from the salt (butyrate).
    I always keep sodium at a safe distance so I will give the calcium-magnesium butyrate "complex" a shot.
    João Santos

    ReplyDelete
    Replies
    1. The other thing you might consider is the MIYAIRI 588 bacteria.

      http://miyarisan.com/english_index.htm

      This will produce butyric acid and is well researched.

      It is available widely in Japan and worldwide via Ebay.

      There is also a comprehensive paper here:-

      http://acnfp.food.gov.uk/sites/default/files/mnt/drupal_data/sources/files/multimedia/pdfs/clostridiumbutyricumdossier.pdf

      It is sold as Miyarisan and Miyarisan Strong..

      For example here, for 1,000 tablets:-

      http://www.ebay.co.uk/itm/MIYARISAN-Strong-Miyarisan-1000-tablets-clostridium-butyricum-/281377365984

      Delete
  3. Have you read this one?
    https://sfari.org/news-and-opinion/in-brief/2014/cognition-and-behavior-epilepsy-drug-alters-rodent-gut
    João Santos

    ReplyDelete
    Replies
    1. It does look like butyric acid is worth a shot.

      Does your son have GI problems?

      Delete
    2. Not really, but sometimes the smallish changes have a great impact.
      I should point that I read the sfari news differently. I read it as the more butyric acid the mice produced, the bigger social indifference towards others (and not as a good thing).
      João Santos
      On the other hand, Its only a mice model of autism and not a very realistic one (valproic acid in utero exposure doesn't strike me as very likely in my son or any other I know about).

      Delete
    3. It certainly is worthy of investigation.

      Delete
  4. The miyairi probiotic bacteria is also available In Amazon

    ...http://www.amazon.com/gp/product/B000FQUNB0/ref=pd_luc_rh_top_sim_04_02_t_img_lh?ie=UTF8&psc=1

    ReplyDelete

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