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Monday, 20 April 2015

Butyric Acid and Autism

Following on the previous posts about Tregs (regulatory T cells) and Short Chained Fatty Acids (SCFAs), today we get to the final steps and some more scientific data.
Butyric acid seems to be the best choice of an SCFA, as a possible anti-inflammatory autism therapy.
We have a research study that measured Butyric acid and compared the levels in people with and without autism.  It also splits out those with and without any GI issues.
We have another study showing that Butyric acid “attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism.” This is as relevant as you want to believe.
Since Butyric acid is widely used worldwide for animals and in Asia for humans, we have a great deal of data available.
The research shows that moderately increasing the level of Butyric acid does do good, but go too far and you lose the benefit. (Farmers do not over feed your chickens)

In both humans and animals two different methods are used:-
1.     Supplement with sodium/calcium/magnesium butyrate
2.     Supplement with Clostridium butyricum, bacteria/probiotic to stimulate the natural fermentation process in the colon.
A problem with the first method is the taste and smell. Butyric acid can be used to make a stink bomb.  Also some people find magnesium acts as a laxative and some people do not want to use sodium.  Sodium acts counter to potassium in the body, and we have seen earlier that, possibly due to potassium channel dysfunction, we generally want more potassium and less sodium.
Taking this into account, I prefer the second option, which follows a well-trodden path.  In Japan alone, over 200,000 packages of the Miyairi 588 probiotic have been sold since commercial production began in 1940.  The product has been used in various forms, ethical and OTC drugs, veterinary drugs, feed and food supplements.

The research on Sodium Butyrate
This compound is used in both human and animal research.  It is sold in tiny quantities as an OTC supplement and in large commercial quantities as an animal feed additive.
It is sold to improve gut integrity and reduce inflammatory disease.  In animals the key selling point is faster weight gain.  In humans I do not expect weight gain, in fact quite the reverse.
A very easy to read presentation is for the animal version:-

The supplement sold to humans just says:- 
Butyrate is a short chain fatty acid that is a potent detoxifier of ammonia and neurotoxins. It encourages the formation of friendly bacteria in the gut.

 The Research on Miyairi 588
Miyairi 588, a form of Clostridium butyricum, is produced by a Japanese pharmaceutical company.  They have recently gained approval for its use in Europe for chickens, pigs and turkey.  Now they have applied to sell the human version.  So there is plenty of information available in English.

Probiotics are microorganisms and in or to know the potency you need to know the number of organisms in your pill.  The more potent tablet, Miyarisan Strong says it has at least 0.45 million.
  








Here is one example of the animal research which shows exactly what I expect, based on the research by Wendy Garrett at Harvard.  She found that raising SCFAs, raised Tregs which then lowered the pro-inflammatory cytokine IL-6.
Wendy’s research was on mice, the following Chinese research was on chickens and my interest is humans.

Abstract
1. The experiment was conducted to investigate the effects of dietary sodium butyrate on the growth performance and immune response of broiler chickens. In experiment 1, 240 1-d-old chickens were allocated into 4 dietary groups (0, 0·25, 0·50 or 1·00 g sodium butyrate/kg) with 6 replicates each. In experiment 2, 120 1-d-old chickens were fed a control diet (without sodium butyrate) or 1·00 g sodium butyrate/kg diet. Half of the chickens fed on each diet were injected intra-peritoneally with 0·5 g/kg body weight of Escherichia coli lipopolysaccharide (LPS) at 16, 18 and 20 d of age. 2. There was no effect of dietary sodium butyrate on growth performance. On d 21, serum interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) were decreased in chickens given 1·00 g sodium butyrate/kg, serum superoxide dismutase (SOD) and catalase activities were significantly increased, and malondialdehyde (MDA) was decreased by dietary sodium butyrate at 0·50 or 1·00 g/kg. On d 42, serum IL-6 was markedly decreased by dietary sodium butyrate, while 1·00 g sodium butyrate/kg greatly reduced MDA and increased catalase. 3. LPS challenge significantly reduced the growth performance of chickens. Serum IL-1β, IL-6, TNF-α, corticosterone, alpha-1 acid glycoprotein (AGP) and prostaglandin E(2) (PGE(2)) were increased in LPS-challenged chickens. Dietary sodium butyrate supplementation maintained the body weight gain and feed intake. Sodium butyrate supplementation inhibited the increase in IL-6 and AGP in serum at 16 d of age and TNF-α, corticosterone, AGP and PGE(2) at 20 d of age. Similar inhibitory effects of sodium butyrate in serum glucose and total protein concentrations were also found at 20 d of age. 4. The results indicated that dietary sodium butyrate supplementation can improve the growth performance in chickens under stress and that this may be used to moderate the immune response and reduce tissue damage.
  
Butyric Acid levels in Humans 
We all have Butyric Acid in our colons; it is produced there via fermentation of fibres in our diet.  Depending on what bacteria you have in your colon and what food you eat, you will have a different amount.










In spite of the title of the above paper, when you look at the above chart, if you rule out 10% that are outliers, you can see that nothing correlates with anything (GI disturbance, gluten free diet, autism or not).


So who does currently benefit from extra Butyric Acid?

·        Humans with Ulcerative Colitis in clinical trials and the early adopters who read about the trials

·        Japanese people with GI disturbance

·        Farmers who feed it to their chickens, turkeys and pigs


Too much may not be good
There is some research showing that large amounts of Butyric acid may not be good and this likely holds true for animal and humans.  Note the very large variation in humans in the chart above.

The recent EU approval of animal version of Clostridium butyricum  called Miya-Gold® for use with turkeys notes that:

“…  a meta-analysis pooling data from these trials showed significant improvement in daily weight gain and feed to gain ratio when Miya-Gold® was supplemented at the minimum recommended dose of 1.25 108 CFU/kg feed.”
  
So a good starting point for humans is likely at the lower end of the suggested human dose. The suggested dose is 3 to 18 human tablets a day.
The good news is that these tablets are inexpensive.  630 tablets cost $17 including shipping from Japan.  If they do nothing for autism, they probably will do some good for the family pet, assuming you have no chickens.





21 comments:

  1. I read your post (brilliant as usual) with great excitement, as I've been researching B. Fragilis and pathogenic gut infections and how their involved (missing) in regressive Autism (as well as colitis). SCFA sounds like a good way of feeding/increasing the beneficial bacteria. I just have three points to make if I may. There is perhaps another option which would be a more permanent solution and that is FMT (or bacterial transplantation) which is done to treat C. Diff infections. My second point is that you mention trying Vancomycin just to see if that is the underlying issue, but wouldn't that further deplete the healthy bacteria. Lastly Miyairi 588 is from the Clostridia species which are G Protein inhibotors/blockers. As a parent of a child with regressive autism and GI issues would that be of a concern?

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  2. The good bacteria make the SCFA, not vice versa. The lack of good bacteria means that the level of some SCFA may be low and this might result in "leaky gut" in some people.

    The problem with "poop transplantation" is that you will not know what you are transplanting. You might therefore transplant something bad by mistake, just as in blood transfusions and insulin/thyroid hormones made from animals.

    Regarding antibiotics, the hypothesis is that, in a subgroup of children, overuse of antibiotics has caused a disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology.

    Vancomycin is indeed an antibiotic, but its role is to kill “bad” bacteria in the intestine. It is not absorbed into the blood and so only has an effect in the intestines.

    If somebody has a positive behavioral response when taking antibiotics, this tells us that somewhere in their body is a problem with bacteria. This could be anywhere in their body.

    I suggested narrowing down the location of the problem by using Vancomycin as a diagnostic tool. If the person’s autism improves with Vancomycin, then the problem should be in the intestines. If they did not respond to Vancomycin, but did to Amoxicillin, for example, then you would know that there is a bacterial problem but not in the intestines.

    There is good and bad clostridia. It does seem that after 60 years of use Miyairi 588 is established as "good" clostridia. But you can never be 100% certain.

    ReplyDelete
    Replies
    1. "If somebody has a positive behavioral response when taking antibiotics, this tells us that somewhere in their body is a problem with bacteria."
      Not always. D-Cycloserine shows potential in overcoming social deficits. It crosses the Blood-Brain Barrier.
      João Santos

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    2. Some antibiotics, like D-Cycloserine, have other effects.

      "It has been found to be effective in the treatment of some neurological disorders, due to its effect as a selective partial agonist of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptors found in the basolateral nucleus of the amygdala. Specifically, cycloserine affects the glycine-binding sites which are important for opening these NMDA channels"

      Maybe it would be better to say that if the antibiotic action, affects/improves autism then we should suspect a bacteria. It seems that most people finding antibiotics have an impact are using very common Penicillin variants, that do not have other known modes of action.

      By the way, my MIYAIRI 588 arrived from Japan. The tablets are tiny, tasteless and dissolve. Have you tried your Butyric Acid supplement?

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    3. I decided to go with the MIYAIRI 588. I´m still waiting for it to be delivered.
      João Santos

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  3. Please allow me two more questions.
    Isn't there the possibility of vancomycin entering the bloodstream in people with Leaky Gut?
    The next question is a general one. I have read that oral probiotics never effect a permanent cure, because they never get embeded in the actual intestinal lining. They only work by crowding the gut as long as you keep up the supply. I'd love to hear your take.

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  4. Yes, I also thought that if the gut was "leaky" then why could not the vancomycin leak out. If you gut was very leaky, you would likely have some serious symptoms. The argument to use vancomycin as a diagnostic tool is still valid.

    Some bacteria, like Miyairi 588, does not set up a permanent home in the gut, but other types do, like the B. Fragilis you are interested in.

    It is now recommended that children on antibiotics also take a particular probiotic with high doses of Lactobacillus rhamnosus and Saccharomyces boulardii. This stops them getting diarrhea.

    http://www.nhs.uk/Conditions/probiotics/Pages/Introduction.aspx

    The big problem with all these supplements is whether they really contain what it says on the label. Often they do not.

    The other interesting way of treating GI problems, that shows some promise, is with parasitic worms. It does not sound pleasant, but they do modify the immune system.

    http://www.foodsmatter.com/natural_medicine_comp_therapies/helminthic_therapy/articles/ht_success_stories.pdf

    As with the FMT therapy, you would have to be careful. Too many parasites is worse than none. It seems much cleverer to use the ones that cannot reproduce in humans, like TSO.

    I think the Miyairi 588 bacteria is the safest choice. There are drugs under development that mimic the action of the TSO worms.

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  5. The million dollar question would then be; how to get B. Fragilis or similar probiotic into the gut (other than FMT)?
    Being that they are anaerobic I would assume that they would die at first exposure to oxygen.

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  6. Hi Peter,

    Are you still doing the Miyairi 588? Any significant changes?

    Thank you,
    RG

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    Replies
    1. We are still using it because even a tiny amount resolves the gas problem, caused by extra potassium. We never had big GI issues, I think Miyairi 588 would be a good thing to try for that subgroup of people. I never tried a large dose, perhaps that might have had a different effect.

      Delete
    2. Peter
      You say miayiri 588 resolves gas problem. You mean bloating or some thing else? Thank you.

      Delete
    3. Salempeacock, some supplements seem to cause flatulence ie smells. This goes away with this bacteria. It is capable of much more than that, but at higher doses. It should be immuno-modulating which is why it is put in animal feed.

      Delete
  7. Hi Peter,
    My Myiari 588 arrived at my house from a long trip out of japan.
    How do you store it? Alot of probiotics have to be cooled to keep em alive, the bottle only says best before 2020.

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    Replies
    1. This one seems to be fine at room temperature. Some others do indeed need to be kept chilled.

      Delete
  8. Ah ok thanks, ive started with 3 times a day 2 tablets after a meal, Im not sure but I think its starting to have some minor effect allready? seem to feel calmer? Might be placebo, will have to use it for a longer period.

    Peter, what dose have you been using? the label is both written in japanese and english and seems to suggest 3 to 18 tablets a day.

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    Replies
    1. This bacteria produces butyric acid and how much it produces will depend on how much fibre you eat. Butyric acid can do some clever things as mentioned in the post, but the effect does vary by dosage. I would start at a low dose and slowly increase to find what dose (if any)has a good effect. One reader who too the other route by using sodium butyrate had a good effect at a small dose (500mg) but lost that effect at higher doses. How much Miyairi equates to 500mg of sodium butyrate I do not know.

      It is really is a case of experimentation. I only ever used a tiny dose and when I tried 500mg of sodium buyrate there was no effect.

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  9. My Miyairi arrived today and i will be adding it to my daughter's daily regimen. I am a bit cringy about the fact it contains talc and lactose as additional ingredients. I will start tiny doses. She already takes other types of probiotics as well. We have never tried antibiotics as a trial but thinking about doing this. She is a leaky gut kid with inflammation in the GI and high calprotectin and lactoferrin in stool.

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  10. I'd like to follow this thread. Where does everyone order the miyairi from? Also, has anyone considered using this supplement?
    https://www.amazon.com/BodyBio-Sodium-Butyrate-Vegetarian-Capsules/dp/B0058A9SF0/ref=sr_1_2_a_it?ie=UTF8&qid=1494368787&sr=8-2&keywords=clostridium%20butyricum

    I started using it and it has had a very pronounced effect on my brain.

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    Replies
    1. Sodium butyrate is the other way to increase butyric acid (see the photo at the start of post). I think it will be a more precise way to implement this therapy idea. One mother gives her young son 500mg and has a good effect, but at 1000mg the effect is lost. What dose are you using? People buy Miyairi via ebay/Amazon from pharmacies in Japan.

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    2. I own the bodybio sodium butyrate you have pictured at the top of the page. 2 capsules contain 313.3 mg of sodium and 1.2 grams of butyric acid. I wonder which is the relevant number - the 313.3 or the 1.2g ???
      I've been taking about one capsule a day, which does seem to be a little bit TOO MUCH.

      Delete
  11. Peter, How was your experience with Miyarisan? I could get it for my son.
    Valentina

    ReplyDelete

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