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Thursday 5 November 2020

Lethargy and Autism

 

That alternative world, where you fix things when they are not working


I do sometimes forget the world that most people live in, when it comes to (not) understanding and (not) treating autism.

I decided to write this post on lethargy and autism, after being prompted by a friend who contacted me and told me that his son with autism is very lethargic (physically and mentally). I replied with the suggestion that he try a little scoop of Agmatine Sulphate.  Now his son is able to go for long walks, without constantly wanting to stop for a rest.  The Dad asked me to share his positive experience with Agmatine.

A few years ago, this boy was diagnosed by Dr Kelley with mitochondrial dysfunction.  People with mitochondrial dysfunction should indeed have poor exercise endurance, this is because they lack the enzymes needed in a process called oxidative phosphorylation (OXPHOS).  OXPHOS is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing the chemical energy in the form of ATP.  If you run low on ATP you need to sit and take a rest.

You can run low on ATP for reasons other than a lack of these mitochondrial enzyme complexes. You also need enough glucose and oxygen.

Agmatine has numerous modes of action.  It affects the following (and more): -

·         Neurotransmitter receptors and receptor ionophores. Nicotinic, imidazoline I1 and I2, α2-adrenergic, glutamate NMDAr, and serotonin 5-HT2A and 5HT-3 receptors.

·         Ion channels. Including: ATP-sensitive K+ channels, voltage-gated Ca2+ channels, and acid-sensing ion channels (ASICs).

·         Membrane transporters. Agmatine specific-selective uptake sites, organic cation transporters (mostly OCT2 subtype), extraneuronal monoamine transporters (ENT), polyamine transporters, and mitochondrial agmatine specific-selective transport system.

·         Nitric oxide (NO) synthesis modulation. Both differential inhibition and activation of NO synthase (NOS) isoforms is reported.[9][10]

·         Polyamine metabolism. Agmatine is a precursor for polyamine synthesis, competitive inhibitor of polyamine transport, inducer of spermidine/spermine acetyltransferase (SSAT), and inducer of antizyme.

·         Protein ADP-ribosylation. Inhibition of protein arginine ADP-ribosylation.

·         Matrix metalloproteases (MMPs). Indirect down-regulation of the enzymes MMP 2 and 9.

·         Advanced glycation end product (AGE) formation. Direct blockade of AGEs formation.

·         NADPH oxidase. Activation of the enzyme leading to H2O2 production.[11]

 

I did make the chart below a couple of years ago to figure out why Agmatine would give such an energy boost, and see how all these substances fit in with each other.  My conclusion was that an increase in endothelial nitric oxide was a plausible explanation, since the effect is fast.

Agmatine increases the enzyme eNOS which the leads to nitic oxide (NO) being produced in endothelial cells, this triggers a series of steps that results in vascular relaxation, which means more blood flow.

More blood flow means more glucose and oxygen to fuel mitochondria to make ATP.

 


When I did a quick Google search for “Lethargy and Autism”, I was surprised to find an entirely different explanation from the “old world”, where autism is still untreatable, at the UK’s National Autistic Society.

 

Autistic fatigue - a guide for parents and carers

Exhaustion (fatigue) and then burnout can happen to anybody. Being autistic can make fatigue and burnout more likely, due to the pressures of social situations and sensory overload. If your child or the person you care for is experiencing fatigue or burnout, helping them to manage their energy levels is essential, as this guide explains. 

There are various things that can cause autistic fatigue. Autistic adults suggest several causes, including: 

·        sensory overload 

·        dealing with social situations 

·        masking or camouflaging their autistic traits

·        suppressing stimming 

·        a sense of not meeting other people’s/society’s expectations of them.

Changes in your routines or day-to-day life, such as a change of school or job, can increase anxiety and can be additional causes for autistic fatigue and burnout.

 

What can I do if the person I care for is experiencing autistic fatigue and burnout?

Use energy accounting

Energy accounting is a system used to set manageable limits on your energy levels so you do not deplete yourself to the point of burnout. 

Help your child or the person you care for to set a limit on how much energy they have in a day or week and estimate how much certain activities drain them. Also work out how much certain activities energise them. 

You can then try to plan and balance their activities and energy over a day or week to try and manage stress limits. Make sure you build in time for relaxation and recovery. 

 

Time off and rest/relaxation

Whether you use energy accounting or not, time off from work or school and other high-stress activities is key to managing stress levels. Ensuring time for activities/interests that re-energise and promote relaxation is key. This could be connecting with family and friends or enjoying hobbies or interests. 

 

Time without having to mask

Autistic people often feel the need to hide or mask their autistic traits in public, for example by suppressing the urge to stim. It can be important to factor times into your child’s day for things like stimming, somewhere they feel comfortable and able to do so.

  

Conclusion

Lethargy with autism in this blog is a biologically treatable condition.

Taking time off to rest is not a cure for lethargy, it is just a coping strategy.

Why just cope, when you can live to your full potential?

The bunny managed to figure this out. (fit alkaline batteries)

 


You would think that hyperactivity would be more often a problem than lethargy in those with autism, but that is another story.




16 comments:

  1. Since Agmatine is illegal in the UK, is there a legal alternative?

    ReplyDelete
    Replies
    1. In most of the world Agmatine is a cheap OTC supplement used by body builders. It is cheap and safe. I buy mine online from iHerb (I am not in the UK).

      In the UK/EU they started to regulate supplements, but not by what is safe or effective. There is a cut off date, anything being sold before that date does not need approval, everything after that needs approval. But who is going to apply and pay for that approval?

      All the BHB ketone products, including those developed at Oxford University, are banned from sale in the EU.

      Is there an alternative to Agmatine sold in the UK? There are some things that do increase blood flow to the brain such as Acticoa/CocoaVia which are made from cocoa flavanols. I did try these, but the effect was not the same as Agmatine, they are though a good idea for older people to avoid/delay dementia and protect against heart disease (based on the research funded by Mars).

      The UK is not a good place to be if you want to treat autism.

      Delete
  2. is is safe to try on me to see if it would help me even If maybe I dont have that? I have been unable to sustain aerobial physical activity since I was a child. It has nothing to do with willpower or lazyness. I can do lift weights as anyone else, but a hike will make me want to die. Through sheer willpower it became gradually better over time but I have always said that something is simply wrong with me on that count.

    ReplyDelete
    Replies
    1. tpes, Agmatine is a moderately effective supplement used by body builders. It is also produced naturally in your body.

      You may find it locally, if not, you can buy online from iHerb.

      I think 1g is a good dose for you to try and see if you get any benefit.

      Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report
      https://pubmed.ncbi.nlm.nih.gov/25247837/

      Delete
    2. That case study (performed by the authors themselves!) was interesting. I've been skeptical because of the negative effect on NMDArs, but if it really was relevant it would induce amnesia in people.

      /Ling

      Delete
    3. tpes,

      Hiking sounds like a lack of stamina, which suggests lack of access to energy from fatty acids to me rather than glucose. If you can lift weights it sounds like your short term energy access is ok. (Admittedly that might not be glucose.)

      If it is lack of energy from fatty acids, that could be low levels in the blood (caused by high insulin?) or lack of ability to access them (caused by ??). You could try to practice accessing this energy source more with e.g. caffeine before breakfast to increase blood levels combined with long and slow exercise (walking or easy cycling / jogging / hiking) to encourage the burning of fat.
      Note that a carbohydrate meal / snack may spike your insulin levels, which will clear a lot of fatty acids from the bloodstream.

      When on hikes, a low carb snack and/or caffeine might help, e.g. low carb, very dark chocolate, which combines both.

      See e.g. https://blog.tacx.com/how-to-become-a-fat-adapted-cyclist/ and many others out there for cyclists, and probably also runners, e.g. Maffetone method.

      Aspie2

      Delete
  3. Hi Peter, hope you are well,I would like to know what do you think about using Pentoxifylline to target neuroinflammation and immune dysfunction in my son. I have it at home because my mother was taking it for brain blood flow.
    Valentina

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    Replies
    1. Valentina, I think Pentoxifylline is a very good idea to trial. It was first suggested for use in autism decades ago. It has the advantage of being widely available and inexpensive.

      It has overlapping effects with Roflumilast (Daxas) and Ibudilast, both of which may help autism, cognition and myelination.

      Other readers do use Pentoxifylline. It is on my to-do list as well. I would try 400mg once a day, taken with food to avoid GI side-effects, which seems to be what works for those using it.

      I tried 100mg of Daxas, but it caused nausea. This might well fade over time. I think these same side effects might occur with Pentoxifylline and Ibudilast. All 3 drugs are PDE inhibitors.

      Delete
    2. Great,I will give it to him now, each tablet is 400 mg. Hope we can avoid side effects. It would be great if it works because I can get it here.Thank you a lot!
      Valentina

      Delete
  4. Agmatine has been great for me.

    ReplyDelete
  5. Hi Peter,
    Any chance you might know of any blog or person that does the same thing as you (looks at the science and gives solutions) but for bipolar? I have no clue how I even found you, that was good luck. I know the standard treatments and don't see anything there... maybe there is all this unused research in that subject too.
    Thanks..!

    ReplyDelete
    Replies
    1. Hi Pat, I am not aware of a blog like this one for bipolar.

      But, many people do go to Reddit:-

      https://www.reddit.com/r/bipolar/

      If you post a message there, I think someone will be able to give you links to good sites.

      I expect there are bipolar groups on Facebook. The autism discussion has moved to Facebook and Twitter.

      There are big overlaps between bipolar and autism, so some off-label autism therapies, beyond Agmatine, may help. A good example is Verapamil, it has been researched in bipolar, but not autism.

      Delete
    2. Thanks I will check out facebook and twitter, I never really thought to look there. Is there any other therapies you can think of that overlap?

      Delete
  6. Hi Peter
    I thought I'd share a few things I've found about bumetanide. As you know my son has had some uncommon reactions to it for the past 6 -9 months. This past month we've reduced the dose by half most of the time and added clonazepam. I still give 1mg here and there if he needs it, along with electrolyte replacements. Although most of the studies have to deal with ppl with heart failure, I think I might've finally found the issue at hand: after prolonged use of loop diuretics which activate the renin angiotensin system (RAS), the sympathetic nervous system goes into overdrive and can cause a host of other issues. One symptom is inhibition of peristalsis, aka your digestive system stops moving food along, which is exactly what he has been suffering from. The low level hypotension has been suspect for some time, as the volume loss also accounts for his lethargy and dizziness. He definitely needed to drink more water than I previously thought, kicking myself on that one. Unfortunately there's nothing that can counteract this issue other than giving more drugs and dealing with more side effects, so for now we are sticking with decreasing the dose and supplying plenty of drinks with replacement electrolytes. My son often craves salt after he's had his bumetanide, so I let him take in a salty snack with a LOT more water and keep K and Mg on the higher side. I though about trying a similar drug like diamox that did what bumetanide does, but likely would affect him the same way.

    https://core.ac.uk/download/pdf/85215033.pdf

    https://ccforum.biomedcentral.com/articles/10.1186/s13054-015-1017-3

    https://mir-s3-cdn-cf.behance.net/project_modules/1400/4f3e8545755339.583c55f295438.png


    MKate

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    1. MKate, thanks for the update.

      You could try Diamox/Acetazolamide, some people with autism do use it long term. Its effects may well overlap with those of Bumetanide (via something called the AE3 exchanger).

      Some people do not tolerate Diamox, it gave my son reflux.

      Delete
    2. Hi again Peter,

      Well I suppose I've proved myself a slacker with reading blog posts, as I've just looked back and seen that you've done several posts on angiotensin going back to 2017. And here I thought myself a bit clever! :) (not really)

      Still trying to play detective and pinpoint exactly what is/has been happening with bumetanide in my son. The main side effects I've seen consistently are constipation, withholding, lethargy, and intermittent hyperactivity. Immediately after taking it he exhibits mild lethargy from Na+H20 loss, followed by spurts of hyperactivity throughout the afternoon, which I'm guessing is caused by a spike in norepinephrine maybe? Nothing telltale but I'm very worried as I really don't want to give up on bumetanide. His concentration and focus are so much better when he's on it. However, I don't want to start treating side effects with more drugs as that will only cause more problems.

      I'm curious about potassium bromide but the only form I could get is veterinary grade which isn't for human consumption. (or so it states)

      Will contact our pediatrician about some urine testing and possibly trying diamox. In the meantime I need to catch up on some of your blog posts.

      Thanks for the feedback.

      MKate

      Delete

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