Friday, 7 April 2017

Treating Mitochondrial Disease/Dysfunction in Autism

In my book I will be covering the science behind hopefully almost all autism, which then naturally leads to translating it into therapy.  In the ideal world you would just skip straight to the therapy and the final section of the book will be just that.  Clearly it would make sense to read the science first, so that you know what are the dysfunctions that you might need to treat.

Hopefully there will also be some case studies from people who have applied a science-based approach to identify and implement effective therapies.

Roger would clearly make a very good example of a reversible in-born metabolic-caused type of autism.

I will be posting on my blog some drafts from the Part III - Translating Science to Treat Autism.  This is of course just one person's collection of other people's ideas and some of his one.  The reader and his/her medical medical team ultimately decide what to implement and must monitor its ongoing implementation.

 * * *

Mitochondrial disease is managed rather than cured. It seems to be present in autism in widely varying degrees of severity.  Extreme cases result in very severe regressive autism with MR/ID.

It is either diagnosed based on detailed analysis of numerous blood tests, or more recently via a sample taken from inside the cheek. These tests cannot be perfect, because mitochondrial disease can be organ-specific.

Someone with body-wide mitochondrial disease will have poor exercise endurance and this will be very noticeable compared to siblings and peers.

Dr Kelley, from Johns Hopkins, has published his therapy for autism secondary to mitochondrial disease (AMD):-

1.      Augment residual mitochondrial enzyme complex I activity

2.      Enhance natural systems for protection of mitochondria from reactive oxygen species

3.      Avoid conditions known to impair mitochondrial function or increase energy demands, such  as prolonged fasting, inflammation, and the use of drugs that inhibit complex I.

Combining the first and second parts of the treatment plan, the following is a typical prescription for treating AMD:

L-Carnitine 50 mg/kg/d                Alpha Lipoic acid 10 mg/kg/d

Coenzyme Q10 10 mg/kg/d          Pantothenate 10 mg/kg/d

Vitamin C 30 mg/kg/d                  Nicotinamide 7.5 mg/kg/d (optional)

Vitamin E 25 IU/kg/d                   Thiamine 15 mg/kg/d (optional)

There are actually five stages in the OXPHOS process in mitochondria and there are five enzyme complexes. Dr Kelley's plan above is for the most common dysfunction, complex 1.

Different clinicians have different treatments.

Also appearing elsewhere are :-

Calcium folinate (2 x 25 mg), but not because of peroxynitrite

Biotin 5-10 mg/day


Methylcobalamin B12


On the basis that peroxynitrite, from nitrosative stress, damages the mitochondria, you might consider:

·         Calcium folinate (leucoverin) in very high doses like 25mg twice a day.

·         Xanthine oxidase inhibitors, typically used to lower uric acid to treat gout. A good example is Allopurinol. It will both lower uric acid and peroxynitrite. Uric acid is itself a potent scavenger of peroxynitrite; this may look odd given the previous sentence. If someone has low uric acid and wants to reduce peroxynitrite then uric acid itself should be therapeutic. The purine metabolism may play a key role in some types of autism, as proposed by Professor Robert Naviaux.

·         Rosmarinic acid, a natural scavenger of peroxynitrite.

There are many anomalies in autism and one is uric acid.  Some people have low levels and some have high levels. Uric acid is itself a scavenger of peroxynitrite.  People with high levels of uric acid do get gout, but almost never MS (multiple sclerosis) and it has been suggested that scavenging peroxynitrite is neuroprotective.

Special, electrically charged, antioxidants have been developed to target the mitochondria.  MitoE is a charged version of vitamin E and MitoQ is a charged version of coenzyme Q10.

Based on the research, you might  also seek to activate PGC-1α, the master regulator of mitochondrial biogenesis. This can potentially be achieved via:-

·         Exercise  (gradual endurance training)

·         Activate PPARγ and perhaps  PPARα (e.g. Bezafibrate  and Rosiglitazone)

·         Activate AMPK (Metformin)

·         Activate Sirt-1 (resveratrol and other polyphenolic ‎compounds)

Carnitine-like analogs may also help in theory.  The standard L-Carnitine, widely used as a supplement, is very poorly absorbed even at high doses. An analog is a modified version of a molecule that keeps the therapeutic beneficial effect, but overcomes a drawback, bioavailability in the case of carnitine. There is some basis in the literature to believe that the Latvian drug Mildronate might be useful to treat complex 1 mitochondrial dysfunction.

more detail at


  1. Are you saying there are milder forms of true mitochondrial disease with autism that do not involve regression? I did not know that.I also was not sure if autism with mito could be severe enough to cause intellectual disability.The description I knew of autism and mitochondrial disease came from Marvin Natowicz's "red flags".I was at first thought to have mito,because I fit this description pretty well,including the regressions from acute illness,both infection and undiagnosed metabolic crises.I had moderately severe autism.Verbal,but low functioning.That was a few years ago,and as we now know,mitochondrial disease is not the only way infection can cause regression.It took a lot more tests,before I found I had a combination of both metabolic and immune disorders.The latter involving multiple serious autoimmune disorders,and was only identified through whole exome sequencing.I reversed my autism by treating the metabolic disorders,but still have all my medical problems.I have had a couple of bad lung infections,but no longer regress.I really wish there was greater awareness among the public at large about regressive autism,and the types of disorders that cause it.

    1. Roger, some of the clinicians use the terms Primary Mitochondrial Disease, when they have identified a specific genetic variance, and Secondary Mitochondrial Dysfunction for when there is impaired mitochondrial function, but they are not sure why. It looks like many people with autism have some impaired mitochondrial function and this was one of Jon Poling's points, after he won his claim for his daughter's severe regression to autism.

      Classic autism gets worse before it stabilizes, perhaps in some people part of the "getting worse" is the onset of additional mitochondrial problems. Nobody can really know.

      If you want to write a guest post about your type of autism and its treatment, I am sure people would like to read it.

    2. You are the second blogger to suggest I publish my story in their blog.I will do that sometime.As my functioning has become better and better,I am in more of a position to do this.

  2. Peter,

    You have raised an important point... Worsening of autism in those who were clearly born with autism could be related to mitochondrial problems, in a subset. My son, though born with classic autistic traits, had started using spoon by the age of one and a half and had a normal gait. But gradually, slowly, his walk became slightly awkward and he just did not develop his cutlery manipulating skills any further....rather seem to lose them. Progression of autism or small gradual regressions... Can't say for sure. Mitochondrial issues or development of sensory not know for sure. But regression in skills, motor at least, which might include speech production, does call for an investigation into mitochondrial dysfunction, don't you feel?

    1. In the US there is now a simple, non-invasive, test for mitochondrial dysfunction, which they claim to be accurate.

      Maybe contact Dr Goldenthal?

    2. It is not unusual for someone with regressive autism to regress to a more severe form of autism than they were before.This happened to me twice.It all depends on the severity of the illness that triggers the regression.Loss of skills is common.Less common,might be the addition of behaviours that were not present before the regression.I have had two acute infections in my life,that caused me to start head banging,when I did not head bang before the infection.In the first case,it persisted for like three or four years,after the infection went away.The head banging stopped,when my condition stabilized,at a new,but more severe point.

      One of the best doctors in the USA for autism with mitochondrial disorders,is Fran Kendall in Atlanta.

  3. Just want to add that I spoke with Dr. Goldenthal last week as I sent him my daughters buccal swab for analysis. He will sent anyone a kit that asks the cost to run the test is 200 US. He may be moving on from his position there and so if anyone wants to do the test they should contact him soon. My daughters results indicated high complex 1 activity and very high complex 1 to 4 ratio. They dont know the significance of this yet but Dr. Frye indicated the mitochondria might be under stress and producing more ROS. This is theoretical. I believe my daughter had a regressive autism. I have ordered another kit to test my NT child and compare.

  4. I haven't posted in awhile,but I wanted to share something that I think is important to think about while parenting your child with autism. As the mom of a 12 year old boy,I feel like I have enough years under my belt to understand the desperation of a newly diagnosed family and also the wisdom that comes as the years go by. I am no expert,but I am a parent who is always searching for something to help make my son's life better and have made mistakes along the way in my quest to do so.
    I continue to have "EPIPHANIES" that make so much sense NOW,but I wasn't ready for when he was younger. In no particular order:
    1. For all kids with ASD, but particularly the emotionally sensitive ones,focus less on skills/academics and more on making them feel safe,acknowledged and that you will help them through their fears/worries. This is crucial and not something you can do occasionally. It must be the cornerstone of the approach that everyone who is close to your child takes when interacting with him.
    2.If after years of trying everything under the sun both pharmaceutical and biomedical and nothing makes a significant impact, find a time to wean off of everything (Christmas break, Summer break)& see what your child's baseline is. You might be surprised. Go slowly and realize that it might be hard,but it's already hard - that's why you keep trying new things. Moving forward,commit to trying one new thing at a time and let it go if it isn't doing anything (be honest with yourself as to it's effectiveness).
    3. If your child has a perseveration (my son's is watching movies) that after years doesn't lessen, but becomes an impediment to being available to all else, have the courage to help him/her let go of it. My son's desperation to control his movies and watch scenes over and over has gotten so bad that it is like a drug addict. He needs it to survive. I allowed it to get this bad because the suffering I had to watch him go through when I tried to limit them broke my heart too much. After some soul searching and talking with a friend I am finding the courage to help him learn to face his fears with my help. It is important to note that you have to explain the process and acknowledge the feelings that are occurring: frustration, sadness, worry, pain and reassure them that you will help them through it. Be prepared to watch them break down. Also be aware that your child might have rich play ideas in their head that they are unable to execute. This is incredibly frustrating for them and lead them to avoid toys/play and cling to their pereveration that much more. You may have to spend time holding them, reading to them, taking walks, or just mirroring them doing the simplest thing like playing with coins or a sensory toy (use little language) and just let them know that you are there and you know how hard it is to let go.
    4.Focus on simplicity, love, acceptance, support. My son's doctor told me many years ago when he was diagnosed that Autism is like that toy (Chinese finger trap)-the harder you pull, the tighter it gets.
    5. Acceptance of where you and your child are at is not the same as giving up.
    *I have had to learn all of this the hard way. Too much intense therapy. Too many drugs/supplements at one time. Too much worry/sadness. It got me nowhere. What has gotten me to a better place is to put more energy into creating a calm, loving, less hectic life.
    Good luck to everyone and thanks for allowing me my perspective.

    1. Christine,

      You are so right... Acceptance is not giving up but strategizing and prioritising on what has to be held onto ..belief, protocols, therapies, and what one needs to bid an adieu to. Also, try not to design dreams for your child or for your own life through your child. That is not his purpose in life...that is if life has any purpose.


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