Autism in Iran: Piracetam, Periactin & Pentoxifylline

This may sound like a very odd subject for my blog.
 
In 2002 US President George Bush first used the term “Axis of Evil” to refer collectively to Ian, Iraq and North Korea.  Later that year the then-Undersecretary of State John Bolton gave a speech entitled "Beyond the Axis of Evil"; in it he added three more nations to be grouped together: Cuba, Libya and Syria. Finally, in 2005 Bush’s Secretary of State came up with “Outposts of tyranny” to refer to Cuba, Belarus, Burma and Zimbabwe.

Many readers of my blog are from the US and may think that not much good can be going on in Iran.  The reality is quite the reverse, at least in the field of autism.

In spite being under all kinds of economic sanctions, Iran has generated a substantial body of insightful research.  There are 75 million Iranians which is just under the population of Germany.  I do not recall seeing much German research into autism. 

One particular researcher, Shahin Akhondzadeh, has done several very interesting studies. His CV lists 128 research papers, including autism, ADHD, schizophrenia, Alzheimer’s and other conditions.  He also writes about herbal medicine for mental health, which I know is popular among readers of this blog, so I included links to some of those papers.

Piracetam, Periactin/ Cyproheptadine & Pentoxifylline

Akhondzadeh is unusual in that he actual makes repeated clinical trials of existing drugs that the science shows could be effective.  In the case of autism he trialled three interesting drugs (with similar names):-

·        Piracetam

·        Periactin/Cyproheptadine

·        Pentoxifylline

Unfortunately his three trials combined them with an anti-psychotic.  But I think it is still interesting to look at the net impact of each of the three drugs.  I did just that.

You have to look at the data and compare the impact after 8 weeks to be consistent and you have to adjust for the fact that in the Periactin/Cyproheptadine trial at week 0 the placebo group was out of line with the trial group.

 

Net improvements:-

 

Piracetam                                        7 points on ABC

Periactin/Cyproheptadine           7 points on ABC

Pentoxifylline                                 3 points on ABC

 

This tells us that Piracetam and Periactin had the greater incremental impact over the antipsychotic and that the change was 7 points on the aberrant behaviour checklist (ABC).  The ABC is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54. It is a 58 item checklist. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech.

 

 

 

 

 

Periactin/Cyproheptadine

I have written about this drug in my recent post on Serotonin.  Periactin is an old first generation H1 antihistamine that happens to have additional anticholinergic, antiserotonergic properties.  It is the effect on serotonin that appears to reduce aberrant behaviours in autism

Periactin is available OTC in the UK.  In the US it is sometimes prescribed to increase appetite.

 

The link to Akhondzadeh’s full study is later in the post.

  

Piracetam

Piracetam was first synthesized in 1964 by scientists at the Belgian pharmaceutical company UCB; struck by its apparent ability to boost mental functioning in even healthy individuals and by its safety, they coined the term nootropic to describe it and other substances. Piracetam (trade name "Nootropil") was launched clinically by UCB in the early 1970s, and currently is in use in many European countries.

Piracetam is a cyclic derivative of the neurotransmitter GABA.

Akhondzadeh writes:-

In addition to serotonergic abnormalities, the strongest evidence implicates the glutamatergic and GABAergic systems are important biochemical factors in autism. One current hypothesis is that autism is a hypoglutamatergic disorder. This hypothesis is based on neuroanatomical and neuroimaging studies and supported by similarities between symptoms produced by N-methyl-D-aspartate (NMDA) antagonists in healthy subjects and those seen in autism. If there is deficient glutamatergic transmission in autism, the most logical treatment would of course be a glutamatergic agent. In the treatment of schizophrenia, that has many similarities with autism either D-cycloserine (glycine agonist) or Piracetam showed promising results. Indeed, autism and schizophrenia have some similarities regarding the role of serotonin and glutamate in their pathophysiology.

 

Piracetam is a member of the nootropic class of drugs, which have cognition enhancing effects, it appears to modulate AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acids)-sensitive glutamate receptors positively and has been used in many countries in the management of dementia. Although its mode of action is not certain, it is said to protect the cerebral cortex against hypoxia and has been used following trauma or surgery and in a variety disorders including senile dementia and behavioral disorders in children. In addition, it is used in the treatment of dyslexia and some type of myoclonus in adults. Indeed. Piracetam is the most studied nootropic in children.

Piracetam was freely available in the US as a supplement until three years ago.  You will see on the web that people were using it, combined with another supplement called choline, to improve their mental functioning.  It had been shown to work in rats, as you can see in this trial.

Profound effects of combining choline and Piracetam on memory enhancement and cholinergic function in aged rats.

  

In the Ukraine it seems that Piracetam has long been given as a therapy in autism.  No mention of choline.

The full study is listed later in this post.

 

Pentoxifylline

Pentoxifylline is a drug that targets the immune system, well established to play a key role in autism.  It is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNF  and leukotriene  synthesis, and reduces inflammation and innate immunity.

So it would be fair to classify it as an immunological treatment for autism.

It is hard to find much about Pentoxifylline and autism.  It was trialled in the 1970s in Japan.

On our experiencein using Pentoxifylline for abnormal behaviour and the autistic syndrome. Sogame,Shiro

Japanese Journal of Child Psychiatry, Vol 19(3), 1978, 137-144

Describes the successful use of Pentoxifylline (150–600 mg/day) with 3–15 yr old children with abnormal behaviour (e.g., self-mutilation, aggressiveness, and hyperkinesis) and with autism. It is noted that while the drug was effective in reducing symptoms of autism, developmental factors in the disorder should not be ignored. (English abstract)

 

Unfortunately I gave not found the full text version of Akhondzadeh’s study on this drug.

 

Autism in Iran

A paper actually entitled “Autism in Iran”, makes very interesting reading and was co-authored by  Akhondzadeh.

 

Links to my selection of Akhondzadeh’s Research

 

Double-blind placebo-controlled trial of pentoxifylline added to risperidone: effects on aberrant behavior in children with autism.     ABSTRACT ONLY

 

Herbal medicine and women's mental health

A Double-blind Placebo Controlled Trial of ... - ResearchGate

 

Autism spectrumdisorders: etiology and pharmacotherapy

ONLY ABSTRACT
 
Herbal Medicine in the Treatment of Alzheimer’sdisease

…   Cyproheptadine in the treatments of autistic disorder: a double‐blind placebo‐controlled … -

 

Cyproheptadine in the treatment of autism 

Authors: GUDARZI S., YASAMYM. and AKHONDZADEH S Eur. Psychiatry, Vol.17, Year. 2002, Page: 230-231,    NO ABSTRACT

A Double-blind Placebo Controlled Trial of Piracetam

Double-blind placebo-controlled trial of pentoxifylline added to risperidone: Effects on aberrant behavior in children with autism

Conclusion

All three drugs would seem worthy of further investigation, but particularly Piracetam and Periactin.  Both seem to be widely used with children and were/are OTC.


 

Controlling Anger in Autism - Part 2

I wrote extensive earlier posts about using H1 anti-histamine drugs to control autism flare-ups.  Summertime allergies can result in anger, loss of control and ultimately, self-injury.

Controlling Anger In Autism with H1 antagonist, Claritin

Histamine, allergies and reducing challenging “autistic-like” behaviours

More on anti-histamines in Autism and introducing H4

 
Although this blog is about pharmacological interventions that can help in autism, I am firmly in the ABA behavioural intervention camp.  The drugs can indeed help, but are always going to be secondary to a very labour intensive intervention.

 

Anger in autism

Depending on how lucky you are, parents experience widely differing levels of anger from kids with ASD.  For those who have not experienced the extremes, here is my summary:-

Level 1           Bad temper

Level 2           Tantrum with screaming, maybe rolling around on the floor but no  violence

Level 3           Self-injury, like hitting head with fist, but no external “objects”

Level 4           Violent self-injury like banging head into a wall

Level 5           Violence towards care givers (punching, kicking, biting etc.)

There seems to be little correlation between anger and intellect.  Some highly verbal kids with ASD exhibit self-injurious behaviours.

 

Drugs

This post is about alternatives to antipsychotic drugs such as risperidone and haloperidol, which I personally do not believe should be given to children.

 

ABA (Applied Behavioural Analysis)

The underlying principle of ABA is to reward good behaviours and, in effect, ignore the bad behaviours.  You are taught to understand behaviours with the “ABC” of antecedent, behaviour and then consequence.

If you take your 4 year old to the Mall and he rolls around screaming on the floor, the typical embarrassed parent would make a swift exit to the car and back home.  So the kid has won and gets to avoid a boring visit to the Mall.  The same behaviour will repeat the following weekend.  Kids quickly learn which adults this behaviour works with and who the hard cases are.  Consistency among the adults is a key part of successful ABA. 

When children are still very small, a violent tantrum can be extinguished by the care giver physically restraining the child.  In some countries, in special schools this is still being done with quite big kids.   Monty’s former therapist, Dule, used to work in the local special school and as one of the few male staff members was regularly the one called upon to do the “restraining”. 

Generally, ABA is more useful for understanding the reason for tantrums and violence, so that it can be avoided in future.  The child can be redirected towards some other activity and thus calm is restored.

 

Alternative Strategies

Faced with a child who has lost control and the tantrum has become self-reinforcing, you are faced with the choice of letting it runs its course, or doing something about it.  This does rather depend on how big the child is, how big you are and where you are at the time.

My son Monty is only 10 years old and so my policy of zero tolerance to violence is still easy to enforce.  It is clear that once bad behaviours (violence) are learned (or self-taught) they can only very gradually fade away and be forgotten.  If violence is allowed to persist, the child will turn to it more readily and as he grows up, big problems will surely lie ahead.

Hit the reset button

I learned a long time ago that if you do something totally unexpected to a child (with or without ASD) it is like pressing the “reset button”.  It clearly depends how old the child is, but what still works for me is picking up my son and holding him upside down, or when he was very small, getting down on all fours and get right in front of him and bark like a dog.  It may sound crazy, it is crazy, but it works.

Chewing Gum

I noticed a long time ago that giving Monty a toy pipe to play with, intended for blowing bubbles, had a strange calming influence.  When I look at people smoking, I think that many of them have no need to inhale at all.  The mere ritual of lighting up, puffing and stubbing might be enough.

Then a few weeks ago Ted, Monty’s older brother, told me that a friend of his had told him something very funny.  She told him that she always has to be chewing something or have something in her mouth, otherwise she gets very stressed.  This fitted with what her Mother had being telling us adults; she declared that she (the Mother) is like Monk in the crime series on TV, where the character Monk has obsessive behaviour and many traits of Asperger’s.  Not surprising, the mother is a smoker, as will be the daughter in due course.

This brings me to our latest experiment, chewing gum.  Not as a reward, but as a therapy.

You may have seen from earlier posts that summertime allergies affect Monty’s behaviour.  With plenty of antihistamine we have the allergy under control, but the associated behaviours are not fully controlled.  It is much better than at the start of the pollen season, but not perfect.  I still do not have the optimal H1 antihistamines.

We just had a visit from our American ABA consultant, who flew in to see us and fine tune Monty’s programme at school and then his home programme.  This spurred me to think further how to give Monty the ability to fully control his behaviour by himself.  He is now able to tell us when he is about to “lose it”, so we have the three minute warning.  We need to give him the ability to himself subdue whatever is going on inside his head.

With an active and stimulating day at school, the problem now only arises at home, and hopefully ,with no pollen in a couple of months, the problem will disappear until next June.  But for now, the new secret weapon is “unlimited” chewing gum.  I say “unlimited” because it is not supposed to be a reinforcer (reward), if it was, the result would likely be the opposite of what I want.  The “calm down son here’s a gummy bear” method would be a disaster  and just prompt future tantrums to “earn” gummy bears.

Calming a tantrum

Giving gum to calm a self-injurious tantrum seems to work .  No restraint is required, just “here’s your gum”.  One minute later all is calm and Monty is joking, “Monty was hitting his head”.

 

Avoiding/anticipating a tantrum

 
The warning signs Monty gives are all verbal; “I want to be nice”; “I want to be happy”; “to hit your head”.  I just need to promptly offer the chewing gum.  Monty starts chewing and indeed calm is gradually restored.

I have since learned that Michael Jordan started a huge trend for basketball players to chew gum, it supposedly helps them be calm and concentrate.  There are actually studies showing health benefits of chewing gum, and not just for your teeth.

Here are some chewing gum facts.

 

Conclusion

I was already a regular buyer of gummy bears, now I am loading up with kid’s chewing gum as well.  If it works, I am happy to continue doing so.  The only side effects are clean teeth and sticky fingers.

 

 

Autism Biomarkers – Serotonin: LSD, SSRIs & Cyproheptadine/Periatin

Researchers are always looking for biomarkers of autism as a diagnostic tool; I am more interested in biomarkers as an indicator of might be going wrong and hence, perhaps, an indicator of what to do about it.

Going back more than half a century, just such a biomarker was found.  Increased platelet levels of 5-HT (5-Hydroxytryptophan) were found in 30-40% of the autistic population.  5-HTP increases the production of the neurotransmitter serotonin and so it was suggested that hyperserotonemia may be a factor in autism.

  

Hyperseratonemia (Serotonin syndrome)

Hyperseratonemia is not treated by reducing the amount of serotonin, rather by using a receptor antagonist that in effect blocks the serotonin effect.

  

SSRIs and other anti-depressants

Several classes of drugs target the 5-HT system including  anti-depressants, antipsychotics, anxiolytics, antiemetics, and antimigraine drugs, as well as the psychedelic drugs and empathogens.

In you live in the US, you will have heard of Prozac (vitamin P) which is a very widely prescribed anti-depressant.  It is in a class of drug called Selective Serotonin Re-uptake Inhibitors or SSRI.  Many autistic children in the US are prescribed SSRIs like Prozac. In Japan Prozac is illegal.

SSRIs are believed to increase the extracellular level of serotoinin by inhibiting its reuptake.  Excessive use of SSRIs is known to lead to hyperseratonemia.  If you are already prone to hyperserotonemia, like 40% of autistic kids, it would seem that SSRIs could be potentially dangerous drugs.

A good deal of research does exist on the use of SSRIs in autism and it pretty much shows that they do not do much good, (and they certainly can have nasty side effects).  Look at page 6, in the review paper below that included all kinds of drugs trialled in autism.

Psychotropic Medications in Children with Autism Spectrum

Disorders: A Systematic Review and Synthesis for Evidence-Based Practice

LSD and other serotonin antagonists

LSD is a banned substance in the US and Europe, but in the time before I was born, it was being used to treat autism.  LSD, among other things, is a serotonin antagonist.  There are indeed several papers published on its use in autism and other conditions.

I was quite surprised to see Ivaar Lovaas, the “father” of Applied Behavioural Analysis (ABA) was merrily giving autistic children LSD at UCLA in the early 1960s.

Modification of Autistic behaviour with LSD-25

These old studies are quite interesting and if you want more just click here.

I am not suggesting you take your child to Amsterdam, but if you look on Google you will see that adults with ASD are indeed using LSD therapy.

It now appears that after being banned from use decades ago, medical research with LSD has been restarted.

Fortunately, there are other serotonin antagonists that are available and will not land you in trouble.  The one that attracted my attention is Cyproheptadine or Periactin.

Cyproheptadine in Research

There has been just one study published on autism and Cyproheptadine and that was in 2004.  It is not exactly what we need, since it was being trialed as an adjunct therapy to haloperidol.  Haloperidol is an antipsychotic.

If you live in the US you will be familiar with Risperidone, which is another antipsychotic shown to be effective in autism. In the UK, only specialists such as child psychiatrists can prescribe risperidone for children with autism.  Risperidone can cause side effects like uncontrollable shaking.

So the trial was in effect to see the effect of the antipsychotic + Cyproheptadine vs antipsychotic + placebo.  This is not exactly what we want, but better than nothing.

As you will see in the charts below, the addition of Cyproheptadine did indeed make a marked improvement.  Sadly this research has not been followed up on.

    

Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial… -

Serotonin and Emotional Response

There was a recent study looking at how the emotional response of adults with autism was affected by lowering serotonin levels, I could not find the full version.

Cognition and behaviour: Serotonin may alter emotion response

Conclusion

Elevated blood levels of serotonin may or may not be a “red herring” in autism research.  The evidence is far from complete and it is not going to be a magic bullet.  Nonetheless, I suspect lowering serotonin levels may have far more impact than those expensive high EPA Omega 3 pills many parents are feeding to their kids.

The latest research does actually indicate that genetic differences cause the high levels of 5-HT in autism.  100% conclusive research does not exist showing the value of counteracting this genetic difference.  A safe, cheap, serotonin antagonist, Cyproheptadine /Periactin does exist; and it is available OTC in some countries.

Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior

Central Hypothyroidism or Low Brain D2 Levels in Autism

I am returning to an old theme of mine, which is my hypothesis that the thyroid releasing hormone (TRH) may be of therapeutic value in autism.  I have been reading up on what some endocrinologists are doing the US and also looking a bit deeper into the underlying biology of the related hormones and thinking about my research sample of one, Monty aged 10 with ASD.   My original hypothesis was argued in an earlier post.

The Peter Hypothesis of TRH-induced Behavioural Homeostatis in Autism

Since none of the TRH researchers care to reply to my emails, I decided to refine and document my hypothesis further and then plan to go and see a child endocrinologist for myself.  In most countries, the doctor does the talking and the patient does the listening, so I know that I need something unusual; I called it “an open minded endocrinologist”.

Peter’s TRH & Central Hypothyroidism Theory

Research has documented which parts of the autistic brain are often damaged.  The Purkinje cell layer and the cerebellum in general has been a focus of my blog; but the hypothalamus, which is very close by, is also known to be different in autistic people.   It has been shown that diminished grey matter exists in a region of the hypothalamus, which synthesizes the behaviorally relevant hormones oxytocin and arginine vasopressin.  My pet hormone “TRH” is also produced in the hypothalamus.  The pituitary gland is a protrusion off the bottom of the hypothalamus at the base of the brain. The pituitary gland is functionally connected to the hypothalamus via a small tube called the pituitary stalk. The pituitary gland secretes nine hormones that regulate homeostatis; one of these is TSH (thyroid stimulating hormone). 

In summary, TRH from the damaged hypothalamus travels down to the pituitary gland where it triggers the release of TSH.  TSH travels a bit further to the thyroid gland where two important hormones, T3 and T4, are produced.

When the levels of T3 and T4 are low a condition called hypothyroidism exists.  T4 is a so-called pro hormone of T3.

I have already noted that when Monty was a young toddler he was tall for his age, about the 90^th percentile; aged 10 his is now about the 25% percentile.  When I started this blog, I saw in the old autism literature there are lots of studies about head circumference in autism.  In summary they found that in autism the head (and by inference the brain) grows very fast in the first couple of years and then by 3 or 4 years of age the brain has prematurely reached adult size.  The brain grew faster than normal and certain parts developed abnormally.  I did not see any research into abnormal development in height.  It would be very easy to study this, since in most countries a child’s height is regularly recorded.

When I recently checked to see what are the effects of hypothyroidism in typical children, I found interesting reading:-

Effects of Hypothyroidism During Infancy. Transient hypothyroidism is common among premature infants. Although temporary, severe cases can cause difficulties in neurologic and mental development.

Infants born with permanent congenital (inborn) hypothyroidism need to receive treatment as soon as possible after birth to prevent mental retardation, stunted growth, and other aspects of abnormal development (a syndrome referred to as cretinism). Untreated infants can lose up to three to five IQ points per month during the first year. An early start of lifelong treatment avoids or minimizes this damage. Even with early treatment, however, mild problems in memory, attention, and mental processing may persist into adolescence and adulthood.

Effects of Childhood-Onset Hypothyroidism. If hypothyroidism develops in children older than 2 years, mental retardation is not a danger, but physical growth may be slowed and new teeth delayed. If treatment is delayed, adult growth could be affected. Even with treatment, some children with severe hypothyroidism may have attention problems and hyperactivity.

Hypothyroidism is usually caused by a failure of the thyroid gland.  TRH is being released to the pituitary, which the produces TSH.  The problem is in the thyroid.  The cure is usually to give T4 in tablet form.  The body is usually able to produce T3 from the T4.

Role of D2 and D3 & Oxidative Stress

Both T3 and T4, are produced in the thyroid gland. The ratio of T3 to T4 released into the blood is 1:20.  Both T3 and T4 then reach the individual body organs, where the prohormone T4 is converted to the biologically active hormone T3. The organ/tissue levels of T3 are regulated locally primarily by the activity of two different selenoenzymes, deiodinases type 2 (D2) and type 3 (D3), although deiodinase type 1 is also involved. In the CNS, approximately 70-80% of T3 originates from intracerebral T4 to T3 conversion, while the plasma contribution amounts to 20-30 %  and D2 is responsible for most of the T3 supply within the brain.

The major source of the biologically active hormone T3 in the brain is the local intra-brain conversion of T4 to T3, while a small fraction comes from circulating T3.

As evidence derived from in vitro studies suggests, in response to oxidative stress D3 increases while D2 decreases (Lamirand et al., 2008; Freitas et al., 2010).  As we know in the autistic brain we have a lot of oxidative stress.

Furthermore, in ASD, the lower intra-brain T3 levels occur in the

Absence of a systemic T3 deficiency (Davis et al., 2008), most likely due to the increased activity of D3.

 

Central Hypothyroidism

There is a supposedly rare condition called Central Hypothyroidism, which occurs when the pituitary gland does not produce enough TSH in response to TRH.  In the research jargon they call it “a blunted response”.  Note that blood levels of TSH, T3 and T4 can be normal in cases of central hypothyroidism.

Research has long ago shown that in autistic children often have a blunted response of TSH to TRH.  Interestingly in many psychiatric conditions, like depression, research also shows a blunted response.

Reduced thyroid-stimulating hormone response to thyrotropin-releasing hormone in autistic boys.

 

The Blunted TSH Responseto TRH — What Does It Tell Us? Biological Monitoring During Psychopharmacological Treatment

Panic, suicide, and agitation: independent correlates of the TSH response to TRH in depression

In the US, psychiatrist have longed prescribed the hormone T3 for depression.  I cannot find much in the way of explanation by psychiatrists of this, other than that some endochronologists do not seem to approve.

In theory if you are low on T3 and T4, the therapy is to give just T4. But as we learned above, if D2 and D3 are misbehaving T3 will not be produced as required.

In the “rare” cases of central hypothyroidism the researchers report being able to correct T4 quite easily but not T3.  So their bodies are not converting enough T4 into T3, because D2 and D3 levels are out of balance.

So the Peter theory has to evolve

In autism there is very likely to be central hypothyroidism, a deficiency of D2 in the brain causes low T3 and I conjecture that there is also a reduced level of TRH being produced in the hypothalamus.  Both the hypothalamus and the pituitary gland are under-responsive.  As a result many hormones are going to be reduced including TRH, TSH, oxytocin, arginine vasopressin and others.

Because TRH also has secondary, only recently understood, behavioral effects, the central hypothyrodism symptoms fits nicely with my earlier TRH theory.

In the US some “holistic” doctors specialized in autism have long been claiming that the majority of kids with ASD are hypothyroid.  They claim that the modern T3 and T4 blood tests are “inaccurate” and that the old TRH stimulation test is more “accurate”.  They then end up prescribing supplementary T3 and T4.  This always looked odd to me; in fact it is yet another case of getting the right answer, but for the wrong reason.

The perfect solution might have been just to give TRH.  You cannot do this because the half-life of TRH is just a few minutes and it needs to be delivered into a vein.   A nasal TRH spray is being developed with funding from the US military.  TRH has mood changing properties and the military has a big problem with suicide.

My idea of using a TRH analog, such as Taltirelin Hydrate, is practical since it has a long half-life and can be taken orally.  It is licensed as a drug, but only in Japan.  It also has a reduced effect on TSH, so you get the benefit of the behavioural properties of TRH rather than just producing more TSH.  This avoids the patient then going hyperthyroid.

A word from the Harvard Medical School

After interest in the 1970s researching autism and the thyroid, not much has been written for decades.  Recently a paper was published by researchers at the Harvard Medical School showing how oxidative stress in the brain, if present, would disrupt thyroid hormone homeostatis.  It has been a long time coming, but it looks like their thinking is spot on.

Environmentally Induced Oxidative Stress and Disruption of Brain Thyroid Hormone Homeostasis in Autism Spectrum Disorders

 

According to this hypothesis, brain region-specific oxidative stress in autism may be associated with increased D3 and decreased D2 activity resulting in a region-specific T3 deficiency in the brain. Future human studies utilizing the CSF of living ASD individuals or postmortem brain tissue of ASD donors will support its validity. Such findings would have several significant implications. They may result in methods of early ASD diagnosis; detection of high brain D3 levels in postmortem human brains may suggest the benefits of measuring the levels of its product (rT3) in the CSF of living patients to assess the risks, monitor the disease progression and efficacy of ongoing treatment. Furthermore, several tissue-specific and TH receptor (TR)-specific thyromimetics have been developed as potential treatment for atherosclerosis, obesity and Type 2 diabetes and might be able to correct local brain TH deficiency without systemic thyrotoxicity (Baxter and Webb, 2009) and may thus be considered as potential therapeutic agents. Finally, confirmation that autism may be associated with increased D3 and decreased D2 activity resulting in a region specific T3 deficiency in the brain could lead to or reinforce dietary treatments, because D2 activity can be modulated not only by selenium but also by xenobiotic compounds (da-Silva

et al., 2007). In conclusion, TH abnormalities in autism warrant a second look.

This paper from Harvard is encouraging and not only concludes that thyroid abnormalities in autism warrant a second look, but suggests ways to raise the level of D2 and correct local brain hypothyroidism

The xenobioyic compound they refer to is the flavonoid kaempferol.

The flavonoid kaempferol looks interesting and there is also much written about its anti-diabetic effects.  This would be a way to raise the amount of D2 and consequently T3 in the brain.  This might be more effective that just supplementing T3.

By the way, just look at all the other things claimed of this flavonoid:-

Numerous preclinical studies have shown kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, antiosteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic, and antiallergic activities.

Kaempferol consumption is also correlated with a reduced lung cancer incidence.

Kaempferol may be a potent prophylactic against NOX-mediated neurodegeneration

If you like natural cures, you will like this paper.  Take a look at page 28.  

A Review on the Dietary Flavonoid Kaempferol

As with other flavonoids, there is low bioavailability – they are absorbed by the body in tiny quantities.  And they are VERY expensive.

 

Conclusion

I wish the Harvard Medical School would follow up fast on its own research, so I do not have to rely on the internet writings of “holistic” doctors.  As the Harvard paper concluded “TH abnormalities in autism warrant a second look”.

Oral T3 clearly does enter the brain in marked quantities, otherwise I suppose US psychiatrists would not keep using it with their depressed patients.  Research shows that most T3 in the brain originates from T4 converted there by D2.  This implies to me that an alternative therapy would be to give something like kaempferol to raise the level of D2.  The problem, as with other useful flavonoids, like Quercetin and Rutin, is low bioavailability – they are absorbed by the body in tiny quantities.  Kaempferol appears to have the basis of being a wonder drug, but let's wait 20 years to see.

In the meantime, I will review all this with my sought for “open minded endochronologist”.  All I can measure is TSH, T3 and T4 in the blood, I cannot even guess at T3 or D2 in the brain.  The old TRH stimulation test involves lots of needles and that is something I have to try and avoid.  Autistic kids don’t sit still for needles.