Showing posts with label Bittker. Show all posts
Showing posts with label Bittker. Show all posts

Thursday 22 June 2023

Autism Research Merry-go-round Keeps Turning


Today’s post again shows that many issues raised in previous posts keep on coming back  is that good news? Only you can decide.

I start with the “old chestnut” (English idiom to imply “a tired old story”) of the Autism Tsunami. 

Then we see what has come up in the world of autism interventions in the research in the last 3 weeks, most of which regular readers will already be aware of.

·        Autism Tsunami – real or not?

·        Vitamin D

·        Bumetanide

·        Ibudilast

·        Niclosamide

·         Non-invasive brain stimulation

·         Simvastatin 

I noted the research about autism incidence coming from Northern Ireland because it was published in the Belfast News Letter.  These days it has a tiny subscription, but I am one of those who know it is the world's oldest English-language general daily newspaper still in publication, having first been printed in 1737. In 1972 a bomb warning was called in to the paper's office and, as people evacuated, an explosion went off nearby killing several people and injuring many more. Back in the early 1990s, when some people in Northern Ireland were still blowing up others with bombs, I made a visit to Northern Ireland to meet the management of this newspaper. 

Their recent article on autism incidence is very well researched considering how only about 8,000 copies are published. Keep up the good work!

Idea that 5% of all Northern Ireland's children are autistic is 'a fantasy' claims international expert

Professor Laurent Mottron was speaking to the News Letter following a claim that the rate of autism in Northern Ireland is double the rate in the rest of the UK.

Back in 2019 Prof Mottron had authored a report warning about a tsunami of over-diagnosis, saying that soon "the definition of autism may get too vague to be meaningful, trivializing the condition"

“If this trend holds, the objective difference between people with autism and the general population will disappear in less than 10 years," he had said then – and has now indicated that this “fuzziness” is what’s helping swell the numbers in Northern Ireland.

Meanwhile Jill Escher, the president of the National Council on Severe Autism, takes a different view.

She says that evidence indicates the "skyrocketing" rate of autism in Northern Ireland is real, adding: "It boggles my mind that it is not the subject of the highest possible alarm and inquiry."

"One in 20 children in Northern Ireland of school age has a diagnosis of autism," he told MPs.

"[It is] one in 57 in the rest of the UK. The need in Northern Ireland is significantly different."

To put that in perspective, that would mean 5% of Northern Irish children are diagnosed with autism, compared with 1.8% in the rest of the UK.

Prof Mottron, a psychiatrist based at Montreal University, told the News Letter "numbers such as 5% are pure fantasy... these numbers correspond to the part of the general population which has less overt socialisation, which has minimally to do with prototypical autism". 

There is a "current fuzziness of autism diagnosis and over-inclusivity," he said, leading to "a situation of perfect confusion between autistic traits and prototypical autism" (that is, mixing up people who exhibit some tendencies of autistic people with people who actually have the full-blown condition). 

"The scientific 'quasi consensus' would be around 1% everywhere on the planet,” he added.


So on one side we have Jill Escher and her NCSA and on the other we have a French/Canadian researcher.  This time Laurent Mottron but in my blog posts I quoted Éric Fombonne.

A paper that was mentioned both in my blog and critiqued by Jill about autism incidence and cost just got retracted.  In reality a better word is “cancelled.”  The 3 authors are very much in the politically incorrect camp of the autism debate.

I was surprised it ever got published.  

Controversial ‘cost of autism’ paper retracted 

Citing methodological issues and undeclared conflicts of interest, an autism journal has retracted a paper that forecast the prevalence and cost of autism.

The retraction note, posted last week, comes two years after Spectrum reported on backlash surrounding the paper, which was published in the Journal of Autism and Developmental Disorders in July 2021. A month after publication, the journal added an editor’s note that the study was under investigation because of criticisms of its conclusions. 

“I am glad to see that it was retracted, although at a pace that maybe is a bit frustrating in terms of how long it took. But it was the right choice,” says Brittany Hand, associate professor of health and rehabilitation sciences at Ohio State University in Columbus.

Outside experts who reviewed the paper on the journal’s behalf found that it misrepresented the rise in autism diagnoses and gave “insufficient attention” to some potential causes of the increase, such as improved surveillance and changes to the diagnostic criteria. The authors also used “higher estimates and assumptions that inflated costs,” according to the retraction note.

The authors — Mark Blaxill, Toby Rogers and Cynthia Nevison — all disagree with the journal’s decision, the note also says.

The cancelled paper is here:-

Autism Tsunami: the Impact of Rising Prevalence on the Societal Cost of Autism in the United States


I assume Blaxill was the driving force behind all the math, because he is the ex- management consultant, with a son with severe autism that his dad attributes to vaccines.

What I found bizarre in their paper was that they has a prevention scenario, based on what they think has already happened in rich parts of California, where they think autism incidence is falling.  It is not falling, all that is happening is that wealthy Californians are paying for treatment using insurance or their own money, and no longer burdening the State.

The “rainbow” researchers that wanted the paper retracted think that preventing autism is akin to eugenics and Dr Mengele. According to Peter, treating autism is good, while Dr Josef Mengele, byname Todesengel (German: “Angel of Death”) was as bad as you can get.    

Jill Escher and her NCSA think that you cannot prevent autism.  According to Peter, you can both minimize the incidence and severity of autism. 

A bugbear of our reader Tanya is that the NCSA have a pet hate of facilitated communication and in particular the rapid prompting method (RPM). This method worked for Tanya’s son and it opened the door to independent, un-facilitated communication. 

Always keep an open mind.




“our Prevention scenario is based on real rates observed among wealthy white and Asian children in the California DDS.  Severe ASD prevalence has flattened and even declined among these children since birth year 2000, suggesting that wealthy parents have been making changes that effectively lower their children’s risk of developing ASD. The Prevention scenario assumes that these parental strategies and opportunities already used by wealthy parents to lower their children’s risk of ASD can be identified and made available rapidly to lower income children and ethnic minorities, who are currently experiencing the most rapid growth in ASD prevalence”


New Paper Makes Case that Autism Tsunami May Threaten American Economy

A major weakness in the analysis was the “Prevention Scenario” in which future costs were projected based on “what might be possible if strategies for reducing ASD risk are identified and addressed in the near future.” As I think everyone knows, at this time there is no way to prevent autism. But the authors use the observation that autism in the DDS is declining among wealthier white families, and thus “suggesting that wealthy parents have been making changes that effectively lower their children’s risk of developing ASD.” No, it’s far more likely that wealthier families are not entering their children into the system because they access services through insurance and school districts instead.


Vitamin D as a cause of autism has been discussed for decades.  As the title below puts it – a never-ending story. Our reader Seth Bittker even wrote a paper about it. He later wrote a paper about the use Acetaminophen/Paracetamol in children under two as a risk factor in developing autism. Good work Seth!


Maternal Vitamin D deficiency and brain functions: a never-ending story 

A large number of observational studies highlighted the prevalence rates of vitamin D insufficiency and deficiency in many populations as pregnant women. Vitamin D is well known to have a crucial role in differentiation and proliferation, as well as neurotrophic and neuroprotective actions in brain. Then, this micronutrient can modulate the neurotransmission and synaptic plasticity. Recent results from animal and epidemiological studies indicated that maternal vitamin D deficiency is associated with a wide range of neurobiological disease including autism, schizophrenia, depression, multiple sclerosis or developmental defect. The aim of this review is to provide a state of the art on the effect of maternal vitamin D deficiency on brain functions and development.

4.2.2. Autism

Autism spectrum disorder (ASD) is a complex neurodevelopmental disease with repetitive behaviour and difficulties in social interaction, communication and learning. Several murine studies and cohorts have demonstrated that early exposure to low levels of VD during pregnancy could be a risk factor for ASD. In 2019, Ali et al. aimed to find out the impact of a maternal VDD on early postnatal, adolescent and adult offspring. By assessing righting reflex and negative geotaxis, they found out that the pups from deficient dams showed a delay in their motor development. P12 rats from deficient females also exhibited increased ultrasound vocalization indicating an alteration in their vocal communication. Adolescent and young adult rats displayed an altered stereotyped repetitive behaviour as they had a reduced digging behaviour. Adolescent rats had less social interaction with longer latency to interact, which was not found in adult rats; however, adults were more hyperactive but showed no anxiety like behaviour.  In another animal study, maternal VDD induced an increase in the vocalizations of the pups accompanied with a decrease in cortical FoxP2, decrease in social behaviour and impaired learning and memory were observed in adult males (Table 1). Using data from the Stockholm youth cohort, Magnusson et al. examined a population of 4-17-year-old children exposed to low levels of VD during gestation and was able to report a positive association between maternal VDD and ASD. Analysing the same cohort, Lee et al. suggested that high levels of VD during pregnancy were associated with a moderate decrease in risk of ASD in the offspring. A prospective study of a multi-ethnic cohort in the Netherlands (generation R study) has also shown an association between maternal mid-gestation VDD and a two-fold increase in the risk of autism in children (Table 2). Interestingly, VD supplementation seems to clinically improve ASD symptoms of affected children.


People do associate this blog with Bumetanide.  Yet another paper has been published showing the benefits of this therapy for autism.


EEG-based brain connectivity analysis in autism spectrum disorder: Unravelling the effects of bumetanide treatment 



·        We investigated the nonlinear brain connectivity and topological changes in brain networks of people with autism spectrum disorders (ASD) after a three-month course of bumetanide treatment.

·        We found statistically significant differences between pre and post intervention in the connectivity patterns using repeated measures analysis of variance (ANOVA).

·        We found that the number of strong connections in response to sad image stimuli seem to be less compared with that of the other two stimuli, especially in the central area.

·        We found that the changes in brain connectivity between pre and post intervention is more significant in response to sad image stimuli.


Emerging evidence suggests that cognitive impairment associated with brain network disorders in people with autism could be improved with medications such as bumetanide. However, the extent to which bumetanide is effective in improving brain function in these individuals has not been adequately studied. The main purpose of this study is to investigate the nonlinear brain connectivity and topological changes in brain networks of people with autism spectrum disorders (ASD) after a three-month course of bumetanide treatment. We used electroencephalography (EEG) data of nine participants recorded during the face emotion recognition activity in two stages before and after bumetanide treatment. Brain connectivity matrix was calculated using a neural network-based estimator. Graph criteria and statistical tests have been used to determine the effects of bumetanide treatment on children and adolescents with autism. Bumetanide treatment significantly alters the brain connectivity networks based on stimuli type. Differences in brain connectivity related to the sad stimuli are more significant. The most of the significant changes of the strength graph metric was in the occipital electrodes and electrodes related to the right hemisphere. These results suggest that bumetanide may affect effective connectivity and be used a promising treatment for improving social interactions in patients with autism. It also suggests that brain connectivity patterns can be considered as a neural marker to be used in the development of new therapies. 

I have also covered in sometimes painful details the potential to treat autism and increase cognitive function using PDE (Phosphodiesterase) inhibitors. One of our psychiatrist readers is a huge fan of Pentoxifylline and takes it himself.

I was recently asked how to obtain Ibudilast.  It is approved in Japan as an asthma drug. Sometimes it is called Ketas and you can get it from an “International Pharmacy” in Germany/Switzerland if you have a prescription. 

I also wrote about repurposing Roflumilast, which as Daxas is approved all over the world as a therapy for severe asthma (COPD). This drug at a 1/5th dose has been patented as a cognitive enhancer.


Phosphodiesterase inhibitor, ibudilast alleviates core behavioral and biochemical deficits in the prenatal valproic acid exposure model of autism spectrum disorder


Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder, presenting with a variety of aetiological and phenotypical features. Ibudilast is known to produce beneficial effects in several neurological disorders including neuropathic pain, multiple sclerosis, etc. by displaying its neuroprotective and anti-inflammatory properties. Here, in our study, the pharmacological outcome of ibudilast administration was investigated in the prenatal valproic acid (VPA)-model of ASD in Wistar rats.


Autistic-like symptoms were induced in Wistar male pups of dams administered with Valproic acid (VPA) on embryonic day 12.5. VPA-exposed male pups were administered with two doses of ibudilast (5 and10 mg/kg) and all the groups were evaluated for behavioral parameters like social interaction, spatial memory/learning, anxiety, locomotor activity, and nociceptive threshold. Further, the possible neuroprotective effect of ibudilast was evaluated by assessing oxidative stress, neuroinflammation (IL-1β, TNF-α, IL-6, IL-10) in the hippocampus, % area of Glial fibrillary acidic protein (GFAP)-positive cells and neuronal damage in the cerebellum.

Key findings: Treatment with ibudilast significantly attenuated prenatal VPA exposure associated social interaction and spatial learning/memory deficits, anxiety, hyperactivity, and increased nociceptive threshold, and it decreased oxidative stress markers, pro-inflammatory markers (IL-1β, TNF-α, IL-6), and % area of GFAP-positive cells and restored neuronal damage.


Ibudilast treatment has restored crucial ASD-related behavioural abnormalities, potentially through neuroprotection. Therefore, benefits of ibudilast administration in animal models of ASD suggest that ibudilast may have therapeutic potential in the treatment of ASD.



I have also written widely about repurposing certain anti-parasite medicines to treat autism. This is not because I think parasites cause autism, it is the secondary modes of action.



Repurposing Niclosamide as a plausible neurotherapeutic in autism spectrum disorders, targeting mitochondrial dysfunction: a strong hypothesis



Autism Spectrum Disorders (ASD) are a complex set of neurodevelopmental manifestations which present in the form of social and communication deficits. Affecting a growing proportion of children worldwide, the exact pathogenesis of this disorder is not very well understood, and multiple signaling pathways have been implicated. Among them, the ERK/MAPK pathway is critical in a number of cellular processes, and the normal functioning of neuronal cells also depends on this cascade. As such, recent studies have increasingly focused on the impact this pathway has on the development of autistic symptoms. Improper ERK signaling is suspected to be involved in neurotoxicity, and the same might be implicated in autism spectrum disorders (ASD), through a variety of effects including mitochondrial dysfunction and oxidative stress. Niclosamide, an antihelminthic and anti-inflammatory agent, has shown potential in inhibiting this pathway, and countering the effects shown by its overactivity in inflammation. While it has previously been evaluated in other neurological disorders like Alzheimer’s Disease and Parkinson’s Disease, as well as various cancers by targeting ERK/MAPK, it’s efficacy in autism has not yet been evaluated. In this article, we attempt to discuss the potential role of the ERK/MAPK pathway in the pathogenesis of ASD, specifically through mitochondrial damage, before moving to the therapeutic potential of niclosamide in the disorder, mediated by the inhibition of this pathway and its detrimental effects of neuronal development.


Note that in earlier posts I explored RASopathies as potentially treatable types of intellectual disability (ID). We also have RAS-dependent cancers as a discrete treatable sub-type of cancer.

The ERK/MAPK pathway is known to interact with multiple genes that have been implicated in autism, and genome-wide association analysis of the same have supported these findings. As such, a dysregulation of this pathway has been found to result in many CNS disorders, including ASD-related syndromes, in many studies. These syndromes are collectively known as Rasopathies, due to the fact that the affected genes include those encoding for elements which function together with Ras, a G-protein responsible for activating ERKs (Levitt and Campbell 2009; Tidyman and Rauen 2009). It has been found that ASD is linked to the occurrence of many Rasopathies, and there have been multiple reports suggesting the possible relation of ERK/MAPK pathway defects with the incidence of ASD (Vithayathil et al. 2018; Aluko et al. 2021)⁠⁠. Moreover, a detailed study has found that single nucleotide polymorphisms (SNPs) in the ERK/MAPK-related genes are more common in subjects presenting with idiopathic ASD.


Niclosamide is an FDA-approved antihelminthic drug which is routinely used to treat tapeworm infections by inhibiting their mitochondrial oxidative phosphorylation and ATP production. In addition, it has long been known to have significant immunomodulating activity, and has been shown to inhibit a number of signaling pathways, including the Wingless-related integration site (Wnt)/β-catenin, nuclear factor kappa B (Nf-κB), signal transducer and activator of transcription 3 (STAT3), and mammalian target of rapamycin (mTOR) (Chen et al. 2018). However, while these targets are known to be rather well-characterized in terms of the effect that niclosamide has on them, there are also other targets, including the phosphoinositode 3 kinase/Akt (PI3K/Akt) and ERK/MAPK pathways, that are seen to be downregulated by the agent. Hence, given the possible relation of the ERK pathway in autism, there has been interest in the potential role of niclosamide in the management of the prognosis of ASD. This article aims to discuss the possible therapeutic benefit of niclosamide in the treatment of autism spectrum disorders.


Now I know that parents like the idea of treating autism with various gadgets you can strap on to your head  things like Transcranial Magnetic Stimulation (TMS). I must say I liked my old post on Photobiomodulation/cold laser/low level laser therapy.

Epiphany: Low Level Laser Therapy (LLLT) for Autism – seems to work in Havana

From China we have a new round-up paper, but the full text does not yet seem to be ready.


Non-invasive brain stimulation for Patient with Autism A Systematic Review and Meta-Analysis

Objective: To comprehensively evaluate the efficacy of non-invasive brain stimulation (NIBS) in patients with autism spectrum disorder (ASD) in randomized controlled trials (RCT),providing reference for future research on the same topic.

Methods:Five databases were searched (Pubmed,Web of science,Medline,Embase and Cochrane library) and track relevant references,Meta-analysis was performed using RevMan 5.3 software.

Results: Twenty-two references(829 participants) were included. The results of meta analysis showed that, NIBS had positive effects on repetitive and stereotypical behaviors, cognitive function and executive function in autistic patients. Most of the included studies had a moderate to high risk of bias, Mainly because of the lack of blinding of subjects and assessors to treatment assignment, as well as the lack of continuous observation of treatment effects.

Conclusions: Available evidence supports an improvement in some aspects of NIBS in patients with ASD. However, due to the quality of the original studies and significant publication bias, these evidences must be treated with caution. Further large multicenter randomized double-blind controlled trials and appropriate follow-up observations are needed to further evaluate the specific efficacy of NIBS in patients with ASD.

Unfortunately, the Chinese have concluded that most of these studies are not reliable. So no laser for me to go out and buy just yet.

No need to dent your bank balance with the next therapy.  We are back to one of the world's most prescribed and therefore affordable drugs, its Simvastatin (Zocor). 

There is masses of information in this blog about the potential to treat sub-types of autism with Atorvastatin, Simvastatin or Lovastatin. They are each slightly different.


Effect of simvastatin on brain-derived neurotrophic factor (BDNF)/TrkB pathway in hippocampus of autism rat model 

Purpose: To study the effect of simvastatin on behavioral performance in a rat model of autism, and its effect on hippocampal brain-derived BDNF-TrkB pathway. 

Methods: Twelve rats with valproic acid (VPA)-induced autism were randomly divided into model group and simvastatin group, while six healthy rats served as normal control group. Rats in the simvastatin group received the drug (5 mg/kg) via i.p. route, while rats in model group and normal control group were injected with equivalent volume of normal saline in place of simvastatin. Capacity for interaction and repetitive stereotyped behavior, as well as results of Morris water maze test were determined for each group. The expressions of BDNF-TrkB proteins were assayed with immunoblotting. 

Results: The frequencies of sniffing normal saline, alcohol and rat urine were significantly higher in model and simvastatin rats than in normal rats, but they were significantly lower in simvastatin-treated rats than in model rats (p < 0.05). There was higher duration of turning, jumping and grooming in the model group and simvastatin group than in the normal rats, but the duration was significantly reduced in simvastatin rats, relative to model rats. Escape latency times was significantly longer in model and simvastatin rats than in controls, but number of target quadrant crossings was significantly reduced. However, escape latency time was lower in simvastatin rats than in model rats, but number of target quadrant crossings was significantly higher. The model and simvastatin rats had down-regulated levels of BDNF and TrkB protein, relative to control rats, but there were markedly higher levels of these proteins in simvastatin-treated rats than in model rats. 

Conclusion: Simvastatin improves the behavioral performance of autistic rats by regulating BDNF/TrkB signal axis. This finding may be useful in the development of new drugs for treating autism.



What is the conclusion? Well, I could say give up reading the new research and just read my old posts.  It seems you are not going to miss very much.

Of course, back in the real world, it is true that things do take time to change and after a few decades the leap might be taken from the research to the doctor’s office.

There already is plenty of research on the causes of autism and what steps can be taken by those who want to treat aspects of it.  It is far from a complete picture, but it is enough to get started.  There are no guarantees of success, but if you want 100% certainty you will wait forever.

Monday 14 March 2016

Benfotiamine for Autism

by Seth Bittker

In recent decades populations of wild bird species in the Baltic Sea have been dying off in large numbers from a paralytic disease.  When some of the birds with signs of this disease are given thiamine, they rapidly improve.  So it would appear the immediate cause of these large scale population decreases among the birds of the Baltic is thiamine deficiency [1]. The same thing appears to be happening to large mammals like elk [2].

Setting aside the question of underlying cause, could it be another mammal high up the food chain also has many members of its population suffering  from thiamine deficiency?  There is no good standardized test for thiamine deficiency that does not involve supplementing with thiamine.  So whether individual humans are somewhat deficient in thiamine is not obvious.  However, a particular constellation of symptoms was recognized as the disease “beriberi” before it was understood that the underlying cause was thiamine deficiency.  And what are the signs of beriberi?  The symptoms are variable but some that have been observed are mental confusion, irritability, difficulty moving, loss of sensation, loss of muscle function, rashes, involuntary eye movements, digestive issues, abdominal pain, and sometimes lactic acidosis [3].

Many of these symptoms match the symptoms of some with autism.  So one might naturally wonder whether some cases of autism are in fact unrecognized cases of beriberi and perhaps more likely that thiamine deficiency could play a role in other cases of autism depending upon other genetic and environmental factors.  A Dr. Luong and Dr. Nguyen previously noticed this similarity and developed this idea into a paper from 2013 which is available here [4].

Pulling from their Abstract:

“A relationship between thiamine status and the development of autism has been established, with thiamine supplementation exhibiting a beneficial clinical effect on children with autism. Thiamine may involve in autism via apoptotic factors (transcription factor p53, Bcl-2, and caspase-3), neurotransmitter systems (serotonin, acetylcholine, and glutamate), and oxidative stress (prostaglandins, cyclooxygenase-2, reactive oxygen species, nitric oxide synthase, the reduced form of nicotinamide adenine dinucleotide phosphate, and mitochondrial dysfunction). In addition, thiamine has also been implicated in autism via its effects on basic myelin protein, glycogen synthetase kinase-3β, alpha-1 antitrypsin, and glyoxalase 1.”

A researcher named Derrick Lonsdale found in 2003 that a set of 8 of 10 children with autism had clinical improvement on suppositories containing thiamine tetrahydrofurfuryl disulfide (TTFD), a thiamine derivative [5].  There was no control group on this study.  So one should be cautious when interpreting these results.  In addition Lonsdale was interested in metals excretion – TTFD can serve as a chelator.  He found that TTFD increased excretion of such toxic metals but it also would increase thiamine levels as well.

I have not experimented with TTFD, but Lonsdale’s work did get me thinking about oral supplementation of thiamine.  I tried experimenting with my son on regular thiamine hydrochloride.   I thought there may have been a very modest effect in terms of increasing his energy but it was not a sizeable effect.  However, there are other forms of thiamine.  One lipid soluble form that has been used with some modest success in diabetic neuropathy is benfotiamine [6].

There are case reports of neuropathy in cases of autism [7].  In addition one symptom of some with autism that are significantly affected is arm flapping.  It seems to me a person may flap his arms if he is feeling numbness and he is trying to get blood flowing to reduce the discomfort.  For the same reason somebody who is cold may move his limbs rhythmically.  In other words, I think arm flapping may typically be a sign of neuropathy and that neuropathy is an under-recognized and often comorbid condition with autism.

My son does not have neuropathy, but we did try benfotiamine on him.  My experience is that on it he had a significant reduction in irritability, increased cuddliness, and more energy.  I also feel he was mentally sharper initially but this diminished with higher doses.  Another result was he had flatulence some of which was pungent soon after starting supplementation.  In retrospect I take this as a sign that his digestion was beginning to operate more efficiently and relatedly he may have been dumping xenobiotics into his bowel when starting benfotiamine but this is pure speculation on my part.

After about a week on benfotiamine he got a rash and I began to feel that his mental acuity was leveling off.  I found that if I gave him biotin the rash went away and his mental acuity became sharper again.  Biotin and thiamine are both sulfur containing B-vitamins  and there are genetic diseases where both are involved [8].   My experience with my son suggests to me that there may be some common pathways with these nutrients.  In other words, I think befotiamine supplementation may exacerbate biotin deficiency.  As some may be aware, biotin deficiency is also sometimes seen in autism [9].  So for this reason I think they should be taken together when given for autism.

Thus, if you do a trial of benfotiamine, I would include biotin as well.  I am currently giving my son about 120 mg of benfotiamine per day and 5 mg of biotin per day.  He is about 90 pounds.  I give these to him in a juice smoothie because benfotiamine tastes a bit tangy.  You might also consider providing them in something sweet.

In interest of full disclosure when communicating about benfotiamine in the comment section of a separate post, Agnieska Wroczynska mentioned that benfotiamine had a positive effect on her child but increased hyperactivity.  So she found it was not ultimately helpful, and RG reported no positive affect whatsoever.  So it is possible that the experience that I have had with it with my son is highly unusual.

If you do wish to do a trial, as with any other supplement, start with low doses first to avoid risk and increase modestly if you see positive effects.  I am interested in others experiences with it and hope if you try it you will leave a comment here with some color on the results.

I thank Peter Lloyd-Thomas for the opportunity to write this guest blog and for providing a wonderful forum on autism treatment and autism research.

Monday 12 January 2015

A protocol for treatment of common autism phenotype(s)

This is a guest post written by Seth Bittker, who previously wrote about Vitamin D in Autsim.

Your child has just been diagnosed with autism.  Now what?  Start some form of behavioral therapy and research autism biochemistry.  You will soon realize by reading blogs like Peter’s that biochemical dysfunction is fundamental to most cases of autism.   For example, some biochemical characteristics that are common in autism are:

1)       Immune dysfunction.  Often this shows up as comorbidity with allergic or autoimmune diseases.
2)       Elevations in monoamine neurotransmitters in the young.
3)       Methylation deficits.  Often the oxidized to reduced glutathione ratios are high.
4)       Low plasma cysteine and higher sulfate excretion than controls.  This means there is a functional sulfation deficit.
5)       Lower levels of fatty acids in blood plasma than controls.
6)       Higher testosterone than controls.
7)       Oxidative stress as demonstrated by markers.
8)       Vascular damage as demonstrated by markers.
9)       Intestinal dysbiosis.  

Given this background, it makes sense to determine whether there are issues in your child’s biochemistry that may be involved in inducing autism and how his biochemistry compares to others with autism.  After all if his biochemistry is similar to what is common it may be that therapies that have proven useful in others with autism will prove useful in the case of your child as well.

How can you get an understanding of your child’s biochemistry?  You can have tests run on your child’s urine and blood.  This typically involves finding a medical doctor who can order such tests and has the inclination to do so.  One test that I believe everybody with autism of an unknown cause should have done is a quantitative urine organic acid test.  A good organic acid test will provide information on fatty acid and carbohydrate metabolism, Krebs cycle function, B vitamin deficiencies, neurotransmitter metabolism, oxidative stress, detoxification, and bacterial and fungal activity in the digestive tract, as well as methylation and sulfation processes.  In short it will provide information on a lot of the biochemistry that is often dysfunctional in autism.  Different providers of organic acid tests include different compounds and provide different information on them.  I recommend Genova’s comprehensive test because it includes a number of metabolites that are of interest in autism, it is quantitative, and the data is displayed in a logical manner.  Here is a link:  To be clear I have no relationship to Genova and I do not recommend that you follow the supplementation guidelines that they typically include with test results.  After reviewing the information from your child’s organic acid test and googling various metabolites, you may have some leads on whether the biochemistry of your child is similar to the biochemistry that is common with autism as described above.

What to do next?  The next step especially if there are indications that your child’s autism is similar to what is common in the medical literature is to develop a food and supplement protocol for your child by experimentation.  To mitigate risk you should find a physician who you can collaborate with, experiment with one therapy at a time, use your child’s biochemistry as determined by tests as a guide, use supplements that have generally found to be helpful in others with autism, and carefully control any experiments.  Always use low doses of any supplements at first.  In fact to obtain positive effects with most supplements, you need not provide large doses and in my view the amounts used in supplement trials are often excessive.

Below are some supplements and experiments and a reasonable order in which to try them.  I recommend that you try these (or some subset of them) if your child’s biochemistry suggests they may be helpful.  If you find significant issues in your child’s biochemistry that may be ameliorated with a single supplement, you should certainly consider trying that supplement first.  Also if something does not work well for your child, leave it out of the protocol that you are developing independent of biologic rationale.  The objective is to improve the functional level and health of your child.  If something does not work, discard it.  You need not do everything.

1)       Fatty acids.  As mentioned previously fatty acids are often low in autism.  You could get a fatty acid panel on your child to determine if they are low in your child.  Two double blinded trials have been done with fish oil (omega 3 fatty acids) in the context of autism with generally positive results.  Interestingly it seems some omega 6 and omega 9 fatty acids are often more deficient than omega 3s in autism.  As omega 6s like omega 3s are essential fatty acids, deficiency can be problematic.  While controlled trials have not been done with omega 6s or omega 9s in the context of autism, it makes sense to experiment with borage oil (omega 6) and olive oil (omega 9) if deficiency is suggested based on a fatty acid panel.

2)       Methylation cofactors.  Are there elevations (even mild ones) of methylmalonic acid or forminoglutamic acid from your child’s organic acid test?  Does your child have a high ratio of oxidized to reduced glutathione (a test by the European Laboratory of Nutrients can measure this)?  If so, then your child may have a methylation deficit.  Jill James among others has found that shots of methylB12 and oral supplementation of folinic acid can help normalize this biochemistry.  MethylB12 is absorbed well orally even in those with dysbiosis.  In addition the methylfolate form of folate is absorbed well and is the active form used in the body.  Also it is methylated which is a plus for those with methylation deficits.  Therefore, if there is any indication of need, I recommend supplementation with oral methylB12 and oral methylfolate rather than the forms that were used by James.  In my experience high doses of methylcobalamin can cause insomnia but low doses are therapeutic.  So be wary of inducing insomnia.

3)       Thiamine.  Deficiencies of this vitamin lead to a disease known as beriberi.  If you set aside the rashes that typically characterize it, there is significant overlap between the symptoms of beriberi and those that are common in autism.  In fact some with autism have rashes as well.  The word thiamine means sulfur containing vitamin and thiamine does indeed contain sulfur.  Sulfur deficits are common in autism as previously noted.  So this is another hint in my view that thiamine may be helpful in general in autism.  Indeed a trial from 2002 of thiamine suppositories found that thiamine deficiency was fairly common in autism and supplementation even in those without obvious signs of deficiency could lead to improvement in behavior. It is my belief that this vitamin is significantly underutilized in treatment of autism.  Some signs that thiamine may be warranted include high levels of lactate or pyruvate, issues of fatty acid or carbohydrate metabolism and rashes.

4)       Vitamin C.  A double blinded placebo controlled trial from 1993 found some improvement in behavior could be attributed to supplementing vitamin C in the context of autism.  This is not surprising given that oxidative stress is common in autism.  Are there indications of oxidative stress from your child’s organic acid test or other sources such as high levels of 8-Hydroxy-2’-deoxyguanosine?  Then a trial of vitamin C is warranted.  I think low doses are preferable to high doses as high doses have effects on digestion as well as neurotransmitters that may be undesirable.  In addition high doses can induce copper deficiency.  Too much copper is not uncommon with autism but copper deficiency can be as problematic as too much copper.

5)       Removal of supplementary and fortified sources of fat soluble vitamins and particularly vitamin D.  This is controversial and the vast majority of practitioners would recommend supplementation with vitamin D.  I believe getting rid of supplemental and fortified sources of vitamin D was vital to improving my son’s biochemistry.  In addition processing oral vitamin D requires sulfation and sulfation deficits are common in autism.  Also many of the biochemical characteristics of autism including excessive levels of neurotransmitters, excessive levels of hormones, and a Th2 skew to the immune system are exacerbated by significant supplementation of oral vitamin D.  I wrote a paper on this available here: If you think there is merit to this view, some indications that excessive fat soluble vitamins could be a problem for your child include elevation in glucarate and sulfate on an organic acid test.  Please note sun exposure is positive for those with autism.  My concern is only with significant supplemental oral sources of fat soluble vitamins and particularly vitamin D.

6)       Probiotics.  A number of excellent studies support the notion that dysbiosis is common in autism.  In addition a double blinded trial from 2010 found marginal improvement in those with autism from supplementation with a probiotic.  If your child has elevations in dysbiosis markers, this is worth a try.  I recommend a trial of a probiotic that is high in bifidobacteria and lactobacilli as there are indications that these are typically lower than controls in the digestive tracts of those with autism.  In addition if there are indications that your child may have clostridia from an organic acid test or other test, it probably makes sense to try the probiotic yeast saccharomyces boulardii as it has proven helpful in cases of clostridia.  Clostridia is common in autism and can lead to dysfunction.

7)       Carnitine.  One study found that about 17% of those with autism have abnormal carnitine metabolism.  In addition a double blinded placebo controlled trial found significant improvements in behavior from carnitine supplementation in the context of autism.  One indication carnitine may be useful is a high lactate to pyruvate ratio.  In addition one can measure the level of carnitine in the blood and low carnitine is an indication that supplementation could be benefical.  I do not use carnitine in supplementation with my son as I have not found it to be helpful but the trial mentioned suggests it will be helpful to a number of others.

8)        Removal of milk from the diet.  I do not believe there have been double-blinded trials showing efficacy for this treatment.  However some open label trials have resulted in positive results and I attest to the importance of this intervention in the case of my son.  Issues of digestion such as diarrhea and especially constipation are indicators that a trial of this may be beneficial.

9)       Removal of gluten from the diet.  As with milk free diets, I do not believe there have been double blinded trials showing efficacy.  However some open label trials have resulted in positive results and it seems helpful to my child.  In addition there does appear to be some comorbidity between celiac (autoimmune disease of the small intestine initiated by reaction to gluten) and autism. Again issues of digestion such as diarrhea or constipation can be good indicators that a trial may be beneficial.

10)   Cruciferous vegetables.  Sulfur deficits are common in autism as previously noted.  In addition a number of trials with sulfur containing compounds have had tantalizingly positive results in the context of autism.  Such trials include: NAC, DMSA, and sulforaphane as well as thiamine (mentioned above).  We have tried small doses of all of these with my son and with the exception of thiamine I have not felt the long term results were positive.  NAC and DMSA both tend to exacerbate dysbiosis in some cases as well.  As dysbiosis can be such a huge issue in those with autism, I am hesitant to recommend them.   We also tried a tiny dose of a sulforaphane supplement with my son and I believe it induced a temporary verbal tick, which was awful.  In fact the researchers who conducted the sulforaphane trial acknowledgement that it might raise the risk of seizures in some.  Seeing the results in my son, I think this caution is warranted and for this reason I feel sulforaphane supplementation can be dangerous despite the positive results that many have seen.  Cruciferous vegetables such as broccoli (which contain sulforaphane) seem to have a marginally positive effect on my son.  As these are foods I also have less fear of negative side effects.  Thus, I recommend inclusion of a trial of cruciferous vegetables  in your child’s diet if there are any indications of sulfation deficits (low cysteine) or high sulfur excretion (high sulfate in urine).

Some other supplements that I believe are useful in autism include biotin, riboflavin, milk thistle, melatonin (for sleep), and prunes (for constipation).  One could write a book about treatment protocols for those with autism and a number of good books have already been written on this topic.  What appears above is a summary of an ebook that I wrote describing this protocol which is available here:  If you have any interest, please feel to preview it on amazon.

In interest of full disclosure, I am not a doctor, I do not consider my son “recovered” from autism, the autism literature I have consulted as well as my own views may later be shown to be incorrect, and independent of what is true generally your child may have negative reactions to the supplements mentioned above.  I thank Peter for the opportunity to describe this protocol here and for his wonderful blog on cutting edge treatments for autism and the science behind them.  I wish you success in your efforts to improve the health of your child.