Thursday 26 May 2022

Bromide for Autism? Plus ça change, plus c'est la même chose!


Hôtel de Ville (City Hall) Tours, France, Gateway to the Loire Valley and Home to iBrain



We do seem to be going round in circles in this blog.  One doctor reader contacted me recently to tell me about Pentoxifylline for cognitive improvement. I told him that I am not surprised and that in the world of autism Pentoxifylline has been known to be beneficial for half a century. 

The abstract below is from a Japanese paper in 1978


On our experience in using pentoxifylline for abnormal behavior and the autistic syndrome


Describes the successful use of pentoxifylline (150–600 mg/day) with 3–15 yr old children with abnormal behavior (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.


You might wonder why it has not been widely adopted, at least for some people with autism. 

When it comes to Potassium Bromide (KBr) I found a case history from 150 years ago of its successful use in a little girl with epilepsy, autism and impaired cognition. She was treated at what is today London’s top children’s hospital, Great Ormond Street.

KBr was the original treatment for epilepsy.  It is still used in countries following German medicine; indeed, it is can be the only effective treatment for those with Dravet Syndrome.

Interestingly, Great Ormond Street Hospital has restarted the use of KBr in childhood epilepsy, specially importing its drugs from Germany.


Bromide for epilepsy – Great Ormond Street Hospital



In the US, KBr is only used for canine and equine epilepsy.  It does not work well on cats, incidentally.

Back in 2016, I did propose KBr as an add-on therapy for those with autism who respond to bumetanide.  This was part of my effort to develop a “super bumetanide”, to increase the bumetanide effect.


In a quote from today’s feature paper, from iBrain at the University of Tours, France:- 

“beneficial effects (of bromide) were superior to those of chronic bumetanide administration” 

in one mouse model of autism. 

When I was asked to give a presentation in the US on bumetanide for autism, there was one condition, “please don’t mention potassium bromide … we don’t want people trying it.”

Yes, it’s OK to talk about treating autism, but please don’t actually do it.

Move forward a few years and a doctor friend recently highlighted to me a new paper from France proposing Sodium Bromide for autism.

I did rather think here we go again, been there done that.

My conclusion back in 2016 was that yes it does provide a benefit; but it does have some drawbacks.  It has a very long half-life, meaning if you keep taking the same daily amount, it will take 5 weeks to reach its peak level in your bloodstream.

It does increase mucous secretions, in a dose dependent fashion.  This is not a problem in canine epilepsy, but in humans it will lead to spots (bromo-acne).  It could make asthma worse.

In the case of children with Dravet Syndrome, they have a high rate of death from epilepsy, or SUDEP (Sudden unexpected death in epilepsy).  So, I don’t suppose parents are going to worry about a few spots.


Potassium bromide in clinical trials for Dravet Syndrome

Potassium bromide has not been tested in randomized clinical trials specifically for Dravet syndrome patients. Some small studies suggest, however, that it might benefit Dravet syndrome patients.

retrospective study analyzed data from 32 Dravet syndrome patients carrying an SCN1A mutation. Six patients received potassium bromide temporarily as monotherapy, while 26 patients received the medication as add-on therapy. The mean treatment duration was 47 months with a mean maximum daily oral dose of 63.2 mg per kilogram (kg) body weight of potassium bromide.

Three months after treatment began, 31 % of the patients experienced complete seizure control. Seizures were reduced by more than 75% in 6% of the patients, and by more than 50% in 19% of them.


My old post from 2016:


Potassium Bromide for Intractable Epilepsy and perhaps some Autism

My idea was to see if you can get a meaningful benefit from a low dose and avoid any side effects. Rather than the 63.2 mg/kg for Dravet Syndrome seizures, I thought a reasonable dose was 8 mg/kg to further treat the E/I imbalance in Bumetanide responsive autism.  Why 8mg/kg? Well, that was half a tablet. 


Sodium Bromide for Autism, proposed by the French researchers


Chronic sodium bromide treatment relieves autistic-like behavioral deficits in three mouse models of autism


Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behavior. To date, no pharmacological treatment has been approved that ameliorates social behavior in patients with ASD. Based on the excitation/inhibition imbalance theory of autism, we hypothesized that bromide ions, long used as an antiepileptic medication, could relieve core symptoms of ASD. We evaluated the effects of chronic sodium bromide (NaBr) administration on autistic-like symptoms in three genetic mouse models of autism: Oprm1−/−, Fmr1−/− and Shank3Δex13-16−/− mice. We showed that chronic NaBr treatment relieved autistic-like behaviors in these three models. In Oprm1−/− mice, these beneficial effects were superior to those of chronic bumetanide administration. At transcriptional level, chronic NaBr in Oprm1 null mice was associated with increased expression of genes coding for chloride ions transporters, GABAA receptor subunits, oxytocin and mGlu4 receptor. Lastly, we uncovered synergistic alleviating effects of chronic NaBr and a positive allosteric modulator (PAM) of mGlu4 receptor on autistic-like behavior in Oprm1−/− mice. We evidenced in heterologous cells that bromide ions behave as PAMs of mGlu4, providing a molecular mechanism for such synergy. Our data reveal the therapeutic potential of bromide ions, alone or in combination with a PAM of mGlu4 receptor, for the treatment of ASDs.


Compromised E/I balance in ASD may result from several neuropathological mechanisms. On the excitation side, glutamatergic transmission was found altered both in patients and animal models, although in different directions depending on genetic mutations/ models [9, 18, 19]. On the inhibition side, decreased levels of GABA [20] and expression of GABAA and GABAB receptors (postmortem analyses, [21, 22]), as well as genetic polymorphisms in GABAA receptor subunits [23, 24], have been detected in patients with autism. Accordingly, decreased GABAergic neurotransmission has been reported in several ASD models [25–29]. Alternatively, it was proposed that GABA neurons remain immature in ASD, maintaining high intracellular concentrations of chloride ion (Cl−) whose efflux through activated GABAA receptor induced neuronal depolarization [30]. Intracellular Cl− concentration is under the control of the main Cl− importer NKCC1 (Na+-K+-2Cl− cotransporter) and its main exporter KCC2. Therefore blocking NKCC1 using the loop diuretic and antiepileptic drug [31, 32] bumetanide appeared a promising therapeutic approach in ASD. Accordingly, bumetanide improved autistic-like phenotype in rodent models of ASD [33] and relieved autistic behavior in small cohorts of patients [34, 35].


Bromide ion (Br−) was the first effective treatment identified for epilepsy [36] and long used as anxiolytic and hypnotic [37]. With the advent of novel antiepileptic and anxiolytic drugs, its use was progressively dropped down, although it remains a valuable tool to treat refractory seizures [38, 39]. At molecular level, Br− shares similar chemical and physical properties with Cl−, allowing it substituting Cl− in multiple cellular mechanisms. These include anion influx through activated GABAA receptor, with higher permeability to Br− compared to Cl− resulting in neuronal hyperpolarization [40], and transport through the NKCC and KCC cotransporters [41, 42]. In view of the E/I imbalance theory, these properties point to Br− as an interesting candidate for ASD treatment.


Here we assessed the effects of chronic sodium bromide administration on core autistic-like symptoms: social deficit and stereotypies, and a frequent comorbid symptom: anxiety, in three genetic mouse models of autism with different etiologies: Oprm1−/−, Fmr1−/− (preclinical model of Fragile X syndrome) and Shank3Δex13-16−/− mice, lacking the gene coding the mu opioid receptor or the FMRP protein for the formers, or the exons 13−16 of the Shank3 gene, coding for the PDZ domain of the SHANK3 protein, for the later. Altered E/I balance and/or modified expression of involved genes have been reported for these three models [28, 43–47]; the Oprm1 knockout model presents the advantage of limited impact on learning performance [44]. We evidenced that Br− treatment alleviates behavioral deficits in these three models and increases expression of various genes within the social brain circuit of Oprm1 null mice. We unraveled that Br− not only increases mGlu4 receptor gene expression but also potentiates the effects of the positive allosteric modulator (PAM) of mGlu4 VU0155041, in Oprm1−/− mice and in hetero[1]logous cells. Our data reveal the therapeutic potential of Br− administration and its combination with a PAM of mGlu4 receptor for the treatment of ASD. 



Chronic sodium bromide relieved autistic-like symptoms in Oprm1−/− mice more efficiently than bumetanide

Chronic sodium bromide relieved social behavior deficits, stereotypies and excessive anxiety in Fmr1−/− and Shank3Δex13-16−/− mice

Chronic sodium bromide modulates transcription in the reward circuit of Oprm1−/− mice

Synergistic effects of chronic bromide and mGlu4 receptor facilitation in Oprm1 null mice

Bromide ions behave as positive allosteric modulators of the mGlu4 glutamate receptor


In conclusion, the present study reports the therapeutic potential of chronic bromide treatment, alone or in combination with a PAM of mGlu4 receptor, to relieve core symptoms of ASD. Beneficial effects of bromide were observed in three mouse models of ASD with different genetic causes, supporting high translational value. Moreover, bromide has a long history of medical use, meaning that its pharmacodynamics and toxicity are well known, which, combined with long-lasting effects as well as excellent oral bioavailability and brain penetrance, are strong advantages for repurposing.




The doctor treating Ida at Great Ormond Street 150 years ago noted that after treatment with KBr she developed age-appropriate play skills.  That is very much the same effect as bumetanide in a young child with severe autism and IQ<70.

My trials of 400mg of KBr produced a “bumetanide+” effect and feedback from other bumetanide super-responders was in line with this. Higher doses than mine were used.

The effects of KBr overlap with those of Bumetanide, but it is possible that there may be more KBr responders than Bumetanide responders.  KBr has interesting effects beyond those of Bumetanide. It is definitely worth considering KBr, even if the person is not a bumetanide responder.

The French researchers in today’s paper propose that Bromide be repurposed for autism – they definitely have the right idea.  They did note the 8-14 day half-life in humans.

In the advisory from Great Ormond Street it is noted:

“Your child will need to have regular blood tests to monitor the amount of bromide in their blood – this usually happens around four weeks or so after starting to take the medication, or four weeks after the dose is increased. 

I think the aim should be maximize the benefits of KBr, without incurring the side effects that will occur at high doses.  KBr might be best as an add-on therapy in autism.

The 60mg/kg dose from Dravet Syndrome is 8 times the bumetanide add-on dosage I suggested.

One of the models used in the French trial was that for Fragile X syndrome, the others were the Mu Opioid Receptor Null model and the Shank3B−/−, lacking the PDZ domain.

Fragile X is one of the most common types of human autism and is apparent from facial features. Bromide for human Fragile X ?

In case you are wondering, whether to choose sodium bromide (NaBr) or potassium bromide (KBr), it is the bromide ions (Br-) that are critical to its effect on the E/I imbalance.  Personally, I prefer KBr, because most people have too much sodium and too little potassium in their diet.  People taking bumetanide should be taking extra potassium anyway.

Interestingly, from the UK guidance: -

“Salt and salty foods can reduce how well bromide works. Try to limit the amount of salty foods your child eats and do not add salt to cooked foods if possible.

One other medical formulation of bromide is called triple bromide and contains three different variations of bromide:  ammonium bromide, potassium bromide and sodium bromide.

Hopefully it will not take 50 years to establish the usefulness (or not) of bromide as an autism therapy.

It was mentioned first in this blog, back in 2016.

In 2017 some French people filed a patent, claiming to be the inventors of bromide as a treatment for autism.


Monday 16 May 2022

Mopping up harmful gut metabolites with Carbon (AB 2004) or Silicone (Enterosgel) to improve GI and behavioral problems in Autism


We have seen in previous posts that certain metabolites produced in the gut can worsen existing autism and even create autism in mouse models.

Much has been written about propionic acid, which when produced in the gut, rather than the beneficial butyric acid, causes behavioral problems.  This is what underlies the Nemechek Protocol, developed by Patrick Nemecheck, DO.  In his therapy you try to increase butyric acid production using inulin as a dietary fiber.  It does work for some people, but they are in the minority; in a small group it makes matters worse.

We also saw that P-cresol, another chemical produced by fermentation in the gut, can trigger autistic behaviors.

P-Cresol, like Propionic acid – a cause of Transitory Autism for some and a further burden for others

A few years ago in the research we did come across a “wonder” bacteria called B. fragilis (Bacteroides fragilis).  This bacterium was able to reverse autism in the mouse model of maternal immune activation (MIA).  The actual mechanism was by reducing a gut metabolite called 4EPS.  It turns out that 4EPS is closely related to P-cresol. The B. fragilis bacteria is essential to healthy gastrointestinal function, but it must not enter the bloodstream because it can cause a fatal blood infection. 

Antibiotics and Autism(s) – Pass the Bacteroides Fragilis?


How to defeat 4EPS

You would think that the easiest way to get rid of that harmful 4EPS would be simply to take B. fragilis, as a probiotic.

An Australian company called Axial decided instead to use a special form of carbon taken orally to “mop up” the 4EPS. The research drug is called AB-2004.

This carbon cannot be selective for 4EPS, so it will also “mop up” other things as well.

It does look like elevated 4EPS in autism is also associated with GI problems and that anxiety is the key feature of autism that is made worse.

I think you could describe AB-2004 as a therapy to restore GI integrity in autism that will also reduce anxiety is a sub-group.

If you have autism with anxiety, but perfect GI function, it does not look like you are going to benefit from AB-2004.


What about Silicone rather than Carbon? 

I was recently introduced to a product normally used to treat IBS-D (irritable bowel syndrome with Diarrhea).  The other type is called IBS-C, with C being for constipation.

It seems that some people with autism and GI problems respond very well to the OTC product Enterosgel, which claims to mop up harmful substances using a silicon gel (polymethylsiloxane polyhydrate) in combination with purified water

As with the experimental AB-2004, the silicone gel cannot be selective for any particular metabolite.

There are clinical trials looking at the benefit of Enterosgel in IBS-D.


Here is a current trial in the United Kingdom:



You can actually measure 4EPS in urine, (as you can P-cresol).  It would not be hard to see if Enterosgel lowers the elevated 4EPS found in people with autism + GI dysfunction. 

Of note is that for our reader Dragos in Romania, Enterosgel worked wonders in his adult son with IBS-C plus challenging behaviors, rather than IBS-D. 



The microbiota modulates gut physiology and behavioral abnormalities associated with autism 

A Serum Metabolite Induces ASD-Related Behavior

MIA-dependent increases of specific metabolites, and their restoration by B. fragilis, suggest that small molecules may play a role in ASD-related behaviors. To test this hypothesis, we examined whether increasing serum 4EPS is sufficient to cause any ASD-related behavioral abnormalities in naïve mice. Mice were treated with 4EPS potassium salt (Figures S7A–C) or vehicle, daily from 3 weeks of age (when MIA offspring display gut permeability) to 6 weeks of age (when behavior testing begins). Remarkably, systemic administration of the single metabolite, 4EPS, to naïve wild-type mice is sufficient to induce anxiety-like behavior similar to that observed in MIA offspring (Figure 6C). Relative to vehicle-treated controls, mice exposed to 4EPS travel comparable distances in the open field but spend less time in the center arena (Figure 6C). Also, in the PPI test, 4EPS-treated mice exhibit increased intensity of startle in response to the unconditioned primary stimulus, but no significant alterations in PPI (Figure 6D), representing anxiety-associated potentiation of the startle reflex (Bourin et al., 2007). Conversely, there are no significant differences between 4EPS-treated versus saline-treated mice in marble burying or USV behavior (Figures S7D and S7E), suggesting that elevating serum 4EPS levels specifically promotes anxiety-like behavior. While not a core diagnostic criterion, anxiety is a common co-morbidity that may contribute to cardinal ASD symptoms. Furthermore, it is possible that complex behaviors may be modulated by combinations of metabolites. In summary, these data reveal that elevated systemic levels of a metabolite regulated by gut microbes causes an ASD-related behavior, suggesting that molecular connections between the gut and the brain maybe associated with autism.

In a proof-of-concept test of the this hypothesis, we reveal that the microbially-modulated metabolite 4EPS, which is elevated in the circulation by MIA and restored by B. fragilis treatment, is sufficient to induce anxiety-like behavior in naïve mice. These data indicate that metabolomic changes contribute to the onset and/or persistence of autism-related behavioral abnormalities. Notably, we show that commensal microbes are required for the production of serum 4EPS in mice. Several species of Clostridium are believed to be producers of the precursor 4-ethylphenol (Nicholson et al., 2012), consistent with our findings that levels of the Lachnospiraceae family of Clostridia and serum 4EPS are elevated in MIA offspring, and both are corrected by B. fragilis treatment. Moreover, the structural similarity of 4EPS to p-cresol, which also derives from Clostridium species (Persico and Napolioni, 2013), suggests they may be produced through similar biosynthetic pathways (see Figure S6A). Although not all autism-like behaviors are affected by 4EPS alone, our results warrant the examination of several other serum metabolites, perhaps in combination, for their potential to impact the spectrum of autism-related behaviors. 


The Gut Microbiota and Autism Spectrum Disorders

AB-2004, its orally administered, drug candidate that has demonstrated the ability to repair leaky gut and improve repetitive behavior, anxiety, and ASD-related sensorimotor gating deficits by removing key microbial metabolites in animal models with Autism Spectrum Disorder (ASD).


The main highlights from the poster presentation titled, “Characterization of GI barrier integrity and gut microbiome-derived metabolites in BTBR, Shank3 and Cntnap2 mouse models of ASD and demonstration of AB-2004 as a potential mitigating therapeutic” include:


·     The Cntnap2-/- mouse model accurately recapitulated the leaky gut phenotype and elevated levels of the gut microbiome-derived metabolite 4-EPS that have been reported in ASD patients

·     Treatment with AB-2004 effectively restored GI integrity and reduced elevated 4-EPS levels in Cntnap2-/- mice

·     The Cntnap2-/- model has been identified as a promising and translationally relevant animal model for the development of microbiome-inspired therapies for the effective treatment of GI and behavioral dysfunctions in ASD

·     These data support the development of AB-2004 as a treatment for GI dysfunction in ASD and potentially behavioral symptoms through reduction of pathologically active microbiome-derived metabolites Axial is currently screening ASD adolescents for its Phase 1b/2a clinical trial of AB-2004.

Scientific evidence has shown there may be a link between bacteria commonly found in the digestive tract, and the brain which could contribute to certain characteristics, such as irritability, in children with ASD. AB-2004 is designed to adsorb certain substances produced by gut bacteria to reduce their ability to enter the bloodstream and reach the brain.   


The active ingredient in AB-2004 is a highly engineered form of spherical carbon designed with human safety and biological selectivity in mind, making it very different from activated charcoal. Each sphere of AB-2004 consists of a network of pores that allows it to selectively adsorb metabolites that may contribute to characteristics associated with ASD like irritability and anxiety.


Axial reports findings of elevated 4-EPS in children with ASD 

The findings showed that concentrations of the bacterial metabolite, 4-ethylphenylsulfate (4-EPS) were elevated as much as six-fold in serum samples from children with ASD compared to healthy controls in replicate analyses.

This research builds on previous work published by Axial's Co-founder and Caltech Professor, Sarkis Mazmanian, Ph.D., that demonstrated causality between 4-EPS and anxiety-like behaviors in the "maternal immune activation" (MIA) mouse model of ASD. The MIA model recapitulates key features of the autism phenotype, including increased anxiety, stereotypic behaviors, and decreased vocalizations and social behaviors. Dr. Mazmanian found changes in the gut microbiome (dysbiosis), increased intestinal permeability (IP), and elevated levels of the putative bacterial metabolite 4-EPS in MIA mice, compared to controls. Oral treatment with B. fragilis, a human commensal gut bacterial species, resulted in restoration of gut microbial profiles, decreased IP, and markedly reduced serum concentrations of 4-EPS.

The current study aimed to evaluate 4-EPS levels in children with ASD compared to samples from control children. Two analyses were performed, a 4-EPS targeted analysis in 103 pediatric subjects and a non-targeted serum metabolomics study involving 230 children (cohorts from the "Childhood Autism Risks from Genetics and the Environment" study ongoing at the Univ. of California Davis). 4-EPS concentrations were found to be significantly elevated in children with ASD vs. healthy controls in both analyses. In addition, elevated levels were associated with worse social performance on two separate measurements. The impact of this elevation on behavior, and the impact of treatment with B. fragilis and with Axial's small molecule therapeutic, AB-2004, will be the subject of subsequent human clinical studies.


Anxiety Linked to Gut Microbial Metabolite in Mouse and Human

In a small, single-cohort pilot study reported simultaneously in a Nature Medicine article titled, “Safety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial“(trial registration no. ACTRN12618001956291), Mazmanian’s team tested an oral drug (AB-2004) that adsorbs 4EPS in the gut in 30 adolescents with autism. In addition to reducing 4EPS levels in blood and urine, and improving gut health, a subset of the tested participants showed reduced irritability and anxiety.



What is Enerosgel?  (click the link)




I imagine both AB-2004 and Enterosgel are removing numerous metabolites from the digestive tract.

We know that at least 3 metabolites (Propionic acid, P-cresol and 4EPS) can induce autism in a previously not autistic mammal.  There are undoubted other metabolites that will be added to this list.  In the case of Propionic acid the autism was reversable using NAC (N-acetylcysteine).

Since you will have to wait years for AB-2004 to become an approved drug, if indeed it ever happens, you might just have to hope that Enterosgel is equally effective at mopping up that 4EPS with silicone.

It is pretty clear that the Australians are targeting anxious Aspies with GI problems, with AB-2004.

Is Enterosgel going to benefit those with autism and without GI dysfunction?  I think it is less likely, but it could happen.  The effect might not relate just to 4EPS. 



Enterosgel for food allergy? 

I do wonder about the use of Enterosgel following an acute food allergy.

Many people take the mast cell stabilizer cromolyn sodium (Nalcrom) to deal with food allergy.  Indeed, for some people, instead of eliminating the food they are allergic to, they take Nalcrom.

Apparently, some people with food allergies are taking Enterosgel regularly.

What happens if you consume a food substance by mistake that you are allergic too?

This is what happened recently to Monty while on holiday in Greece.  Two small red patches appeared on either side of his face and his mood and behavior changed dramatically.  It was like his pollen allergy triggered summertime raging, but it was not due to pollen allergy.

The effect of an allergic reactions continues even after you remove the allergen.  If you are allergic to bee stings you might end up needing a steroid injection to settle your immune system down.  In the immediate term you can take an oral H1 antihistamine.

Monty had his H1 antihistamine and a single oral dose of Prednisone; after 3 days he was back to his usual self.

People who get severe allergic reactions carry an Epipen (an epinephrine autoinjector).

In Monty’s case there is never a severe allergic reaction, but there is a severe behavioral reaction to a modest allergic reaction.  I think this is likely to be quite common in people with autism and challenging behaviors.  It often goes untreated, or is poorly treated using anti-psychotic drugs, which then cause serious side-effects including tardive dyskinesia (motor tics), obesity, males growing breasts (drug-induced gynecomastia) etc.

Even though Monty has no GI problems, perhaps I should acquire some Enterosgel to use in case of a future acute food allergy attack?

Wednesday 4 May 2022

High dose Betaine/TMG, Low Dose Ponstan, Galavit, Humira, HMB (β-hydroxy-β-methylbutyrate) and Cetirizine for Palilalia/Scripting


Our reader in Canada, AJ, did highlight a case series from Norway that showed that high dose Betaine/TMG was effective in improving functioning in people with autism due to creatine transporter deficiency.  The use of Betaine/TMG was really just stumbled upon and the authors considered what the beneficial possible mode of action could be. 

Betaine (TMG) and Gene Therapy as potential alternatives to Bumetanide Treatment in Autism? 

The effect was only present at high dose (7-10 g a day) not the much lower dose used by some DAN/MAPS doctors, who do prescribe TMG and the closely related DMG.

The paper suggested that one possible effect might have been lowering chloride levels within neurons.  This is also the effect of Bumetanide.

AJ suggested that Betaine/TMG might be an alternative to Bumetanide and one that does not need a prescription.

Our reader Nancy reported a benefit in her adult son.

The question is not whether or not high dose TMG is a useful therapy, we already know that it is, in some cases. The question is whether it is a bumetanide alternative.

My conclusion is that high dose TMG does not seem to be a bumetanide alternative.  If it was an effective alternative then I would be suggesting everyone using bumetanide should go and buy some.

I did try TMG for s couple of weeks and did not see any additional effect over the continued therapy of 2mg of bumetanide.  In our case there is a benefit from additional bumetanide/Azosemide. If TMG shared the same mode of action as Bumetanide then 7g TMG + 2mg Bumetanide should show some improvement over 2mg Bumetanide.  It did not.

There is a long list of other modes of action to explain why Nancy’s son and the two Norwegians improved.


Low dose Ponstan for sound sensitivity

Low dose Ponstan (Mefenamic Acid) was proposed as a treatment for sound sensitivity.  Within Europe it seems that Greece is the place to buy Ponstan; it is sold OTC and cheap.  One pack (15 x 500mg) costs less than 2 USD/EUR.

In some people the effect of 250mg lasts all day, while for others it lasts for a few hours.

Ponstan is also widely used as a syrup to reduce fever in young children (antipyretic).

In the US the common brand name is Ponstel, but the price is dramatically higher.

Galavit + Cromolyn Sodium

The combination of the common mast cell stabilizer Cromolyn Sodium, used by many readers, with a Russian drug called Galavit is used by at least two readers. Dragos recently told us that the combination has put an end to his adult son’s aggressive behaviors.

Galavit has multiple anti-inflammatory modes of action.  It is not a mast cell stabilizer like Cromolyn Sodium.

Galavit is not expensive, but may hard to get hold of.

It does look like there is an overlap between responders to Verapamil and responders to Galavit.  So, if you respond well to Verapamil but get one of the rare side effects, like Maja’s daughter, it might be worth investigating further. 


Humira is a TNF alpha inhibitor normally used to treat auto-immune conditions like rheumatoid arthritis, Cohn's disease, ulcerative colitis, psoriasis and juvenile arthritis.

I was recently contacted by an Aspie lady with auto-immune conditions, who found Humira not only controlled those conditions but moderated her autism symptoms, notably sound sensitivity.  One injection produced a benefit that lasted 7 weeks.

Kanner’s subject #1 went on to develop juvenile arthritis and this made his autism much worse.  There was no Humira back in his day, but his arthritis did respond to treatment.

Apparently, many children with autism and GI problems are taking Humira. 

IVIG seems to be the “go-to” therapy for immunomodulation in autism.  It is now quite commonly used in the US, but much less so elsewhere due to the cost.

I wonder if Humira might be an alternative for some?


HMB (β-hydroxy-β-methylbutyrate)

Our reader Natasa did mention the sports supplement HMB to me.

It has many interesting modes of action and it is a precursor to the ketone BHB, which has been covered in great depth in this blog.

Ketone Therapy in Autism (Summary of Parts 1-6)

In Europe ketone supplements like BHB fell foul of the rules on supplements and have been banned. In the US they are widely sold.

If you want to try BHB, by cannot buy it in Europe, you might want to look into HMB (β-hydroxy-β-methylbutyrate).


Cetirizine for Palilalia/Scripting 

I am a big fan of the OTC antihistamine Cetirizine/Zyrtec and I was interested to read the recent comment below about its effect on one 12-year-old boy.

“I realize this is 5 years old, but as a result of this blog, I tested cetirizine on my 12 yo yesterday. He has a nonstop palilalia (obsessive speaking that is nonsense or only makes sense to him). It's his "chief feature" and inhibits social development. For 4 glorious hours, it went away. Today, I gave him 5 mg of Zyrtec again. Yet again, the palilalia went away, AND he had strong focus on school (he has serious attention issues).”


Many people’s autism gets worse when auto-immune conditions flare up.  In some cases, the auto-immune condition is very mild, but the consequences are not.  For one person the result is aggressive behavior, while in another it is talking nonsense.