I have been blogging about quack medicine, charlatanisms and debunking claims about the blood-brain barrier for few years now. But nothing reach the level of indignation and anger than the treatment reserved for children diagnosed as “on the spectrum” (for autism spectrum disorder or ASD), especially those treated with the “CD/MMS protocol” aka “the bleach protocol”, as recently discussed in various blogs and in news outlet here and there.
“Autism spectrum disorders” that is an umbrella medical definition that is defining children presenting deficiencies in social skills, a particular focus on patterns or objects including certain rituals or organization (e.g. sorting toys by their colors, lining cars in a perfect order, bed linen to be perfectly folded), hyper-sensibility to environmental cues (sounds, light, colors….) and in some cases neurodevelopment or communication delays. Not all autistic children are equals, with very different types of syndromes or conditions (e.g. Asperger’s Syndrome, Rett’s Syndrome……).
Although the etiology of ASD is deeply anchored into genetics as a major risk factor (followed by neuroinflamamation during gestation due to infectious diseases), the diagnostic still remains flexible and have been standardized only recently through the “Diagnostic and Statistical Manual for Mental Disorders”, currently in the fifth edition. Such standardization is as recent that a notable number of adults often get diagnosed “on the spectrum” late in their life, often during their adulthood.
Until now, there is no therapies to address such condition and mostly involves medication for treating other conditions associated with the disease (epilepsy is often diagnosed in children on the spectrum) or behavioral therapy (also known as applied behavioral analysis).
Because the diagnosis of autism is perceived and feared amongst parents and the lack of therapies are obvious, such environment creates a fertile ground for charlatans and snake oil seller preying on fear to make profit, selling parents a “cure-it all” potion or interventions, using these children as “guinea-pigs” by pushing protocols or treatment that are best have poorly fared in the scientific literature (most of the time published in low-impact factor journals) if not completely bogus.
A few example of such doubtful or quack remedies are dietary restrictions (gluten-free/casein-free diets), injection of biologics (GcMAF), if not dangerous interventions such as the use of hyperbaric oxygen treatment or use of chelation therapy. But amongst them reside one of the worst treatment: the CD/MMS protocol, or as we should call it the “bleach protocol”.
The CD/MMS protocol: a fancy name for a bleach protocol targeting autistic children
CD stands for chlorine dioxide (O=Cl=O) a bleaching agent used mostly for industrial purposes. CD shares similarities with the household bleach (O=Cl-) and both as referred as chlorinated bleaching agents.
Until recently, Kerri Rivera has been actively promoting the CD/MMS protocol as a “cure for autism” through her book co-authored with other charlatans named “Healing The Symptoms Known As Autism”. in this book, they promote the use of CD via ingestion of droplets or via enema administration. Such aggressive chemical is enough to damage the mucosal layer lining the luminal wall of the gastrointestinal (GI) tract and its detachment. Such detached mucosal layer is often labelled as “parasites” which indeed any respected parasitologist will quickly debunk such fallacious claims. Kerri Rivera promotes the use of this protocol to cure “autistic children” and up until recently was promoting such treatment in the Autism One conference. She discussed in details about this protocol on the Chapter 8 of her book and makes disturbing claims about the blood-brain barrier.
Fallacious things Kerri Rivera said about the blood-brain barrier in her book:
The first fallacious claim from Kerri Rivera appears on Chapter 3, pages 48 and 49. In this chapter, she promotes the gluten-free/casein-free/soy-free diet as a treatment for autism with the excuse of the “leaky gut syndrome” as the following: “This results in poor digestion, which facilitates the entry of these harmful proteins [gluten and casein] directly into the bloodstream, where they can cross the blood-brain barrier.“. I never heard about gluten and casein crossing the BBB, especially considering that these are large peptides and therefore have to use transporters and receptors. Of course, her claims is not backed by a reference to a study.
Then she refers to this ” Improperly digested gluten and casein fragments can both enter the bloodstream and cross the blood-brain barrier. Because of their opioid properties, these peptides can react with opiate receptors in the brain to cause effects similar to those of an opiate drug such as heroin or morphine.7 These opiates are called gluteomorphin (or gliadorphin) and casomorphin, and can react with some parts of the brain, for example, the temporal lobes, which are actively involved in the process of the integration of language and hearing. Interestingly, these are two of the areas most affected by autism.“
She cites this page for her claims. Interestingly, if you look at the page this claim is based on making a parallel between celiac disease and a speculation and hypothesis as cited: “Now in terms of autism, the situation is somewhat different because children with autism generally do not have celiac disease and do not have the DQ2 genotype problem. Whereas the problem of celiac disease is well proven in scientific studies, the problem with gluten sensitivity in autism is less well studied. The autism hypothesis involves, like celiac disease, the toxic effects of small peptides, generally in the range of five to seven amino acids in length (termed casomorphin and gliadorphin, as noted below). It is believed that these peptides from gluten, as well as certain peptides from cow milk protein (casein), can somehow cross the intestinal microvillus barrier and reach the blood stream.”
In a previous edition, Rivera went further and cited two papers to back her claims (now this claims has been watered down and put in the FAQ section of this chapter): a study from Reichelt1 and colleagues and a review from Shattock and colleagues2. Firstly, the citation of Shattock review is outdated and only provide an exhaustive overview of published studies supporting or dismissing the theory of opioid-excess. It has no scientific value as it does not provide a direct evidence of such claim. More troublesome is the following study led by Hunter and colleagues published by Hunter and colleagues in 2003 investigating the presence of opioids mimetics in patients urine and published in Developmental Medicine & Child Neurology3, a journal with an acceptable impact factor (IF=3.29). Using liquid chromatography coupled with mass-spectrometry (a common analytical technique used for measuring metabolites in biological fluids), the authors have investigated the presence of opioids in a cohort of 10 children with ASD and used siblings as controls. Interestingly, the authors failed to notice notable differences (as defined by presence of unique peaks) in the urine chromatogram of ASD children compared to controls. The authors further investigated the presence of opoid peptides previously cited by Shattock, in particular beta-casomorphin (a peptide byproduct obtained from casein degradation) and alpha-gliadin (a peptide byproduct obtained from gluten degradation). The authors failed to identify the presence of both peptides, based on retention time compared to standard or based on the m/z index. This publication irated enough Shattock to be followed by a comment to Editor and a scientific joust between Shattock and Hunter4, however an editorial published by John F Mantovani resumes well the context in which the initial statement of Shattock was published5. At this time, ASD etiology was completely unknown and remained highly speculative. The publication (and subsequent retraction) of the so-called “Wakefied study” 6 linking MMR vaccines to ASD cases, but also documenting the presence of inflammatory bowel disorder in ASD patients, such condition is known to triggered by gluten and casein in patients suffering from celiac diseases. As Mantovani mentioned, the adoption of the theory of gluten and casein was correlating with the same approach than the vaccine without any scientific rationale. The study from Hunter indeed showed the lack of evidence about the claim made by Shattock. The amount of studies linking autism and exorphin remains very low. A query on Pubmed (the database of the National Library of Medicine) using the keywords “autism” and “exorphin” results in only 7 publications with 3 publications from Reichelt, KL and two publications from Brudnak, MA.
This brings the concern of data reproducibility. In order to have a scientific claim that have strong significancy you need two factors: a significant number of publications that investigated such statement and the publications of findings from different research groups. Having the monopoly of such investigation solely on a single research laboratory raises the issue of data reproducibility and reliability.
In this case, the study of Reichelt is very interesting, as its publication quality appears dubious at different levels. The journal of Microbial Ecology and Health Disease has recently adopted the “open-access” policy. Prior its publication as open-access, the journal has an 2013 unofficial impact factor of 0.933. The “open access” and the low IF raise red flags: such journal may be a potential “predatory journal” (a term coined by Retractionwatch.org, a website tracking scientific articles retraction). In this model, the cost of open-access is levied by the payment of hefty publication fees ($3000-5000) usually higher than subscription-based journals. Because of such financial gain, the peer-review process may be altered and even may be completely omitted, removing the quality control accomplished by peer-review. This lack of peer-review process is particularly blatant by the absence of clearly structured “methods” sections, odd wordings for a scientific (“ELISA typed as Elisa, thaw over night, eight-hundred microliters”), the source of samples (Association Planet Autism (Italy), samples from Slovenia, Serbia and Australia) and the overall format of the paper figures with some appearing as a screenshoot of a Powerpoint presentation or from printed copies. It raises some skepticism about why the author (based in Norway) failed to collect samples from Norwegian ASD patients.
In the previous edition, Rivera linked these studies to a “leaky bowel syndrome”. A major flaw in this claim is the absence of citing the original publication for Hsaio and colleagues7 that have demonstrated the presence of a “leaky gut syndrome” in mice showing an ASD phenotype. Instead Rivera cites the Gluten Free Society webpage as a source of information (http://www.glutenfreesociety.org/gluten-free-society-blog/dr-fasano-on-leaky-gut-syndrome-and-gluten-sensitivity/).
Dr. Alessio Fasano is certainly a respected researcher in celiac diseases but as noted with pseudoscience and activists groups lacking the scientific knowledge, cherry-picking and extraordinary extrapolation. In particularly in this case by the Gluten Free Society, those as their Facebook webpage mentions, identify themselves as alternative and holistic health society. This is again a red flag on the mission and purpose of this society that have little or no scientific evidence to support their claims except deviating, cherry-picking and reformulating genuine studies to push for their agenda.
Under normal conditions, the intestinal and the blood-brain barrier (BBB) (Figure 1) provides a tight cell monolayer creating a gut-blood and a blood-brain barriers respectively. Under normal conditions, such barrier is achieved by the presence of tight junctions complexes stopping the diffusion of electrolytes and water between the two compartments. Only digestion byproducts such as amino-acids or glucose are transported through dedicated nutrient transporters or solute carriers, whereas bigger entities such as peptides, proteins and pathogens have virtually no diffusion). Only lipids (fatty acids, cholesterol…) and drugs (designed as lipid-soluble chemicals) can passively diffuse across the barrier by mixing themselves with the phospholipid bilayers making the cell membranes.
In the study from Hsiao, the authors demonstrated indeed the presence of a “leaky gut” as measured by an increase in FITC-dextran permeability with an estimated size of 4kDa (that’s about the size of a peptide of 36 amino acids). Even is such peptides can cross a “leaky gut”, they still have to cross the BBB. Some scientific studies have demonstrated the biological activity of opioids analogs obtained from digestion byproducts, including gluten and casein. Yet, a review from Lister and colleagues 8 denoted that a majority of these studies were based on intracerebroventricular (ICV) injections (or intracranial). This drug delivery approach allows to bypass the BBB but also is a very invasive approach that is used in clinical settings only for emergency and severe cases.
If such peptides were to cross the BBB and exert the biological activity discussed by Rivera, they have to have a dedicated peptide transporter that can deliver such peptides from the blood to the brain side. The number of peptides capable to cross the BBB has been recently reviewed by Banks 9, a well-established BBB scientist in the transport and delivery of peptides and inflammatory cytokines across the BBB. There is no mention about any of the opioids mentioned by Reichelt or Shattock publications. Furthermore, the increase in gut permeability appears unlikely or indirectly related to gluten or casein-sensitivity, as the authors demonstrated a change in the gut microbioma, in particular changes in Bacteorides fragilis as well as changes in metabolites discovered in serum plasma. However this study has to be taken with a lot of precaution due to the differences related to interspecies variation, the behavioral representation of mice to model ASD and more importantly, similar studies in human patients investigating samples from stools and plasma levels to observe if similar trends or biomarkers are noted in humans.
The next chapter that talks about the BBB is the Chapter 5, in which she discussed about the use of CD/MMS protocol, claiming to hunt their imaginary parasite inside the brain as mentioned by the following: ” In early 2011, we added enemas to the protocol to kill the pathogens causing dysbiosis in the large intestine (we didn’t know about parasites yet). We wanted to get the chlorine dioxide into the blood stream so it could kill the biofilm that exists in the blood. In this way, the blood can carry the CD past the blood-brain barrier to kill pathogens in the brain
When we are detoxing, it is absolutely critical to keep the colon moving and avoid the reabsorption of toxins through the intestinal walls. Enemas allow us to do just this. Some toxins can exit the intestine through the intestinal wall (more so if leaky-gut syndrome is present), and cross the blood-brain barrier, therefore affecting cognition and behavior. When we cleanse the colon, we get those out before they can cross into the brain, and we detoxify the lymphatic system, liver, and gallbladder.”
The following argumentation of Rivera is very interesting as she is referring to Dr. Andreas Kalcker and the parasites at the base of her bleaching-based therapy. Let’s first identify Dr. Kalcker. According to his official biography (http://www.andreaskalcker.com/en/biography.html), he studied economics in Barcelona and has earned a Ph.D. in biophysics and alternative health without mentioning his alma matter. This is very puzzling, as any genuine Ph.D. holder will mention the institution that granted his/her degree. Furthermore, the deliverance of a Ph.D. in biological and biomedical sciences (and I believe in any scientific domains) requires the publication of at least one publication in a peer-reviewed journal. Notably, the search of Dr. Kalcker publication in either Pubmed (NLM) or in Sciencedirect (Elsevier) database leads to inconclusive results. At this stage, his Ph.D. degree claim is highly doubtful and raises concern about the credentials of Andreas Kalcker to hold such title.
The main question that can arise is on which expertise Dr. Kalcker discusses about autism, parasites, blood-brain barrier and nutrition? The author of this critique has 11 years of scientific research experience in the blood-brain barrier, 15 peer-reviewed publications.
The gut-brain axis is still a fairly new concept in the BBB field. Up to now, there is only one study that have demonstrated the beneficial effects of gut microbioma on the BBB development during gestation 10 and requires more studies to further confirm this single report. Furthermore, ASD diagnosis and mechanisms of disease have highly progressed since the original retracted publication of Wakefield and colleagues. It is now a consensus that ASD is triggered by two major factors: a genetic and an environmental factor11-14.
The current consensus is the predominance of the genetic factor that set the risk of ASD development and different factors in particular exposure to environmental toxins may trigger the onset of the condition. This second aspect is very interesting, as the penetration of such toxins across the BBB is poorly understood and believed that the presence of efflux drug transporters and phase II metabolism enzymes would void the penetration of such compounds across the BBB and target neurons. Such statement is supported by the ability of the BBB to act as a very strong barrier towards xenobiotic (drugs and toxins), we estimate than less than 5% of current drugs are capable to cross the BBB. The presence of such BBB is a main challenge for drug delivery 15, 16. However, scientific literature yet has to demonstrate how such environmental polluants mar the BBB and how they may affect brain development during gestation that leads to the ASD onset.
Therefore, we can reasonably ask the following question:
- On which scientific basis Kelly Rivera supports the claim of parasitic infection? There is no published scientific literature supporting her claim.
- Furthermore, under which expertise and scientific literature Dr. Kalcker built his theory on the improper digestion?
According to the Merriam-Webster Dictionary (http://www.merriam-webster.com/dictionary/theory), the definition of theory is “the analysis of a set of facts in their relation to one another”. Neither Kerri Rivera nor Dr. Kalcker have the credential to set a theory because there is no scientific facts to support their theory.
Therefore their tentative to explain their rationale is deeply flawed and should be considered as wrong until a significant number of studies with the adequate scientific quality and neither Rivera or Dr. Kalcker have demonstrated the credentials to exercise a diagnosis or establish a treatment regimen and are legally unlicensed to practice medicine (diagnosis) or pharmacy (treatment) and may face severe legal issues to do so.
The most compelling fact of Rivera and Dr. Kalcker are their active participation in the sell of MMS and CD as a treatment from autism. Such behavior is a clear sign of conflict of interest, a modern form of snake oil sell and a deliberate act of poisoning. Such misuse of public trust and poisoning has lead to the arrest of Dr. Kalcker in Spain in 2014 as reported by the bancdmms website (http://www.bancdmms.com/#!about1/c157n) as well as pro-MMS groups.
In conclusion, until now there is not direct evidence of a gut-brain axis interaction triggering ASD is until now a fallacious statement. There is no clear evidence of such statement, only a series of meticulous cherry picking studies from predatory journals and retracted articles. The direct evidence of gluten and casein peptides in ASD patients is weak and doubtful and would requires a substantial re-evaluation of such claims until other independents research groups demonstrates similar outcomes under controlled conditions.
Furthermore, the etiology of ASD as presented by Rivera and Dr. Kalcker is pure fallacy as none of them have the expertise, credentials and the scientific evidence to make such claims but also have deliberately ignored a sustained and solid publication records concerning the diffusion of peptides across the BBB and the etiology of ASD as a neurological disorder with a high genetic background (supplemented by an environmental factors).
Because the etiology of ASD at this time remains elusive, the treatment of ASD by medication remains until now undocumented, even using pre-clinical models. Only an early diagnosis and intervention by behavioral therapy have been proven successful to improve behavioral and social outcome in ASD patients.
Using common tactics of pseudoscience to distract a non-scientific literate audience, Rivera shows her ability to build an argument on fallacious statements with a an obvious conflict of interest (the endpoint is to sell her MMS/CD cure), as well as a documented harmful outcome of such treatment.
- Reichelt KL, Tveiten D, Knivsberg AM, Bronstad G. Peptides’ role in autism with emphasis on exorphins. Microb Ecol Health Dis 2012; 23.
- Shattock P, Whiteley P. Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets 2002; 6(2): 175-83.
- Hunter LC, O’Hare A, Herron WJ, Fisher LA, Jones GE. Opioid peptides and dipeptidyl peptidase in autism. Dev Med Child Neurol 2003; 45(2): 121-8.
- Shattock P, Hooper M, Waring R. Opioid peptides and dipeptidyl peptidase in autism. Developmental Medicine & Child Neurology 2004; 46(05).
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- Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013; 155(7): 1451-63.
- Lister J, Fletcher PJ, Nobrega JN, Remington G. Behavioral effects of food-derived opioid-like peptides in rodents: Implications for schizophrenia? Pharmacol Biochem Behav 2015.
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