[Sciences/Junk Sciences/Vaccines] HPV vaccine safety – a tale of two studies

“It was the best of times, it was the worst of times” Charles Dickens – A Tale Of Two Cities

If you are following a bit the current news about immunization and vaccines, you likely heard about two studies in regards of the effect of HPV vaccines on population safety, in particular in terms of risk of developing complications or chronic conditions.
Interestingly two studies (to be honest one study and one comment) weighing the pros and cons of HPV public immunization were published within weeks.
One of them was claiming that HPV vaccines increased the risk of cervical cancer in the Swedish population, the other the incidence of autoimmune diseases in the Canadian population, in particular in the population of Ontario province.
One of them was published in a society journal with an reasonably impact factor (IF~8 and Scimago score of 1.7), the other in a journal with inexistent impact factor (Scimago score of 0.2) showing behavior similar to “predatory journals”.
One of them was published “in a peer-reviewed general medical journal that publishes original clinical research, commentaries, analyses, and reviews of clinical topics, health news, clinical practice updates and thought-provoking editorials.”; the other “is a multi-disciplinary academic journal providing a platform for publication of original material and discussion on all aspects of healthcare ethics and the humanities, relevant to and/or from the perspective of India and other developing countries.
One of them was a full-length study with several authors, the other one a rapid communication labelled as “comment” and purposely falsified the author’s name and affiliation (hiding behind an outlook email address), claiming the fear of retaliation by the opposing group.
One of them was a controlled population study, investigating two groups (vaccinated versus unvaccinated) with a sample size of 100’000+ each; the other one tossed epidemiological data together without further stratification and cherry-picked the information.
One of them was concluding the safety of HPV vaccine and absence of increased risk of autoimmunity, the other questioned the safety of HPV vaccine straight from the abstract as “I discuss the possibility that HPV vaccination could play a role in the increase in the incidence of cervical cancer by causing instead of preventing cervical cancer disease in women previously exposed to HPV. A time relationship exists between the start of vaccination and the increase in the incidence of cervical cancer. The HPV vaccines were approved in 2006 and 2007, respectively and most young girls started to be vaccinated during 2012–2013.
After a media firestorm and the strange support of the editorial board towards the author (and still consider the data as legitimate), it got finally retracted. The corresponding author has also been informed he will have four other retractions upcoming.
Guess which one was the flawed study published with a falsified author information and in a journal with a scope outside the content of the article published?
You can these publications here and here.


[Vaccines/Junk Sciences] “Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin” (Aratani et al., Sci Rep 2016 – RETRACTED) Lesson from a paper that went completely fritz on the scientific method

You maybe heard about the recent retraction notice of a study published in Scientific Reports that raised concern about the safety of Gardasil(R) (HPV vaccine) and got retracted this week. Another anti-vaccine paper that bit the dust. I would have say, I am not surprised at all. Anti-vaccine studies have this very annoying habit of either being a proven fraud (remember the latest Shaw paper?), botching the experimental protocol with omission of proper controls (thats the Exley paper I have reviewed) or conveniently sweeping under the rug some data that are not fitting the narrative (that goes for one recent paper published by Gherardi).
But this one is interesting at several levels, because there is a bit of blood-brain barrier in  it, and also adds to the list of papers retraction in Scientific Reports and recent threats by scientists in the editorial board to resign from their positions due to ambiguous and unjustified decision on a flawed paper (Disclaimer: I have a study authored in this journal and I have peer-reviewed for them a couple of times).

To be honest, I only heard about this paper during the last weekend and took some times to read the paper. I will be honest, I don’t see any scientific fraud in the sense of data manipulation. What concerns me is how such a botched study could even pass through peer-review process? Considering I self-impose a quality of standard in my manuscripts and still get challenged by peer-reviewers, seeing such junk studies getting a free pass is a bit vexing. I agree that open-access may not have the same stringency in terms of peer-review filter but considering Scientific Reports as part of Nature Publishing Group, you expect a rigor found for any Nature-related journals applied in this journal too.

But lets go through the paper, it is retracted but you can still access it here.

What is the wrong with this paper?

1. The experimental design in terms of groups

The first problem arises from Figure 1.


We have six groups: vehicle (PBS), pertussis toxin (PTX), Gardasil(R) (MSD, HPV vaccine 4-strains) (G), G+PTX, EAE and EAE+PTX. Let’s breakdown first these oddities.  Why the author has included a PTX group, even more adding PTX with Gardasil? There is not much explanation in the text explaining the rationale (also the writing style is odd, very odd. I completely understand that the first author is not a Native English speaker. As an ESL myself, I completely understand that). Also, I am not aware about a higher risk on contracting pertussis upon vaccines.
The second aspect is the use of the EAE mouse model. EAE stands for experimental autoimmune encephalitis. It is the “gold standard” for a mouse model of multiple sclerosis (MS). The idea behind is to inject a brain protein (myelin basic protein or MBP), which will trigger an immune reaction (as the brain is a immune-privileged organ) and result in symptoms similar to MS. I would understand to compare the incidence of Gardasil(R) on MS patients by comparing EAE mice versus non-EAE mice but that is never the case (they even administer PTX to a sub-group).
So here we already start with a wrong experimental design: it just make no sense. A more rationale approach would have been the following:
Vehicle (PBS), Gardasil (G), EAE, EAE+G. That would have saved two groups and precious lives sacrificed in another useless study.

2. The experimental design in terms of statistics and power of analysis

Another important issue is the blatant dismissal of consideration of biostatistics and the power of analysis in the experimental design. For those that are not familiar with scientific research, you have to ensure you have a statistical meaning to your data to ensure the effect observed is real and not due to simple coincidence. This statement is especially true when working with vertebrates animals. Any animal experiment has to be approved by the institutional IACUC that ensure you have a clear idea of what are the purpose of your experiments, how you will ensure a humane treatment to animals and also have an optimal number of animals to achieve a statistical significance.
An important aspect for in vivo (animal) studies is to achieve at least a sample size of 8 or more animals per group (n=8). From Figure 1a, we have already a violation of this as only the G and the G+PTX have enough animals (n=14 and 21 respectively). All other groups are below the n=8 threshold. In addition, you have very different number of animals per groups (control has n=6, EAE has n=5) making the statistical power weak and also restricting the use of common statistical methods such as the use of ANOVA (ANOVA recommends that all groups have an equal number of samples).

3. The experimental procedure and treatment

This is where the firestorm came in: the experimental data. So lets bring this to the table: “Groups of 11 week-old female C57BL/6 mice were intramuscularly administrated 100 μ l of Gardasil or phosphate-buffered saline (PBS) for a total of five times. Ptx was intraperitoneally administrated 2 and 24 hours after immunization. The Gardasil vaccine or Ptx were administrated at 2- weeks or 4-week intervals“.
A key element in a paper is the methods section and this one utterly failed. Based on this information I have absolutely no idea why they injected five times (Gardasil immunization is maximum 3 times), why they injected the PTX right after the immunization (2 and 24 hours, suggesting a double-induction) and when they injected the Gardasil and PTX (how do they separate the 2-weeks versus the 4-weeks? When did they started?).
Also the use of 11 week-old female is not reflective of a human case scenario. If we approximate 1 human year to about 3.6 mice-days, you would expect to use young mice (males and females, to have a gender-balanced study) that are about 6-weeks old (~43.2 days). That would be about 12 years, the age of puberty.
Here we are basically injecting HPV to adult females, which is known to not provide an additional benefit as such population may have already been exposed to HPVs.
The next problem is the injection dose. It is 100microL, thats the equivalent of 0.1mL. A single dose of HPV is 0.5mL. Lets ignore the scale law and assume a mouse is an equivalent to a human. A 50th percentile weight at age 12 is about 40kgs. Lets assume a 6-weeks old mice to be about 20g.
If we assume 0.1mL injection to a 20g mouse, then the human dose-equivalent would be about 200 dose-equivalent injected at once! This is a serious issue because there is absolutely no chance that such things to happen in a lifetime (at grand maximum you may have 3-4 HPV injections, spaced in time). Also, if we assume the age scale, we are expecting to have mice receive their two doses within 48 to 96 hours, not 2 to 4-weeks.
I am not even entering the rationale to inject PTX right after immunization, which is utterly no-sense and just scramble defining the effect of HPV versus the effect of PTX. Another disastrous example of how this paper was flawed from the beginning.

4. Failure to report weight and clinical score

If we want to follow an EAE protocol, it is important to show the evolution of animal weight over a period of times (up to 15-21 days) as well as a clinical score. The clinical score is a well-described protocol in which features found in EAE mice are score from mild (tail flaccid) to severe (inability to move hindlimb or complete immobility).
These two graphs are almost present in any EAE paper outside in the literature.
I assume this is what Figure 1b and 1c wanted to show but very poorly. Indeed Figure 1c does not really show up anything. We dont know when these data have been taken, we have no idea about the onset time of symptoms and furthermore we have no indication of a statistical differences. This is already a waste of data.

5. The constant cherry-picking of the data and incomplete picture

The methods used are honestly laughable: some hematoxylin-eosin staining (a common histological stain that does not tell much unless you have massive brain damage or the growth brain tumor),  Kluver-Barrera staining (for myelin staining), TUNEL stringing (for apoptosis), a behavioral test relegated in Supplementary Figure S1 (in which the author thinks that a P-value of 0.1 has a statistical meaning).


Where is the Evans blue extravasation staining to show a disrupted BBB? Where are the GFAP staining to show astrocytes activation? Where are the CD11b and F4/80 staining to show microglial cells activation and macrophages infiltration? Nowhere to be seen. We have to comptent ourselves with some miserable histological staining in Figure 2 and 3. Also no-one of the data about EAE is never shown past Figure 1. Figure 4 is even more laughable as the author only shows the staining of the G+PTX, giving the middle finger to the reader to how such staining looks like in vehicle, or G.


How can the author be confident that it was the Gardasil treatment, not the PTX treatment (despite being mentioned as a BBB disrupting toxin) being the sole contributor of all this?

6. Conclusions

Another anti-vaccine study, another case of botched science resulting in a junk paper, the sacrifice of animals over a useless experiment. That should not have been passing through the peer-review filter at all because of its deficiencies, yet was able to go through. If I was the reviewer behind it, I would have been ashamed to have this paper not outright rejected for major flaws in the study. Should we assume that the author recommended some complacent reviewers  to this paper? Or should we question the integrity of the editorial board in accepting papers for publication that fail to address some scientific integrity? Again, anti-vaccine studies shows that they cannot challenge vaccine safety and can only make fool of themselves by producing junk studies like this time.

The first and senior authors of this paper produced a paper that is so bad, they should feel ashamed to even had published at first.


[BBB/Autism/Junk Sciences] Autism, bleach and the blood-brain barrier: how the CD/MMS cult is promoting child abuse on bogus scientific claims.

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:

  1. On which scientific basis Kelly Rivera supports the claim of parasitic infection? There is no published scientific literature supporting her claim.
  2. 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.


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  15. Cucullo L, Aumayr B, Rapp E, Janigro D. Drug delivery and in vitro models of the blood-brain barrier. Curr Opin Drug Discov Devel 2005; 8(1): 89-99.
  16. Abbott NJ. Blood-brain barrier structure and function and the challenges for CNS drug delivery. Journal of inherited metabolic disease 2013; 36(3): 437-49.


[Sciences/Junk Sciences] Remember the deadly turmeric IV infusion done in a holistic clinic? Lessons from the FDA report

You have remember this story of this young woman that died shortly after recieving an IV infusion of turmeric acid (aka curcumin, a bioactive compound found in Curcuma) in a holistic clinic in California few months ago (http://www.10news.com/news/team-10/encinitas-woman-dead-after-i-v-infusion-of-turmeric).
This story baffled me for many reasons. First, it was really puzzling me on how quack medicine (rebranding itself as “holistic” and “integrative” to appear more sciencey) have been moving slowly but surely into medical procedures normally held by medical staff, with some dubious claims of “IV therapy” in which the onset of an IV line and pumping up vitamins straight into your systemic circulation will help you “detox” or “rejunevate”.
Second, how turmeric acid that have been bounced by some “health/food gurus” as superfood (move on kale and quinoa, you are so 2015!) quickly moved on as therapeutics without even having the right science to back it up (until now only preclinical studies done in cells grown on Petri dishes and in rodents), with the glittery “cures-it-all” sticker all over it.
You see, turmeric acid is way far from being the next wonder drug as sold by woo peddlers. Why? Lets see some of its features (https://pubchem.ncbi.nlm.nih.gov/compound/curcumin#section=Top).
First thing, turmeric acid has a problem. A huge problem. This problem is solubility. It has a calculated xLogP of 3.2, this is already telling us this compounds is lipophilic (likes fat). It will dissolve well in oil, but not well in water (less than 0.1mg/mL according to Santa Cruz Biotechnology data sheet). If you try to go beyond that value, you will have a saturated solution with turmeric acid precipitates. These precipitates can have serious effect if injected into an IV line, if these particles are big enough to clog some capillaries.
You can circumvent things around by tweaking nanoparticles carriers. Still, even from food intake, turmeric has a very low bioavailability. From 100g of pure turmeric acid swallowed, only 1g will effectively reach the circulation and circulate through your body.
The second problem with turmeric is its pharmacokinetic profile. According to the reference cited by the FDA report, turmeric is highly unstable at physiological pH (7.4). According to this review, the elimination half-life (t1/2) for turmeric is very low (1.7+/-0.5h). By 6 hours, most of the turmeric injected via IV route will be gone. Therefore, if turmeric was considering for therapeutic, it would require multiple dosing that are either ridiculous (Dosing interval of about ~2 hours, therefore swallowing a pill every two hours) or being on a constant IV infusion (that is not realistic for everyday life).
Third problem with turmeric? Its pharmacological activity. Two important parameters have to be accounted for a drug candidate: its selectivity (does the drug targets one or several proteins?) and IC50 (what is the concentration needed to achieve 50% inhibition).
The problem with turmeric is that it is considered as a “dirty” molecule because it hits a bit of everything, with many signaling pathways affected by it. The second problem is its very high IC50. Anti-cancerous activity of turmeric swings around 10microM in various cancer cell lines in a Petri dish and have other targets at higher doses. This is not a horrible value, not a good value either. Usually we want to reach an IC50 in the nanoM range (10’000 less concentration than 10µM). Thats not the case for turmeric. Maybe by tweaking the chemical structure we may improve its IC50, but since the compound itself has so many targets trying to optimize it for therapeutic purposes maybe simply a waste of time.
If we stick to the 10µM concentration and an average molecular weight of 328g.mol-1 for turmeric, we need a concentration of 3mg/L or (0.003mg/mL) to expect some biological activity. Now the problems come in with the FDA report. There are two reported cases of adverse events, including the fatal cases. In both cases, patient had an IV line of turmeric acid. In both cases, both patients were mentioned an IV infusion of turmeric acid at 10mg/mL. First, this concentration would have made no sense. It is 300 times higher than the hypothetical dose needed to achieve a biological activity in vivo. Second, the final concentration in the IV bag was much less than this concentration, as the FDA reported only 1% of the prescribed concentration was found in the IV bag (0.00235mg/mL).
Someone has been not only been deceiving their customers by selling you less product than advertised (1% net content is honestly a huge rip-off) but also had absolutely no clues on what they were injecting. So we can blame two actors: either the compounding company that prepared the turmeric or the holistic clinic (I guess you can point who is the crook in the story).
Both cases involved ImprimisRX, a compounding pharmacy. These are laboratories under the responsibility of a pharmacist holding a specialization in compounding. He or she has to follow established rules and protocols, adhere to good manufacturing procedures in compliance with the FDA. It seems there is no wrongdoing from the compounding. The compounding produced an emulsified form of turmeric (to increase its solubility). Yet, the final concentration in the vial was about 0.205mg/mL or about 2% of the amount put on the label. Since turmeric is highly unstable under aqueous solution (even in its emulsified form) we cannot exclude a degradation of the product from the time it got compounded to the time it was administered. In aqueous protein-free solution, 90% of turmeric acid is degraded within 30 minutes (https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/UCM466380.pdf).
Now comes an another problem: was there any deception between ImprimisRX and the holistic clinic? One of the reason is the use of polyethylene glycol 40 (PEG40) castor oil in the compounding process. PEG40 may contain traces of diethylene glycol (DEG), a very well known toxic compound if ingested, with a toxicity of about 1mg/kg. DEG is a byproduct of PEG production, therefore the FDA has different quality grades of PEG whether it is destined for non-medical usage or for human consumption. DEG was found at a concentration of 0.21% (0.21g pure DEG in 100g of PEG40). The PEG40 used for the compounding was 1.25% with the clear label “CAUTION: For manufacturing or laboratory use only.” Why the compounding pharmacy used that ungraded PEG40? We don’t know yet.
PEG40 oils are used for cosmetics and considered safe for cosmetics usage  because the bioavailability of this compound is small and suited for topical application (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505343/). But you have to remember that a product that is considered safe in an administration mode is not in another administration route. This is probably explaining the adverse effect observed.
The second possible issues is a possible allergic reaction to PEG40, as the FDA cited previous reports of allergic reactions of patients exposed to PEG formulations following IV infusion of anti-cancerous agents.
By now, your enthusiasm for cur turmeric should (rightly) wind down. Turmeric is certainly great for spicing your food, not much for your health. But most of all, don’t let a “holistic clinic” perform any type of IV infusion.
IV infusion is a very delicate procedure, used for restricted applications (chemotherapy, anesthesia, infectious disease……) by a trained personnel in a medical environment (hospital or medical clinic).

[Sciences/Junk Sciences] Essential Oils: The good, the bad and the ugly science behind some claims

Essential Oils (EOs for simplicity). These little bottles are almost everywhere. Advertised as “natural”, “pure”. Some even are trying to sell them as the next big fad. as the next “miracle cures all” remedy.

Everybody swears by EOs, giving them some curative properties despite the lack of evidence backing such claims. Their therapeutic activity is far from being demonstrated, but their ability to siphon wallets and fill bank accounts of those selling them is as efficient as  the Bernouilli’s principle.

The problem with EOs is to sort the good, the bad and the ugly science behind them.

@MommyPhD recently pointed this out in a nice chart taken from a company making a living on EO.

What I can tell, as the pharmacologist that I am, I was not only perplexed but mind-blown by this chart. It was not a nice mind-blowing effect. It was more like a trigger that turned into a “ballistic mode”.

Just see by yourself the chart below:


What is wrong? Well, all the claims from the original infographic (left) are wrong! It just simply no sense if you have any basic in pharmacokinetics. Its time for the BBB scientist to deflect such woo with some science deflector shields.

First, in order to understand EOs, you have to understand their origin. To understand their origins, you have to have some basic understanding of pharmacognosy.

Pharmacognosy and EOs:

Pharmacognosy is the science that studies the chemical and biological properties of substances produced by plants and fungi. They are seasoned experts in botany, plant biology and analytical chemistry. Their main interest is to extract chemicals from different part of the plant (stem, sap, roots, leaves, flowers, fruit….), identify the substances present in such extract and identify their possible biological properties (this is often linked with ethnopharmacology, in which scientists are trying to identify the potential of some medicinal plants with their use from healers and shamans).

Plants and fungi synthesize two major classes of molecules: those involved in the primary metabolism and those involved in secondary metabolism.

Primary metabolism mostly aimed to ensure growth plant and reproduction. You can consider it as the core chemical plant. These are chemicals important for the plant function.

The second metabolism is on its own very interesting. At first, these compounds have no role in plant growth and therefore may appear useless. Indeed compounds produced from secondary metabolism are very important for the plant because these are essential for its survival. Plants evolved to have limited mobility and therefore are easy target for predators. But what plants traded out for limited mobility have indeed traded in one of the most sophisticated chemical warfare. Plants have evolutionary developed one of the most advanced and versatile chemical warfare aimed to control and deter any dangerous entities that may compete for limited resources (water, minerals, oxygen, light, CO2…).

Here are some examples of chemicals synthesized by plants secondary metabolism: Caffeine, atropine, cocaine, morphine, tetrahydrocannabinol, strychnine, nicotine, digoxin, ouabain, terpenes, cyanide, colchicine, vinblastine, paclitaxel, acetylsalicylic acid, phalloidin, forskolin, turmeric acid…….these are all products from the secondary metabolism. Many of them sounds like “poisons” and they are rightly called poisons because they can kill you at the right dose. But if you use these compounds at the right dose, these compounds can also be used to treat cancer, heart failure, glaucoma……..considering the dose makes the poison.

EOs are a particular class of chemicals, because they harbor particular chemical features. They are volatile (they belong to the superclass of volatile organic compounds or VOCs), lipophilic (soluble in fat and oils) and are odorant (this is why we can smell them). They are also capable of some biological activity.

These EOs have to be extracted from the plants via the use of organic solvent. One of the most common solvent is ethyl alcohol or ethanol (CH2OH), that is convenient organic solvent. Ethanol can help dissolve both lipophilic and hydrophilic substances. It is also has a low evaporation temperature (78ºC), allowing it to dissipate fast once on skin contact.
Another property of these compounds contained in EOs is their ability to become volatile. We can refer these compounds as volatile organic compounds (VOCs). This is why we use them as fragrance. Because they are volatile, these compounds are spread in the air and can be caught by our olfactory receptor neurons (ORNs), making what we refer a smell a smell. Smells are very powerful stimuli, even for humans. This is why we are all fond of “eau de toilette”, “eau de parfum” and all these molecular cues that can turn our reptilian brain upside-down.

EOs are very diverse by their origin and their composition. For the simplicity of this article, I will focus on the major source of EOs by their production: Citrus sirensis (sweet orange) and Mentha arvensis (mint) EOs. These are the two most prevalent sources of EOs worldwide.

Two studies that I have found listed the EO composition from these two plants.  C. sirens is  has about 50 different compounds identified, mostly classified as terpenes. M. arvensis  have about 30-40 compounds including terpenes and other organic compounds (http://www.ifrj.upm.edu.my/18%20(04)%202011/(10)IFRJ-2011-062.pdf and http://citeseerx.ist.psu.edu/viewdoc/download?doi=

EO composition vary between cultivars, between crops, between extraction procedures. …..It means that EO by nature are anything but “pure”. EOs are therefore impure because you have a mixture of different compounds at different concentrations. It also means  that such EOs are setting the perfect storm for some drug interactions and some toxicity due to photo activation (some terpenes like limonene are know to become phototoxic following exposure to light)  or induction of an allergic reaction.

Pharmacokinetics and EOs:

In this second part, we will refute the claim brought about the penetration and tissue targeting mentioned in the infographic. The infographic have it wrong at so many different levels but two are striking: firstly, the sequence of events followed the extent of these events.

In order to understand the rebuttal, we have to understand some basic aspect of pharmacokinetics (PK). PK is the science that will tell you the fate of a chemical in your body. It will tell you how it is absorbed, how much reach the bloodstream and the tissue, how it gets detoxified and finally how it gets eliminated.
PK focuses on the fate of drugs inside our body, whereas toxicokinetics (TK) focuses on the fate of poisons and toxins inside our body.

Both follow the ADME acronym: Absorption (tegumentary/skin, intestinal/gut….), Distribution (bloodstream, tissues and brain), Metabolism (“detoxification” via chemical transformation and inactivation by the liver) and Elimination (via the liver and kidneys).

This is where the infographic has it completely wrong. It makesthe assumption that the EOs enter the brain, then the bloodstream and finally cells is just what I call “bullshit” and simply a reflection of a sheer ignorance of human anatomy and physiology. I dragged a small sketch to described the EOs ADME profile.

EssentialOilFirst, EOs have to pass the skin (or gut) barrier and diffuse all the way through the bloodstream. This operate through a passive gradient that result in the progressive loss of EOs compounds during the diffusion (depicted by the yellow arrow) into the bloodstream. This phenomenon is called “bioavailability” and investigate how much of a compound can reach the bloodstream following an administration route that is not obtained via direct injection into the bloodstream (intravenous or intra-arterial).

At the end of the day, this is the appropriate order of sequence: skin->bloodstream->brain (if you are lucky enough).

The amount of compounds contained in the EOs reaching the blood circulation remains unclear and poorly understood. But we can use some analogies with known chemicals. We will discuss the case of hydrocortisone (a topical steroid) and nicotine (a known compound capable to cross the BBB and act on the central nervous system).

Hydrocortisone is commonly used by practitioners to treat skin rashes and other irritations with a cream. The good thing about it is that such cream act topically. A thesis has documented previous studies that estimate about less than 5% of the amount of hydrocortisone applied to the skin was able to get a full ride into the kidneys (https://www.unispital-basel.ch/fileadmin/unispitalbaselch/Bereiche/Querschnittsfunktionen/Spital-Pharmazie/Diss_Pellanda.pdf). It is also telling you that a topical administration is probably not the best option for administration of a drug.

Now, there are other cases of topical administration that result in brain delivery. This is the case for nicotine and nicotine patches. These delivery systems are good in giving a good bioavailability, but yet these compounds will take some time to reach the brain. Considering the tmax (time by which a compound reaches a maximum plasma concentration), such delivery systems can only deliver nicotine with a tmax of 5-6 hours following patch application (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364642/?page=4). You can understand that the probability of compounds contained in EOs to reach the brain within 30 seconds is impossible, unless you perforate the skull and perform an “intraventricular injection”. This is a very invasive procedure requiring a brain perforation and the insertion of a canule deep inside the brain.

Now we can argue that some drugs can reach the brain within minutes following injection. This is true for anesthetics like propofol. However propofol administration route and chemical properties are very different from EOs: they are injected via IV infusion and propofol penetration across the blood-brain barrier (BBB) is known and documented. Yet, it still takes about 4 mins for a IV infusion of propofol to achieve tmax , making the alleged claims of 22 seconds in the infographic completely bogus (https://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4354b1-01-FDA.pdf).

Even if your compounds can diffuse the skin barrier at the speed of light (100% absorption and bioavailibity) and have no metabolism (0% loss in EO compounds), you still have to demonstrate that such compounds can cross the blood-brain barrier (BBB). The BBB  blocks about 95% of chemical compounds known by humans. Therefore it is very unlikely that all these EO compounds magically fall within the 5% range.

In addition, analyzing the fate of every single chemical compound present in one EO can be an analytical nightmare even for the most seasoned analytical chemist. @SciBabe can explain you that in more details.

In conclusion, the ability of EOs to exert their biological activity beyond their skin application is simply “dead in water” and subsequently the claims posted in the infographic.

EOs and their “therapeutic claims”: the FDA warning letters
EOs may smell good but they have no scientific basis to support their claims of therapeutic use as depicted on their website. This is why the FDA has decided to enforce its authority via warning letters to two companies.

In 2014, the Food and Drug Administration (FDA) sent two warning letters to Young Living (https://www.fda.gov/iceci/enforcementactions/warningletters/2014/ucm416023.htm) and DoTerra (https://www.fda.gov/iceci/enforcementactions/warningletters/2014/ucm415809.htm) noticing them of the violation of the Food, Drug and Cosmetic Act by advertising therapeutic claims that have not been asserted. Unless you file an application in which you document with a great care the safety and the efficacy of a therapeutic agent, you have no rights to make a claim that compound X will prevent or cure cancer or other illnesses. What was true for these two companies also applies for any companies selling EOs.

Do not use EOs to treat or cure any illnesses because their therapeutic activity have not been proven by scientific methods. Worse, if misused these EOs can become dangerous poisons if swallowed  (http://www.poison.org/articles/2014-jun/essential-oils). You have been warned.

In conclusion,  EOs make great scents and fragrances to make your house smell nicely. But that should be their only application. Use them as personal fragrances with extreme precautions and avoid their swallowing and use as medicines.

[Junk Sciences] About that Dr. Neides article published in Cleveland.com

I am sure you have now heard about the infamous opinion article published by Dr. Daniel Neides, MD (Cleveland Clinic) titled “Make 2017 the year to avoid toxins (good luck) and master your domain: Words on Wellness” and published in Cleveland.com, the online site of “The Plain Dealer”, a local newspaper (http://www.cleveland.com/lyndhurst-south-euclid/index.ssf/2017/01/make_2017_the_year_to_avoid_to.html).
What was sounding first as a silly title just in time for the post-holiday “detox diets” and other scientific fallacy, quickly spinned into a conspiracy nightmare. I would not have been surprised if it came from some quack doctors that make a living on selling supplements, books and other premium services.
What was the most concerning was this article came from a medical director from a highly regarded US Health Institute, as the article was signed as “Dr. Daniel Neides is the Medical Director and Chief Operating Officer of the Cleveland Clinic Wellness Institute.
You can check for yourself but the content of this opinion article was simply frightening (I am commenting on the article as it was published on 1/8/17 at 10:52AM.
LYNDHURST, Ohio–I am tired of all the nonsense we as American citizens are being fed while big business – and the government – continue to ignore the health and well-being of the fine people in this country. Why am I all fired up, you ask?
I, like everyone else, took the advice of the Centers for Disease Control (CDC) – the government – and received a flu shot. I chose to receive the preservative free vaccine, thinking I did not want any thimerasol (i.e. mercury) that the “regular” flu vaccine contains.
Makes sense, right? Why would any of us want to be injected with mercury if it can potentially cause harm? However, what I did not realize is that the preservative-free vaccine contains formaldehyde.”
The article first sentence just set the tone: Dr. Neides has a grief about Big Gov and Big Business in general. I am mad on the government too, but not for the same reasons. We have been facing one of the most polarized election with the two parties trenched into their ideological trenches, with the average Joe in the cross-fire. We cannot have a ruling government without having a bipartisan consensus that help find a common ground to move on.
Then things gets sour as he is fingerpointing on the CDC, again using the allusion of Big Gov for his grief on this institution. It quickly turns into a anti-vaccine diatribe, with spelling errors (it is “thimerosal/thiomersal” not “thimerasol”). Not only Dr.Neides fail to name his grief correctly (and you cannot blame autocorrect on that one) but also makes a scientifically fallacy by associating “thimerasol” as mercury. As previously mentioned in my blog, there is a huge difference between mercury as an element (Hg) and the organomercury compounds such as methylmercury (CH3Hg) and ethylmercury (CH3CH2Hg). Considering organic chemistry part of the pre-requisite courses for any medical school, this type of mistake is not acceptable.
In a common anti-vaccine move, Dr. Neides quickly played the “goalpost moving” tactic. If you first argument failed following its refutation by facts, move to another target and play the same spiel. If it is not thimerosal, then it is the formaldehyde. If it is not the formaldehyde, then it is the aluminum……..
We are not yet at the end of the first paragraph and already Dr. Neides has taken a dangerous slippery slope in pseudoscientific claims. He will continue into the “appeal to authority” fallacy, claiming the government is condoning the global population health. This is why the government has agencies like the Department of Health and Human Services (DHHS), the Food and Drug Administration (FDA), the Center of Diseases Control (CDC) and the Environmental Protection Agency (EPA). They have doing their job, could be better but it could be worse. Considering our next government line-up, we will likely soon regret how “red tapes” is sometimes needed.
But lets go to the second part of his article with this very interesting quote:
We live in a toxic soup. There are over 80,000 chemicals used in various industries country-wide. There are over 2,000 new chemicals being introduced annually. We breathe in these chemicals through exhaust, eat them in our processed foods ( just look at the labels that have 20 or 30 ingredients and good luck pronouncing their names), textiles (clothing, bedding, furniture), and personal care products, including make-up, deodorant, shampoos, and soaps.“.
Of course we are living in a chemical soup, but not all of them are toxic. There are some that are neutral, some are toxic (this is what we refer as poisons and toxins and are extensively studied by a discipline called toxicology) and some are even beneficial (these are identified by a a discipline called pharmacology).
Authorities are constantly testing these chemicals for 40 years now and there is a huge effort from international agencies to provide a formidable toxicological database to document the toxicity of any existing chemical inventoried.
A side-note, the quote “good luck pronouncing their names” sounds eerily familiar to a quote from a certain Babe “If a third grader can’t pronounce it, don’t eat it“. I am guessing I should ditch the addition of “alpha-D-glucopyrannosyl-1,4-alpha-D-fructofurannoside” from my morning cup of Joe. Thats by the way the biochemical name for sugar.
It is followed by a mishmash of different terms that just sound like a nightmare for anyone teaching pharmacokinetics to healthcare professional.
Toxins accumulate in our fat cells if they are not eliminated and interrupt normal bodily functions. Your body should be a finely tuned machine with all of the organ systems working in concert together. But when toxins disrupt normal function, problems can occur. Those problems include cancers, auto-immune diseases, neurologic problems like autism, ADHD, and Parkinson’s disease, and the most prevalent chronic diseases like obesity, diabetes, and heart disease (note: so high blood pressure is not a chronic disease, then?).
Why are we so sick in 2017 despite the best access to healthcare? The body has wonderful built-in systems to help us detoxify. The liver and kidneys try to do an exceptional job keeping up with filtering out the “stuff” (toxins included) we don’t need. Our skin – the largest organ in the body – will release toxins in the form of perspiration (what did they teach you in med school? How did you graduated from your biochemistry class?). Our breath will release toxins with each exhalation (same “boingboing” moment). When our gut is healthy and our microbiome (100 trillion organisms that live in our intestinal tract, within our airway, and on our skin) intact, our bowel movements help rid unwanted toxins.
I like to think of our detoxification system as a big bucket. As long as the toxic soup stays within the bucket, our body can naturally eliminate what we don’t need and help us live at the highest quality of life. But what happens when the bucket starts to overflow – which is exactly what many of us have been facing our entire lives? The body may not have the capacity to eliminate our current exposures and THAT IS WHEN BAD THINGS START TO OCCUR.”
We, as animals, have evolved to deal with many chemicals in nature that can have a possible threat to use. In pharmacokinetics, we refer to ADME for Absorption, Distribution, Metabolism and Elimination.
Absorption of compounds is limited for water-soluble compounds, they need a special door (called solute carriers) to enter inside your body. Now some (and many drugs in general) are fat-soluble (we call them lipophilic compounds) and can diffuse passively through the intestinal barrier and get into the bloodstream. Even if these drugs can make it through the gut, they have to face a firs-pass metabolism by the liver (we will discuss later about it) and deactivate some if not all of them. Those who were not affected by the first-pass are ongoing a distribution phase. Distribution occurs by the spread of the compounds throughout the central compartment (blood circulation). From this compartment, compounds can diffuse into peripheral (tissue) compartments. One of this compartment is named the “deep storage compartment” (a nice word for your fat tissue) that can retain some lipophilic drugs. As long as you ingest them, you can accumulate these compounds. Once you stop, these compounds move from the periphery back into the central compartment. We know which compounds can store (the lipophilic ones) and such feature is considered in toxicological studies to define if a compound is toxic or not. After circulating, compounds are perfusing through the liver and undergo of series of chemical reactions called metabolism. Metabolism is ensured by a series of enzymes grouped into two phases: Phase I enzymes (called cytochrome P450s or CYPs) and Phase II (conjugating) enzymes. Phase I enzymes transform compounds from a fat-soluble into a water-soluble compounds. Phase II enzymes tag these compounds to ease their elimination. Finally, the elimination phase is the one by which the body get rid of these compounds. There are two major routes: hepatobiliary (liver via the bile duct and eliminated via feces) and renal (kidneys).
Again, the fallacious claim that skin and respiration are considered as major elimination routes is simply outrageously wrong, especially considering from a healthcare professional.
The third part is directly playing the classical anti vaccine tropes “vaccines cause autism” that have debunked again and again.  I will not into it, there are great resources about what this claim is purely wrong and not supported by science.
But I just wanted to add my take on Hepatitis B (HepB) and newborns vaccination. The general public has a global misconception about HepB being only an STD. Indeed it is not. HepB is the same type of virus than HIV when we talk about mode of transmission: a blood-borne pathogen (in addition to its sexual transmission). This is a vaccine we highly recommend to any staff working in lab research and handling any blood or blood-based products. Because there is always a risk of HepB transmission via accidental cut and exposure to blood, this is even supported by being an “healthy carrier” (you have circulating HepB in your blood but you are not having any liver condition). it is better safe than sorry, considering than HepB can lead to severe liver pathology such as cirrhosis.
Finally the fourth part was fairly alarming. You may have heard about Orac, a seasoned MD and oncologist that is doing a great job in his website “www.sciencebasedmedicine.org“. Orac has been raising his concern that pseudoscience and quackery has been percolating inside mainstream medicine, using names like “functional medicine”, “integrative medicine” or “holistic medicine” as a wolf with a sheep cloth, appearing harmless.
He cites then a quote from a colleague named Jessica Hutchins, MD and IFM-certified (certification from a certain Institute of Functional Medicine) as described as the following:
In a 2015 article in U.S. News and World Report (Link to her article), Jessica Hutchins, M.D., IFM certified practitioner, states , “Information on eating toxin-free food and pushing food manufacturers to stop using harmful ingredients can be found at foodbabe.com. When we vote with our dollars by choosing to buy products that are sustainably produced and chemical-free, we actively shape the market place. Help change the way [loved ones] nourish their precious bodies, starting with yourself as an example.
Using Vani Hari (aka the FoodBabe) as a source of information and as a reference for health advices, from an MD, is simply insane! “What did they teach you at the IFM?”. At first glance, the certification program provided by the IFM seems legitimate (https://www.functionalmedicine.org/certification_program/About/) however one single item appear intriguing:
Comprehensive assessment of the fundamental physiological systems that organize the key clinical imbalances and are affected by the mental-emotional-spiritual core: Assimilation, Communication, Defense and repair, Transport, Energy, Structural Integrity, Biotransformation and elimination
Until now, we have little or no evidence of prayers and thoughts work in healing someone, lesser than any evidence faith healer healed someone solely on their spiritual powers. Also the presence of chiropractors as instructors (and we know how well chiropractors have a scientific training) is also disturbing.

In conclusion, 2017 comes in with a bang as I feared: a year in which evidence, facts are discredited by gut-feeling, smooth talks and snake oil sellers.

Post-scriptum: when you have woo peddlers lauding your article, you know that our article is a complete #NaturalNonSense (courtesy: Chow Babe).

[Junk Sciences/BBB] Does bone broth leads to a leaky brain? (aka the stupid, it burns!) 

Everyone should have recovered from the post-Thanksgiving food comatose (no, it was not due to the turkey’s tryptophan), the post-election discussion and the Blck Friday melee fight for that 55″ UHDTV that is justin time to play on your XB1S with a 4K resolution.
Seem the woo is never running short of idea, piling up fallacy over another fallacy as iHop piled up pancake in a post-Thanksgiving breakfast ride.
The latest fallacious claim cames from a “nutrition blog” claiming that bone broth, leads to elevated glutamate levels following bone digestion (!), such glutamate results into a leaky gut. Leaky gut means utomtically leaky brain, letting glutamate flows into the brain as boiling pasta water flows through the hole of the pasta strainer and ultimatelly leads to neurological disorders, with a special mention of neurodevelopmental disorders such as ADHD and ASD, because these are two conditions that scares parents as hell nd therefore makes a juicy alibi to milk on parents withtheir precious $$$ and torture kids with dubious or completely scam treatment (including bleach enema, putting kids on casein-free/gluten-free diet, hyperbaric oxygen chamber or chelation treatment).
Because I am the one claiming the claim of this blog post is bogus, it is my duty (and my pleasure as a BBB Scientist) to debunk it.

1. About the bone broth….

In the post, the author first claim that bone broth prepation (slow cooking) results in a dissolution of the tendrils and connective tisues to dissolve, as cited as the following
So what’s the dark side of Bone Broth? It lies in the “long” part of the “slow and low and long” cook time. Bone Broth simmers at a low temperature for many hours, long enough to allow the connective tissues to dissolve and the minerals to be drawn into the broth.Thats partially true. Bone broth is composed by two major type of tissue: connective (bones, tendrils, muscles) and non-connective tissue (basically the bone marrow). The preparation of bone broth will primarily dissolve the bone marrow (rich in bone marrow stem cells) that gives that yummy flavor in dishes, my fond being the French “Pot-Au-Feu” (the yummiest soup during the holiday season). The cooking process will tenderize the meat but very unlikely to dissolve bones and tendrils.
To dissolve bones and tendrils, you need something……very acidic. Only an extreme acidic and hot environment will dissolve bones and tendrils.
Therefore her first claim is not fully backed by science. Now let’s assume you have some connective tissue that solubilize, you will have mostly collagen dissolved. Collagen is the main protein involved in most connective tissues. The author claims that such processing releases tons of glutamic acid (that is also glutamate) as described here “The result of such long cook times is a tremendous amount of glutamic acid. And that’s the dark side of Bone Broth
.Collagen is a polymer made of a same repeat motif Glycine-X-Y, with X and Y being often proline and hydroxyproline (the hydroxylation of proline into hydroxyproline is made by prolylhydroxylase, using vitamin C as a co-enzyme. This is why scurvy (lack of vitamin C) is characterized by defect in connective tissues).
It comes with different flavors depending on the function (collagen type I  being the predominant form in connective tissue; collagen II found in tendrils; Collagen III in cartilages and bones; Collagen IV in basement membranes……). This second fact discredits her claim that collagen will increase the amount of glutamate.

2. What is the blood-brain barrier (BBB) and how glutamate is processed?
After giving her culinary explanation, the author jumps into explaining glutamate into her own terms: “As you may or may not know, glutamic acid and glutamate are highly regulated by the human brain“. You can already note the red herring about the author as she treats glutamic acid and glutamate as two distinct chemical entities.  This is an obvious lack of understading of biochemistry  as glutamate is the the ionized (salt) form of glutamic acid. This is a typical misconception that I see with folks peddling on woo (folate/folic acid anyone?). It also raises concern about the credentials of someone making dubious health claims. Garbage in, garbage out.
Not only the author makes blatant mistakes but also makes fallacious associations as mentioned here If you have a leaky brain, as those with a leaky gut often do, high amounts of glutamic acid can trigger seizures if you’re prone to them. Yes, seizures. It can also trigger other neurological symptoms you may already be sensitive to, including brain fog, migraine headaches, dramatic mood swings, stimming, and nervous tics, to name a few.
I have been discussing over and over about the BBB in my blog, so I will not repeat over and over again. I will keep it simple. The BBB is what we call a component of the neurovascular unit (a combination of the cardiovascular and nervous system) that is designed to protect the brain from any interferences from the periphery. Therefore the environment in which the brain bathes in is strictly controlled, with a defined composition. The BBB provides two kind of barrier: a physical and a chemical barrier supported by the brain microvascular endothelial cells (BMECs) lining the inner side of blood vessels. They provide a tight blood-brain interface that strictly regulates what comes in and out the brain. The physical barrier is harbored by the presence of tight junction complexes, whereas the chemical barrier acts as a selective filter that pick and choose which molecules goes into the brain through an array of transporters, represented by the super-family of solute carriers (SLCs). Each solute carriers are adapted to let the entrance of specific molecules (for instance SLC2A1 lets glucose enters the brain, SLC16A1 lets T3 thyroid hormone enters the brain….).
In many aspects, BMECs share a lot of features than intestinal cells. But a leaky gut and a leaky BBB cannot explain her claims.  In order to understand how her claim is bogus, I will argument using a recent review by Hawkins RA and Vina JR (the first author has a publication records in regards of glutamate transport accross the BBB). If glutamate
However, glutamate is firstly poorly transported inside the brain because it remains trapped inside the BBB . Thats already hit her claim.
If we follow her logic, we are facing a massive increase in glutamate level in the food uptake (due to the broth). Because you have a leaky gut (a concept I have been already explained in my previous blog as still debated and mostly inaccurate in terms of diseases), you have your body flooded with glutamate and ultimatelly flooding your brain with glutamate. This makes sense only if you have a deficit. Chemicals flows into two compartment following the Ficks law, it diffuse from the most concentrated to the least concentrated compartment. Because it is considered as a non-essential amino acid (your body knows how to build it up from other molecules), the brain is not in need for glutamate and can produce its own. Glutamate plasma concentrations range from 50-100microM, brain concentrations ranges from 10’000-12’000 microM. We are talking about 200 times more in the brain than in the plasma. Therefore, you need to achieve a concentration higher in the brain to expect to see any changes. Thats simply impossible and destroy the rest of her argument!

3. But, but…….I have a leaky brain! (No you have not).
The idea of a leaky brain is simply the most ridiculous claim. If your brain was indeed leaky, you would not be here reading this post. You will be six feet under, dead from a massive brain edema.
Leaky brain happens when you have a disruption of the BBB, in particulat from the tight junctions lining BMECs. This results into an onset of “vasogenic cerebral edema” and in an unrestricted entrance of water and ions inside the brain.
This happens if you are experiencing high-altitude mountain sickness (in particular high-altitude cerebral edema), stroke or brain trauma (traumatic brain injury). Because the brain is contained inside a rigid structure (skull), it cannot expand and swell as you would experience if you experience and injury in the periphery. This results in an increase of an intracranial pressure (ICP) and brain injury by mechanical stress (imaging squishing a sponge in your hand) that leads to neuronal cell death. Untreated, brain edema is fatal. However, there are cases of cerebral microbleeds that do not induce cerebral edema formation. This could be something that can be considered as “leaky brain” but their intensity and extend is a far cry of the former word meaning. 
Thus, the concept of leaky brain is completely fallacious as it is taken out of context and grossly exagerrated.