[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:

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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=10.1.1.927.8806&rep=rep1&type=pdf)

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).
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[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. 

[Pharmacology/Junk Sciences] About the FDA recall on Dr. Hyland’s homeopathic tooth relief….

You may have heard about the recent FDA recall for Dr. Hyland’s homeopathic teeth relief and any products similar to it as listed in their report below (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm523468.htm).

There are 10 children deaths and 400 adverse events reported with the association of this homeopathic product. Homeopathy has always lauded itself as “natural, effective and harmless”. Even when it was faced with the lack of efficacy, proponents of homeopathy always use the “what’s the harm?” as a defense. Seems that not only it will not treat your ailment. Worse it can kill you. Why? Simple pharmacology.

A tenet of pharmacology is known since Paracelsus with his famous citation “Every substance is poison. No substance is no poison. The dose and only the dose makes a substance a poison”. Even the natural products are poison. You see, Mother Nature in all its grandeur has developed a certain affinity for developing some of the most toxic substances designed to kill living species. Because of evolutionary constraints, plants have been very good as being “chemical plants” and use chemical warfare as a method of invasion and defense.

Now, you can use this poison effect to treat certain conditions. If you find the right dose, you may treat a condition. This is how pharmacology works. Under a certain dose, there is no effect. We only start to see some biological activity after a certain dose. This is what we call the Minimum Efficacy Concentration (MEC). On the other hand, if you reach concentrations high enough, then you start to hit on off-targets and develop the minimum toxic concentration (MTC). This is where we start to see side effects and if the doses are high enough you will see adverse and toxic effects.

Homeopathy is by definition an unproven therapy because its principles defy common laws of physics and chemistry. Because it is relying on extreme dilutions to explain its activity, the amount of active substance is so low that it can be compared to dilute one single molecule into a swimming pool.

In this case, we don’t exactly know what compounds and what amount of each alkaloids are extracted. We know the total amount is 0.0000000000003% or 0.3 pico-grams per 100mL of solution or 100g tablets.

belladonna

That amount is simply ridiculously low. First, we have to assume that its PO administration will result in a 100% bioavailability (that is probably false and surely below). Second, you should be able to detect the compound in plasma samples. At that level (pg), the odds of detection are very low if not non-different from background. Therefore the odds of having this single molecule finds its target inside a body is almost zero (and the probability is something like 0.0000000000000000000000000000001%).

Yet, homeopathic treatment are all starting from raw extract (usually an hydro-alcoholic solution as extracting solvent) called “tintura matter”. Thats a concentrate and it contains indeed active substances in a high concentration. The nature and quantity of active substance in it are not known and not even reported since homeopathic products are not falling under the FDA supervision (you can thanks the DHSEA provision for that). Basically, no one (even the manufacturer) will tell exactly what and how much of active compounds are inside this tintura matter.

This raises a problem because Mother Nature has been excelling in producing poisons, what only matter is the dose. In the case of the teething relief product, the main culprit appears Atropa belladonna, a common poisonous plant that get easily confused with edible berries.  One of the classical substances purified from Atropa is atropine, an acetylcholine muscarinic receptor blocker. Because Atropa belladonna is known for its poisonous activity, we had some disaster in waiting that was cooking here. Anyone working with drugs will tell you how dangerous it is to overdose on an active substance.

Acetylcholine is an important neurotransmitter in mammalian cells, with peripheral (heart, muscles, lungs….) and central actions. Acetylcholine is a key target of organophosphates and sarin gas, as these agents block its degradation by acetylcholine esterases (this is why you have atropine administered as a side treatment for poisoning).

However, atropine can and will have severe side effects if ingested in a poisoning event (see this case report of accidental ingestion of Belladona: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361210/)

So whats exactly happened in this situation? We dont know and only now the FDA can provide clues. The FDA is toothless and cannot execute any order unless there are fatality cases involved. On their page, they are aware of the anticholinergic side effects of it but minimized the risk (that logically make sense since the amount is ridiculously low)

belladonna2

At this point, I speculate that something wrong likely happened with these homeopathic products. My speculation is something went wrong with the preparations, resulting in inconsistant extraction and effective concentrations in tintura matter. Because homeopathy are not ruled by FDA, they do not have to follow the stringent quality control and good manufacturing practices (GMP) imposed on pharmaceutical companies. So we have here a production that was on a free ride without any oversight on the QC. Now you can easily imagine that we may have ended up on with overdosed preparations.

Considering the special population (pediatrics), this risk of overdosing was even more amplified. One thing we consider when we develop a drug and prescribe a drug is the benefits/risk ratio. If the risk or adverse effects are too high, the drug cannot be used because it overcomes the benefits.

In that case, not only the benefits were quasi-null, we provided access to a product that was deemed “safe because natural” but indeed has a risk of adverse effect. Now we have likely some precedent in directly demonstrating the danger of poisoning with homeopathic products. This is already the case with essential oils (there are cases of children poisonings with Eos) and now we have the same with homeopathic products.

[Junk Sciences] Thanks, Michael Phelps, for glamorizing cupping quackery!

Olympic games are a great time to see the accomplishment of athletes, years of hard work and sacrifice to achieve their best athletic performance. Yet, not everything is all shiny and pristine with Olympic games. Between corruption scandals, doping, abuse from coaches over their proteges, misogyny to female athletes, I guess we can add pseudosciences and quackery as the plight on our athletes.
Proof? The recent cupping fad that have been glamorized by some athletes including Michael Phelps.
Oral from Respectful insolence has been, as usual, debunking that quackery that will give you as much superpowers as a chicken soup!

Source: Thanks, Michael Phelps, for glamorizing cupping quackery!