[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. 

[Junk Sciences] The Fair Trade Commission clamps on OTC homeopathic products

Winter is coming, thanksgiving is one week away and of course comes the classical cold/fever/pain reliever triad. If you use to shop on OTC products, you often cross on homeopathic products. Not only these products are basically useless, but these products use packaging tactics making you believe that they are as efficient as conventional OTC.
Of course, you realize that you picked the wrong bottle as your condition does not improve even after swallowing the whole bottle. Because they are not designed as drugs, homeopathy gets a free-ride by escaping the FDA regulations unless serious and fatal effects are reported following their use (see the teething gel story that I posted few weeks ago).
Because homeopathic products efficacy have not been backed by science, they avoided to put themselves in hot water by providing a statement like this one: “the case for efficacy is based solely on traditional homeopathic theories and there are no valid studies using current scientific methods showing the product’s efficacy“.
In other words, it works only if you believe in it enough. It has the same validity to say that unicorns exist only if you believe in them. There are no scientific proof that unicorns exist but if you believe enough in it, you can see unicorns.
The Fair Trade Commission decided such statement as deceptive and ordered any OTC homeopathic produces to harbor the following statement:
1) there is no scientific evidence that the product works; and 2) the product’s claims are based only on theories of homeopathy from the 1700s that are not accepted by most modern medical experts.”.
Although such statement will not stop the sell of homeopathic products, it sets the fact straight. There is no scientific evidence that it will work, such treatment is simply outdated and not recognized as medicine.

Source: FTC Issues Enforcement Policy Statement Regarding Marketing Claims for Over-the-Counter Homeopathic Drugs | Federal Trade Commission

[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!

[Junk Sciences] About that scientific paper retracted from Scientific Reports yesterday and the limits of peer-review

A tenet of becoming a scientist and earning a doctoral degree (Ph.D) in hard sciences is to be able to develop a critical thinking and skepticism over scientific findings. We learn how to not accept scientific claims as facts “just because someone said it” and learn to fact-check such claims by analyzing the data and see if the data are robust enough to support the claims or if they are simply inaccurate, non-conclusive or worse…..simply fabricated.
Data fabrication, adulteration, plagiarism and manipulation is unfortunately present in science. This is why peer-review is playing an important role in filtering out studies that are robust enough from studies that are murky or questionable enough. That latter is usually what I refer as “junk science”, scientific studies that are not standing to scientific rigor and should not have been reaching the publication stage. The peer-review process is not the most optimal one. If you want an analogy, consider peer-review as the wooden fence lining your backyard: it will not stop a burglar to climb over it but it will stop trespassers and marauders to come too close from your home.
Yesterday, I woke up straight in a middle of a Twitter firestorm about the retraction of a paper. Seeing papers retracted is not uncommon, there is even a website for that called “Retraction Watch” that track studies retracted by scientific journals. But yesterday it was such a bad paper that yesterday’s Dr. Derek Lowe that hold a PhD in Chemistry from Duke University had a fiery blog post about it (the access was denied soon after I read it but seems to be online again this morning) named “Crap, courtesy of a major scientific publisher“.
The problem was not facing a junk scientific paper, there are plenty around nowadays since Open-Access journals started to kick inside the world of scientific publishing and thanks to predatory publishers (I will talk about it later). The problem was the journal that has such junk paper published: Scientific Reports (SciRep, from Nature Publishing Group) (Disclosure: I have co-authored a paper published in Scientific Reports). Scientific Reports is the response of NPG to open-access (OA) journals such as Public Library of Sciences (PLoS). Because it is coming from NPG, everyone is expecting to attain a certain rigor for peer-review (Nature is one of the hardest journal to get your scientific study published). I always joke around that it is so demanding that we are facing “icebergs” papers, studies with five main figures and 50 supplemental figures that are only accessed online.
Using this debacle, I thought it would serve well as a poster child to expose some scientific fraud and provide some tips to distinguish good papers from bad papers.

1. Scientific Publishing 101: Peer-review, open-access, predatory journals and publication fees.

Publications in peer-reviewed journals is the bread and butter of academic researchers. It is as vital for a researcher as a credit report is for anyone living in the US. Two criteria matters in big time decisions such as finding a job or earning tenure in an University: how many papers you have your name affiliated to and which journals. These metrics are very important, especially with the latter driven by the impact factor (IF). The IF is the equivalent of a BBB rating: the higher, the better. Two giants dominates the field: Nature (from NPG, IF ~42) and Sciences (From the American Association of Advancement of Sciences or AAAS, IF~32).
It is so important that the number of papers coming from these two journals conditions the odd of a researcher to get a job in prestigious institutions such as Harvard, MIT, Stanford or UC Berkeley.
Papers are part of a particular cycle that I don’t know if we should call it vicious or virtuous.
1. To publish papers you need data.
2. To obtain data you need research funds.
3. To obtain funds, you need to write winning grants.
4. To have a grant having a chance to get funded you need papers
5. Repeat step 1.
All peer-reviewed journals follow the same procedure: I submit my draft manuscript that I consider solid enough for peer-review to a journal. The editor-in-chief (usually a well seasoned scientist) decides using both an objective and subjective point-of-view what to do with it: the objective one is if the paper fits into the editorial policy (for instance publishing my work on BBB into a plant biology journal is fairly no-sense) and the subjective one is if the paper is “attractive” enough for the editor-in-chief or not. If not, it will toss it fast. If it is, it will proceed and pick 2 reviewers that have more-or-less the adequate expertise. Such reviewers are kept anonymous for most journals with very few exceptions. Reviewers have a moral obligation to keep their review objective and fair. Sometimes they do, sometimes they don’t. You can easily imagine that if reviewer X is a scientist working on the same topic than me, that reviewer feels the risk of being scooped and therefore will work hard to find flaws to get my paper rejected and work hard to scoop me.
At the end, 2 or 3 reviewers will provide their comments and feedback giving the editor-in-chief the decision to accept or reject your paper. Once rejected, you have no other choice to move on to another journal and restart the same game.
The competition is fierce, with only less than 1% of papers submitted to the top 2 journals will end up being published. This also raised a race-arms to publish only papers that are groundbreaking science in big way and usually can shake up an entire field and a fierce competition for getting published. This is what I call the “wow factor”. But thats only a small problem that raised to OA journals and sometimes it can backfire due to scientific misconducts (examples: Two stem cells papers retracted because of data fabrications such as the Hwang paper about the cloning of hESCs from human oocytes published in Science in 2005 and the STAP “pickled stem cells” published in Nature in 2014)
The main problem is that once accepted, this study will suffer from a double-jeopardy in terms of publication fees: the authors have to pay publication fees to get the accepted paper published (usually goes from ~$1000-3000 per study). Once published,  you secede the copyrights to the publisher, this publisher will ask anyone wanting to read the paper to pay for its accession (~$50 per study). This second fee hinders how many scientists can read your study, limit access of scientists from developing countries to these studies and also limit the number of studies that will cite your study. Certain public health agencies like the National Institute of Health (NIH) responded to such issue by asking any studies funded with $$$ from NIH grant to be available free 12 months after publication through their “Pubmed Central” portal.

OA journals were born from these concerns. The OA publication follows the same protocol than regular published journals except for two aspect: they will accept any papers based on the robustness of the data rather than the novelty or “wow factor”. If your paper is not as exciting and breaking ground as higher journals but it solid and can provide the field with small but solid information, it will get accepted.
once published such studies are made open-access. Anyone can read them freely. This is because once accepted, the journal recover the costs by asking higher publication fees (~$2500-$3500) from the author of the study.
This is an interesting alternative publication method, however it also opened a new wild wild West in academic publishing. Like any good Western movies, you have wandering snake oil sellers and in academic publishing these snake oil sellers are represented by predatory journals and publishers. These publishers found some easy preys to feed on: academic scientists with studies that are so poorly designed or just simply fraud and could not pass the peer-review filters. As long as you give them money in form of publishing fees, they will publish your paper through an expedited review. This lead in recent years in the appearance of “junk papers” that are little or no scientific merit and yet get the right to get cited. This lead to a hall of shame through the Beall’s list of predatory publishers providing a database of journals and publishers with suspicious or demonstrated predatory practices. There is even one publisher found with a mailing address pointing….to a suburban house. How serious this can be? This is what feed most of the pseudoscience outside. Anti-GMO, anti-vaccines, chiropractic, naturopaths and homeopaths are all relying heavily on such “junk science” to provide a scientific rationale to their claims.

2. What was about this paper that made such firestorm and retraction by Scientific Reports?
The paper in question is titled “Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties” by Samie and colleagues from the University of Malaya, Kuala Lumpur, Malaysia and published in SciRep last April. As today, the paper was not available through SciRep yesterday and seems back online today. I guess the academic firestorm put the server into severe stress.
I will go step by step and explained in comments what is wrong with this paper (see figures below).

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3. Conclusions

After reviewing the paper, you can notice how many flaws and blatant data manipulation was mined inside this paper. Peer-review cannot be a fool-proof system, as some very elaborated data fabrication may go unnoticed even by the most seasoned reviewer. I am not surprised either to see such junk study to made it through publication, if it was coming from a predatory journal. But seeing such paper coming from Scientific Reports being unnoticed although a fairly reasonable turnover (it was received in October 1 2015, accepted March 23 2016 suggesting at least one round of review and the submission of a revised form) is disturbing. Scientific Reports editorial has to consider what went wrong and investigate the review history of this paper but also whether reviewers assigned to review this study displayed the expertise needed and the objectivity to do it.
At that time, I would not be reviewer 1 or 2 (even 3) that reviewed this junk paper. Garbage in, garbage out.