Following yesterday’s post let’s turn our attention to the Daily Wire article featured in TheQuartering’s video, which by extension will also include the New York Post article. However, unlike TheQuartering and media outlets we will engage in fact checking through, well, actual fact checking by examining the literature and seeing what we can find. Yes, a shocking revelation for science to look through...the science. I’ll first present all of the arguments made within both the New York Post and the Daily Wire article and then address them properly.
One thing I find quite shocking is how often the media will quote other media sources. It’s as if one journalist decides to cover a topic and instead of other journalists doing their own research in order to cover the topic they decide instead to cover the journalist’s coverage. Talk about taking the easy way out.
Ah, there goes that whole “horse dewormer” approach journalists love now being applied to Methylene Blue. We’re first presented with the idea that Methylene Blue, the compound in question which is not even labeled in the header, as a fish tank cleaner. Again, we should all know better than to immediately jump to conclusions and freak out over the phrase “fish take cleaner”. It’s a shame how quickly people fall for such clickbait titles.
Here’s some more from the New York Post article:
Doctors are slamming fitness influencers hawking the health benefits of methylene blue — an anti-fungal dye often used to clean fish tanks.
The substance — which can be injected or consumed orally — is prescribed by physicians to treat methemoglobinemia, a medical condition in which blood cannot deliver oxygen to different parts of the body.
However, while it is not harmful for most humans to consume methylene blue in therapeutic doses, some experts are trashing claims from influencers that the dye helps enhance cognitive abilities, boost metabolism and fight aging.
“I have just discovered the trend of fitness influencers sticking methylene blue on their tongue as a ‘metabolic or cognitive enhancer,’ and I can’t stop laughing,” Australian Dr. Darren Saunders wrote on Twitter.
“OMG, of course it also ‘slows down your chain of aging’ — whatever the hell that is,” he further sniped.
So we see that mention Methylene Blue being used to clean fish tanks. Do we care that it cleans fish tanks? No, keep in mind that refers only to the application of MB. The important question here is why it is being used, which is even mentioned by the journalist because it works as an anti-fungal (among other reasons). Now, if I say it is an anti-fungal agent instead of a fish tank cleaner that doesn’t sound as bad, does it? If the mention of the phrase “fish tank cleaner” damages your perception know that you are intentionally being misguided.
It makes it even more strange that the journalist then mentions that it actually serves some therapeutic benefit. Again, you wouldn’t have known that from the header would you?
We’ll address more of the claims being misrepresented further on (including the fish tank cleaner remark in a bit more detail), but if you read further on you’ll notice that the New York Post didn’t even quote Dr. Darren Saunders properly Dr. Saunders never stated the person he knew consumed the Methylene Blue, he mentioned that they dropped and broke a bottle of the stuff. BIG DIFFERENCE. A news outlet purported to be engaging in fact checking couldn’t bother scrolling through a few tweets.
Like always, I suggest people read both the Daily Wire and the New York Post article, but the last thing I will comment on will be a Tik Tok video posted on the Daily Wire article from a Dr. Jon, in which he chastises a Tik Tok user for spreading so-called “dangerous” information (transcribed by Daily Wire):
Remember that appeals to authority should not sway your perception of a drug. It is the mechanism of action or its adverse reactions here that should be taken into consideration. I don’t think people should be taking the advice of Tik Tok influencers, but I also don’t think appeals to authority of any nature matters in this regard as well. We’ll take a quick look at the paper and the claims made here, but what’s strange is that this Tik Tok video came from May of 2021. It’s hard to argue that a nearly year old video in a two year old pandemic would hold up with all of the information and studies that are being accumulated.
Providing Context and Clarity
So here are the key points made in both of these articles that we will address:
MB is a fish tank cleaner
Enhances Cognitive Abilities
Fights aging; “slows down your chain of aging”
Is dangerous for those with G6PD deficiency
As a note, I have decided to cover the COVID aspect last because of its relevance.
Fact Check: Is MB used to clean fish tanks?
In short, the answer is yes. But again, do we care about a compound’s application, or do we care about what it does (i.e. its mechanism of action)? MB has many antimicrobial properties, likely stemming from its ability to cause oxidative damage to microbes. Because it’s ionic it is also water soluble unlike other dyes and flavanoids. Being a water soluble antimicrobial & antifungal makes it a very appealing agent to use in cleaning fish tanks, especially when the safety of the marine life need to be taken into consideration (Sipos, A.J. & Urakawa, H.):
Chemicals such as methylene blue used to treat fish diseases may weaken or kill nitrifying micro-organisms resulting in increased ammonia levels in tanks (Tieman and Goodwin 2001). Compared to other chemicals, methylene blue is low in toxicity to fish and low in cost (Tieman and Goodwin 2001). While not approved for use in food fish, methylene blue is traditionally and frequently used by hobbyists and in the ornamental aquaculture industry as a disinfectant, anti-fungal, and anti-parasitic chemical (Levine and Meade 1976; Picón-Camacho et al. 2012). Methylene blue is safe for use with fish eggs and fry for the prevention of fungal and bacterial infections such as fish fin rot (Gratzek 1981). Methylene blue is also used to treat ammonia and nitrite poisoning of fish by increasing the oxygen-carrying capacity of the fish's haemoglobin (Wedemeyer and Yasutake 1978).
In this study by Sipos, A.J. & Urakawa, H. researchers found that use of methylene blue in aquariums and aquaculture could kill various nitrifying micro-organisms, and thus could be useful in commercial fishing procedures adding to the idea that MB can serve as a beneficial antimicrobial. So once again, MB is used to clean fish tanks, but it’s because it serves as an antifungal and antimicrobial, as well as a relatively safe ionic molecule that it is used to clean fish tanks. It is these properties that have led researchers to look at MB for treatment in humans as well.
Remember to not fall for such semantic trickery. “Fish tank cleaner” is using the exact same semantic argument as “horse dewormer” and we know better than to fall for the latter, therefore be very careful of the former.
Fact Check: MB Enhances Cognitive Abilities
Drugs and supplements that supposedly enhance cognitive function are called nootropics. Nootropics such as certain mushrooms on the market may increase cognition through upregulation and stimulation of the brain. However, some may provide neuroprotective benefits through reductions in ROS and oxidative damage within the brain.
MB has a high affinity for mitochondria. In biology you may have heard the phrase that “the mitochondria is the powerhouse of the cell”. It’s apparently the only thing anyone ever remembers from their high school biology. Mitochondria are organelles that produce many of the energy-captured molecules that our cells use. In particular, mitochondria use their electron transport chain (ETC) to produce the molecule ATP by moving electrons through various complexes of the ETC. However, this movement of electrons may cause the production of ROS in “leaky” mitochondria. MB’s affinity for mitochondria and its antioxidant properties may inhibit the production of ROS by mitochondria and thus provide some protection.
What I haven’t mentioned before is that inflammation is extensively tied to the production of ROS. Many of our cells’ processes utilize ROS to break down pathogens, aid in cellular apoptosis, and help with stimulating an immune response. Therefore, antioxidation agents that inhibit the production of ROS actually serve as anti-inflammatories as well.
Because mitochondria can produce ROS, and because ROS and mitochondrial dysfunction have been implicated in many instances of neuroinflammation and brain injuries, we can assume that MB may alleviate some of the damage to the nervous system and the brain (Tucker et. al., Yang et. al.).
The important thing to note here is that most applications of MB for neuroinflammation have examined it through the lens of acute brain injury, and usually using rat models (Ahmed et. al.). The literature is quite sparse in regards to actual use in humans, which may actually require direct application to the areas of concern. Doing so to the brain would prove quite challenging and may be harmful. There’s also no clinical studies on long-term use of MB that I was able to find, which means that its effects on dementia are more hypothetical than reality. Considering that long-term use of MB may end up causing more harm through its oxidation processes, reasonable concerns would suggest that prolonged use of MB should be heavily disregarded.
Overall, the evidence is not quite there to indicate that MB may improve cognitive function. Its neuroprotective benefits may only work in acute brain injuries as prolonged use may end up causing unintended oxidative damage. It’s also difficult to tie neuroprotective processes directly to MB, especially for diseases such as dementia. There are plenty of other compounds and supplements on the market who purport to aid in cognition. That doesn’t mean people should take them, but there may be other supplements with a higher record of providing actual nootropic effects that may be worth considering over MB.
Since we are on this topic and cognition is tied to metabolic health we can kill two birds with one stone. When it comes to increased metabolism and MB the evidence isn’t quite there as well. I am unsure where the idea came from, but a less than generous interpretation is that many of these influencers saw the benefits for mitochondrial dysfunction, thought about the “powerhouse of the cell” concept, and thus ascribed MB with the possibility of improving metabolism. Just like with the idea of improving cognition the evidence doesn’t quite stand up to indicate that aiding in mitochondrial dysfunction may improve metabolism.
We also have to take into consideration that many diseases such as obesity and diabetes lead to metabolic dysfunction as well. If the attempt is to improve metabolic health it would be far more beneficial to target the root causes such as obesity rather than to take something with no direct evidence of helping. Considering that many of these influencers are also health and fitness gurus I would argue that the more active lifestyle is aiding in metabolic health more than the actual supplementation.
Both phrases of “improved cognition” and “increased metabolism” are quite ambiguous and don’t tell us much of what MB is actually intended to do. In many instances it is likely that the research may be misinterpreted by those not quite knowledgeable of the literature. It’s a big problem when people without a foundation for examining papers report on the results of said papers. It’s better to examine such research and evidence for yourself and see if the evidence supports the claims being made, and as it stands I would argue that the evidence is not there for now to substantiate these claims.
After writing up this portion I dug a little deeper and looked more into the cognitive aspect of MB. It appears that one hypothesis is that MB may bind to dopamine receptors and thus provide some antipsychotic benefits. MB shares a similar molecular backbone to Promethazine which was first developed to be used as an antipsychotic. However, Promethazine is now used for allergies and may be found paired with Codeine in prescription cough syrups. It appears that MB may also be used as a precursor for the development of various tricyclic antidepressants. Although this provides some merit to the cognitive benefits of MB including those with schizophrenia, I would argue that there still is not enough sufficient evidence. This would also explain why antidepressants are considered a contraindicator for MB. Instead of deleting this section I am keeping it for posterity sake but keep this information in mind as well.
Fact Check: Does MB fight aging and “slows down the chain of aging”?
Aging is quite the interesting topic. The search for “eternal youth” is heavily dominated in movies and television shows. But what exactly does it mean to fight against aging?
In molecular biology aging usually refers to a term called senescence and is applied to cellular senescence more specifically. All cells have a built-in, finite number of replicating capabilities. As we age many of our cells begin to reach the end of their ability to undergo mitosis, divide, and provide new replacements cells. This limited replication capacity of cells is referred to as the Hayflick limit.
One of the major dictators of a cell’s ability to divide depends upon telomeres. Telomeres are repeated segments of nucleotides found at the end of our chromosomes. During mitosis chromosomes need to be replicated. However, the replication process truncates the telomere length a bit after each cycle. Repeated replication leads to repeated shortening of the telomeres, and eventually when the telomeres are completely depleted the cell is no longer capable of dividing without cutting off necessary nucleotides, which would cause deleterious effects to the cells.
Aging is attributed to many factors, but the shortening of telomeres has been considered one of the main targets of anti-aging, although poor cellular health and function are prime contributors to senescence as well. By extension, it should come as no surprise that oxidative damage is being examined for its contribution to telomere shortening.
In the search for preventing aging some researchers are looking into the role of enzymes called telomerases, which actually lengthen telomeres and may prolong the replication capabilities of cells. Other forms of research are looking at the roles that poor diet and overall health have on acceleration the shortening of telomeres as well as cellular dysfunction.
To provide a steelman approach to these Tik Tok influencers, the “chain of aging” may refer to telomeres, or it may refer to the process of aging as a whole, but that’s probably being more charitable to influencers than I should be.
Surprisingly, some research has indicated that MB may help prevent the senescence of cells. In one study by Atamna et. al. 2015 researchers treated IMR90 cells with MB and measured oxidants and telomere lengths of the cells. Their results suggest that MB helped reduce oxidative damage and reduced the erosion of telomeres, although I would use some caution in interpreting these results as the results of their gels are very difficult to discern. However, these results build upon a prior study from the same researchers which indicated that MB reduced oxidative stress and helped to reduce senescence in IMR90 cells (Atamna et. al. 2007).
A caveat to this study is that the cells used (IMR90) are fibroblasts. Fibroblasts are cells that release collagen into the extracellular matrix, and thus are found on the skin and other connective tissue regions of the body. This means that the actual effects of MB on senescence are not well known for other cells. Also, these in vitro assays don’t translate well into the clinical setting. The bio-distribution of MB should be questioned when considering what organs or tissues it should target. Even if the intent is to reduce skin aging, MB may not be readily distributed to the skin to provide protection. Also, topical MB, aside from turning someone blue, may form ROS through overextended light exposure which may cause more harm than any benefit.
For now, many researchers are hypothesizing looking into very dilute MB for possible anti-aging properties, but there’s not enough evidence to suggest it be used for such a thing as of now. As it stands, the search for an anti-aging elixir is still ongoing, and may continue until the end of time. People should not put their hopes into one molecule, especially when there is not enough evidence to support MB’s use for reducing aging. Instead, it may be more appropriate to examine the aging process through a wide lens that takes into account diet, exercise, and exposure to stressors that accelerate aging.
Fact Check: Is MB dangerous for those with G6PD Deficiency?
Every substance has a lethal dosage, and many may have a therapeutic dosage. Modern medicine takes this into account with an understanding that a cure cannot be worse than the disease. Sometimes there are groups of people that may be more susceptible to the toxic effects of a drug relative to many others. This term is called contraindication, and it refers to confounding variables that make it inadvisable for a physician to prescribe a medication to a patient because it may cause unintended side effects. Typical contraindications are usually drugs that alter the effects of other drugs, or genetic differences that change how someone metabolizes a drug or its metabolites.
Glucose-6 phosphate (G6P) is a precursor molecule that gets oxidized and used to reduce cellular cofactors for use in other cellular processes including NAD+. This process is catalyzed by the enzyme G6P dehydrogenase. In those with G6PD deficiency these individuals are unable to metabolize G6P to get the necessary reducing agent. Fortunately, those with G6P are usually unaffected by the lack of this enzyme until excessive oxidation occurs.
G6PD is a contraindicator for MB because the lack of G6PD makes it difficult to reduce MB into Leucomethylene Blue (LB; refer to the 1st image from yesterday’s post). The buildup of MB causes oxidative damage and leads to hemolysis (blood cell death) which may become harmful especially under continued, chronic exposure.
So in a sense MB can be dangerous for those with G6PD deficiency. The important thing to note here is that MB is not the only dangerous compound. As taken from this list, both acetaminophen and Vitamin K may also cause problems in those with G6PD deficiency. In fact, doctors are more likely to warn patients with G6PD deficiency of taking too much Vitamin K over something like MB.
So there are valid concerns with MB and those with G6PD deficiency. However, those with G6PD deficiency may already be aware of contraindications. Being informed and talking with healthcare professionals should always be done before trying something new. Although many people with G6PD deficiency may not know they have this deficiency people should always be aware of their bodies and notice if any changes may occur. Staying vigilant and active in understanding what you put in your body will help prevent serious issues from happening in the first place, and when you are unsure whether something may be beneficial it may be better to err on the side of caution and just decide not to take it.
All drugs have a lethal dose, and for some the lethal dose may lower than we expect. Always keep this concept in mind when examining pharmaceuticals and supplements.
Fact Check: MB is effective against COVID
We’ll end this fact checking with probably the most pertinent question for our times. There’s no other area where researchers are heavily invested into finding treatments than there is for COVID. Just like all other drugs we have examined beforehand, tons of other drugs have been examined to see whether they can be repurposed against SARS-COV2. Although not all searchers prove fruitful, the intent to search is what matters.
The intent to search for a viable treatment has been considerably dampened by those who act as if nothing of merit is actually out there to help fight COVID.
That brings us to Dr. Jon’s castigation of the Tik Tok influencer. I always find it strange with how much those within the medical community have embraced social media. No matter how important it us to dispel myths and provide information the limitations of social media don’t support the proper arena for open discourse in many instances. Instead, it can sometimes feel as if the only proper way to engage on social media platforms is to embrace the way that others use it. This usually results in truncated ad hominem tweets or messages that provide no merit. There’s a certain epidemiologist/nutritionist that I was shocked to find out extensively used emojis like a teenage girl (no offense to those teenage girls).
All this to say that Dr. Jon’s comment isn’t anything different than what one would find with immediate online searchers. We should be fully aware by now that nonclinical studies may not be reflective of...clinical studies. We also know that certain drugs should not be used by certain people. The issue here is that many people who are G6PD deficient may not know it, but just like anything else out there we should first start with a good faith intention that these people will do research and not listen to the words of anyone on social media.
But that’s more of my old curmudgeon self showing itself. The main issue here is what the literature states in regards to MB and COVID.
Just like with many of the drugs that have been repurposed, we tend to rely on observational studies to look for any signal that stands out more than it should.
In March of 2020 doctors in France reported about a cohort of over 2500 cancer patients being provided cancer treatment who also did not succumb to influenza-like illnesses during the time of treatment (Henry et. al.). The hypothesis proposed by these doctors was that the treatment with Methylene Blue may have provided these cancer patients with an antiviral prophylactic, suggesting that MB should be looked at for treatment against SARS-COV2.
A big caveat to this report is the timing. March of 2020 is right at the beginning of the pandemic when very few people were beginning to be infected. The researchers even suggest that this may be due to just lack of exposure at the time. There was also no indication as to what types of cancers were being treated and these patients were also provided α-lipoic acid and hydroxycitrate along with MB and standard chemotherapy. In fact, not much else is presented in this report as the rest of the report examines why MB may be beneficial through a mechanistic perspective. For those interested I would suggest you read the paper. But just like with all observations this spurs on the need to investigate further into MB.
A very simple in vitro assay by Gendrot et. al. looked at the effects of pretreating Vero E6 cells with both MB and chloroquine analogues and examined their effective concentrations. The results here suggest that MB was more effective against SARS-COV2 infection than other antivirals in use. Paired with a relatively low cytotoxicity profile this would suggest that MB may be something to look into further as a possible treatment option.
The study looked at by the Tik Tok influencer and criticized by Dr. Jon is this study by Bojadzic et. al. In which researchers looked at the ability of various dyes to hinder the protein-protein interaction (PPI) between the SARS-COV2 virus’ spike protein and ACEII receptors. The results here suggest that MB hindered this PPI. However, the researchers also indicated that MB can engage in interactions with several other proteins making it a promiscuous molecule. This would mean that MB may target other proteins as well which may be detrimental to the functions of a cell. We also have to keep in mind that the targeting of the spike protein should be met with hesitancy as the spike protein undergoes many mutations. Just like antibodies that target the spike other molecules that may bind to the spike protein itself may easily be affected by mutations and thus lose binding affinity. This may not be the only mechanism of action for MB, but I wouldn’t hedge my bets with depending solely on MB’s PPI between the spike and ACEII receptor.
As of now there’s a few clinical trials being evaluated for MB and COVID. In one RCT, open-labelled Phase II study patients were provided an MB syrup and their oxygen levels and hospital stay time were evaluated (Hamidi-Alamdari et. al.). Treatment groups who received the MB syrup showed increased oxygen saturation, reduced hospital stay, and reduced mortality relative to the group who received standard of care only. Like with all clinical trials in COVID the sample size here was very small (40 in each group). The syrup provided to the treatment group also contained Vitamin C and N-Acetyl Cysteine (NAC) which are also being investigated as therapeutic agents against COVID. Therefore, the results here may be confounded by the other additional supplements.
Other clinical trials for MB are continuing to be investigated. Because MB has been used in dental procedures some researchers have pondered whether MB mouthwashes may reduce viral load within the throat similar to other mouthwash treatment options (Arakeri, G. & Rao Us V.).
So where does MB stand in regards to COVID? I would argue that MB may suffer from the same issues that both Hydroxychloroquine and Ivermectin are, albeit to a less extent. The evidence is not so clear cut with respect to COVID, but just like other repurposed drugs MB has had prior history as a possibly viable antiviral. As clinical trials are ongoing they may become obfuscated by claims that either dismiss MB or are adamant about its effectiveness. MB also falls within the same realm as a relatively cheap, widely available compound that lends itself both appeal and caution by doctors and users alike. It’s a difficult position to be in where people must battle between the idea of trying something that may not work or do nothing and hope for the best.
Therefore, this is one area where I will abstain from providing my opinion because the evidence isn’t there right now to support or refute its use. The evidence so far suggests it may be a viable candidate but there isn’t much else to work off of with, and the evidence so far is rather small as well. Once again, I would encourage people to do their own research and seek out physicians that they can have open dialogue with.
Is Methylene Blue Right For You?
For something as simple as a molecule designed to dye cotton, Methylene Blue has been implicated for a wide variety of therapeutic benefits. From aging, neurocognition, and antimicrobial properties the research into Methylene Blue is continuously ongoing.
However, as a daily supplement to use chronically the evidence is not there to support such usage. The clinical studies are ongoing and have not validated any of the health claims made by many of these Tik Tok influencers, at least to the extent that I would be comfortable with. In an attempt to push fads to gain notoriety many of these influencers may be entering into a world in which they are not knowledgeable enough to provide accurate, nuanced information to their audience. Pushing such absolutism or misinterpreting studies does not help add to the discourse.
But the same can be said for many reactionaries, who themselves may use misleading headlines and phrases when reporting on these stories in order to garner attention and views. Unfortunately, many of these YouTubers and Twitter users may engage in the same notoriety-seeking behaviors as the influencers they criticize. There’s a lot of nuance to the discussion that is completely overshadowed by taking absolutist positions on the manner.
As it stands, the evidence is not so clear cut to really consider Methylene Blue for all of its purported benefits. But do remember that this is the opinion of one person. As always, do your own research and engage in dialogue with medical professionals you trust will act in good faith. But more importantly, always be weary of those who try to influence you with promises of a panacea or with appeals to authority.
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