Yup. And so it is in NZ - say the Gov to those living in or near the repeatedly contaminated forests and waterways who refuse compliance: “are there not workhouses?...and if they die, then so they should, and decrease the surplus population.” (Isn’t that how it goes?)...
Your posts are trustworthy and meaningful. I respect the caveats and cautious reporting in a chaotic info sphere. I cannot understand why Ohioians have not demanded better precautions for these folks -- shouldn’t they have been evacuated until the risk analysis is done?
Thank you MClark! I try to tell people that they should still have some level of skepticism with the information they come across, especially if it's someone they trust because it can become easy to just follow the information without thinking critically. I mentioned I3C because I heard some people talking about it, looked it up, and realized that it can't "detoxify" dioxin given that they share the same mechanisms.
To your question I really don't have any idea what evidence was used. I'm just aware that people were told it was "safe" but what science was used? The air monitor data is limited and the water data didn't come out until after everyone was told to return I believe so how could they claim that the water was safe? My timeline of events are off but the fire happened on February 6th and they were told to come back on February 8th which was hardly any time away from the site which is pretty crazy.
Thank you for the details. I saw the i3c comments by you and wondered if it represented a competitor for the pathway to displace dioxin — but you said that dioxin has affinity towards storage (my wording - was it lipid based). If you don’t mind a question from someone who loves mechanism — would something be a detox agent because it attaches to dioxin and moves it toward an excretion / elimination pathway ? And, does an I3c molecule have any role in blocking the entry of dioxin into a derangement pathway whilst a true detox agent circulates against it? In sun: a 1-2 punch. Thanks again for all your teaching and especially in the realm of critical reasoning. Sometimes I feel like the demento ring wraths of the NIH Psyop league are undermining most of the heuristics that found common sense and clinical reasoning. I am a discontentor too 😊
So as a whole I'm very skeptical of the "detox movement", mostly because it takes interesting ideas and exaggerates it (this is mostly from a cursory perspective). Take juice cleanses and things of the like, and they always just appear to be surface level, gimmicky talking points that seem convincing but may start to fall apart as it gets into the science.
This, unfortunately, also happens with many supplemental studies given the level of heterogeneity.
But if we look at dioxin let's consider how it acts as a toxin if one were to "detox" from it because one would have to understand how something acts as a toxic agent. I think this part gets missed and so the only thing that's known is that dioxin is associated with increased risk of cancer.
The literature notes that dioxin binds to receptors called aryl hydrocarbon receptors that are found all throughout the body, and it appears that binding of dioxin to these receptors activates them making dioxin what's know as an agonist to these receptors. We know this from studies in which people have been exposed to extremely high levels of dioxin and develop chloracne and hyperpigmentation, which in my dioxin article argues is due to high AHR activation.
So with that we know what dioxin's main role is in the body, although given its structure it's likely to also act as an endocrine disruptor but that will again get into the weeds.
Given this information dioxin would be argued to be a toxin by activating AHR. However, recent research into AHR has noted that the receptor does more than just dealing with toxins and in fact some researchers are looking into AHR agonistic drugs as possible therapeutic agents. This makes the role of dioxin more complicated given these recent findings. Animal models which show dioxin as being very toxic don't appear to have this weird role that us humans do which may point to an evolutionary branch in its functionality, and so animal studies which show high toxicity may not occur in humans (I'm speculating on this part since I haven't looked deeper into the literature).
Now, because dioxin appears to exert toxicity by acting as an AHR agonist, an argument could be made that blocking dioxin or by using an AHR antagonist may reduce the activation of AHR and the cascading effect. This is likely what people are referring to when they refer to a "detox" of dioxin since it would, hypothetically, stop widespread AHR activation.
Overall, this general effect would be considered the pharmacodynamics of a compound or therapeutic- where does it bind and what does it do by binding.
The other side of "detoxing" is one people generally consider with their juice cleanses and liver detoxing of agents which would be considered pharmacokinetics, which is where the compound ends up, how long does it stay in the body, how much of it is available, and how much is excreted.
With pharmacokinetics the acronym ADME is used (Absorption, Distribution, Metabolism, Excretion).
With dioxin, a key issue is that it appears to have a fairly long half life in the body, and so even if one where to inhibit binding of dioxin unless one can actively clear it you'd probably have to keep blocking the activation of AHR in order to prevent dioxin. But again, AHR is far more complex than "no dioxin binding".
Then we have I3C which is derived from various plants. The argument around I3C is highly ambiguous. I've only heard of it being a "detoxing agent" against dioxin hence my reservations. Again, given dioxin's agonistic activities we would argue that an antagonist may be able to prevent binding and activation of AHR.
However, the literature doesn't suggest that I3C and the resulting ligands are antagonists, but rather are agonistic to AHR. This is sort of where the issue resides in the use of these compounds as it almost essentially would flood the body with AHR agonists.
Now, one argument that can be made is that some of these compounds don't bind as well to AHR and may not activate to the same extent. In this case these compounds may be seen as competitive binders to AHR, and one hypothesis could be that flooding the body with a different AHR agonist that doesn't bind well may help to compete against dioxin.
This itself gets into the weeds even further about receptor activation, and like I said I've only seen people saying that L3C is a detoxing agent without much additional information. So my hesitancy is to the fact that many people may see this information and just go along with it rather than spending time and getting into the more nuanced aspects. I've more been concerned that this information gets passed around without anyone spending time looking at the data. We're seeing this with East Palestine and not many people actually trying to look for water, air, and soil data but just speculating and pontificating.
We also saw this with widespread talk about antibodies in egg yolks without many people realizing that to get the antibodies into egg yolks you have to vaccinated the hens. 🤦♂️
Anyways apologies for the long post. Please let me know if it helps clear things up a bit or is even more confusing.
Dear MD — Thank you very much for responding to my questions about mechanism and your critical consideration of the complex and perhaps double edged consequences of intervening in pathways without a comprehensive understanding of all the potential cascades that intervention might trigger. I found a review of potential interest that supports your carefulness with respect to Ahr activation questions. It’s a broad review, which also manages to be granular. PMID: 36110860 Front. Immunol (2022) J Wu, et Al (Free)
Thank you again for sharing your critical thinking processes and disciplined writing. I think the best part of the Substack model is the opportunity we have to think aloud and reason together about mechanism. 🙏
Thank you for the link! I'll take a look when possible since there's a ton I'm trying to read through. It's important to remember that science evolves and much of the mechanisms on AHR are now coming to light after research correlating dioxin to cancer has come out, so when looking at this information it's important to look at it within the context of what is known and see where the pitfalls are.
I'm learning as I read so my knowledge about these things are very minimal but I at least try to see what else is out there. It's a good reminder that things are more complex than we assume. I hope that my Substack, as well as many others, help ease people into their curiosity and engage that critical thinking/inquisitive side. I find that I'm more critical of being told what to think and would rather spend some time looking things up for myself.
I will add this remark. When writing my post I looked up possible antagonists as this would be, hypothetically, the approach to inhibit dioxin. However, I wanted to be careful in posting it in case it suggested that there was concrete evidence to support this claim. To that, I came across this article on resveratrol being a possible AHR antagonist and may help with dioxin, although I haven't been able to read the article to see the actual information:
You’re right to be cautious about the interpretation of lab results. Here in NZ for example, the water sampling after another aerial 1080 (sodium monofluoroacetate - yes, one of the world’s most toxic synthetic poisons, with no antidote) operation, the authorities deliberately wait until after the immediate presence of the toxin is likely to be found, and then do a 25 year old test which doesnt look for the metabolites of the poison that are likely to be present (and also toxic). Needless to say, those labs are paid for an endorsed with a ‘quality standard’ by...yup, you guessed it, the New Zealand Government. Incidentally the raw poison is made by Tull Chemicals in Alabama, I wonder if its transported by train (?) And the poisoned food-baits are manufactured here in NZ, by factories that are funded by the Government too. Money-laundering operation? Isn’t it always?
Yes I've been trying to parse the GC/MS results. I don't trust the dissemination of things being safe without spending time showing people the results. I don't think many people are even aware of all of the sample results which is why I'm trying to collect as much information as I can find to at least provide that information to others.
Let me answer all your questions: Voters that matter live in cities and the suburbs thereof. Not in gutted towns like East Palestine.
Yup. And so it is in NZ - say the Gov to those living in or near the repeatedly contaminated forests and waterways who refuse compliance: “are there not workhouses?...and if they die, then so they should, and decrease the surplus population.” (Isn’t that how it goes?)...
Your posts are trustworthy and meaningful. I respect the caveats and cautious reporting in a chaotic info sphere. I cannot understand why Ohioians have not demanded better precautions for these folks -- shouldn’t they have been evacuated until the risk analysis is done?
Thank you MClark! I try to tell people that they should still have some level of skepticism with the information they come across, especially if it's someone they trust because it can become easy to just follow the information without thinking critically. I mentioned I3C because I heard some people talking about it, looked it up, and realized that it can't "detoxify" dioxin given that they share the same mechanisms.
To your question I really don't have any idea what evidence was used. I'm just aware that people were told it was "safe" but what science was used? The air monitor data is limited and the water data didn't come out until after everyone was told to return I believe so how could they claim that the water was safe? My timeline of events are off but the fire happened on February 6th and they were told to come back on February 8th which was hardly any time away from the site which is pretty crazy.
Thank you for the details. I saw the i3c comments by you and wondered if it represented a competitor for the pathway to displace dioxin — but you said that dioxin has affinity towards storage (my wording - was it lipid based). If you don’t mind a question from someone who loves mechanism — would something be a detox agent because it attaches to dioxin and moves it toward an excretion / elimination pathway ? And, does an I3c molecule have any role in blocking the entry of dioxin into a derangement pathway whilst a true detox agent circulates against it? In sun: a 1-2 punch. Thanks again for all your teaching and especially in the realm of critical reasoning. Sometimes I feel like the demento ring wraths of the NIH Psyop league are undermining most of the heuristics that found common sense and clinical reasoning. I am a discontentor too 😊
So as a whole I'm very skeptical of the "detox movement", mostly because it takes interesting ideas and exaggerates it (this is mostly from a cursory perspective). Take juice cleanses and things of the like, and they always just appear to be surface level, gimmicky talking points that seem convincing but may start to fall apart as it gets into the science.
This, unfortunately, also happens with many supplemental studies given the level of heterogeneity.
But if we look at dioxin let's consider how it acts as a toxin if one were to "detox" from it because one would have to understand how something acts as a toxic agent. I think this part gets missed and so the only thing that's known is that dioxin is associated with increased risk of cancer.
The literature notes that dioxin binds to receptors called aryl hydrocarbon receptors that are found all throughout the body, and it appears that binding of dioxin to these receptors activates them making dioxin what's know as an agonist to these receptors. We know this from studies in which people have been exposed to extremely high levels of dioxin and develop chloracne and hyperpigmentation, which in my dioxin article argues is due to high AHR activation.
So with that we know what dioxin's main role is in the body, although given its structure it's likely to also act as an endocrine disruptor but that will again get into the weeds.
Given this information dioxin would be argued to be a toxin by activating AHR. However, recent research into AHR has noted that the receptor does more than just dealing with toxins and in fact some researchers are looking into AHR agonistic drugs as possible therapeutic agents. This makes the role of dioxin more complicated given these recent findings. Animal models which show dioxin as being very toxic don't appear to have this weird role that us humans do which may point to an evolutionary branch in its functionality, and so animal studies which show high toxicity may not occur in humans (I'm speculating on this part since I haven't looked deeper into the literature).
Now, because dioxin appears to exert toxicity by acting as an AHR agonist, an argument could be made that blocking dioxin or by using an AHR antagonist may reduce the activation of AHR and the cascading effect. This is likely what people are referring to when they refer to a "detox" of dioxin since it would, hypothetically, stop widespread AHR activation.
Overall, this general effect would be considered the pharmacodynamics of a compound or therapeutic- where does it bind and what does it do by binding.
The other side of "detoxing" is one people generally consider with their juice cleanses and liver detoxing of agents which would be considered pharmacokinetics, which is where the compound ends up, how long does it stay in the body, how much of it is available, and how much is excreted.
With pharmacokinetics the acronym ADME is used (Absorption, Distribution, Metabolism, Excretion).
With dioxin, a key issue is that it appears to have a fairly long half life in the body, and so even if one where to inhibit binding of dioxin unless one can actively clear it you'd probably have to keep blocking the activation of AHR in order to prevent dioxin. But again, AHR is far more complex than "no dioxin binding".
Then we have I3C which is derived from various plants. The argument around I3C is highly ambiguous. I've only heard of it being a "detoxing agent" against dioxin hence my reservations. Again, given dioxin's agonistic activities we would argue that an antagonist may be able to prevent binding and activation of AHR.
However, the literature doesn't suggest that I3C and the resulting ligands are antagonists, but rather are agonistic to AHR. This is sort of where the issue resides in the use of these compounds as it almost essentially would flood the body with AHR agonists.
Now, one argument that can be made is that some of these compounds don't bind as well to AHR and may not activate to the same extent. In this case these compounds may be seen as competitive binders to AHR, and one hypothesis could be that flooding the body with a different AHR agonist that doesn't bind well may help to compete against dioxin.
This itself gets into the weeds even further about receptor activation, and like I said I've only seen people saying that L3C is a detoxing agent without much additional information. So my hesitancy is to the fact that many people may see this information and just go along with it rather than spending time and getting into the more nuanced aspects. I've more been concerned that this information gets passed around without anyone spending time looking at the data. We're seeing this with East Palestine and not many people actually trying to look for water, air, and soil data but just speculating and pontificating.
We also saw this with widespread talk about antibodies in egg yolks without many people realizing that to get the antibodies into egg yolks you have to vaccinated the hens. 🤦♂️
Anyways apologies for the long post. Please let me know if it helps clear things up a bit or is even more confusing.
Dear MD — Thank you very much for responding to my questions about mechanism and your critical consideration of the complex and perhaps double edged consequences of intervening in pathways without a comprehensive understanding of all the potential cascades that intervention might trigger. I found a review of potential interest that supports your carefulness with respect to Ahr activation questions. It’s a broad review, which also manages to be granular. PMID: 36110860 Front. Immunol (2022) J Wu, et Al (Free)
Thank you again for sharing your critical thinking processes and disciplined writing. I think the best part of the Substack model is the opportunity we have to think aloud and reason together about mechanism. 🙏
Thank you for the link! I'll take a look when possible since there's a ton I'm trying to read through. It's important to remember that science evolves and much of the mechanisms on AHR are now coming to light after research correlating dioxin to cancer has come out, so when looking at this information it's important to look at it within the context of what is known and see where the pitfalls are.
I'm learning as I read so my knowledge about these things are very minimal but I at least try to see what else is out there. It's a good reminder that things are more complex than we assume. I hope that my Substack, as well as many others, help ease people into their curiosity and engage that critical thinking/inquisitive side. I find that I'm more critical of being told what to think and would rather spend some time looking things up for myself.
I will add this remark. When writing my post I looked up possible antagonists as this would be, hypothetically, the approach to inhibit dioxin. However, I wanted to be careful in posting it in case it suggested that there was concrete evidence to support this claim. To that, I came across this article on resveratrol being a possible AHR antagonist and may help with dioxin, although I haven't been able to read the article to see the actual information:
https://pubmed.ncbi.nlm.nih.gov/10496962/
There's also this one which I haven't looked at yet:
https://pubmed.ncbi.nlm.nih.gov/19376845/
And thank you for the thanks! I do hope people find value in my writing so it's always nice to hear and helps put the work into perspective!
You’re right to be cautious about the interpretation of lab results. Here in NZ for example, the water sampling after another aerial 1080 (sodium monofluoroacetate - yes, one of the world’s most toxic synthetic poisons, with no antidote) operation, the authorities deliberately wait until after the immediate presence of the toxin is likely to be found, and then do a 25 year old test which doesnt look for the metabolites of the poison that are likely to be present (and also toxic). Needless to say, those labs are paid for an endorsed with a ‘quality standard’ by...yup, you guessed it, the New Zealand Government. Incidentally the raw poison is made by Tull Chemicals in Alabama, I wonder if its transported by train (?) And the poisoned food-baits are manufactured here in NZ, by factories that are funded by the Government too. Money-laundering operation? Isn’t it always?
Yes I've been trying to parse the GC/MS results. I don't trust the dissemination of things being safe without spending time showing people the results. I don't think many people are even aware of all of the sample results which is why I'm trying to collect as much information as I can find to at least provide that information to others.
Thank you so much!! ❤️🙏
How odd
EPA Lab Results: Water (through 02/14/23) - East Palestine, OH Response (csv)
has no results for 2,3,7,8-Tétrachlorodibenzo-p-dioxin, or any related dibenzodioxin or dibenzofuran. Kind of an important oversight.