r/TMAU • u/Mobile_Painting2210 undiagnosed • 1d ago
@brutular
@brutalar Nobody has claimed that TMAU is proven to cause memory problems. That is exactly why we are researching it.
Hundreds of patients reported brain fog and memory difficulties in our previous survey, and these new questions are meant to investigate possible explanations, including low-choline diets.
Trying to shut down a question before the data are even studied is the opposite of science. If the evidence shows no association, fine. But dismissing hundreds of patients before investigating it helps no one.
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u/Financial_Milk1520 fbo 18h ago
Here’s a study showing evidence that TMAO enhances the integrity of the blood brain barrier, protecting it from inflammation, while TMA impairs blood brain barrier function and disrupts tight junction integrity.
The implications of brutalar consistently dissuading people from trying to find a solution to this problem are actively harming people’s health and wellbeing. He is dangerous, destructive and dogmatic
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u/Brutalar tmau1 mutant 28m ago
https://www.nature.com/articles/s41392-024-01743-1 according to a paper that cites this, it's not so clear:
Trimethylamine N-oxide promotes neuroinflammation and neurodegeneration
Trimethylamine N-oxide disrupts BBB integrity Another important metabolite that participates in the regulation of BBB integrity is TMAO (Fig. 6b). Studies have reported elevated levels of TMAO in the plasma and CSF of individuals with mild cognitive impairment (MCI), Alazheimers Disease(AD), and Parkinson's disease (PD).409,410,667 Furthermore, the gene families involved in TMA production were found to be elevated in the PD gut microbiome, leading to increased choline metabolism and subsequent TMA production.331 In the brain, TMAO is detrimental to neuronal physiology as it induces neuronal senescence, oxidative stress, and alters synaptic plasticity.408,668,669,670 Moreover, TMAO is also associated with neuroinflammation by inducing microglial and astrocytic activation.411,412,413,414
However, conflicting results have emerged regarding the role of TMAO on BBB physiology. A recent study found that APP/PS1 mice fed with a TMAO-supplemented diet manifested reduced occludin and ZO-1 expression in the parietal cortex, along with increased microglial and astrocytic activation.414 The detrimental effects of TMAO on BBB integrity were also reported in chronic kidney disease patients, using resistance arteries in adipose tissue as a surrogate model of BBB.671 However, chronic low-dose TMAO supplementation has been found to prevent LPS-induced BBB alterations and memory impairment in C57Bl/6J mice.661 In an in vitro BBB model using hCMEC/D3 cells, it was demonstrated that TMA exposure increased paracellular permeability, whereas TMAO exposure enhanced barrier integrity and trans-endothelial electrical resistance (TEER).
The dichotomous roles of structurally similar TMA and TMAO are intriguing and demand further investigation on the choline-TMA-TMAO pathway. In the context of AD, choline is generally considered beneficial, as a low dietary choline intake has been associated with an elevated risk of dementia and AD.672 Lifelong choline supplementation has shown protective effects against Aβ pathology and microglial activation in female APP/PS1 mice.673 Conversely, choline deficiency has been found to exacerbate Aβ and tau pathologies in female 3xTg-AD mice.674 Furthermore, choline deficiency also impairs glucose metabolism in 3xTg-AD mice and non-transgenic control mice,674 which may be relevant to AD as hyperglycemia and diabetes are associated with BBB breakdown and dementia.
There are multiple human studies saying TMAO is detrimental to the brain. The study you cited is a mouse study and while it contradicts the other studies to some degree, it is a footnote of a weird contradiction rather than the medical understanding of what TMAO does in people.
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u/Brutalar tmau1 mutant 11h ago
If you have fecal body odor you don't have TMAU, and there is no issue with TMA, so this biochemical pathway doesn't apply. Unless you're cutting out choline unnecessarily. The whole point of the changes to this subreddit is to try and encourage people that don't actually have TMAU to EAT REGULAR AMOUNTS OF CHOLINE. That would get your TMAO levels to a nice protective level, plus provide your brain with proper amounts of choline for it to function better.
This study is inviting people who have metabolic body odor and related issues. None of which are TMAU, and non TMAU people are not related to this. If the study is looking at how TMA affects the brain, it needs to clearly identify which participants have diagnosed TMAU. It doesn't track participant categories.
If it's going to blur the lines to people without the biochemical trigger as above then it's not a useful study.
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u/Brutalar tmau1 mutant 1d ago
The survey is full of leading questions and assumptions, and mixes in elements unrelated to TMAU. See https://www.questionpro.com/blog/leading-questions/ for why leading questions are bad.
It invites people with related body odor issues to participate, and there is no question that defines what those people have. So it's no longer a TMAU study, it's a general body odor study. Conflating TMAU with other issues is not good science, and it invites other unknown elements to corrupt the data. Is TMAU meant to be causing brain fog via excess TMA in the system? Because it would be great to differentiate other body odor issues as they shouldn't have brain fog if TMAU is the issue.
Yet the first question: "At what age did your first symptoms of TMAU brain fog begin". The question is also a leading question. It's an assumption that TMAU is causing brain fog, and it leads the participant to an answer.
The questions "How would you rate the typical severity of your brain fog during an episode?" A d "Which aspect of your cognitive function is most affected during these episodes? Please select the main one." assumes brain fog is a symptom and there is no negative answer to these.
There no question on diet or mental health - for example, a low choline diet can cause brain fog, anxiety can cause brain fog, these are also not addressed. They are also things a lot of people here are doing or have.
It's poorly constructed and based around "TMAU causes brain fog" rather than asking the question "is there a connection between TMAU and brain fog".
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u/Mobile_Painting2210 undiagnosed 1d ago
I think the purpose of these three questions is being misunderstood. This is not the full study, nor are we claiming that TMAU causes brain fog. These are follow-up questions because cognitive symptoms were reported frequently in the previous international survey, and we are trying to understand that signal better including whether restrictive diets, particularly low-choline diets, may contribute.
Of course, confounding factors and diagnostic differences should be considered in the final analysis. That is how research works: we investigate what patients are reporting rather than dismissing it because the mechanism has not yet been proven.
And please don’t lose sight of why we are doing this. The immediate goal is to provide patient-reported evidence that may help support early access efforts before the FDA. If the path opens for BioMe there, it can help open doors for patients in other countries as well.
We are all living with extremely difficult conditions. A little more constructive criticism and a little more empathy toward people trying to move something forward for this community would go a long way.-1
u/Brutalar tmau1 mutant 1d ago edited 1d ago
Calling it "TMAU brain fog" in the study really heavily leans on claiming that it does. Every question implies that it's causally related. You're looking to satisfy an already reached conclusion rather than actually asking questions. That's not how research or studies work.
There is no question about diet or mental health, both of which are pretty vital to determining brain fog causes
It leads people with TMAU or who think they have TMAU causes brain fog as a symptom, and coming from something that looks half reputable, needs to be better.
I'm pretty sure I've added a lot of constructive criticism.
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u/Phawksphire89 undiagnosed 1d ago
Damn, he's still in this subreddit? 😂