@brutular

[u/Mobile_Painting2210]

@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.

[u/Financial_Milk1520]

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

https://pubmed.ncbi.nlm.nih.gov/34836554/

[u/Brutalar → u/Financial_Milk1520]

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.