The Acetyl Story: ALCAR, TMAO & Magnesium Acetate
- The ALCAR/TMAO Finding
- My Follow-up Bloodwork: TMAO Normalized After Quitting
- Vinegar / Acetic Acid As The Mechanism
- Magnesium Acetate
- Sources
Research and education, not medical advice.
For years I recommended ALCAR as one of the best dopamine and antidepressant agents we had. I ran it myself from 2021 to 2025. Then a 2025 study, plus my own bloodwork, forced a full reversal. This page collects how that played out, in order: the TMAO finding, my follow-up bloods, the acetate mechanism that explains what ALCAR was actually doing, and the product that replaces it. See also Dopamine for ALCAR’s place in that picture, and What To Avoid.
The ALCAR/TMAO Finding
ALCAR Officially Proven to Convert to TMAO At High Rate (90%)
I can no longer recommend ALCAR for any purpose, unless it is injected. A possible alternative is Vinegar/ acetic acid, since it also showed antidepressant effects and could possibly donate acetyl groups in a similar way. Sorry, I know this is disappointing to many people who have read promising studies on ALCAR. I did get my bloods tested on it though, and the results were awful. That is despite being on PQQ, which is literally proven to reduce TMAO levels.
This is ALCAR, not L-Carnitine. It’s a 2025 study, so it’s still news. It’s pretty conclusive if you compare it to the larger body of data on carnitine. (https://pubmed.ncbi.nlm.nih.gov/39064748/) Seems like I said vinegar could suffice.
Elevated TMAO, at least in some studies, can have a detrimental effect to cardiovascular health. And it’s heavily correlated to stroke and other incidents. There is reason to believe it might be causative, like with this study but there’s others. Not many things increase TMAO besides sources of choline and carnitine, which is an extreme minority of supplements.
Alpha GPC also was shown to cause TMAO production and as a result increased stroke risk by 46% in studies (https://pubmed.ncbi.nlm.nih.gov/34817582/). Choline and carnitine are the biggest factors here. CDP-Choline is shown to have less TMA-generating risk, and so less TMAO.
Literally just find me one human being besides myself that didn’t get elevated TMAO from ALCAR. To my knowledge im the only person from this community to even order the test after being on it chronically.
My Follow-up Bloodwork: TMAO Normalized After Quitting
Update: My TMAO after quitting ALCAR
This is my final post speaking about the dangers of ALCAR. I ran ALCAR from 2021-2025. I really hope I don’t live to regret that. For anyone still on it, I highly recommend quitting.
The TMAO high was ALCAR, TMAO low no ALCAR. No other TMAO related compounds. Most people, the study on ALCAR and TMAO shows that within their group, TMAO was raised significantly. It’s scientifically impossible to account for everyone.
Theres 0 proof that anything reduces TMAO from ALCAR. And even then it’s completely illogical to not simply remove it or inject it. Just look at the stroke rates on Alpha GPC, and all evidence points to it being from fucking TMAO.
People bring up that fish have high amounts of TMA, but that people who eat a lot of fish have lower amounts of heart disease. Thats caused by the fish oil content and it being a lean meat. Correlation is not causation.
I want to release another acetate-related product without as high Magnesium content. Stay tuned.
Vinegar / Acetic Acid As The Mechanism
More evidence vinegar may replace ALCAR for us
Previously I explained that the carnitine of ALCAR is largely metabolized to TMAO, and that vinegar (acetic acid) at 3g/ day had antidepressant effects in humans. I’d like to go into further detail here.
Firstly, acetic acid can bind to sodium, etc. to form acetate salts that are bioavailable: https://pubmed.ncbi.nlm.nih.gov/20924150/ Acetate acetylates deacetylated histones and even can have an HDACI-like effect: https://pubmed.ncbi.nlm.nih.gov/21359531/ And excess acetate also seems to join choline to form acetylcholine: https://pubmed.ncbi.nlm.nih.gov/9125430/
Acetate appears to have at least one study in rodents showing improved cognition: https://pubmed.ncbi.nlm.nih.gov/39253503/ And apple cider vinegar shows a neuroprotective effect in Alzheimer’s rodent models: https://pubmed.ncbi.nlm.nih.gov/33084094/
The only critical piece of literature I’m missing here is a study on dopaminergic neurotransmission in rodents from either acetate or acetic acid ingestion. But since in the past I showed neurotrophic growth factors such as GDNF and NGF downstream of histone acetylation are at least partly responsible for the dopamine-enhancing qualities of ALCAR, it’s not a stretch to assume it’s possible. It should be dopaminergic as I outlined in the post.
It would seem that mitochondria biogenesis is still reliant on Carnitine, however: https://www.sciencedirect.com/science/article/abs/pii/S0197018613000077 But acetic acid ingestion does improve skeletal muscle retention: https://pmc.ncbi.nlm.nih.gov/articles/PMC9101554/ Apple cider vinegar is also hepatoprotective.
On the dose, it has absolutely nothing to do with it being acidic. No its 3g pure acetic acid. That’s 4 tablespoons. No. Youre not getting 3 grams of acetic acid from fucking tobasco sauce. I don’t think it matters what you take it alongside. But the amount of vinegar you’d need may be a problem.
Magnesium Acetate
Magnesium Acetate New Innovation
To be frank, if you told me a year ago that vinegar might be a valid treatment for Parkinson’s, I would’ve looked at you like you’re crazy. But you’ll be surprised reading what I’ve discovered over the past couple months, and what has led me to Everychem’s new original project: Magnesium Acetate.
In a practical sense, Magnesium Acetate should be the answer to ALCAR, Magnesium supplements, and Apple Cider Vinegar (ACV). It is a highly bioavailable form of both Magnesium and Acetate, both of which are absorbed in the upper digestive tract and contribute to cardiovascular, physical and cognitive health.
Why it beats Magnesium L-Threonate
For a while I have advocated against using Magnesium L-Threonate due to L-Threonate facilitating supraphysiological brain levels of Magnesium through enhancing its transport across the BBB, which could easily saturate the synapse causing preferential accumulation outside of that domain and antagonism of extrasynaptic NMDA. While this may be good in the context of excitotoxicity and can cause rapid synaptogenesis, extrasynaptic NMDA are required for stress resilience and adaptation, and antagonizing them may increase susceptibility to social defeat. This raises concerns about someone’s mental stability and social performance while using Magtein (and Memantine, which is also an eNMDA-biased NMDA antagonist). By not trying to bypass the BBB’s limitations of Magnesium penetration, Magnesium can be allowed to play a more constructive role in memory guidance and the fine tuning of memories. (See What To Avoid on Magtein.)
What ALCAR was actually doing
Acetyl-L-Carnitine has a poor oral bioavailability of just 2.1-2.4%, which led to it being injected for its treatment of alcohol withdrawal-induced anhedonia. Indeed, injecting ALCAR solves its greatest pitfalls, that being poor absorption and its high metabolism into TMAO caused by its disassembly into L-Carnitine in the gut. On the surface the danger of TMAO may seem debatable, but upon deeper inspection, is a legitimate problem.
In a meta-analysis on older subjects, ALCAR was shown to be as effective as SSRIs in reducing depression. The way it works, however, is more interesting. ALCAR donates an acetyl group to deacetylated histones, which allows it to perform similarly to a HDAC inhibitor, elevating neurotrophic growth factors including Artemin, which has similar properties to GDNF and appears to form the basis of ALCAR’s neurotrophic effects.
This increase in Artemin is likely why ALCAR was shown to upregulate dopamine even months after discontinuation, as GDNF also had lasting positive effects in Parkinson’s patients for years after treatment. Similarly, ALCAR was neuroprotective during, and prevented withdrawal from methamphetamine, representing the importance of Artemin in dopaminergic function. Artemin itself is antidepressant, meaning this too explains the antidepressant effects of ALCAR. Likewise, ALCAR’s clinical effects in attention deficit disorder (ADD), but not ADHD, improvements to fatigue in Multiple Sclerosis and protective effects in early Alzheimer’s appear connected to this neurotrophic growth factor, although could also be mediated by an increase in Acetylcholine, as choline also accepts an acetyl group from ALCAR. (More on ALCAR’s dopaminergic role under Dopamine.)
Acetate does it too
Acetic Acid, the active component of Apple Cider Vinegar, raises blood Acetate levels when taken orally and reduced depression when taken by people at 3g/ day. While Acetate is less discussed, it cleaves the most important mechanism of ALCAR, Acetyl- donation, which is evidenced in literature to perform the exact same function at histones that leads to Artemin and subsequent antidepressant effects. In a similar fashion to ALCAR, Acetate increases Acetylcholine by acting as an Acetyl- donor. And has a study in female rodents where it improved spatial memory. Again like ALCAR, Acetic Acid was protective against Alzheimer’s in a rodent model.
While mitochondrial biogenesis is still dependent on L-Carnitine, Acetic Acid helped to maintain muscle in aging rodents, which is thought to be caused by it activating AMPK. Likewise, this AMPK activation supports the historical use of Apple Cider Vinegar in diabetes and weight loss, as it led to an improvement in fat-to-lean mass ratio, blood glucose, triglyceride and cholesterol levels. However, Acetate can also be used as an alternative energy source in muscles, as Acetyl CoA, Acetyl-L-Carnitine and ATP were increased in an animal study testing exercise-induced glycogen depletion.
The compound
In short, Magnesium Acetate is a broadly impactful nutrient compound that provides a favorable ratio of Acetate and Magnesium. Improvements across the board to biological function are to be expected, and many of which can be narrowed down to the high likelihood of it increasing Artemin which can upregulate dopamine long-term.
When Magnesium Acetate is consumed, it will split into Magnesium and Acetate in the stomach, where it will then begin to be rapidly absorbed in the upper digestive tract. Its high bioavailability allows for stable digestion, helping to avoid diarrhea caused by extended osmotic laxative effects, like with Magnesium Oxide for example. Unfortunately, due to the high hydrophilicity of Magnesium Acetate, it is currently available in Tetrahydrate form only on Everychem, which slightly reduces the active content.
Dosage
One gram of Magnesium Acetate Tetrahydrate should provide around 113.3mg Magnesium (45% of RDA), 550.6mg Acetate, 336.1mg water. This would put the dosage at around 1-4 grams, but possibly more depending on one’s metabolic sensitivity to Magnesium-induced diarrhea and dosing schedule. I tried up to 3 grams, 1-2g was fine but 3g caused me diarrhea. Others have tried 4g and say it doesn’t cause diarrhea. A 1/4 teaspoon of Magnesium Acetate weighs out to exactly one gram.
Despite being already in acetate form, acetic acid converts at a high rate to Acetate, and Apple Cider Vinegar is typically used in amounts that achieve 750mg. So, a couple grams would be a bit higher than that. Since Magnesium tolerability is somewhat variable, and the strongest evidence of Acetic Acid in humans used up to 3g across the day, a combination of Potassium Acetate and Magnesium Acetate is also being considered. Regardless, Magnesium Acetate alone seems like a significant improvement to what’s currently out there.
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