The Aging Gut Microbiome Produces More Trimethylamine, Harming Arterial Function

In recent years academic interest has grown in the study of the gut microbiome. Researchers are making inroads into understanding the considerable influence of these microbial populations over the progression of health and aging. The gut microbiome may be as influential as physical activity in these matters. The balance of microbial populations shifts unfavorably over time, for reasons that are yet to be fully mapped and understood. This leads to greater numbers of inflammatory microbes, or those that produce harmful byproducts, and fewer microbes that produce beneficial metabolites. Researchers have identified some of the more important beneficial metabolites that decline with age, such as indoles, butyrate, and propionate. In the research materials I'll point out today, the authors note a harmful metabolite, trimethylamine, that is produced in greater amounts in older individuals.

What to do about these issues? It is possible in principle to supplement missing metabolites, as they are identified. Removal of harmful metabolites is more challenging as a general rule, for all that it seems plausible in the specific case of trimelthylamine. A better approach to the problem is to fix the age-related disruption of the microbiome. Various options exist: fecal microbiota transplants, for example, are already used in human medicine, and transplanting young microbes into old individuals has been shown to be beneficial in animal studies, a method to reset the balance of microbial populations. Equally, less comprehensive methods such as innoculation against flagellin, to rouse the immune system into destroying more of the harmful microbes present in the gut, are also possible. It is also the case that very aggressive use of probiotics might work, though not yet all that well explored at the high doses likely required.

What makes arteries age? Study explores new link to gut bacteria, diet

Eat a slab of steak or a plate of scrambled eggs, and your resident gut bacteria get to work immediately to break it down. As they metabolize the amino acids L-carnitine and choline, they churn out a metabolic byproduct called trimethylamine, which the liver converts to trimethylamine-N-Oxide (TMAO) and sends coursing through your bloodstream. Previous studies have shown that people with higher blood levels of TMAO are more than twice as likely to have a heart attack or stroke and tend to die earlier. But to date, scientists haven't completely understood why.

The researchers measured the blood and arterial health of 101 older adults and 22 young adults and found that TMAO levels significantly rise with age. (This falls in line with a previous study in mice, showing the gut microbiome - or your collection of intestinal bacteria - changes with age, breeding more bacteria that help produce TMAO). Adults with higher blood levels of TMAO had significantly worse artery function, the new study found, and showed greater signs of oxidative stress, or tissue damage, in the lining of their blood vessels. When the researchers fed TMAO directly to young mice, their blood vessels swiftly aged.

Preliminary data also show that mice with higher levels of TMAO exhibit decreases in learning and memory, suggesting the compound could also play a role in age-related cognitive decline. On the flip side, old mice that ate a compound called dimethyl butanol (found in trace amounts in olive oil, vinegar and red wine) saw their vascular dysfunction reverse. Scientists believe that this compound prevents the production of TMAO. Everyone - even a young vegan - produces some TMAO. But over time, eating a lot of animal products may take a toll.

Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans

Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated dilation.

In young mice, 6 months of dietary supplementation with trimethylamine-N-oxide induced an aging-like impairment in carotid artery endothelium-dependent dilation to acetylcholine versus control feeding (peak dilation: 79±3% versus 95±3%). This impairment was accompanied by increased vascular nitrotyrosine, a marker of oxidative stress. Trimethylamine-N-oxide supplementation also reduced activation of endothelial nitric oxide synthase and impaired nitric oxide-mediated dilation. Acute incubation of carotid arteries with trimethylamine-N-oxide recapitulated these events.

Next, treatment with 3,3-dimethyl-1-butanol for 8 to 10 weeks to suppress trimethylamine-N-oxide selectively improved endothelium-dependent dilation in old mice to young levels (peak: 90±2%) by normalizing vascular superoxide production, restoring nitric oxide-mediated dilation, and ameliorating superoxide-related suppression of endothelium-dependent dilation.

Lastly, among healthy middle-aged/older adults, higher plasma trimethylamine-N-oxide was associated with greater nitrotyrosine abundance in biopsied endothelial cells, and infusion of the antioxidant ascorbic acid restored flow-mediated dilation to young levels, indicating tonic oxidative stress-related suppression of endothelial function with higher circulating trimethylamine-N-oxide.


Hi there! Just a 2 cents.

''Preliminary data also show that mice with higher levels of TMAO exhibit decreases in learning and memory, suggesting the compound could also play a role in age-related cognitive decline. On the flip side, old mice that ate a compound called dimethyl butanol (found in trace amounts in olive oil, vinegar and red wine) saw their vascular dysfunction reverse. Scientists believe that this compound prevents the production of TMAO. Everyone - even a young vegan - produces some TMAO. But over time, eating a lot of animal products may take a toll.''

Another study had showed this by feeding mice high-fat western diet (aka. junk food, sugar, salt, excess sat. fat) and saw changes in the gut/flora where the type of bacteria was increase fermiculate/bacteroides instead of the Good bacteria, baccilli/lactobacillus, those ones that help in production of intestinal short-chain fatty acids (SCFAs) like pyruvate, butyrate, propionate that help to fuel the body and promote ketosis/fat burning/instead of relying on glucose as main source. These SCFAs reduce weight and energize the body. The bad bacterias are the ones that produce TMAO. Thus, diet is a large explication why the gut flora is wacked out. If you eat bio yogourt full of active bacterial cultures (like bifidobacteria/lactobaciillus) this helps to improve gut flora - but it does not stop things. For a while I took a ton of those, for now it is discovered that intestinal flora contributes to atherosclerosis; it's not just the circulating LDL; although it is the major one reason; intestinal flora changes during atherosclerosis towards that bad profile and sure enough, TMAO production; as this study shows it will accelerate endothelial/vasculature weakening and cause ROS/oxidations at atherosclerotic lesions; I am even guessing the LDL turns bad because of this, it's not 7-ketocholesterol, LDL, vLDL,'s down in the intestine, with TMAO; one more 'oxide' to deal with. When I took those good bacteria yogourts that I bought from bio places; these are 'pharmaceutical' yogurts with 5 billions bacterias...welll, let's just say, it was mixed bag...good and bad.

There is a saying ''too much is just as bad as too little''; at a certain point I stopped them, I was ill eating these bacterial cultures; most likely messed up my intestinal flora... Worse.

If you are healthy and your intestinal flora is going well, no problem, are sick/ill and have a serious disease; watch out. IT can be a double-edged sword.

Bacterial Overload; overkill...Even if it's the supposed Great Lactobacillus and the ones that remove TMAO....I think we have a threshold about bacterial load in the intestine; no matter the type of flora tehre. The more bacteria...the more chances of Bad ones in that Lot...

When I stopped doing this (eating bacteria from yogourts etc), I became better/less ill; the reason was because I became vegetarian and Cut the Fat/Junk food out and Cut LDL down drastically by producing HDL; the intestinal flora on its own did not solve things...the changes that I made for sure changed the flora and Then yes my health improved;; but while I was sick, there could be Toxicity with these bacterialrich food; and they could actually Accelerate the disease rather then help. It goes to show it depends on your current health state, if benefit or non-benefit/ becomes an Promoter of the disease.

Just a 2 cents.

Posted by: CANanonymity at July 8th, 2020 4:12 PM

PS: ''dimethyl butanol (found in trace amounts in olive oil, vinegar and red wine'' Took a ton of olive oil (thus dimethyl butanol), yes vinegar/acetic acid/the Mother apple cider vinegar/ took that en masse and yes red wine (one glass a day almost), 99% cacao dark chocolate (binged on it - full of sat fat) while sick for long periods (took them for years)...none of that did much on my disease. If you do not cut the culprits (such as junk food) LDL will still accumulate and atherosclerosis will continue Despite taking these at the same time. Same thing with fruits, veggies, they did help for sure, but themselves were not the real's because I changed the cholesterol profile by having my liver/body produce HDL over LDL and have a correct ratio. They cannot Stop on their own; you must stop the bad/junk diet, no exercise, sedentarity, being stressed, do fasting/CR ( careful..strong CR may Accelerate the disease/fragility..because can create frailty/lack of nutrients/calories/energy) etc...

Posted by: CANanonymity at July 8th, 2020 4:51 PM

I found this info online. Comments? It came from a site I like

In a tiny study of 5 men and 5 women, PQQ supplementation caused a reduction in a number of different inflammatory markers, including TMAO:

NOTE ON liposomal formulas: stay away from supplements that encase nutrients in liposomal formulas.
Because lecithins and phospholipids can increase levels of TMAO. If PQQ reduces levels of TMAO, and that is a primary driver of the decision to consider it in your supplement regimen, it doesn't make a ton of sense to take preparations that are encased in lecithins, and many of the blends are.

Posted by: august33 at July 8th, 2020 9:05 PM

Hi august! Thank you for asking. Just a 2 cents.

Absolutely, agree with you, makes no sense, it defeats the purpose of taking PQQ; it is very akin to Omega-3s...some of them where encapsulated not fully hermetically or turned rancid...thus you were actually consuming already-peroxidized O3s... peroxidized O3s have catastrophic lipoperoxidation effects; akin to ALEs (Advanced Lipoxidation End Products) they will destroy DNA/cause macro-molecular damage quickly. It's the same thing with lecithins and phospholipids (the actual carriers of the fatty acids like Omega 3s DHA/EPA PUFAs which are highly peroxidizable; they have antioxidant potential by their signaletic effect when incorporated in the mito phospholipids; but they Themselves are highly subsceptible to O2/oxygen ROS, which then makes lipid peroxide formation from O2 ROS exposure);

in order to mitigate the effects of increased TMAO, it would be to take gut-flora changing bacterial cultures (like in food), this would remove the capacity of the intestinal flore to produce TMAO - despite taking PQQ; I am not aware if TMAO is produced elsewhere, but if it is, then it would be to supplement antioxidation - for PQQ; I know this is totally self-defeating, since the whole point of PQQ is that ITself Is an why would you need Another antioxidant to protect That antioxidant (PQQ); but it was shown that anti oxidats combining could help to alleviate sudden depletion or oxidation of an oxidant (just like for example the Redox; it uses two main systems; Glutathione and Thioredoxin; they work in tandem...when glutathione is depleted; thioredoxin takes over and tries to mitigate the lacking;....when Thioredoxin is dysfunctional, glutatione 'doubles-up' and 'increases it levels' to make up for lack of thioredoxin a nice balance to offset one or the other being 'lacking/dysfunction/oxidized'...Together, they form the redox; and it Cannot work without both; I mean clearly see that at some point there will be defects because you can't run forever without one or the other; they are Balance and Both needed; for that (redox) balance to work (between Oxidation vs Antioxidation). I often read that Vitamin E/tocopherol (or even better tocotrienols) help to mitigate things, they 'add it' as a preserving element/antioxidant, like in food; taking with PQQ will synergize and help PQQ do better job of reducing TMAO; if you can obtain PQQ in some other form that is best; because you don't want to ingest any 'TMAO-producing bacteria-enhancer' like those phospholipid/lecithin.
I'm sure some of them have substantial levels of oxidanst in them too; possible TMAO itself directly In the capsule (when normally speaking it is produced by bacteria from intestine; but bacteria is present everywhere); a bit like rancid O3s loaded with oxidants.

Just a 2 cents.

Posted by: CANanonymity at July 8th, 2020 10:12 PM

PQQ + Astaxanthin taken together make unbelivably good combination of antioxidants, they nullify all the immflamation during flu, which none of them taken separately can do.

Posted by: SilverSeeker at July 9th, 2020 4:31 AM

That animal study on young biome transplants was 3 years ago, where are they with it now? Why is this stuff taking such an obnoxiously long time to reach humans? What could be the harm?

Posted by: Nathan McKaskle at July 13th, 2020 3:57 PM
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