Animal protein: TMAO and/or AGEs?

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
circular
Senior Contributor
Senior Contributor
Posts: 5072
Joined: Sun Nov 03, 2013 10:43 am

Animal protein: TMAO and/or AGEs?

Postby circular » Mon Nov 11, 2019 8:45 am

Is it my imagination, or is there a general lack of consideration, in studies that link high animal protein consumption to adverse health events, of the adverse effects of advanced glycation end products? TMAO comes up over and over, but I don't read that these studies are examining how the animal protein is prepared among participants who eat high amounts of it. One has to really change cultural food prep habits to eat higher amounts of animal protein while keeping AGEs low, so I'm quite sure we could assume that study participants eating high animal protein are eating a very high level of AGEs. I'm wondering whether, even if TMAO may contribute its own adverse effects, more work needs to be done to parse the different contributions of TMAO and AGEs. I would think there needs to be a very well designed study that has a cohort eating animal products that are extremely low in AGEs compared with a cohort that eats lots of grilled, broiled and roasted meats and other high AGE animal protein foods, compare the TMAO and AGE levels and then look at endpoints.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

User avatar
TheresaB
Mod
Mod
Posts: 1030
Joined: Wed Feb 03, 2016 9:46 am
Location: Front Range, CO

Re: Animal protein: TMAO and/or AGEs?

Postby TheresaB » Mon Nov 11, 2019 11:59 am

circular wrote:is there a general lack of consideration, in studies that link high animal protein consumption to adverse health events,
...TMAO/AGEs

Just this past weekend this paper was published Undigested Food and Gut Microbiota May Cooperate in the Pathogenesis of Neuroinflammatory Diseases: A Matter of Barriers and a Proposal on the Origin of Organ Specificity

On the other hand, shifting from a vegetarian diet to an energy dense Western diet, based on the intake of saturated fat, meat and eggs, and only a little fiber and few polyphenols, may provide substrates to the microbiota, such as carnitine and choline. Trimethylammine (TMA) is a detrimental product of their metabolism in the gut, converted into its oxide TMAO in the liver. TMAO may be associated with cardiovascular events [75], may also be present in human cerebrospinal fluid [76] and is elevated in Alzheimer’s disease [77]. Furthermore, the carnivorous diet provides high amounts of saturated fatty acids and cholesterol that increase the production of bile acids. Their subsequent conversion by the gut microbiota into deoxycholic acid and lithocolic acid, which are toxic for other, mainly beneficial, gut microbes, may lead to a decrease in microbial biodiversity and gut dysbiosis.


The paper goes on to its ultimate conclusion that decreased microbial biodiversity and gut dysbiosis leads to increased gut permeability, which leads to break down of the blood-brain barrier which in turn leads to neuroinflammation. It's a fascinating paper.
-Theresa
ApoE 4/4

User avatar
Julie G
Mod
Mod
Posts: 8522
Joined: Sat Oct 26, 2013 6:36 pm

Re: Animal protein: TMAO and/or AGEs?

Postby Julie G » Mon Nov 11, 2019 12:55 pm

I have to applaud Theresa for finding the paper mentioned above. She recently published it on our Facebook page. I encourage EVERYONE to treat themselves to a careful read. This paper is one of the strongest endorsements of a pescatarian (with fasting) diet, that many of us have settled upon for protection from neurodegeneration. The mechanisms connecting gut and brain health are among the best that I've ever seen.

circular
Senior Contributor
Senior Contributor
Posts: 5072
Joined: Sun Nov 03, 2013 10:43 am

Re: Animal protein: TMAO and/or AGEs?

Postby circular » Mon Nov 11, 2019 8:12 pm

TheresaB wrote:
circular wrote:is there a general lack of consideration, in studies that link high animal protein consumption to adverse health events,
...TMAO/AGEs

Just this past weekend this paper was published Undigested Food and Gut Microbiota May Cooperate in the Pathogenesis of Neuroinflammatory Diseases: A Matter of Barriers and a Proposal on the Origin of Organ Specificity...

Thanks for that. Aren't these the concepts behind some of the Cyrex panels like 'Neurological Autoimmune Reactivity Screen - Expanded' and 'Multiple Food Immune Reactivity Screen' (oddly the latter appears to be more comprehensive than the same array '90x')?

The paper doesn't mention AGEs since it has a different legitimate focus.

It's frustrating not to have time to go deep, but I find some more interesting titles:

2015 Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients
Conclusions:
This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD [hemodialysis] patients might be ascribed partly to its inhibitory actions on AGE. [Emphasis added]

I'm not sure how the context of hemodialysis affects things here, but it's interesting that the researchers suggest that low AGEs may modify the effects of TMAO. This goes back to my point. In the studies showing independent and dose dependent relationships between high TMAO and CVD risk, have they included a cohort on a low AGE diet? At the same time, if carnitine inhibits AGE, then why are high meat diets associated with high AGEs? Maybe the cooking methods override carnitine's protective effect? Then why not in the study of HD patients? Totally confusing.
_______

These next three papers all seem to report different aspects of the same small study of 20 people. (Have I not read warnings about studies with too many endpoints?)

July 2018 (n=20?) L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women
Results:
L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers.

June 2019 (n=20) Plasma Trimethylamine-N-oxide following Cessation of L-carnitine Supplementation in Healthy Aged Women
During this period, no modifications in serum lipid profile and circulating leukocyte count were noted.

Sep 2019 (n=20) Increased Trimethylamine N-Oxide Is Not Associated with Oxidative Stress Markers in Healthy Aged Women
... there were no significant changes in serum ox-LDL, myeloperoxidase, protein carbonyls, homocysteine, and uric acid concentrations due to supplementation. Significant reduction in white blood cell counts has been observed following 24-week supplementation, but not attributable to L-carnitine. Our results in healthy aged women indicated no relation between TMAO and any determined marker of oxidative stress over the period of 24 weeks

_____

I confess that I want to think that despite the barrier/antigen issues and the TMAO/CVD risk issues, that actual individual outcomes of a diet higher in animal protein are, like everything else, context dependent. I'm not sure we can just look at the broad strokes and make assumptions about what's happening in an individual's body. The studies above suggest some markers to investigate if one is eating this way, although some probably aren't readily available and I'd like to better understand why some were chosen:

Markers of Atherosclerosis
serum C-reactive protein
interleukin-6
tumour necrosis factor-α
L-selectin
P-selectin
vascular cell adhesion molecule-1
intercellular adhesion molecule-1
lipid profile markers
leukocytes

Markers of Oxidative Stress
serum ox-LDL
myeloperoxidase
protein carbonyls
homocysteine
uric acid

At the same time, when I read that TMAO affects lipid metabolism, and knowing that ApoE4 also does, then I sure wonder about compounding issues there.

My predicament is that I am doing better eating more animal protein but also test high for serum TMAO along with chronically elevated hsCRP. The latter could be due to chronic bursitis in at least eight bursas, but apparently the contribution of this sort of tissue issue to hsCRP hasn't been studied. I've stopped betaine and choline supplementation to assess their contributions to the high TMAO.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

User avatar
SusanJ
Senior Contributor
Senior Contributor
Posts: 2801
Joined: Wed Oct 30, 2013 7:33 am
Location: Central Florida

Re: Animal protein: TMAO and/or AGEs?

Postby SusanJ » Tue Nov 12, 2019 6:51 am

circular wrote:My predicament is that I am doing better eating more animal protein but also test high for serum TMAO along with chronically elevated hsCRP.


Sarah Ballantyne agrees that it's probably related to microbiome and as she points out, fish is high in TMAO, but is generally heart healthy (see my post on that here).

The only thing that seems clear about TMAO is that gut health seems to be the key.

circular
Senior Contributor
Senior Contributor
Posts: 5072
Joined: Sun Nov 03, 2013 10:43 am

Re: Animal protein: TMAO and/or AGEs?

Postby circular » Tue Nov 12, 2019 10:00 am

SusanJ wrote:
circular wrote:My predicament is that I am doing better eating more animal protein but also test high for serum TMAO along with chronically elevated hsCRP.


Sarah Ballantyne agrees that it's probably related to microbiome and as she points out, fish is high in TMAO, but is generally heart healthy (see my post on that here).

The only thing that seems clear about TMAO is that gut health seems to be the key.

I think I see what you mean. So this thinking goes: If your microbiome is well balanced the TMAO isn't an issue? Of course to my knowledge I don't eat a diet that otherwise contributes to a messed up microbiome; ie, no processed foods, lots of veggies, fermented veggies etc. I still eat low mercury fish or seafood almost daily as one of my 'animal' protein sources, and I limit red and big game meat as well as additional AGE load. I'm working on ways to increase the nose-to-tail aspect, hating organs they way I do. As of yet, I'm not too concerned about this, but open to shifting back at some point if I can still maintain the muscle mass and sleep gains I'm slowly achieving (amidst other odds against me).

(By the way the sleep gains you might understand, since I think we both have issues with eating enough calories during the day to sustain intermittent fasting. This is even harder when I'm getting exercise and burning more calories. The additional animal protein helps keep hunger from compromising my sleep in a way that just relying on higher fat and veggie fiber keto never did very well. The sous vide sans searing is helping me make this enjoyable too!)
ApoE 3/4 > Thanks in advance for any responses made to my posts.

User avatar
SusanJ
Senior Contributor
Senior Contributor
Posts: 2801
Joined: Wed Oct 30, 2013 7:33 am
Location: Central Florida

Re: Animal protein: TMAO and/or AGEs?

Postby SusanJ » Wed Nov 13, 2019 6:30 am

circular wrote:So this thinking goes: If your microbiome is well balanced the TMAO isn't an issue?


I think it's tied up in the type of bugs you have. Her take is that archaea like Methanobrevibacter use methyl compounds like TMA and TMAO to generate methane but are also particularly important to maintaining levels of Bifidobacteria (which we all know are important to overall health), who like to hang out with archaea to better utilize glucose.

Here's her take on how to increase those bacteria:
More broadly, though, in humans, Methanobrevibacter abundance is positively associated with higher carbohydrate consumption (both recent and long-term), and negatively associated with recent consumption of fat (especially vegetable fat and polyunsaturated fat intake) and amino acids. Although more research is definitely needed, the picture getting painted so far is that archaea benefit from a variety of plant polysaccharides, and not so much from animal-based diets.

However, this isn’t because the archaea themselves eat carbohydrate. In fact, methanogenic archaea have an almost complete lack of enzymes for breaking down complex carbohydrates into simple sugars. What does appear to be happening is that archaea thrive off the metabolic products of carbohydrate-loving bacteria, and therefore are still dependent on dietary carbohydrate for their own survival!

So, for those of us who have trouble doing IF and keeping on weight without additional protein, it seems that an ultra low carb diet might be problematic because we need to make sure we have the right bugs to break down TMA and TMAO that comes with eating protein.

Last time I tracked in September, I was getting about 100-125 net carbs per day.

PeteWilliams
Contributor
Contributor
Posts: 25
Joined: Fri Jul 06, 2018 10:04 am
Location: London, England
Contact:

Re: Animal protein: TMAO and/or AGEs?

Postby PeteWilliams » Wed Nov 13, 2019 10:35 am

I am sure I just read that garlic seems to offset the TMAO from meat. Will look to see the reference.

PeteWilliams
Contributor
Contributor
Posts: 25
Joined: Fri Jul 06, 2018 10:04 am
Location: London, England
Contact:

Re: Animal protein: TMAO and/or AGEs?

Postby PeteWilliams » Wed Nov 13, 2019 10:40 am

Paper is here:
and garlic can be preventative, as can resveratrol.

circular
Senior Contributor
Senior Contributor
Posts: 5072
Joined: Sun Nov 03, 2013 10:43 am

Re: Animal protein: TMAO and/or AGEs?

Postby circular » Sat Nov 23, 2019 8:36 pm

PeteWilliams wrote:Paper is here:
and garlic can be preventative, as can resveratrol.

Sorry, I think you forgot to link the paper?
ApoE 3/4 > Thanks in advance for any responses made to my posts.


Return to “Prevention and Treatment”

Who is online

Users browsing this forum: No registered users and 12 guests