Supplementary Choline Raises Risk Of Blood Clots; Aspirin To The Rescue

haidut

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Ray has written about the dangers of choline and its close relationship with estrogen. The histamine and acetylcholine receptors are perhaps the two main systems through which estrogen negatively affects the systemic health of the organism. As such, antihistamine and antocholinergic drugs can help block the effects of estrogen. Peat has even written separate articles on both systems and their role in disease, as well as the failure of choline and cholinergic drugs in treating brain conditions like Alzheimer and other dementias.
Now, we can add increased risk of blood clots to the list of negative effects of (excess) dietary choline. It seems that the mechanism is the same as the one for dietary carnitine raising CVD risk - i.e. increased synthesis of the substance TAMO.
Trimethylamine N-oxide - Wikipedia

It should be noted that choline and carnitine by themselves do not raise TMAO. It is gut bacteria that makes that metabolic conversion, so the role of gut bacteria in vascular health is once again very prominent and finally starting to be recognized by mainstream medicine. Be that as it may, the study found that (possibly excessive) dietary choline in the form of a supplement raised TMAO levels, and platelet aggregation in humans and a low dose aspirin reversed not only the platelet aggregation but also the increase in TMAO levels. The reduction of platelet aggregation by aspirin is not novel, it is a soidly established benefit. But the reduction in TMAO levels is a new and previously unknown benefit of aspirin, and as such it may explain at least one of the mechanism by which aspirin prevents CVD. So, for diets heavy in eggs and meat proteins, taking aspirin 2-3 times a week may be a good idea. Keeping the gut as clean of bacteria as possible should also help, and aspirin may actually be lowering TMAO levels through its antibacterial effects I posted about in the past.

Gut Microbe-Generated Trimethylamine N-Oxide From Dietary Choline Is Prothrombotic in Subjects | Circulation
Diet and gut bacteria linked with blood clots

"...Consuming too much choline, a nutrient sold in over-the-counter dietary supplements, can boost the risk for blood clots, researchers warn. That’s because bacteria in the intestines interact with choline to produce a compound that encourages platelets to clump together and form clots. Choline is found in a variety of foods including meat, eggs and milk. It’s what’s known as an essential nutrient, which means the body can’t make enough choline on its own and so it must be provided in food. But “unless prescribed by your doctor, avoid supplements with choline,” said senior study researcher Dr. Stanley L. Hazen of the Cleveland Clinic in Ohio, in a statement. Hazen and colleagues had previously shown that bacteria in the intestines interact with choline and other dietary nutrients to produce a substance called TMAO, and they linked high levels of TMAO in the blood to an increased risk of cardiovascular diseases. Also, in studies in animals, they linked higher levels of TMAO to a higher risk for blood clots. Their latest research, reported in the American Heart Association’s journal Circulation, shows that choline in food can affect blood clotting risk in humans, and in some cases, that risk can be minimized by taking low-dose aspirin."

"...Aspirin, which reduces the stickiness of platelets, reduced both the increases in TMAO and the increases in platelet clotting associated with choline, but it didn't completely eliminate them, the researchers found. The findings are of particular concern in people at high cardiovascular risk, whose increased risk of blood clots may not be overcome by low-dose aspirin. The researchers recommend further study. They also say it's worth exploring whether low-dose aspirin is beneficial in otherwise healthy people with high TMAO in the blood – although at this point, they can’t explain why the aspirin seemed to bring down TMAO levels. Dr. Herbert Tilg from Medical University Innsbruck, Austria, who has studied the link between gut microbes and blood clots, told Reuters Health by email, “This and earlier studies show that we now definitely have to consider dietary aspects in this context, i.e., diet drives thrombosis risk.” “These associations are totally new and unexpected: a link between diet - gut microbiota - and thromboembolic events,” he said. “They are extremely relevant for the public and in medicine,” given that clots are “very, very common” and can be fatal, he said."
 
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Then there is this interesting possibility that developing fatty liver requires low choline

https://chrismasterjohnphd.com/2010/11/23/sweet-truth-about-liver-and-egg-yolks/

Based a lot on this study
The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. - PubMed - NCBI

Abstract
Hepatocytes obtained from rats fed a choline-deficient diet for 3 days were cultured in a medium +/- choline (100 microM) or methionine (200 microM). We investigated how choline deficiency affected hepatic lipogenesis, apolipoprotein synthesis, and lipoprotein secretion. The mass of triacylglycerol and phosphatidylcholine secreted was increased about 3-fold and 2-fold, respectively, by the addition of either choline or methionine to the cultured cells. Similarly, a 3-fold stimulation in the secretion of [3H]triacylglycerol and [3H]phosphatidylcholine derived from [3H]oleate was observed after the addition of choline or methionine. Fractionation of secreted lipoproteins by ultracentrifugation revealed that the reduced secretion of triacylglycerol and phosphatidylcholine from choline-deficient cells was mainly due to impaired secretion of very low density lipoproteins (VLDL) (but not high density lipoproteins (HDL)). Fluorography of L-[4,5-3H]leucine-labeled lipoproteins showed a remarkable inhibition of VLDL secretion by choline deficiency. The addition of choline or methionine stimulated the synthesis of phosphatidylcholine and increased the cellular phosphatidylcholine levels to that in normal cells. While there was little effect of choline on the synthesis and amount of cellular phosphatidylethanolamine, the addition of methionine diminished cellular phosphatidylethanolamine levels. Choline deficiency did not change the rate of incorporation of L-[4,5-3H]leucine into cellular VLDL apolipoproteins, nor the rate of disappearance of radioactivity from L-[4,5-3H]leucine-labeled cellular apoB, apoE, and apoC. These results suggest that hepatic secretion of VLDL, but not HDL, requires active phosphatidylcholine biosynthesis. Secondly, the inhibitory effect of choline deficiency on VLDL secretion can be compensated by the methylation of phosphatidylethanolamine.
 
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haidut

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haidut

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Then there is this interesting possibility that developing fatty liver requires low choline

https://chrismasterjohnphd.com/2010/11/23/sweet-truth-about-liver-and-egg-yolks/

Based a lot on this study
The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. - PubMed - NCBI

Abstract
Hepatocytes obtained from rats fed a choline-deficient diet for 3 days were cultured in a medium +/- choline (100 microM) or methionine (200 microM). We investigated how choline deficiency affected hepatic lipogenesis, apolipoprotein synthesis, and lipoprotein secretion. The mass of triacylglycerol and phosphatidylcholine secreted was increased about 3-fold and 2-fold, respectively, by the addition of either choline or methionine to the cultured cells. Similarly, a 3-fold stimulation in the secretion of [3H]triacylglycerol and [3H]phosphatidylcholine derived from [3H]oleate was observed after the addition of choline or methionine. Fractionation of secreted lipoproteins by ultracentrifugation revealed that the reduced secretion of triacylglycerol and phosphatidylcholine from choline-deficient cells was mainly due to impaired secretion of very low density lipoproteins (VLDL) (but not high density lipoproteins (HDL)). Fluorography of L-[4,5-3H]leucine-labeled lipoproteins showed a remarkable inhibition of VLDL secretion by choline deficiency. The addition of choline or methionine stimulated the synthesis of phosphatidylcholine and increased the cellular phosphatidylcholine levels to that in normal cells. While there was little effect of choline on the synthesis and amount of cellular phosphatidylethanolamine, the addition of methionine diminished cellular phosphatidylethanolamine levels. Choline deficiency did not change the rate of incorporation of L-[4,5-3H]leucine into cellular VLDL apolipoproteins, nor the rate of disappearance of radioactivity from L-[4,5-3H]leucine-labeled cellular apoB, apoE, and apoC. These results suggest that hepatic secretion of VLDL, but not HDL, requires active phosphatidylcholine biosynthesis. Secondly, the inhibitory effect of choline deficiency on VLDL secretion can be compensated by the methylation of phosphatidylethanolamine.

Actually the study says that the choline deficiency is only bad when combined with methionine deficiency. Providing methionine fixed the issues.
These results suggest that hepatic secretion of VLDL, but not HDL, requires active phosphatidylcholine biosynthesis. Secondly, the inhibitory effect of choline deficiency on VLDL secretion can be compensated by the methylation of phosphatidylethanolamine.

Methionine is an essential amino acid but the dietary needs for most humans are under 200mg a day and methionine restriction below 0.3mg/kg has been shown to extend lifespan and reverse obesity, diabetes, etc. I posted those studied on the forum.
 

Dan W

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I'm too lazy to track it down while on mobile, but I think Chris Masterjohn has an article making the case that food sources of choline don't seem to raise TMAO, unlike supplemental forms. It was pretty old though, so maybe new data's available.

And if I read the study correctly, it doesn't actually support their part specifically about "choline in food [affecting] blood clotting risk."

Worth noting several authors are involved with Cleveland Heartlab. They're the sole providers (from what I could tell when researching it) of consumer-level TMAO testing. They fully disclose it though, and I don't mean that to imply it invalidates the research.
 
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haidut

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I'm too lazy to track it down while on mobile, but I think Chris Masterjohn has an article making the case that food sources of choline don't seem to raise TMAO, unlike supplemental forms. It was pretty old though, so maybe new data's available.

And if I read the study correctly, it doesn't actually support their part specifically about "choline in food [affecting] blood clotting risk."

Worth noting several authors are involved with Cleveland Heartlab. They're the sole providers (from what I could tell when researching it) of consumer-level TMAO testing. They fully disclose it though, and I don't mean that to imply it invalidates the research.

Yes, the study said they used exogenous supplementation. So, not the same as dietary choline. I will change the title to "supplementary" instead of "dietary".
 

yurt

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The study posted by Haidut used choline bitartrate at 500 mg twice daily, for a total of about 450 mg choline per day. According to the study, "platelet aggregation responses" increased significantly after one month of supplementation.

Tartaric acid (or its salts) are not suitable for ingestion in more than trace amounts either, due to their known negative effects on metabolism.
 

ddjd

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best sources of choline are beef liver and eggs then?
 

Dan W

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best sources of choline are beef liver and eggs then?
I'm starting to think the whole thing's under-researched enough that it's hard to know what to choose if you're trying to optimize against TMAO. It seems like a lot of the studies where they just throw an isolated food at people raise TMAO, but habitual intake doesn't necessarily correlate with actual levels or with cardiovascular health. See this new review if you're curious.

A few newer tidbits I've come across:
 

morgan#1

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Dan Wich,
This is a good find, it maybe the one you were looking for on Masterjohn https://chrismasterjohnphd.com/2010/11/23/sweet-truth-about-liver-and-egg-yolks/
This is very interesting to me, as I have no gallbladder and I have no “fat” accumulation, due to very ridiculous gym ideas and rigid views about self.

I don’t know if that means that I have a fatty liver. I do have high cholesterol, the hdl is higher. Just when I think I’ve got the hang of it, there’s a roadblock. I was a real gym warrior. Now I just go every other day and lift heavy, no cardio. My pulse has gone up from 60 to 72ish. I eat around 3,000 cal. (Also I have 0 appetite, unless I’m high.) I don’t know if that means I have a fast metabolism, eating that amount, or possibly that I’m not very efficient in handling my calories. Sometimes (if I’m really high and if I have time-and guts, it takes time to eat :cow:. I push up to around 4000 calories!) And my weight is stable. I do have a lot of muscles; not to brag, just saying that they need a lot of calories.

I’m just getting the hang of all of this. I’m about 500-600 carbs, ( I add 6-7 tsp of fructose) 50-90 fat, and 120ish protein. I feel like I’m getting way to many carbs. But I guess I’m my own experiment. Interesting to me, I was eating 2 eggs every morning since I’ve become introduced to all of this (about 3 months), and recently I’ve also included a hard boiled egg. So 3 eggs, phew the pufa! possibly my body needs the choline. Now, I’ve been trying to keep the pufa under 4-5. So just 1 egg. I’m mentioning this because possibly my body needs choline?

At the gym today, I was doing chest and shoulders and triceps, and I was slow, that’s what this has been doing to me. I just feel most of the time not aggressive, and nice and calm. Except when the estrogen rears it’s head, histamine sinus issues and serotonin are handcuffed to it. Used to be I was all fired up, adrenaline was rushing through me at the gym, and it carried over.

Now I think I have a problem with cortisol; I’m not tired but it is hard to wake up. I just want some Ferrari inside. Some power. Anyway, I am interested in this topic. I incessantly look for the magic pill, and then I take 2:thumbsdown:, but I’m learning.

I don’t know if my having no gallbladder is any indication to this at all. I’ve recently been taking Taurine, and I think that’s a good find for me. But I just want some get up and go with all these calories I’m taking in, I want to really seize the day. I’m just rambling. Anyway that’s an interesting article, hope you guys will enjoy :cool: I’m just getting started on all of this. I’ve made mistakes in the past 3 months, but nothing compares to the info I’ve been bombarded with by my doctors. Also, the last leptin test I got (granted it was 3 yrs ago) was in the range of a little boy. Lol
 
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morgan#1

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I think I’m gonna try Haidut’s MitoLipin.
I’ve heard that supplemental choline might be a bad idea, and blacken my moods. Maybe the cardiolipin will give me some solid energy. I imagine if Georgi’s selling it, of course it must pass the muster of Peat. Choline (definitely not a biologist) might bring up the acetylcholine, and, although it seems to be energy, I believe that Peat says that this becomes more with age.
But these are indications of someone in distress:



Hopefully, I am edging away from being in distress, ie noticing the factors of stress in my life, and not feeding them. I wonder if he feels differently for someone with different hormones available. Or possibly we are all on the cusp of the proverbial cliff.

These are sites on cardiolipin, and probably why Peat organically leans towards this way of thinking???

Fatigue, Exhaustion and Muscle Weakness - East West Healing


Coming to Terms with My Life as a Walking Aquarium

Sorry, this really had nothing to do with topic chosen, maybe you could put me in a different site...whoops.

I guess I’ll keep eating liver and eggs and I’m sure my body will find it’s way. It has with all the ***t I’ve put it through before. And I’ll get some MitoLipin. Good stuff
 

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Effects of Choline From Eggs vs. Supplements on the Generation of TMAO in Humans - Full Text View - ClinicalTrials.gov
"The investigators have also recently shown a 10-fold increase in plasma TMAO levels following supplementation with choline bitartrate supplements [to amount 450mg of sucholine a day (original post above)]. However, another pilot study by a collaborator (unpublished) did not show the same increase in plasma TMAO levels following the ingestion of whole eggs, a major dietary source of choline. Therefore, with this study the investigators wish to examine the differences, if any, between the ingestion of an equivalent mass of total choline in the free form (as bitartrate salt) as a supplement vs. within whole eggs."

It will be nice to compare if eggs fare better..
 

ddjd

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That 's why I said "possibly excessive" intake is what is pathological. Acetylcholine is an important neurotransmitter, so obviously some choline is needed.
do you think its dangerous to use a product like Alpha GPC choline daily? around 300mcg....i noticed significant cognitive improvement when i tried it
 
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haidut

haidut

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do you think its dangerous to use a product like Alpha GPC choline daily? around 300mcg....i noticed significant cognitive improvement when i tried it

I would not use supplemental choline unless it is the saturated variety. I would avoid choline in general unless it comes from dietary sources like eggs.
 

InChristAlone

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What about soy lecithin? Would that be a bad source too? People have such good effects from lipo C but that's what it uses to create liposomes.
 

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