95 replies to this topic

[niner]

serum choline has nothing to do with choline intake (in healthy, presumably non-deficient people): http://www.ncbi.nlm..../pubmed/6699336

On the basis of a dietary history. DHs are notoriously unreliable, FWIW. They presumably didn't include choline supplementation or many people with unusually PC-heavy diets. Be that as it may, choline isn't the bad guy here; it's TMAO. The degree to which TMAO depends on dietary PC and/or choline intake is going to depend on a number of factors that will vary from person to person.

I agree that we shouldn't paranoiacally eliminate all choline/PC intake. At the same time, I wouldn't eat endless quantities of it.

[ChooseAName]

I find the mouse research largely ignorable, but the human data in this study shows pretty much a straight line between plasma levels of choline and CVD risk. The amount of choline in a daily dose of Vimmortal is close to the average intake. In my mind, this should be cut to a trace amount.

[kismet]

I would need the full version of this paper, can someone share? (the one w/ RRs <1)

Eur J Clin Nutr. 2008 Mar;62(3):386-94. Epub 2007 Mar 21.
Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women.
Dalmeijer GW, Olthof MR, Verhoef P, Bots ML, van der Schouw YT.

I just skimmed a few papers. So far I did not find any convincing studies for or against dietary choline intake, and none that would clearly suggest going a couple hundred milligrams lower or higher than the Adequate Intake is beneficial, so I would stick to the AI as both an AI and an approx. Upper Limit.

Edited by kismet, 10 April 2011 - 02:16 PM.

[asdf]

Christopher Masterjohn wrote an article on April 13th at westonaprice.org:

Does Dietary Choline Contribute to Heart Disease __ Mother Nature Obeyed

He finishes with the following:

Perhaps future work will in fact elucidate a role for harmful gut bacteria in increasing TMAO levels and subsequent development of heart disease, in which case the clear implication would be that we should figure out how to normalize the gut bacteria. Right now, we have no evidence that eating choline-rich animal foods increases TMAO at all, so a hypothesis dependent on this apparently fictitious process is as yet an impotent one.

Pass the liver and egg yolks please. And maybe some folks fasting for Lent may say pass the fish, shrimp or octopus. Consuming these choline-rich foods will produce much better mental health than worrying in the face of contrary evidence that they are clogging your arteries.

[rwac]

Christopher Masterjohn wrote an article on April 13th at westonaprice.org:

Does Dietary Choline Contribute to Heart Disease __ Mother Nature Obeyed

To expand, Choline Chloride, Stearate increase urinary excretion of TMA.
Additionally commercial PC (all commercial PC!) is contaminated with TMA, so excretion increases somewhat.
PC doesn't increase TMA once it's cleaned of TMA.
And Liver/Eggs don't have this effect at all.

[Sillewater]

The paper that Masterjohn cites (1) has an interesting discussion of the results. Apparently most of the dietary form of choline is not free but is in the form of lecithin (which is not easily broken down into free choline). Apparently the release of choline from lecithin is dependent on the type of bacteria found in the gut (which our new paper is discussing).

What I find interesting is that when subjects were given pure carnitine it increased TMAO however when meat was given there was no increase. Here's an excerpt from the study:

More recent studies suggest that eggs contain only small amounts of free choline (0.003% by wt), and indeed, that most of the choline we are presumed to eat is actually in the form of lecithin (Wurtman, 1979). Peanut and soyabean, foods that provide relatively large amounts of trimethylamine on alkali hydrolysis (unpublished data), also contain lecithin which, from the present investigation, is not a biological precursor of trimethylamine and its N-oxide. This is also true for meats, especially lamb (Zeisel, 1981). It has been estimated that the total daily intake of free choline is about 9 mg (Wurtman, 1979), suggesting that dietary choline is probably not a common source of urinary trimethylamine. Perhaps suprisingly, meat products which contain carnitine, a demonstrated precursor of trimethylamine when given in pure chemical form, did not elicit significant increases in total urinary trimethylamine output following their ingestion. Carnitine has a known role in lipid metabolism and as such, within the skeletal muscle, it may be in a form not readily accessible to biological degradation. Such problems highlight the importance of examining ‘whole foods’ as well as assumed chemical components.

1. Food Chem Toxicol. 1999 May;37(5):515-20.Dietary precursors of trimethylamine in man: a pilot study.Zhang AQ, Mitchell SC, Smith RL.

Edited by Michael, 14 July 2011 - 03:29 PM.
fix link

[HaloTeK]

Chris Masterjohn has done a pretty good write up on why he feels this study shouldn't concern us that much. Choline is super important, but I agree we shouldn't go overboard with it.

http://www.westonapr...-heart-disease/

I would still be a little wary of eggs though.

[ChooseAName]

That's a helpful article, but nothing in the article demonstrates that artificially sourced choline, such as choline bitartrate, is safe for consumption in supraphysiological doses. The studies he references build a case that naturally occurring choline in the form of lecithin is likely to be safe, but don't provide support for free choline like that in most supplements.

[health_nutty]

Chris Masterjohn has done a pretty good write up on why he feels this study shouldn't concern us that much. Choline is super important, but I agree we shouldn't go overboard with it.

http://www.westonapr...-heart-disease/

I would still be a little wary of eggs though.

That blog talks about pure carnitine being an issue. Would ALCAR have the same problem?

[albedo]

Have been using PPC and TMG (for homocysteine). Will likely give a break on both (also because you need TMG with (high) Folic (and B12 and B6) and you have all those disturbing news on folic and cancer risks). Comments? Can you challenge this?

[kismet]

Have been using PPC and TMG (for homocysteine). Will likely give a break on both (also because you need TMG with (high) Folic (and B12 and B6) and you have all those disturbing news on folic and cancer risks). Comments? Can you challenge this?

good choice, a lil' late though. (remember, all the hyped hcy-lowering RCTs that failed? TMG is an evidence-free supplement)

[Dorian Grey]

As all dietary choline produces trimethylamine (all of which is oxidized to TMAO), presumably this phenomenon is not isolated to phosphatidylcholine alone, though PC is certainly a rich source of choline.

What I'm wondering, is correlation of dose linear? Do lower doses create some, but fewer plaques? Or is there a tipping point where high choline/TMA/TMAO start creating plaques where normal dietary choline will not?

Is this like the NAC (N-Acetylcysteine) study, where extremely high doses caused pulmonary hypertension in rats, but normal doses do not?

As choline is an essential nutrient, we shouldn't think of choline as a bad thing...

From Wikipedia/Choline:
"Studies on a number of different populations have found that the average intake of choline was below the Adequate Intake (AI)"
The choline researcher Dr. Steven Zeisel wrote: "A recent analysis of data from NHANES 2003–2004 revealed that for [American] older children, men, women and pregnant women, mean choline intakes are far below the AI. Ten percent or fewer had usual choline intakes at or above the AI."[2]
"Choline deficiency is considered to both initiate and promote cancer activities."


So how much is too much? Do current PC and or PPC supplements cause dangerous spikes in choline, or simply provide adequate nutrition?

Should PC/PPC supplements be offered at lower doses to avoid these spikes?

Someone needs to get to the bottom of this!

[Dorian Grey]

Interesting info from a compilation of studies by K. J. Gundermann, PhD, MD on PPC (polyenylphosphatidylcholine) AKA "Essential Phospholipids" or EPL

The Essential Phospholipids as a Membrane Therapeutic
http://www.nutrasal....rary/pdfs/5.pdf

4.2.3 Antiatherogenic Effect of EPL:
"In 22 studies on 7 different animals species could be demonstrated that
diet- induced atherosclerotic changes in the aortas, arteries and coronary
vessels of the animals were largely prevented or reduced with the help of
simultaneous or curative administration of EPL"

[Mind]

Considering the huge odds ratios they saw for choline metabolites vs CVD, it looks like we're going to be re-thinking a lot of things. Like hyperlipid paleo diets, some of the supplements we take, the choline in Vimmortal, or the amount of animal products we eat

Seems like a rather rash statement, for a mouse study (natural herbivores). Every bit of evidence needs to be evaluated in context and added to the volume of research that exists. I have seen a lot of wild swings in opinions about various supplements and nutrients through the years, so much so that I have become less likely to "jump" on one result. Personally, I'm cautious on this news but still wait-n-see for future studies.

[niner]

Considering the huge odds ratios they saw for choline metabolites vs CVD, it looks like we're going to be re-thinking a lot of things. Like hyperlipid paleo diets, some of the supplements we take, the choline in Vimmortal, or the amount of animal products we eat

Seems like a rather rash statement, for a mouse study (natural herbivores). Every bit of evidence needs to be evaluated in context and added to the volume of research that exists. I have seen a lot of wild swings in opinions about various supplements and nutrients through the years, so much so that I have become less likely to "jump" on one result. Personally, I'm cautious on this news but still wait-n-see for future studies.

It wasn't just a mouse experiment- there's some pretty good human data here as well:

In studies of more than 2,000 [human] subjects altogether, blood levels of three metabolites of the dietary lipid lecithin were shown to strongly predict risk for cardiovascular disease: choline (a B-complex vitamin), trimethylamine N-oxide (TMAO, a product that requires gut flora to be produced and is derived from the choline group of the lipid) and betaine (a metabolite of choline).

Once again we find a situation where the wrong gut bacteria cause problems. I'm going to up my probiotic dose, and maybe branch out to some different species as well. I'm taking antibiotics for a sinus infection ATM, so this is doubly important.

[Dorian Grey]

I think my old standard of Low Doses of many things, and Mega Doses of nothing may be the wise choice here...

If 90% of adults don't get optimal levels of choline, and choline deficiency carries many serious risks (liver & kidney damage and higher cancer risk), we've either got to up our egg consumption (or other high choline foods) or take a low dose choline supplement.

Phosphatidylcholine provides not only choline, but phospholipids, which have remarkable properties of their own.

I think I'll stick with my one PPC/PhosChol per day. Cardiac issues when you get old are no walk in the park, but having your liver or kidneys wear out before you do, or having some doc drop the cancer bomb on you one fine day is not a good trade in my book.

I spoze a lot depends on your familial cardiac risks. None in my family.

[Dorian Grey]

Just to confuse things further...

"Choline is an essential nutrient found in foods such as eggs, is associated with a 24 percent reduced risk of breast cancer, according to a study supported by a grant from the U.S. National Institutes of Health (NIH), to be published in The FASEB Journal’s print issue in June."

"A study published in 2003 by researchers at Harvard University found that women who reported higher consumption of eggs, vegetable fat and fiber during adolescence had a smaller risk of developing breast cancer as adults. Specifically, eating one egg per day was associated with an 18 percent reduced risk of breast cancer.(5)

A study of Chinese women published in Cancer Epidemiology, Biomarkers & Prevention in 2005 showed that those who consumed the most fruit, vegetables and eggs were significantly less likely to have breast cancer. For those that reported eating at least six eggs per week, the risk of developing breast cancer was 44 percent lower than for those who ate two or less eggs per week."

http://www.molecular...cer-24-percent/

----------------------------------------

"A new study has reported that choline and betaine intake do not influence the risk of breast cancer in postmenopausal women"

"Study participants in the highest fifths of choline and betaine consumption had the same risk of breast cancer as those in the lowest fifths of intake."

http://foodforbreast...enopausal-women

[triplecrown]

I currently take a product from LEF called Cognitex basics which contains alpha- gpc and phosphtydly serine. Given this research I will probably continue to take it because I don't receive high amounts of choline from my diet (I'm not a big egg lover:))
I was thinking about randomizing supplementation somehow. What I mean is using a randomizing tool or even possibly flipping a quarter everyday ( heads I take it, tails I don't sort of thing) I know this may sound borderline crazy, but hey it
might work, right.
Any thoughts?

Edited by triplecrown, 21 April 2011 - 01:47 AM.

[niner]

I was thinking about randomizing supplementation somehow. What I mean is using a randomizing tool or even possibly flipping a quarter everyday ( heads I take it, tails I don't sort of thing) I know this may sound borderline crazy, but hey it might work, right.
Any thoughts?

Instead of a coin flip, I'd take it every other day. I suppose you could use an evolutionary argument to say that there was randomness in our diets, but that might not make randomness superior. If deficiency is clearly harmful, then setting up occasional deficiencies doesn't seem particularly useful. I suspect that we have natural reservoirs for most if not all nutrients, as a way of dealing with that dietary randomness anyway. I think the real key is avoiding a deficiency over a long timescale, as well as avoiding excess.

[Jay]

Just to confuse things further...

What's confusing? Choline, as it is found in food, does not increase serum levels of TMAO in humans. Dietarty choline also does not increase serum choline levels in humans. References for both of these statements have now been provided above. So, this research on dysbiotic CVD prone mice is just not applicable to humans period. There's no confusion. Choline also prevents and reverses non-alcoholic fatty liver disease, a precursor to the metoboic train wreck that is metabolic syndrome. As you point out, there is some evidence that choline prevents cancer too. So, it's not really confusing at all. Choline from food is healthy. As has been pointed out above, the same may not be true for choline from supplements.

[Dorian Grey]

People with Trimethylaminuria (TMAU) definitely get trimethylamine odor from choline found in food, as well as lecithin/PC. Presumably, this is all converted/oxidized in normal folks who do not have the genetic issues with TMA into TMAO.

As you note, fatty liver/metabolic syndrome is at epidemic status now days, and as 90% of people aren't getting enough choline from their diet, it would seem supplementing should be a good idea.

Choline from food or supplements should do the same thing, unless the brief spike in choline levels after taking a supplement is going to cause the damage described in the new study, and a more spread out intake of choline through diet or low dose supplements would be better.

This is what I am curious about... Is it total daily intake of choline that causes problems (which is perhaps unavoidable if you want to stay healthy), or short high spikes from supplementation, that might be smoothed out with lower dose supplements or simply switching to a high choline diet and evening out your blood choline levels that way.

[niner]

Choline, as it is found in food, does not increase serum levels of TMAO in humans. Dietarty choline also does not increase serum choline levels in humans. References for both of these statements have now been provided above. So, this research on dysbiotic CVD prone mice is just not applicable to humans period.

In the paper that started this thread, they looked at 2000 humans, and found that serum levels of choline, TMA, and TMAO correlated (strongly) with CVD. The mouse part of the paper was just a way to probe for the mechanism of the correlation seen in humans. If dietary choline doesn't increase choline levels in humans, what controls it? I doubt that many of the human subjects were supplementing choline in significant quantity. Far and away the strongest correlation to CVD was with TMAO, and that is a choline metabolite produced by certain gut bacteria, at least in mice. It's not much of a leap to suggest that humans could have the same bacteria in their gut, that different people will have different intestinal flora, and that probiotics are a way to alter the flora and reduce production of TMAO, as seen in the mouse work.

[rwac]

In the paper that started this thread, they looked at 2000 humans, and found that serum levels of choline, TMA, and TMAO correlated (strongly) with CVD. The mouse part of the paper was just a way to probe for the mechanism of the correlation seen in humans. If dietary choline doesn't increase choline levels in humans, what controls it? I doubt that many of the human subjects were supplementing choline in significant quantity. Far and away the strongest correlation to CVD was with TMAO, and that is a choline metabolite produced by certain gut bacteria, at least in mice. It's not much of a leap to suggest that humans could have the same bacteria in their gut, that different people will have different intestinal flora, and that probiotics are a way to alter the flora and reduce production of TMAO, as seen in the mouse work.

Isn't choline also needed to repair cell membranes ? Could elevated serum choline be a sign of attempted repair, similar to high Cholesterol levels ?
After all, the human body does manufacture choline...

How would we falsify this hypothesis ?

[Dorian Grey]

Choline, as it is found in food, does not increase serum levels of TMAO in humans. Dietarty choline also does not increase serum choline levels in humans. References for both of these statements have now been provided above. So, this research on dysbiotic CVD prone mice is just not applicable to humans period.

In the paper that started this thread, they looked at 2000 humans, and found that serum levels of choline, TMA, and TMAO correlated (strongly) with CVD. The mouse part of the paper was just a way to probe for the mechanism of the correlation seen in humans. If dietary choline doesn't increase choline levels in humans, what controls it? I doubt that many of the human subjects were supplementing choline in significant quantity. Far and away the strongest correlation to CVD was with TMAO, and that is a choline metabolite produced by certain gut bacteria, at least in mice. It's not much of a leap to suggest that humans could have the same bacteria in their gut, that different people will have different intestinal flora, and that probiotics are a way to alter the flora and reduce production of TMAO, as seen in the mouse work.

So we would need to know what bacteria generates the TMA (which always gets oxidized to TMAO) and which probiotic might supress this bacteria. I assume it is possible the wrong probiotic could make things worse!

[Jay]

As you note, fatty liver/metabolic syndrome is at epidemic status now days, and as 90% of people aren't getting enough choline from their diet, it would seem supplementing should be a good idea.

Choline from food or supplements should do the same thing, unless the brief spike in choline levels after taking a supplement is going to cause the damage described in the new study, and a more spread out intake of choline through diet or low dose supplements would be better

Nope. You (and several others, it seems) have to read the article by Chris Masterjohn referenced above. There may well be a difference between dietary choline and supplemental choline, at least some forms of it.

Edited by Jay, 21 April 2011 - 04:25 PM.

[Jay]

In the paper that started this thread, they looked at 2000 humans, and found that serum levels of choline, TMA, and TMAO correlated (strongly) with CVD. The mouse part of the paper was just a way to probe for the mechanism of the correlation seen in humans. If dietary choline doesn't increase choline levels in humans, what controls it? I doubt that many of the human subjects were supplementing choline in significant quantity. Far and away the strongest correlation to CVD was with TMAO, and that is a choline metabolite produced by certain gut bacteria, at least in mice. It's not much of a leap to suggest that humans could have the same bacteria in their gut, that different people will have different intestinal flora, and that probiotics are a way to alter the flora and reduce production of TMAO, as seen in the mouse work.

Agreed, serum levels of TMAO and choline in humans may indeed correlate with CVD. However, those same serum levels do NOT correlate with dietary (i.e., from food) intake of choline or betaine.

So, what controls serum choline and TMAO levels? Dunno. But I would guess it's the liver and that people with high serum levels of TMAO and choline probably have damaged livers - maybe even NAFLD (which is cured by dietary choline - go figure).

[Mind]

It wasn't just a mouse experiment- there's some pretty good human data here as well:

Thanks for the clarification niner. Still, there are many reasons why someone might supplement with choline and it is an essential nutrient so I am not going to toss it out over one study. CVD is a multi-factorial disease and I wonder if other lifestyle and diet factors would overwhelm anything negative from exogenous choline.

[Dorian Grey]

As you note, fatty liver/metabolic syndrome is at epidemic status now days, and as 90% of people aren't getting enough choline from their diet, it would seem supplementing should be a good idea.

Choline from food or supplements should do the same thing, unless the brief spike in choline levels after taking a supplement is going to cause the damage described in the new study, and a more spread out intake of choline through diet or low dose supplements would be better

Nope. You (and several others, it seems) have to read the article by Chris Masterjohn referenced above. There may well be a difference between dietary choline and supplemental choline, at least some forms of it.

Found the Masterjohn article on page 2 ( http://www.westonapr...-heart-disease/ )... It seems to indicate "choline lecithin" (AKA phosphatidylcholine) is as safe as dietary choline. From his charts it appears only choline chloride and choline stearate generate high spikes in TMA which would be oxidized to TMAO.

I feel better now. Many thanks for your help with this Jay!

[Soma]

probiotics are a way to alter the flora and reduce production of TMAO

Do we know what particular species are able to achieve this?

[nameless]

probiotics are a way to alter the flora and reduce production of TMAO

Do we know what particular species are able to achieve this?

Without knowing which species reduces TMAO I'd expect there is no way to know if probiotics would help or hurt the situation.

Maybe one could look at population data, and see if there is any correlation between heart disease (pro or con) and probiotic-types of foods (Kefir, etc.)? And then figure out what species are in that particular food.

But even that probably would be iffy data, as you'd have to rule out a lot of other factors too.

Edited by nameless, 23 April 2011 - 05:52 PM.