Skip to comments.Researchers find link between common dietary fat, intestinal microbes and heart disease
Posted on 04/08/2011 1:19:41 PM PDT by decimon
How specific digestive tract microbes react to a dietary lipid increases risk of heart attack, stroke and death
A new pathway has been discovered that links a common dietary lipid and intestinal microflora with an increased risk of heart disease, according to a Cleveland Clinic study published in the latest issue of Nature.
The study shows that people who eat a diet containing a common nutrient found in animal products (such as eggs, liver and other meats, cheese and other diary products, fish, shellfish) are not predisposed to cardiovascular disease solely on their genetic make-up, but rather, how the micro-organisms that live in our digestive tracts metabolize a specific lipid -- phosphatidyl choline (also called lecithin). Lecithin and its metabolite, choline, are also found in many commercial baked goods, dietary supplements, and even children's vitamins.
The study examined clinical data from 1,875 patients who were referred for cardiac evaluation, as well as plasma samples from mice. When fed to mice, lecithin and choline were converted to a heart disease-forming product by the intestinal microbes, which promoted fatty plaque deposits to form within arteries (atherosclerosis); in humans, higher blood levels of choline and the heart disease forming microorganism products are strongly associated with increased cardiovascular disease risk.
"When two people both eat a similar diet but one gets heart disease and the other doesn't, we currently think the cardiac disease develops because of their genetic differences; but our studies show that is only a part of the equation," said Stanley Hazen, M.D., Ph.D., Staff in Lerner Research Institute's Department of Cell Biology and the Heart and Vascular Institute's Department of Cardiovascular Medicine and Section Head of Preventive Cardiology & Rehabilitation at Cleveland Clinic, and senior author of the study. "Actually, differences in gut flora metabolism of the diet from one person to another appear to have a big effect on whether one develops heart disease. Gut flora is a filter for our largest environmental exposure what we eat."
Dr. Hazen added, "Another remarkable finding is that choline a natural semi-essential vitamin when taken in excess, promoted atherosclerotic heart disease. Over the past few years we have seen a huge increase in the addition of choline into multi-vitamins - even in those marketed to our children - yet it is this same substance that our study shows the gut flora can convert into something that has a direct, negative impact on heart disease risk by forming an atherosclerosis-causing by-product."
In studies of more than 2,000 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).
"The studies identify TMAO as a blood test that can be used in subjects to see who is especially at risk for cardiac disease, and in need of more strict dietary intervention to lower their cardiac risk," Dr. Hazen said.
Healthy amounts of choline, betaine and TMAO are found in many fruits, vegetables and fish. These three metabolites are commonly marketed as direct-to-consumer supplements, supposedly offering increased brain health, weight loss and/or muscle growth.
These compounds also are commonly used as feed additives for cattle, poultry or fish because they may make muscle grow faster; whether muscle from such livestock have higher levels of these compounds remains unknown.
"Knowing that gut flora generates a pro-atherosclerotic metabolite from a common dietary lipid opens up new opportunities for improved diagnostics, prevention and treatment of heart disease," Dr. Hazen said. "These studies suggest we can intelligently design a heart healthy yogurt or other form of probiotic for preventing heart disease in the future. It also appears there is a need for considering the risk vs. benefits of some commonly used supplements."
Lecithin supplements REDUCE blood cholesterol levels.
fatty fish such as salmon and sardines also reduce blood cholesterol.
It increases levels , not decreases them.
That raises the question about whether current “probiotic” supplements and yogurt generate the bad stuff or displace the bacteria that do.
Yes, an excess of choline/lecithin being bad is how I'm seeing this.
Gotta go get more sardines. Sardines in mustard sauce! Yum! Not sarcasm.
Doesn't seem that they yet have a fix on that. I guess the message is to not overdue the lecithin/choline supplements.
I know that’s what it says. I’m saying that is opposite of conventional wisdom
lecithin SUPPLEMENTS (hello as in vitamins?) are proven to LOWER blood cholesterol.
I probably eat ten to twenty bucks worth of sardines a week. I get plain in olive oil or in water and use my own horseradish mustard on them.
This article doesn’t mention cholesterol. Maybe cholesterol levels are not a factor in this.
The working hypothesis here is that certain types of gut flora metabolizes lecithin into trimethylamine N-oxide, which in mice was associated with arterial plaque formation.
Choline and betaine are also metabolites of lecithin. “Excess” levels of serum choline “promotes” plaque formation (At tleat according to this writer).
Lecithin and choline are commonly used as feed additives for cattle, poultry and fish because they purportedly promote rapid muscle growth, but “[W]hether muscle from such livestock have higher levels of these compounds remains unknown.” Right...
Humans often use lecthin and choline as dietary supplements. How it is produced - God only knows. Can dietary supplements give you “excessive” serum choline levels promoting plaque formation - probably so is the inference I get from this article. Does lecithin as a dietary supplement keep trimethylamine N-oxide producing gut flora happy and you full of arterial plaques - seems logical to me.
Thus, “juiced up” livestock and dietary supplements may be “juicing up” gut flora that increase serum trimethylamine N-oxide and serum choline that “produce” arterial plaques. Not yet marketed probiotics, such as some type of yougurt, may change the gut flora to reduce trimethylamine N-oxide production.
Solution today: stay away from “juiced up” meat and get your vitamins (lecithin and choline) in a naturally occurring form while they are still contained in plants and animals, the less cooked the better - Quarter Pounders seven days a week will not keep you healthy and and vitamin pills ontop of that might make you worse than no vitamins at all. There is no free lunch, and that includes dietary supplements.
Excellent summary! Thanks so much.
The working hypothesis here is that certain types of gut flora metabolizes lecithin into choline and then into trimethylamine N-oxide, which in mice was associated with arterial plaque formation. Additionally, serum choline is associated with arterial plaque formation.
So lethicin and choline supplements may reduce cholesterol in some people, but those same people nevertheless remmain at risk for arterial plaques, depending upon the type of gut flora that inhabits them. Cholesterol levels are not the be all and end all to prevent plaque formation.
Specially designed yogurt may reduct the amount (good health) of the gut flora that likely is flourishing on excessive levels of artificially introduced (human or animal dietrary supplements) lecithin and choline.
where do you propose we get meat that is not “juiced up”? There’s not enough wild meat to feed all the people
Our health is quantified by insurance companies by our bloodwork and our body mass index. Therefore, regardless whether lecithin supplements increase plaque while decreasing cholesterol levels, lecithin is a benefit to our insurance rates.
I suppose next you will say cholesterol lowering drugs have no effect on plaque buildups either?
It's not the lecithin/choline that's the problem. It's the particular bugs in the gut that break it down that are. The correlation is between disease and blood concentration of TMAO(trimethylamineoxide), which is a breakdown product resulting from bug metabolism.
The inconsistent results of studies showing the effects of lecithin on cholesterol and HDL may be do to the lack of control of gut bugs in the lecithin effect studies.
If it matters to you for this particular issue, go with meats labeled “no hormones” or “no antibiotics”
or with organics
Choose wild caught fish, if you don’t care about mercury, because farmed fish have been given “feed”
Choose locally produced meats, wherever possible. Do not ever buy “factory” meats.
>>>I suppose next you will say cholesterol lowering drugs have no effect on plaque buildups either?<<<
Hey, I’m just interpreting what the article says. If you are happy with what the “consensus” about what drugs to take, that’s fine too. But I don’t believe in global warming and I remember that a consensus view put Gallileo under house arrest. Nobody has all the answers.
I'm reading this as saying it is the amount of choline determining what the gut bugs do with it.
Is there such a thing as farm raised:
Seems to me these species are not farmable.
I’d like to know which strains of gut flora are good and which are bad. Are the ones in Dannon yogurt the good ones?
Those are supposed to be some of the good ones. I've read that there are hundreds of good ones and that getting a handle on just what they all do will be quite a task. Maybe it's enough to know that replenishing the good ones helps to crowd out the bad ones.
"These studies suggest we can intelligently design a heart healthy yogurt or other form of probiotic for preventing heart disease in the future. It also appears there is a need for considering the risk vs. benefits of some commonly used supplements."
The first is that gut bugs matter, though it's hard to tell if what matters is what kind they are or how much of them you have. The second conclusion is that excessive choline and other subtances can be turned into plaque-causing compounds by gut bugs, with less emphasis on the bugs' particular kind or quantity.
Do you happen to know if yogurt contains a particular strain of gut bugs, or is it a blend? I know you can buy pro-biotic capsules. I wonder if those have a select blend of the good ones.
That might vary by brand but it's listed on the yogurt container. Wikipedia does a better job of this than I can: http://en.wikipedia.org/wiki/Probiotic
Salmon and tuna are indeed farmed. Buy wild.
Then, of course, you have the studies that show the exact opposite effect.
Maybe. Can't tell. How does that refute the dose-dependent results of this study?
Thanks, good info there. Some wikipedia pages are really good, and that is one of them.
Well, it’s not the exact opposite. But it points out the anti-inflammatory effects of serum lecithin.
It’s pretty well determined by now that the primary correlation is between CRP (C Reactive protein, an indicator of inflammation) and the formation of arteriosclerotic lesions.
Heart disease is not caused by what you do eat. It’s caused by what is missing from your diet. Linus Pauling proved that and won a Nobel prize in the process.
Slightly more than half of all people who suffer sudden cardiac dilemmas have normal or lower than normal cholesterol.
I guess I’ll stick with sardines and kipper snacks then. I really like fresh salmon and fresh tuna though.
"I'm reading this as saying it is the amount of choline determining what the gut bugs do with it."
This article is written quite poorly and no particular metabolites of choline, TMAO, or betaine that are implicitly referenced are given. The blood conc. of these molecules is only used to indicate the probability of developing CVD. Choline metabolism by gut bugs isn't determined by choline concenttration though. This article is claiming it's the type of bug that produced the bad metabolic end products. The article abstract just says the following about excess choline...
I don't know what you're arguing for or against.
"I don't know what you're arguing for or against."
I'm saying this article is junk. This article says, "...and supplementation with choline or TMAO promoted atherosclerosis.", but that's not supported by the article's abstract. The article's abstract says that without the metabolic action of the gut bugs on these substances, there is no effect on CVD by choline, TMAO, or betaine. Take a look at the quote given in the link in my last post and the link to the abstract for the article itself.
That quote I gave in post #34 is from the abstract, not the article.
From the abstract: "...and supplementation with choline or TMAO promoted atherosclerosis."
For anyone not familiar with the term macrophage, it's a type of white blood cell. It's part of the innate immune system. This diet and some gut flora elicits inflammation. Here's the abstract:
Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholinecholine, trimethylamine N-oxide (TMAO) and betainewere identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
"A certain form of phosphatidylcholine (polyunsaturated phosphatidylcholine) might provide protection against liver fibrosis and liver damage caused by drinking alcohol, although the exact mechanisms are not completely understood."
So phosphatidylcholine itself refers to a variety of molecules depending upon what fatty acids were used in its synthesis.
This is a tap dance.
This nonsense was demolished by Ottobani over a decade ago.
>> “The way I’m reading it, excess Lecithin (usually in supplements and food additives) when combined with gut flora is metabolized into an artery plaque.” <<
Lecithin is present in most nuts, seeds and legumes. Its also present in all milk before it is heated. This is more psuedo science from the masters of grant applications.
"That quote I gave in post #34 is from the abstract, not the article."
OK. Both say essentially the same thing, but in order for it to be true, gut bugs must work on the choline to produce at least TMAO. That conditional is present in both this article and the original article in Nature and it is- without the action of the gut bugs on choline, choline supplementation, or excess dietary choline has no effect on CVD.
No, it's when the bugs metabolize phosphatidylcholine, an ester, they produce TMAO, betaine and choline. Part of the metabolim is the reverse of the reaction shown below. A fair amount of the choline is used to regenerate the neurotransmiiter acetylcholine which is used in many parts of the nervous system including parts ennervating the gut.
Organic caids and alcohols make esters, as in polyesters. Phosphatidylcholine will get hydrolyzed, i.e. add water, the reverse reaction, yielding phosphatidic acid and choline in the presence of an enzyme.
"No, it's when the bugs metabolize phosphatidylcholine, an ester...
Yes. That pathway just produces choline. The original paper only worked with choline for the particular conclusion and conditional I mentioned. Here's the link to hte abstract I gave above in post #33, that includes the finding for dietary choline, which does not include any dietary phosphatidylcholine: From the Abstract: "Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis."
I agree with the others who say this is a poorly written article. It looks to me like this is all based on what happens in mice. They assume that the same happens in humans with no evidence that it does, then go on to claim all sorts of actions to be taken in human diets based on that assumption. If I’m reading this right, then that is quite a stretch.
Wild salmon is available and is labeled as such if you can trust your purveyor. “Atlantic Salmon” is farmed and usually dyed pink. The Palins caught and sold wild Alaskan salmon, the best. Enjoy.
No, not quite. The connection with supposedly "juiced up" meant was speculative. But the connection with fruit, vegetables and fish was not.
"Healthy amounts of choline, betaine and TMAO are found in many fruits, vegetables and fish."
A "healthy amount" would depend on how much was in the specific vegetable and how much you ate.
About the meat, "...whether muscle from such livestock have higher levels of these compounds remains unknown."
Avoiding the Quarter Pounders and filling up on vegetables instead may have precisely the opposite effect you intend.
That's just taking the comments here at face value, which may not be justified.