Researchers find link between common dietary fat, intestinal microbes and heart disease

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."

>> “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.” <<

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Its nonsense!

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.

Re: "supplementation with choline or TMAO promoted atherosclerosis."

"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.

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.

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.

Re: "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."

"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.

"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."

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.

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