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Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

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April 10 2013

Does Red Meat Clog Your Arteries After All?

By Mark Sisson
155 Comments

T-boneI’ve been asked to comment on the latest media deluge to suggest that red meat is again the primary cause of atherosclerosis, heart disease, and your impending doom. At least this time they’re targeting something other than cholesterol: this time it’s carnitine.

Carnitine is found in red meat, mostly, as well as dairy, tempeh, and some other meats, and it performs a number of important roles in the human body, foremost of which is the transportation of fatty acids into the mitochondria for breakdown into useable energy. It’s so important to basic function that we make endogenous carnitine by synthesizing it from the amino acids lysine and methionine. Vegans and vegetarians, who tend to run deficient in carnitine, benefit greatly from supplementation (or a nice steak). It’s even been used to reduce atherosclerosis (albeit in rabbits), improve arterial function, and help heart failure patients recover. Carnitine is not some evil compound.

Oh, the study. Let’s get into it. It consisted of several sections, actually.

First, they fed humans eight ounce steaks (amounting to roughly 180 mg carnitine) with a side of 250 mg carnitine tabs. Omnivores showed increased blood and urine levels of Trimethylamine oxide (TMAO), a compound associated with cardiovascular disease, while vegetarians and vegans (who were somehow able to get the steak down) showed far lower levels of TMAO in their blood and urine.

Next, they tested what was producing the TMAO by administering antibiotics. Eliminating gut flora populations with antibiotics also eliminated the food-induced increase in TMAO, showing that the intestinal microbiota were metabolizing carnitine into TMAO. After allowing the subjects’ guts to repopulate, they ate more steak. The increase in TMAO after eating steak reappeared, confirming that gut flora metabolism of carnitine was responsible. Subjects with higher levels of Prevotella bacteria in their guts saw the biggest increases in TMAO.

(As it turns out, gut flora convert carnitine to TMA, which the liver then converts to TMAO using a hepatic enzyme called FMO3, but it’s easier to just say carnitine converts to TMAO.)

They also tested ApoE-deficient mice and got similar results. Feeding mice carnitine increased TMAO levels in serum and doubled arterial plaque formation over control, while giving antibiotics abolished this effect. So, in a certain strain of mice, dietary carnitine increases TMAO levels, which accelerates atherosclerosis. If you recall from this week’s Dear Mark, ApoE status is strongly associated with cardiovascular disease risk, and these mice were totally deficient in it. They were bred to be extremely sensitive to atherosclerosis in order to facilitate research. It’s a common and useful tool – it’s not like they’re trying to pull a fast one – but we should be aware of it.

They also examined how TMAO increases atherosclerosis in mice: by reducing reverse cholesterol transport. In other words, it impaired the mouse’s ability to remove cholesterol from the arterial wall without decreasing cholesterol uptake or synthesis to the same degree, creating a net surplus of cholesterol in the wall and speeding up atherosclerosis.

Now, before you unplug your chest freezer full of grass-fed beef and start buying wheat futures, keep reading.

The initial association between TMAO and cardiovascular disease in humans is just that – an association. Causation is not established, and it may even be that cardiovascular disease or some other common event increases TMAO as a response to injury or disease. An increase in serum TMAO is, for example, a marker of certain kidney injuries (PDF). It could merely be correlation or even reverse causation. We simply don’t know.

We don’t know if the experimental results in rodents apply to humans. Sure, the omnivorous people who ate steak and took supplements saw an increase in serum TMAO, but atherosclerosis was not measured. The same mechanisms that affect ApoE-deficient mice may not apply to humans.

It was the gut flora, not the carnitine. While subjects who typically ate meat saw the biggest increases in TMAO – which the researchers saw as evidence of the gut flora adapting to the host diet – and were characterized as having Prevotella-dominant guts, most evidence suggests that Prevotella bacteria are associated with carbohydrate-rich diets. That said, accumulating evidence suggests that the hundreds of species living in our guts can’t be quite so easily and neatly cataloged or categorized.

You know what else raises TMAO? Fish. That’s right – heart attack-inducing, artery-clogging, linked-to-every-disease-state-known-to-man fish actually contains TMA, the metabolite that converts to TMAO in the body. TMA is what gives fish the “fishy smell,” and when people eat fish, urine TMAO increases. Strangely, the latest research shows that fish is consistently associated with better cardiovascular health, not worse (despite the TMA content and effect on TMAO levels).

FMO3, which as you’ll recall from the parenthetical above is responsible for the conversion of TMA to TMAO, does things other than produce heart disease. It is also involved in the metabolism of selenium (an important cardioprotective, thyroid-protective, and cancer-protective nutrient).

TMAO itself may not be “all bad.” It’s an osmolyte – a protein stabilizer. It’s even been used to prevent cataract formation in mammalian eye lenses.

Choline, another important nutrient found in eggs, meat, dairy, and offal with a similar structure to carnitine, was shown a couple years ago to convert to TMAO after exposure to certain types of gut flora, causing researchers to suggest it too promotes atherosclerosis (see Chris Masterjohn’s take on it). And yet eggs have been vindicated over and over again for their beneficial or neutral effects on heart health, including the most recent one I mentioned this past Sunday.

It’s complicated, in other words.

That’s not to discredit the results of this latest study; sufficient amounts of TMAO do appear to accelerate atherosclerosis in rodents. Impaired reverse cholesterol transport, which TMAO produces (again, in rodents), probably accelerates atherosclerosis regardless of species, all else being equal. We should definitely keep an eye on this and any other future research. I’m particularly interested in what this means for research into the effects of gut flora on human health.

Ultimately, this admittedly interesting research is all very preliminary. Rodents bred to be especially sensitive to cardiovascular disease (ApoE-knockouts) develop atherosclerosis at twice the normal rate when exposed to TMAO in the diet and/or serum. That’s all that they’ve established. Humans with the right (wrong?) gut flora composition also generate serum TMAO in response to dietary carnitine, but increased atherosclerosis has not been shown. And, contrary to their assumptions, a relationship between red meat (not processed meat) and cardiovascular disease has not been established in the literature. Quite the contrary: recent epidemiological evidence seems to exonerate the fresher, redder stuff.

If anything, this serves to underline (not undermine) the basic gist of the Primal eating philosophy. Eat a variety of foods. Don’t just eat steak. Eat fish, and eggs, and chicken liver, and pork chops. Don’t just eat meat. Eat vegetables. Eat probiotic-rich foods (probiotics have already been used to lower TMAO levels, while kimchi consumption was said to account for the inter-individual differences in TMAO production in another study). Eat prebiotic-rich foods, so as to provide food for your gut and diversify the population.

That last bit is key. We have to realize that it’s the gut flora modulating the effects of carnitine and TMAO – not the carnitine (or red meat) itself. It may be that we Primal eaters (as if you could categorize us so easily) have the absolute worst kind of gut flora, the kind that produces TMA by the truckload to be carted off to the liver for conversion into TMAO, and we’re about to start dropping off like flies. But I doubt it. I think the way we eat is more likely to diversify our guts and give us a floral profile associated with better health, rather than worse. But we’ll see. We still have a lot to learn about what lurks – and lives – inside us.

I’m sure you’ll be inundated with other writers giving their thoughts today and in the near future, but these are my initial ones. Hope it helps!

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155 thoughts on “Does Red Meat Clog Your Arteries After All?”

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  1. So… I should be supplementing with daily antibiotics to lower my dangerous TMAO levels? Seems legit.

    1. Yep…time to replace your daily probiotic with a daily antibiotic! Imagine what they could do for the Pharmaceutical Industry!

    2. IV pennicilin, here I come! hahah…. Who would volunteer to wipe out their gut flora, that’s what I’m wondering. There had better be lifetime compensation involved.

  2. I currently supplement Acetyl L-Carnetine, so now I am wondering if I there is any cause for concern. Is there any reason to believe that I could be causing myself harm?

    1. It depends on how much Acetyl L-Carnitine you are taking and for how long. I usually don’t take it for much longer than 10 days at a time, in order to help reduce excess bodyfat prior to competition.

      Too much and it seems to dry out my muscles.

    2. I would assume that if you’re eating meat and seafood on a regular basis, than the carnitine supplement isn’t necessary.

      I think this falls in line again with the “get your nutrients from whole food sources” mindset since supplementation is often at levels beyond what we’d naturally get from a food source.

    1. Why would you laugh at the study? It is what it is. The media may have interpreted it in whatever fashion it chose to do, but I doubt you’re qualified to “LMAO” at the study.

      1. +1 Do most people actually bother to read Mark’s posts before firing off broadsides? Mark certainly did not LHAO at the study.

        1. Yes Harry, on here I doubt anyone is actually reading Mark’s post on it, (tongue planted firmly in cheek).

      2. T. Colin Campbell. China Study.

        Just because someone’s “qualified” doesn’t mean they’re right.

        Though it might be more appropriate to LAAO (laugh anyone’s ass off) at the study *conclusion.* That’s pure opinion, not pure data.

  3. These “studies” that continue to vilify red meat, fat, & cholesterol are getting out of control. Once again, data that shows association, not causation.

    1. Right. Red meat is what eggs were a few years ago. Most such studies are flawed for one reason or another and shouldn’t be blindly taken as gospel. If researchers want to legitimately demonize something, why aren’t they taking a closer look at sugars and grains? Why are those always such a sacred cow?

      1. It is just big Pharma and Agra trying to secure their future. There are more people waking up to the truth about sugars and grains every year. It is their life blood, they cannot afford to loose it.

  4. Every scientific research study that concerns red meat should be required to classify the source of their meat. Grass/grain/GMO fed is a variable known to make a difference in the scientific community.

    These studies just seem to be getting more ridiculous, as if they are digging for new reasons to stop people from eating meat…

    1. +1

      It seems as if their aim is to vilify meat, red meat in particular.

      1. Grass fed, grass fed, grass fed…once and for all. Can we please get studies that demarcate between the crap and the good stuff? We intuitively know that there is a difference!

        1. Agreed!
          This is how I feel about studies vilifying hormone replacement therapy ( when appropriate) that do not differentiate between bioidentical hormones and such shite as Premarin. Progestin is NOT progesterone! Etc.

      2. Lets be clear,

        Their aim is to get results that help them get more funding for further research.

    2. Except that the researchers trying to vilify meat don’t care what kind of meat it is – they don’t want us eating any.

  5. Also, do we know who funded this study? Who are the key players behind this and what are their affiliations? Not that it isn’t already dubious enough on its own, of course.

    1. This paper made it into a high-impact (Nature) journal because it is a rigorous big study on a topic that has a lot of public health interest and relevance. We do, in fact, know who funded the work. You can look at the link above; it was published in Nature Medicine. Most of the contributing authors are at legitimate major research centers (The Cleveland Clinic, UCLA, etc). The funding is primarily from federal (NIH) grants, some from the American Heart Association. You can actually ready the paper yourself if you wish.
      This is not a BAD study. The authors do not say that eating red meat will give you heart disease. The authors say what Mark said, that mice have this reaction, and that gut microbiota are important, and that carnitine supplementation should be looked at more closely, and that more work is needed.
      The MEDIA say that red meat will kill you. Scientists (disclosure: I am one, though I don’t work on this stuff) just tell you what the data are, and these authors were very thorough in describing the work they did and the methods they used. Metabolism is really complicated, as are the causes of complex disease like heart disease, and it’s impossible to design a perfect study using enough humans to get meaningful results. So I guess I’m defending the researchers; they did a pretty good job working with all the variables.
      It’s never clear that results of studies in which the subjects ate the SAD will apply to Team Grok. I’d love to see some long-term data on the health of the paleo/primal cohort, but those data just don’t exist. No single research study should be the basis for your diet or dietary changes. Knowledge accumulates over a long time, so it’s important to look at the whole picture rather than individual pixels.

      1. Come on anabelle, legitimate research centers? They can’t even use real meat that’s grass fed! Just more conventional wisdom poppycock!

        1. Whether you’re eating grass-fed or grain-fed beef, you’re stilling ingesting the same amount of carnitine. And really, since the majority of America eats grain-fed beef, it really makes more sense if they did in fact use grain-fed beef in the studies. And it would also make more sense for readers to then worry about their consumption of beef. If you eat only grass-fed beef and you believe this study does not apply to grass-fed beef, then you have nothing to worry about.

        2. What I meant by “legitimate research centers” is that this study was performed by actual scientists rather than researchers at the “Vegan Center Performing Studies To Stop People From Eating Animals.” (which I made up. I hope that doesn’t exist)

        3. I eat CAFO meat fat, thank you. Someone broke down the fatty acid composition, I think it might have been Kresser, and the biggest difference between CAFO and grass-fed meat is the CAFO has lost its omega-3. You can make that up by eating whole fish, or using cod liver oil.

          One of the selling points of grass-fed meat is its leanness, because we kill our ruminant animals too young now for maximum profits, and instead of letting the cattle get older before slaughter, they kill them at the same age the CAFO-finishing ranchers do. The grain-finishing, in fact, was supposed to make up for the lack of age.

          A hunter-gatherer nearly always favors a fatty animal over a lean one. Good luck adding extra ruminant fat to make up for the lack of it in your meat cuts. It’s expensive and eventually, if everyone wises up about this, and until practices change, there will not be enough to go around, particularly among the dairy-sensitive, which is a heck of a lot of people.

      2. Clearly your wisdom is lost on most of the people here who are obviously highly qualified to make judgments on the validity of the research. Don’t forget, it’s acceptable in modern times to view science in a manner identical to religion. It’s belief based… (i.e. I don’t “believe” in global warming and my “belief” is just as valid as scientific research).

      3. +1 I said something similar. Honestly people, most of the time it’s not the researchers being the pricks, it’s how it’s being reported which is an entirely different problem.

      4. Well done Annabelle. Two types on here…1) they type to objectively consider new information…2) “defenders” who drank the kool-aid and lost their objectivity. Everything isn’t black and white and there will much more to this story, be patient and follow along objectively, and don’t…jump…to conclusions (although it would make a cool mat).

        1. I think the Kool-aid may be what you are drinking. What do you think when you see red meat? How broad a statement can you get? Where did the red meat come from? What was it fed? I hope they do keep up all the research, the more legitimate the better,but when the testers use terms like red meat…they already lose me.

      5. There is plenty of obvious bias in this article, Annabelle. The title alone shows bias. L-carnitine, available in many foods, and gut flora are the focal points of this study, but the title of it singles out red meat.
        The obvious bias of the researchers shows in the last sentence of the abstract: “Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.”
        What “well-established” link?
        The only place I know of that this “well established link” exists is in the well-debunked book “The China Study” by T. Colin Campbell, also well known as a “Vegan Bible”. Mark has debunked it with the help of blogger and MDA contributor Denise Minger (Raw Food SOS).

        1. SAD gut may be different from Primal gut, Nocona, let it play out, you may get what you want in the end. These are some pretty bright people working on this, and there’s always more to do.

        2. They chose this project to study red meat.
          If you read the first paragraph of the introduction, you will see that they were trying to suss out why red meat has been associated with CVD (and you can see their citations for that information), as previous work has shown that the fat and cholesterol are maybe not the cause (citations for that, too), which surprised the world of CW (not us) and has therefore launched further research.
          The title singles out red meat because the broad question is about red meat, although the specific finding is about carnitine + microbiome.
          It is not perfect, but it is rigorous research. Science builds off of previously published work, so all work is somewhat biased because is framed in the context of what is generally considered to be true (in this case, CW).

          Would I rather see work on the effects of grass-fed beef on the grain-free gut? You betcha.

        3. Seriously. If red meat made people sicker than grain does, I shouldn’t have started feeling better when I cut back the grain and ate more of the meat. If these “everybody knows” statements they trot out were in any way valid, there shouldn’t be any exceptions to the rule on the scale of normal variation. They say “red meat increases CVD risk” the way they would say “liquid cyanide above X quantity is always a poison to humans” or “you die in X number of minutes without oxygen”. The two statements are not even on the same *planet* in terms of meaning.

      6. Actually, if you read the interview in NYT by the lead researcher, he directly says he loves meat, but that he is dropping his personal consumption based on this work (his own), because it is SO absolute. 🙂 So they do assume meat is bad for you in public related to the study.

      7. I don’t find the American Heart Association a good source for science. Any study that hits the mass media is going to be misinformation, we’ve seen that time and time again. When are we going to stop allowing these people to cloud our minds? Long term data solidifying primal/paleo… try hundres of thousand (probably even millions, see book “Hidden History of the Human Race”) of years of existence. Not to mention grass fed was never even addressed.

        Reminds me of the Monsanto study on their rats… Monsanto conveniently stopped their findings at 3 months, and an independent study found that all the detrimental health benefits occured at 4 months (kindney failiure, massive tumors)

        This garbage science needs to stop.

      8. There has been studies of epigenetics. A diet change can change how our genes are expressed(turned on or off). It does the same to the bacteria in our bodies. They change /adapt rapidly to a diet change as well. Bacteria are literally a part of our mitochondria, and serious consequences occur if they are killed off. A diet change can be beneficial to a person, and the bacteria adapt to help the person in a different way. E Coli deprived of sugar will adapt to a stain that ferments glutamate(handy if too much glutamate in the brain). If a diet is really bad, the bacteria change as well, and whether they are able to adapt to help us, or adapt to harm us, we are still trying to figure that out.

        I am a science geek, but never worked as a scientist, and never went to college, although I took all those college prep biology 1, 2 and chemistry. I won a Bausch & Lomb Honorary Science award medal back in 1970. Now it is more of a hobby, applying our diet to my understanding of how my body works, and what the diet can do to improve my health. If there are any risks associated with this diet, they should be minor, compared to using drugs to fight disease, as they can be a much too potent a change to our mitochondria, and our epigenetics.

        http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1001380

        http://microbewiki.kenyon.edu/index.php/Escherichia_coli_O157:H7

        http://aac.asm.org/content/early/2012/05/15/AAC.00678-12.abstract

        Epigenetics helps explain how our Paleo diet changes our bodies so strikingly. .

        http://www.palgrave-journals.com/biosoc/journal/v6/n2/full/biosoc20111a.html

        http://www.cdc.gov/pcd/issues/2009/jul/09_0011.htm

        There are studies done on animals, and how the grains, and other food affects the bacteria inside the animal.

        http://openagricola.nal.usda.gov/Record/IND85036414

        Any comments appreciated.

    2. It behooves us to differentiate between bad science, and bad science reporting. The study seems pretty solid. It’s not making any connections that aren’t there, and is useful for ideas for other research. It’s how it’s being touted in the newspapers that’s the problem, and it’s a recurring one. Half the studies used to demonize meat aren’t actually saying that, and the researchers can get pretty pissy about how their work gets misused, justifiably so.
      We look at the study, see what it actually says. Sometimes the researchers are pushing an agenda, sometimes they’re not. This time, they’re really not. It’s interesting information, once you look past the hype. There’s a type of bacteria in our gut that takes this nutrient and turns it into something that’s correlated to heart disease, and killing it stops that. It doesn’t take a biochemist to figure out the problem’s not the meat, it’s the bacteria, assuming there’s a problem at all, which we’re not certain of, and that’s all the *study* is saying. Don’t get so annoyed you get biased the other way. The researchers are mostly sane, though it would be nice if they’d started considering what the meat ate in their notions, though it also makes sense to use what the general population eats in a study like this looking for ideas of questions to ask later. It’s the reporters we need to ride the butts of.

      1. EXCEPT in the title of their study……why point out the connection to red meat, when l-carnitine is in so many other foods?

  6. Just curious… under ‘red meat’ does the study mean only beef? Or would it also include other red meats, like lamb, buffalo, venison, etc.?

  7. Breathing oxygen causes heart disease! Oxidative stress leads to damage of the endothelium, which leads to atheroma, and then to heart disease, therefore OXYGEN is the cause of heart disease! So all we need to do is stop breathing and then we won’t die of heart disease (just asphyxiation.)

    1. Hmm… Could it be that we were not (gasp!) meant to live forever?

  8. My main issue with this study would be the supplementation of the carnitine tablets. That introduces a variable to the study right there. No human is ingesting tablets of the stuff, we get it from food. The study should have been done solely with the meat to test levels. But that would require people to consume ~1.25 lbs of red meat and if the meat was consumed in a single sitting would make the study damn near impossible.

      1. Yes they do, but do they also eat red meat every day? Probably some do both, but at the price of halfway decent red meat, I would guess that most of us don’t.

        I agree with the others who thought the study would have more credibility if they had omitted the carnitine supplements. As it is, it looks more like they were just try to beef up their case (no pun intended) against red meat.

      2. Are the supplements the same type as the compound found in the meat? Genuine question since I don’t know about carnitine but iron in meat for example can have a different molecular composition than an iron supplement. If they are the same, does the body process them the same? Since the meat has other compounds that may hinder/help the body to utilize the carnitine. Questions like this are usually why I’m skeptical of nutritional science. Scientific studies strive to eliminate all variables other than the one being testing but to do so with food, you have to eliminate the other elements of the food that we would otherwise eat along with it. Which would then introduce variables to the study.

        1. Same for choline. Supplemental choline increases TMAO; choline from lecithin (which you find in egg yolk and probably liver) does not. As Chris Masterjohn pointed out.

        2. Does anybody know if the carnitine profile is different with CAFO and Grass Fed beef? It may be the same amount of carnitine, but what of the molecular composition?

  9. Once again Mark, your pragmatic approach (as opposed to the knee-jerk, gloom and doom of traditional media) is refreshing and very much appreciated.

  10. I’m still having my Fish Tacos with Citrus Dressing tonight.

  11. Carnitine supplements are readily available at health food stores and in energy drinks. The study looked at multiple facets of carnitine metabolism in multiple species. Although it was not a human intervention using cardiovascular disease/atherogenesis as an outcome, it is a strong study. It would be a shame to dismiss it without looking into it as many here are doing.

    The lead author of the study was quoted in the mainstream write ups as being a lover of a good steak. I don’t think he was setting out to condemn meat consumption. Analysis of a study should be done first and foremost on the study itself.

  12. How many ‘Fred Flintstones’ dropped dead at the Bedrock Quarry from clogged arteries? I’m thinking not many.

    According to this study, Mr. Slate would have been out of business long ago.

  13. It is hard to come to the conclusion they did about red meat when they made them supplement the carnitine. If they had just eaten the meat, maybe. To me, it seems they forced them to eat more carnitine than one would usually get in any meal.

  14. So the things that increase TMAO:

    Carbohydrates, red meat, choline (eggs, meat, dairy, and offal).

    Clearly there is a “mediator” variable accounting for this. The primary problem I see with these studies is that they compare “health conscious vegetarians” against any old person that also eats meat (smokers, dunkin donought aficionados, carbaholics and maybe a few primal “outliers” they likely removed from analysis). There is 0% effort to compare “health conscious vegetarians” against “health conscious fat/meat eaters”, until this is done I’m going to continue to assume that “process carbs are bad and make ANY diet worse”.

    Until researchers (like me) control for their sample populations and remove their bias against ANYONE who eats fat/meat, there is no relevant study. I DO knock this study, I knock it hard.

  15. Just another time wasting smoke screen by big agra, the government and the vegans. It’s time they learn we no longer listen to their agenda driven BS. We listen to commonsense and our bodies (how we look feel and perform).

  16. “It’s complicated”

    Reading that sums it up pretty well… It’s amazing how we take isolated ideas/studies (which are cool that we do them) and attempt to make such broad assumptions in something as complex as the human body/experience.

    It never fails to amaze me.

  17. A good response to the media misinterpretations of an otherwise interesting but not Earth-shattering research paper. It’s too bad many studies are blown out of proportion and publicised by journalists who don’t understand the basic aims of the study they are reporting on, let alone the conclusions.

    Thank you Mark for taking a more level-headed look at it. (And for breaking down the trickier sciencese for the rest of us :D)

  18. What about all those animal studies suggesting that supplements combining l-carnitine with alpha lipoic acid reduce age-related damage?

  19. the thin red line – red meat is bad
    maybe the study is fine but they just accumulate “material” against red meat
    all they do is scare people until we stop eating altogether

  20. Another really good example of why you have to read and understand the study and not just the headline.

  21. And with that, I am off to eat a burger – lol!

    Thank you Mark for clarifying everything. Honestly though, considering how long I have enjoyed grass-fed red meat and how healthy I feel, I don’t feel like any study is going to make me stop eating it!

  22. The carnitine supplementation was necessary so they could identify that it was the carnitine being metabolized into TMAO. Theoretically, there should be no difference in the TMAO levels resulting from Grass fed vs. conventionally raised beef, or any other red meat. It could, perhaps, even be higher in elk, venison, etc. due to higher metabolic demands of active tissue (increased carnitine). Red meat makes up the majority of Carnitine consumption for pretty much everyone. Dismissing good research will do more to push your views to the fringe than anything else. Great points above, Mark, and thanks for not dismissing this!

    1. It may all have to do with the gut flora in the end. Hope they do better syudies in the future. I like your ideas on elk, venison, etc. maybe having higher carnitine levels and what that might mean. Why would you theoretically say there should be no TMAO difference in grass fed vs. conventionally raised beef? I would think the whole profile would be different. Feed on GMO corn and soy, or grass fed and finished like they were meant to eat, and I know which one I would choose.

      1. I know which one I choose as well. And we can probably modify our heart disease risk based on the types of fats we are consuming (omega-3/6 balance) But in this study we are looking at a nutrient, L-Carnitine, which is necessary for muscle function. Both grass fed beef and conventionally raised beef need muscle function. There is little to none TMAO in either type of beef. Just the ‘pre-cursor’ which is turned into TMAO in the presence of certain intestinal bacteria.

        I don’t see any reason why grass-fed would have less of the L-carnitine which allows their muscle’s to function.

      2. Probably because the carnitine is the same regardless of what the cows ate.

      3. The primary difference between grass-fed and conventionally fed beef is in the ratio of fatty acids (e.g., more omega-3 fats in grass fed beef) and increased levels of some of the vitamins associated with grass (beta-carotene, vitamin E, volatile fat-soluble compounds that contribute to flavor, etc.). Carnitine does not fall into this category, but rather is synthesized from amino acids lysine and methionine. Carnitine is required for very very important metabolic processes, and because it is both acquired through diet and biocynthesized, I would heavily suspect that levels are the same intra-species. Nevertheless, I cannot be sure that there is no difference between grass-fed and conventional, because it has not been conclusively demonstrated to my knowledge.

        Another reason they probably did not control for grass-feeding is because so few people consume grass-fed beef compared to conventional red meat. If you are trying to answer PUBLIC HEALTH questions, then you want to study what will be most relevant to public health, and in the United States that is consuming conventional beef. Why would the researchers studying this particular topic go through the money and the hassle to satisfy the theoretical qualms of a relatively small (from a public health perspective) group of health-minded paleo advocates?

        I would urge everyone to please see the perspective of the scientists before you attack them. It’s not like they jumped on the cholesterol and saturated fat bandwagon. They considered the gut flora, which is very new and cutting edge research, and one of the newer fields of interest to those in the Paleo community, too!!

        There are many good reasons to eat grass-fed, but avoiding dietary carnitine is not one of them. This is a fantastic and well-controlled study, and just as fantastic is Mark’s tempered and reasoned treatment thereof. When some individuals attempt to disregard or debunk science on a reflexive basis as I see in some of the comments, we delve into the fringe, into pseudoscience, and into the land of unfalsifiability, which is antithetical to the principles of our Paleo and Primal movement.

        1. Well said. It doesn’t do anyone any good to simply become parroting apostles without understanding the reasons for choosing to eat or live a certain way.

          Even the tried-and-true “I feel better so I must be doing the right thing” should be questioned. Things like high blood pressure and atherosclerosis can’t be “felt.” Whether red meat causes heart disease or not, it’s at least a good idea to attempt to understand metabolic processes.

          Think about this: we’re one of only a handful of countries in the world where beef is a primary protein source. We’ve also perfected factory-based agriculture to the point where the vast majority of beef consumed is a factory product, not a natural food. This has happened in large part because of government subsidization and protectionist laws that allow big ag to flourish. Why would there be any kind of conspiracy, government or otherwise, that would poke holes in this very profitable system? And if the vegans really are behind it, we should thank them because none of us really want these grotesque and inhuman farming practices to continue either.

          Much of the rest of the world relies on a much wider variety of proteins than we do here in America. Sheep, goats, pigs, chickens (and other domesticated fowl like turkeys guinea hens, squab, quail), rabbits, game meats, ostrich, etc. The list goes on and on. And in many cases, these alternate meat sources are raised naturally on the food they are meant to eat because they come from small farms where it’s probably the cheapest and easiest way to raise them. Maybe we do eat too much beef. Maybe there are consequences. Just a thought.

  23. I’m relieved to hear your comments, Mark. But lots of people do take carnitine supplements. My ten year-old, for example, has been taking carnitine for the last seven years and we were told he would need it for the rest of his life. He has a mitochondrial disorder, and needs the carnitine supplement to help his processing of fatty acids. I am concerned about this study. The field of genetic medicine and those who specialize in metabolic disorders are scrambling now to reevaluate the children taking carnitine long term.

  24. The fact that the same people that have said for the last 60 years that sat fat in meat causes heart disease are all of a sudden saying “We were wrong. It’s not the sat fat its the carnitine”…hmmmm….I’m I bit inclined NOT to believe them. I heard this on the radio the other day. They actually used the word CAUSE. I just don’t get it anymore.

  25. I’m just hoping that all these silly meat-hating articles lead to a decrease in demand and price for red meat leaving more for me and my Primal friends. Is that wrong? 😉

    1. Wow, love the thought! Let’s keep these anti-red meat articles flowing…

    2. But then I worry about my lovely lovely butcher at my favourite farm shop going out of business. He’s already had to half his days open because of drop in business due to austerity. These unscientific reporters with their fear-mongering headlines must be really terrible for hard-working, conscientious small-scale farmers who are endeavouring to produce healthy, well-butchered meat at affordable prices.

  26. I just saw this study on the news the other day. I continued to eat my pork sausage, one heart-attack-laden bite at a time. *sarcasm*.

  27. As a vegetarian who eats lots of eggs and consumes whey protein drinks and has embraced most all of the other (non-meat) aspects of the primal diet … and have learned a great deal from Mark, I suspect he is right on about this. If you eat a variety of food including a lot of veggies and leafy greens and ingest probiotics, eating some grass fed beef once or twice a week should not be a big deal IMHO. I like Mark’s quip about the vegetarian test subjects that “were somehow about to get the steak down” LOL.

    1. Somehow *able* to get the steak down, sorry about that, oh for an edit button. 🙂

  28. In an unusual turn of events, I read about this study before seeing your take on it on MDA! I knew you would get to it soon enough… I’m pleased to see that my own interpretation was very similar to yours (score 2 points of validation for me!). I was left with the questions of “what intestinal flora (or should that be fauna) composition would be optimal?” and “does my primal diet help me keep a diverse collection or result in a narrow representation of different flora/fauna?” I was disturbed by the implied goal of future research of learning which to wipe out with antibiotics or other chemical approaches — as if there is enough information on the variety of populations, what influences their diversity and numbers or how you could selectively target just the “bad” ones… Anyway, I think the take-aways for me were stick with variety in what you consume, minimize supplements (since you should get what you need through the variety) and monitor the many, many potential indicators of health rather than fixating on single details that may or may not be the driving determiner of YOUR situation.

    Thanks as always for the great info, thorough analysis, and well-documented peer-reviewed literature references. I am so inspired!

  29. What irks me about studies like this is that the researches don’t really bother to take into account other aspects of their test subjects diet.

    For instance: vegetarians who ate the steaks did not have higher levels of TMAO, while the omnivores did….so what’s REAL difference here? Vegetarians tend to eat much more fresh produce and fiber than the typical American SAD omnivore. Without enough fresh produce and fiber, your body cannot eliminate unneeded cholesterol. Cholesterol serves a purpose to a point in the body (injury repair and hormone production), when the body is optimally healthy and getting the proper nutrition it needs, it’s able to regulate cholesterol levels quite efficiently and remove what it doesn’t need, but someone eating a SAD omnivore diet filled with sugar, grains, and unnecessary starches, and not enough antioxidants and fiber, has a much, much harder time regulating cholesterol—and a bleaker future for their heart health.

    So, it is really the red meat that’s the culprit or not enough fresh produce? I’m still more inclined to think it’s the latter.

    Dr. Mercola also analyzed this study and came to this same conclusion but also added that it’s low-level antibiotics found in most CAFO meat that wreck our gut symbiosis and make us much more prone to high levels of TMAO.

    So my conclusion:
    1. Stay away from antibiotic-laced meat
    2. Take/eat probiotics everyday
    3. Eat at least 7 servings of fresh produce everyday
    4. Stay away from added sugars and highly starchy foods since they seem to feed the less friendly bacteria in the gut, and
    5. Optimize your omega-3 intake.

  30. So now I’m confused. I have to take a statin (genetic form of high cholesterol; nothing else works and I eat primally for the most part). I supplement with 100 mg coq 10 to fight against its depletion and recently added l carnitine 330 mg daily. I eat red meat about two times a week. I also supplement with magnesium, b complex, fish oil and am adding in a high potency antioxidant. Should I stop the l carnitine?

    1. Did your doctor advise you take the L-cardnitine? Just because you have high cholesterol doesn’t mean you HAVE to take a statin drug. Have you been officially diagnosed w/ heart disease or did your doctor just push it onto w/ fear mongering about having a heart attack? Statin drugs should be used for the most severe cases of heart disease, otherwise they’ve been shown to do more harm than good.

      Have you had your cholesterol analyzed for composition? Is your LDL the large, fluffy kind (which is actually protective and the most desirable), or the small, dense particle kind?

      These answers play into the decision to continue w/ the L-carnitine or stop it.

      You could also add a high quality probiotic to your daily supplement regime to control the bacteria that feed off l-carnitine, while still benefiting from it’s heart support.

      1. Rokzane, thanks for this info. I have a strong family history of heart disease (strokes, heart attacks) and diet has no impact. My tests are always for LDL, total cholesterol, HDL, triglycerides and lipoproteins a and b. i have elevated total cholesterol and triglycerides with good hdl levels.

        With regards to the type of LDL or is there another test to determine the type of LDL I have other than lipoprotein a or b? Fyi, i have elevated lipoprotein a and normal b. I understand that the elevated a puts me at increased risk for coronary heart disease.

        I have this horrible feeling that I am one of those individuals with a genetic makeup that necessitates a statin as I have researched in vain for alternatives. Nothing yet.

        1. There’s a specific test that’s used for determining particle size, and you have to specifically ask for it, but an educated guess can be made based on your current tests.

          If your triglycerides are elevated and your HDL is low, then you most likely have small dense particle LDL. However, your HDL is in the high range, so you may be borderline in this area. The best way to bring your TG levels down is to get really strict w/ your carb intake: no added sugar, restrict fruit intake to 2 servings/day, no potatoes, no pasta, no bread, no refined grains at all, and very little whole grains. You may also have to restrict the most common inflammatory foods from your diet for a time (inflammation has a great deal of influence on cholesterol, since the body produces and hordes cholesterol in response to inflammation–it’s gearing up for injury repair). These include: gluten, eggs, dairy, and peanuts. You should replace these foods w/ more antioxidant rich produce: dark, leafy greens, berries, and citrus fruit.

          The best way to determine levels of inflammation is to have your C-reactive protein levels tested…this should be done w/ every cholesterol test.

          Personally, I would do everything I could to get off the statin drug. They are so dangerous, and I don’t think the benefits outweigh their risks!

  31. The conclusion I got from this “study:” Don’t feed your mice steak.

  32. Don’t base your life on mice studies would be my take-home message from this study.

  33. Mark, within your 3rd & 4th paragraphs, I thought, how is this silly study relevant? What threw me was the supplementation of 250 mg carnitine in addition to actually eating a steak PLUS administering of antibiotics. Long before I had ever heard of eating primal, I knew all too well how detrimental antibiotics are to our gut flora. Mess with the flora = mess of troubles in the body. But as you said, we’re fine as long as we eat red meat (grass fed & hormone free) in moderation and also a variety of other good foods. Too much of any one good thing can be bad.

  34. I’m thinking yet again, confounding variable(s). Every time we try to laser in on a really bad or really good thing, there’s always more to the story.

    Sadly, I don’t see Veggie | Paleo | SAD control groups coming to a rigorous study any time soon, so we’re left to our own devices and this does give us a bit to think about.

    As usual, we need to approach the system, not the constituent parts and as usual, Mark is doling out pragmatic, practical advice.

  35. So… any scientific study showing the dangers of sugar or carbs is the gospel truth, but a study showing a correlation between red meat and heart disease warrants a LMAO? The lack of objectivity and critical thinking on this forum is laughable.

  36. I remember getting my test results back from my doctor after eating low carb/clean protein (grass-fed/finished beef, lamb, pork, chicken), clean veggies/fruits (organic/local grown) and having the occasional goody (dark chocolate or other) if I wanted it. No “exercise” regime as we have a farm and I can walk up and down some steep inclines, haul feed bags, etc. I ate this way for about 6 months before the blood work tests. Her note to me? “Whatever you are doing, keep it up! These numbers are PERFECT! And you’ve lost 25 lbs.” The proof for me is in my own body 🙂

  37. One of the concerns about the lead author was that many energy drinks contain carnitine as a supplement, and that many teenagers drink a lot of that crap. Might be useful to know if this is a bad idea for developing children.

    Also, the NY Times write up indicated that the association between TMAO levels and CVD risk had previously been established by a study which had examined blood from 10,000 people who had come though the Cleveland Clinic system. They were then followed for several years to monitor the subsequent development CVD. The point was to look for associations between trace chemicals in the blood that might be associated with increased risk of CVD. Such associations are useful for formulating mechanistic hypotheses for further testing.

    Why did they bother to do this? Well, apparently, lots of people still die of heart disease. And unlike the experts here who seem to know everything there is to know about the cause and prevention of heart disease, most medical professionals still aren’t sure that they have all the answers.

  38. I think you do not have to be so careful if you are eating a small plate only and well balanced with many types of food. Too much of anything is a bad thing of course!

  39. Another useless study, that doesn’t contribute any insights into the broad picture.

  40. As well as the ‘quality’ of the mice used for testing, the ‘quality’ of the human would be just as critical. Its like saying ‘meat is bad for you’, because in many trials vegetarians have lower levels of cancer/cardiovascular disease. This in no way implies that meat is bad for you. Perhaps the vegetarians eat far more vegetables, or predominantly eat organically, and are avoiding pollutant-rich processed meats. The cause is not so discernible.

    In this case, the carnivores chosen for the test may have had poor gut flora balances or a host of other digestive disorders, and are therefore converting far more TMAO than a healthier individual might. An unhealthy test group is no way to test health….

  41. What bothers me in this study is, that 69% of participants were smokers and all were suffering from some kind of cardiac disease. 70% were men age 54-71. Their blood carnitine levels correlated with smoking, male gender, triglycerides as well as use of ACE-inhibitors (hypertension med). Correlation of these were in the same ballpark as ingested carnitine. So, makes one wonder, if high levels of carnitine in blood are result of deficient metabolism due to those other correlating factors?

  42. See also Paul Jaminet’ excellent post on this topic on perfecthealth.com Or did someone already mention this?

  43. I think what we forget with these studies is that yes although they test theories on humans, but they also test them (mostly) on mice and other rodents. We are omnivores, mice are herbivores, so wouldn’t it make sense that a mouse we respond much more aggressive to this type of thing, because their digestive track is much less used to digesting these substances then we are? It’s like us, we have started developing all sorts illnesses since we started incorporating grains in our diet, so who says the same thing doesn’t happen to a herbivore mouse who usually eats seeds, grains and fruit….???? Maybe I am seeing this too simplistic, who knows, but I won’t give up the Paleo lifestyle, as I feel the best I have ever felt since I’ve stopped eating the SAD/SBD (stands for standard british diet :-))

  44. Thanks for the article Mark. Grok didn’t have the benefit of these studies and somehow he made out fine. All things in moderation and variety sounds good.

  45. Research into gut flora is pretty exciting!

    I agree with previous comments that it’s media reports on science that trigger the misinformation cascade. For example, it was media reporting that said “red meat kills” when the studies implicated “red and processed meat” together. Sure, the study could have been designed better to separate whole and manufactured foods, and other confounding variables (since these types of studies are usually just meta-analyses of other questionnaire-type studies, so you’re getting two layers of “oops”) but it wasn’t the study itself that said “Oh my God, put down your fork!” That was sensationalism and cherry-picking on the part of whichever media outlet reported on it in order to increase viewership by feeding on the fear of food we already have.

  46. Annabelle is so correct. I’d like to see people here respect the tremendous work of researchers in journals like Nature instead of bashing a negative result.

    An emotional litmus test – If the study concluded that TMAO was REDUCED with meat consumption, would you question the study/ study title/ journal with the same vigour?

    +1 on the need for long term Paleo Primal data. I’ve been transitioning to the Primal diet slowly, 60/40 since January and experienced great results. After 1 month on the 80/20 rule, and taking good notes on what I eat, I am scheduling a full lipid and triglyceride profile – at my own expense. I will share the results with this community.

    Others have done this and putting together the results can be beneficial (Mark Sisson et. al?). It will NOT constitute a rigorous scientific study; however, it WILL provide nutritional scientists a grouping of anecdotal evidence. This is often the first step in designing a proper scientific study.

    Look for my blood work results in June.

    For all future studies – Be critical or supportive, but steer clear of douchebaggery! We are all self-experimenting here, with mostly good results.

  47. Especially for men, steak is very healthy for us. It’s got a chock full of vitamins and minerals that we need to eat.

    It is funny the media portrays steak as unhealthy. There is a certain tribe in Nigeria that is known for their physical prowess. They eat everything on the animal including the liver (said to be the most healthiest part) and even the blood is given to the little kids!

    It is the same with the egg yolk having “bad cholesterol”. Egg yolk is a GREAT testosterone boost. It pains me to see how bad the media is influencing our society.

  48. I have always heard that eating red meat was bad for you and your cholesterol levels. I never would have thought that fish contains the same TMA and that’s what gives it it’s fishy odor.

    I wonder if the more fishy it smells the more tma it has?

  49. I have to laugh myself, not at the study but at everyone who continues to sluff off all the actual medical research and science that has proven over and over again exactly how a diet focused so heavily on meat and dairy is killing us. Its nice to have folks tell you good things about your bad habits but lets be real. As tasty as bacon and hamburger are, grassfed or not, I think on some level intellectual level we all know its just not healthy for us.

    I wish it were so, I really do because I love bacon and I love deliciously grilled meat, but having switched the focus of my diet to more plant based (whole plants) I can’t denie the obvious benefits, improved elimination, more stable weight, and my cholesterol which has been chronically high my whole life is finally starting to come down.

    I doubt I will ever be able to completely eliminate animal based foods from my life but I have no doubt that if I could the true health benefits possible would continue to make themselves evident.

    I would encourage everyone to start looking at the real medical research, not what the media reports and certainly not what all these self proclaimed expert AKA Bloggers say. Plants are where its at folks but again I think when we get passed what we all WANT to be true and accept what we really know is true, we all know that.

  50. I shared this study with both of my cats, who by the way are unable to synthesize carnitine. They both pointed out if I eliminated carnitine from their diet, they would die of dilated cardiomyopathy. I told them I understood but that I would keep it from them because I didn’t want them to die from atherosclerosis.

  51. Study shows that we need to go back at creation in the garden of Eden. Before sin entered the world, they were vegetarians. They only eat fruits, nuts, and herbs. After the fall, that’s the time they experience death. Adam and Eve realized the penalty of sin when Cain killed his brother Abel. I believed that vegetarian diet is more safer that the flesh eating diet. We will live more longer.

  52. This reminds me of an example of causation vs association my high school science teacher told us… “The more ice cream that is consumed in a certain area, the number of car stereos stolen also increases, therefore, we need to eat less ice cream and not just because it’s not primal”.

    The rise in theft is caused by the fact that people leave their car windows down more when it gets hot. People also eat more ice cream wen it gets hot. Association, not causation.

  53. For the past 33 years, I have looked in the mirror every morning and asked myself: ‘If today were the last day of my life, would I want to do what I am about to do today?’ And whenever the answer has been ‘No’ for too many days in a row, I know I need to change something.

  54. The NY TImes is reporting on a study claiming that lecithin in eggs breaks down into choline and promotes gut bacteria production of TMAO. The study is by the same group as the carnatine study. (including Stanley Hazen)

    http://www.nytimes.com/2013/04/25/health/eggs-too-may-provoke-bacteria-to-raise-heart-risk.html?hp&_r=0

    Mark’s article above comments on an older version of the same finding on choline. This TMAO alarm may take a while to get sorted out. At least I hope it gets sorted out.

  55. I think there are a bunch of things wrong with this study, although effects of gut flora composition are probably important and worth a lot more study.

    1) There is a huge conflict of interest. The authors filed a patent in 2008 initially (latest http://www.google.com/patents/US20120157397) where they ‘invent’ a protocol for analysis and treatment of TMAO levels. If they can persuade everyone who’s having a questionably effective lipid panel and buying statins to do the same with their test, and a patented probiotic, they’ll be doing very well out of the royalties.

    2) They definitely have drawn the association with meat on purpose – it’s core to their abstract, ignoring the fact that TMA+TMAO levels are elevated to significantly higher levels than beef by fish, beans and other un-demonized food ingredients. It would appear that this story’s been actively marketed to the mainstream media and the hard links to meat in the abstract and conclusions would certainly not hurt that cause.

    3) The parallels between atherosclerosis-prone mice at huge doses, and humans with a normal diet seems pretty flaky

    It’s bad science I think – and it’s an interesting coincidence that TMAO is the compound that gives fish that ‘fishy smell’ – some of it has definitely rubbed off on the study.

  56. Indians consume 28 times less meat than Americans and 20-30 less than Europeans and have major problems with heart disease. The patients are getting younger every year. High LDL, low HDL. Lots of refined carbs and a diet increasingly American but with extremely low meat consumption. Their problem with heart disease is a multiple compared to the western world and their meat consumption is a tiny fraction. Funny that nobody is using that correlation to scare people away from carbs. And even funnier that they are blaming meat for heart disease even in India, saying that the meat consumption has “increased”. They are blaming their lack of exercise, their genes, their bad luck, anything except the carbs:)

  57. Meat must be a $100billion market in the states alone. Even a small shift to other types of food is worth billions to the usual suspects.

  58. I think that the major distinction that you need to make is that processed and non-grass fed red meat are going to be the types of red meats that increase your risk of cardiovascular disease. Honestly, if we look at the majority of the population, most people are eating steroid and antibiotic ridden red meat, which is not ideal.

  59. Mark, the study you mentioned as having shown that “probiotics have already been used to lower TMAO levels” was (a) in mice, and (b) showed that one of the probiotic supplements had no effect on liver TMAO levels, and the other actually *elevated* liver TMAO levels; either there was no effect on TMAO levels in the plasma, which is the most relevant compartment, or they didn’t measureit there :
    http://msb.embopress.org/content/4/1/157.long

    Another +1 to Annabella, FWIW.

  60. This article is in no way helpful. If the study is in first place supposedly discussing the carnitine amounts in red meat, then why are the subjects given also carnitine supplements along with meat. And some vague drawn up correlation between gut bacteria and heart disease allows this crap to pose as informative. This is some ass backwards science , if you can even justify reffering to this waste of a study as that. Time and resources need much more direction than unto the misguided efforts portrayed here.