Red Meat and TMAO: Cause for Concern, or Another Red Herring?

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This article is part of a special report on Red Meat. To see the other articles in this series, click here.

I’m sure many of you have seen reports on a recent study published in the journal Nature suggesting a possible mechanism linking red meat consumption to heart disease. The day after one such report was published in the New York Times, I received numerous emails and numerous Facebook and Twitter messages from concerned red meat enthusiasts. This is understandable, but rest assured it’s not yet time to switch over to soy burgers.

The researchers in this study published a paper a while back proposing that a chemical called TMAO (trimethylamine N-oxide) increases the risk of heart disease. In this study, they hypothesized that eating red meat may increase levels of TMAO in the bloodstream, which would in turn ramp up your chances of having a heart attack. Sounds plausible, right?

There’s another hypothesis that also seemed plausible for why red meat increases the risk of heart disease (if we even accept that, which I do not; more on this in a moment). It’s called the “diet-heart hypothesis”, and you’re all very well aware of it whether you know it by name or not. It holds that eating cholesterol and saturated fat increase cholesterol levels in the blood, and high cholesterol levels in the blood cause heart disease. This theory became so widely accepted that few people even question it anymore. The problem is it’s simply not true. Recent research has shown that dietary saturated fat and cholesterol are not associated with heart disease after all, and even if they were, high cholesterol levels in the blood are not the culprit. I’ve written about this extensively in the past, and I will be starting a brand new series with updated information this month.

Is TMAO the new cholesterol? Find out why red meat is still innocent.Tweet This

The mistaken blame of saturated fat and cholesterol as drivers of heart disease led to a decades-long campaign to encourage low-fat, high-carbohydrate diets. Unfortunately, the effects of this campaign were not harmless. Not only did it unnecessarily deprive people of nutrient-dense, nourishing (and delicious!) foods like meat, butter and eggs, it may have indirectly contributed to the epidemics of obesity, heart disease and diabetes. Studies have shown that when people replace saturated fat with carbohydrates, the risk of heart disease doesn’t go down—it goes up. (1) This is not because of the carbohydrates, per se, but because 85% of the grain consumed in the U.S. is in the highly refined form. (2)

The diet-heart hypothesis should be a cautionary tale that prevents us from jumping to rash conclusions based on limited evidence. Alas, the almost complete lack of criticism or scrutiny in the popular media reports on this study indicate that caution has been thrown to the wind. Let’s now examine three reasons why I’m not yet ready to take the conclusions of this study (i.e. red meat causes heart disease via TMAO) at face value.

Epidemiological evidence is inconsistent

If red meat consumption elevates TMAO, and elevated TMAO increases the risk of heart disease, we’d expect to see higher rates of heart disease in people that eat more red meat. The epidemiological evidence examining this question is mixed. A large meta-analysis published in Circulation by Micha et al. covering over 1.2 million participants found that consumption of fresh, unprocessed red meat is not associated with increased risk of coronary heart disease (CHD), stroke or diabetes. (3) On the other hand, a smaller prospective study including about 121,000 participants from the Nurses Health Study and Health Professionals Follow-up Study did find an association between red meat consumption (both fresh and processed) and total mortality, cardiovascular disease (CVD) and cancer. (4)

If eating meat increases heart disease risk we might expect lower rates in vegans and vegetarians. Early studies suggested this was true, but later, better-controlled studies suggest it’s not. The early studies were poorly designed and subject to confounding factors (i.e. vegetarians tend to be more health conscious on average than general population, so there could be other factors explaining their longevity, such as more exercise, less smoking, etc.). Newer, higher quality studies that have attempted to control for these confounding factors haven’t found any survival advantage in vegetarians. For example, one study compared the mortality of people who shopped in health food stores (both vegetarians and omnivores) to people in the general population. They found that both vegetarians and omnivores in the health food store group lived longer than people in the general population. (5) This suggests, of course, that eating meat in the context of a healthy diet does not have the same effect as eating meat in the context of an unhealthy diet. (Hold this thought: we’ll be coming back to it shortly.) A very large study performed in the U.K. in 2003 including over 65,000 subjects corroborated these results: no difference in mortality was observed between vegetarians and omnivores. (6)

Taken together, these data do not suggest a strong relationship between red meat and heart disease. It’s also crucial to remember that epidemiological evidence does not prove causality. Even if red meat intake is associated with a higher risk of CVD (or any other health problem), such studies don’t tell us that red meat is causing the problem. If you’re new to this concept, I suggest reading these excellent articles by Denise Minger and Chris Masterjohn.

The “healthy user bias” strikes again

The healthy user bias is the scientific way of explaining the phenomenon I described above, where people that engage in one behavior that is perceived as healthy (whether it is or not) are more likely to engage in other behaviors that are healthy. (7, 8) Of course the flip-side is also true: those that engage in behaviors perceived to be unhealthy are more likely to engage in other unhealthy behaviors. The healthy user bias is one of the main reasons it’s so difficult to infer causality from epidemiological relationships. For example, say a study shows that eating processed meats like bacon and hot dogs increases your risk of heart disease. (9) Let’s also say, as the healthy user bias predicts, that those who eat more bacon and hot dogs also eat a lot more refined flour (hot dog and hamburger buns), sugar and industrial seed oils, and a lot less fresh fruits, vegetables and soluble fiber. They also drink and smoke more, exercise less and generally do not take care of themselves very well. How do we know, then, that it’s the processed meat that is increasing the risk of heart disease rather than these other things—or perhaps some combination of these other things and the processed meat? The answer is, we don’t. Good studies attempt to control for some of these confounding factors, but inevitably some will not be controlled for. And one of the most important potential confounding factors that is never controlled for is the gut microbiome.

Numerous studies, which I’ve written about on this blog and spoken about on my podcast, suggest that the balance of bacteria in our gut may be one of the most important factors—if not the most important—that determines our overall health. Gut dysbiosis (an imbalance between healthy and unhealthy bacteria in the gut) and small intestine bacterial overgrowth (SIBO, a condition involving an inappropriate overgrowth of bacteria in the gut) have been linked to health problems as diverse as skin disease, depression, anxiety, autoimmunity, and hair loss.

The study we’re discussing here found that those who eat red meat produce TMAO, whereas vegans and vegetarians who hadn’t eaten meat for at least a year do not. The researchers claimed that this means eating red meat must alter the gut flora in a way that predisposes toward TMAO production. However, there’s another explanation that I believe is much more plausible: the red meat eaters are engaging in unhealthy behaviors that have led to dysbiosis and/or SIBO. This could include eating fewer fruits and vegetables and less soluble fiber, and more processed and refined flour, sugar and seed oils. All of these behaviors have been shown to be more common in the “average” red meat eater, and all of them have been associated with undesirable changes in the gut microbiota. (10, 11, 12) In other words, the problem isn’t the red meat, it’s the gut bacteria. This is supported by the finding in the study that the red meat eaters did not produce TMAO after a course of antibiotics. It is also supported by data indicating that a breakdown in the intestinal barrier, which occurs in dysbiosis and SIBO, may increase heart disease risk by elevating the number of circulating LDL particles in the bloodstream. (13) I will be covering this (i.e. the connection between LDL particles and heart disease) in my updated series on heart disease.

In the last section I presented evidence suggesting that eating meat in the context of a healthy diet does not have the same effect as eating it in the context of an unhealthy diet. This study is likely yet another example. In order to know whether red meat is really to blame for changes in the gut flora that increase TMAO production, we’d have to do another study with two groups: one that follows a Paleo diet rich with fruits, vegetables and soluble fiber, as well as red meat; and another vegan/vegetarian diet with equivalent amounts of plant matter and no meat. If the Paleo diet followers still had higher levels of TMAO, this hypothesis would be a lot stronger.

The jury is still out on TMAO

The evidence linking TMAO production to eating red meat, and serum TMAO levels to heart disease, is not as cut-and-dry as the study authors suggest. For example:

  • The Nature paper on TMAO contained data from two studies: an epidemiological study on humans, and a clinical study on mice. The human study compares a single vegan that they managed to convince to eat a steak to five “representative” meat-eaters. A sample size of six people, with only one in the vegan group, is hardly adequate to draw firm conclusions from.
  • The mouse study used a carnitine supplement. While it is well established that free carnitine increases TMAO production, previous studies have not shown that carnitine-rich foods like red meat increase TMAO. In fact, in one 1999 study, out of 46 different foods tested, including red meat, only one food elevated TMAO levels in the participants: seafood (see graph to right, from Chris Masterjohn’s article referenced below). This makes perfect sense since trimethylamine occurs naturally in seafood. Does this mean we should cut back on fish and shellfish because they’re going to give us a heart attack?(15)

TMA1-267x300

Another obvious question we should ask is whether there are alternative explanations for why we see elevated TMAO levels in meat or seafood eaters (if indeed we do see them in a wide sample of meat eaters, which at least one earlier study didn’t support)? According to a 2011 article by Chris Masterjohn touching on TMAO in a different context: (16)

Elevated TMAO could reflect dietary trimethylamine or TMAO from seafood, but it could also reflect impaired excretion into the urine, or enhanced conversion of trimethylamine to TMAO in the liver.

The enzyme Fmo3 carries out this conversion, mainly in the liver, as reviewed here. There are a number of genetic variants affecting the activity of this enzyme, some of which appear only in certain ethnicities, and the enzyme also processes a number of drugs used to treat psychoses, infections, arthritis, gastro-esophageal reflux disease (GERD), ulcers, and breast cancer. Iron or salt overload may also increase the activity of the enzyme. TMAO could, then, be a marker for ethnicity, drug exposure, genetically determined drug efficacy, or other conditions.

As you can see, it’s overly simplistic to suggest that eating red meat causes elevated TMAO; there are many other factors at work.

But even if Paleo meat eaters have higher TMAO levels than vegans and vegetarians, we still don’t have evidence proving a causal relationship between TMAO and CVD. Once again, the supposed link between cholesterol and saturated fat and heart disease should serve as a reminder not to jump to hasty conclusions that unnecessarily deprive people of nutrient-dense, healthy foods. It is virtually impossible to control for all of the possible confounding factors, and the study we’re discussing in this article only further highlights this problem.

Conclusions

I’d like to end with an observation from the discussion section of the TMAO paper. The authors state:

Numerous studies have suggested a decrease in atherosclerotic disease risk in vegan and vegetarian individuals compared to omnivores; reduced levels of dietary cholesterol and saturated fat have been suggested as the mechanism explaining this decreased risk. Notably, a recent 4.8-year randomized dietary study showed a 30% reduction in cardiovascular events in subjects consuming a Mediterranean diet (with specific avoidance of red meat) compared to subjects consuming a control diet.

This might sound like damning evidence against red meat. However, when you look at Table One in Mediterranean Diet trial, you’ll find that the Mediterranean diet allowed more red meat than the control diet (a low-fat diet)! The Mediterranean Diet allowed for “one serving or less of red or processed meat per day“, whereas the low-fat diet only permitted “one serving or less of red or processed meat per week“. (You can see this for yourself. Click here to access the PDF version of the study, then scroll down to Table One.) Clearly this paper does not support the authors’ conclusion that red meat increases the risk of heart disease. [UPDATE: Stephan Guyenet brought my attention to the Article Supplement, which I had missed before. On  Page 9, it does show that the investigators asked those on the Mediterranean diets to choose white meat instead of red. However, on Page 26 the data indicate that the amount of red meat consumed during the study by the Mediterranean diet groups was virtually the same as the amount consumed by the low-fat/control group. This is a common problem in diet studies: the participants don't always do what they're told! What this means, of course, is that the 30% decrease in CVD observed in the Mediterranean group was caused by something other than reducing red meat consumption—which the Mediterranean group did not do.]

They also claim that vegan and vegetarian diets reduce the risk of atherosclerotic disease compared to omnivorous diets; but the studies they reference fail to adequately control for the “healthy user bias”. The study I mentioned in the beginning of this article compared heart disease risk amongst omnivores and vegetarians that shop at health food stores (which is a big step toward reducing healthy user bias), and did not find a difference in deaths from heart disease, stroke or all causes.

If you read the media reports and full-text of this study, you might have noticed something interesting. The study itself, and even most of the media article about it, quite simply and without much fanfare stated that saturated fat and cholesterol have little to do with the supposed increase in heart disease observed with red meat consumption. Hold the press! Shouldn’t THAT be front-page news?!? Apparently not. Of course, they’re only willing to admit this publicly in the context of an article where they’re proposing yet another mechanism for how red meat will kill you.

Finally, the most remarkable and sad part of this for me is seeing just how deep most people’s fear and distrust of red meat is, even if they’ve been following a Paleo diet for a long time. The day after the TMAO study was published, I woke up to no fewer than 20 emails and the same number of Facebook messages and Tweets from people expressing concern that their choice to eat red meat might be killing them. It really is a testament to the power of brainwashing. Most of us grew up with the idea that red meat is harmful, and it’s perhaps not so easy to leave that behind—even when you think you have.

Chris Masterjohn has also published a superb, detailed analysis of the underlying data in the study, and I highly recommend reading it. Frankly, the conclusions of the authors (that eating red meat increases the risk of heart disease via TMAO production) are so incongruous with the data in the study that it’s difficult to imagine how it could have passed peer review.

I believe we may be seeing more “red meat is bad because of TMAO” studies in the near future, so as always, when you see a media report on such a study, take it with a heavy grain of salt (which, by the way, doesn’t cause high blood pressure in most people!).

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Comments Join the Conversation

  1. says

    Thanks Chris. It’s increasingly difficult to find thoughtful critique and discussion of “science” and nutrition amidst all the hype and posturing going on in the media today. You are on the short-list of people I trust to cut through the crap. Thanks for being a voice of reason in the wilderness.

  2. says

    Thank you for this, Chris! I didn’t get a chance to tell you @ PaleoFX last month, but you have helped me a TON on getting back on the road to health! Also, much like Carrie, you are one of the few people, and literally, the only Doctor, I trust in this world!

  3. Syd says

    Thanks for this very thoughtful piece. I will continue to eat red meat in the context of a healthy diet.

    QUESTION: I take an acetyl-l-carnitine supplement per my doctor. Could that contribute to an increase in TMAO?

  4. says

    This was my explanation too at the Reddit thread about this research paper the other day: that the research was conducted on SAD eaters with an altered gut flora, not on Paleo people who eat fermented foods. I went unnoticed, I hope your article gets read a lot.

  5. Kristoffer says

    What have you got against refined grains? Ever heard about antinutrients and insoluble fiber in whole grains? Also billions of asians eat refined rice as a staple like 60% of caloric intake, and they aren’t very fat, are they?

  6. Lexie says

    This is fine. Less people eating red meat ought to mean more for me!

    On a more serious note, this is an excellent discussion of the facts. Much appreciated!

        • Richard says

          Animal production in the US creates more CO2 than all the modes of transportation. Creates even worse gases than CO2 and uses loads of water and land space.
          In my mind, there is little doubt that if people consumed less meat, cheese and milk they would be healthier and thinner as a result of more vegetables and fruits and the country would save bundles on health costs.

  7. says

    Chris, look at the Supplementary notes PDF. Do you see the huge fall in glucose and insulin when mice were fed antibiotics?

    Could the gut flora be producing glucose as well as TMAO? If so, and the patient is insulin-resistant, perhaps this is what’s responsible for increased CHD risk?

  8. Colleen says

    I get a brief moment of panic because now I am feeding red meat to my 4yo a number of times a week whereas previously we rarely ate it. But I’ve been reading you (and others) for a year now so I look at these articles and can see thru much of it (though not as easy without access to the full text study). These “journalists” do a disservice in writing these articles on such studies with no critical analysis, but then again I think there is an agenda on the part of the NYT writer, so I am not surprised. So, when I saw the article the other day, my initial dismay was quickly replaced by skeptiscism.

    Glad to see your aticle and I appreciate the timely analysis.

    • Johnny says

      Colleen, The research the NYT reported on was very extensive and well done. They did not try to draw conclusions ie red meat will lead to heart attacks, but to show statistically that you are much more likely to die from stroke or heart disease if you consume red meat. In the study, people were 2.5 times more likely to die then non-meat eaters.

      Statistically, that is a HUGE increase in risk. For instance, people who smoke their whole lives are not even 2.5 times as likely to die of lung cancer then those who don’t smoke.

      So yes, from what we KNOW now, eating meat will kill you.

      • Craig says

        Oh please, show me a double blind, controlled study that accounts for confounders that proves what you supposedly KNOW

    • Richard says

      Dead soldiers during the Korean and Vietnam wars(?) proved that men in the 20s already had CVD.

      Do you really think eating the same diet they did will provide different results? Maybe you think most of them smoked or lived in a smoke filled environment? I do not know for sure what causes the CVD but I see plenty of it in the world so I will choose to follow the diets of the cultures where CVD is low. Check those out and you will not find loads of meat being consumed like in the Standard American Diet (SAD).
      Make your own conclusions or wait for the meat industry to tell you what to do, it is up to you!

      • says

        “Make your own conclusions or wait for the meat industry to tell you what to do, it is up to you!”

        Funny you should say that, Richard. Cuz what I’ve read from you indicates that once we made up our own conclusions, if we happen to disagree with yours, you’re just gonna call us morons. Here, that’s what you said: “Haha, do some research….that is a typical response from a moron!”

        In my mind, you’re doing it wrong, Richard.

        • Richard says

          Ahhhhh you are right, I should not have called him a moron but when someone says “Do some research” it touches a sensitive point because I think that is as bad as calling someone a moron. It certainly was not because I disagree with the author since the little he did say makes me think that we are in agreement about grains.
          Please notice that I included an url in my response so that the original commenter has something to go to besides “Do some research”.
          However, your point is well taken and I will try to control my choice of words…

  9. Barbara says

    Will read the article, but wanted to point out a typo: in second paragraph, you’ll want to change “intern” to “in turn”.

    Love your blog!

  10. says

    Thanks for taking the time out of your busy schedule to write this, Chris! It’s frustrating to see how easily people can get disheartened by these things, even when they’ve trusted in Paleo a long time.
    I’m rather pleased that when I originally read the original TMAO article, my first conclusion was that it was about gut flora, not about the red meat, and that their conclusions were not soundly thought out. It’s because of people like you who’ve better taught me how to critically evaluate these sort of things that I was able to come to that conclusion. So thank you. :D

  11. Michael says

    And then there are people like me who have Trimethylaminuria (TMAU), which is a genetic disorter that limits the activity of the FMO3 enzyme. I don’t have enough (or properly working) enzymes to convert (oxidize) the TMA to TMAO. Wish I did though, because TMA smells like rotten fish which them makes me smell like rotten fish. So my question is, is there a way to increase my TMA oxidation to make up for my faulty FMO3 Enzyme activity? Currently, I just have to limit my Choline intake and I take probiotics.

  12. says

    Thanks Chris,
    I love knowing that I can count on you to tell it like it is, picking apart these studies and telling us the facts one by one. I think most people read the first paragraph or two of a study and take it as gospell.
    My husband and I eat red meat at least once a day, often 2 or 3x/day…have never been in better health at 60 and 67.
    It always seems to come back to grains and gut flora!!
    Thanks again for all the great work you do. I’m in Richmond/El Cerrito. I hope we get to meet some day. :-)

    • Chris Kresser says

      There’s no gold-standard test right now, so it’s still in part a clinical diagnosis. There’s a breath test used in conventional settings, but it’s not very accurate. I use the Organix Dysbiosis profile from Metametrix as a starting point.

  13. Ody says

    Hello, what about supplements of l-carnitine for Fibro, following the mentioned above, should one avoid using them?
    thanks much.

    • Chris Kresser says

      I will have to investigate this further. Free carnitine is readily converted into TMAO, but the clinical significance of that is not clear.

  14. Cassie says

    Weird, where did the study mention it was red meat only that was providing L-Carnitine?
    L-Carnitine is in all complete amino acid foods, namely whole proteins. Yes?
    And yet in the article it seemed (magic, mirrors and sleight of hand) to be all about red meat.
    Weird but oh so very human, if you want a good headline.

    • Holly says

      No, l-carnitine is not in all whole proteins. One thing that few people seem to mention – though it was brought up in the interview with the study’s author – is that l-carnitine is also abundant in salmon.

  15. michael says

    This was an awesome deconstruction on what is a very convoluted, elaborate hypothesis that grabs at least a few straws to keep holding the link between SFA and disease. Thank you for this, Chris.

  16. Brad says

    I think one reason that many ancestral eaters became concerned was not due to a lack of faith in their prior knowledge, but because TMAO is a term to them. At least it was for me. I had never heard of it before. And the article seemed to be convincing that elevated TMAO caused bad things at least in mice. So it would be concerning if (big if) red meat actually did elevate TMAO in a large sample of humans and *if* that elevated level really has any negative consequences when it’s part of an otherwise healthy well rounded diet… even a diet that is read meat heavy, or seafood heavy. These are important things to know as well since many people, esp bodybuilders, consume lots of meat protein.

    Good write up, thanks. Looking forward to Chris M.’s feedback as well. I will be keeping an eye out for learning more about TMAO.

  17. says

    Chris, pretty good rebuttal. I’d have liked to see more of a direct point-by-point analysis of the study itself, but that’s just me. Incidentally, the study you cited (3) PMC2885952, also happens to be the second reference in the TMAO study.

  18. says

    Thank you Chris, Very well argued debunking the imaginary fish. I hope all understand to take the red meat daily and real herring weekly, all with greens and a pinch of salt for best health of bone, body and brain function.

  19. John McDonell says

    gosh, thanks very much for this very thouvht-filled piece, Chris.

    Michael: you may wish to give supplemental taurine a try. One of the things taurine does is in the final stages of protein breakdown inside the mitochondria. Amino acids (depending on type) will break-down to either mercaptans(sulpher-containing & very smelly); or to, ammonia. BOTH of these are highly toxic . While ammonia is often-hard to detect; mercaptans are easy to find. The SMELL (like in natural gas) betrays their presence every time. You’ll notice tis smell even after a shower … it persists and persists.

    When experimenting, even a small amt of taurine (>250mg/day) made ‘my smell’ disappear. Taurine self-sacrifices ankd stands-in at the final stage of amino acid reduction. Not only are mercaptans and amonia never produced, but the taurine breaks into two innert compounds.

  20. says

    I cannot wait until the day when beef and other red meat can be looked as health gems – Remember when coconut was plagued as being terrible for you? Well look at where it is now! Your day will come red meat!

  21. Jen says

    I appreciate your work and your thoroughness in looking at these type of ‘controversial’ subjects. There’s a lot to sort through and it’s great to have resources who take the time to look more thoroughly at some of these health topics and studies which often become generalized headlines.

  22. Miriam says

    Thank you for a very thorough and insightful follow up to the misleading report. As I read your counter I’m eating my grass fed ground beef and pastured egg with kimchee!

    I’ve been on paleo for nearly a year and not only do I feel better coming out of a raw vegan diet, my cholesterol result is better than it has been in the last several years!

    The published study is most likely biased judging by who sponsored it. Can’t wait to see the published peer reviews.

    • Jospeph says

      That term doesn’t mean what you think it means. The “peer review” process happens BEFORE a paper is published. Perhaps you mean “follow-up studies.”

  23. Tatiana says

    thank you Chris for your cool minded response to this “study” and their conclusions…
    i would be interested to see the same study done on Gauchos from Argentina and South Brasil,they have a heavy meat diet and i never heard of them dropping dead from heart attacks or higher incidence of cancer for that matter.
    so fortunately we still have reality to fall back on.

  24. dan says

    I have a question although it isn’t really important. I was curious why a friend follows my advice on following a paleo diet which my blood work shows to be working great for me. It made his get even worse. So he switched back to lowering intake of meat to almost not eating any, and increasing a more vegetarian diet. His blood work showed a great improvement. My question is since he is a huge beer drinker does the beer make a paleo diet bad or is it just an individual response.

    • says

      I’m no expert (I do a lot of research though, as I am working on healing my own gut), if i may, two things to look at in this situation: beer is acidic and contains gluten. Just a thought.

    • Heather says

      When you first go paleo it can send your cholesterol levels out of whack. This is normal. This is the body’s beginning of the healing process. Tell him not to worry about it right now. Give the diet time to do its job

    • Bet says

      Beer is a carb. Even if he doesn’t have a problem with gluten, the carbs will cause him to have more insulin output which will increase his cholesterol (especially the bad one). He needs to give up the beer.

  25. David says

    The NY Times article also says: “It [Carnitine] is also found in other foods, he noted, including fish…”
    So that means it would be healthier to also stop eating salmon?!
    That seems absurd!

  26. says

    There’s no question that it’s really, really hard to tease nutritional truths out of epidemiological data and careful reading of the various studies is required. Re: “If eating meat increases heart disease risk we might expect lower rates in vegans and vegetarians. Early studies suggested this was true, but later, better-controlled studies suggest it’s not.”

    You dismiss the early studies without citation, and go on to cite two studies that purportedly support your contention that there is no link between meat eating and heart disease. The first study is about health food store shoppers, and doesn’t compare meat-eaters to vegetarians at all. The second study is from the long-term EPIC-Oxford study, which does indeed find no significant difference in all-cause mortality. It does, however, find lower heart disease risk in vegetarians vs. non-vegetarians (http://www.ncbi.nlm.nih.gov/pubmed/23364007).

    I’d be careful with those accusations of agenda-driven data interpretation.

  27. says

    Hi Chris,
    Great article and timely!. I especially enjoyed your keen observation that the recent Mediterranean Diet study cited in the paper does not support the conclusions. But can we really conclude that fruit and fiber (we agree on veggies, oils and too many carbs overall) are the knights in shining armor coming to the rescue?

    You states that “red meat eaters are engaging in unhealthy behaviors that have led to dysbiosis and/or SIBO. This could include eating fewer fruits and vegetables and less soluble fiber, and more processed and refined flour, sugar and seed oils. All of these behaviors have been shown to be more common in the “average” red meat eater, and all of them have been associated with undesirable changes in the gut microbiota. (10, 11, 12) In other words, the problem isn’t the red meat, it’s the gut bacteria”

    Reference 10, the Cordain paper is about Paleo eating but does not mention the impact on gut microbe populations, at least at my quick read.

    Reference 11, on the “Impact of diet in shaping gut microbiota” is of general interest though it’s well known that different diets promote different gut microbe populations. But it falls short of truly connecting the different populations (of microbes) to digestive disease or other diseases.

    Reference 12 cites a mouse study and the authors note: “However, there is a caveat about applying results obtained from gnotobiotic mice carrying mouse-derived microbial communities to humans: culture-independent comparisons have revealed that, although the distal gut microbiota of mice and humans harbor the same bacterial phyla (Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia, Cyanobacteria, TM7, Fusobacteria, and Spirochaeates), most bacterial genera and species found in mice are not seen in humans (6)”

    While I support the notion that a varied whole food diet is likely to promote the most diverse (and healthy) population of gut microorganism and agree with eating a ton of non starchy vegetables for optimal health, but there is quite a bit of evidence that fructose (high amounts in many fruits), resistant starch and many types of fiber actually promote SIBO, dysbiosis and functional gut problems as opposed to curing them. Note, my research focuses mostly on Western populations.

    It may very well be that rural tribes that have eaten high fiber diets for many generations have adapted with stable, healthy gut populations to help them breakdown these foods and don’t suffer from SIBO-related disease, but you might find the same thing in populations that have eaten a lot of animal products for many generations. I am open to reading these studies if they exist.

  28. Lynn says

    Thanks, Chris. I’ve been waiting for your analysis of this latest attack on red meat consumption. I did a double-take on the opener, “….saturated fat and cholesterol have little to do with the supposed increase in heart disease”. Say that again, and in BOLD, red, flashing text! I said to my husband they are grasping at straws now that the science cannot be ignored (at least by those willing to think rationally) and it isn’t the sat fat and cholesterol killing us by causing heart disease. I am curious as to what will be next demonizing red meat……

  29. says

    Very nice analysis and summary. I’m curious about the health food store shopping meat eaters vs vegetarians; one of your comments suggest the data is actually different. I’ll look it up.

    I wonder if it isn’t a residue of our long-standing Cold War with the Soviet Union that makes scientists hate “Red” meat so much?

  30. Dana says

    …And when salt *does* increase blood pressure, it’s usually because your *insulin* is high!

    (Insulin being high triggers sodium retention… so eating more sodium pushes the BP up… etc.)

    Thanks for this. All I needed to know is I feel better with red meat in my diet, but “because I say so” doesn’t fly with people who are scared by the study, so…

  31. Susan says

    Hi Chris, it seems like it could be quite some time before the results of new studies using paleo candidates could inform us on this important subject. So, I’m wondering if you would have your own TMAO levels tested and be willing to publish the results, so we could all feel more content with our meat eating ways? I know I would feel happier, and you too Must be a little curious…

  32. Laura says

    Thanks, Chris! I do want to point out, however, that the previous study mentioned by Chris Masterjohn measured urinary *excretion*, which could be quite different than plasma level. It’s even possible that a higher excretion level of TMAO (e.g. seafood) correlates with a lower plasma level, not higher. Many, many questions to be answered, still :)

    • Chris Kresser says

      The kidney filters TMAO from the serum. So while the levels may not be equivalent, it’s difficult to guess how urinary levels could be high without serum levels also being high at some point, unless the rate of kidney filtration and excretion is ramped up significantly.

  33. Barron Ebenstein says

    I forwarded Chris’ comment about the authors use of Mediterranean diet study as supporting evidence to their claims to Dr. Stanley Hazen, the guy who directed the TMAO study. He replied. Comment back, Chris?

    “You are mistaken. See page 9 of article supplement describing the Mediterranean diet groups. Red meat was to be avoided and instead select white meats used. Second paragraph sub section “g”.

    The control diet was permitted to eat red meat. They had 30% increase in cardiovascular events.

    • Chris Kresser says

      I didn’t see the article supplement initially, but Stephan Guyenet brought it to my attention last night (I read your comment this morning). As usual, what the researchers recommended people eat and what they actually was not the same. Look at Page 27 in the Supplemental Materials. Examine first the column called “Mean Baseline”; this refers to the intake of the listed foods at the beginning of the study. You’ll see that the control group ate 0.8 x 150g of meat per day. The Med + olive oil group ate 0.9 x 150g, and the Med + nuts ate 0.9 x 150g. So the control group was actually eating slightly less meat to start. Now look at the “Within Group Mean Changes”; this refers to the actual increase or decrease in consumption of various foods during the study. The control group decreased by 0.10 (bringing them to 0.7) and the Med + olive oil and Med + nuts groups both decreased by 0.11 (bringing them to 0.79). The takeaway is that there was no significant difference in red meat consumption at the beginning of the study, or at the end. The Mediterranean diet groups ate just as much red meat as the control groups. This means that the 30% decrease in CVD risk was caused by something other than reducing red meat consumption.

      I just updated the article with this information.

      • says

        Thank you for digging into the evidence to refute the anti-red meat scare mongers. I can almost feel your frustration and exasperation at having to explain the obvious to health challenged people who have become so disconnected from the natural world that others can exploit their irrational fears.
        My immediate reaction is to let them believe what they will, it is their problem and too much discussion only gives credibility to misinformation.(Shakespeare,’Thou dost protest too much’).
        That said I am very grateful as a producer of grass/greens fattened beef that you and others have realized the truths of history and now modern science and are prepared to collate and disseminate the evidence having regard to all of the circumstances.
        We have evolved because of our symbiotic and synergistic relationship with red meat ruminants of which the most agisted around the world and nutrient dense is modern beef cattle as you have pointed out in recent posts. Simple logic points to this. One seasonally fat big game ruminant would provide all of the of the protein and fat in balance, plus clothing and shelter over time for a family of five (ten at today’s average per capita consumption) as does one properly fattened modern beef. The same amount of nutrients in fish or fowl would require 500 to 1,000 to replace the food value without the clothing or shelter factor and greens in the form of fruit and vegetables, would obviously be seasonal and require consumption of 10 to 50 times the volume of red meat, severely restricting human habitation around the world.. In other words we would still be big apes in a small part of Tropical Africa..
        Partial truths and a little knowledge are exceedingly dangerous in the wrong hands or heads. For example most understand gasoline, in a controlled burn with a number of variables allows us to drive cars. But in isolation in contact with an open flame can cause serious injury or extinguish life in the blink of an eye.
        All the facts and evidence needs to be considered in context and again thank you Chris and Chris Masterjohn.

    • Chris Kresser says

      Also, Table S5 on Page 26 specifically lists the red meat (rather than total meat, listed in S6 on Page 27) intake across all groups throughout the study. As you can see, there’s no difference in red meat intake. This is an egregious misrepresentation by the authors—unless there is an explanation that is not included in their paper or the supplement, in which case it’s an egregious omission.

  34. John McDonell says

    Much of the present problems with PALEO food eating is not presently done with PALEO lifestyle considerations. Foods were never eaten out-of-season nor were they transported vast distances across climatic zones. Never would an organic banana or pineapple be eaten in LA or NYC in January (any year). Fruit is a seasonal food, and should be eaten seasonally … in the fall. The flora (like most gardens) also has a seasonal rythmicity to it, especially the size of he bacterial populations. AKA grass-fed meat is eaten only when there are pasteurs. Consideration of seasonal cycles and circadian cycles receive too scant attention.

  35. Lisa Y says

    Has anyone looked at this from the omega 3 vs omega 6 standpoint? Seems to me that this very important point is extremely neglected…

    a lack of 3′s causes inflammation which we all know is a huge contributor to arterial diseases….

    • says

      Hi Lisa,
      I am sure Chris has referenced the importance of Omega 3′s and the ratio with Omega 6 etc. I certainly have and agree with you with regard to the whole picture.
      It is for this reason that I started researching grass fats of evolution, both of land and sea because the mainstream were and still are to some extent promoting grass or pasture fed meats as high protein healthy lean meats yet it is the fat profile that contains the essential fatty acids, Omega 6;3 in balance. Our problem today is that they have got out of balance as much as 20 to 1 with grain fatted meats.
      We discovered this on our farm in 1996 and since have not used artificial fertilizer, hormones or antibiotics in producing our beef. It is very hard to go against the grain and industrial ag which is why I respond to these sites because the whole truth is beginning to emerge courtesy of Chris Kresser and others.
      Many producers of grass fed beef do not understand the importance of fat cover on beef historically and the grading system which evolved from it. This is evidenced by many of the pictures on grass fed producers web sites which to the experienced eye depict less than desirable eating quality cattle even though amongst beautiful scenery. Many of these I know from experience would not grade with sufficient fat cover ( I personally have hands on graded over 40,000 head leaving the farm) and, whilst omega 6;3 might be in ideal ratio, is very little more than grain fed cattle. (I believe an average of a little over 60mg per 100g serving compared to 46mg per 100g serving of average grain fed.
      On the other hand cattle fattened to US high select, Low choice, or Canada AA fat cover and marbling will run over 200 to 220mg Omega 3′s in rough balance with Omega 6, certainly less than 1.5 to1 via independent tests of our cattle and other experimentation around the world. This is in ground beef trim samples which constitute about 45% of the average fat beef in medium to lean trim, which visually looks lean due to the omega 3 oily fat(similar to fat in cold water fish) content, compared to grain fed.
      Of course Organ meats, bone marrow and some of the so called tougher cuts such as brisket have much higher nutrient values similar to wild cold water oily fish, salmon, herring etc. with the average ground beef being as good or better than Atlantic cod. Such beef is truly a functional food of the highest nutrient value in balance as a human health food.
      From my research it is patently obvious that we evolved eating this type of red meat and in the last ten years have cut out most other meats and grain/oilseed derivatives from Industrial, arable, fossil fuel dependent Agriculture. At 71 years of age blood lipids and general health is much improved and the research of Chris and other is really credible and as near as I can tell without the vested interest leveled at such as myself and other grassland red meat producers.
      Sorry for length of reply. Please also see my response above to Chris at 11.50 am regarding human food consumption and the reasoning some of the other so called healthy meats and plants could not have played a great part in our evolution.

  36. 4ndy says

    I found a mistake in your article, or what it seems you would call “an egregious misrepresentation” if you’re not in a practice of using Hanlon’s Razor:
    “The human study compares a single vegan that they managed to convince to eat a steak to five “representative” meat-eaters. A sample size of six people, with only one in the vegan group, is hardly adequate to draw firm conclusions from.”
    That sample of six was their first test case. When they found something interesting they followed up with more tests on 51 ‘omnivores’, and 23 ‘vegetarians and vegans’, where their sample of long-term non-meat-eaters were given carnitine, not meat. Page 3: http://www.natap.org/2013/HIV/nm.3145.pdf

    On “While it is well established that free carnitine increases TMAO production, previous studies have not shown that carnitine-rich foods like red meat increase TMAO. In fact, in one 1999 study, out of 46 different foods tested, including red meat, only one food elevated TMAO levels in the participants: seafood”,
    that study (http://www.sciencedirect.com/science/article/pii/S0278691599000289) echoes observations of this one, as it is possible for people to eat carnitine-containing foods and not produce significant TMA excretion, but where in that pilot study did they control for long-term diet and hence gut flora? Of course TMA rising only with seafood can be explained by the presence of TMA in seafood, because the participants’ gut flora did not include sufficient amounts of the bacteria that digest carnitine into TMA.
    Your statement that “it’s overly simplistic to suggest that eating red meat causes elevated TMAO” is attacking a straw-man, because the carnitine study authors were not suggesting this. Their emphasis is on the long-term formation of gut flora in normally ‘omnivorous’ diets. The mice in their study were supplemented with carnitine long-term, which had an effect of increasing their production of TMAO compared to the control diet, both at baseline and upon acute exposure.

    You are very right to bring up the confounding problem of ‘healthy users’ or lifestyles. This requires further study to carefully examine what factors may be in the lifestyle of those ‘omnivores’ that are promoting gut bacteria that produce TMAO, but they already have a mechanism to implicate carnitine in this by their use of a far more controlled study in mice.
    Also see these from their references:
    17. Muegge, B.D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332 , 970–974 (2011): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303602/
    18. Zimmer, J. et al. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur. J. Clin. Nutr. 66, 53–60 (2012): http://www.hablemosclaro.org/pdf/noticias/A_vegan_diet_alters_the_human_colonic_faecal_microbiota.pdf

    • Chris Kresser says

      Chris Masterjohn directly addresses all of your points in his article. I’d suggest reading it if you haven’t already.

      • 4ndy says

        Not unless by ‘address’ you mean he actually mentions their sample sizes correctly and goes into fair detail on the study’s statistical weaknesses. He does elaborate on a crucial detail, the level of variance in the TMAO produced by the ‘omnivores’, making it clear that there must be some quite different people in that group, and other factors need to be controlled for.

  37. RupertDBear says

    Chris Masterjohn also brought up the the key point (for me at least) questioning whether elevated TMAO causes CVD or is the result of it. The TMAO-CVD study (not the Cleveland study) I read identified a link but not a direct mechanism, although the authors supplied a hypothesis.

    From the Nature abstract for the Cleveland Clinic study:
    “Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.”

    Bias?

  38. jennifer ford says

    I’m a strict Paleo eater who has recently shed over 13 lbs of fat following the meat, veg and fat diet. Ill volunteer for your study!! I eat grass fed beef at least 4x per week! And I’m 14% body fat with amazing blood panels! I always ignore.mainstream media…I’m tired of being lied to.

  39. Rosario says

    Chris,

    Thanks for a clear, objective analysis!

    I’m very interested in this gut microbiome issue. Any suggestions on how to restore a gut that was subjected to two rounds of antibiotics last year? I haven’t been “right” for months (you know what I’m talking about.) Probiotics haven’t helped, because good gut bacteria are much more complex than what probiotics provide. Short of a fecal transplant, what would you recommend? Thanks.
    R

  40. John O. Ruud, DDS says

    Of course I’ve been accused of being a “sugar nut” because of my profession. However, around l970 the Harvard School of “Nutrition” released a statement to the effect that sugar was good for you because it was required for energy! Their “objectivity” did not include the fact that our metabolic system can create that “needed” sugar out of anything we eat. Visualize a Paleo man chasing down a wooly mammoth (huge energy requirement), so his family could have lunch!! (They did not have available the 150 pounds per capita/year of refined sugar that “we” consume today.) We came to believe that the sugar industry funded that daunted “research institution”, and the the results of their sugar studies came along with the funding! Witness the study out of eastern Canada about the same era that claimed that artificial sweeteners were bad for our health and alas, sugar was better! (As was the sugar industries funding.)

    The present emphasis on the causes of obesity, heart disease, diabetes, etc., is puttting immense pressure on our food industries to reduce or eliminate the use of natural sweeteners in food products, socalled soft drinks and candy. The sugar “lobby” is attacking, in survival mode. They know, that we know, that the sugar molecule is the singular most responsible element in the health crisis faceing mankind today. So their perfect target is meat and fat, for all the old reasons. They also know that refined carbohydrates, which become a too large part of an alternative diet, are unpalatable without sweetener. Couple that with an addiction to anything else that makes our tongue feel good and the sugar industries addiction to money. The real beneficiaries become big pharma, medical symptomologists and morticians, the only innocents in the group!! Nuff said,.

  41. D'Aun says

    Question: Do you think that grass-fed/grass-finished beef used in a study would have different results? It’s almost like different meat from what I’ve read (and tasted)…

  42. Matt says

    I do not feel it is the red meat causing increased CVD, CHD, CAD, PAD, etc. The gut flora and bacteria are the causes. I would like your opinion on H. Pylori infection being underdiagnosed and undertreated which lead to increased CHD and MI. I feel H. Pylori is way underdiagnosed and treated. However I did speak directly with Stanley Hazen, who told me that antibiotic use had no effects on production of TMAO.

  43. Thamnophis says

    It amazes me to no end that some guy with no real scientific or medical training, i.e. Mr Kresser, can feel OK about encouraging so many people to consume red meat – a practice that is certainly killing them, damaging the environment, and causing so much pain to millions of animals.

    Why would anyone do something that is so destructive to themselves and their world?

    • says

      I am in the opinion of many, just a foolish farmer of grassland and livestock, but I know enough to know that ancestral diets of red meat and epigenetics beget brains and intelligence, not science or medical degrees.
      From my experience, inquiry and observation of humanity and life in nature, lead me to conclude that Mr. Kresser as you call him has done the research and is qualified, always citing peer reviewed scientific and medical research in support of his opinions.
      Yes I have a vested interest in the whole truth and survival of the species, which does not result from tunnel or selective vision to support vegetarianism.
      Please check out the following and it may help broaden your horizons:-Regenerating Grasslands–https://www.facebook.com/photo.php?fbid=653177971434015&set=a.603596089725537.1073741827.603538613064618&type=1&relevant_count=1

      • Thamnophis says

        Anyone can site research to support their view – it doesn’t take a professional to do that. But ask your doctor, then ask another doctor…and another. What you’ll find is that the vast majority of medical professionals will tell you that the best diet is one that is largely plant based. Add to this the fact that meat production is extremely damaging to the environment and in 99% of the cases, torture of the animals and you’ll have all the reasons you need to make vegetarianism the only logical choice.

        Recommending a high meat diet is tantamount to malpractice.

        • says

          So, forget the research, but ask the doctors? OK, here’s a few doctors that have been asked about that:

          Dr Eric Westman: http://www.youtube.com/watch?v=dSLf4bzAyOM

          Dr William Davis: http://www.wheatbellyblog.com/

          Dr Michael Eades: http://www.proteinpower.com/drmike/

          Dr Andreas Eenfeldt: http://www.dietdoctor.com/

          Dr John Briffa: http://www.drbriffa.com/

          Dr Peter Attia: http://eatingacademy.com/

          And a few more doctors: http://authoritynutrition.com/17-low-carb-paleo-doctors-with-blogs/

          What do you think all those doctors do to support their views?

          • thamnophis says

            No, pay attention to the research, AND ask the doctors. Of course, given the internet you can find a handful of renegade quakes who ignore the larger body of evidence in order to promote themselves or some product or lifestyle they benefit from. But as I said, the huge majority of people trained in medicine and nutrition will all agree hands down that a high red meat diet will kill you. Not to mention the environmental destruction and the utter cruelty to the animals being raised so we can eat them.

            • says

              I think I understand. If the doctors disagree with you, then they are “renegade quakes who ignore the larger body of evidence in order to promote themselves or some product or lifestyle they benefit from”.

              You said “…trained in medicine _and_ nutrition…”. (my emphasis) But you said earlier “But ask your doctor, then ask another doctor…and another.” Few doctors are trained in both medicine and nutrition. Standard nutrition course for medical doctors is 1 week. It’s unlikely that my doctor (or any other doctor at random for that matter) would have expertise in nutrition. The best I can expect is they refer me to the official recommendations, cuz that’s what they’re taught in that week-long course on nutrition.

              This begs the question, how “huge” is this “majority of people trained in medicine and nutrition” you speak of? Maybe it would be best if you told us exactly which doctor we should ask all these questions. Give us a name or two.

              Finally, I don’t see why you bring up the environment in your posts. If it’s bad for my personal health, then the environment is a distant worry by comparison. Me first, everything else second. Grok?

              • Louise says

                OK, here’s a physician trained in both medicine and nutrition, maybe the only one in the USA who holds both distinctions: David Perlmutter, author of GRAIN BRAIN. He’s a Board-Certified Neurologist as well as a Fellow of the American College of Nutrition. Over his long career he’s discovered that getting people off grains, especially gluten-containing ones, and onto a diet rich in saturated fats that includes grass-fed beef, eggs and fish, is vital for brain and neurological health. His excellent track record speaks for itself. (The book is quite good, too.)

                • says

                  Thank you Louise, Dr Perlmutter appears very credible. I have listened to several of his U Tube presentations and have cross checked the evidence cited as far as possible on line. His work is corroborated in parts by more and more experts in the fields mentioned.
                  Reading these comments and others disparaging the work of Chris Kresser is very discouraging as I realise that those who have been brainwashed since Ancel Keys half a century ago will probably have to die off before the truths of history and nature again become self evident. It is almost as if they cannot hold a thought and grasp the truth and must ‘parrot’ their beliefs, thinking it makes it true.
                  It is therefore a pleasure to read that some such as yourself and Martin Levac ‘get it’.

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