TMAO and Red Meat - What is it and is it Harmful | Chris Kresser
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Red Meat and TMAO: Cause for Concern, or Another Red Herring?

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What is the impact of red meat consumption on TMAO in the bloodstream? iStock.com/Eraxion

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!).

110 Comments

Join the conversation

  1. I’ve been taking acetyl l-carnitine for years, and I’m a meat eater. I also have heart disease. Thus far I have not believed that meat is the problem. My doctor thought it would be worth having the Cleveland Lab work done. The results show that my TMAO is nearly 6 times the recommended level. I’ve tried a lot of things to reduce my coronary calcium score, which last tested 693. I eliminated my only symptom, atrial fibrillation, by taking magnesium. I take vitamins K, C, E, D. I run and lift weights six days per week, vigorously. I had a root canal tooth removed, which did slow the advancing coronary calcium significantly. But I’m ready to try the vegetarian diet. I’ll let you know how it goes.

  2. I propose a study wherein those with TMAU (those unable to process TMA, and ever make much TMAO anyway) be tested against meat eaters. If those who truly cannot create TMAO are in general far healthier by the numbers (familial cancer/heart disease rates, cholesterol, etc.) then we must find a way to help create a way for TMA oxidation to decrease in “normal” livers. However, given the unfortunate side effects of those who have TMAU, we also need to find a way to combat the horrible body and breath odors that accompany TMAU, and share that with the general public once they figure out how to “un-oxidize” TMAO. Just a suggestion.

  3. Kidney disease too:

    Cleveland Clinic research on a
    substance produced by gut bacteria during the digestion
    of red meat, eggs and high-fat dairy called TMAO, or
    trimethylamine-N-oxide, has already established a link
    between these foods and increased risk of heart disease,
    and now points to an independent and equally troubling
    link to chronic kidney disease. In the journal
    Circulation Research, researchers Dr. Stanley Hazen and
    Dr. Wilson Tang report that patients with chronic kidney
    disease had higher blood levels of TMAO and were at
    higher risk of death, according to the 5-year study.
    In a vicious cycle, TMAO appears to contribute to the
    decline of the kidneys, further increasing the amount
    of the substance in the blood. More TMAO means higher
    heart disease and heart failure risk, and further
    decline. bit.ly/1v0wTiO

    • The link to kidney disease with TMAO is odd, but its well established that those with kidney failure/disease should avoid eating red meat. This being because the load put on the kidneys will be too much due to its weakened state, which in turn can cause further deterioration.

  4. Just a note on “meat.” When using the word, when doing experiments, what is meant by that word “meat?” My understanding is that most meat we eat has hormones added to it to make the animals larger. These hormones may survive processing and cooking and affect our health. Commercial meat also has food coloring, possibly pesticide residues from the food the animals graze on, and if they don’t graze but are fed packaged food, then the very composition of the meat may be less healthy than if they grazed. Contrast these animals with so-called “organic” cows that do graze, are not shot with hormones, and do not have other artificial ingredients injected or fed into them. Are we as healthy eating non-organic vs. organic animals?

    When we blithely compare the modern “paleo” diet with what humans may have eaten eons ago, I don’t believe we can duplicate that diet with modern food. Vegetables are lacking in nutrients, even according to the USDA, meat is not what it used to be, and the air we breathe is not what it was either.

  5. Just a note on “meat.” When using the word, when doing experiments, what is meant by that word “meat?” My understanding is that most meat we eat has hormones added to it to make the animals larger. These hormones may survive processing and cooking and affect our health. Commercial meat also has food coloring, possibly pesticide residues from the food the animals graze on, and if they don’t graze but are fed packaged food, then the very composition of the meat may be less healthy than if they grazed. Contrast these animals with so-called “organic” cows that go graze, are not shor with hormones, and do not have other artificial ingredients injected or fed into them. Are we as healthy eating non-organic vs. organic animals?

    When we blithely compare the modern “paleo” diet with what humans may have eaten eons ago, I don’t believe we can duplicate that diet with modern food. Vegetables are lacking in nutrients, even according to the USDA, meat is not what it used to be, and the air we breathe is not what it was either.

  6. I wonder if anyone clicked any of your references? Because the vegan/veg vs. meat ones don’t all necessarily say what you claim they do.

  7. 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?

    • 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

      • 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.

        • 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?

          • 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.

            • 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?

              • 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.)

                • 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’.

            • You think doctors are trained in nutrition????? LOLOLOLOL! Check out the minuscule amount of nutritional training doctors ACTUALLY get. You’ll be shocked. As a professional in a chemistry-related field, I have consistently found that talking to docs about biochemistry is a bigger waste of time than talking to your dog about it. I have had to deal with docs that don’t know a tocopherol from a retinol, who don’t understand the hazards of transporting cryo gases like liquid nitrogen in a thermos bottle (high-school chemistry!), etc. People who think their docs are knowledgeable about nutrition are very naive.

      • Check out The China Study. One of the biggest nutritional studies ever done which conclusively links high animal protein diets with all of the “big” modern diseases and is very well researched and referenced. Animal protein is bad for us and the production of livestock is bad for the planet. 2nd biggest producer of greenhouse gases in the world . The grain alone used to feed livestock in the USA alone per year would feed 800 million people. I’m not even going into the amount of water used to produce all this meat . The third world sells it’s grain to first world for us to feed to livestock while their own people starve. For many reasons especially health we need to get meat out of our diets. If people had to actually kill their own then there would be a huge reduction in meat eaters. Paleo man were hunter gatherers. How much meat did they eat killing it with a spear with a bit of flint on it? Mostly they were living a vegetarian diet. People are what they eat. The healthiest diet in the study only 7 grammes of protein per day. Half packet of peanuts equivalent and the big diseases only appear when their diet changes to a more western diet of more meat and diary. What does that tell you?

        • The China Study has been thoroughly debunked by a number of qualified professionals. It is rife with the biases and pitfalls that Chris indicates plague many studies. For a debunking that is fairly easy for a layman (non-scientist) to follow, check out Denise Minger’s analysis.

    • Animals do not destroy the environment, people do. Otherwise are world would not have had so many issues in the last 75 years compared to eons before. Cows reduce the carbon footprint if they are allowed to graze normally. Industrial farming is a major culprit. People eat too much meat and there is a lot of us compared to before.

  8. 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.

  9. 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)…

  10. 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,.

  11. 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

  12. 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.

  13. 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?

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

      • 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.

  15. 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….

    • 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.

  16. 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.

  17. 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.

    • 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.

      • 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.

    • 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.

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