Tag Archives: tmao


At the heart of the scientific process is debate. Debate is critical because everything in science is a theory and theories can only be improved by constantly challenging and refining them.

In nutritional science the debate often gets heated and even that can be a good thing. Scientists debating the merits of various diets often cite vastly different and contradictory studies. Sometimes they can even doggedly argue polar opposite interpretations of the same study.

But as long as you can back it up with research, almost anything is fair game.

Almost anything.

One thing you cannot do is create your own definition of a theory and then debate the merits of that definition.

For example, if we were going to debate the merits of the Paleo Diet vs the Mediterranean Diet, we couldn’t argue that the Mediterranean is unhealthy because people on the diet eat a pound of Oreos every day. They don’t. That’s not part of the definition.

In fact, we recently wrote an article comparing the nutrient density of the Paleo Diet to the Mediterranean Diet. To make this comparison we used the gold-standard Mediterranean sample menu as defined in the literature.[1] It took me hours to find the most acknowledged version, but it was time well spent because we wanted to debate the Mediterranean Diet and that meant debating the accepted definition.

Unfortunately, not everyone shares our standards and right now there’s a study making the rounds in the media that broke this important rule.

The study by Genoni et al has made claims about serious health concerns with the Paleo Diet. The authors found that people on a Paleo Diet have significantly higher levels of serum trimethylamine-N-oxide (TMAO) which has been associated with heart disease.[2]

Not only was the definition of a “Strict Paleo Diet” in their study not Paleo, but it matched up almost perfectly with fad low-carbohydrate diets which advocates of the Paleo Diet have stated clearly are neither Paleo, nor healthy.[2, 3]


Comparing the Diets: Why It Wasn’t Paleo

The study focused on a group that the authors referred to as the “Strict Paleolithic group” Their primary finding was that “consumption of a long-term Paleolithic diet was associated with markedly higher serum TMAO concentrations, but only in those who adhered to the diet strictly.”

So just how Paleo was this strict Paleo group?

In the Revised Edition of The Paleo Diet – the original Paleo Diet book and still recognized as the book that defines the diet – Dr Loren Cordain dedicated the first chapter not to defining the diet, but to warning readers against confusing fad low-carbohydrate diets with the Paleo Diet. In fact, this first chapter is titled “Not Just Another Low Carb Diet.”[3]

On page 24, the book breaks down a standard Paleo Diet next to a fad low-carb diet and shows what makes them different.

In Table 1 below, we have reproduced that comparison and placed next to them the breakdown of the three diets in the TMAO study by Genoni et. al.. We also included the breakdown of two sample Paleo Diet menus created by Dr. Cordain. One is from page 29 of his book and the other is from a 2002 study Dr Cordain published in the Journal of the American Neutraceutical Association (JANA) showing the nutrient composition of a sample Paleo Diet.[4]

Table 1. Comparison of the compositions of the three diets in the Genoni et. al. to two sample Paleo Diet menus and compositions of a proper Paleo Diet and Fad Low-Carbohydrate Diet as defined in the Revised Edition of The Paleo Diet.[2, 3]

* taken from the 2011 Revised Edition of The Paleo Diet, the first and still considered the definite definition of the Paleo Diet
** taken from a 2002 study by Dr Cordain published in JAMA containing one of the first analyses of a sample Paleo Diet menu
***6.7g of the polyunsatured fats (32%) were in the form of Omega-3s compared to 1.0g in a typical Western diet

What is most striking is that the “Strict Paleo Diet” group in the study by Genoni et. al. lines up almost perfectly with the definition of a fad low-carbohydrate diet and does not line up at all with the Standard Paleo Diet (highlighted in pink.)

In fact, strictly by the breakdown in the table, the Control group, which was defined as “consuming a diet typical of national recommendations,” lined up better with the Standard Paleo Diet than the Strict Paleo Diet group in the study.

What’s equally striking is how easy it is to see these contradictions. Anyone can recreate this table simply by looking at page 24 of The Paleo Diet and the diet chart in the TMAO study. You don’t need a degree in statistics nor do you need a Ph.D.

However, a Ph.D. leading a major research study should know better.

The fact is, the authors did not work with the accepted definition of the Paleo Diet. Instead, they worked with their own definition. Literally. In their Introduction they claim, “The Paleolithic diet can be classed as a low carbohydrate diet [5}.” That sole references is to a study by the same lead author – Genoni.[5] In other words, they referenced themselves for their definition of the diet.

And unfortunately, the criteria in their definition were woefully inadequate. Subjects only needed to eat minimal grains and dairy. That is not a sufficient definition of the Paleo Diet and as the study unfortunately proved, does not differentiate between a fad low-carb diet and a true Paleo Diet.

The two Paleo groups in this study were actually following a fad low-carb diet and the inability of Genoni et al to make this differentiation brings into question the primary conclusions of their study:


The Paleo Diet is Not Another Low Carbohydrate Diet

In a recent Newsweek article, lead author Genoni pointed to the low carbohydrate nature of the Paleo Diet as one of the major concerns. “We also found that populations of beneficial bacterial species were lower in the Paleolithic groups, associated with the reduced carbohydrate intake.”

It’s worth pointing out that their healthy control group fits within the carbohydrate range for a standard Paleo Diet. And while the sample Paleo Diets in table 1 are lower in carbohydrates than this control group, the two Paleo groups in the study clearly do not fit within the Paleo Diet carbohydrate definition.

We actually share the author’s concerns with very low-carbohydrate diets and have written about it.


Can She Blame Low Fiber Consumption?

In another interview with Paleo Magazine, Genoni said that elevated TMAO from consuming fish is not a concern because it is transient. Her concern was chronic TMAO elevation on a Paleo Diet due to the low-fiber in the diet. However, not only is the Paleo Diet not low in fiber, the breakdown of the two sample Paleo Diet menus in Table 1 have a higher fiber content than any of the diets in the study at 42.5g and 47g respectively. The control diet in the study only averaged 29.7g.


Or Fats?

“Conversely the direction of the shift in microbiota composition associated with fat consumption was in the opposite direction and suggests a more deleterious profile.” That’s a heavy quote. But it was a lead in to a substantial portion of the conclusions where the authors explained that the high-fat and particularly high-saturated fat content of the Paleo Diet may cause unwanted changes in our gut bacteria.

While the fad low-carbohydrate diets in the study are very high in fats, the two sample Paleo Diets published by Dr Cordain are comparable to the study’s control diet in total fat. In fact, the sample Paleo diets are actually lower than all of the study’s diets in saturated fat at 18g and 21g respectively. Even the study’s control diet averaged 27.3g of saturated fat.


In a Good Scientific Debate, You Come Armed with Scientific References

As we already pointed out, the sole reference the researchers had for claiming a Paleo Diet is low carbohydrate was one of their own studies. But that wasn’t the only place Genoni et al made strong claims with little backing.

The very first line of the study states that “The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support this claim.” Their sole reference for this prominent line in the study is a 2016 Australian cookbook.[6]

If you’re going to reference books instead of studies, what about all the books that actually popularized the Paleo Diet internationally. Better yet, what about referencing actual research about gut health. To start with, what about all the respected scientists who spent years living with and studying still existent hunter-gatherer societies. Their large body of research has consistently reported a robust microbiome, remarkable gut health, and nearly non-existent heart disease in these societies despite the fact that they’ve never eaten a single whole grain. [7-14]

We recommend starting with The Diverse Microbiome of the Hunter-Gatherer published in Nature – one of the most respected journals in the world. Scientifically, it certainly has more to say than an Australian cookbook.


We’re Ready to Debate… When You Are

To the authors of this study, we welcome a debate with you. We will give you full credit that the statistical analysis in your study was high quality, and you found concerning trends in plasma TMAO related to diet.

However, we have real concerns with the design of your study. Not the least of which is the fact that you did not study the Paleo Diet. The diet in your study was a fad low-carbohydrate diet that we have already stated is not Paleo and agree is not healthy.

So, before we engage in a debate with you, we ask two favors:

First, please make sure you stick to the rules of debate and learn the definition of the Paleo Diet before you show up. The one thing you do not get to do is create your own flawed definition of the diet and then attack those flaws.

Frankly, we’re sure your study was very expensive. It seems like it would have been prudent, before investing that sort of time and money, to have done your background research and learned what the Paleo Diet is. You know… read the first 30 pages of the New York Times bestseller that defined the Paleo Diet.

The truth is that we know you have done that. And what baffles us is that you seem to have completely forgotten the definition. You did conduct an earlier group of studies in 2016 where you had subjects read The Paleo Diet by Dr Loren Cordain and follow it’s guidelines. Those subjects did not see a rise in TMAO levels and actually saw health improvements including significant weight loss.[5, 15] How exactly did you forget the definition of the diet over those three years?

Second, until you understand the definition – or perhaps stop conveniently forgetting it – please stop using the term “Paleo Diet” or making claims about it. The fact is, your current research doesn’t study it.


Click Here to read a response to this study by fellow member of the Paleo Diet Editorial Board, Dr Mark J. Smith. Mark dived into the politics of this research and the Dieticians of Australia Association’s long standing debate with the Paleo Diet. Mark dives deeper into the fact that this was not actually the first study Genoni et al conducted of the Paleo Diet. In their first study, they gave subjects copies of “The Paleo Diet” by Dr Loren Cordain and instructed them to follow the books guidelines. That study found benefits to the Paleo Diet.



1. Ryan, M.C., et al., The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol, 2013. 59(1): p. 138-43.

2. Genoni, A., et al., Long-term Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations. Eur J Nutr, 2019.

3. Cordain, L., The Paleo diet : lose weight and get healthy by eating the foods you were designed to eat. Rev. ed. 2011, Hoboken, N.J.: Wiley. xv, 266 p.

4. Cordain, L., The nutritional characteristics of a contemporary diet based upon Paleolithic food groups. Journal of the American Nutraceutical Association, 2002. 5(5): p. 15-24.

5. Genoni, A., et al., Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial. Nutrients, 2016. 8(5).

6. Evans, P., The complete gut health cookbook. 2016, Sydney: Pan Macmillan Australia Pty Ltd.

7. Schnorr, S.L., The diverse microbiome of the hunter-gatherer. Nature, 2015. 518(7540): p. S14-5.

8. Fragiadakis, G.K., et al., Links between environment, diet, and the hunter-gatherer microbiome. Gut Microbes, 2019. 10(2): p. 216-227.

9. Mancabelli, L., et al., Meta-analysis of the human gut microbiome from urbanized and pre-agricultural populations. Environ Microbiol, 2017. 19(4): p. 1379-1390.

10. Rampelli, S., et al., Metagenome Sequencing of the Hadza Hunter-Gatherer Gut Microbiota. Curr Biol, 2015. 25(13): p. 1682-93.

11. Crittenden, A.N. and S.L. Schnorr, Current views on hunter-gatherer nutrition and the evolution of the human diet. Am J Phys Anthropol, 2017. 162 Suppl 63: p. 84-109.

12. London, D. and D. Hruschka, Helminths and human ancestral immune ecology: What is the evidence for high helminth loads among foragers? Am J Hum Biol, 2014. 26(2): p. 124-9.

13. Cockburn, T.A., Infectious diseases in ancient populations. Curr Anthropol, 1971. 12: p. 45-62.

14. Davis, E.W. and J.A. Yost, The ethnomedicine of the Waorani of Amazonian Ecuador. J Ethnopharmacol, 1983. 9(2-3): p. 273-97.

15. Genoni, A., et al., Compliance, Palatability and Feasibility of PALEOLITHIC and Australian Guide to Healthy Eating Diets in Healthy Women: A 4-Week Dietary Intervention. Nutrients, 2016. 8(8).


The Paleo Diet and Vegetables


When you have been a proponent of Paleolithic nutrition for nearly 30 years, have read the research on its health benefits, and have knowledge of thousands of individuals that have benefited by its adoption, you receive negative research1 with a healthy dose of skepticism.  That being said, one still has to examine the research and make an objective assessment to either include it in the database of relevant studies, move it into the “more research needed” column, or confidently challenge it as yet another biased attempt to discredit an important area of nutritional research.

I say this because we’ve been here before.  In fact, last time we felt the research/reporting was so poor and biased, that three of us from The Paleo Diet® Team wrote articles addressing the issue.  This previous research came out of Australia, as does this new research paper published by Genoni et al. claiming the Paleolithic Diet raises serum trimethylamine-N-oxide (TMAO), a potential biomarker of cardiovascular disease (CVD).  In fact, the few negative studies published about the Paleo Diet all appear to come from Australia. So, it might be worth starting by taking a quick look at some of the nutritional politics down under.

The Dietitians Association of Australia (DAA) presents itself as “the peak body for dietetic and nutrition professionals, representing more than 7,000 members around Australia and overseas.”  Further, the DAA states that, “we recommend looking for the Accredited Practising Dietitian (APD) credential when choosing a dietitian.”  The DAA, of course, is responsible for bestowing that title on any nutritionist wanting the same.  That also means anyone coming along with something successful that they don’t own, or control, would obviously be competition and in theory could result in their member number decreasing.

So, when Australian celebrity chef, Pete Evans embraced the Paleo Diet® and simply used his skills as a chef to create recipes to share with his followers, the DAA made it a cause to discredit him at every opportunity.  They have chosen to frequently attack him as unqualified and create the impression that he came up with the concept of Paleolithic nutrition, rather than address in detail the enormous body of peer-reviewed literature that supports the Paleolithic nutritional template.

You can see that the DAA doesn’t have a particularly favorable opinion of Paleolithic nutrition by viewing their assessment of the diet on their website.  In their opening remarks, they state, “There is debate whether the Paleo Diet is truly healthy or not.  Higher-protein diets have been examined in research and a local version has been promoted by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), called the Total Wellbeing Diet[i].  However, compared to the Paleo Diet, the CSIRO Total Wellbeing Diet has been extensively studied in a variety of groups.”  This is a remarkable statement as it is a complete misrepresentation of the facts.  As the screen shots below show, a search on the US National Library of Medicine’s website (aka PubMed.gov), for (Paleolithic[Title]) AND Diet[Title] returns 46 results, while a search for (CSIRO[Title]) AND diet[Title] returns only 2!


Screenshot #1


Screenshot #2


The DAA wants their audience to think that the Paleolithic diet is a crazy celebrity fad with little to no research.  They do attempt to address a few research papers in their assessment, but the interpretation leaves much to be desired and of course they conveniently ignore the vast body of research that exists today supporting Paleolithic nutrition.

From what I’ve seen, the DAA are doing everything they can to discredit the Paleo Diet® and protect their brand irrespective of the vast majority of the research, showing a benefit of following the Paleolithic dietary template.  Which is actually a great shame, as I think the DAA is missing out on a wonderful opportunity to help the Australian populace.

As will be discussed, what the current study does highlight is that there is clearly confusion as to what actually constitutes a modern Paleolithic diet.  One of the major downsides of Dr. Loren Cordain’s research going viral and the subsequent creation of the Paleo diet movement, was the simultaneous creation of many self-determined experts.  They have in turn, created their own versions of a Paleolithic diet that, and unlike the template created by Dr. Cordain, have not been supported by the peer-reviewed process.  So, it would make sense for the DAA to include the science and practical implementation of a modern Paleolithic Diet within their APD program to help with this confusion.


What does all this have to do with the newest research paper on the Paleo Diet from Australia?

Well, first, the research was conducted at Edith Cowan University which has a dietetics education program accredited by the DAA.  On its own, that shouldn’t be a red flag, however, there are a number of other issues that need to be considered.  First, the research paper, to me, was not written with the impartial tone that one is used to seeing in research papers.  The very opening statement in the abstract appeared unusual.  It stated, “The Paleolithic diet is promoted worldwide for improved gut health.”  This statement stood out because while I am certainly aware of the benefits both clinically and from the research, it is a rather specific point given the relatively limited research related to the adoption of a Paleolithic diet and its effect on gut health.

If you conduct an advanced search at PubMed.gov using Paleolithic AND Diet AND Gut AND Health, as of this writing, you will be presented with just 13 studies that match this search criteria.  One of which is this current study, leaving 12 studies that match the search.  One could argue that seven of these studies could be related to the adoption of a Paleolithic diet and gut health, which again, seems limited to justify such a statement.

So, I was interested in seeing why this study used that statement about the Paleolithic Diet being promoted worldwide for gut health.  It was cited, so I quickly turned the pages to see the source of this front and center statement, and was shocked to see that the hypothesis of this research paper was citing a 2016 book, entitled “The complete gut health cookbook” written by Pete Evans.2  Yes, that’s correct, the same celebrity chef that I referred to above that the DAA has made a common target.

Now, with no disrespect to Pete Evans, finding a book with that title does not justify a scientific research group stating that the Paleolithic diet is being promoted worldwide for improved gut health.  But again, on its own, it also doesn’t mean that the research isn’t a valid topic to be investigated, I think looking at how Paleolithic nutrition can influence gut health is a great idea, and there is a significant body of research that shows that the microbiome of hunter gatherers is far more diverse than industrialized populations and correlates to the health of the host.3-33

However, it did make me think we need to dig a little deeper here as to any potential conflicts of interest.  In doing so I found it very interesting to learn that Edith Cowan University banned high fat proponent and Bring Back the Fat author, Christine Cronau from speaking at the University, saying it did not align with the institute’s “evidence-based approach”.

Following the reference to Pete Evan’s “The complete gut health cookbook” was the statement, referring to the Paleolithic diet, “However, it excludes grains and dairy, food groups that form part of the evidence-based national Australian and international dietary guidelines.”  “Evidence-based”, suggesting that excluding grains and dairy is not evidence-based.

Well let’s examine this statement a little further.  As I have previously stated in other articles, Dr. Cordain’s book “The Paleo Answer” references over 900 sources, with only a handful not coming from peer-reviewed journal articles34.  There’s also Dr. Cordain’s large body of published peer-review research, each with hundreds of references.  So I would say that’s pretty much evidence-based!  But how about the Australian and international dietary guidelines, are they really evidence-based?  Well that’s another story, but thankfully there is an eye-opening paper published in 2015 in the British Medical Journal by Nina Teicholz, that tackles that very question.35  I highly recommend you take the time to read it.

Further, while it is correct that the Paleolithic diet excludes grains and dairy, it also excludes legumes and all processed foods.  It is interesting to see how many people represent these exclusions as a negative, but when one appreciates the benefit to detriment ration of consuming these foods, one quickly understands the net benefit of elimination.

So before getting into the details of this particular study, let’s take a quick look at the database of published research on the effects of adopting a Paleolithic diet.  We’ve been keeping track of this since, somewhat ironically, the landmark aboriginal study by O’Dea that demonstrated a marked improvement in carbohydrate and lipid metabolism after a temporary reversion to a traditional lifestyle36.  The list of published studies can be seen at our website here.


Earlier Research By the Same Authors Actually Finds Benefits to the Paleo Diet

Of the now nearly 50 published papers looking at Paleolithic nutrition, only a few, report any negative consequences (one study’s title indicated a negative result, but the data actually revealed a positive outcome!).  Dr. Angela Genoni is responsible for three publications reporting negative findings.  However, her first published study37 demonstrated beneficial outcomes of adopting a Paleolithic diet but subsequent results have been negative, or perhaps better stated, they have been presented as negative findings.  Consequently, I think it prudent to examine these publications ahead of her most recent paper.  To clarify, in her earlier research only one study was actually conducted, and the data was presented in three separate publications.37,38,39

The opening line in the abstract of the first published paper, while certainly open for interpretation, seems grossly inaccurate, at least to me.  The paper states that “limited literature surrounds the dietary pattern” and referenced three published papers despite there being over 30 studies at the time of publication (see, again, our chronological publication list).  This just supports my concern that the research was not being conducted with impartiality as it is very easy to use PubMed.org and obtain these studies.  And this of course does not even include the many studies that support the negative consequences of consuming grains, legumes, dairy and processed food, foods not included in the Paleo Diet®, listed in Dr. Cordain’s book, The Paleo Answer.34

In Dr. Genoni’s first study, the dietary intervention is described as follows: “Those in the Paleolithic group were provided with meal ideas obtained from “The Paleo Diet” book [Cordain, L. The Paleo Diet; JohnWiley & Sons, Inc.: Hoboken, NJ, USA, 2011.] and advised to consume lean meats, fish, eggs, nuts, fruits and vegetables, and small amounts of olive or coconut oils.  Grains, cereals and dairy products were not permitted.  Dairy products were replaced with unsweetened almond milk.  Sugarless black coffee and tea were allowed.  All vegetables were permitted on the diet, except for corn, white potatoes and legumes.  To ensure adequate carbohydrate, additional fruit was recommended.  Dried fruit was limited to one tablespoon per day.”  I’d say this is a good recommendation to implement a modern Paleo Diet®, although one should point out that corn, potatoes and legumes are not vegetables, and there should be no need to recommend additional fruit.

The study concluded that in healthy females, the Paleolithic diet induced a more favorable effect on body composition over the short-term intervention period.  The full paper can be accessed here.

The second study, published just a few months after the first publication, was titled “Compliance, Palatability and Feasibility of PALEOLITHIC and Australian Guide to Healthy Eating Diets in Healthy Women: A 4-Week Dietary Intervention”.38  As already stated, this research was part of the first study examining the cardiovascular and metabolic impacts of the diets.  If you are interested in reading about the findings, you can get access to the full article here.

I would only like to make one important point.  In the discussion, the authors state, “While both groups viewed the diets as healthy, a greater proportion of the Paleolithic group felt that the diet did not fit with the belief of a ‘healthy’ diet.  This may reflect participant belief that the while the Paleolithic diet is high in ‘healthy foods’ such as fruits, vegetables, eggs, meats and nuts, the elimination of grains and dairy products makes the dietary pattern less healthy or unhealthy.”  Well is this really that surprising given that the DAA is shouting from the rooftops, that the elimination of dairy and grains is a really, bad idea!

The third publication presented data on the dietary intake of resistant starch (RS), a dietary component that has similar physiological effects as dietary fiber and potentially related to bowel health, and the serum concentrations of TMAO, a potential biomarker of CVD.39  The full paper is also available on-line and can be accessed here.  The data showed a significant reduction in RS for the Paleolithic diet but did not show a significant difference in TMAO between the two diets.

The authors speculated that the inability to see a difference in TMAO, may have been due to a small sample size and the low total energy of the diet.  However, it should be emphasized that this data is from the same study that did show the Paleolithic diet to significantly improve body composition.  With respect to RS, increasing RS in typical western diets may well confer a benefit, because of the low fiber intake, however, when total dietary fiber intake is high, which it is on a Paleolithic diet (confirmed by the groups own research37), increasing RS likely has little benefit.


The Most Recent Study by This Group Fundamentally Changes Their Study Design

Because the initial study only examined the effect of a Paleolithic diet over a short-term, 4-week intervention, the current study was designed to see if long-term adherence to a Paleolithic diet, compared to controls, would also see a significant reduction in RS and an increase in TMAO.  Recruitment for the study was done via online advertisements.

Unlike the initial research where no increase in TMAO was seen, the data from this study did show an increase, as well as a reduction in RS.  However, TMAO is a complicated topic and we will be addressing this in a detailed follow-up article in the coming weeks.  But suffice to say, one cannot state that increased TMAO concentrations is causative of CVD, rather there has only been shown a correlation between high TMAO levels and CVD.

While the current study has shown an increase in TMAO, this does not match the findings of many previous studies already referenced that have shown a Paleolithic Diet to decrease markers of CVD.  And correlation is not causation.  Further there is a difference between exogenous TMAO from foods, primarily fish and red meat, and endogenous TMAO produced by microorganisms in the gut.  To highlight this point, fish is one of the greatest dietary sources of TMAO40 and yet, fish has been well established as being cardio-protective.41  So, while fish can elevate TMAO but not be the cause of CVD, CVD could certainly be responsible for increasing TMAO, two very different physiological outcomes.

But of major concern with the current study is its design.  The authors categorized Strict Paleolithic (SP) as subjects that consumed <1 serving of grains and dairy per day and Pseudo-Paleolithic (PP) as subjects that consumed >1 serving of grains and dairy per day.  I think a more appropriate categorization would be SP as having <1-2 servings of grains and dairy per week and PP having <1 serving of grains and dairy per day, and even that might be a stretch (no data was presented with respect to legume consumption in the present study, although the first study did, and consumption was minimal).

So, the big question to ask here\ is: did the subjects assigned to the respective Paleolithic diets even consume a Paleolithic diet?  My colleague on the Paleo Diet® Team, Trevor Connor, has also written an article about this study and shared the same concern with me regarding this question.  So Trevor compared the reported dietary data and shows it in a table in his article.  What it confirms is that the current study did not examine a Paleolithic diet compared to the template developed by Dr. Cordain, particularly when one compares the dietary fiber.  Interestingly, when one looks at the fiber content of their initial study, as a percentage of caloric intake, the fiber content matches up very closely to the Paleolithic diet presented by Dr. Cordain in his 2002 paper.42  And this initial study showed the Paleolithic diet to improve body composition while not increasing TMAO.

So, in summary, since the current research paper didn’t actually examine a Paleolithic diet, the conclusion cannot be made that the Paleolithic diet raises serum TMAO.  However, earlier research conducted by Genoni et al., when an appropriate Paleolithic diet was administered, did demonstrate a Paleolithic diet to improve body composition in a 4-week intervention, without increasing TMAO.  Perhaps the most important finding of this study, is that there are many people thinking they are following a Paleolithic diet when they are not doing so, which highlights the importance of from where individuals are obtaining their information!



1. Genoni, A., et al., Long-term Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations. Eur J Nutr. 2019 Jul 5. doi: 10.1007/s00394-019-02036-y.

2. Evans, P., The complete gut health cookbook. 2016, Sydney: Pan Macmillan Australia Pty Ltd.

3. Cockburn, T.A., Infectious diseases in ancient populations. Curr Anthropol, 1971. 12: p. 45-62.

4. Nasidze, I., et al., High Diversity of the Saliva Microbiome in Batwa Pygmies. PLoS One. 2011;6(8):e23352. doi: 10.1371/journal.pone.0023352. Epub 2011 Aug 16.

5. Bengmark, S. Nutrition of the Critically Ill—A 21st-Century Perspective Nutrients. 2013 Jan 14;5(1):162-207. doi: 10.3390/nu5010162.

6. Bengmark, S. Nutrition of the critically ill – emphasis on liver and pancreas. Hepatobiliary Surg Nutr. 2012 Dec;1(1):25-52. doi: 10.3978/j.issn.2304-3881.2012.10.14. Review.

7. Adler, C.J., et al., Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions. Nat Genet. 2013 Apr;45(4):450-5, 455e1. doi: 10.1038/ng.2536. Epub 2013 Feb 17.

7. London, D. and Hruschka, D., Helminths and human ancestral immune ecology: What is the evidence for high helminth loads among foragers? Am J Hum Biol, 2014. 26(2): p. 124-9.

8. Martinez, F.D., The Human Microbiome Early Life Determinant of Health Outcomes Ann Am Thorac Soc. 2014 Jan;11 Suppl 1:S7-12. doi: 10.1513/AnnalsATS.201306-186MG.

9. Quercia, S., et al., From lifetime to evolution: timescales of human gut microbiota adaptation. Front Microbiol. 2014 Nov 4;5:587. doi: 10.3389/fmicb.2014.00587. eCollection 2014.

10. Rook, G.A., Microbial ‘old friends’, immunoregulation and socioeconomic status Clin Exp Immunol. 2014 Jul;177(1):1-12. doi: 10.1111/cei.12269. Review.

11. Schnorr, S.L., Gut microbiome of the Hadza hunter-gatherers. Nat Commun. 2014 Apr 15;5:3654. doi: 10.1038/ncomms4654.

12. Bligh, H.F., Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin

homeostasis: an acute-effects randomised study. Br J Nutr. 2015 Feb 28;113(4):574-84. doi: 10.1017/S0007114514004012. Epub 2015 Feb 9.

13. Logan, A.C., et al., Natural environments, ancestral diets, andmicrobial ecology: is there a modern “paleo-deficit disorder”? Part I J Physiol Anthropol. 2015 Jan 31;34:1. doi: 10.1186/s40101-015-0041-y. Review.

14. Logan, A.C., et al., Natural environments, ancestral diets, andmicrobial ecology: is there a modern “paleo-deficit disorder”? Part I J Physiol Anthropol. 2015 Mar 10;34:9. doi: 10.1186/s40101-014-0040-4. Review.

15. Obregon-Tito, A.J., et al., Subsistence strategies in traditional societies distinguish gut microbiomes. Nat Commun. 2015 Mar 25;6:6505. doi: 10.1038/ncomms7505.

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