Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations

Doomed to premature death?

Ever heard of TMAO? Click that link and you’ll find that “In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported.” Uh-oh!

From European Journal of Nutrition:



The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes.


To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease.DESIGN:In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC-MS/MS.


Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = - 0.34, P < 0.01).


Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health.

Source: Long-term Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentr… – PubMed – NCBI

Click pic to purchase book at

2 responses to “Paleolithic diet is associated with lower resistant starch intake, different gut microbiota composition and increased serum TMAO concentrations

  1. What kind of “paleo diet” was being tested? We know from archaeological evidence, the anthropological record and hunter-gatherer studies that there is no single non-agricultural diet.

    Even among the present paleo diet crowd, there is disagreement about many aspects: low or moderate carb, high or moderate fiber, high or moderate protein, etc; including resistant starch, legumes, dairy, etc or not. There are paleo adherents advocating a mostly plant-based diet, sometimes essentially a Mediterranean diet minus grains, while others are advocating a mostly animal-based diet, including as far as carnivore.

    Paleo is more of a lifestyle than any specific diet. That is a point many people regularly make. So, how does one test the paleo diet? The closest one can do is to look at the health of still independent hunter-gatherers following their traditional diets. But that isn’t what these researchers did.

    As for TMAO, that is a complicated issue. Red meat will only lead to greater production of TMAO in the presence of a high-grain diet. It is the microbe Prevotella that turns carnitine into TMAO and Prevotella’s favorite food is grains. Without grains in one’s diet, one is unlikely to have a large population of Prevotella in the gut.

    Besides that, TMAO is found in other foods or produced from other foods at a higher level than with beef. Even vegetables will contribute to this. Dr. Paul Saladino and Dr. Steven Gundry did a video together. Saladino pointed out that patients of his that are on the carnivore diet measure as being low on Prevotella. And Gundry gave the example of two patients of his who are long-term vegans and measured high levels of TMAO.

    There is obviously more going on here than has been understood or often acknowledged.