A Gut-Heart Connection: A Different View on Eggs, Red Meat, and Heart Disease

  A Gut-Heart Connection: A Different View on Eggs, Red Meat, and Heart Disease

Eggs and red meat cause heart disease according to recent posts by popular media (1, 2). Both articles state that ingestion of either eggs or red meat result in increased TMAO which causes heart disease. The egg specific article suggests that gut bacteria metabolize the choline in eggs and produce TMAO, which then enters circulation and causes atherosclerosis. The red meat article suggests a similar mechanism, except carnitine is being metabolized into TMAO by gut bacteria instead of choline. Both of these studies are fraught with limitations that preclude us from drawing the conclusion that eggs/choline or red meat/carnitine cause heart disease. As Chris Masterjohn’s analysis of these limitations is thorough and articulate, I defer readers to his work for an in-depth look at those limitations. While we cannot make the conclusion that eggs or red meat cause heart disease, these studies do in fact suggest something rather important, there is an association between our gut health and our heart health. Chris Kresser has written extensively on the gut-skin and gut-brain connection, and in light of these recent studies, I believe it is salient to discuss the gut-heart axis. As the evidence currently stands, I believe the gut plays a role in the pathogenesis of heart disease through the inflammatory process via “leaky gut” and the gut microbiome.

Heart Disease and Inflammation

Despite the prevalence of the lipid-heart hypothesis in mainstream media, the most accurate and prevailing hypothesis for the development of heart disease is inflammation. While the inflammatory mechanisms are complex, the concept is simple. Briefly, inflammation results in macromolecule and vascular damage, this then results in the deposition of plaque in the vascular tissue (Figure 1.). A full review of this concept is beyond the scope of this article; however, Libby et al. (2002) wrote an extensive review of the topic and can be found here. His review is extensive and covers potential sources of inflammation including: obesity, diabetes, and infection. However, as with most reviews of inflammation as it relates to heart disease, he neglects the role the gut plays in inflammation.

Figure 1. Inflammation and Atherosclerosis. Image c/o http://www.imcar.rwth-aachen.de/news/2009/03-03-carolus-therapeutics-scibx/

Figure 1. Inflammation and Atherosclerosis. Image c/o http://www.imcar.rwth-aachen.de/news/2009/03-03-carolus-therapeutics-scibx/

Leaky Gut and Inflammation

Our bodies interact with our environment in various ways, including our gut. The gut serves as the interface between food intake (environment) and our metabolic processes. Maintaining gut integrity is critical in providing a solid barrier between our environment and our internal processes. Think of your gut as an internal skin. When you have a scrap on your hand and you get dirt (bacteria) in it, your body mounts an inflammatory immune response to combat the pathogens. The same concept applies in your gut. Disruption of the gut barrier integrity results in translocation of bacteria into circulation (endotoxemia) (3). The presence of bacteria, specifically lipopolysaccharides (LPS) results in an inflammatory response (Figure 2.). Therefore, chronic disruption of the gut barrier will result in chronic inflammation (4).

Figure 2. Leaky Gut and Inflammation. Image c/o http://www.medicalcentersatlanta.com/The-Leaky-Gut-Syndrome

Figure 2. Leaky Gut and Inflammation. Image c/o http://www.medicalcentersatlanta.com/The-Leaky-Gut-Syndrome

Causes of Leaky Gut

Perhaps the most “popular” cause of leaky gut is grain consumption. Gliadin, a specific protein in many grains, including wheat, barley, and rye interacts with the cells lining your intestinal tract (enterocytes) and modulates the tight junctions, resulting in a permeable/leaky gut (5). This effect is heightened in individuals with Celiac disease who display an overactive immune response to gliadin. Ask any individual with celiac or IBS and they will tell you the devastating effect these small, problematic proteins have on their gut. While many people argue that gliadin and other grains are problematic only to those individuals with a specific autoimmune condition (i.e. Celiac or Chron’s), recent work by Dr. Alessio Fasano has demonstrated that gliadin does indeed modulate tight junctions even in non-celiac individuals (6).  Thus, grain consumption may indeed be a play in promoting gut-induced inflammation.

            Another potential cause of gut related inflammation is the microbiome. Research surrounding the microbiome is nascent and is providing a wealth of information in regard to how the gut impacts heart disease.  Using a mouse model, Cani et al (2008) demonstrated alteration of the gut microbiome modulates endotoxemia and resulted in lower inflammation (7). A later study by Cani (2009) demonstrated the change in gut microbiota controlled inflammation by improving gut permeability (8). This improvement in gut permeability was associated with lower systemic and hepatic inflammation. Together, this suggests the gut microbiome plays a role in modulating gut permeability and inflammation, indicating the gut may play a role in the pathogenesis of heart disease.

A Different View on Eggs, Red Meat, and Heart Disease

This brings us to the egg and red meat studies. First let us examine the evidence of TMAO and heart disease, as I do believe this is valid data given the evidence presented above. An analysis of survival data and TMAO levels in individuals with heart failure suggests there is indeed an association between TMAO levels and survival in heart disease (Figure 3). This association does indeed suggest some relationship between TMAO levels and heart disease.

Figure 3. TMAO and Heart Disease Related Survival.

Figure 3. TMAO and Heart Disease Related Survival.

In light of all this evidence, lets revisit the egg and red meat studies for I believe they hold some key evidence. Both studies followed similar designs and found similar results. While there is complex science involved in these studies and I will be making some assumptions, I think the major concepts and results paint a clear picture.

Briefly, the major findings from the “egg study” demonstrated that specific gut flora are required for the formation of TMAO from dietary phosphatidylcholine (PC) in mice, and that this TMAO from gut bacteria metabolism appears in circulation. The egg study also demonstrated an association between PC metabolites heart disease in humans. Perhaps most importantly, they demonstrated that suppression of the TMAO producing gut bacteria via antibiotics inhibited the choline-supplementation induced atherosclerosis in mice. While mouse models can be problematic for various physiological reasons, the evidence presented in the egg study suggests that our microbiome is indeed a major dictator of what molecules end up in circulation and that modulation of gut bacteria impacts the development of heart disease in mice.

The “red meat” study, while severely limited in its ability to draw direct conclusions on red meat and heart disease, it presents interesting evidence. The results of their study were virtually identical to the egg study and the same concepts apply. However, there is additional information in this article suggesting the microbiome does indeed play a role in heart disease. The data suggests that high TMAO levels, but not carnitine levels result in marked decrease in survival rates (Figure 4).   Also, as with the egg study, the authors found and clearly state “Dietary L-carninitine promotes microbiota-dependent atherscholerosis”.  While the evidence presented suggests it may be the carnitine and TMAO that results in atherosclerosis due to reduced reverse cholesterol transport, even the authors state, “as the L-carnitine–supplemented mice that received antibiotics did not show enhanced atherosclerosis, these results are consistent with the notion that it is a downstream microbiota-dependent metabolite, not L-carnitine itself, that promotes atherosclerosis.” Again, suggesting it is the gut bacterium that is associated with the change in metabolism, gut function, and decreased cardiac survival.

Figure 4

Figure 4. Carnitine and TMAO levels and event-free survival. Image c/o http://www.nature.com/nm/journal/v19/n5/full/nm.3145.html

In Summary

 From the concepts and evidence presented in this article, I believe it is clear the gut plays a role in heart disease. While the precise mechanisms are not completely understood, I would argue we can draw the conclusion that gut integrity and a healthy, robust microbiome is key in promoting “heart health”.  You can promote a “healthy gut” by minimizing or avoiding problematic dietary proteins (i.e. Gluten and gliadin), consuming foods high in prebiotics and probiotics (vegetables and fermented foods) and avoiding smoking and excessive alcohol consumption. Such a diet and lifestyle is easy to follow in the context of an “evolutionary approach” to health.

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