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Back in 2011, researchers published a paper proposing that a naturally occurring compound called TMAO (trimethylamine N oxide), most commonly found in red meat, increases the risk of developing heart disease (1). If we use our deductive reasoning skills this means that if red meat consumption elevates TMAO, and elevated TMAO increase the risk of heart disease, we'd see higher rates of heart disease in people that eat more red meat. However the epidemiological evidence examining this question is mixed.
For example there was a large meta-analysis study published in 2010 that covered over 1.2 million participants found the contrary. That is the consumption of non-processed red meat was not associated with increased risk of coronary heart disease, stoke, or diabetes. (2) 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 a positive association between red meat consumption (both fresh and processed) and total mortality, cardiovascular disease (CVD) and even cancer. (3) So for example, let's say a study shows that eating bacon increases your risk of heart disease. If we apply the patterns I described above, these people will tend to eat more processed foods, refined sugars with less fruits and vegetables. They also may drink and smoke more while exercising less. Some studies most mostly those looking at two variables with a large population set generally don't take these confounding factors into consideration. An elevated level of TMAO could reflect perhaps an over consumption of dietary trimethylamine (be it from red meat, or sea food); it could also reflect an impaired excretion of TMAO into the urine, or even an enhanced conversion of TMAO in the liver to undergo it's metabolic breakdown. These's an enzyme called Fmo3 which carries out it's conversion, and theres a number of genetic variants affecting the activity of this enzyme which can found only in certain ethnic groups....the enzyme may also be impaired by numerous types of drugs, or can be overexpressed my excess iron or salt. So as you can see, it's largely oversimplistic to suggest that eating red meat causes elevated TMAO. (4) If I were to propose a study, I'd take a population and split them in half: one group with TMAU (trimethlaminuria) which is a rare metabolic disorder that causes a defect in Fmo3; and the other group being "normal" metabolizers of TMAO. If those with TMAU are in general far healthier by numerous health factors (cancer/heart disease rates, cholesterol, CAD, etc.), then we should create a way to help for TMA oxidation to decrease in normal livers.
(1) Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., … Hazen, S. L. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57–63. http://doi.org/10.1038/nature0 9922
(2) Micha, R., Wallace, S. K., & Mozaffarian, D. (2010). Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes: A systematic review and meta analysis. Circulation, 121(21), 2271–2283. http://doi.org/10.1161/CIRCULATIONAHA.109.924977
(3) Pan, A., Sun, Q., Bernstein, A. M., Schulze, M. B., Manson, J. E., Stampfer, M. J., … Hu, F. B. (2012). Red Meat Consumption and Mortality: Results from Two Prospective Cohort Studies. Archives of Internal Medicine, 172(7), 555–563. http://doi.org/10.1001/archinternmed.2011.2287
(4)Motika, M.S., Zhang, J., & Cashman, J.R. (2007). Flavin containing monooxygenase 3 and human disease. Expert Opinion in Drug Metabolism Toxicology, 2(6):831-45. https://www.ncbi.nlm.nih.gov/pubmed/18028028
TMAO Chemical Structure https://en.wikipedia.org/wiki/Trimethylamine_N-oxide#/media/File:Trimethylaminoxid.svg
Fish, Steak, Pork, Eggs http://assets.labroots.com/_public/_files/system/content-articles/images/profile/9302_855x575.jpg