Is TMAO a missing link in the heart disease debate?
New debate on red meat and saturated fats was again triggered recently with a study linking more associative evidence that red meat consumption may lead to heart disease.
The New York Times, Wall Street Journal, Scientific American, ScienceDaily, and The Scientist broke the story with the provocative headlines:
The articles discuss new research that may show a missing link in the debate on heart disease . The research suggests that atherosclerosis may be related to an increase of carnitine in the diet which is thought to raise trimethylamine-N-oxide (TMAO) levels when processed by gut bacteria.
TMAO does not seem to be present in vegan or vegetarian patients, and TMAO levels were shown to disappear following antibiotic therapy in meat-eating participants.
TMAO levels have been correlated with heart disease and is responsible for fishy smell. In fact, TMAO is also the reason fish smell like fish.
Initial questions immediately rise:
1.) Correlation should never be confused with causation. If A is correlated with B, three conclusive possibilities exist:
a. A caused B
b. B caused A
c. C variable(s) could be interacting with both A and B causing the correlation.
2.) TMAO is naturally high in fish which is largely associated with heart disease protection. If TMAO is a cause of heart disease, high fish consumption should be associated with heart disease. As of time of this writing, no association exists.
3.) The gut bacteria responsible for converting more TMAO appear to be the real culprit. Could TMAO levels be the smoke and not the fire? What other factors are involved? Does chronic or excessive red meat consumption lead to higher levels of TMAO-converting bacteria? Does a low-fiber (low-vegetable) diet play a role? Intake of whole grains? Chronic infection? Other causes of gut dysbiosis?
For instance, Paul Jaminet, PhD remarks in Lessons From The Latest Red Meat Scare:
“…the gut flora is a much better predictor of blood TMAO levels than whether someone eats meat. Those with high Prevotella, low Bacteroides averaged about triple the TMAO levels of those with low Prevotella, high Bacteroides flora.”
But then evidence in a small study of 14 children showed that intake of whole grains was most likely associated with high Prevotella and Bacteroides in the gut flora (http://www.ncbi.nlm.nih.gov/pubmed/20679230).
The headlines could have just as likely read: “New Link Between Whole Grains and Heart Disease“!
Forbes magazine also jumped on the report with the article: Why You Should Never Believe Heatlh Headlines.
Key to their response is mention of another report that was released this week by the Mayo Clinic Proceedings on some health benefits of L-carnitine supplementation following a heart attack.
L-Carnitine, when supplemented in the context of an acute myocardial infarction may:
- Improve mitochondrial energy metabolism in the heart
- Reduce ischemia
- Replenish carnitine concentrations in failing heart tissue.
So one media source is saying carnitine is the hero, while the other says carnitine is the enemy, who do you believe?
The answer is you skip the headlines and believe both studies, because they are just pieces to a greater puzzle where more context needs to be filled.
It’s not a sexy answer, but it’s true.
For more thorough review and thoughtful analysis, please see the following discussions:
Adele Hite, MPH, RD
Chris Kresser, L.Ac.
Huffington Post – Chris Kresser, L.Ac.
The scientific paper in question:
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis