Eating red meat increases TMAO levels. Should we care?

Cutting Juicy Beef Steak

A new study published in the European Heart Journal says we should care about blood levels of a metabolite trimethylamine N-oxide (TMAO), but is that true?

NBC News: Study explains how red meat raises heart disease risk

For starters, this was a well run and controlled study. Researchers randomly assigned 133 subjects to one of three isocaloric diets with the only difference being the presence of red meat, white meat, or vegetarian protein. Similar to the study by Dr. Ludwig that we referenced earlier, a strength of this study was that the study team supplied all meals for the subjects. Therefore, there was no guessing about what the subjects ate or if they complied with the recommendations. That makes this a strong nutritional study.

Subjects stayed on each diet for four weeks and then had a washout period before transitioning to the next diet. The main take home is that eating red meat increases the blood level of TMAO, which declines after four weeks off the red meat diet. As described in the article:

a red meat diet raises systemic TMAO levels by three different mechanisms: (i) enhanced nutrient density of dietary TMA precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Interestingly, discontinuation of dietary red meat reduced plasma TMAO within 4 weeks.

It is important to note in our era of frequent conflicts of interest, NBC news reported that the lead investigator for the study is “working on a drug that would lower TMAO levels.” While that in no way invalidates the findings, it does legitimately raise suspicion for their importance.

Interestingly, the study did not test eggs, another food reportedly linked to TMAO. They did, however, note that increased choline intake, the proposed “culprit” in eggs, had no impact on TMAO levels.

The study also did not investigate fish. Fish, traditionally promoted as “heart healthy,” has substantially higher concentrations of TMAO than meat or eggs. One thought, therefore, is that high TMAO levels are produced by gut bacteria rather than the food itself. Although this is an unproven hypothesis, it would also explain variability among subjects.

Now for the harder question. Does any of this data matter? For this study to be noteworthy, we have to accept the assumption that TMAO is a reliable and causative marker of heart disease.

The main NEJM study linking TMAO to an increased risk of cardiovascular disease is not as conclusive as many promote. First of all, only those at the upper quartile of TMAO level had a significant increase in cardiovascular disease risk. Lower elevations had no significant correlation.

Second, those with increased TMAO and cardiovascular disease risk also were more likely to have diabetes, hypertension and a prior heart attack; furthermore, they were older, and their inflammation markers, including myeloperoxidase, a measurement of LDL inflammation, were significantly higher. With so many confounding variables, it is impossible to say the TMAO had anything to do with the increased cardiovascular disease risk.

This study in JACC that saw a correlation with TMAO and complexity of coronary lesions, also found an increased incidence of diabetes, hypertension, older age in the high TMAO group.

Finally, this study found no association at all between TMAO levels and increased risk of cardiovascular disease.

Based on these mixed findings, the jury is still out, and we have plenty of reason to question the importance of elevated TMAO as an independent risk marker or causative factor of coronary disease.

Most importantly, however, since multiple studies continue to show no significant association between meat and egg consumption and increased heart attacks or mortality risk (references here, here, here, here and here) the weak surrogate markers don’t seem likely to matter much. Don’t get caught in the minutiae. Focus on a real-food diet that helps you feel better and improves the vast majority of your markers. And if you have elevated TMAO, the studies suggest you should also check your blood pressure, blood sugars, and inflammatory markers as they may also be elevated. In my opinion, until we have much more convincing data on TMAO, you are far better off targeting those more basic parameters than a blood test of questionable value.

Additional coverage:

MedPage Today: Red meat diet bulks up atherogenic metabolite, but it can be reversed

Cleveland Clinic: Cleveland Clinic studies reveal role of red meat in gut bacteria, heart disease development

The Boston Globe: 2 new studies take a little more sizzle out of red meat

Thanks for reading,
Bret Scher, MD FACC

Earlier

Cardiologist in Houston Chronicle: ‘Want a healthier heart? Eat a steak’

Does cholesterol cause heart disease? New study says no

Could an all-meat diet cure some diseases?

Heart disease

8 comments

  1. Jürg Kuoni
    Very interesting comment, thank you! Can somebody explain me what: LDL inflammation means?
    ......they were older, and their inflammation markers, including myeloperoxidase, a measurement of LDL inflammation, were significantly higher.
  2. Susan
    Very complicated article, more for experts... I do not eat beef because I signed petition to reduce beef production because cows contribute towards global warming by 60%. Yes sixty. ....and I do not miss the beef at all. And now I know I did something good for my heart, it makes me feel twice happy.❤.
    Reply: #4
  3. Gentiann
    It is not true that cows contribute to global warming by 60%.
    Honestly, it's probably less than 10%.
  4. Pablo
    agriculture, contributes even more!
  5. Nick
    From what I have read, grass fed pasture cows sequester more carbon in the soils than they produce. Have a look at work done by Alan Savory and his institute.
  6. 1 comment removed
  7. Nancy Shupe
    I have a TMAO level of 11 which is over the highest range number. My doctor told me it indicted I have SIBO due to consuming saturated animal fats. I have no symptoms or gut distress. Since being diagnosed with Hashimoto's over 4 years ago, I have been gluten free and have eaten two eggs along with a half an avocado almost every day. As I have searched for information about TMAO I have found articles stating that choline is one of the major factors in high TMAO numbers, even though it is so good for you. It seems that everyone doing a Keto diet would have these high numbers. I have just completed a five-day water fast to help clear my gut and am wondering what dietary changes I should make going forward. Your article gives me hope that this is not as serious as I first thought.
  8. Vicki
    Cauliflower is high in choline, i.e. potentially contributing to high TMAO and feeding related gut microbiota, but it would seem counter-intuitive to consider a large bowl of cauliflower for dinner a heart risk.
  9. Honeymay
    People need to just listen to their bodies instead of believing all the so-called "studies" and "research" and "expert opinions". Really listen to your body to see what it needs to function. Stop trying to dictate to it what to have for survival. I almost killed myself trying to be vegan because I believe so-called "experts" in the field, McDougall, Greger, Fuhrman. When I listened to my body, it requires animal protein and fat. That's all. I'd probably be a carnivore except I really like vegetables and variety in my diet.

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