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.

Thanks for reading,
Bret Scher, MD FACC

Dr. Scher’s one-on-one Consultation was extremely valuable in my search for advice about cardiovascular health on a low-carb diet. During our discussion, I learned that interpreting lab results using the standard reference ranges can be misleading for anyone on low-carb or keto. He helped me better understand my test results and develop effective strategies to improve my cardiovascular health through nutrition and exercise. Dr. Scher is a good listener and a pleasure to work with. He is an excellent preventive cardiologist with a deep understanding of lipidology and metabolism, and the issues and challenges specific to a low-carb lifestyle.

Gabriel B.

We hear the words Heart Healthy a lot, especially when it comes to our nutrition.

By now, you’re likely used to seeing cereals with the “heart healthy” moniker. Is it really heart healthy? We all too frequently refer to foods as “heart healthy”, or we say that our doctor gave our hearts a “healthy” checkup.  

It all sounds nice. But what does it mean? How do we define heart health?

How does LDL Cholesterol affect Heart Health?

Unfortunately, most of our current definitions center around LDL cholesterol concentration.  While LDL cholesterol plays a role in heart health, it by no means defines heart health in totality.

In fact, in many cases it is the least important factor.

Our healthcare system has simplified things too much, so as a result we focus on one bad guy, one demon to fight. In reality heart disease is caused, and made more likely to occur, by a constellation of contributing issues.

Elevated blood sugar, elevated insulin levels, inflammation, high blood pressure, poor nutrition, and yes, lipids all contribute to heart health.  It does us all an injustice to over simplify it to one single cause.

What food is heart healthy?

Our superficial definition of cardiac risk is how industrial seed oils containing polyunsaturated fatty acids (PUFAs) became known as “heart healthy.”

Studies show that they can lower LDL. But they can also increase inflammation and have no clinical benefit and even increase risk of dying. According to our simplified definitions, that doesn’t stop them from being defined as “heart healthy.”

 That’s right! Something that increases our risk of dying is still termed “heart healthy.”  How’s that for a backwards medical system?!

Same for blood sugar. If you have a diagnosis of Type 2 Diabetes (DM2) that is a risk for cardiovascular disease. If you don’t have the diagnosis, you are fine. That ignores the disease of insulin resistance that can predate diabetes for decades and increases the risk of heart disease and possibly even cancer and dementia.

Cereal can also be called “heart healthy” as they may minimally lower LDL. But is that a good thing if they contain grains that also worsen your insulin resistance and metabolic syndrome? I say definitely not.

Time has come to stop this basic, simplified evaluation and start looking at the whole picture.

How Low Carb High Fat Diets Improve Heart Health

Low carb high fat diets have been vilified as they can increase LDL. But the fact of the matter is that it does so only in a minority of people. The truth is that they can improve everything else!

These diets reduce blood pressure, reduce inflammation, improve HDL and triglycerides, and reverse diabetes and metabolic syndrome! Shouldn’t that be the definition of “heart healthy” we seek? Instead of focusing on one isolated marker, shouldn’t we define heart health by looking at the whole patient?

Only by opening our eyes and seeing the whole picture of heart healthy lifestyles can we truly make an impact on our cardiovascular risk and achieve the health we deserve.

Join me in demanding more. Demand better.

Thanks for reading,

Bret Scher, MD FACC

I recently had a one-on-one Health Coaching Consultation with Dr. Bret Scher. I cannot adequately express the gratitude and respect I have for Dr. Scher. He took the time to consider all facets of my health and really listened to me and my concerns. He was not quick to insist I be on prescription medications, but rather he explored various avenues of suggested treatment/preventative measures I might consider taking…guiding, as opposed to dictating a plan of of action. The consultation was well worth my time and money! Loved his approach so much that my husband and I have decided to work with him long distance.

Jami Miltenberger
MS Counseling Psychology

Dr. Scher’s six-month program has been helping me make progress on my health journey. I started the program five months ago after I decided to get more serious about my health and reduce my coronary heart disease (CHD) risk by making healthy diet and lifestyle changes.

The program is not only providing me with excellent video and written content that helps me progressively realize my health goals with effective plans of action, but also individualized attention via email and with monthly video calls with Dr. Scher. I’m grateful for this individualized attention and for Dr. Scher’s insights and suggestions. His advice has honored my preference to continue following a low-carbohydrate lifestyle and has helped me select appropriate macronutrient targets such as daily intake of carbohydrates and protein based on my goals and his review of my medical history and lab test results.

Ken Carrillo
Chemical Engineer