Despite what the sugary beverage and processed snack food companies want us to believe, all calories are not created equal.

A new study from Harvard shows that individuals following a low-carbohydrate (20% of total calories) diet burn between 209 and 278 more calories per day than those on a high-carbohydrate (60% of total calories) diet. So the type of calories we eat really does matter.

The New York Times: How a low-carb diet might help you maintain a healthy weight

This isn’t the first study to investigate this topic, but it is likely the best.

The current study was a meticulously controlled, randomized trial, lasting 20 weeks. Even more impressive, the study group provided all the food for participants, over 100,000 meals and snacks costing $12 million for the entire study! This eliminated an important variable in nutrition studies — did the subjects actually comply with the diet — and shows the power of philanthropy and partnerships in supporting high-quality science.

After a run-in period where all subjects lost the same amount of weight, participants were randomized to one of three diets: 20% carbs, 40% carb, or 60% carbs, with the protein remaining fixed at 20%. Importantly, calories were adjusted to stabilize weight and halt further weight loss, thus making it much more likely that any observed difference in calorie expenditure was not from weight loss, but rather from the types of food consumed.

After five months, those on the low-carb diet increased their resting energy expenditure by over 200 calories per day, whereas the high-carb group initially decreased their resting energy expenditure, exposing a clear difference between the groups. In addition, those who had the highest baseline insulin levels saw an even more impressive 308-calorie increase on the low-carb diet, suggesting a subset that may benefit even more from carbohydrate restriction.

Why is this important? It shows why the conventional wisdom to eat less, move more and count your calories is not the best path to weight loss. Numerous studies show better weight loss with low-carb diets compared to low-fat diets, and now studies like this one help us understand why.

Our bodies are not simple calorimeters keeping track of how much we eat and how much we burn. Instead, we have intricate hormonal responses to the types of food we eat. It’s time to accept this and get rid of the outdated calories in-calories, calories-out model, thus allowing for more effective and sustainable long-term weight loss.

Originally Posted on the Diet Doctor Blog 

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

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

What do I mean by “misunderstood?” Look no further than the common misnomer of “good” or “bad” cholesterol.

Good and Bad Cholesterol

While it may be true that High-Density Lipoprotein (HDL) has potentially beneficial functions (reverse cholesterol transport), we have to remember there is no such thing as good and bad cholesterol. The cholesterol carried by HDL is the same as that carried by LDL. The only thing that makes it good or bad is if it ends up synthesizing our hormones or bile acids (good), or if it ends up in our vessel walls (bad).

If it’s true there is no such thing as good and bad cholesterol, why do we care about our HDL levels?

First, let’s start with the basics.

HDL is the smallest and most densely packed lipoprotein and has one or more ApoA protein on its surface. HDL can help lipids move around in circulation by accepting triglycerides or cholesterol from other particles, thus helping a VLDL turn into an LDL, or helping an LDL contain less cholesterol (turning a small dense LDL into a less densely packed LDL).

Like LDL, HDL transports cholesterol to the liver for recycling or excretion, or to the hormone producing cells like in the adrenals. Unlike LDL, HDL does not have the potential to get retained in the vascular wall and does not, therefore, contribute to plaque formation. In fact, functioning HDL can remove cholesterol from the vessel wall, thus putting it back into circulation and possibly removing it from the body.

Back to the question at hand.

Why should we care about HDL levels?

Early epidemiological trials showed that lower HDL levels were associated with a higher risk of cardiovascular disease and even death.  With such a strong association, the medical profession promoted elevated HDL levels as protective and low levels as something we need to avoid.

Since these were observational epidemiological studies, they do not prove that the low HDL caused the problems, only that HDL was associated with it. For instance, HDL is also known to be low in diabetes, metabolic syndrome and insulin resistance. It may, therefore, simply be a marker of underlying metabolic dysfunction that contributes to increased risk.  Yet, HDL’s function in reverse cholesterol transport, and its ability to remove cholesterol from vessel walls suggests a more direct impact on cardiovascular health.

It is also important to note that the Framingham data suggested that increased cardiovascular risk with elevated total cholesterol and LDL-C was lost in the presence of high HDL. In fact, very low levels of LDL combined with very low HDL levels had a much higher risk than markedly elevated LDL levels when combined with elevated HDL.

Thus, HDL proves to be a useful marker to help predict cardiovascular risk. For instance, one large meta-analysis showed that total cholesterol/HDL ratio was a much stronger predictor of cardiac mortality than total cholesterol alone.

In addition, the PURE study, an observational trial in over 135,000 subjects, showed that when considering lipid changes brought about by nutritional changes, ApoB/ApoA1 (essentially LDL-P/HDL-P ratio) is the best predictor of clinical outcomes.

Thus, HDL level is important in assessing cardiovascular risk.

Drugs Muddy the Picture

While HDL may be a good predictor of risk, raising it with drugs does not seem to confer added benefit.

For instance, cholesterol ester transferase protein inhibitors (CETP inhibitors) significantly reduced LDL by 20-30% and increased HDL 100-fold, yet showed either no clinical benefit or even worse, an increased risk of death.

This was a shock to many in the lipid world as the notion of “good” and “bad” cholesterol would clearly predict lowering LDL and raising HDL would confer dramatic health benefits. So much so, that multiple pharmaceutical companies invested hundreds of millions of dollars developing these drugs only to abandon them when the trials showed no benefit.

Part of the issue is that not all HDL lipoproteins function the same. There are subsets of people with genetically determined markedly elevated HDL levels who have an increased risk of CVD. They may have plenty of cholesterol circulating in HDL particles, but the HDL particles are dysfunctional and therefore  do not effectively remove cholesterol from vessel walls or LDL and do not effectively transport it to the liver. Conversely, there are those with a specific genetic mutation called ApoA1 Milano who have very low HDL-C and lower cardiovascular risk.

Simply measuring the HDL cholesterol content, therefore, may not accurately reflect its function. While we do not have easily available tests to measure HDL function, we can potentially use HDL particle assessment as well as the company it keeps (i.e. low triglycerides, larger less dense LDL particles) to better assess the potential benefits of HDL. Thus, if there is any concern about potentially dysfunctional HDL, I usually recommend advanced lipid testing to see the specific subtypes of HDL.

What can we conclude from all the HDL confusion?

Raising HDL with drugs does not reduce cardiovascular events, yet having a naturally low HDL is associated with increased risk.

The best answer, therefore, is to live a lifestyle that helps you have a “not low” HDL level. This means first and foremost avoiding the medical conditions associated with low HDL (i.e. insulin resistance, diabetes, and metabolic syndrome).

Textbooks predictably state the interventions to naturally raise HDL include exercise and moderate alcohol intake. Unfortunately, these have minimal effects. In fact, they pale in comparison to a low carb high fat lifestyle. In my 20+ years in the medical field, I have never seen an intervention as effective as LCHF in raising HDL, and the studies agree.

This brings us back to our question once again.

Why are HDL levels important?

HDL levels are important because it is a reflection of our underlying metabolic health and our lifestyle. A properly constructed LCHF lifestyle lowers triglycerides, raises HDL, and reduces the small dense LDL, among other benefits. Such a lifestyle likely reduces overall cardiovascular risk and will likely be shown to improve longevity and health span. While HDL may not be the main reason for this, we can’t ignore its role simply because it is more nuanced than “good” and “bad” cholesterol.

My advice, therefore, is to see the whole picture. Embrace the nuance. And make sure you get a thorough and proper evaluation of your cardiovascular risk.

If you are hungry for more, I created my Truth About Lipids program, a program focused on Cholesterol, to help break through the confusion and provide you with everything you need to thoroughly understand cholesterol and its impact on your health.

Learn more: Truth About Lipids Program

If you still have questions, you may want to consider a one-on-one health coaching consultation so you can get the individual attention you deserve  with a thorough assessment of your lifestyle and its impact on you as an individual.

Please comment below if you have any questions or comments that may help further the discussion.

Thanks for reading.

Bret Scher MD FACC

Don’t look now, but the updated clinical practice cholesterol guidelines from the American College of Cardiology, the American Heart Association and others are getting personal. Although the guidelines still contain their familiar approach — that I consider too aggressive with drug therapy — the latest 2018 version of the guidelines now includes an impressive update to emphasize lifestyle intervention, plus a more individualized approach for risk assessment.

MedPage Today: AHA: Revised Lipid Guide Boosts PCSK9s, Coronary Calcium Scans

Could this be the start of a progressive trend away from shotgun statin prescriptions? I sure hope so.

Prior guidelines emphasized the 10-year ASCVD risk calculator as the main determining factor for statin therapy. In the 2018 update, the guidelines acknowledge that the calculator frequently overestimates the risk in those individuals who are more involved with prevention and screening. (In other words, those patients more interested in and proactive about their health; I find many in the low-carb world fall into this category.)

The ensuing discussion with a healthcare provider should then focus on:

[T]he burden and severity of CVD risk factors, control of those other risk factors, the presence of risk-enhancing conditions, adherence to healthy lifestyle recommendations, the potential for ASCVD risk-reduction benefits from statins and antihypertensive drug therapy, and the potential for adverse effects and drug–drug interactions, as well as patient preferences regarding the use of medications for primary prevention… and the countervailing issues of the desire to avoid “medicalization” of preventable conditions and the burden or disutility of taking daily (or more frequent) medications.

I appreciate the attention the new guidelines bring to the depth of the discussion that should ensue between doctor and patient. Considering the treatment burden is equally as important as the burden of disease, and possibly even more important in patients who have not been diagnosed with heart disease, these individualized discussions about trade-offs are critical to personalized care.

Also worthy of mention is the increased use of coronary artery calcium scores (CAC) to help individualize risk stratification. The updated guidelines specify CAC may be useful for those age 40-75 with an intermediate 10-year calculated risk of 7.5%-20%, who after discussion with their physician are unsure about statin therapy. They specify that a CAC of zero would suggest a much lower risk than that calculated by the ASCVD risk formula, and thus take statins off the table as a beneficial treatment option.

This is huge. I cheered when I read this! I have been critical of prior guidelines that focused on ways to find more people to place on statins. The mention of finding individuals unlikely to benefit from statins is a giant step in the right direction.

The guidelines go even further: they mention that a CAC either over 100 or greater than the 75th percentile for age increases the CVD risk and the likely benefit of a statin. A CAC between 1-99 and less than the 75th percentile does not affect the risk calculation much and it may be worth following the CAC in five years in the absence of drug therapy. I would still argue that a CAC >100 does not automatically equal a statin prescription and we need to interpret it in context, but I greatly appreciate this attempt at a more personalized approach.

The guidelines also go beyond the limited risk factors included in the ASCVD calculator by introducing “risk modifying factors” such as:

• Premature family history of CVD
• Metabolic syndrome
• Chronic kidney disease
• Chronic inflammatory conditions such as rheumatoid arthritis and psoriasis
• Elevated CRP > 2.0 mg/L
• Elevated Lp(a) > 50 mg/dL or 125 nmol/L
• Elevated triglycerides > 175 mg/dL

Although they use these criteria to define an increased risk, the opposite would likely hold true. An absence of those criteria could define a lower risk situation.

Some changes deserve mention from a controversy standpoint as well. For instance, the new guidelines recommend checking lipid levels as early as two years old in some circumstances. Two!

They also recommend statin therapy for just about everyone with diabetes with no mention of attempting to reverse diabetes before starting a statin, a drug that has been shown to worsen diabetes and insulin resistance. In addition, the new guidelines do not mention the likely discordance between LDL-C and LDL-P in those with diabetes.

Last, the new guidelines define an LDL-C > 190 mg/dL as an absolute indication for statin therapy with a treatment goal of 190 mg/dL is in familial hypercholesterolemia populations (and even then has heterogenous outcomes). There is a clear lack of data supporting that same recommendation for metabolically healthy individuals with no other cardiac risk factors and no other characteristics of familial hypercholesterolemia. This is a clear example of when a guideline turns from “evidence based” to “opinion based.”

In summary, the guideline committee deserves recognition for its emphasis on an individualized care approach, its use of CAC, and its broader description of discussing potential drawbacks of drug treatment. It still combines opinion with evidence and believes all elevated LDL is concerning, but I for one hope it will continue its progression away from generalizations and someday soon see that individual risk variations exist, even at elevated LDL-C levels.

Thanks for reading,
Bret Scher MD FACC

Originally Posted on the Diet Doctor Blog