Top 3 Myths about Lean Mass Hyper-Responders

With the New JACC Advances paper, myths about LMHR have arisen again like Zombies that Won't Die. Let's Slay 3.

A day many of you have been waiting for has finally arrived, the publication of the first full set of data from the Lean Mass Hyper-Responder (LMHR) study that is measuring coronary plaque, by coronary CT angiography (CCTA) in LMHR.

The main findings were:

• Despite exposure to an mean LDL-C level of 272 mg/dl for a mean of 4.7 years, LMHR on a ketogenic diet exhibited no increase in plaque on CCTA as compared to a matched control groups

• There was no correlation between LDL-C level and plaque on CCTA.

I cover the finding of this paper, published in JACC Advances, in this video. Please view it before moving on.

This constitutes our 10^th paper on the topic of LMHR.

And with every new paper, I notice a new wave of myths and misunderstanding about LMHR. This Newsletter addresses the top 3 Myths.

#1. Lean Mass Hyper-Responders are Caused by High Saturated Fat Intake.

This common retort is unequivocally false for several reasons.

• First, there are LMHR on low saturated fat diets, and observations of uncoupling of saturated fat intake and LDL-C in LMHR.

• Second, there is no suggestion in the literature that dietary saturated fat intake is sufficient to raise LDL-C levels to those seen in many LMHR, some with LDL-C of >500 mg/dl. That’s not a flex, it’s a fact.

• Third, if high saturated fat intake caused the LMHR phenotype, addition of saturated fat with carbs should raise LDL-C, not lower it. #OreoVsStatin

• Fourth, high saturated fat intake doesn’t explain the LMHR triad of high LDL-C, high HDL-C and low triglycerides.

• Fifth, high saturated fat intake doesn’t explain the inverse association between LDL-C and BMI on low-carbohydrate diets, as observed in meta-analyses.

For more on this myth, see these two videos:

This does not mean saturated fat doesn’t impact LDL-C in LMHR. However, saturated fat is not the factor driving the LMHR phenotype. Anyone who suggest this is the case – and there are many – is simply underinformed or misinformed.

#2. Lean Mass Hyper-Responders are Flippant about their LDL-C Levels.   

While it’s certainly true that some people with the LMHR phenotype do ascribe to the position that “LDL doesn’t cause heart disease” and that “high LDL is harmless [with certainty],” these are NOT - I repeat NOT - the universal positions of those with the LMHR phenotype. They are also not my positions, for what that’s worth.

Many LMHR are uncomfortable with their high LDL-C / high ApoB status and actively seek ways to mitigate their risk through lifestyle and/or pharmacotherapy.

However, many also find themselves in a rock and a hard place scenario: they have used a ketogenic diet to treat a chronic disease and improve their quality of life but – to their surprise – find themselves with sky-high LDL-C and ApoB. For these individuals to make truly informed decisions requires more data on LMHR as a population.

One must understand the absolute risk (be it small or large) associated with a biomarker in a particular context to make an individually reasoned choice on whether or what steps to take to lower to risk presumed to be associated with that biomarker.

For more on “cause and consequence” with respect to LDL-C, see this video:

The data from the recently published trial are, while preliminary, the first of their kind addressing the LMHR population.

For more on my position, read our editorial I the Journal of Clinical Lipidology.

#3. Lean Mass Hyper-Responders are a small, specific population. Therefore, these data are irrelevant to the majority.

It’s true that the union of the populations of persons who are low-carb and who are lean is rather small. However, with increasing use cases for ketogenic diets beyond obesity and diabetes, the proportion of lean persons on low-carbohydrate diets will continue to increase. In parallel, so with the population of LMHR.

But the (true) argument that LMHR are becoming more prevalent is not my main argument for the present importance of studying LMHR. Rather, I’d highlight the following two points:

• First, as LDL-C remains the “boogeyman” of low-carbohydrate ketogenic diets (and this is true irrespective of your opinion on the Lipid Heart Hypothesis). Thus, understanding the physiology underlaying LDL-C changes on low-carbohydrate diets will help overcome or compensate for a barrier to the clinical implementation of therapeutic carbohydrate restriction.

• Second, insofar as the LMHR phenotype represents an extreme of an adaptive metabolic response in humans, studying the “extremes” or “outliers” often affords deeper insights into general human physiology.

I’m keep this Newsletter concise. But for those who want to dive deeper down the rabbit hole, you can find a >30 video playlist on LMHR, the Lipid Energy Model and Cholesterol on my YouTube Channel.