If you follow a low-carb diet, your cholesterol might rise. But if you’re a lean mass hyper-responder, it might end up rising a lot.
More and more people are adopting low-carb diets, which means more and more people are taking steps to become metabolically healthy. So how do we explain people on low-carb diets who double or even triple their LDL cholesterol?
These are people we call ‘hyper-responders’: those who have abnormal cholesterol spikes in response to low-carb, high-protein, high-fat diets. A subcategory called lean mass hyper-responders (LMHRs) have some of the highest LDL-C scores of all.
Numbers like these would call for statins in a traditional medical setting. And yet, LMHRs appear to be metabolically healthier than the average global population.
Here’s what we know about lean mass hyper-responders, including how to identify the signs in your blood work.
Defining lean mass hyper-responders
At its simplest definition, a lean mass hyper-responder is someone with a low BMI and high LDL cholesterol level who follows a low-carb diet (often at or below 25 grams). They carry very little body fat and are much more active than the average person. And yet, their LDL cholesterol levels (and ApoB levels) are much higher than what we consider ‘healthy.’
For context, the reference range for LDL cholesterol is 100 mg/dL. Most lean mass hyper-responders average around 300 mg/dL. A handful of others reach as high as 500 mg/DL.
It’s true that low-carb diets often result in higher overall cholesterol levels — at least, in the early stages. Studies show total cholesterol eventually drops, with HDL rising and triglycerides and LDL dropping.
But hyper-responders rarely see reductions in their cholesterol without adding carbohydrates back into their diets.
There are a couple hypotheses for why this happens:
- Low body fat makes the body demand more fat for energy, which mobilizes in the blood
- LMHRs eat fewer carbs and have higher energy demands, meaning they have scarce glycogen stores and burn through them quickly
So the question is, is it safe for LMHR to remain on a keto, carnivore, or low-carb diet? Or is there a risk of developing heart disease?
The short answer is that none of us know.
But Dr. Nick Norwitz’s research is beginning to shed some light.
Examining the data
For the unfamiliar, Dr. Nick Norwitz is a researcher/educator who specializes in studying metabolic health. He and several other brilliant minds, including David Feldman, Adrian Soto-Mota, Tommy Wood, and others, published a paper in JACC: Advances called Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial.
Norwitz and the other researchers examined 100 LMHRs who exhibited extremely high LDL levels on a ketogenic diet. They performed imaging of the participants’ hearts (CAC and CCTA scans, respectively), then performed them again after 12 months of tracking.
The conclusion of the paper reads as follows:
“In lean metabolically healthy people on KD, neither total exposure nor changes in baseline levels of ApoB and LDL-C were associated with changes in plaque. Conversely, baseline plaque was associated with plaque progression, supporting the notion that, in this population, plaque begets plaque but ApoB does not.”
So what does that tell us about this population?
- High ApoB levels (a protein on LDL and other cholesterol particles associated with heart disease) is not associated with plaque buildup.
- High LDL cholesterol levels are also not directly associated with buildup.
- LMHRs who already had plaque buildup were more likely to build up more plaque.
So if you already have plaque in your arteries, you may see more. But the interesting thing is that it’s an independent factor from cholesterol levels and ApoB.
This also challenges the conventional lipid-heart hypothesis, which has told us for years that high cholesterol leads to heart disease.
The ultimate conclusion is that high cholesterol levels may not be a health risk for lean mass hyper-responders.
Identifying the signs of LMHR
There are a few ways to tell if you’re a lean mass hyper-responder.
First, test your blood. This is likely 50% higher than your pre-keto or pre-carnivore numbers. Dr. Nick Norwitz suggests the following reference range:
- LDL at or above 200 mg/dL (5.2 mmol/L)
- HDL at or above 80 mg/dL (2.1 mmol/L)
- Triglycerides at or below 70 mg/dL (0.8 mmol/L)
Second, measure your body fat percentage. LMHR are often very lean with low body fat ~20% for men and 23% for women.
Third, check your diet. This is usually very low-carb, with most people eating under 25 grams per day. You might also notice your fasting glucose stays high even while fasting (many LMHRs struggle to fast multiple days in a row).
So what should you do if you’re a LMHR?
At this point in time, not much.
The best course of action is to keep an eye on your health and stay up-to-date with new research.
I’d recommend:
- Scheduling regular blood work at least twice per year. Pay close attention to your LDL, HCL, and triglycerides and look for changing patterns.
- Booking a CAC scan if you’re at or over 40. This will help determine the amount of calcium in your arteries and track the progression of heart disease.
- Speaking with a metabolic health specialist about your results. If you are a lean mass hyper-responder, high cholesterol levels may not necessarily point to health problems. But if you have a suboptimal CAC score or unbalanced triglycerides, there’s a chance you’re not a LMHR and may have underlying issues you need to address.
- Continue to follow the evolving science on this topic. There will be additional data released from this trial and hopefully there will be other trials that help us continue to refine our understanding of this metabolic phenotype and the response to low carb diets in general.
Are LMHRs at risk for heart disease?
We don’t know enough to say for certain. But based on Norwitz’s research, we can assume they’re not in any immediate danger.
LMHRs look very different from most people with high cholesterol — they’re typically athletic, have low triglycerides, and higher HDL than other high-risk groups.
But the science is not settled, and more research will be necessary.
If you’re curious to do more reading on cholesterol, one of the following might be interesting to you: