What is a Hyper-Responder?
The term, “hyper-responder” has been used within the ketogenic / low carb, high fat (keto/LCHF) community to describe those who have a very dramatic increase in their cholesterol after adopting a low carb diet. This increase can be anywhere from 50% to 100% or more of their original, pre-diet cholesterol numbers.
Typically, a keto/LCHF hyper-responder will have LDL cholesterol (LDL-C) at 170 mg/dl or higher.
How many of those practicing a keto/LCHF diet are hyper-responders?
Because the keto/LCHF community is relatively small, the total number of hyper-responders as a percentage of the whole is unknown. But estimates vary between 5% to 33%.
Is having high LDL cholesterol (LDL-C) on a keto/LCHF diet dangerous?
This is the important question, of course. The short answer is – we don’t know.
As of this writing, I have much more confidence there are good reasons LDL-C could be high and bad reasons LDL-C could be high. And these reasons aren’t mutually exclusive.
Possible good reasons:
- The body is transporting more fat for energy to your cells due to being on a high-fat diet. Since cholesterol “ride shares” with these fatty acids in lipoprotein “boats”, it shows up in higher quantities in a blood test. This is typically shown in a blood test where there are low triglycerides (the cargo is distributed easily). For more on this hypothesis, see CholesterolCode.com/model
- The body is healing from a temporary injury. (You probably want that)
- The body is recovering from a temporary infection. (You probably want that too)
Possible bad reasons:
- The body is attempting to provide energy to your tissues with triglycerides via lipoproteins, but cells are insulin resistant or they are overloaded, and thus unwilling to take in more. This leads to more residence time of VLDLs (the precursor to LDLs) in a “traffic jam” of the bloodstream. This is typically shown in a blood test where there are high triglycerides (the energy “cargo” is difficult to distribute). Often, this suggests a particular profile with the LDL particles which — when combined with low HDL-C — is known as Atherogenic Dyslipidemia.
- The body is trying to heal from a chronic condition, yet failing. This leads to chronically elevated LDL.
- (More will be added to this section soon, but the above two cover the largest categories…)
Is having a high LDL particle count (LDL-P) on a keto/LCHF diet dangerous?
In my personal research, I find most lipidologists are confident that high levels of LDL-P (total LDL particles) are strongly correlated with a higher risk of atherosclerosis (buildup of plaque in the arteries) and can point to several modern studies that suggest this. It’s also worth noting that prominent voices in the field of cholesterol, such as Dr. Peter Attia and Dr. Thomas Dayspring, likewise consider high LDL-P as a potential risk factor for atherosclerosis.
However, those who argue against this will point out that these studies did not include people practicing a low carb diet. It is commonly asserted—but has yet to be determined with absolute certainty—that the presence of higher LDL-P is inconsequential if it isn’t coupled with the inflammation that is commonly remedied through following a keto/LCHF diet. Ivor Cummins is one such voice and regularly provides counter-analysis in articles and videos (such as Cholesterol Conundrum).
Are there any factors that might predispose one to be a hyper-responder?
- In my research to date, I believe the largest influence of one being a hyper-responder is how lean and/or fit they are while likewise following a keto/LCHF diet. While unintuitive, those who are lean and/or fit often exhibit the highest LDL-C and LDL-P numbers we see (along with impressively high HDL and incredibly low triglycerides). At the furthest end of this spectrum is a profile I call “Lean Mass Hyper-responder” and detail it here. [Geeky technical explanation: This makes perfect sense mechanistically, as the body is both fueled by fat while likewise working with adipose tissue (body fat) mass for “staging”, thus theoretically, there is the likely greater need for “global distribution” of fat-based energy via VLDL turnover than “local distribution” via adipocytes. more on that in an upcoming post.]
These are the four other most commonly referenced factors to becoming a hyper-responder:
- Familial hypercholesterolemia (FH) – A genetic disorder that presents early with higher cholesterol, and in particular, high LDL. However, this is less likely if the hyper-responder had “normal” ranges of cholesterol before starting the low carb diet given FH would have likely shown beforehand as well. (See here for more information.)
- One or two copies of the ApoE4 gene – this gene has long been identified with higher risk for elevated cholesterol. Anecdotally, many hyper-responders find they have one or two copies of the ApoE4 gene; 3/4 or 4/4 pattern. (I myself have the 3/4 pattern, which I found through my test with 23andMe. See here for more information.)
- Hypothyroidism – when the body’s thyroid slows down, it leads to a slow down in the production of LDL receptors. These receptors are important for usage, and, ultimately, clearance of LDL from the bloodstream. (See here for more information.)
- Hyper-synthesizer. Generally in reference to someone with insulin resistance who experiences an abnormally high production of cholesterol. (See BJJ Caveman’s lecture notes for more information.)