Note: This is intended to be a living document, and thus will be updated to reflect new information as it becomes available, and our perspectives as they change. Due to the growth of CholesterolCode (both in userbase and post number) we hope this will become a useful site navigation resource.
The original “Hyper-responder FAQ” has been archived in its original form, and can be accessed at the original URL here.
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-low carb diet cholesterol numbers.
Typically, a keto/LCHF hyper-responder will have LDL cholesterol (LDL-C) at 170 mg/dl or higher.
A subset of hyper-responders called Lean Mass Hyper-responders (HDL >80 mg/dL, Triglycerides <70 mg/dL, and LDL >200 mg/dL), have also been noted in the community. You can read more about this unique profile here.
How many of those practicing a keto/LCHF diet are hyper-responders?
Because the keto/LCHF community is relatively small, and the question has largely been unexplored, 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. A “good reason” would be defined as higher LDL resulting from non-pathological processes (e.g. not due to a non-resolving disease or dysfunction), while a “bad reason” would be the opposite.
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
The body is recovering from a temporary infection
Note that infection and injury are on the list as “good” – this isn’t because they’re desirable states to be in, but rather because higher LDL in such cases can be a part of innate immunity and/or a part of the normal healing process and should resolve on its own after the damage/infection is handled (non-pathological). You can read more about infections and lipids here.
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, but is failing. This leads to chronically elevated LDL.
- (More will be added to this section soon, but the above three cover the largest categories…)
It’s worth noting that just because the process that results in higher LDL can be classified as “good” or “bad” (non-pathological or pathological) doesn’t necessarily mean the result (higher LDL) will match. There is the potential that high LDL from a “good” process is still “bad” – until this context is studied this is left ambiguous.
Ultimately, we cannot say whether one should be concerned or not if they are a hyper-responder, as further study is needed on this specific phenotype. As of this writing we are currently in the process of putting together such a study at CitizenScienceFoundation.org
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 focus on the context of people practicing a low carb diet. It is asserted that the presence of higher LDL-P is inconsequential if it isn’t coupled with the inflammation that is commonly resolved 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 very high HDL and low triglycerides). At the furthest end of this spectrum is a profile I call a “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.]
These are the four other referenced factors to becoming a hyper-responder, although these aren’t a requirement of the profile:
- 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 (though not all, or most) 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.)