Lean Mass Hyper-responder
A Superior Low Carb Profile?
Dave Feldman
CholesterolCode.com
Lean Mass Hyper-responders are changing
the world of cholesterol as we know it…
… and they don’t even realize it yet
Of those going on
a Low Carb diet…
Some will see a
dramatic increase
in their total and
LDL cholesterol
We call these
“Hyper-responders”
Some will see a
specific pattern that
includes the highest
total and LDL
cholesterol of all
We call these
“Lean Mass
Hyper-responders”
(LMHR)
Lean
Fit
Powered by Fat
Lean Mass Hyper-responder Characteristics
• Generally lean, with low body
fat (≤20% men, ≤23% women).
• Usually moderate to very fit.
Many are very athletic.
• Usually very low carb (typically
<25g net carbs)
• Often lower BHB (Blood Ketones)
levels than sedentary low carbers
(often 0.3-1.0 mmol/L)
• Generally higher fasting glucose,
possibly through adaptive glucose
sparing (often 90-105 mg/dL)
• Difficulty doing multi-day fasting
The Lipid Energy Model
Powered by Fatty Acids
ApoB48
Energy Delivery
ApoB48
ApoB100
Support
Support
ApoB100
Energy Delivery Support
ApoB48
ApoB100
Energy Delivery
ApoB48
ApoB100
Support
ApoB100
Energy Delivery Support
ApoB100
LDL-P
But wait… aren’t high VLDLs and triglycerides
associated with disease?
• Yes, if they are found lingering in the bloodstream.
• It isn’t the VLDL and Triglyceride use that is the problem, it is their
lack of use – something commonly associated with insulin resistance
and exceeding one’s Personal Fat Threshold*.
• This inability to “park” their triglycerides necessarily means VLDLs will
remain longer in the bloodstream, a clear sign of trouble.
* See the excellent work of Gabor Erdosi
VLDL
IDL
LDL
High, Healthy Lipid Energy Trafficking
• High VLDL secretion, trafficking, and use leaving little VLDLs and more
of their successor LDLs
Unhealthy Lipid Energy Trafficking
• Even in low VLDL secretion, if use is lower due to poor uptake, it can
result in abnormally long VLDL residence time before remodeling
Question: What’s the key similarity between an adipocyte
and a Very Low Density Lipoprotein?
Answer: Each is primarily staging triglycerides as fat-based
energy to make available to cells on demand.
Question: What’s the key difference between an adipocyte and
a Very Low Density Lipoprotein?
Answer: An adipocyte is stationary, a VLDL is mobile.
In other words, a VLDL is effectively an adipocyte on the go.
Are LMHR Cholesterol Levels Risky?
The most relevant question of all
Three Flavors of Cholesterol Studies
Lipid System
modified by drugs
Lipid System
modified by genetics
Lipid System
with no specific
modification
Drug Trial Evidence and Selection Bias
• See Dr. David Diamond’s presentations
and his recent paper: Exaggerated report
of benefits in a flawed long term statin
treatment study. [BMJ]
• See Dr. Maryanne Demasi’s many ABC
specials and her recent paper: Statin
wars: have we been misled about the
evidence? A narrative review [BMJ]
FOURIER
CVD Death/MI/Stroke
Reduced
No statistically sig change
In All-Cause Mortality
CVD Death
Reduced
No statistically sig change
In All-Cause Mortality
ODYSSEY
No Reduction in
CHD/CVD Mortality
Reduced
All-Cause Mortality* **
* By just 1.4% ARR
**In >100 LDL-C Subgroup
Do Gene Studies Hold the Answer?
• The assumption is that genetic variability
resulting in higher and lower LDL could
show an association with cardiovascular
disease.
• And indeed, there are a number of SNPs
that have both an association with higher
LDL and higher cardiovascular disease.
• But there’s a catch-- the majority of SNPs
used in these studies also include a third
complication…
Newsflash: Cells need lipids!
Majority of SNPs selected inhibit lipid uptake
Proposed new term:
Cellular Lipid Malabsorption (CLM)
Any disruption or dysfunction that prevents the normal uptake of
lipids or lipoproteins by the cell.
There are actually many SNPs that alter LDL levels
with little or even the opposite effect expected
Are there any SNPs without lipid malabsorption
that result in high levels of LDL cholesterol?
YES!
And one of them is especially important to Lean
Mass Hyper-responders…
Konstantinos Karageorgos: Hey Dave, why not
check into Glycogen Storage Disease?
And sure enough – Glycogen Storage Disease is
associated with “Severe Hyperlipidaemia”
Working our way to the right question
• No populations with lipid systems
categorically altered by specific drugs or
genetic profiles
“If I had an hour to solve a problem
and my life depended on the solution,
I would spend the first 55 minutes
determining the proper question to
ask, for once I know the proper
question, I could solve the problem in
less than five minutes.”
~ Albert Einstein
What falsifies the Lipid Energy Model for CVD/CHD?
Clearly high HDL and low triglycerides show a properly working lipid
metabolism… thus high CVD in spite of this would help to falsify it.
0.08% difference!
HDL ≤46
TG ≥142
HDL ≤46
TG ≥142
HDL ≥57
TG ≤97
HDL ≥57
TG ≤97
Less than
2/3rds of a 1%
difference!
Low LDL? High LDL? Does it matter? HDL and TG matters!
HDL ≤46
TG ≥142
HDL ≤46
TG ≥142
HDL ≥57
TG ≤97
HDL ≥57
TG ≤97
HDL ≤46
TG ≥142
HDL ≤46
TG ≥142
HDL ≥57
TG ≤97
HDL ≥57
TG ≤97
HDL ≤46
TG ≥142
HDL ≤46
TG ≥142
HDL ≥57
TG ≤97
HDL ≥57
TG ≤97
Lilly’s Story
Struggling to find balance
• Lilly’s epilepsy appeared to be improving on a ketogenic diet
• But once her cholesterol rose, her doctor insisted she modify the diet to:
• 80% Fat, 15% Carbs (mostly fructose), and 5% protein
• This did result in a drop of her LDL-C
• But it also dropped her HDL-C into the 30s and spiked her Triglycerides into the 100s
• Lilly gained weight, lost energy, and her neurological condition worsened
Course Correction
• After many talks with Lilly’s parents, they decided to take her back to
a keto diet
• 75% Fat, 20% Protein, 5% Carbs
• Her LDL-C and LDL-P have gone up, but her triglycerides are now
under 100 and her HDL is back into the 50s
• Her energy has returned, her weight is dropping, and her neurological
symptoms have improved
My Personal Message to LMHRs
My Personal Message to Lean Mass Hyper-responders:
• I recommend researching all major opinions on cholesterol. No Echo
Chamber-ing.
• For contrarian opinions, I like Thomas Dayspring and Peter Attia in particular
• If you decide to take steps to lower your LDL, everyone should respect
that decision and we give advice on this as well at
CholesterolCode.com to help you.
My Personal Message to Lean Mass Hyper-responders:
For those of you have every intention of remaining a Lean Mass Hyperresponder, you should know the following:
• If at any point I find compelling evidence this is indeed a dangerous
profile, I will provide this opinion at CholesterolCode.com. My journey
is one of science, not of advocacy.
• As of right now, evidence appears to be strongly suggesting the
opposite. Indeed, I suspect there are many benefits of LMHRs that
will show in both greater health span as well as lifespan.
I believe you may hold the answer to one of the most
important medical questions of our time:
Do high levels LDL cholesterol (LDL-C) or the particles
that carry them (LDL-P) independently cause heart
disease?
The Perfect Individuals to test the Lipid Hypothesis
Would have low cardiovascular risk factors:
• Low insulin
• Low blood pressure
• Low waist-to-hip ratio
• Low body fat
• Low triglycerides
• High HDL
• Yet very high LDL-C and LDL-P
They see this…
I see this…
Share your data, help us advance the science!
• If you’re on Twitter, use the hashtag
#LMHR4Science
• If you’re on Facebook, join our new group for LMHRs and everyone
interested in the research:
Facebook.com/groups/LeanMassHyperResponder
• We’ve set up a special page at our site:
CholesterolCode.com/LMHR
Thank you for watching
For more information on my research, please visit:
CholesterolCode.com
Or contact me on Twitter: @DaveKeto