Lean Mass Hyper-Responders: An Exception to the Cholesterol Rule? - Revisited

Physionic

Apr 20, 2025

Episode description

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Created with Biorender

0:00 - Introduction
1:11 - Study Background
2:59 - Plaque in the Arteries
3:48 - Is ApoB linked to Plaque?
4:09 - Plaque begets Plaque
5:01 - Corrections and Critiques
5:53 - Pre-Registration Critique and Unreported Outcomes
7:51 - Absolute Plaque Growth Critique
17:38 - Lack of ApoB association Critique
21:43 - Take-Aways
23:18 - Quick Word of Thanks and Spiders

References
[Study 436] Soto-Mota A, Norwitz NG, Manubolu VS, et al. Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial. JACC Adv. Published online March 18, 2025. doi:10.1016/j.jacadv.2025.101686

Funding/Conflicts: Non-Profit Funding [Citizen Science Foundation] // Potential direct Conflicts of Interest [Dr. Nicholas Norwitz is a co-author of a Mediterranean low-carbohydrate diet cookbook. He donates all royalty payments from the book to nutrition research and education; David Feldman has received financial contributions through membership platforms (e.g., Patreon) to support ongoing research and is a partner in Own Your Labs LLC; All other authors reported no conflicts of interest relevant to the contents of the paper.]

Dr. Nicola Guess: https://drguess.substack.com/p/lean-mass-hyper-responders-and-atherosclerosis
Dr. Stanfield: https://www.youtube.com/watch?v=JE1EACWZiWw
Dr. Kevin Klatt: https://kcklatt.substack.com/p/keto-ldl-c-and-lmhr-oh-my
Alex Leaf: https://alexleaf.com/lean-mass-hyper-responders-are-not-protected-from-atherosclerosis/
Dr. Norwitz Rebuttal: https://youtu.be/sv5apthpLGs?si=nth2PH7PectkBG_v
Dr. Budoff Rebuttal: https://youtu.be/lEKFMeg8AmY?si=q4lNADnFtBlQB-Qu

My Original Video: https://youtu.be/U9xSqdzGIXI

********CRITIQUES, RULES, AND NOTES********

Be aware of the following rules before posting comments:
- Please do not post summaries of the video in the comments - it damages retention on the video and YouTube is less likely to promote it (these videos cost me a lot of money to produce).

Critiques of my work are welcome! Please be aware of the following notes & rules before submitting critique:

Be mindful that this content is not all encompassing on the subject at hand and is self-limited for brevity to reach a wider audience. Also, be aware that I receive hundreds of YouTube comments per day, so the only way your critique can be considered is if you follow the steps outlined below. Finally, YouTube auto-deletes links, so I do not see most comments with links attached.

RULES:
If your comment is rude, you will be banned.
If your comment is not about the studies/topics at hand (i.e. extending to other outcomes not discussed) or offers critique with no scientific basis, it is unlikely to receive a response.

If you can follow these rules, I will try to address your critique and if there is merit, I will add an AMENDMENT to the content in question and pin it so everyone can see it (thank you!).

Please use the following link to submit your critique: https://bit.ly/PhysionicCritique

Disclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.

Episode description

*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*
Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2

*HEALTH AUTONOMY [COURSE]*
Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy

*JOIN THE COMMUNITY*
Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2

*EMAIL LIST*
1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6

*HIRE ME FOR CONSULTING:*
Consulting: https://bit.ly/3dmUl2H

Created with Biorender

0:00 - Introduction
1:11 - Study Background
2:59 - Plaque in the Arteries
3:48 - Is ApoB linked to Plaque?
4:09 - Plaque begets Plaque
5:01 - Corrections and Critiques
5:53 - Pre-Registration Critique and Unreported Outcomes
7:51 - Absolute Plaque Growth Critique
17:38 - Lack of ApoB association Critique
21:43 - Take-Aways
23:18 - Quick Word of Thanks and Spiders

References
[Study 436] Soto-Mota A, Norwitz NG, Manubolu VS, et al. Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial. JACC Adv. Published online March 18, 2025. doi:10.1016/j.jacadv.2025.101686

Funding/Conflicts: Non-Profit Funding [Citizen Science Foundation] // Potential direct Conflicts of Interest [Dr. Nicholas Norwitz is a co-author of a Mediterranean low-carbohydrate diet cookbook. He donates all royalty payments from the book to nutrition research and education; David Feldman has received financial contributions through membership platforms (e.g., Patreon) to support ongoing research and is a partner in Own Your Labs LLC; All other authors reported no conflicts of interest relevant to the contents of the paper.]

Dr. Nicola Guess: https://drguess.substack.com/p/lean-mass-hyper-responders-and-atherosclerosis
Dr. Stanfield: https://www.youtube.com/watch?v=JE1EACWZiWw
Dr. Kevin Klatt: https://kcklatt.substack.com/p/keto-ldl-c-and-lmhr-oh-my
Alex Leaf: https://alexleaf.com/lean-mass-hyper-responders-are-not-protected-from-atherosclerosis/
Dr. Norwitz Rebuttal: https://youtu.be/sv5apthpLGs?si=nth2PH7PectkBG_v
Dr. Budoff Rebuttal: https://youtu.be/lEKFMeg8AmY?si=q4lNADnFtBlQB-Qu

My Original Video: https://youtu.be/U9xSqdzGIXI

********CRITIQUES, RULES, AND NOTES********

Be aware of the following rules before posting comments:
- Please do not post summaries of the video in the comments - it damages retention on the video and YouTube is less likely to promote it (these videos cost me a lot of money to produce).

Critiques of my work are welcome! Please be aware of the following notes & rules before submitting critique:

Be mindful that this content is not all encompassing on the subject at hand and is self-limited for brevity to reach a wider audience. Also, be aware that I receive hundreds of YouTube comments per day, so the only way your critique can be considered is if you follow the steps outlined below. Finally, YouTube auto-deletes links, so I do not see most comments with links attached.

RULES:
If your comment is rude, you will be banned.
If your comment is not about the studies/topics at hand (i.e. extending to other outcomes not discussed) or offers critique with no scientific basis, it is unlikely to receive a response.

If you can follow these rules, I will try to address your critique and if there is merit, I will add an AMENDMENT to the content in question and pin it so everyone can see it (thank you!).

Please use the following link to submit your critique: https://bit.ly/PhysionicCritique

Disclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.

Mindsip insights from this episode:

Understand plaque progression variability in LMHRs

Plaque progression was extremely fast in the minority of LMHRs who already had calcified plaque, but much slower in the majority who did not.

Identify lean mass hyper-responders on low-carb diets

A lean mass hyper-responder is a lean person on a low-carb diet with LDL cholesterol over 190 mg/dL, low triglycerides, and high HDL.

Recognize arterial plaque progression in lean mass hyper-responders

Contrary to some beliefs, the study showed that lean mass hyper-responders, on average, still experience arterial plaque progression over one year.

Challenge assumptions: High APOB and LDL levels do not drive plaque growth

The study's most controversial finding is that there was no association between high APOB or LDL levels and the rate of plaque growth in this group.

Challenge percentage metrics in plaque increase analysis

Researchers argue you cannot use a percentage to measure plaque increase because the starting amount was so low, making any absolute change seem astronomically high.

Recognize uniqueness of treatment-naive LMHRs in research comparisons

A key defense is that you cannot fairly compare this unmedicated group to other studies where participants are on statins or other plaque-slowing therapies.

Challenge the ironic 'threshold' hypothesis for LDL understanding

Some now propose a new, unproven 'threshold effect' for LDL to explain the data, which ironically contradicts the standard models they usually oppose.

Get a CT angiogram to assess plaque burden if you're a lean mass hyper-responder

Given the uncertainty, if you are a lean mass hyper-responder, you should consider getting a CT angiogram to determine your current plaque burden.

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