Executive summary
* Lean Mass Hyper Responder (LMHR) was the term developed by Dave Feldman to describe lean, fit, metabolically healthy people, who exhibit striking increases in cholesterol when adopting a ketogenic diet.
* Last week we looked at the latest paper from the LMHR research team. The paper was called “Plaque begets plaque, ApoB does not: Longitudinal data from the KETO-CTA Trial.”
* In last week’s note, we reviewed how the definition of LMHRs had changed over time and characteristics of the 100 participants involved in the research along the way. We also noted the aim and primary outcome of the KETO-CTA Trial, as documented in the February 2023 clinical trial registration and the June 2024 study design and methodology paper.
* This week we look at the results from the KETO-CTA trial and five critiques that have been made in a rapid response pre-print paper. These five themes reflected much debate on social media.
* The main results were that plaque progression:
i) was not associated with baseline ApoB; change in ApoB; or total LDL-C exposure.
ii) was associated with all baseline plaque metrics (coronary artery calcium, NCPV, total plaque score, and percent atheroma volume).
* The key factor of interest in LMHRs from the outset has been the level of LDL-Cholesterol. The recent paper did not report this measure; it focused instead on ApoB and a new outcome of interest – LDL-C exposure. Why?
* The five critiques can be summarised as:
1) The pre-registered primary outcome was not presented as a value in the paper.
2) Having since been informed about the percent change in non-calcified plaque volume (NCPV), it’s comparatively high. The percent atheroma volume (PAV) is also high.
3) The main finding from the paper about ApoB (and LDL-C) not being associated with plaque progression cannot be made.
4) The main finding from the paper title “Plaque begets plaque” is not new or explanatory.
5) The research should have been called KETO-CTA study not KETO-CTA Trial.
This note goes through each of these critiques and the authors’ responses, to try to assess if they were valid.
* I close by reiterating the research question for the LMHR team and trying to evaluate whether it has been answered.
Introduction
Last week we looked at the latest paper from the Lean Mass Hyper Responder research team. The paper was called “Plaque begets plaque, ApoB does not: Longitudinal data from the KETO-CTA Trial” (Ref 1). The lead author was Professor Adrian Soto-Mota. The senior author was Professor Matthew Budoff. Other authors of interest include Dave Feldman and Dr Nick Norwitz.
This week we are looking at the results from the latest paper and the reaction to those results. This is my 735th Monday note. It’s the first where I have spent as long reading threads on X (twitter) as I have reading academic literature. The debate about this research is being played out on social media.
In an interview about the research and the paper, the senior investigator, Professor Budoff, said “I presented the initial data at the World Congress of Insulin Resistance & CVD. The presentation was filmed and that YouTube video had over a million views, where I probably have hit maybe 100 views on any other video I’ve ever made” (Ref 2).
The paper attracted a lot of attention because it sought a lot of attention. There are pros and cons of this. More people check X than read academic publications. Social media can extend the reach of research but social media can also be a ‘cesspit’, for want of a better word. Some of the critiques were well made and valuable. Some were nasty and vitriolic. There was no need for the latter and I did feel for the team for the abuse that they received from some people.