Flawed KETO-CTA Study Nail In The Coffin For Keto Diet

This study was published in a social media storm claiming that it showed something that it didn't show at all. The authors are being disingenuous and misrepresenting the truth. There are several very problematic issues with this study and it's authors. It also appears that they may have photoshopped the grapahics and images to make it look like the participants had half the amount of plaque build up that they have. An independent data scientists re ran the data using the same program, and ended up with twice as much plaque progression as they are reporting. 

LDL Cholesterol and apoB Did Not Correlate With Plaque Progression

The authors are claiming that the trial showed that LDL cholesterol and apoB did not correlate with plaque build up. The trial was not designed to detect whether or not plaque would progress based on LDL cholesterol levels. They are also unwilling to release the raw LDL data for analysis by others, which is very suspicious.

All of the participants had an LDL cholesterol level of approximately 270 mg/dL on average, with some as high as 500 mg/dL. All of these values are over the 99th percentile of LDL cholesterol. Meaning that all participants were at an LDL cholesterol level that would promote plaque progression. You will not see a difference based on LDL level alone, but rather other factors.

A good way to understand this is to think of smokers who smoke 10 packs a day and compare them to smokers who smoke 20 packs per day. All of the people in the study are above the 99th percentile of smokers and will end up with lung cancer. At this level of smoking, it is not the number of packs of cigarettes that will predict who develops lung cancer faster. It will be other factors.

If you look at their own graphic, everyone shaded in red had plaque progression. The one green dot below the thick red line had plaque regression. This chart shows that nearly all participants had plaque growth, some excessively so. Only three participants showed no growth. But over 95% of participants had growth of plaque to varying degrees.

This is vastly different than the authors' original claim that no one had plaque progression.

Plaque Begets Plaque

Another bizarre headline the authors are promoting is that the people in the study that had faster progression of plaque were the ones who already had ASCVD. This isn't news. People who are more prone to making plaque are going to make more when you fuel that fire with more LDL cholesterol. If your genetics are such that you already have plaque or have formed plaque despite being otherwise healthy, then you will form more plaque (and faster) when you add more LDL cholesterol to the equation. This just confirms that LDL cholesterol is what causes and promotes plaque formation.

In an environment of insanely high cholesterol, those who are already building plaque, will have more. 

If you took a bunch of smokers who already have COPD or lung cancer, and put them in an environment of very high versus extremely high smoking rates, the ones who already have COPD and lung cancer will progress faster.

I am not sure why the authors are trying to spin this as anything else.

What About Those With 0 Calcium Score?

If you look at those that started out with a calcium score (CAC) of 0, most had extensive progression and their calcium scores were no longer zero.

Some went as high as 50 and 100. This is an incredible increase for one year!  This has never been seen before.

The LMHR Group Had The Fastest Plaque Progression Ever Recorded

The LMHR group had one of the worst plaque progressions ever recorded. They had an 18.3 mm3 increase in plaque volume in 1 year (others have analyzed the data and said it was closer to 20 mm3). This is 4 times higher than similar cohorts in other studies. And if you look at the independent data scientist's analysis below, they likely had 8X plaque progression, due to the authors altering the graphics and charts.

Even when we use the author's reported data of 18.3 mm3, when compared to diabetic, obese, hypertensive smokers, the LMHR had faster plaque progression in 1 year than those less healthy cohorts had in 5 years. This is very troubling, since they seem to claim that being healthier makes them immune to ASCVD.

Massive Increase In Coronary Plaque On Keto Diet

Because the authors did not provide any numerical values nor report the primary endpoint, we have to use their graphics to extrapolate the data. If they were honest they would just report the raw data, the MEAN increase in NCPV and each individuals information. Instead, we have to use these graphics to extrapolate the data.

Here is what a few people online got when these were plugged into statistical analysis models.

The mean or average plaque volume increase was somewhere between 30-40 mm3, not the 18.8 mm3 that the primary author is reporting. Now granted, he is reporting MEDIAN, not MEAN. Why? Because median looks better and does not looks as crazy. Median is the number where half the participants were above and half were below. This doesn't tell the whole story. In most studies they report the MEAN because of this.

Further analysis has shown that the average increase in plaque volume appears to be around 70%. This is obviously an insane amount of increase in plaque volume in one single year.

It would be nice if the authors would just publish the data. Instead we have to extrapolate. A 70% increase in plaque is very, very high.

Dr. Michael Mindrum who has criticized these authors previously for their sloppy and incomplete work, said the following:

Not Reporting The Primary Outcome

When a study is registered, you must explain what you are looking for, what are you trying to demonstrate? They registered the trial stating that they wanted to look at total non calcified plaque volume progression over time. In the article that they published, they did not even report the primary outcome. 

This is troubling on many fronts. Firstly, were they afraid to report that the LMHR people had very aggressive plaque progression? Why not just report your findings. It's ok if it doesn't fit your narrative. Why try to bend the data and the truth?

Secondly, this has become a pattern of behavior among these researchers. Time and time again, they have bent the truth and manipulated data. You can't trust researchers that continue to misrepresent data and misrepresent the truth.

Social Media Circus

If they would have reported their primary outcome without the social media circus and trying to hide the data, no one would have cared. We would have just said, "Interesting study, it just shows what we already know, that young healthy people with high LDL cholesterol are going to have heart disease". No one would have cared. It's just another observational study that adds to the body of evidence, despite being very poorly designed and executed.

Instead, they tried to spin as some huge victory for the keto diet in young healthy people. This was the exact opposite. This is the nail in the coffin for the keto diet. This showed that very young healthy people with no other risk factors had incredibly fast plaque progression. That's the actual story and should be the headline.

Conflicts Of Interest Not Reported

In every trial you must report the conflicts of interest and funding. They reported only conflicts that two of them may have, but not the conflicts that they primary investigator has. Dr. Matthew Budoff has received over $8 million dollars in funding from the pharmaceutical industry. Perhaps that should be mentioned and whether or not any of that was from the makers of the CT scanners. This was omitted and it is unclear why. He has listed on his profiles that he works intimately with the makers of various CT scanners.

What's even worse is that the primary investigator, Dr. Budoff, did not even read the study and in unfamiliar with the  findings. He has stated in several interviews and posts on social media that LDL cholesterol played no role in plaque formation in this "healthy" population. Every single participant had progression of plaque to various degrees. He was unaware that the participants had plaque progression.

One participant had a 150% increase in plaque volume in one year.

One Participant Had Plaque Regression?

This is likely due to CT scan errors and streaming. There is no evidence that plaque will regress with an LDL cholesterol level in the top 1% of all levels. This just isn't physiologically possible. You can not use that one outlier. It was due to artifact and internal errors in the way the CT scanners work.

What About The Argument That Cleerly CTA Is Better Or Different Imaging?

The authors are now claiming that the Cleerly CT scanner used in the KETO-CTA trial was more sensitive for plaque and more likely to "over read" plaque vs other types of CT scanners used in the past? This is just false. The other studies used humans instead of AI to correct for the imaging artifacts. But what if we compare the keto people to other cohorts using Cleerly AI based CT imaging?

All of the above studies used Cleerly AI enabled software and as you can see the KETO-CTA results were astronomical compared to other less healthy cohorts.

What About The NATURE-CT Cohort?

The NATURE-CT was done by Dr. Budoff, in his own lab using the same CT scanners and same Cleerly technology on a very healthy population that matches the LMHR "healthy" population.

The folks in the NATURE-CT had plaque progression of 4.9 mm3 in one year, versus the LMHR who had 18.8 mm3 in one year. Again, this is if we believe the 18.3 mm3 number is accurate and not a severe under estimate.

Study:
https://www.ahajournals.org/doi/10.1161/circ.150.suppl_1.4139340 

Ethical Violations

This is a perfect example of how not to conduct a study and how not to behave on social media. Not reporting the primary outcome because it will impact your social media popularity and go against your "diet religion" is poor form, and likely premeditated. This is a great example for medical students and researchers to use and give examples of how not to conduct research and how not to conduct yourself.

JACC Should Retract This Study and Issue An Apology

Despite the peer review process usually being robust, sometimes poor papers sneak through the peer review process. Hopefully, they can rectify this situation before more damage is done.

Stop Publishing The Nonsense

Journals need to stop publishing papers and "research" by this group. They continue to make a mockery of science and intentionally mislead people, This is now the third publication by this group that comes with serious flaws and misrepresentation on the data. 

Lead Author Says That They Had So Much Plaque Progression That They Couldn't Explain It

Four months after releasing the study in JACC, the main author was speaking at a low carb keto conference in the UK and stated in his presentation that the participants in the study had so much plaque progression that they could not explain it. His entire presentation is on YouTube. When they were finally confronted with the facts and truth they had to try and explain away the excessive plaque progression.

Some screenshots from his presentation:

Essentially, they can't seem to explain how otherwise healthy individuals had such massive amounts of plaque progression in one year. So they went from, "No one had plaque progression", to "they had so much plaque progression, we really can't explain it".

 Data Scientists Analyze The Raw Data In Great Detail

These are two independent data scientists that went through the data and ran it through the same analysis software that the authors used. They got the same graphs, but with a different Y axis. In fact, the original paper authors had a negative Y axis. Which is not possible. It also appears that the authors photoshopped (allegedly) the graphics to make it look like the plaque progression was half of what it should be, which is obviously unethical.

New Imaging Analysis

Now the authors want to re analyze the data with a different software or different algorithm hoping for a different result. This is not needed. We don't need to continue to bend the science to make it fit our pre conceived beliefs. This is why people don't trust science. Because people who are untrained in the scientific method are trying to play scientist. Not by testing a hypothesis, but by knowing the conclusion they want ahead of time, and trying to design studies to help them get that result. Even with that, they have not been able to prove their point. They will probably misrepresent the data again.

LDL Is Still Undefeated

No matter how you try to bend the science, LDL cholesterol has withstood the test of time. Sure, we are finding out more and more about the atherosclerotic process, but for the last 110 years, the higher the LDL-C, the higher the cardiovascular event rates, mortality, and death from any cause. Since, we have ways to completely eliminate atherosclerosis, we should focus on that. 

In every study that has ever been done, when you lower LDL cholesterol, you lower cardiovascular event rates, death, and overall mortality. This holds true even if the intervention was a diet intervention.

Hopefully this article has helped clarify some important details and points regarding this study, because the authors have not been very honest nor very forthcoming. The one piece of data that they still haven't released is the data linking LDL levels to plaque progression. Which patient had which LDL? It does not appear they plan to release that, hence, we can't really ever know the truth about this study. 

More commentary on this trial

https://kcklatt.substack.com/p/keto-ldl-c-and-lmhr-oh-my

https://mailchi.mp/4d3f549bab05/mho-6743212?e=c934f4988a

https://drstanfield.com/blogs/articles/lean-mass-hyper-responders-see-rapid-plaque-progression

https://gregorykatz.substack.com/p/how-does-a-low-carb-diet-impact-heart

https://drguess.substack.com/p/lean-mass-hyper-responders-and-atherosclerosis

https://www.instagram.com/reel/DIZFulxCBXZ/?igsh=YTV0aWdrYmh3a2V3

https://x.com/AlexJLeaf/status/1911548013991932129?t=FeSSMhBLfPN2L7ADaaiTpQ&s=19

https://www.instagram.com/reel/DIZPWBSTHgS/?igsh=MWIzOTcweHp1bG1ndA%3D%3D

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