Appreciate your time to address this paper. And your estimation on change of NCPV in 1 year is right. Adrian Soto-Mota revealed the number which is 18.8 mm3 via twitter 3 days ago rather than in the published paper!!!.
It is so sad to know that the name of the published paper, the objective of the study were changed, the primary outcome has not been reported per the pre-registered trial.😭
I have followed you for more than 2 years. You are the trustworthy, credible source of Nutrition science❤️. Really appreciate it. Greeting from Thailand. 🇹🇭
That is absolutely wild and completely unacceptable. I cannot believe any responsible scientist - especially for an issue as important as heart disease - would be so frivolous and careless as this.
Brilliant summary, thank you Dr Guess. Also as stated you’re completely right, one of the authors revealed the progression to be 18.8mm3 on twitter acting like this is all totally fine. It’s laughable really. He and the other authors have flooded social media commenting on this study hailing it as revolutionary. Luckily a few people I know are doing their best to fight back. Watch this space.
It’s absolutely mad. It’s such a shame that they have taken funding, and used it for this. I think most people would have given them credit for trying to explore a really important area and what is a valid clinical question - “does a rise in LDL cholesterol in isolation represent a risk for cardiovascular disease if all the cardiovascular risk factors are normal?” Yet for some reason they have chosen to report their study in such a way it seems like their primary aim after all was to promote their own beliefs. Very, very shocking, and it’s even more unreal that they are discussing this on social media like it’s a joke, and furthermore that this paper even got past peer review.
Seriously! I don't have a Phd, but as a layman, I can see that you're completely missing the point here, and so are your followers. The conclusion of the paper is not that there was no increase in plaque, but that the increase in plaque was not associated with ApoB or LDL -c, but with the baseline plaque (At least that is what I get from reading plain english)
As to the comment on the lack of control group, that is addressed in the original study that was published a year ago, where they paired the Keto group with the Miami heart study cohort with low ApoB levels and did not find any association with plaque build up based on CTA scores over a 4 year duration. This one is a follow up to that paper. Please refer to that paper, if you haven't already
When folks repeatedly use the phrase 'totality of evidence', they should not be selective about the 'totality' on one side and ignore the other side.
You have to take note of the fact that these studies are the only ones among a few out there that addresses the question whether Apob is a relevant marker indicating cardiovascular risk for metabolically healthy individuals. When the proponents of the cholesterol hypothesis claim that the issue is settled, based on the 'totality of evidence', they cannot cite even one study that controls for the metabolically healthy (people who have low triglycerides, high HDL, normal levels of blood pressure, low HbA1c and good insulin sensitivity - all of these ). The studies conducted by this team is probably the only ones that attempts to do that.
I don't follow the Keto diet, I am more of a plant based person, so my view on this is not based on the political rivalty between plant based and carnivore, but based on my curiosity and search for minimally biased perspectives. I often am amazed by the bias and hyperbole on both sides. But this team - Dave Feldman, Nick Norwirtz, Dr. Matthew Budoff, Soto moto are among the least biased people that I could find among the professionals who put their opinions out there on this topic.
Wrong. The point of having a primary outcome is that it is the entire point of your study!!!! As in, the primary purpose of doing this study according to the investigators (and we know this because they wrote this on the clinical trials database) was to measure change in unstable plaque (stated primary outcome was % change NCPV at 12 months). And yet they did not report this in their manuscript. It’s absolutely shoddy, shoddy academic and scientific standards.
It’s fine to report secondary/post hoc analyses in a paper as long as they are acknowledged to be speculative/hypothesis-generating. However, even having said that, some of the secondary analyses here are bonkers because theyre running correlations between baseline parameters and follow-up of the same parameter: and of course they’re going to be correlated because they contain the same value!!!
I am sorry that these investigators have misled you (and I am sure many others) with their open access paper and irresponsible promotion of it. I would encourage you and anyone else to consider elevated LDL-C as a risk factor for heart disease, and this study absolutely does not change that.
ok, let me tell you this. I have had high LDL C, ApoB and LP(A). Based on the AHA guidelines, I should have been under statins 20 years ago. Based on all other metrics, I am in perfect health. I follow a diet very similar to the mediterannean diet and exercise reguarly. Since all my other metrics are excellent, I did not take the statin advice seriously. Now, after nearly 20 years of having been diagnozed with high cholesterol, I still have a CAC of 0.
The fact is, a person like me is not represented in totality of evidence that you guys point out, and these studies are the only ones that come close to what I am looking for. The only reason, they have to promote it so strongly is that despite all of this, mainstream researchers ignore these results, and continue with their choesterol hypthesis as a gospel truth and recommend universal statin therapy, when the evidence behind that is deeply flawed.
You're not the only one. Very high LDL & ApoB for over 10 years (following low carb/keto diet. My CAC scores (I have had 5) have all been zero. Not so good in the carotids though after my doctor heard a bruit. I am following with annual CIMT scans and now taking lipid lowering medications. Might be worth looking into for you. Not all disease is in the coronaries and a stroke scares me more than an MI!
Doesn’t CAC measure calcified plaque, and the primary outcome of this study was supposed to be non-calcified plaque? It takes a while for calcification to occur, right? But the non-calcified plaque is potentially worse than calcified.
I agree with your comment that studying this so-called lead mass hyper responders phenotype is of value. Any research that seeks to move our understanding of biology forward is to be commended. This study design itself did have flaws, which is a shame such as the lack of a control group. Nevertheless, I agree with you at least they tried to do something. But that’s where my credit must stop. as a responsible scientists and investigators they should present their findings transparently and not try to bury their primary outcome amongst Twitter Memes and speculative post-hoc analysis.
First, the social media hype and buzz needs to be set aside. Everyone can comment as they like, it is a free world, but in the end each of us must read the papers and use the data to guide our health decisions.
As a research chemist with significant numbers of publications in another field, I think it is important to note that not reporting the deltaNCPV median/mean is not super critical. From the chart it is easy to guess around 20mm3 as you did. However, for those that are commenting without knowledge of the CCTA methodology, deltaNCPV numbers are "raw data" not corrected for coronary artery volume measured (and as we all should know, heart sizes and coronary artery volume varies based on sex, body area, fitness, prior plaque volume and length measured.) That is the primary reason the PAV was reported and the authors report a median value of 0.8% for one year. Isn't PAV change the primary outcome? I don't hear anyone thanking the authors for that graph with its reported median value!
While you were being critical of the methods and reporting in this paper, thanks for speaking to people who use keto diets for other health reasons. I am personally thankful for this article. As a healthy LMHR who went on a low carb diet for another medical reason (successfully corrected I might add) and found my LDL and HDL numbers increasing dramatically, this is the first CCTA data that I could find showing the implications over any followup period (do I wish it was a larger study, do I wish the follow-up was longer, do I wish it was a randomized control trial? - YOU BET! But Have you or others tried to raise the money to do a larger trial? It is an immense undertaking with funding in the millions required!). Thankfully, LMHRs can dramatically reduce their cholesterol numbers by adding relatively small amounts of carbs back in.
Interesting. It is indeed weird that the primary outcome wasn't measured. But while we're softly meta-analyzing anyway, I just thought of the many people who have driven down their plaque to zero while on KD. I wonder why this population barely had any of that kind of secondary outcome.
I do a lot of N1 experiments w food and most of them give some benefit and some downsides. It makes me wonder if there isn’t an adjacent issue, like people who feel better on keto actually have MTHFR and feel better bc any source of folic acid is removed, not bc of the carbohydrate itself. So in the short term someone feels better but then a marker like LDL makes for problems long term.
I have definitely seen patients get benefit from a ketogenic diet or even just a low carbohydrate diet. And the rise in LDL cholesterol doesn’t seem to happen in all people. However, I think it’s really important that if it does that we don’t ignore it and pretend it’s fine, rather that we modify the diet in such a way that a person can get the benefits of a ketogenic diet without the increasing cardiovascular risk or people just go and talk to their doctor about pharmaceutical therapies to improve lipids.
I’m still curious to hear if you have any thoughts if the people who get benefit from keto/LC are doing so because it removes a stressor like folic acid for MTHFR or FODMAPs/histamine. I find studies need to be read with the knowledge it’s impossible to control for everything. I personally did not do well on keto the few times I tried it. A functional MD recommended it bc he liked it for himself and my A1c was high (like your other athlete articles) My LDL was also high 3 yrs ago even though I eat very low sat fat and I’m very active. I had genetic testing done and found several areas to support and my LDL went down (not FHC). I also tried a statin when LDL was high and that was one of the worst experiences of my life. LDL was the marker, not the underlying pathology as you are good at stating. Isn’t high LDL showing the existence of oxidative stress somewhere?
Appreciate your time to address this paper. And your estimation on change of NCPV in 1 year is right. Adrian Soto-Mota revealed the number which is 18.8 mm3 via twitter 3 days ago rather than in the published paper!!!.
It is so sad to know that the name of the published paper, the objective of the study were changed, the primary outcome has not been reported per the pre-registered trial.😭
I have followed you for more than 2 years. You are the trustworthy, credible source of Nutrition science❤️. Really appreciate it. Greeting from Thailand. 🇹🇭
Also greetings to Thailand - my sister in law is from Thailand so I know that 555 means lol. Hahaha. 555.
That is absolutely wild and completely unacceptable. I cannot believe any responsible scientist - especially for an issue as important as heart disease - would be so frivolous and careless as this.
Brilliant summary, thank you Dr Guess. Also as stated you’re completely right, one of the authors revealed the progression to be 18.8mm3 on twitter acting like this is all totally fine. It’s laughable really. He and the other authors have flooded social media commenting on this study hailing it as revolutionary. Luckily a few people I know are doing their best to fight back. Watch this space.
It’s absolutely mad. It’s such a shame that they have taken funding, and used it for this. I think most people would have given them credit for trying to explore a really important area and what is a valid clinical question - “does a rise in LDL cholesterol in isolation represent a risk for cardiovascular disease if all the cardiovascular risk factors are normal?” Yet for some reason they have chosen to report their study in such a way it seems like their primary aim after all was to promote their own beliefs. Very, very shocking, and it’s even more unreal that they are discussing this on social media like it’s a joke, and furthermore that this paper even got past peer review.
Great summary!
So glad you're taking the time to do this, thank you!
Love this!! Was hoping you'd address this! Ty, ty!!!
Seriously! I don't have a Phd, but as a layman, I can see that you're completely missing the point here, and so are your followers. The conclusion of the paper is not that there was no increase in plaque, but that the increase in plaque was not associated with ApoB or LDL -c, but with the baseline plaque (At least that is what I get from reading plain english)
As to the comment on the lack of control group, that is addressed in the original study that was published a year ago, where they paired the Keto group with the Miami heart study cohort with low ApoB levels and did not find any association with plaque build up based on CTA scores over a 4 year duration. This one is a follow up to that paper. Please refer to that paper, if you haven't already
When folks repeatedly use the phrase 'totality of evidence', they should not be selective about the 'totality' on one side and ignore the other side.
You have to take note of the fact that these studies are the only ones among a few out there that addresses the question whether Apob is a relevant marker indicating cardiovascular risk for metabolically healthy individuals. When the proponents of the cholesterol hypothesis claim that the issue is settled, based on the 'totality of evidence', they cannot cite even one study that controls for the metabolically healthy (people who have low triglycerides, high HDL, normal levels of blood pressure, low HbA1c and good insulin sensitivity - all of these ). The studies conducted by this team is probably the only ones that attempts to do that.
I don't follow the Keto diet, I am more of a plant based person, so my view on this is not based on the political rivalty between plant based and carnivore, but based on my curiosity and search for minimally biased perspectives. I often am amazed by the bias and hyperbole on both sides. But this team - Dave Feldman, Nick Norwirtz, Dr. Matthew Budoff, Soto moto are among the least biased people that I could find among the professionals who put their opinions out there on this topic.
Wrong. The point of having a primary outcome is that it is the entire point of your study!!!! As in, the primary purpose of doing this study according to the investigators (and we know this because they wrote this on the clinical trials database) was to measure change in unstable plaque (stated primary outcome was % change NCPV at 12 months). And yet they did not report this in their manuscript. It’s absolutely shoddy, shoddy academic and scientific standards.
It’s fine to report secondary/post hoc analyses in a paper as long as they are acknowledged to be speculative/hypothesis-generating. However, even having said that, some of the secondary analyses here are bonkers because theyre running correlations between baseline parameters and follow-up of the same parameter: and of course they’re going to be correlated because they contain the same value!!!
I am sorry that these investigators have misled you (and I am sure many others) with their open access paper and irresponsible promotion of it. I would encourage you and anyone else to consider elevated LDL-C as a risk factor for heart disease, and this study absolutely does not change that.
ok, let me tell you this. I have had high LDL C, ApoB and LP(A). Based on the AHA guidelines, I should have been under statins 20 years ago. Based on all other metrics, I am in perfect health. I follow a diet very similar to the mediterannean diet and exercise reguarly. Since all my other metrics are excellent, I did not take the statin advice seriously. Now, after nearly 20 years of having been diagnozed with high cholesterol, I still have a CAC of 0.
The fact is, a person like me is not represented in totality of evidence that you guys point out, and these studies are the only ones that come close to what I am looking for. The only reason, they have to promote it so strongly is that despite all of this, mainstream researchers ignore these results, and continue with their choesterol hypthesis as a gospel truth and recommend universal statin therapy, when the evidence behind that is deeply flawed.
I rest my case.
You're not the only one. Very high LDL & ApoB for over 10 years (following low carb/keto diet. My CAC scores (I have had 5) have all been zero. Not so good in the carotids though after my doctor heard a bruit. I am following with annual CIMT scans and now taking lipid lowering medications. Might be worth looking into for you. Not all disease is in the coronaries and a stroke scares me more than an MI!
Doesn’t CAC measure calcified plaque, and the primary outcome of this study was supposed to be non-calcified plaque? It takes a while for calcification to occur, right? But the non-calcified plaque is potentially worse than calcified.
After 20 years of hypercholesterolemia, one would theorize some of that soft plaque would have been calcified by now.
I agree with your comment that studying this so-called lead mass hyper responders phenotype is of value. Any research that seeks to move our understanding of biology forward is to be commended. This study design itself did have flaws, which is a shame such as the lack of a control group. Nevertheless, I agree with you at least they tried to do something. But that’s where my credit must stop. as a responsible scientists and investigators they should present their findings transparently and not try to bury their primary outcome amongst Twitter Memes and speculative post-hoc analysis.
First, the social media hype and buzz needs to be set aside. Everyone can comment as they like, it is a free world, but in the end each of us must read the papers and use the data to guide our health decisions.
As a research chemist with significant numbers of publications in another field, I think it is important to note that not reporting the deltaNCPV median/mean is not super critical. From the chart it is easy to guess around 20mm3 as you did. However, for those that are commenting without knowledge of the CCTA methodology, deltaNCPV numbers are "raw data" not corrected for coronary artery volume measured (and as we all should know, heart sizes and coronary artery volume varies based on sex, body area, fitness, prior plaque volume and length measured.) That is the primary reason the PAV was reported and the authors report a median value of 0.8% for one year. Isn't PAV change the primary outcome? I don't hear anyone thanking the authors for that graph with its reported median value!
While you were being critical of the methods and reporting in this paper, thanks for speaking to people who use keto diets for other health reasons. I am personally thankful for this article. As a healthy LMHR who went on a low carb diet for another medical reason (successfully corrected I might add) and found my LDL and HDL numbers increasing dramatically, this is the first CCTA data that I could find showing the implications over any followup period (do I wish it was a larger study, do I wish the follow-up was longer, do I wish it was a randomized control trial? - YOU BET! But Have you or others tried to raise the money to do a larger trial? It is an immense undertaking with funding in the millions required!). Thankfully, LMHRs can dramatically reduce their cholesterol numbers by adding relatively small amounts of carbs back in.
Interesting. It is indeed weird that the primary outcome wasn't measured. But while we're softly meta-analyzing anyway, I just thought of the many people who have driven down their plaque to zero while on KD. I wonder why this population barely had any of that kind of secondary outcome.
Bot? Troll?
There is a good rather scathing write up of it by Sigma Nutrition as well
https://mailchi.mp/4d3f549bab05/mho-6743212
Thank you, Dr Nicola Guess! Your analysis is cogent, concise, and even fun to read. I deeply appreciate your contribution to science and health! 🫶
Thank you! More BS shredded. 👌
So so good 🤟
I do a lot of N1 experiments w food and most of them give some benefit and some downsides. It makes me wonder if there isn’t an adjacent issue, like people who feel better on keto actually have MTHFR and feel better bc any source of folic acid is removed, not bc of the carbohydrate itself. So in the short term someone feels better but then a marker like LDL makes for problems long term.
I have definitely seen patients get benefit from a ketogenic diet or even just a low carbohydrate diet. And the rise in LDL cholesterol doesn’t seem to happen in all people. However, I think it’s really important that if it does that we don’t ignore it and pretend it’s fine, rather that we modify the diet in such a way that a person can get the benefits of a ketogenic diet without the increasing cardiovascular risk or people just go and talk to their doctor about pharmaceutical therapies to improve lipids.
I’m still curious to hear if you have any thoughts if the people who get benefit from keto/LC are doing so because it removes a stressor like folic acid for MTHFR or FODMAPs/histamine. I find studies need to be read with the knowledge it’s impossible to control for everything. I personally did not do well on keto the few times I tried it. A functional MD recommended it bc he liked it for himself and my A1c was high (like your other athlete articles) My LDL was also high 3 yrs ago even though I eat very low sat fat and I’m very active. I had genetic testing done and found several areas to support and my LDL went down (not FHC). I also tried a statin when LDL was high and that was one of the worst experiences of my life. LDL was the marker, not the underlying pathology as you are good at stating. Isn’t high LDL showing the existence of oxidative stress somewhere?