Keto diet and high LDL study – Diet Doctor Podcast

Foreign Welcome back to the diet doctor podcast I'm your host Dr Brett sure today we Have a special episode focusing on the Preliminary data release for the lean Mass hyper responder study now the Background we've talked about this Before on the diet doctor podcast with Dave Feldman with his hypothesis of why LDL is elevated in someone who's on a Ketogenic diet that is because of of Energy needs basically an energy Transport he's published papers about His lean mass hyper responder phenotype And his mechanistic hypothesis about the Energy model and now he has been Designing along with Dr Matt budoff and Others and an actual study to measure uh With a CT angiogram the amount of plaque At Baseline and one year later for those Who have elevated LDL while following a Ketogenic diet and of course meeting Other criteria that we will discuss Otherwise very healthy basically he Presented the preliminary data at low Carb San Diego and there was a lot of Excitement and on social media a lot of Pushback and part of this has to do with Just our own interpretations people's Individuals interpretations and Reactions to the presentation rather Than the presentation itself so what I Want to do in this episode is we're Going to talk with Dave and we're going

To talk with uh Dr Matt budoff and we're Going to go over uh sort of the Intention of presenting the data the Caution of how to interpret the data What it shows what it doesn't show and What we can learn from it and you know What the future is going to show for This study so I think we're going to Cover a lot of interesting topics that Will really help clear the air so let's Get on with this with the rest of this Interview [Applause] So first year we're going to hear from Dave Feldman you've probably seen on the Diet doctor podcast before he's been on Multiple times and he's an engineer and A citizen scientist but he's not just Your average engineer I mean he comes up With great theories and philosophies Um and partial mechanistic hypotheses About LDL and its role in Atherosclerosis especially with the Within the low carb setting but he Doesn't stop with his theories he takes The next step to organize the study to Try and find the result and that's what We're talking about today and he Deserves a huge a huge Applause and Recognition for taking the step to Organize the study whether you agree With the way the study was designed or The outcomes or the data or anything Just the fact that he's an engineer

Non-medically trained putting his hat in The ring to say I'm going to try and Make a difference here and gather data Not just about hypotheses but gather Data so with that uh with that intro you Can find him at Trying to help people get access to less Expensive Labs on their own and of Course on Twitter the real Dave Feldman So let's hear from Dave Feldman well Dave Feldman great to see you again on The podcast how you doing today thanks For having me on Brett I'm doing good Good yo I just saw you a couple days ago At low carb San Diego and you had some Big news you know there was a big a lot Of excitement around your talk where you Revealed some of the preliminary data From your study that you're doing along With others to look at people with the Lean mass hyper responder phenotype with High LDL who are on a ketogenic diet With high HDL low triglycerides and Getting Baseline CT angiograms on them Along with genetic tests and other blood Markers with the goal being to follow Them for one year to see for plaque Progression Now you presented some initial data Which has created quite a bit of Excitement and some some blowback and Criticism so why don't you give us sort Of the the summary of what that data was

And then we can get into the details of Sort of what it means and what the Reactions have been and how we should be Interpreting this sure it was certainly A major Benchmark it was about a One-year snapshot of data so I had Announced the lean mass hypersponder Study last year at about the same time Literally within days of when we had the One year of preliminary data up to that Point which includes 64 participants the Baseline demographics were Quite interesting we have about an Average age of 53 years and about 66 Percent male Uh granted that's a little a little Heavy on the male side but frankly to be Very upfront I if we were going to lean In One Direction or the other I'd prefer The the side that's a little bit higher Risk which I'm sorry if you didn't know This Brett but you and I are as males a Little bit more likely to develop Atherosclerosis right but particularly Being middle age 53 was I mean one of the worst scenarios we Could have ran into is if it was frankly A lot of very young females for example Um so I did I did like a lot of the Means as they looked and then sure Enough as I showed there was an Interview with Dr Matt budoff our Principal investigator where we talked Through a lot of these top lines along

With uh the calcification score though That's not the major endpoint of Interest the non-calcified plaque is and So we had some qualitative analysis not Quantitative qualitative analysis on Both the calcification and on this total Plaque score And probably the most exciting thing is That indeed the total plaque score was a Bit lower than what would be expected For that population particularly given And here's probably Um the biggest line I guess you could Say is that even though it was a Two-year eligibility you need to be on The diet for two or more years we had an Average of just over four years for These participants so a fairly sizable Amount of time and at an average of 233 LDL cholesterol which turns out if you Look at it against Den Haynes is in not Just the top one percent of the total Population of say inhanes but actually In the top 10 percent of the top one Percent so fairly decent Um fairly decent population a good Cohort to actually take a look at this Question yeah so so very interesting Baseline data But and rightly so some of the pushback You've been getting is that this is not You know outcome data this is not the Intended data of the study to measure Plaque progression this is Baseline data

Which is interesting but can you really Draw conclusions from it I mean for sure I would I was saying this in the Presentation I'll say this now a it's Preliminary and that I would not want Anyone to over interpret it it's it's at An early stage it is crude data so I Mentioned earlier that this is a Qualitative analysis not a quantitative Analysis think of a qualitative is a bit More high level and granted Dr budoff Reviews all these scans for safety and Is able to make those qualitative Measurements uh the quantitative Measurements are a lot more granular and They get a lot more detailed so it's Kind of the difference between say a 50 000 foot View and a you know a five foot View or something along those lines you Can still get a fairly good sense of What the uh actual levels of say plaque Are but that's important to understand When talking about preliminary data Right but you're exactly right the Outcome we're most interested in is Going to be the longitudinal data or to Put another way the comparison data so It's not just what we have at Baseline But it's also what we're going to have After each person completes their year And gets the second scan and then we can Compare the first scan to the second Scan Why this has been pretty exciting for us

Is this is the first time That we've been able to even get a Baseline Glimpse at all I mean that's What's so fascinating Brad is you and I We've speculated for a long time as have So many other low carbers as to whether At least this is a clear and present uh Degree of high risk such that This study might even get closed earlier Because we would find that there was Indeed a lot of placate Baseline even For what would otherwise be assumed to Be a relatively low risk population Other than the high levels of LDL that's Very important to be clear about so Because a lot of people reading or Seeing the the preliminary results or Looking at the study want to know does This apply to me so if someone has Type 2 diabetes or it doesn't meet that Criteria then no you are at a different Risk profile than the people enrolled in This study and that's something you've Been very clear about from the beginning But I think it's important to be very Explicit here about that as well so People can know does this sort of Reflect their type of population or not And because the findings were as you Said sort of better than expected in Terms of Um plaque amount of plaque and calcium Scores part of it could be because it's Sort of a selected lower risk population

With really the only risk factor being That elevated LDL would you say that's Accurate I would say it's accurate and Quite literally this is what we were Going for is we wanted to specifically Get a population that didn't have Otherwise traditional cardiovascular Risk factors but save the one of Interest extraordinarily high levels of LDL yeah now I do want to be sure that I Inject with Um absolute passion that not only is This preliminary but everybody's Individual care is individual so while This may be six to four individuals While this may look great and while I Think that this is a very big deal I'm Sure you'd agree with me that it's not The only deal this is kind of the first Big step and what I believe is going to Need many more steps to come and I know That we're sort of in a space Brett Where things are often kind of placed in A black and white kind of uh you know Series of categories I really think when It comes to atherosclerosis as much as I May be cautiously optimistic about this Population that there is so much more That we still have to learn and Everybody should be treating it exactly Like that as as something that while This data is coming in and while it's Very exciting Um I at the same time wouldn't want

Anyone to have this effect their Individual care too predominantly yeah That's well said and a very important Take home now the it seems like the Excitement is coming from the the fact That the plaque the presence of plaque Was lower than expected for people who Have had LDL an average of 233 for four Years when their age you know 55 or so Like you like you said in the in the Findings but is that actually compared To a cohort similarly or is that more Just sort of like what people expect and The comparison will is going to happen Later in the study and here's where it Does get kind of important to emphasize We don't have a control group in our Study what we are going to do though is We're going to do match comparisons with Miami heart which is another study That's being done then Dr budoff I know You'll be chatting with soon can talk About a little bit more in depth but for Which we can actually pull a number of People for which they also don't have as Many cardiovascular risk factors and not Have high LDL but for which we can get a Sense of how another other low-risk Group of roughly the say the same age Same demographics would match up now all Of that said there is something Important to note here which is that the Existing lipid hypothesis is in a sense Its own control with regard to the

Expectation of a dose-dependent log Linear Association of the LDL to Resulting cardiovascular disease I'm Sure you've seen many of the heuristics That are out there that there's many Great papers including the the very Famous One the review from EAS that came In 2017 That shows that this is this is Remarkably you know consistent across All these different lines of evidence so The first biggest question is is there a Line of evidence where we can look to Those people who don't have some form of Dysfunction and lipid metabolism such as When you're born with like FH or when You ultimately acquire such as diabetes And atherogenic dyslipidemia that's what I think lean mass hyper responders can Bring to us is this is now a time where We can look at this high level of LDL Without that dysfunction possibly it's a Hypothesis and see if we see that same Level of dose-dependent log linear risk Because As you know an LDL of 200 shouldn't be Twice as bad as an LDL of 100. Technically it's several fold worse as You work out these graphs and especially Going through these heuristics you see Why so for example Um I think they're using in some cases Milligram years it's kind of like pack Years with smoking yeah which you can

Start kind of calculating how the risk Increases and it is cumulative past a Certain point and the one that I'm Thinking of I think it starts at around Age 40 if that person was say at an LDL Of 125 and here we're looking at Population that's at say 53 with an LDL Of you know 233 for four years that Actually increases on the curve but I Think here's kind of the important take Home for me or at least the thing that I'm focusing on a lot right now is the Big magnitude question is easier to Answer than the small magnitude question Is it a is it a high risk group or a Low-risk group I think we can get to That answer sooner than is it a low risk Sub-optimal group versus a low risk Optimal group Because I'm sure you agree that right Now the vast majority of lean mass Hypersponders could have excellent Cardiovascular risk factors across the Board save An LDL of 233 they're not walking into Their doctor's office and the doctor's Office is going oh actually you're Pretty low risk but you could be Slightly better yeah be slightly better If you had lower LDL no they would Consider it very high risk the Guidelines considered a high risk and as Always they could be right which is why We want to get this data to better

Understand yeah I think that's so Interesting because I mean I see so many Patients who said my doctor tells me I'm A ticking time bomb and a walking heart Attack and I'm going to have a heart Attack any any day now and that's Certainly not science based but it's Very emotional so will this data help Tamper that down knowing it's Preliminary knowing it's you know There's not a control group right all The caveats just this sort of Observational data that's what I get Where you're going with this that that Maybe it would allow the doctors to take A breath and be like okay this is Definitely not optimal the guidelines Say it should be treated but maybe I Need to check myself as a doctor and say You know tamper my my strength strength Of the immediacy of the risk do you Think that's an accurate statement That's reflected in this data or even That level we can't really conclude yet I think patients in the doctors it's Very individual and I'm and I think That's a good thing for a lot of Patients certainly a lot of folks that Are part of the groups they say look my Doctor just wants something some data so That I can at least discuss with them Some option that's you know in the Middle such as hey Um my doctor would be more okay with me

Going and getting a CAC scan to Determine my risk but right now they say I don't even see if there's any point Because all the data I've ever seen Shows high LDL being high risk so what's The point of getting a CAC so in that Example it might be that that could be Something that would matter for the Fence sitting again I wouldn't want to Interject or or you know press that this Data should have that impact but if it Did that might be relevant but again That's between the patient and the Doctor so one other cool part about the Preliminary data You released was the Prevalence of FH I think if you look at A general population FH being familial Hypercholesterolemia if you look at the General population of people with an Average LDL of 233 there's going to be a Pretty high percentage of people with Familial hypercholesterolemia again we Would need sort of a a similar control Group to reference to to find out but in This study how many people had FH of the Original participants that you shared The data with Rudolph mentioned that we Just had one that had I believe it was Monogenetic Heterozygous FH at least heterozygous FH That actually showed up on the genetic Testing but this is important Brett Because this is why there's kind of a Confluence of

I guess you could say scientific Opportunity that all came together at The same time it wasn't just that I Personally went on a ketogenic diet and Seven years ago I saw my cholesterol go Up Under any other circumstances I was part Of kind of the way of a people going low Carb who saw this outcome were it not For a lot of people Who are now in this leaner possibly more Athletic State who would have observed This quote unquote hyper response we Wouldn't have this pattern recognition And then ultimately this cohort that we Could be looking at so that's that's Kind of the irony is you're right at Probably any other point before now Before the rise of the ketogenic diet We wouldn't have had this scientific Opportunity to sort of look at it in This light separated from the genetic Aspect that can result in the higher Levels of LDL again that dysfunctional Lipid metabolism typical of monogenetic FH is what I'm especially interested in In separating those two things out and How much the higher LDL is independent Of that in its association with Atherosclerosis yeah I think that's a a Great learning point for all clinicians And again even if it's not part of the Outcome data or you know the primary Outcome data it's a lesson in FH in what

FH is for clinicians to know because Again I see so many patients saying I Have an LDL of 200 and my doctor said I Familiar hypercholesterolemia no Questions asked and you know no room to Debate it and that's not true and so That's where doctors need to become Familiar with the Dutch criteria in the Simon broom criteria and this is the Perfect example of how something else Can raise your LDL Beyond FH it doesn't Mean mean there aren't some other Genetic involvement that we just don't Know about yet but that's very different From having LDL that's elevated from the Moment of birth because of FH I think That's a great learning point from this Preliminary data so beyond the FH data And the preliminary Plaque burden data Are there other Nuggets or take-homes from the Preliminary data or at this point is it We've learned what we're going to learn And now we wait for the the one-year Data there's discussion right now on a Paper that we may ultimately be putting Out on preliminary data which may or may Not include more I can't say that much On that because of course this is Ultimately up to our principal Investigator Dr budoff and there's Certainly a lot of insights I'm so many More

And that I wish uh we could be looking Into but that rightly are carefully Controlled so as to preserve the level Of blinding we need for Um the outcome data to have the Strongest validity right so let me give You some examples we're measuring LP Little a we're measuring C-reactive Protein we will also have data on LDL Particle size on APO B and APO A1 There's also very high level lipid data That we're going to be getting out of Finland But we have to send Frozen samples to Them we're going to do it in one batch Because it's crazy expensive to send Frozen blood samples overseas And that probably won't be until like The very end of the study but it will Give us a new level of insight on Exactly how lean mass hypersponders Compare and we'll actually have a great Comparison group with say the UK biobank So we can actually see these Compositions let me give you an example Of something that I'm excited about but I know we're years away from knowing but That I can't wait to get from this data Set which is Have long held the belief that lean mass Hypersponders will find that the Lipoproteins particularly apob Containing lipoproteins they will have a Different composition of a higher

Level of cholesterol lower level of Triglycerides than you would find in the Same size LDL particles with say Somebody with severe type 2 diabetes Which by the way matches with the lipid Energy model Somebody with severe type 2 diabetes is Probably going to have a higher Triglyceride versus cholesterol Composition in their LDL particles and I Realize the current Paradigm is to go oh So then that must mean if this is more Associated with atherosclerosis than This this must be more of an atherogenic Particle but as you know Brett from Knowing me a long time I think that Actually more of these lipid patterns Are a reflection of the state of Atherogenicity more so than they are Independently atherogenic this isn't to Say that I'm ruling out The latter just that I think metabolic Health and how it is reflected in our Lipid profiles I think in time will become a much more Important thing to look at and to Understand and I I honestly think lean Mass hypersponders will be a big step Forward in bringing us to that level of Understanding but that's just my Hypothesis yeah I mean and that's what You do you come up with very clever and Well thought out hypotheses which Doesn't prove anything but then you've

Shown that you put your money where your Mouth is so to speak to try and design a Study to elucidate that now To design a study to quote unquote prove It is very challenging takes a lot of Money a lot of people a lot of time so What you have here is a basically a Pilot study to get the ball rolling but That's part of the pushback of the way The study is designed and the outcomes And the duration and you're not going to Have enough people it's not long enough Atherosclerosis is a decades-long Process and Um this isn't going to show anything I Guess you know that's some of the Pushback so one do you think it's valid And two you know the concept of if you Can't do the the end-all study why Bother doing you know the preliminary Study I don't agree with that statement But that's sort of a lot of the the Pushback I think you're getting so I'm Curious how you responded that well First of all I think yeah a lot of Pushback there's a lot of pushback that I myself would give in the course of Designing and developing this and Raising money for it and so on and so Forth Data comes in a spectrum and always has Again I know we're in a space that likes To just try to find a way to just cast All data out the door depending on the

Nature of what it is right but I think It's fine for a lot of data for example To be considered hypothesis generating Certainly I feel a lot of epidemiology Is exactly that right but in the case of This we had a very unusual circumstance We had people who we knew would likely Be at levels that by current guidelines Should be on the maximally tolerated uh Dose of Statin without any further Consideration if you have an LDL of 190 Or higher is the current guidelines that It doesn't matter whatever other Cardiovascular risk factors you have you Should be taking very serious steps to Lower it right and therefore even just Trying to determine if this is a High-risk population or not is important Well of course we were going to run into Challenges in trying to get a population That may have this strip of diabetes or Heart disease or anything else that Might be a little bit more commonplace In the average standard American Population so exactly as you said as a Pilot study this at least says hey What's our best shot at trying to really Isolate the higher LDL in its outcome as Is commonly referred to for those such As you know children born with Homozygous FH I mentioned the seminal work of brown And Goldstein they bring forward that Point and it's a compelling point that

Hey if it's just the concentration of LDL not the dysfunction of lipid Metabolism to explain this higher level Of atherosclerosis then sure we should Be able to find people like we're doing In this study with everything else Looking Stellar but with very high LDL And thus very high above B Uh demonstrating atherosclerosis in a Fairly short amount of time And again I just want to State one more Time it doesn't mean that this study Will effectively get to that granular Level I think it's a defensible position If many people are saying hey I think That these are a low-risk population but That they could be even lower risk if Their LDL were lower and this study Won't be good at finding that out which I said on the announcement of it but the Big magnitude question We do have I mean we do have an Expectation that the high LDL will show This and I don't know if that's what We're going to see but we'll find out Particularly once we have the Longitudinal data in hand I like how you Phrase that that there are different Questions that are brought up anytime You're talking about LDL and Cardiovascular risk and this study is Not going to address all of them for Sure what first study ever does right But it's I I don't know I think it's

Important to view it for what it is a Pilot study that's going to show proof Of concept in a way and then hopefully Open the Spectrum for bigger funding Sources bigger studies longer studies That will continue to look at this I Mean this is not an end-all be-all but One question is so the average is 233 For the LDL but yet we see examples of Lean mass hyper responders with ldls of 400 500 600. do you think the findings Of this study with the average LDL being What it is will also apply to the LDL of 400 and 500 because if it is You know the the energy metabolism and Not a dysregulation of lipid metabolism Um then one Theory would be it doesn't Matter how high it is the same the same Conclusions apply and I know this is Hypothesis so I want to I want to couch It as such but or do you think there Could still be some effect of the Gradation and if it's five or six Hundred that's very different than the 200 or 250. kind of putting you on the Spot there no it's fine it's it's an Important question and I'm going to be Very upfront and that I actually think a Threshold point from a strict physics Standpoint has never made a lot of sense To me at least in terms of hey we may Find You know an LDL of 200 or 250 is Actually fine

But an LDL of 300 or 400 is the point in which the Lipid hypothesis as we understand it in The broader sense sort of kicks in once You actually get in and I did I've kind Of gotten into the math of what the Actual Size and volume of LDL particles were in Mass against total blood volume well as I this is just a geeky exercise but for Example the typical LDL particle is like Say let's say 22.5 nanometers and if you Figure out what the surface to volume is And compile them all together for what Might be like say let's say that you've Got 500 nanomoles of LDL particles sorry If I'm going to lose a whole lot of People I'll be quick this will just take Like 60 seconds right but I figured this Out for 2 000 animals it I think it came To somewhere in the thousandths I want To say something like uh one two Thousandth of total blood volume if my Blood volume were say five liters Of what the total size would be so if if You think it has to do with actual Viscosity like there's literally so many LDL particles that it's actually Disruptive in that fashion Um I'm just less convinced given what I've learned in that regard But that changes once you have something Like hypertriglyceridemia then you can Actually see

You can see the LDL particles in mass Given their volume is now super large Right because that's that's a lot of um Say chylomicrons which are more like 1.2 Microns again sorry if I've totally Geeked out here for a sec but my point Is that threshold escape velocity point Doesn't make as much sense to me if We're looking at it strictly Mechanistically To the degree that I think that's as Plausible I think it's more likely the Liberal hypothesis as stated And without context makes sense in a Kind of more absolute fashion in the way That it's presented to us now yeah or Perhaps so that there really is Something to be said about the degree With which these patterns are influenced By our metabolism and metabolic pathway Of what we're choosing I I think that's a distant third for me Personally I it shouldn't surprise me that you you Took an engineer's perspective on this And and really thought about it Differently and did the calculations and Did the math and and thought about the Physics of it that that's a fits for an Engineer perspective which most Physicians would not do but I think that The physician standpoint at my Standpoint is that we still have to be Open to the idea that there is still

Some threshold or gradation of of Elevation and that's why homozygous FH Has a much worse course than Heterozygous of age knowing that that is In you know inborn genetic mutation so It isn't exactly the same as the Situation we're talking about but the Other point is that this study won't Answer that question right we have we Have to be open and honest about what Questions this study will address and What questions it won't address and that Would be one of them so when we think About the take homes for people either Now or more importantly at the end of The study you know if you're sitting With an LDL of 500 or 600 I guess the point I'm trying to make is Maybe this study doesn't reflect your Um results or your pattern as much as as We wish it would and maybe future Studies will I don't know if you agree With that or not or um I think I think There's I think your statement's fine It's always difficult with How best to approach addressing this Because Brett as you know I I take very Seriously how How best to say two things at the same Time that hey this is a big deal but It's not the deal yeah hey this is a a Step forward but there's many more steps To go right that this is a beginning Uh it's it's the beginning of a

Conversation but it's not the end of the Conversation and to the extent to where There are a lot of folks who have Extremely high levels of LDL Uh whenever they approach me even if You're somebody who's listening to this And you haven't approached me I'm always Saying the same thing which is First of all be aware that this is Uncharted Territory especially at these Levels of magnitude You know work with your doctor try to Understand everything you can and for What it's worth nothing in my opinion Beats the actual detection of the Disease itself the reason we're using CT Angiograms is because it's literally Looking right at the plaque so blood Markers and everything else aside for Anybody in my opinion who might be Concerned about their risk or does have A number of things for which they Um would consider you know what their Doctor would consider to be risky I think that it might be a wise move to Get a CT angiogram or at least a CAC to At least get an assessment of the Baseline if you're still waffling if You're still trying to figure out what You want to do next now at the time We're filming this it's been I guess About a week or not even a week since You since you gave your presentation and Already there have been some people

Responding saying this is great news LDL Doesn't matter that's wonderful and then There have been some people responding Saying this is a misuse of science to Report the data this way and it's Totally inapplicable and you know no Conclusions can be drawn I think both are a little maybe Misguided Um but are you surprised by the reaction So far and Can you think of a a way to prevent sort Of the extremes of potential Misinterpretation it's a two-part Question there [Laughter] You could have asked me this before I Did the release it would have been Exactly the same of course that there Were of course there are a number of People who would uh believe that this Was the death knell and that there Really doesn't need to be any further Research done I of course disagree with Those folks uh well-intentioned as they May be Likewise those people who are saying oh This this data doesn't matter it's Already disqualified itself it's you Know it's it's kind of fascinating a Friend of mine actually put it pretty Well and said look if if the chief Criticism you're getting right now is This population is way too healthy to be

Considered for their high LDL then That's already a massive change in the Conversation and he hadn't made a good Point there right that that if you're Already coming at this from oh well we Couldn't have expected a lot of plaque Development in this group that's already A significant difference uh from you Know how we understand lipid hypothesis Today but as I said in my talk right and As I'm sure you probably agree with me On there are a lot of folks who disagree With me strongly who I think are very Much well-intentioned uh that you know Are looking out for the care of their Patient they're concerned that Um this data could get circulated and Feed too much into the first group that You mentioned and all we can do is is Continue measuring continue putting out The data and continue our best to try to Make it a nuanced conversation yeah I Think that's a that's a great Perspective so what can we expect next From you then well that's that's a good Question again there's some discussion On the preliminary paper but really I I'd want people to Um try to hold out Um before fully assessing the study Until we're actually at the point of Fully assessing and fully analyzing the Study that said I will say up front that Part of the decision-making process for

This preliminary data was so that we Could get our recruitment completed it Is a challenge because it is true that We require a certain amount of evidence For what your blood work was before Versus what your blood work is now as You well know lot of people are into the Low carb space don't always have Historic blood work data from what they Had just before they'd gone on a low Carb diet but that is something Important to us and so while we've gone Very far and as and I can't say how many We have as of this recording we're not Yet completely there so if anybody is Listening to this and either they or Somebody they know might qualify if you Don't mind me doing the plug one more Time plug it please you can go to and I'll take you to the IRB approved page so until we announce Otherwise we're still recruiting we want To close that recruiting soon Brett so That we can finally get to this final Analysis right because whenever that Last person is scanned It's one year from then that we get the Final bit of data and we can really Button this thing up and find out what The data really tells us oh great right If yeah I mean I that's what I really Hope comes out of this release of the Preliminary data to ignite the Excitement and the questions

Um about the study but to get people Signing up so that we can get to the Data and learn as much as we can from it And know what we know know what we don't Know and decide how to move on from There so again I like I said at the Conference I mean you deserve a huge Thanks for not just coming up with Creative inventive and interesting Theories but organizing the science to Try and investigate those theories it's That second step that is the most Difficult step that you have taken and I'm sure you've had lots of headaches uh In doing so but I think just the world Of medicine is going to be much greater For it so thank you thank you Brad next We're going to hear from Dr Matt budoff Who's the principal investigator of this Trial so he's a professor of medicine at UCLA and the endowed chair of preventive Cardiology at Harbor UCLA he's also an Author or co-author on more than 50 Books and more than 2 000 papers and Articles uh he's on the editorial board Of multiple cardiovascular journals and He's a researcher with the Lundqvist Institute he has some of the the best Pedigree I guess you could say from a Researcher Um very well known very well respected With a ton of Publications and Experience so I think it's important to Get his perspective as the principal

Investigator of this study what he Thinks about the preliminary data Releasing it and some of the reaction to It so let's hear what Dr budoff has to Say Dr Matthew budoff thank you so much For joining me today on the diet doctor Podcast Oh it's a pleasure to be here thank you For having me yeah well we just heard From from Dave Feldman so we heard about The study and we heard a lot about sort Of the the fallback or the pushback from Announcing some of the preliminary data And also certainly what Dave's Intentions were but I want to rewind for A second now that I have you on the line Here that we can talk about talk to About you getting involved in this study In the first place I mean as I said in The intro you're a very decorated Research in in cardiology and have so Many Publications and it seems like Getting involved in a study like this Started right off the bat with some Controversy so I'm curious if you had Any hesitation with this study because Of the high LDL because you know Guidelines say to treat because these Are patients who are not being treated And sort of going against the Conventional wisdom of all LDL does Elevate or all elevated LDL is harmful And there's no debate but yet this is Sort of saying well maybe there is so

Was there some concern about that in the Beginning I mean I certainly thought About it you know I have to say though That I'm I I've read a lot of the work That that people have put out such as Dave and other other people have put out On on the LDL rise with with the keto Diet and and I I really think that there Is a ongoing uh a question and I think The best way to address those is to is To get some research done so I thought It was safe it's only one year these are Already people who are not on statins by Choice so I'm not like withholding Therapy from people who wanted to start Therapy and we're only asking them for One year of observational data to see What happens to their plaque so I didn't Think it raised any ethical issues and I Thought I had enough equipoise about Whether or not there would be Um extra plaque and and what would Happen that I thought it was worthwhile Studying and obviously the IRB agreed With you because they said go ahead with The study so that's obviously a very Good sign so now we have some of the Preliminary data so and as I emphasize My with Dave this is preliminary data of Sort of the Baseline characteristics of The patients with some notable findings But this is not outcome data this is not You know what the study was intended to Do so tell me first like what was the

Idea behind releasing some of the the Preliminary data and talking about it Before the study was completed Yeah I mean again The intent of the study is to see change Over the course of a year and we have Not released any of that information yet So the study is completely Remains completely closed and the Readers here are completely blinded Um to LDL levels to any other values That might sway their their Interpretations so nothing has changed From that perspective we always as a Matter of practice and almost every Trial I've been involved with Um prevent present some of the Baseline Characteristics and presents the study To the medical community so we we say Here's you know here's what we're doing And this is just the people we've Enrolled so far and we're going to study Them for a year and we'll tell you if it Works or not at the end of a year and we Can't tell you anything yet so you know I think in that light we were just Trying to make people aware of the study I think it's a very interesting study I Know some of my colleagues in cardiology Were very excited about the prospect of Learning more about this uh LDL Hypothesis and whether or not it's it's Detrimental or not to the coronary Artery

Yeah I think it's it's nice to hear you Know Physicians cardiologists Researchers with that intellectual Curiosity to want to learn more but then There's the other side of the equation Too have you gotten some pushback from People individually saying like that They were concerned about this and maybe Thought it was it was unethical to do The study and how could you be involved Have you gotten that kind of pushback as Well or not so much no not so much I Think most cardiologists I mean as you Said the IRB approved it it's ethical It's only one year Um you know these are people who are Already chosen not to be on statins for Their LDL it's not like they were Unaware that they had high LDL and that There was any Treatment available these Are already people who've chosen this Course and it's totally ethical to do The study so I've got no personal Pushback from the scientific community And and I to be honest I just don't Participate as much in the social media Community to know what is or is not Being said yeah well it's a good Differentiation between your colleagues And the people you work with and do Research with versus you know people on Twitter but it's not that people on Twitter are completely off base I'd have To say if

The presentation of the preliminary data Was look at this the plaque is much Lower the plaque scores are much lower Than we would have expected therefore This is safe if that was the message Then of course they would have Significant pushback but that but that Hasn't been the message and like you Said it was just sort of presenting the Preliminary data but um do you think There's a need for sort of Extreme Caution when presenting the preliminary Data about what it shows and what it Doesn't represent no absolutely and I Spoke with Dave Feldman quite a bit Before presenting it to make sure it Wasn't represented as a definitive Answer or as proof of anything we Haven't matched these patients yet Remember these are very healthy patients So big asterisks next to not finding a Lot of plaque is these patients except For this LDL elevation are remarkably Healthy people and when we match them They might match up very similarly to The population or who knows maybe even Have more plaque than once we do our Matching which is part of the uh Analysis so I I think we it's very Important not to Um you know derive any conclusions from This preliminary data other than to say We've been very successful at getting Patients in

Um I think it's interesting that there's Not a lot of plaque at Baseline but Again that's not the study and point in Any way and we just need to take that as A as a point of interest and say okay I'm going to wait for the final results To to make any any conclusions So do you think the the matching part of This will be its own paper that once the Enrollment is complete you have the Baseline data you can do the matching And publish that without having to wait For the the full one-year data coming Back yeah yeah I think that would be Very legitimate and obviously it will Make sure you know the IRB and everybody Else is comfortable with that locally Here Um but I don't see any problem if we do A formal matching and just compare Baseline of patients with uh with this Uh high LDL from a keto diet and Compared to compared to the you know Lean mass hyper responders compared to Non-uh to similar patients who are not On this diet and and see if there is Differences at Baseline again with the Final conclusion having to be reserved For for the final end of the study right Now we talked about how the plaque was Presumably low but all right needs to be Compared to to a control but what about What about or not compared but to a Control but matched to another similar

Group which we talked about but what About the FH and I brought this up with Dave that there was Um one patient with familial Hypercholesterolemia and I bet if you if You surveyed cardiologists and said we Have a group of 64 patients with LDL Averaging 233 they would probably guess I don't know maybe 75 percent of them Would be FH that's just a number I'm Coming off the top of my head but there Was only one so are you surprised by That and what was your expectation going In for the prevalence of FH yeah no I I'm with you on that I think at least 75 And I think those patients who had ldls Above 300 uh which was a good proportion Of them definitely would have FH of Heterozygous FH no matter what so I was Very very surprised that we only found One person out of the first 80 or so That we that we screened with genetic Testing we've only had to exclude one Person based on that value I think that In itself is a pretty remarkable finding Uh just from the preliminary data that Cardiologists and Physicians should take Note that not all elevated LDL is FH and There are other mechanistic reasons for It which sort of leads into Dave's whole Hypothesis about why LDL would be Elevated in this situation and I know This isn't a mechanistic study but what Do you think about that you know it's an

Interesting mechanism and hypothesis That he came up with and you are Co-author on a on his other paper about That what do you think about the the Mechanism if it if it makes sense you Know I I do I I think that that Definitely has legs and I think seeing These ldls and seeing you know the lack Of FH in this background of this Population reinforces that obviously There's some you know significant change In body metabolism that causes LDL to Kind of go crazy uh if you will of these Patients but again as as you know as Davis pointed out and I'm totally Agnostic still you know maybe it's not As bad as as it looks just from an LDL Value by itself Yeah and I think that I like that you Said you're you're agnostic about it and That's so important to have you as part Of the study because you're not part of The quote-unquote keto Clan or the the Keto community so I'm curious before Getting involved in the study had you Paid much attention to ketogenic diets And and their use and for metabolic Health and their risk for uh lipids if That is a thing you know had you paid Much attention to that you know I've Seen a few patients with the with the Ketogenic diet and and when their ldls Come back that high just traditional my Traditional mindset kicked in I wasn't

You know super aware of all these Different hypotheses and I just said Look you know I don't mind you being on The keto diet but I'm not comfortable With your LDL of 250 let's go yeah you Know I want you to be on a Statin uh and Get that number down Um and you know if the diet's working For you and you're losing weight or Achieving other goals then then that's Fine by me so uh I I reacted to the LDL Because there was no other data to to Assure me that it wasn't pathological so Do you think this study will help change That approach or do you think it's a First step for what will come next which Then would alter clinical practice or do You think the study's enough if you get You know results that certainly Dave Expects or hopes for uh would it be Enough to change clinical practice I Think it may I think we we've seen these Type of well well-controlled CTN Geography trials be able to change Practice patterns we did it with Icosapendethyl with a fish oil Supplement vasipa we did a trial called Evaporate and clearly had good uptake by The community seeing that it reduces Plaque in the coronary so that was very Supplemental data that people really Reacted well to and I think this will be Very reassuring for those patients for Those doctors or those patients who

Believe that this may not be so Pathological and can can just uh you Know observe it rather than actively Treat it it's obviously not going to Change the practice patterns of all They're going to be some people who say I don't care I don't I don't believe in LDL above 190 should ever exist and I'm Going to get rid of it whenever I meet That number and I that's obviously not Going to change their practice patterns But I think this will go a long way to Reassure those people and if it does Work out that way and again a big if but If it does work out the way that that Dave hopes it does and again I'm I'm Totally on the fence here but if it does Work out positive that it's not Pathological and it's not causing Atherosclerosis I think that's you're in A remarkably reassuring for those of us Who run into these patients on a keto Diet who don't want to take a Statin and Maybe they're maybe they're correct and Maybe we can we can just keep an eye on Them and and not be so worried yeah yeah Well and I should I I phrase it this way But maybe I shouldn't the way that Dave Hopes it turns out and he's always been Clear that he's cautiously optimistic But he just wants to be able to answer The question he is one way or the other He wants to know and it's not that he's He's purely vested in it turning out one

Way but I guess part of the issue is and This has been brought up by some of the Uh criticism on social media is that It's a one-year study and you know Cardiovascular disease is a decades-long Process so is it reassuring enough at a One-year study or or you know is it just A drop in the bucket I mean how do you Respond to those criticisms looking at Plaque black oppression all of our Trials are one year so this is it's not An outcome study I agree if we're Looking at outcomes and we want to show That there's going to be more heart Attacks or Strokes or no increase in Heart attack or Strokes we need a much Larger and a much longer study but these Patients are coming in on average with Four years of these type of LDL Elevations and some of them much longer Than that so we will have in some Patients perhaps a decade of exposure When we look at these CT angios but the One year defined endpoint matches up With all the other one-year studies Which will allow us to match these Patients to other patients who have two CT angios at one year apart that's why We designed the trial to be parallel to All the others so from a plaque Progression standpoint one year is Absolutely standard uh and there can be No pushback because that's just how all The trials are done from uh proof that

It doesn't cause a heart attack I agree It's a decade aids-long process so Decades-long process and needs needs More time if you really wanted to prove Outcomes yeah but I think that's a Fantastic point to compare it to the Existing literature and the standard for Plaque progression studies with CT Angiogram and one year as you said is Absolutely the standard so I think That's great that it was designed that Way and can be compared and of course All this is coming this is going to be Data coming in one year two year three Years down the road so something to look Forward to but clearly nothing Conclusive yet I wanted to bring up one More thing though there was another Comment about are there safety protocols That if someone was enrolled in this Trial with an LDL of 230 not on lipid Lowering therapy and had you know a 70 Percent lad stenosis is there something Is there a protocol in place to address That or does it just continue as as part Of the study no so absolutely so I I'm My my primary role is I do the safety Reads so I'm not reading for plaque Quantification I'm looking for high Grade stenosis left main disease Multi-vessel disease and then if we find That for any study I reach out to the Participant make sure they're not having Symptoms

Um you know and if they are then they Need to be intervened upon and we're not Going to just watch them for a year and Hope that they live another year to to Help our trial no there's definitely That's my role in the trial and we read All the studies the day or the day of or The day after they're performed for that Safety purpose specifically yeah okay Well that's very good to hear and you Know I think as with a lot of things When when we're dealing with you know Part of the information and Interpretations of information that Maybe wasn't explicitly said by those Involved things can get out of control And things can can kind of blow up and I Think that is a little bit that is what Happened in this case but certainly Speaking with you it seems very Reasonable the way you're approaching This and I think it's wonderful to have You involved in this study do you have Any other take homes or or last comments You want to make about the study and the Data presented and kind of what we can Expect in the future no you know I I Think that that you know again I just Would caution anybody for making any Firm conclusions this was this was just Presented as kind of what we've seen so Far and I think it's of interest Um again all of the participants nobody Has dropped out of the trial based on on

This presentation Um I've had a couple people reach out to Me and Um said that they're you know they're Glad that they're participating and They're planning on completing their Their one-year participation and we've Had a lot more people who've shown Interest since since the presentation so I think it will achieve its goal Dave's Goal was only to Stir stir excitement to get more Enrollment so we can finish the Enrollment of the trial so we can answer The question because we were kind of Stalled at about 80 patients looking for A hundred and we wanted to get that Final push over the top so I think that Was our intent I think that was what's Happening we're seeing a lot of phone Calls of people are interested in Participating and again no we're not you Know writing up any papers with any Conclusions as far as the safety or lack Of safety of having an LDL this high at This point great well thank you so much For clarifying all that and thanks for Taking the time to meet with me today Well it's a pleasure thank you for Having me on well that's a wrap on this Issue of the lean mass hyper responder Study the preliminary data and some of The blowback and criticism about that Data but I think as you can see as

Presented by Dave and by Dr budoff it it Seems like it was very reasonable to Present the Baseline characteristics to Help generate some excitement to finish The enrollment But it does have to be messaged very Carefully right this is not conclusive Data this is not outcome data it hasn't Been compared to a a matched group those Are all things that are going to happen There's going to be a lot of information Coming but we don't have that Information yet so yes there's a very Low rate of familial hyper Cholesterolemia and yes there was a Subjectively low rate of plaque but what Does that really mean well we don't know Until it's compared to a matched group So there's much more to come but this is Science this is how science is done and And this is why we need excitement about This to ask questions generate Hypotheses and and start the studies Which is exactly what they're doing so I Look forward to reporting again when we When we get the outcome data and it's Going to be very interesting of course We have to be careful how we interpret It of course we have to be careful how We message it and uh and I'm here to Help with that so hopefully this was Helpful for you to help understand a Little bit better with these preliminary Data mean and what's Yet to Come thanks

A lot we'll see you here next time on The diet doctor podcast [Music] [Music]

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