Today we talk to Dr. Ethan Weiss, board-certified cardiologist and professor of medicine at UCSF, where he researches metabolism, obesity, and diabetes. He's also been on a low-carb diet for about five years, so I thought he'd be the perfect person to ask some common questions that the viewers, you guys, often ask about low-carb, cholesterol, and saturated fat. So here's our conversation. I was really curious and really interested in talking to you because you have this very unique combination. You have the clinical experience, you have the research experience, and you have the personal experience of eating a low-carb diet. And we get so many questions and so much interest from viewers on low-carb that I was really interested in talking to you and kind of getting your take on this whole thing and the common questions, the FAQs. I didn't ever think it was for me, and then I quite accidentally sort of started doing

low carb myself, and at that time I was doing ketogenic. I was actually measuring ketones, got very interested in using ketones as a biosensor to be able to kind of provide feedback to people, maybe in the hopes that that would sort of replace the attention people were placing on the scale. I was working with a guy at the time who was developing a breath sensor, and this all started when he gave me one of his prototype breath sensors to play around with. I started to kind of experiment and honestly sort of got gamified by it almost instantly. I never tried to eat low carb in my life and wouldn't have thought I ever would, and I just kind of, I guess I have a little bit of an addictive personality, and the game of seeing my ketones go up was quite addictive to me. And then what happened concurrent with that, and I used to have this

graph. I'm sure I could find it somewhere where concurrent with my ketones going up, my weight started to come down. I was not heavy back then. I was six feet, 180 pounds, middle-aged, had some plumpness in the midsection, but I watched this weight come off, and I had to buy all new clothes. Yeah. I lost like 20-something pounds in six weeks. The relationship between ApoB, let's keep it simple, between ApoB and ASCVD risk is extremely high. It's linear. It's been demonstrated across multiple different lines of experimental evidence, from epidemiology to animals to human genetics, again and again and again, to now three different classes of drugs, again and again and again and again. And the models are all identical, and what we see is a linear relationship, and you can predict for every milligram per deciliter reduction in LDL-cholesterol or ApoB, you'll see X (whatever percent) reduction in risk, and again, I

just I don't see how it's controversial, but then again lots of things in the world shouldn't be controversial, and they are, so I've stopped kind of beating myself up about it. Yeah, I think putting myself in the shoes of the viewers who ask these questions, because I obviously agree with that, the data is as strong for apoB as for anything in biomedicine, but the question people, I think in their minds, is the low carb context maybe is an exception, kind of an oasis where this undeniable risk factor for most people just stops mattering in this context. Right, my position has been all along, the burden of proof is actually, since we have these multiple lines of evidence again and again and again in every context, literally every context, so if there's a new context where it doesn't matter, where the relationship is not as severe or not as steep or where there may be some sort of mitigation of the risk afforded by a high APOB,

it needs to be demonstrated. You can't just say, Oh well, it's not risky because I'm on a low carb diet. Says who? There's no evidence for that. So, I think, again, am I going to, in the spirit of being open-minded and considering anything reasonable being possible, do I allow that there's a chance that there may be a difference? Yeah, of course, but it better be demonstrated. I'm not going to believe it until I see it, so until then, I treat it the same, and that's what I tell my patients, and they seem to understand that and agree with it. So, that's the way I look at this now, is that making up some arbitrary reason why we think it might be safer is silly. Now, here's the truth, is the people who make that argument that it's the low carb context that makes this safe relative to... That doesn't bother me quite as much as the other group of

people who say LDL's just not important or ApoB is not important at all in any context, that to me is the sort of much more poisonous argument. At least the people making that sort of former argument are allowing that apoB is a problem in most contexts, but my interpretation of how this worked in the old days was that people found this diet, they had a huge benefit from it, they lost a bunch of weight, they felt better, so anytime you do something and it's successful you feel great. People, like I said with me, people told them they looked great, they bought new clothes, it's like an amazing experience and everything improved except their LDL-cholesterol went from, whatever, 80 to 375. And so that provided some cognitive dissonance so they had to do something to kind of resolve that. How do you resolve that? Well, you go out and you demonstrate that in

that context. It's not dangerous. That was what I thought, but I actually think, given what I've seen in the past couple of years especially, there is just a brand of person out there who just wants to be different. And I think it's actually much more about marketing and branding than anything else. I think people get a lot of love in social media circles for just being that stick it in the eye of the big Western medicine or big Pharma or whatever it is. We're just gonna poke them, and we're not gonna buy into that. They're trying to poison us. Interestingly, you were talking about the different diet tribes, I think you called them, and I've seen this exact same logic from other diet clubs. I've seen some vegan gurus do exactly the same thing. Yeah, cholesterol matters if you are on the standard Western diet, but if you're on the vegan diet, you're protected. Cholesterol

is just a number, it doesn't matter. So, I don't think, sometimes I think it's unfair that it gets put on the low carb people exclusively, but maybe they are more vocal about it. But I have seen the exact same diet exceptionalism from these other diet clubs like I've basically gotten to, sort of the simplest answer is, what's your ApoB? The role of HDL itself in atherosclerotic coronary disease is fascinating, and there's a 50-year journey of trying to understand it, and it's still controversial. Triglycerides are also controversial, even though I think there's better evidence for the role of triglycerides in ASCVD. I think if you look at it carefully, and I'm not an epidemiologist, but I think if you look at it carefully that it's the apoB component of triglycerides probably that contributes to risk.

so the simplest way to think about this is what's your apoB. So what's incontrovertible is that there is a strong association between low HDL and increased risk. That's true, we know that, and we know that low HDL is a terrific marker of risk. But what we now know is that it's almost certainly not a mediator of risk. And so I think, unfortunately, because we all want neat packages and clean stories, we all want to build that there's a sort of causal nature to all these things instead of just being honest with ourselves and everyone else. This is why I've taken to following Daryl Francis, a London cardiologist who started using the term, I don't know, four or five years ago, that statins are not LDL-reducing drugs or apoB-reducing drugs. They're heart attack risk-reducing drugs. They happen to also reduce LDL, which we think certainly has a component, but there's probably something else.

we can't exclude that there's something else going on. There looks to be an impact on inflammation, plaque stabilization, whatever it is. There's probably something else going on, so I think it is fair to say in a super reductionist way that they reduce the risk of heart attack. That's clear, that there's almost certainly a significant component of LDL or apob reduction among that, but that there are probably other things as well. So HDL is a great marker. If people want to use it as a marker of risk, fantastic, but what I tell them is, don't go out of your way trying to change it because the evidence is pretty strong that modulating HDL, and whatever you do, whether it's exercise or drinking alcohol or taking a drug, it's not going to change your risk. If anything, it might increase it. So that's the kind of take-home for me, is, let's just clearly communicate what we

know and be more circumspect about what we don't know, and I think we'll get a lot farther. And if someone has high ApoB and a high HDL-cholesterol, is that in your mind, is that a reassurance? I mean, I guess on a relative scale, it's somewhat reassuring, but it's all context-dependent. I mean, if you're talking about somebody who's like, secondary prevention, no, I couldn't care less. If it's a 27-year-old who's got an ApoB of 90 and there is..., it's all context-dependent, but yeah, is it somewhat reassuring if the HDL is higher? Yeah, it probably reflects better metabolic health, it probably does reflect some reduction in risk relative to this similar... yeah, modulator factors on top of ApoB that might raise risk even more. That's right. So just as if somebody came to see me and was a smoker and

I was comparing somebody with the same ApoB, smoker and non-smoking. I use that knowledge as well. The absolute risk would be higher because you're compounding risk factors, yeah. My view on calcium scoring is, again, I try to keep it really simple, and it's maybe not in line with the sort of power of zero calcium CT gurus. I probably disagree with them. I think there is a power of zero. I think the power of zero is much more impactful in an older person, so I think there's zero power of zero in a 20-year-old. If you have calcium in your arteries at 20, you got a problem, so to me, it's meaningless when I hear that somebody's got a calcium score of zero if they're much less than 50, certainly less than 40. It's almost unheard of, so yeah, I think in a 65-year-old, if the ApoB is modestly elevated and the calcium score is zero and it's a man, I'd

be more willing to be sort of nuanced about sort of how aggressive we were going to be if there was a good reason, and so it helps, I think it helps in those edge cases, I think it's extremely helpful if it's positive in a young person, it's extremely helpful if it's negative in an older person, and then there's this sort of in-between where it's usually not very helpful. it's a very late marker of disease, isn't it? so having zero calcium score after three or four or five years of having hypercholesterolemia or high apoB doesn't necessarily tell us much, you could be growing soft plaque. that's right. you could have calcium 10 or 20 years down the line. absolutely. it's absolutely meaningless in that context and it really shouldn't be checked serially unless, except in sort of extreme cases where you're already low or zero and you want to

see if it's still low or zero, but people always are confused by, well, my calcium score is super high, I want to make it lower, and they don't understand why I tell them that just doesn't make any sense. And people are doing things like taking vitamin K and other things to try and chelate calcium. The reduction of calcium in a coronary artery has never been shown to my knowledge. I've asked, no one's been able to show it to me. It's never been shown to confer lower risk. I think serial calcium scanning is probably not very useful unless, like I said, there's somebody you're following who has sort of got borderline risk factors and they've got zero calcium score and you want to kind of make sure they stay that way as they get a little bit older. And don't statins, statins can raise the calcium score, right? At the same time as they lower risk. So

it's another indication that the calcium score is just kind of a flagpole that we can kind of use to gauge some things, but it's not this end-all and be-all. No, and that's a great point that people struggle with, understandably, right? Well, how can statins be lowering my risk but then this risk marker goes up? And that's a legitimately confusing concept, and it requires a sort of careful laid-out understanding of the fact that calcium in the arteries is a marker of prior damage or prior healing, and that yes, there is some not well-understood mechanism whereby statins do increase the deposition of calcium, but despite that, they reduce risk. Sometimes people ask, Is it the saturated fat itself or is it the carbs that people tend to consume with them, so if I'm on a low-carb diet, maybe that eliminates the risk? There's all these different ideas,

what's your experience with that? There's good evidence that high saturated fat confers high apoB, but I know people, I don't know how that's so difficult. There have been hundreds of studies over 50 or 60 years showing that. There's mechanisms that people, that you understand. There's upregulation of transcription factors that respond to different length fatty acids. I mean, it's sort of a no-brainer. So, the question that I get asked from time to time that I think is, so first of all, on a personal level, I would not say no saturated fat. I do eat some saturated fat, but I eat a reasonable amount. And when I do, I try to sort of maximize the amount from plant sources versus those from animal sources. Do I never eat animal-based saturated fats? Of course, I eat them all the time. Not all the time, but I eat plenty. But for me, it all comes back to ApoB.

so if you are one of the lucky people who can eat a hamburger, a ground chuck, whatever, every day of your life and your ApoB is still good, optimal, I still wouldn't recommend it but I certainly wouldn't have a strong objection if you said you wanted to keep eating that hamburger every day, I think there probably are some other reasons why it's not optimal but again, I'm not an epidemiologist and I think that the data are very murky and I'm not, that's not why they're coming to see me, they're coming to see me for coronary risk, and from a coronary perspective it's hard for me to go beyond the ApoB, in other words, it's hard for me to make an argument that with a given ApoB, let's say your ApoB is 60 and you're eating a hamburger every day, it's hard for me to argue that that's a problem. yeah. even though I don't do it. so for me it's

all individual driven, it's all driven by ApoB. Where things get interesting is if somebody says, all right, well, I'm on a statin now, my ApoB is 60, is it okay? Yeah, that's the, those are the harder ones, but I think I sort of feel like we do ourselves a disservice if we lose consistency over the value of this marker that we all hang our hats on as being really important, so I think, again, I'm not talking to people about colon cancer risk, I'm not talking about the environment, I'm not talking about animal rights, I'm talking about ASCVD risk. This theory of oxidized or sort of modified LDL or ApoB has been around forever and again, it's all pure association, it's extremely hard to demonstrate experimentally that it actually matters and I think it ends up being a distraction, so until that point... I'm more

than happy to admit that I'm wrong if and when I'm wrong, but at this point, my interpretation of the data is that there's just no data there yet. What I base that on is a handful of attempts to develop drugs to specifically modulate oxidized LDL independent of overall LDL, and those drugs have all failed. Now, maybe they were bad drugs, maybe they were bad studies, who knows, but as of today at least, I think it's probably a distraction. And if you have less residence time, if it's there for less time, right? In other words, if your LDL receptors are upregulated and you're clearing it, then it's less likely to be modified anyway, so that's how I kind of feel about it. You're referring to the antioxidant trials? Well, those are all negative, no, but there was Genentech and I think one other company

were trying to develop monoclonal antibodies against oxidized LDL to reduce it specifically, and those trials all failed. We also talked about how to design low carb diets to maximize cardiovascular health, and we're going to cover all of that next week in part two, in detail, all the specific foods he eats, so let me know if this type of video, these conversations help, we can make more videos like this. Take care, I'll catch you next week.

Low Carb Cardiologist on Saturated Fat, Cholesterol & ApoB | Dr. Ethan Weiss

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