The Peter Attia Drive - #376 - AMA #78： Longevity interventions, exercise, diagnostic screening, and managing high apoB, hypertension, metabolic health, and more

00:00:00.000 Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the drive podcast.

00:00:15.820 I'm your host, Peter Atiyah. At the end of this short episode, I'll explain how you can access

00:00:20.280 the AMA episodes in full, along with a ton of other membership benefits we've created,

00:00:24.900 or you can learn more now by going to peteratiyahmd.com forward slash subscribe.

00:00:30.600 So without further delay, here's today's sneak peek of the ask me anything episode.

00:00:38.980 Welcome to ask me anything AMA episode 78. In today's AMA, we take on a wide ranging mix of

00:00:46.880 some of the most common listener questions from lifespan interventions and cardiovascular risk

00:00:52.460 to fasting, blood pressure management, hormone replacement therapy, diagnostic screening,

00:00:57.120 and more. This conversation is less about the deep research dives that we typically do and more about

00:01:03.500 how I think through each of these topics in practice, personally, clinically, and even

00:01:08.380 somewhat philosophically. So in this episode, we discuss the single most important intervention

00:01:12.720 for extending lifespan and healthspan, how to motivate midlife patients to prioritize training

00:01:18.000 using the centenarian decathlon framework, the interplay between lifespan and healthspan,

00:01:22.980 and why separating them is a false dichotomy, how to manage high APOB and cholesterol, even with

00:01:28.520 perfect metabolic health, and biomarkers such as a zero calcium score, optimal blood pressure targets,

00:01:35.440 lifestyle levers, and when to use pharmacologic therapy, how to assess and monitor metabolic health

00:01:40.540 beyond the hemoglobin A1c test, including insulin, triglycerides, and zone 2 output,

00:01:45.580 common mistakes people make when trying to improve health and why sustainable habits beat short-term

00:01:51.720 intensity, the effects of time-restricted eating and fasting when calories and protein are

00:01:56.620 controlled, the nuances of ultra-processed food from practical trade-offs to the difference between

00:02:02.120 nutrient loss and caloric density, approaches to hormone replacement therapy for women in

00:02:07.140 perimenopause and menopause, the evolving understanding of testosterone replacement therapy in men,

00:02:12.520 the risks, the benefits, and certainly the misconceptions, why I recommend earlier and

00:02:17.920 expanded screening and diagnostics, including colonoscopy, PSA, coronary imaging, and low-dose

00:02:23.620 CT for lung cancer, the pros and cons of full-body MRI, how I treat patients with prediabetes,

00:02:30.700 tailoring interventions across sleep, nutrition, and exercise, exercise programming for those who are

00:02:36.100 especially time constraint, including strength and zone-based cardio, and how to safely introduce

00:02:42.280 high-intensity training to older adults. If you're a subscriber and want to watch the full video of

00:02:47.720 this podcast, you can find it on the show notes page. If you're not a subscriber, you can watch a

00:02:52.920 sneak peek of the video on our YouTube page. So without further delay, I hope you enjoy AMA 78.

00:02:59.580 Peter, welcome to another AMA. How are you doing?

00:03:08.080 Good. Thanks for having me back.

00:03:09.500 I'm happy it worked with my schedule and your schedule for you to be here. Also like the boxing

00:03:15.140 shirt. Any boxing that's going to come up in the conversation today, you think?

00:03:20.020 Boxing's not that good for longevity, so I'm not sure, but I wouldn't rule it out.

00:03:25.340 Okay. All right. Maybe we can use it as a yin-yang kind of answer. 0.62

00:03:29.580 You could manage your ApoB, or you could pick up some concussions. Which one might be better?

00:03:36.440 On that, today is going to be a very random episode. So what we did is we've been gathering

00:03:43.880 questions from listeners on various topics, all unrelated, and the focus here will be much less

00:03:50.840 a deep dive into the science behind it and much more what you do, how you think, and how you approach

00:03:56.080 things personally, clinically. So it's going to be a little more informal, a little more candid,

00:04:01.260 and we just combined a lot of questions we have recently. So we're going to cover a huge variety

00:04:06.500 of topics, including treating ApoB, blood pressure, metabolic dysfunction, thoughts on time-restricted,

00:04:12.880 eating and fasting, ultra-processed food, HRT, testosterone, screening and diagnostics,

00:04:18.520 what to do if you're pre-diabetic, how you think about exercising if someone's on a huge

00:04:23.060 time crunch, and more. So I think it should be a fun, kind of a little different pace. But

00:04:28.660 before we get rolling, anything you want to add?

00:04:32.360 I don't think so. I think you got it. That's why I'm here.

00:04:34.380 All right. So first question, let's say tomorrow, every lifespan intervention vanishes except for

00:04:43.100 one. So if you can only do one intervention for lifespan, what is your non-negotiable for you?

00:04:51.560 This is for me personally or for society or?

00:04:54.680 It's a good question. Let's get you personally and then your patients.

00:04:59.200 Well, you've worded the question for lifespan, but honestly, my answer doesn't change

00:05:05.120 that much if you make it for lifespan and healthspan. Although if you say lifespan,

00:05:09.260 healthspan, the answer becomes even more obvious. It would be exercise. And the reason is simple.

00:05:15.460 If you simply look at the data, there's really no intervention we have, including smoking cessation,

00:05:23.640 management of hypertension, management of lipids, reduction of type 2 diabetes.

00:05:28.980 All of those things have a significant impact on either disease specific or all cause mortality.

00:05:35.740 But when you look at cardiovascular fitness, when you look at muscular strength and even muscle mass,

00:05:44.160 the benefits are greater. And again, this is just talking about it through the lens of mortality.

00:05:48.620 So I think the answer from a lifespan perspective is exercise. But again, if you expand that and ask

00:05:54.220 the question through the lens of not just lifespan, but also healthspan, then I think it becomes even

00:05:57.900 more clear because for most people, the reduction in quality of life in that final decade is actually

00:06:05.880 a movement problem. It is a movement problem. It is a pain problem. It is a fitness problem.

00:06:11.920 And that's what I think we should be training for. There's more detail we could get into here,

00:06:16.140 but I think in the spirit of, I know we want to be a little quicker today. I'd probably just leave it at

00:06:19.580 that. One follow-up there, which is you kind of mentioned at the end, a lot of what happens

00:06:25.820 towards the end of life is a result of issues around muscle mass, stability, cardiorespiratory

00:06:33.000 fitness. So how do you talk to patients who are maybe in their thirties, forties, fifties,

00:06:38.520 and they're like, I can do everything I want to do now without issue. I'm busy exercise. Look,

00:06:46.160 I get it's important, but it's hard. Can I kind of do it later? How do you encourage people to focus

00:06:52.760 on this now when they think about what they want to do at the end of their life? It's very easy for

00:06:57.740 them to do that currently. Yeah. I mean, we've developed a tool to actually take the exercise

00:07:04.540 of thinking about that and having that discussion from an abstract discussion into a very tangible

00:07:09.960 discussion. So what we do with our patients, regardless of their age, is force them to rank

00:07:19.180 the 10 most important things to them physically that they want to be able to do in their last

00:07:24.780 decade. We call those the centenarian decathlon goals. And some of these goals are just what we

00:07:30.700 would call activities of daily living, but we want people to be ambitious and be thoughtful. So really

00:07:35.520 think about what it is you'd want to do. Each of those activities is deconstructed into movement

00:07:41.000 patterns and physiologic requirements. We've gotten pretty good at this now. This took a couple of

00:07:45.740 years to really, really get down to as close as we could go from an art to a science. And then for each

00:07:51.700 of those activities, we look at the requirements, the movement requirements, the strength requirements,

00:07:56.820 the physiologic requirements, and parameters all across the board. And we say, okay, well,

00:08:00.600 if you want to play 18 holes of golf and walk around, this is what you have to be able to do. You want to be able to

00:08:06.080 hike for an hour, averaging a pace of two miles per hour on this type of terrain, down to how much ankle

00:08:12.060 movement you'd have to have, hip stability, et cetera, et cetera. This is what you have to have. Then we project back by

00:08:17.680 decade. So the only thing you don't know in this exercise is exactly when someone is going to live to, but you want to be

00:08:22.400 ambitious and say, let's assume we're having this discussion and you're 90 years old. If you're going to be able to do those

00:08:26.960 things at 90, at 80, you have to be this much better. And at 70, you have to be this much better. And at 60, this much

00:08:35.240 better. And we back that all the way up until where you are at say 30 or 40. And then we measure you against those

00:08:40.940 things right now. And lo and behold, almost without exception, there is a big gap between where a person is today and

00:08:49.720 where they need to be today in order to take that gravitational slide down to where they're going to

00:08:56.420 be at 90. For me, that is the most potent way to have this discussion because it's not as abstract

00:09:02.360 anymore. Now they've sort of can look and see, oh gosh, even though I can do it now, when I bake in the

00:09:08.560 rate of decline, I'm not going to be sufficient. In other words, sort of like saying like, look, just because

00:09:12.880 you have more money in the bank today, then you will need at retirement on the day you retire.

00:09:19.500 It doesn't mean you will have enough two years or 10 years after retirement, because you have to

00:09:24.860 account for how much money you're going to spend when you're no longer making money. Getting into all

00:09:29.100 the details of how that is done, it would be beyond the scope of any podcast. But I think the macro point

00:09:35.160 is it's never too early to start training, but it can be too late to hit all of your goals. Never too

00:09:41.900 late to start training. But if you show up at 80, unable to do anything, it's going to be hard to

00:09:48.060 be skiing at 90. But if you want to ski at 90, the time to think about it is when you're 30. And so

00:09:53.160 that you can kind of compound those benefits. Another thing you said earlier, which is something

00:09:57.560 that we get a lot of questions on is you were talking about your answer for lifespan and your

00:10:03.000 answer for healthspan. In that case, it was very similar for both. But oftentimes you hear people talk

00:10:08.500 about doing interventions for lifespan. Other people really focus on doing interventions for

00:10:14.300 healthspan, sometimes at the expense of lifespan. And so how do you kind of reconcile the two concepts

00:10:21.960 to you of lifespan, healthspan?

00:10:25.060 I think it's a bit of a false dichotomy to separate them. The truth of the matter is people actually want

00:10:30.400 both. When I hear people say, I don't care about how long I live, I just want to live a better quality

00:10:36.100 of life. I understand what they're saying. And I think that's sort of shorthand for I don't want

00:10:41.560 to get old in a declining state of health. Totally reasonable. But if we're being honest, I think all

00:10:48.500 of us would love to live longer, provided we can live better. And the good news is most of the things

00:10:55.840 that you do to pursue healthspan will also improve lifespan. The reverse is true if you focus

00:11:05.720 on it the right way. So I'll elaborate. And I've devoted an entire chapter of Outlive. I think

00:11:11.300 chapter four is dedicated to making this point, which is you could take two strategies to approach

00:11:18.100 lifespan elongation. One strategy might be, let's figure out ways to live longer with chronic disease.

00:11:27.060 By the way, that is the strategy that is largely employed today. That's the Medicine 2.0 strategy.

00:11:31.940 Again, I explain the context of why that's the strategy and why. I think without assigning judgment,

00:11:38.860 I explain why that's a reasonable conclusion based on the early successes of Medicine 2.0.

00:11:43.500 But what I argue is, I don't think that's a great strategy for longevity. I think for longevity,

00:11:48.340 this right strategy is, how can I live longer without chronic disease and therefore elongate the

00:11:55.000 period of life that I am free of chronic disease? And I think if that's your pursuit of lifespan

00:12:00.440 elongation, you're also getting healthspan. So I guess in summary there, I would say with every

00:12:07.260 intervention that you can think of, whether it's exercise, nutrition, sleep, pharmacology,

00:12:12.540 whether you're pursuing lifespan or healthspan with these things, and of course, you're often

00:12:17.620 pursuing both concurrently. If you're pursuing lifespan through the lens of delaying the onset of chronic

00:12:23.540 disease, you're getting healthspan benefits. If you're pursuing healthspan for the sake of healthspan,

00:12:29.500 and you're doing it at least through a reasonable definition, we can maybe talk about that,

00:12:33.860 you're going to be getting healthspan benefits. So let's now ask the question through the lens of

00:12:38.220 when are these at odds? Okay, well, if I define healthspan, which by the way is subjective,

00:12:44.200 I don't want to suggest that my definition of healthspan is the right definition. It's just the

00:12:49.220 one that resonates with me and frankly with my patients, which is it has a physical, cognitive,

00:12:54.320 and emotional component. But the physical component is not extreme. The physical component isn't that

00:13:01.180 I want to win the CrossFit games. And I'm not here to dunk on the CrossFit games. I just use that as

00:13:05.680 an example because everybody understands what it means. But if an individual said, look, the only

00:13:09.380 thing that matters to me is to be the CrossFit champion of the world or to be the world's best MMA

00:13:14.340 fighter, I mean, that's a remarkable physical task. But at that level, you might actually be working

00:13:20.740 against your long-term interests in terms of health, at least in physical health and injury.

00:13:25.840 So every healthspan optimization must also be viewed through the lens of does this carry

00:13:31.160 much more risk than I want for later in life, whether it be through head trauma or whether it

00:13:36.720 be through significant orthopedic risk. That was a great way to tie in boxing to an answer really early

00:13:41.960 on. So props on that. A follow-up just because I have to. Your age right now, what do you think

00:13:47.980 you'd have a better chance at? Becoming a CrossFit champion in your age bracket or winning the in-house

00:13:55.460 chess tournament? Undoubtedly winning the in-house chess tournament. That's good. That's good to

00:14:01.680 know. So that's some shout out to CrossFitters out there. You're talking about just the same three or

00:14:06.580 four people in the in-house tournament though, right? Like it's not like we're bringing Magnus in

00:14:09.920 or anything. I'm talking the children you play with. Yes. So not even adults, just the young kids.

00:14:15.880 All right. That's good to know. Next question. Question we actually get a lot, which is let's

00:14:20.880 say you have someone, 40-year-old coming to you. They are in shape, no issues with insulin,

00:14:27.920 metabolically very healthy. They get some lab work done and they have a very high ApoB or LDL-C,

00:14:35.800 but they have a zero CAC score. So they got a CAC done, zero. Again, 40 years old. So when you're 0.88

00:14:42.500 thinking about this, let's say from a patient perspective, are you treating their ApoB? Are

00:14:47.040 you trusting their high level fitness, good VO2 max, metabolically healthiness? Well, first of all,

00:14:52.720 I love seeing a patient like this because the hardest things to fix are the things that this

00:14:57.540 person is already showing up with in great shape. And it's not that I don't love fixing. We're trying

00:15:01.800 to fix the hard stuff, but for the sake of this person, this is a great place to show up because

00:15:05.820 high cardiorespiratory fitness, insulin sensitivity are absolutely protective against not just ASCVD,

00:15:11.640 but all chronic diseases. The problem is they don't neutralize completely the role of ApoB and

00:15:16.640 atherosclerosis. And the unfortunate reality of this is that the graveyards across this country and

00:15:24.580 around the world are littered with people who have high ApoB, otherwise don't have risk factors,

00:15:31.320 including hypertension, and yet develop ASCVD and can die prematurely. That's not the majority of

00:15:36.620 people. The majority of people who are dying prematurely of ASCVD have multiple risk factors.

00:15:40.660 Now, ApoB particles are the proximate driver of the atheroma, and therefore every LDL particle

00:15:46.300 is a potential seed regardless of metabolic health. It's also worth pointing out a zero calcium score

00:15:51.760 carries with it an approximate 15% risk of being a false negative. I've personally seen,

00:15:59.440 I don't know, 10 cases of zero calcium scores that are not zero. No more than that. Gosh,

00:16:07.680 if I really stopped to think about it, I would be 10 over the last two years if I go back and look

00:16:11.900 longer, where a person has a zero calcium score, but shortly thereafter a CTA is done and we do

00:16:17.860 indeed see soft plaque, which means that there really is some advancing disease. So I carve that out

00:16:23.600 here, but I'm going to one-up you, Nick, and just assume this person has a perfect CTA.

00:16:27.100 And let's just assume that you've done all of the advanced testing, you've applied the algorithms

00:16:32.920 that can be layered on the CT scan, and you're really, really confident this person has pristine

00:16:37.040 coronary arteries. So now the question is, what should you do? Well, it all comes down to a

00:16:42.940 fundamental question of causality. Do we believe ApoB is causally related to ASCVD? I'm not going to

00:16:49.920 address that in detail here because I've done so many, many times. And the answer is unambiguous.

00:16:55.520 This is one of the few things in biology where there just isn't ambiguity. As much as anything

00:17:00.980 can be unambiguous in biology, I want to be clear, there has to be some ambiguity in even physics.

00:17:06.520 So if you believe that ApoB is causal, then you treat it regardless. Now, maybe you don't treat

00:17:13.240 it as aggressively. So if this person shows up with an ApoB of 150, maybe a reasonable goal for them

00:17:19.500 is 60. Versus if this person shows up with an ApoB of 150, and they have coronary arteries that

00:17:26.100 are littered with plaque, at which point the goal is 30. So again, there's different ways and different

00:17:30.940 degrees of aggressiveness. But the reason you treat causal risk factors is not because you are sure

00:17:38.260 that this person is going to get ASCVD, but because you understand that by treating something

00:17:43.260 that's causal, you reduce the risk. And again, the example I've given in the past, and I'll give

00:17:47.700 again is, Nick, I have a 40-year-old person who's insulin sensitive, super healthy, everything about

00:17:54.560 them looks great, and they just started smoking last month, and they're in my office. Let's just

00:18:01.180 assume I did the most high-fidelity lung scan in the world. They don't have any evidence of lung cancer,

00:18:07.420 or COPD for that matter. Should I encourage them to stop smoking? Or should I say, look,

00:18:13.340 it's okay to keep smoking, but the moment we start to see evidence of lung cancer, we're going to stop?

00:18:20.060 Of course, the answer was obvious here. Nobody would disagree. We would get that person to stop

00:18:23.800 smoking immediately. Not because I know for certain that if they keep smoking, they will get lung cancer.

00:18:29.560 Many smokers do not go on to get lung cancer. And by the way, 15% of people who get lung cancer have

00:18:35.040 never smoked, but there is still causality between smoking and lung cancer. And that's, of course,

00:18:41.520 why we would tell this person to stop smoking immediately. Another question we see come through

00:18:46.600 a lot, blood pressure, high blood pressure. Obviously, we've talked a lot about how high

00:18:52.340 blood pressure can be a silent killer. And in your view, what do you want the average person's

00:18:58.680 target blood pressure to be? And let's say someone comes to you and it's higher than that,

00:19:03.680 what are some of the highest impact levers they can have to lower their blood pressure?

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The Peter Attia Drive - December 15, 2025

#376 - AMA #78： Longevity interventions, exercise, diagnostic screening, and managing high apoB, hypertension, metabolic health, and more

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