The Peter Attia Drive - December 15, 2025


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


Episode Stats

Length

22 minutes

Words per Minute

175.30916

Word Count

3,889

Sentence Count

209

Hate Speech Sentences

2


Summary


Transcript

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.
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
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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