5 Longevity Drivers That Actually Increase Lifespan by 500%

Dr. Zain Hakeem [00:00:00]:
Sleep is overrated. Yeah.

Nick Urban [00:00:01]:
My Controversial Opinions you’re listening to High Performance Longevity, the show exploring a better path to optimal health for those daring to live as an outlier in a world of averages. I’m your host Nick Urban, bioharmonizer, performance coach, and lifelong student of both modern science and ancestral wisdom. Each week we decode the tools, tactics and timeless principles to help you optimize your mind, body and performance span. Things you won’t find on Google or in your AI tool of choice. From cutting edge biohacks to grounded lifestyle practices, you’ll walk away with actionable insights to look, feel and perform at your best across all of life’s domains. Are you chasing the wrong metrics in your quest to live longer and better? What if there was a simpler way where you could strip out all of the noise of trending hacks and endless biomarkers? This episode focuses on what our guest deems are the four highest impact biomarkers that you should track. Less data, but more meaning. Our guest this week is Dr.

Nick Urban [00:01:20]:
Zayn Hakim. He is a dual board certified physician in Internal Medicine and Pediatrics with a background in philosophy, but he also blends acute care with preventative strategies. If you want to check out the resources and everything we discuss, that will be in the show notes for this episode which you can [email protected] the number 220. To follow Dr. Z’s work, you can either check out his website which is riverrockmedical.com or his YouTube channel which is named the same River Rock Medical. I’ll put those in the show notes for this episode which will [email protected] the number 220 I had a great time recording this conversation and chatting with Dr. Z. I hope if nothing else, his way of thinking, our discourse back and forth and the Bradford Hill criteria get you to reconsider your own approach.

Nick Urban [00:02:23]:
As a little spoiler, the Bradford Hill criteria, I view them as so important because that helps us tease out the effect size and the utility of interventions that are very hard to study through a controlled experiment. A double blind, placebo, controlled randomized crossover study because they just don’t fit that model. So with that teaser out of the way, sit back, relax and enjoy this conversation with Dr. Z. Dr. Z, welcome to High Performance Longevity.

Dr. Zain Hakeem [00:02:54]:
Thank you. Great to be here.

Nick Urban [00:02:56]:
I’m going to give listeners a little bit of context here about how we crossed paths months ago, maybe actually six months ago, we were both at a business event and we were going around the room introducing ourselves. We happen to be Standing right next to each other, and we were the only two in the room doing very similar things in similar spaces. You’re a doctor, I’m not. And when you mentioned your longevity framework, I found it very fascinating. We had a couple conversations. Since then, they’ve been thought provoking, a bit controversial. And so I wanted to have you on the podcast to discuss your approach to longevity.

Dr. Zain Hakeem [00:03:32]:
Love it. Absolutely. Happy to dive in.

Dr. Zain Hakeem [00:03:35]:
Cool.

Nick Urban [00:03:36]:
Let’s begin right there with your framework of longevity, what you focus on specifically, because there’s a lot of talk about this or that molecule, these protocols and therapeutics, they can all have their time in place, but you make it a lot simpler with your patients.

Dr. Zain Hakeem [00:03:55]:
Sure. One of my pitches for my practice is that you’ll see many practices, many practitioners, saying, we measure 100 biomarkers, we measure 200 biomarkers. And my pitches, I measure five. But they’re the right five. And so the five that I think are the big drivers of longevity are VO2 max strength, social connectedness, don’t smoke, and manage your blood pressure, if after all those things, it’s still an issue. And that’s in descending order of importance. So you and I talked a little bit about the notion of effect size. If you Compare the lowest VO2max category with the highest VO2max category, the difference in mortality is something like 5x or 500%.

Dr. Zain Hakeem [00:04:45]:
If you compare someone with completely uncontrolled blood pressure and then you control their blood pressure with pharmaceuticals, you get about a 15% reduction.

Dr. Zain Hakeem [00:04:55]:
Right.

Dr. Zain Hakeem [00:04:56]:
So that gives you a sense of the difference in the sizes of those things. Now, it’s a real reduction, unlike some other things I could name. And even. Even on standard medicine, you know, for healthy people taking a statin, there’s no reduction in mortality.

Dr. Zain Hakeem [00:05:14]:
Right.

Dr. Zain Hakeem [00:05:15]:
So not just pointing at, you know, more advanced peptides or influencers or this or that. Whatever. You see, even in standard medicine, the dramatic the case for certain things is dramatically overblown, in my opinion. Those five, I think, are the big drivers.

Nick Urban [00:05:33]:
And so this is for mortality specifically and not necessarily factoring in quality of life.

Dr. Zain Hakeem [00:05:39]:
Not at all, actually. In really interesting ways, actually. So, for instance, I mentioned social connectedness as the third out of the five. I did not say loneliness. And what’s interesting is that the mortality data seems to. Seems to support that. Social connectedness, meaning the number of contacts you have with different types of people, different levels of closeness, is the driver of the mortality effect, whether or not you feel lonely subjectively. So that does not address the quality of life issue that’s a pretty significant issue in itself, but it’s a separate issue.

Nick Urban [00:06:18]:
So how would you go about measuring something like that? How do you know if you’re optimized there or you’re suboptimal?

Dr. Zain Hakeem [00:06:24]:
Well, the nice thing about that is that since we are not having to quantify the quality of those social interactions, we can kind of just count them.

Dr. Zain Hakeem [00:06:32]:
Right.

Dr. Zain Hakeem [00:06:32]:
The way the studies have been done is they say, do you have direct contact with, you know, parent or child, with a non immediate family member, with social groups like clubs, organizations, religious groups, are you married, cohabitating with? So pretty quantified yes or no questions to count the level of your social connectedness or isolation. I suppose none of the questions, at least on the mortality data set. Sorry. And I shouldn’t say that researchers have investigated the qualitative what is the quality of your interactions? Do you feel lonely? Those don’t seem to be the driver of mortality, they seem to drive quality of life.

Nick Urban [00:07:19]:
That seems controversial in itself because you often hear it’s not the number of friendships you have or relationships you have, it’s the quality of those. And the people who would take three close relationships over 25, say, medium relationships.

Dr. Zain Hakeem [00:07:34]:
Absolutely. And here’s the. If you want to get really interesting, the challenge is that the bar for achieving your sort of maximum mortality is incredibly low. It’s one family member, one non family member, one friend, one community or group organization. It like you we’ve talked about, or we talked about this on some of our previous conversations. There’s a diminishing returns curve in all mortality endeavors. If your VO2 max is 60, getting to 70 is not going to do nearly as much as if your VO2 Max is 10 and you want to take it up to 20.

Dr. Zain Hakeem [00:08:17]:
Right.

Dr. Zain Hakeem [00:08:18]:
The same is true of social connections. If you have, you’re living with a partner, you have a, you’re married, if you have a friend, you talk to family members, you talk to community members once a month, I think is the, is the qualification there. It’s direct contact, so it can’t be mass communication. So like a mass email doesn’t count.

Dr. Zain Hakeem [00:08:39]:
Right.

Dr. Zain Hakeem [00:08:41]:
But that’s it, that’s, that’s the, the border. It’s astonishing how many people don’t have that.

Nick Urban [00:08:48]:
A lot of times throughout this interview, I’m gonna be asking you about the distinction between correlation or causation. Do you know, for something like that, is it possible that perhaps the people who don’t have each of the one relationship under each of those categories are obviously already going through something else in their life, they’re already very stressed. They’re like, in their monk mode, if you. You call it that, where they’re just, like, focusing on themselves or whatever that means. And instead, like, maybe adding that extra relationship won’t actually address what’s underlying all of that.

Dr. Zain Hakeem [00:09:24]:
That’s a. The perfect question. I love this. I love this topic. This is my favorite topic. So this topic came up, and I asked that question of Dr. Lundstadt, who is one of the top researchers on loneliness, one of the episodes of my podcast, and she introduced me to the concept of the Bradford Hill criteria.

Dr. Zain Hakeem [00:09:47]:
Right.

Dr. Zain Hakeem [00:09:48]:
And. Yeah, and so I’m happy to deep dive into it, but one of the important things to realize is that we never did a randomized control trial on smoking. There’s zero random. You can’t force people to smoke for 10 years randomly. Or placebo smoke. I don’t know what that would even be.

Dr. Zain Hakeem [00:10:07]:
Right.

Dr. Zain Hakeem [00:10:10]:
And so we figured out that smoking was harmful by applying a set of criteria to fundamentally correlative data.

Dr. Zain Hakeem [00:10:21]:
Right. So.

Dr. Zain Hakeem [00:10:24]:
Those criteria are intended to bridge the gap from correlation to presumption of causation in situations where you cannot ethically perform a randomized control trial. Like we can’t randomly go into the population, kidnap a thousand people, and isolate them and then see what the effect of isolation is.

Dr. Zain Hakeem [00:10:46]:
Right.

Dr. Zain Hakeem [00:10:47]:
So barring that, we have to figure out what else we can do. Now we can try and do interventions in the other direction.

Dr. Zain Hakeem [00:10:55]:
Right.

Dr. Zain Hakeem [00:10:55]:
Where we say, okay, hey, we’re going to take relatively isolated people, we’re going to try and build systems to create social connections for them and see if that improves things. One of the things I pointed out in that conversation was, what if they have some biological biomarker that means that they’re unhealthy and other people can smell it below the level of perception, like a pheromone, and avoid them.

Dr. Zain Hakeem [00:11:24]:
Right.

Dr. Zain Hakeem [00:11:25]:
And that’s why they’re so isolated. Well, yeah. So it’s possible, theoretically, that this is is driven by something else. And that’s the big thing with correlation causation. That then the reason I bring that top that specific example up is when you see a correlation between A and B, there are three possibilities, and we always forget the third one. The first possibility is A causes B. The second possibility is B causes A.

Dr. Zain Hakeem [00:11:53]:
Right.

Dr. Zain Hakeem [00:11:54]:
And the third one is that C, some unknown third factor causes both.

Dr. Zain Hakeem [00:11:59]:
Right.

Dr. Zain Hakeem [00:12:00]:
So ice cream sales and shark attacks are very strongly correlated, but they’re not causative to each other.

Dr. Zain Hakeem [00:12:06]:
Right.

Dr. Zain Hakeem [00:12:09]:
Now, that is obvious when I talk about ice creams and shark attacks. But if I tell you that lipoprotein A is strongly correlated with cardiac events, all of a sudden your brain goes into storytelling mode and says, oh, well, it must cause, oh, we got to lower the lipoprotein A, right. In a way that it doesn’t do. When I say ice cream and shark attacks and you’re not immediately like, hey, we gotta ban the sale of ice cream.

Dr. Zain Hakeem [00:12:32]:
Right.

Dr. Zain Hakeem [00:12:34]:
And so the notion there is, how do we go beyond that? Okay, we have this problem, correlation causation. We understand that. What could we do to bridge that gap like we did with smoking? And there are, I believe, nine Bradford Hill criteria. I don’t know, I actually have them all memorized. I look them up each time, but I remember the big ones. So one is consistency. There are no studies that show that smoking is beneficial to health.

Dr. Zain Hakeem [00:13:00]:
Zero, right?

Dr. Zain Hakeem [00:13:02]:
So you take an issue like testosterone and some studies say it’s positive, some studies say it’s negative. You can find stuff across the map that’s not true of smoking.

Dr. Zain Hakeem [00:13:10]:
Right.

Dr. Zain Hakeem [00:13:11]:
Another one is dose dependence is the more you smoke, the more the risk it seems to go up.

Dr. Zain Hakeem [00:13:16]:
Right.

Dr. Zain Hakeem [00:13:18]:
A third one is the notion of biological plausibility. And this is the one where every. It’s a great, it is one of the criteria, but it’s the one where everybody gets hung up, right? We have so much biological plausibility. And I can tell you, look, there’s a pharmaceutical in most people’s cabinets right now that it has a well known effect of inhibiting an enzyme that causes the process of prostaglandin formation to change and increases the risk of, of clotting. But that pharmaceutical is aspirin, right. Which decreases the risk of clotting. But you can draw a biochemical pathway to the opposite effect.

Dr. Zain Hakeem [00:14:03]:
Right?

Dr. Zain Hakeem [00:14:03]:
And it’s a true biochemical pathway. But in the context of what it actually does in humans, it’s literally steering that, that biological plausibility would steer you incorrectly. And so although it is one of the criteria, I think it’s the overused criteria, the underused criteria, and the most important criteria is strength of effect. Going right back to where we started, right? Smoking in the original studies had like a 200% effect on mortality. So even if the real effect was smaller, which I think it is a little bit, it’s like 180% or something. But even if the real effect was smaller, we had strong confidence it was a significant effect. Now if I say, hey, eating dark chocolate is associated with a 10% lower, you know, cardiovascular risk that’s in the error. That’s in the, in the margin of error of anything.

Dr. Zain Hakeem [00:14:59]:
Right.

Dr. Zain Hakeem [00:15:00]:
So it sounds important, but it’s not. And that size of effect is a really profound differentiator. It’s actually the only criteria that. That appears to not be hackable without outright deception. And that’s an important. We can come back to that idea. But. But yeah, I think that those Bradford Hill criteria, if I could sort of like get those up into people’s minds, at least to look them up, because I have to look them up most of the time, that would save us from a lot of confusion when we’re talking about these kinds of correlation studies.

Dr. Zain Hakeem [00:15:41]:
Yeah.

Nick Urban [00:15:41]:
And I think narrowing it down to really focusing on strength of effect first and foremost is a great place to start because you can look at the other ones. But if it has a really small strength, as you were just mentioning. Okay. A 10% difference, that’s within the realm of an error.

Dr. Zain Hakeem [00:15:56]:
Absolutely. And, and now before I mentioned blood pressure, which has like 15% difference. So what’s different there? Well, different there is we could do a randomized control trial, and we’ve done it in thousands and, you know, 30,000, 40,000 people, meta analysis in even bigger size groups, and we see that the effect is consistent, we can dial it in and we can get a measurement of such a small effect because we have more powerful tools. If we only have correlational tools, we can’t get down to that level of accuracy. And so the randomized control trial is powerful because it allows a sort of the difference between a CT and an mri.

Dr. Zain Hakeem [00:16:37]:
Right.

Dr. Zain Hakeem [00:16:38]:
Or, you know, it allows you a more focused picture so you can see more detail with that tool. But there are some cases where we can’t do randomized control draws.

Nick Urban [00:16:47]:
Wouldn’t that be the exact contradiction of the utility of this kind of tool, though, if, like, something like, say, blood pressure wouldn’t check out, it wouldn’t pass each of the nine steps with flying colors, and therefore, you might see that it would fail the Bradford Hill criteria. I’m not sure if it actually does, but then clinically, you actually see a pretty significant effect from controlling blood pressure.

Dr. Zain Hakeem [00:17:10]:
Actually, this is a great way to nuance the Bradford Hill criteria in a way that the original authors did not. Bradford and Hill did not nuance it this way, but it’s an important, important nuance. They treated all of the criteria as equally weighted, and I think that’s incorrect. In fact, randomized control diet, Randomized control data was one of their criteria.

Dr. Zain Hakeem [00:17:33]:
Right.

Dr. Zain Hakeem [00:17:33]:
It’s one of the Nine criteria as randomized controlled trials. Now, it is true that randomized controlled trials can also lead us astray. There are interesting situations where incorrect placebo choice will slant the trial.

Dr. Zain Hakeem [00:17:50]:
Right.

Dr. Zain Hakeem [00:17:50]:
So there’s an interesting challenge in for instance, doing randomized controlled trials on psychedelics, because how is the placebo going to work?

Dr. Zain Hakeem [00:17:59]:
Right.

Dr. Zain Hakeem [00:18:01]:
And so placebo choice can be an important aspect of randomized control trial. You can throw off a randomized control trial. It’s hard. Harder. Not hard, it’s harder.

Dr. Zain Hakeem [00:18:12]:
Right.

Dr. Zain Hakeem [00:18:15]:
So that’s why it’s one of their criteria. They don’t consider it a lock in for a lot of reasons, I think. You know, for instance, the Jupiter trial is a randomized control trial. I think it was incredibly biased by pharmaceutical, you know, by special interests. It was stopped early. They didn’t expect Jupiter trial. It’s a cholesterol trial for statins. I pick on it a lot because I think that it had all the earmarks.

Dr. Zain Hakeem [00:18:36]:
Earmarks of a trial that should be squinted at suspiciously. Even though it’s a randomized controlled trial.

Dr. Zain Hakeem [00:18:43]:
Right.

Dr. Zain Hakeem [00:18:45]:
But it is one of the criteria. With all that said, if you have a randomized control trial that’s done well, that is a much stronger bit of evidence. It’s a more heavily weighted criterion than bioplausibility or even dose dependence.

Dr. Zain Hakeem [00:19:01]:
Right.

Dr. Zain Hakeem [00:19:01]:
Because exercise reduces mortality. But there is an ultimate level of exercise where it’s too much, where it drops off.

Dr. Zain Hakeem [00:19:10]:
Right.

Dr. Zain Hakeem [00:19:10]:
It’s a long way, but it’s there.

Dr. Zain Hakeem [00:19:13]:
Right.

Dr. Zain Hakeem [00:19:15]:
Anyway, for all these reasons, I think that the Bradford Hill criteria should be weighted. They shouldn’t just be treated equally. And the randomized control trial is certainly the heaviest weight among the nine.

Nick Urban [00:19:26]:
Okay. And then after that, would you put strength.

Dr. Zain Hakeem [00:19:28]:
The strength, yes. After that, strength of effect. Got it.

Nick Urban [00:19:31]:
Well, that’s an important nuance because I was thinking about this a long time ago. Like how can you possibly run a placebo controlled, double blind, randomized controlled trial of exercise? Like, pretty hard to fake someone into exercising like that. You can’t really deceive them that way. And so that’s a, it’s a really useful heuristic to be able to figure out the effect of something when you can’t really have a placebo group or you can’t run the experiment for whatever reason.

Dr. Zain Hakeem [00:19:56]:
Yeah, exactly. Yeah. And it also would especially the strength of effect would eliminate a lot of these things.

Dr. Zain Hakeem [00:20:03]:
Right.

Dr. Zain Hakeem [00:20:04]:
If you said, look, I’m not interested in talking about anything that has less than a 50% effect.

Dr. Zain Hakeem [00:20:10]:
Right.

Dr. Zain Hakeem [00:20:11]:
And that’s generous. I mean, smoking is close to 200. Social connectedness is above 200%. If you said, okay, 50%, give me even 50%, it would eliminate large swaths of published information because you’d be like, yeah, I don’t care.

Dr. Zain Hakeem [00:20:30]:
Right.

Dr. Zain Hakeem [00:20:33]:
Yeah.

Nick Urban [00:20:34]:
What about if you were to take and synthesize or compile a bunch of the things that have a 30% or 50% net effect, but you take like say 10 of them and you add them all together and perhaps it’s, it doesn’t work like that because the biochemistry behind the interventions, but I mean, would you expect to see a good effect size? And I guess it’s also very hard to generalize. But like if you saw say 30%, 30%, 30%, you added them together, it could theoretically surpass the 50% cutoff.

Dr. Zain Hakeem [00:21:05]:
So if you’re doing the statistics correctly and this gets into nuance, right, if you have three different trials showing a 30% effect size, you actually just get more confident in that 30%. So the number of trials, the number of people increases your confidence level. It doesn’t change the number, it doesn’t change the size of.

Nick Urban [00:21:25]:
Yeah, but like different interventions, like say this molecule over here, this fitness modality, and I combine them together.

Dr. Zain Hakeem [00:21:30]:
The problem there is that we don’t know how these things work. And I’ll give you a real world example actually. So you may have, you may have known a few years ago metformin was kind of on the longevity radar for reducing mortality. And at least correlationally in the general population that seems to be true. Non correlationally in diabetics that seems to be true. Like even placebo controlled trials seem to support a longevity effect there. But what seems to be happening is that it’s mimicking the effect of exercise to some degree, partially in the, in the biochemistry. And so people who exercise who are already fit did not see any change.

Dr. Zain Hakeem [00:22:14]:
Right.

Dr. Zain Hakeem [00:22:15]:
So that’s the problem of not having a trial in the group that you’re considering. Statins are the same way. Statins are very effective, I shit them all the time. But they’re very, very life changingly effective medications in people who have already had a heart attack.

Dr. Zain Hakeem [00:22:32]:
Right.

Dr. Zain Hakeem [00:22:33]:
So secondary, what we call secondary prevention, prevention of the second event, they’re very effective. Now, prevention of a first event in people that have never had a heart attack. If you look in the highest of high risk groups, people that are overweight, smoke, have high blood pressure, have high perturbing hearts, also high cholesterol and family, like the highest of high risk individuals, you can prevent or reduce the risk of the first heart attack by maybe half a percent if you squint at the data.

Dr. Zain Hakeem [00:23:08]:
Right.

Dr. Zain Hakeem [00:23:09]:
So the populations are totally different. They’re just. You’re not doing the same thing. So the study doesn’t quite capture that. Getting back to your original question, if I’m testing multiple modalities, it’s possible that they conflict with each other, interfere with each other, reduce the effect, amplify the effect. Maybe they’re synergistic, maybe, maybe, you know, metformin partially mimicked exercise. Maybe some other molecule mimics the other half of that exercise.

Dr. Zain Hakeem [00:23:36]:
Right.

Dr. Zain Hakeem [00:23:36]:
And you can get the mortality effect without it. But we don’t know how.

Nick Urban [00:23:39]:
Do you think of that in general? Like the polypharmacy of combining multiple ingredients, substances together and. Or lifestyle interventions? Because there’s really never been someone to combine the things that you combine with your unique genetics, your epigenetics, your nutrition, all these things.

Dr. Zain Hakeem [00:23:56]:
Yeah, I think all of those things are totally fair. I think that effect size, once again is a little bit your savior.

Dr. Zain Hakeem [00:24:04]:
Right.

Dr. Zain Hakeem [00:24:04]:
Because there is almost certainly some interference between VO2 max and strength.

Dr. Zain Hakeem [00:24:13]:
Right.

Dr. Zain Hakeem [00:24:13]:
Like they’re both huge effects. Strength is like a 300% difference, VO2 max, 500%. But if you are a really strong individual, even weightlifting has some cardiac component. Not a lot, depending on how you do it.

Dr. Zain Hakeem [00:24:29]:
Right.

Dr. Zain Hakeem [00:24:30]:
But there’s some.

Dr. Zain Hakeem [00:24:32]:
Right.

Dr. Zain Hakeem [00:24:33]:
And so and personality wise, people that are relatively fit lifters, barring specific body lifter or bodybuilders or strength athletes, often also do some sort of cardio. They’re just generally health conscious, they probably eat differently, they probably do other things. So there’s almost certainly some overlap there. Right. So doing both probably doesn’t get you 800. It may get you 550 or it may get you 600.

Dr. Zain Hakeem [00:25:07]:
Right.

Dr. Zain Hakeem [00:25:08]:
But we know that those are both probably big effects. You can try and control for it a little bit in the statistics, but I have not seen great studies that try to control over those Factors.

Nick Urban [00:25:19]:
You’ve mentioned VO2 max several times now. I haven’t actually explored that on the podcast at all. Will you break down what that is and why it’s so important not only to your protocol, but also what the data is saying?

Dr. Zain Hakeem [00:25:31]:
Yeah, totally. It’s a really cool number. Here’s here. I use a car analogy, which is a common analogy, I think, in the field. If your body were an engine, which it basically is.

Dr. Zain Hakeem [00:25:41]:
Right.

Dr. Zain Hakeem [00:25:41]:
Like carbohydrates are very close to, you know, other gasoline. Like, you know, they’re, they’re hydrocarbons, they’re Both hydrocarbons, right? So you mix hydrocarbons with oxygen, it releases energy. And that’s what we’re fueled. That’s what your, your car is fueled on. That’s what we’re fueled on. The biochemistry is a little different. We control it a little bit more there. It’s just a spark, right? The question is, if you, you know, ran your engine, your car’s engine all the way to redline, like you just pushed it as hard as it could, how much fuel could it consume per minute?

Dr. Zain Hakeem [00:26:23]:
Right?

Dr. Zain Hakeem [00:26:25]:
The fuel consumption per minute, at least biologically, turns out to be a reasonable estimate of your limitations. Now, the big difference between people and cars is that people are fairly similar. Cars can be quite different, right? So it’s a little bit more like if you take, know, a hundred.

Dr. Zain Hakeem [00:26:46]:
Of.

Dr. Zain Hakeem [00:26:46]:
The same car, Dodge Caravans, right? You take 100 Dodge caravans and you say, okay, this one can burn this much fuel per minute, this one can burn this much fuel per minute. It becomes a measure of the health of the system, right? Because you, you’ve all, all the cars are the same. So the ones that are burning less, there’s something gumming up. Either the exhaust or the intake or the fuel, something is being blocked. Otherwise it would have the same sort of maximum VO2 max. Is that fair?

Nick Urban [00:27:17]:
And so then as you’re, when you’re younger, I’d assume your VO2 max is going to naturally be higher as you get older. Kind of like a car that’s gone through more wear and tear, it will decline in the absence of like doing something to skew it, such as training harder or something like that.

Dr. Zain Hakeem [00:27:32]:
In the absence of. That’s a big. Is a big question. And your, your question cuts to the heart of how the, the car human analogy breaks down, right? Because yes, humans overall have the same parts as each other. Yes, we have the same sort of rough systems overall, but training is something that a car can’t do. A car can only wear and tear, right? So one of my favorite concepts from the scene to lab is called anti fragility. And he defines fragility as things that get worse in response to volatility or disorder and antifragility as things that tend to get better in response to volatility and disorder. And biological systems tend to be antifragile.

Dr. Zain Hakeem [00:28:12]:
And so exercise is on some level a disorder. Volatility, you know, harm, semantic. If you look at all the things that have happened to your body biochemically when you exercise, they’re all bad. Free radicals go up, you know, Heart rate goes up, adrenaline goes up, like, you know, parasympathetic vagal activity goes down. You know, basically, literally everything that every health influencer would tell you is a bad thing is exercise. Exercise does that. But as we adapt to that, when we recover, that is where the magic happens.

Dr. Zain Hakeem [00:28:51]:
Right.

Dr. Zain Hakeem [00:28:52]:
And so it’s adaptation to stress, not stress avoidance, that creates the biological growth to optimize our systems and improve them. Yeah.

Nick Urban [00:29:01]:
One of the things we discussed in a previous conversation too, is that because it’s the adaptation specifically that’s responsible for the overall health improvement when otherwise, if you look at the paper, all the mechanisms, what’s going on, it looks like if you didn’t know you’re exercising, that your health is deteriorating rapidly, that a lot of people, they go in either of two extremes under exercising not making a priority, or the people who are all about the data and are following this field can go the opposite route. And whether it’s VO2 max or strength or that, and a whole lot more, they go to the upper limit. And from there it’s like you’re adding a lot more wear and tear in your body and perhaps not getting enough recovery because of how spacing, how spaced your training is to actually stimulate the healthy, beneficial adaptations.

Dr. Zain Hakeem [00:29:56]:
I think all of those things are true. I think that things get very tricky and this goes loops back to our previous point of quality of life.

Dr. Zain Hakeem [00:30:04]:
Right.

Dr. Zain Hakeem [00:30:05]:
So I’ll give you a very theoretical. So don’t. The audience, don’t take what I’m saying here to be fact, but it is an alternate way of interpreting data that we know.

Dr. Zain Hakeem [00:30:19]:
Right.

Dr. Zain Hakeem [00:30:20]:
So I think it isn’t. You may be familiar with this. We know that men typically live less long than women. They have a higher mortality in old age.

Dr. Zain Hakeem [00:30:32]:
Right.

Dr. Zain Hakeem [00:30:33]:
What people, what fewer people are aware of is. That’s actually true at every age group. Middle aged men die more, adolescent age men die more children, male children die more, male infants die more, male newborns die more.

Dr. Zain Hakeem [00:30:47]:
Right.

Dr. Zain Hakeem [00:30:47]:
And that gets a little odd, Right, because the newborns don’t have. Well, part of what’s happening here is that the male mutation rate is higher.

Dr. Zain Hakeem [00:30:55]:
Right.

Dr. Zain Hakeem [00:30:56]:
So now we’re going to do a little bit of storytelling. Evolution says, hey, you know what? We need a way of adapting genes to the environment. Environment’s changing. How do we do that? Well, we have half the population that just conserves the genetics we have, and then we increase the mutation rate in the other half and, and we get them to compete. And whoever dies wasn’t suited and whoever survives was better Suited to the environment, we’ll let them reproduce with the, with the conserved line. Fair. That sexual dimorphism at its core.

Dr. Zain Hakeem [00:31:28]:
Right.

Dr. Zain Hakeem [00:31:29]:
Now the interesting effect of that would be that you would say that testosterone was an anti longevity factor because you’re trying actively to kill young men. That’s nature’s plan, right? Like get them to compete with each other, get them to compete with the environment, do stupid shit and whichever of them manages to survive, that’s the ones we want, right? So you would want 40 year old men to drop their testosterone and survive and reproduce, or 30 year old men, right? Now you want 18 year olds, dumb and competitive, right? So the issue is socially though, attractiveness wise, maybe we want to look 18. Now we have a quality of life issue conflicting with a potential longevity issue.

Dr. Zain Hakeem [00:32:16]:
Right.

Dr. Zain Hakeem [00:32:17]:
And I’m just spinning this story by the way. I do, I tend to believe it, but I don’t want to be, I want to be clear with the audience where I’m speaking from data and where I’m storytelling, right? And so this storytelling element would account for a large amount of data that for instance, plenty of correlational data or non randomized control trial, I would say. But eunuchs, people that have been castrated live much longer, right? So they’re male, but if you get rid of the testosterone, they live longer, right? So there are some interventional data indicating that removing testosterone is a pro longevity factor, Right. Bodybuilders that use anabolic testosterone is steroids live less long by a significant margin.

Dr. Zain Hakeem [00:33:05]:
Right?

Dr. Zain Hakeem [00:33:05]:
So there’s some interesting data suggesting that testosterone is anti longevity. But we like the way we look when we’re on testosterone, right? We like the musculature, we like the low body fat, we like the, you know, and so there is a mental competition with looking younger versus the perhaps longevity factor. So where I was going there is that when you’re talking about exercise, right, you have to ask are we truly optimizing for pure longevity or are we optimizing for quality of life? Because there are many people, I have several friends for whom exercise is stress relief, mental relaxation time away from kids, right? If it kills them, that’s fine. They need it, right? Like so the, the, the optimization has to be framed towards what? If you’re talking about towards longevity specifically, then yes, there probably is a limit of too much exercise, right? The things I’ve seen I think are something like 60 mets or 70 mets of activity per week, something like that.

Nick Urban [00:34:15]:
How does that translate into like a strength or VO2 max session?

Dr. Zain Hakeem [00:34:19]:
You see, let me put it this way, you see it mostly in Olympic bicyclists.

Dr. Zain Hakeem [00:34:23]:
Right.

Dr. Zain Hakeem [00:34:24]:
So you have to, it’s, it’s. I don’t have an exact. Because a met is an interesting measurement. It’s energy expenditure per hour or per minute, depending on which one. So it’s a. Per time. So it’s the degree of activity per unit time exercising. And so there’s not a great immediate.

Dr. Zain Hakeem [00:34:43]:
You can’t say, well, one hour of cycling, you cycling, me cycling and Olympic cyclists. Those are different mets.

Dr. Zain Hakeem [00:34:48]:
Right.

Dr. Zain Hakeem [00:34:49]:
Um, but the bigger point is there is a degree of exercise. Just like there’s a degree of leanness.

Dr. Zain Hakeem [00:34:57]:
Right.

Dr. Zain Hakeem [00:34:57]:
Like, look, having 5% body body fat, bodybuilders know their incre. Their immune system goes down, their energy levels go down.

Dr. Zain Hakeem [00:35:07]:
Right.

Dr. Zain Hakeem [00:35:07]:
And, and so they do it for stage, but they don’t live there.

Dr. Zain Hakeem [00:35:12]:
Right.

Dr. Zain Hakeem [00:35:14]:
I don’t know. I feel like maybe I got, I got. Wandering off, off the topic that’s.

Nick Urban [00:35:19]:
I’ve seen some research that like the upper limit on exercise in terms of like pure longevity is less than I was doing at one point. I think it’s like six hours. And of course it’s going to be like six hours at what intensity? Like what, what muscle groups, like what type of training, all these different factors. But it was like, I think it was six hours in the gym per week before you started seeing an increase in mortality.

Dr. Zain Hakeem [00:35:41]:
Oh, interesting. That’s sharper than I think what I’ve seen. But yeah, I couldn’t give you the exact numbers, but I, I suspect they’re. The plateau I suspect is pretty long.

Dr. Zain Hakeem [00:35:54]:
Right.

Dr. Zain Hakeem [00:35:55]:
A lot of U shaped curves are kind of like, okay, you’re falling off the edge.

Dr. Zain Hakeem [00:35:58]:
Right.

Dr. Zain Hakeem [00:35:59]:
But exercise, from what I’ve seen, has a fairly long plateau before you start dropping back down.

Nick Urban [00:36:05]:
Yeah. And then also based on what you’re saying, if, if it’s. What you were seeing is based on mets, that’s going to obviously punish more of the like high intensity endurance type training that’s like usually on a more frequent basis, higher max heart rate that’s sustained. I guess the important distinction there is that it’s sustained. When I lift weights, I can get my heart rate up to like 151, 60 when I’m lifting, but then it drops right back down because usually the working set is a short period of time.

Dr. Zain Hakeem [00:36:32]:
Sure, that’s. I always joke that the reason I prefer weightlifting is it’s the exercise that’s closest to sitting. Um, and so it, you know, I, I exercise primarily for. Well, other than my specific Cardio workouts.

Dr. Zain Hakeem [00:36:46]:
I.

Dr. Zain Hakeem [00:36:46]:
My lifting exercises are not done. Sort of like circuit style.

Dr. Zain Hakeem [00:36:52]:
Right.

Dr. Zain Hakeem [00:36:53]:
I. I listen to a podcast. I hang out between sets. I take a long time. I’m hanging out in the gym, you know, walking around.

Dr. Zain Hakeem [00:37:00]:
Right.

Dr. Zain Hakeem [00:37:01]:
Um, now I have the luxury of doing that. I’m single and, like, got no responsibilities. Right. So other people may have to duplicate and do their cardio with weights by doing circuit style just for time compaction, but those are different things.

Nick Urban [00:37:14]:
So how do you train VO2 max? Because you said that your favorite is. Tends to be on the resistance training side, and there’s a lot of different protocols out there. I personally hate the really famous Norwegian 4×4 protocol. Curious what you do.

Dr. Zain Hakeem [00:37:27]:
So I am not super driven, by the way, by the notion of longevity, personally, so I do optimize it casually, but I’m very. I’m very loose on that notion. So I can tell you what I do, which is a fair amount of zone one and zone two. So I do try to get my 10,000 steps. I try to walk at a pace that gets me at least into zone two to some degree.

Nick Urban [00:37:58]:
Will you break down the zones? I don’t think I’ve mentioned those either.

Dr. Zain Hakeem [00:38:00]:
Yeah, let’s come back to that, because it’s actually a bit. A bit more complicated. And then I’ll just finish that quickly by saying, I try to get some Zone 5 training as well. I’ve been a little lax on that over the last three months, so that’s a recent thing. But in general, I try to get one sprint workout per week, and it doesn’t take much. You try to just max your heart rate a couple times in the session. Tabata style, 30 seconds on. I.

Dr. Zain Hakeem [00:38:27]:
I use an air bike that was recommended. I did a podcast with one of the head metabolics guys at. At Duke University. He pointed out that the nice thing about the air bike is there’s no cardiac arrest period, because as one is pushing, the other’s pulling. And so even when you’re running, technically, you’re at rest for that brief moment in the air, Right? But with the. With the air bike, you’re truly never at rest, and so you can max your heart rate relatively quickly.

Nick Urban [00:38:55]:
It’s also a great option for people who aren’t used to sprinting, because that puts a lot of strain on your body and your joints, your ligaments, your tendons, everything. So it’s much simpler to start there and to not injure yourself immediately removes.

Dr. Zain Hakeem [00:39:08]:
The skill element, right? Removes the fall risk. So, yeah, for all the reasons I, I, well, and I do VO2 max in my office, and that’s the equipment I use, so it’s right there. So it’s very convenient as well. So that’s my. Yeah, I mostly do hypertrophy for aesthetic reasons. And then the sprint work and steps work. Steps work also helps with calorie expenditure.

Nick Urban [00:39:35]:
Steps work meaning like climbing stairs?

Dr. Zain Hakeem [00:39:38]:
No, no, sorry. Just walking. Just getting your steps. Just getting your steps in.

Dr. Zain Hakeem [00:39:42]:
Right.

Dr. Zain Hakeem [00:39:42]:
The 10,000 per day, whatever. I can have an extra taco or whatever. And so, yeah, that’s roughly my workout. I would say primarily directed at esthetics and secondarily directed at longevity for me personally.

Dr. Zain Hakeem [00:39:59]:
Yeah.

Nick Urban [00:40:00]:
And then the zones.

Dr. Zain Hakeem [00:40:02]:
The zones, yes. So the reason I think that that’s important to differentiate is there’s sort of two versions of the zoning. The first version is to take a calculation of 220 minus your age as your max heart rate. That was a rough average estimate. It is actually not your max heart rate.

Dr. Zain Hakeem [00:40:27]:
Right.

Dr. Zain Hakeem [00:40:28]:
Your max heart rate could be more than that, less than that, could be totally different. But the way it’s usually done, you do that yellow calculation and then you divide the, the space into zones based on some percentage of that max heart rate.

Dr. Zain Hakeem [00:40:45]:
Right.

Dr. Zain Hakeem [00:40:47]:
The original concept of zones, or maybe the more physiologically accurate version of zones, is to divide the zones based on what your body is doing at the time. And so, and this will actually bring us back to VO2 max as well, in some sense. So that is a good loop. So zone two is up until the point where your body is burning a 50, 50 mix of carbs and fats. Now, what do we mean by that? If I’m just sitting here and I’m relatively metabolically healthy. So we’re not talking about diabetics, we’re not talking about anybody with severe metabolic dysfunction. You and I sitting here, we’re burning mostly fat.

Dr. Zain Hakeem [00:41:35]:
Right.

Dr. Zain Hakeem [00:41:35]:
If I get up and walk, I will be burning more calories, like a slow walk.

Dr. Zain Hakeem [00:41:40]:
Right.

Dr. Zain Hakeem [00:41:41]:
All of those calories should come from fat. So I’ll just be burning more fat.

Dr. Zain Hakeem [00:41:46]:
Right.

Dr. Zain Hakeem [00:41:47]:
Part of the reason for that is the reaction speed to burn fat is relatively slow. But you have a ton of it. We all have a ton of it.

Dr. Zain Hakeem [00:41:56]:
Right.

Dr. Zain Hakeem [00:41:56]:
Even the leanest person still has pounds of fat on their body.

Dr. Zain Hakeem [00:42:00]:
Right.

Dr. Zain Hakeem [00:42:01]:
Now, if I start walking faster and faster and I break into a run, or I go faster on the air bike and gradually increase the intensity of the energy expenditure or the speed of the energy expenditure, at some point, that fat reaction speed is too slow and can’t keep up with the demand, at that point, your body starts burning carbs. Because the reactions are faster, Right. Biochemically, so it can generate energy faster, but the carbs are a more limited energy source. You only have so much blood sugar, you only have so much glycogen in your muscles. So that leads to, you know, if you go and you run at 95% of your top speed, right. You won’t be able to keep doing that. At some point, relatively quickly, you’ll slow down. But why? It’s because your body ran out of sugar and can no longer support that speed of energy expenditure.

Dr. Zain Hakeem [00:42:55]:
Right.

Dr. Zain Hakeem [00:42:56]:
So it has to drop it back to a rate that it can keep up with. So the different energy systems are fat carbs, lactate, creatine, and then free ATP.

Dr. Zain Hakeem [00:43:10]:
Right.

Dr. Zain Hakeem [00:43:10]:
And those roughly correlate to the five zones. And so when you reach a 50, 50 burn of fats and carbs, that’s the end of zone two. When you start turning on your lactate burn, that’s sort of the end of zone three. When you start engaging creatine, it’s zone four. And when you’re down to free ATP, that’s zone five. Zone four and zone five are actually, I would say, probably the hardest to differentiate because creatine and free ATP are very tightly knit biochemically. So they’re different energy systems. And that’s the reason that that’s important is that if your body is having a metabolic issue in zone 2, training in zone 4 will not address that issue.

Dr. Zain Hakeem [00:43:53]:
You’re not, you’re strengthening the wrong system.

Dr. Zain Hakeem [00:43:56]:
Right.

Dr. Zain Hakeem [00:43:56]:
It’s like, hey, my quads are weak, so I’m gonna, like, go lift curls. Well, that’s not gonna address the quad issue.

Dr. Zain Hakeem [00:44:02]:
Right.

Dr. Zain Hakeem [00:44:03]:
And so a lot of people that have, you know, metabolic derangements, metabolic syndrome, diabetes, that kind of stuff actually benefit more from a higher number of minutes of lower intensity work, maybe combined with some Zone 5 work.

Dr. Zain Hakeem [00:44:19]:
Right.

Dr. Zain Hakeem [00:44:21]:
But not as much stuff in the middle.

Dr. Zain Hakeem [00:44:24]:
Right.

Dr. Zain Hakeem [00:44:24]:
And that’s because they’re burning different energy systems.

Nick Urban [00:44:26]:
And obviously, barring sports specific movements where you need to train those other zones, I think a lot of people do best having a lot of low intensity zone one, zone two, and then zone five, and really skipping a lot of the middle. I’ve also seen research like there’s not really an upper limit on zone one and zone two. So you can get a lot of repetition and make that a big cornerstone of your movement practice.

Dr. Zain Hakeem [00:44:50]:
Absolutely, yeah. And again, from an aesthetic standpoint, part of the reason I try to get my steps in is that for whatever reason, zone one, zone two burns calories and yet seems to not trigger as much hunger per calorie.

Dr. Zain Hakeem [00:45:07]:
Right.

Dr. Zain Hakeem [00:45:08]:
That may be psychological, it may be placebo. We don’t, studies haven’t been done there. But observed effect is that if you go out and you do a hiit workout, you’re going to be hungry that night, right. You go burn an equivalent number of calories by going for a long walk. Now it will be a long walk, but you won’t necessarily get that same hunger effect. And so in terms of maintaining leanness and that kind of stuff, it can be a hack in that regard.

Nick Urban [00:45:35]:
It probably has an impact on the.

Dr. Zain Hakeem [00:45:37]:
Hunger hormones too, whatever the mechanism. Yeah, again, this kind of goes back to our. I’m, I’m like whatever I can make up, I can make up some mechanism for anything I want to say.

Dr. Zain Hakeem [00:45:46]:
Right.

Dr. Zain Hakeem [00:45:46]:
I can say this hormone, that hormone. I’ll, I’ll come up with something. But the observed effect overall I think is probably the more important part.

Nick Urban [00:45:55]:
So if someone’s really interested in their longevity, as you’ve made a quite clear case, if they have a low VO2 max, then getting it up a bit can be like the highest impact thing they can do. Are you a fan of any of the at home technologies for approximating VO2 max? Like obviously they’re not going to be as great as a metabolic cart like coming into a lab and actually getting it clinically tested. But like I think my ring even measures VO2 max now. I have a chest strap that claims to measure it. I have a bunch of different devices that all claim to measure VO2 max accurately and I’m unsure about the quality of that data.

Dr. Zain Hakeem [00:46:31]:
So those devices, the accuracy is all over the map.

Dr. Zain Hakeem [00:46:36]:
Right.

Dr. Zain Hakeem [00:46:37]:
I, I often suggest to people getting one lab VO2 max done and if you are the person where it’s accurate for you, then great, you can use those technologies forever after and you’re, you’re going to be in that group. If you’re in the group of people for whom it’s not accurate, then that’s important to know.

Dr. Zain Hakeem [00:46:54]:
Right.

Dr. Zain Hakeem [00:46:56]:
So if there’s a wild difference between what your ring is telling you and what the actual data tells you, that could be important. With that said, I’m not sponsored, but I love their device. The caliber biometrics device is basically at home. It’s like 500 bucks, 600 bucks, something like that. I mean not cheap, but not 30,000.

Dr. Zain Hakeem [00:47:17]:
Right.

Dr. Zain Hakeem [00:47:18]:
And yeah, you can buy it. It’s consumer available. No, you don’t need a prescription or anything like that. And they’ll help you set it up. They are, I hear, finally redesigning their app. That’s been a sore point for me in recommending them for a long time, but I hear they’re redesigning it, and theoretically, you could do your own true VO2 Max testing at home, and it would actually measure your VO2 Max. So that’s an exciting new kind of development in terms of accuracy.

Nick Urban [00:47:49]:
Yeah, I came across that company in 2022, and I was just mentioning it that company earlier on a presentation I was giving today, so it’s funny.

Dr. Zain Hakeem [00:47:56]:
Oh, interesting.

Nick Urban [00:47:57]:
You were talking about for the cheaper, more readily accessible devices like the rings, when you say that they can be inaccurate for people, are you talking about a difference of like, 10% or, like, over 100% inaccuracy?

Dr. Zain Hakeem [00:48:11]:
100% would be hard, but I personally have seen a device that rated someone’s VO2 max at 60, and we measured it at 40. Oh, so significant.

Dr. Zain Hakeem [00:48:24]:
Okay.

Dr. Zain Hakeem [00:48:25]:
I mean, look, the same is true of DEXA scans. You see, DEXA scans measure, you know, advertise all over the place. And on a population level, yes, they’re accurate. But if you compare versus mri, which is the most accurate body fat measurement, the spread around that is wide. There are people who have, you know, a 10 difference in their body fat measure on MRI, either plus or minus in either direction.

Dr. Zain Hakeem [00:48:50]:
Right.

Dr. Zain Hakeem [00:48:50]:
Now, that’s not most people, but there are some, and you don’t know which one you are.

Dr. Zain Hakeem [00:48:55]:
Right.

Dr. Zain Hakeem [00:48:56]:
And so that’s kind of the challenge is it becomes tricky to know whether you’re in that, yes, this test is accurate for me or no, it’s not. And Dex is a good example of those. Sorry, both are good examples. The reason for the inaccuracy is that there is a set of assumptions built into the way the calculation is done. If those assumptions don’t apply to you, then the device will not be accurate for you. So for dexa, there’s an assumption about how much the your body fat will deflect the X rays as they go through, which assumes that the density of your fat in the front and the density of your fat in the back are the same. And if you happen to have more dense back fat than front fat, it throws off the whole set of assumptions in the machine. Similarly, for the rings, there’s a set of assumptions about how they calculate VO2 max where they project, for instance, like your running speed versus.

Dr. Zain Hakeem [00:49:56]:
That’s a great one. So if you do something that projects based on Your running speed versus your heart rate and the change in those two. Well, I’m a shitty runner. Like, I’m not great at cardio in general, but I’m a particularly shitty runner, right? Like, I did CrossFit for a while, and they would do the. Like, they would have, like, oh, you can go run one kilometer, or you can row a thousand or 1500 or 2000 meters on the bike, on the rower, Right. If I went for the run, I could never finish that workout. I was so far behind on the run and so wiped and exhausted. Whereas if I did the equivalent quote, unquote work on the rower, I was fine.

Dr. Zain Hakeem [00:50:43]:
I got through it.

Dr. Zain Hakeem [00:50:44]:
Right.

Dr. Zain Hakeem [00:50:44]:
There’s something about my running mechanics that I’ve never figured out. How to fix my tendon spring, who knows what? But the biomechanical inefficiency of my running would tell the device that I have a terrible VO2 max because he’s dying and barely moving forward.

Dr. Zain Hakeem [00:51:03]:
Right.

Dr. Zain Hakeem [00:51:04]:
Whereas my measured VO2 max would be better because it’s more in keeping with, you know, I’m actually measuring the real. The real effect.

Nick Urban [00:51:12]:
Okay. And to measure vomax for you, you are doing it not through the traditional treadmill test, but through bike.

Dr. Zain Hakeem [00:51:19]:
Air bike. Airbike. Yeah, air bike. The nice thing about the air bike is that, number one, like I said, it’s a steady state on the heart because you’re pushing and pulling. So the. The heart sees a flat curve of energy expenditure, if that. Sees if that makes sense.

Dr. Zain Hakeem [00:51:36]:
Right.

Dr. Zain Hakeem [00:51:38]:
The other thing is the way an air bike is built, the faster you pedal, the higher the resistance. So the resistance goes up naturally just through the design of the bike as you go faster and faster. And so you get, again, a very smooth sort of intensity ramp. Anyway, I didn’t know all of this. This is my conversation with one of the head guys at Duke’s University Metabolics Lab. I did a podcast with him and learned a ton about VO2 max during that conversation. I feel like I’m parroting back, like, it’s not me, as I just learned this stuff. But, yes, for that reason, I switched to the.

Dr. Zain Hakeem [00:52:19]:
To the air bike. I was doing the treadmill all these years. I’ve been doing VO2 maxes since 2018, 2019 in my office. But, yeah, recently switched.

Nick Urban [00:52:31]:
I hadn’t considered that if there’s something to do with your gait or your movement efficiency or. For example, I’ve had shin splints for a long time, and I don’t think they’re much of an issue now, but that would definitely put a Damper on any VO2 max test I was taking if it was on a treadmill, whereas if I was biking or taking it literally any other way, aside from longer distance running, mid distance running, then I’m.

Dr. Zain Hakeem [00:52:55]:
Going to see very different scores on those devices. You will. Now the, the actual measurement is independent of any of those things.

Dr. Zain Hakeem [00:53:02]:
Right.

Dr. Zain Hakeem [00:53:02]:
Because the actual measurement is literally measuring how much oxygen your body is extracting from the air and how much carbon dioxide it’s putting in. So regardless of how much forward, you know, I could have a VO2 max. That’s amazing. And I can’t run faster than four miles an hour or something because I’m so inefficient right now. Okay. There’s limits to that. That probably not literally true, but I think it’s also true that somebody with a, with a slightly lower VO2 max would be a better runner for a variety of biomechanical reasons. And so.

Nick Urban [00:53:37]:
Yeah, interesting. So if you were a very efficient runner, you wouldn’t necessarily expect to see a high VO2 max.

Dr. Zain Hakeem [00:53:44]:
It depends on how you got to be a high, high efficiency runner.

Dr. Zain Hakeem [00:53:47]:
Right.

Dr. Zain Hakeem [00:53:47]:
So if you did it through training, then yes, your VO2 max would be, would be quite high. Um, running is interesting, Right. Because theoretically, biomechanically, when you step at least 50% of the power coming back should be tendon spring.

Dr. Zain Hakeem [00:54:02]:
Right.

Dr. Zain Hakeem [00:54:03]:
So should not be muscular activity at all.

Dr. Zain Hakeem [00:54:05]:
Right.

Dr. Zain Hakeem [00:54:07]:
Now I feel like part of the problem with me is like 5% of that is tendon spring. So it’s all muscle activity.

Dr. Zain Hakeem [00:54:13]:
Right.

Dr. Zain Hakeem [00:54:14]:
Just as an example, I’m just kind of throwing this out. And so you could be a very efficient runner just by your, your genetic build of your tendons. Maybe your tendons are springier than average. And so 60% of your spring is, or of your return is, is tendon activity rather than muscle. And so you wouldn’t need as high a VO2 max to get the same performance as somebody else with a different set of tendons. Yeah.

Nick Urban [00:54:40]:
But longevity wise, it wouldn’t change very much. That’s just more for performance.

Dr. Zain Hakeem [00:54:45]:
That’s for performance, right? Yeah. From a longevity perspective, it seems like the issue is how much is your cardiovascular system limiting supply to the muscles.

Dr. Zain Hakeem [00:54:55]:
Right.

Dr. Zain Hakeem [00:54:56]:
So if your muscles are demanding more oxygen and your heart can’t supply it, that’s an indication of the longevity aspects. That seems to be where it is. And, and there is that difference. Right. Is that like, if you take a totally untrained, sedentary person, their restriction is likely to be a Cardiac cardiovascular restriction. Right now, if you take a really well trained runner, often the restriction is muscular enzyme activity. Their heart’s supplying more than enough blood.

Dr. Zain Hakeem [00:55:31]:
Right.

Dr. Zain Hakeem [00:55:32]:
Their muscles can’t use it that fast. That often ends up being the. The bigger limiting factor.

Nick Urban [00:55:38]:
Dr. Z, I want to pivot a little bit because we’re already starting to run up on time. We can talk about each of these factors. They could each be their own podcast for sure. I want to go on. So you mentioned VO2 max and strength being two of the big ones. Even with strength, the usual measurement that you see in the research, or at least sometimes in the research, is like grip strength and different measures of strength. And then there’s whole schools of thought online that everyone should just drop what they’re doing and start training their grip strength.

Nick Urban [00:56:11]:
And to me, it seems like that’s another. Yeah, I could see a mechanism by like, if you’re falling, you catch yourself, prevents a fracture, prevents you from dying in the hospital, that kind of thing. But it doesn’t seem to me like that’s the. It’s more of a correlation versus causation issue. And it’s generally a proxy or has been a proxy for overall full body strength. So what’s your take on the importance of strength and how you measure it?

Dr. Zain Hakeem [00:56:33]:
You nailed it. I mean, I’ll. I’ll add color to the commentary here. One of my favorite laws is called Goodhart’s Law. And Goodhart’s law says that once a metric becomes a target, it ceases to be a good metric. What that means is if you measure something independently, when nobody’s training it, nobody’s trying to optimize it, it can be a very accurate metric. And I think that’s true of grip strength is if you take a bunch of people that have never heard that grip strength correlates to longevity and you measure their grip strength, it’s a good marker of overall body strength. And in those people, it will therefore correlate very strongly with longevity.

Dr. Zain Hakeem [00:57:13]:
If you go to a bunch of biohackers who have heard that grip strength is correlated strongly with longevity and have all been doing this for the last, you know, six months, Right. You have broken the relationship between grip strength and total body strength, and therefore it will no longer be a good metric.

Dr. Zain Hakeem [00:57:32]:
Right.

Dr. Zain Hakeem [00:57:33]:
So it’s. Exactly. It’s a different version of the correlation causation problem. Better, I would say, is the studies that have used a knee dynamometer. And so imagine that this is my knee. You put a machine that sort of locks. Actually, Jeff Nippard’s latest video with his brother. I don’t know if his latest video at the time of this recording, it probably won’t be, but he did a video on a one year journey he did with his brother and they show him doing the knee dynamometer.

Dr. Zain Hakeem [00:58:01]:
So if you want to see it, it’s actually in that video. He injured his leg actually doing it. But you lock in both sides of the joint and you just flex it as hard as you can against the machine and it measures the torque that’s being generated at the knee.

Dr. Zain Hakeem [00:58:17]:
Right.

Dr. Zain Hakeem [00:58:17]:
So that’s another way of measuring or another researcher’s way of measuring strength. Now in my office, I kind of like hack that into a leg extension.

Dr. Zain Hakeem [00:58:32]:
Right.

Dr. Zain Hakeem [00:58:33]:
So I basically have people load up the leg extension and gradually progressively increase the one leg leg extension as far as they can.

Dr. Zain Hakeem [00:58:41]:
Right.

Dr. Zain Hakeem [00:58:41]:
And so we’re just trying to see at what point do you fail on the single leg leg extension. And that correlates somewhat to the knee dynamometer measurements. But they’re both intended as overall body strength estimates.

Dr. Zain Hakeem [00:58:58]:
Right.

Dr. Zain Hakeem [00:59:00]:
I think knee strength is probably more related because again, the fall and fracture your arm has a relatively, it doesn’t have a huge mortality rate. You fall and fracture your hip and that has a 30% mortality rate.

Dr. Zain Hakeem [00:59:14]:
Right.

Dr. Zain Hakeem [00:59:14]:
So it’s not the fall on the outstretched arm that that’s going to save you.

Dr. Zain Hakeem [00:59:18]:
Right.

Dr. Zain Hakeem [00:59:19]:
It, it’s not falling on your hip, it’s having the leg strength, I would say, or the balance or the, the speed of movement to move your leg back into position and catch yourself. Those are all strength metrics that matter to prevent falls in the elbow with a grip.

Nick Urban [00:59:35]:
I’m not thinking so much as like falling on your wrist and like the strong wrist is what saves you, but it’s like you’re falling down, having the grip strength to be able to hold onto a railing or something. So you don’t actually even hit the ground to begin with.

Dr. Zain Hakeem [00:59:47]:
Oh, I see.

Nick Urban [00:59:49]:
I like what you’re saying though, because even if you do game this test and you say, okay, I’m going to like just really work hard on my lower body, get a strong lower body that’s going to have so many like spillover effects in beneficial ways to your overall health. Whereas having really strong grip strength may have like some slight effect on overall health, quality of life and performance.

Dr. Zain Hakeem [01:00:10]:
At best. Yeah, at best. I mean, unless you’re a rock climber, in which case, I guess call it. Yeah. I mean there are sports specific benefits.

Dr. Zain Hakeem [01:00:17]:
Right.

Dr. Zain Hakeem [01:00:19]:
The other thing, I mean, the other example I like to give is if you plot out the correlation between hair, scalp hair follicle density and longevity, you will see a very strong correlation.

Dr. Zain Hakeem [01:00:32]:
Right.

Dr. Zain Hakeem [01:00:33]:
Like as we get older, hair thins, scalp den, you know, hair density gets less in both men and women.

Dr. Zain Hakeem [01:00:40]:
Right.

Dr. Zain Hakeem [01:00:40]:
You would see an incredibly strong correlation between those. The notion that hair transplants are longevity enhancing is not logical.

Dr. Zain Hakeem [01:00:50]:
Right.

Dr. Zain Hakeem [01:00:50]:
So again our brains get thrown off when it’s those kinds of examples, ice creams and sharks or hair transplants or whatever it seems. Oh, okay, yeah, I see why that’s silly. But when it’s grip strength, somehow that doesn’t kick on.

Dr. Zain Hakeem [01:01:06]:
Right.

Dr. Zain Hakeem [01:01:09]:
If we got time actually I’ll circle back to the notion of strength of effect one more time. There’s a great article that a patient recommended to me actually on the Slate Star Codex called the Control Group is out of control, Turn of it. Okay. It’s a phenomenal analysis of science.

Dr. Zain Hakeem [01:01:31]:
Right.

Dr. Zain Hakeem [01:01:32]:
Because there are researchers who have taken everything you could want, double blind, placebo controlled, randomized, all of it, and applied it to the notion of psychic phenomena.

Dr. Zain Hakeem [01:01:45]:
Right.

Dr. Zain Hakeem [01:01:46]:
So simple example, the researcher will meet the subject, greet them, bring them to a room, sit them in a room. There’s a camera in the room.

Dr. Zain Hakeem [01:01:57]:
Right.

Dr. Zain Hakeem [01:01:58]:
And the camera has a feed that goes across the building to another control room. Across like literally across the building.

Dr. Zain Hakeem [01:02:08]:
Right.

Dr. Zain Hakeem [01:02:09]:
Somewhere else. And either there is or is not someone in that monitoring control room watching the screen, watching the person.

Dr. Zain Hakeem [01:02:21]:
Right.

Dr. Zain Hakeem [01:02:21]:
And the person is instructed to say whether they think they can or whether they think someone is watching or they think they’re not being watched.

Dr. Zain Hakeem [01:02:29]:
Right.

Dr. Zain Hakeem [01:02:31]:
And there are studies that indicate that people can tell whether they’re being watched.

Dr. Zain Hakeem [01:02:38]:
Right.

Dr. Zain Hakeem [01:02:40]:
You can’t complain about the methodology of these. They have, the statistics are done exactly the way you would want. Now they had a skeptical researcher say I don’t believe this, I’m going to replicate this experiment. He replicated it, found no effect. So amazing that both these people are good scientists. Actually he teamed up with the guy who had seen the effect and they did a joint study.

Dr. Zain Hakeem [01:03:07]:
Right.

Dr. Zain Hakeem [01:03:08]:
And on the days where the guy who believed it greeted the people saw an effect on the days when the skeptic greeted them, but they neither, they basically said hi, here’s the room, thank you for this. That’s all they did. And yet somehow I believe in that article they noticed that there’s the only paper where they suggested there were both co authors suggested that the other one had hacked their computer as a possible explanation of the data because otherwise there was none. I Bring all this up to say that every bit of scientific rigor you could ask for was there in those studies.

Dr. Zain Hakeem [01:03:45]:
Right?

Dr. Zain Hakeem [01:03:47]:
Except strength of effect, because the effect they detected was statistically significant. Was well done, but it was 49.8, 50.2.

Dr. Zain Hakeem [01:03:59]:
Right.

Dr. Zain Hakeem [01:04:00]:
It’s a tiny effect. Now it’s statistically valid, but it’s a tiny bias one way or another. If they had insisted on, Well, I need 10%, then all of it’s gone.

Dr. Zain Hakeem [01:04:11]:
Right?

Dr. Zain Hakeem [01:04:12]:
So I kind of insist on the same thing is we need to have some standard above which, hey, if you can’t show me a 50% improvement in correlative data, I’m just not interested in having the conversation, right? If you say 10, if you say 25, if you say 30, call me when you hit 50.

Dr. Zain Hakeem [01:04:33]:
Right?

Dr. Zain Hakeem [01:04:34]:
And I think that would save us from a lot of things. I think insisting on double blind placebo controlled trials more would save us in humans, by the way, right? Mice data doesn’t translate. The number of things that work in mice and doesn’t work in humans is huge. 99 plus percent of things. So the movement from a mouse model to human model is very, very poor, even on a pharmaceutical basis. So, you know, double blind placebo controlled randomized trial in humans done well to completion, not stopped early with proper con. Proper placebo control placebo or Bradford Hill criteria over the set of significant correlative data, one or the other of those. I think if we could get people to really take in those ideas, I think we would have less opportunity for being fooled by.

Dr. Zain Hakeem [01:05:27]:
By influencers.

Dr. Zain Hakeem [01:05:28]:
Yeah.

Nick Urban [01:05:29]:
Does the Bradford Hill criteria take into account safety or theoretical safety in what? Like, okay, save this intervention I’m planning, this molecule has a 75% like improvement over placebo, but also I have like a 20% chance, greater chance of dying or having like massively complicating side effects or something.

Dr. Zain Hakeem [01:05:55]:
Yeah. So it does, it does not account.

Nick Urban [01:05:59]:
For.

Dr. Zain Hakeem [01:06:02]:
Non lethal safety, I would say. And this is one of the challenges, right? So one of the ways that statin drug makers will advertise their product is they’ll say, hey, there’s a 33% reduction in cardiac events.

Dr. Zain Hakeem [01:06:16]:
Right?

Dr. Zain Hakeem [01:06:17]:
Now the reduction was from, you know, 3 to 2, which is a 33% reduction.

Nick Urban [01:06:22]:
Absolute versus relative risk.

Dr. Zain Hakeem [01:06:24]:
Absolute versus relative risk. The other problem is it was a reduction in cardiovascular events, but not death. Death overall, there was no change.

Dr. Zain Hakeem [01:06:33]:
Right.

Dr. Zain Hakeem [01:06:34]:
And so I always, I always joke, I’m like, well, what if the statin creates a mild muscle soreness, right? And so all these people are dying by Getting hit by buses they can’t get out of the way of.

Dr. Zain Hakeem [01:06:47]:
Right.

Dr. Zain Hakeem [01:06:48]:
But it’s not reducing, but it’s not increasing their cardiac mortality.

Dr. Zain Hakeem [01:06:52]:
Right.

Dr. Zain Hakeem [01:06:52]:
They’re dying of something else and maybe that something else is accidental. That’s why I like all cause mortality as a measure is it’s hard, relatively hard to fake.

Dr. Zain Hakeem [01:07:01]:
Right.

Dr. Zain Hakeem [01:07:03]:
And so I usually try to say, look, if you can show me a reduction in all cause mortality, then I’m willing to talk to you about cause specific mortality. So with the intervention you’re talking about here is, yes, it would account for, hey, if it increases your longevity through cardiac means, but decreases it by some other means, yes, the Bradford Hill criteria would account for that aspect of safety because you’d have a smaller strength of effect.

Dr. Zain Hakeem [01:07:28]:
Right.

Dr. Zain Hakeem [01:07:30]:
But not if it only cripples you. So that’s the downside, right, is there are effects we care about other than longevity that are not necessarily well accounted for by these data.

Nick Urban [01:07:40]:
Well, Dr. Z, we have still a lot to cover and man, there’s.

Dr. Zain Hakeem [01:07:44]:
You can go forever, right?

Nick Urban [01:07:45]:
I didn’t even talking about these things because one of your big passions and which I loved about your practice is entirely separate from what we’ve discussed throughout the majority of this interview so far. So we’ll have to do another one because I’m sure people are gonna be really curious to hear what it is beside from like these physical biochemical things that you’re doing to help people like not just reach longevity, but also health span in a way that matters to them. Not just giving them more time on the planet if it’s low quality time, but making sure they’re actually enjoying themselves, living the best they can.

Dr. Zain Hakeem [01:08:20]:
Absolutely.

Dr. Zain Hakeem [01:08:20]:
Yeah.

Dr. Zain Hakeem [01:08:21]:
This is just a duration of life is only half of it. Depth and, and quality of life are the other half and a lot. Most of what I’m excited about in the practice is optimizing that that second half is the depth and quality. So yeah, love to have it.

Dr. Zain Hakeem [01:08:35]:
Cool.

Nick Urban [01:08:35]:
If people want to connect with you, to follow your work, to tune in, how do they go about getting in touch with you?

Dr. Zain Hakeem [01:08:41]:
I have a YouTube channel is YouTube.com riverrock medical. River Rock Medical is the name of my practice. I’m here in Austin, Texas and riverrockmedical.com of course they can reach out. I do not react emotionally well to Twitter, so though I have an account, you may find me there. I am usually not responsive there. So reaching out through the website is probably the better bet.

Nick Urban [01:09:05]:
Okay. And one last thing before we part ways. You mentioned to me in Passing sleep is overrated. Why is that?

Dr. Zain Hakeem [01:09:14]:
Sleep is overrated. Yeah. My controversial opinions. So, a couple things. Number one, I think the most popular book out why we Sleep, Matthew Walker, I think. What’s the name of that guy? Alex Guzman, maybe. Yeah, Misquoting that.

Nick Urban [01:09:31]:
I read the article.

Dr. Zain Hakeem [01:09:32]:
Great. Yeah. Did a great breakdown on the methodological and scientific clause in that book.

Dr. Zain Hakeem [01:09:38]:
Right.

Dr. Zain Hakeem [01:09:40]:
Number two, I think the. Even within that book, or even with. Sorry, even within the data that does exist on sleep and mortality, it’s a very significant U shaped curve that slants upward much more strongly with more sleep than it does with low sleep. So, you know, it’s not a U shape like this, it’s like a U shape like this.

Dr. Zain Hakeem [01:10:01]:
Right.

Dr. Zain Hakeem [01:10:02]:
So the, the lowest mortality was like at seven and a half hours.

Dr. Zain Hakeem [01:10:06]:
Right.

Dr. Zain Hakeem [01:10:06]:
And then it’s a little bit higher in, you know, if you sleep 6, a little bit higher if you sleep 5, a little bit higher if you Sleep 4. But if you start sleeping 9 or 10 or 12, it’s actually a pretty sharp rising curve.

Dr. Zain Hakeem [01:10:19]:
Right.

Dr. Zain Hakeem [01:10:20]:
First thing. Second thing, these are self reported data. These are not measured data.

Dr. Zain Hakeem [01:10:24]:
Right.

Dr. Zain Hakeem [01:10:24]:
They walked up to people and be like, hey, last week about how much do you sleep?

Dr. Zain Hakeem [01:10:28]:
Right.

Dr. Zain Hakeem [01:10:28]:
That’s the scientific rigor that we’re talking about most of these studies. Number three, even in those studies, if you look at people that exercise, the. The effect vanishes, right? So why. I don’t know. I have no explanation for this. But we don’t understand sleep in general.

Dr. Zain Hakeem [01:10:45]:
Right.

Dr. Zain Hakeem [01:10:48]:
So that’s the other factor. The effect is significantly less in women, Right. So men are more susceptible to the negative health outcomes of, of short sleep. I also have to wonder, pure speculation, again, I’m in storytelling mode here. But we do know that sleep is important for muscle development, for recovery from exercise, which is what we said. That’s where all the magic happens, Right. And so maybe these people are not that fit, maybe they’re not that strong.

Dr. Zain Hakeem [01:11:19]:
Right.

Dr. Zain Hakeem [01:11:19]:
Maybe the. Maybe the real issue is that their poor sleep prevents them from exercising, working out, developing muscle building, VO2 max. And so the real health risk is the VO2 max or the strength lack.

Dr. Zain Hakeem [01:11:32]:
Right.

Dr. Zain Hakeem [01:11:32]:
None of the data have been segmented on fitness or strength.

Dr. Zain Hakeem [01:11:38]:
Right.

Dr. Zain Hakeem [01:11:39]:
And so I have many questions and hesitations about sleep as a pure marker for longevity. And this does get into. Exactly. The thing is that if I were to definitively tell you somehow that sleep has no impact on longevity, would you suddenly lose all interest in quality sleep? No.

Dr. Zain Hakeem [01:12:01]:
Right.

Dr. Zain Hakeem [01:12:01]:
So why do we need to justify it with longevity? Why isn’t it enough to to say, hey, this impacts my quality of life and therefore it matters and we should optimize it for that reason, Right? We don’t need a longevity reason to drive everything we do. Like quality is enough of a reason.

Nick Urban [01:12:20]:
Yeah, exactly.

Dr. Zain Hakeem [01:12:21]:
That gets into the other half of my practice, so we’ll have to save that for another podcast.

Nick Urban [01:12:25]:
Sounds good. Thank you so much again for joining me. This is really fun and I hope people got a lot out of the not only the Bradford Hill criteria but but also like your way of thinking and approaching interventions and also looking for the magnitude of effect of certain interventions because it really helps cut down 80%, 90% of the noise out there when you actually look at the total effect size. And ideally, if things are run through randomized human clinical trials, great. But if not, we can use a whole other set of criteria to make sure that we’re going to benefit and not chase our tail or worse, go down the wrong road and cause issues that wouldn’t have otherwise been there.

Dr. Zain Hakeem [01:13:05]:
Absolutely. I appreciate you having me on. It’s been been enjoyable as always just to have the conversation.

Nick Urban [01:13:10]:
So thanks for tuning in to high performance longevity. If you got value today, the best way to support the show is to leave a review or share it with someone who’s ready to upgrade their health span. You can find all the episodes, show notes and resources [email protected] until next time, stay energized, stay bioharmonized, and be an outlier.