Outlive - by Peter Attia
Published:
Outlive - by Peter Attia
Read: 2024-07-28
Recommend: 10/10
This book is worth your time. It educates me on building movement and cognitive reserves, allowing me to lead healthier and longer lives. The author explains the abundance of so-called experts on various types of diets (vegetarian, keto, etc), despite the lack of supporting evidence. Additionally, the book encourages reflection on the importance of mental health.
Notes
Here are some text that I highlighted in the book:
Four Horsemen: heart disease, cancer, neurodegenerative disease, or type 2 diabetes and related metabolic dysfunction. To achieve longevity—to live longer and live better for longer—we must understand and confront these causes of slow death.
Healthspan is typically defined as the period of life when we are free from disability or disease, but I find this too simplistic.
I watched the five stages of grief described by Elisabeth Kübler-Ross in her classic book On Death and Dying—denial, anger, bargaining, sadness, and acceptance—flash across the executives’ faces.
Risk is not something to be avoided at all costs; rather, it’s something we need to understand, analyze, and work with. Every single thing we do, in medicine and in life, is based on some calculation of risk versus reward.
a hypothesis, which as Richard Feynman pointed out is basically a fancy word for a guess.
This reported 24 percent risk increase sounded scary indeed. But nobody seemed to care that the absolute risk increase of breast cancer for women in the study remained minuscule. Roughly five out of every one thousand women in the HRT group developed breast cancer, versus four out of every one thousand in the control group, who received no hormones. The absolute risk increase was just 0.1 percentage point.
She continued: “Why would you want to live longer if you’re so unhappy?”
The life-extending effect of CR seems to be almost universal. Numerous labs have found that restricting caloric intake lengthens lifespan not only in rats and mice (usually) but also in yeast, worms, flies, fish, hamsters, dogs, and even, weirdly, spiders. It has been found to extend lifespan in just about every model organism on which it has been tried, with the odd exception of houseflies. It seems that, across the board, hungry animals become more resilient and better able to survive, at least inside a well-controlled, germ-free laboratory.
your liver can recover from fairly extensive damage, up to and including partial removal.
But in our modern world, this fat-storage mechanism has outlived its usefulness. We no longer need to worry about foraging for fruit or putting on fat to survive a cold winter. Thanks to the miracles of modern food technology, we are almost literally swimming in a sea of fructose, especially in the form of soft drinks, but also hidden in more innocent-seeming foods like bottled salad dressing and yogurt cups. Whatever form it takes, fructose does not pose a problem when consumed the way that our ancestors did, before sugar became a ubiquitous commodity: mostly in the form of actual fruit. It is very difficult to get fat from eating too many apples, for example, because the fructose in the apple enters our system relatively slowly, mixed with fiber and water, and our gut and our metabolism can handle it normally. But if we are drinking quarts of apple juice, it’s a different story
The problem he recognized was that much of the basic research into cholesterol and atherosclerosis had been conducted in rabbits, which have a unique ability to absorb cholesterol into their blood from their food and form atherosclerotic plaques from it; the mistake was to assume that humans also absorb dietary cholesterol as readily. “There’s no connection whatsoever between cholesterol in food and cholesterol in blood,” Keys said in a 1997 interview. “None. And we’ve known that all along. Cholesterol in the diet doesn’t matter at all unless you happen to be a chicken or a rabbit.”
Back then, nearly fifteen years ago, the apoB test (simply, measuring the concentration of apoB-tagged particles) was not commonly done. Since then, evidence has piled up pointing to apoB as far more predictive of cardiovascular disease than simply LDL-C, the standard “bad cholesterol” measure. According to an analysis published in JAMA Cardiology in 2021, each standard-deviation increase in apoB raises the risk of myocardial infarction by 38 percent in patients without a history of cardiac events or a diagnosis of cardiovascular disease (i.e., primary prevention). That’s a powerful correlation. Yet even now, the American Heart Association guidelines still favor LDL-C testing instead of apoB. I have all my patients tested for apoB regularly, and you should ask for the same test the next time you see your doctor. (Don’t be waved off by nonsensical arguments about “cost”: It’s about twenty to thirty dollars.)
I take a very hard line on lowering apoB, the particle that causes all this trouble. (In short: get it as low as possible, as early as possible.)
By how much does one need to lower it (or its proxy LDL-C) to achieve meaningful risk reduction? The various treatment guidelines specify target ranges for LDL-C, typically 100 mg/dL for patients at normal risk, or 70 mg/dL for high-risk individuals. In my view, this is still far too high. Simply put, I think you can’t lower apoB and LDL-C too much, provided there are no side effects from treatment. You want it as low as possible.
With a few exceptions, such as glioblastoma or other aggressive brain tumors, as well as certain lung and liver cancers, solid organ tumors typically kill you only when they spread to other organs. Breast cancer kills only when it becomes metastatic. Prostate cancer kills only when it becomes metastatic. You could live without either of those organs. So when you hear the sad story of someone dying from breast or prostate cancer, or even pancreatic or colon cancer, they died because the cancer spread to other, more critical organs such as the brain, the lungs, the liver, and bones. When cancer reaches those places, survival rates drop precipitously.
A randomized trial in 131 cancer patients undergoing chemotherapy found that those who were placed on a “fasting-mimicking diet” (basically, a very low-calorie diet designed to provide essential nutrients while reducing feelings of hunger) were more likely to respond to chemotherapy and to feel better physically and emotionally.
MRI has a distinct advantage over CT in that it does not produce any ionizing radiation but still provides good resolution.
The more of these networks and subnetworks that we have built up over our lifetime, via education or experience, or by developing complex skills such as speaking a foreign language or playing a musical instrument, the more resistant to cognitive decline we will tend to be. The brain can continue functioning more or less normally, even as some of these networks begin to fail. This is called “cognitive reserve,” and it has been shown to help some patients to resist the symptoms of Alzheimer’s disease. It seems to take a longer time for the disease to affect their ability to function.
There is a parallel concept known as “movement reserve” that becomes relevant with Parkinson’s disease. People with better movement patterns, and a longer history of moving their bodies, such as trained or frequent athletes, tend to resist or slow the progression of the disease as compared to sedentary people. This is also why movement and exercise, not merely aerobic exercise but also more complex activities like boxing workouts, are a primary treatment/prevention strategy for Parkinson’s. Exercise is the only intervention shown to delay the progression of Parkinson’s.
The brain is a greedy organ. It makes up just 2 percent of our body weight, yet it accounts for about 20 percent of our total energy expenditure. Its eighty-six billion neurons each have between one thousand and ten thousand synapses connecting them to other neurons or target cells, creating our thoughts, our personalities, our memories, and the reasoning behind both our good and bad decisions.
There is some evidence that supplementation with the omega-3 fatty acid DHA, found in fish oil, may help maintain brain health, especially in e4/e4 carriers.
Studies have found that hearing loss is clearly associated with Alzheimer’s disease, but it’s not a direct symptom. Rather, it seems hearing loss may be causally linked to cognitive decline, because folks with hearing loss tend to pull back and withdraw from interactions with others. When the brain is deprived of inputs—in this case auditory inputs—it withers. Patients with hearing loss miss out on socializing, intellectual stimulation, and feeling connected; prescribing them hearing aids may help relieve some symptoms.
In Medicine 3.0, we have five tactical domains that we can address in order to alter someone’s health. The first is exercise, which I consider to be by far the most potent domain in terms of its impact on both lifespan and healthspan. Of course, exercise is not just one thing, so I break it down into its components of aerobic efficiency, maximum aerobic output (VO2 max), strength, and stability, all of which we’ll discuss in more detail. Next is diet or nutrition—or as I prefer to call it, nutritional biochemistry. The third domain is sleep, which has gone underappreciated by Medicine 2.0 until relatively recently. The fourth domain encompasses a set of tools and techniques to manage and improve emotional health. Our fifth and final domain consists of the various drugs, supplements, and hormones that doctors learn about in medical school and beyond. I lump these into one bucket called exogenous molecules, meaning molecules we ingest that come from outside the body.
One way I like to explain this is through the example of car accidents, which also happen to be a minor obsession of mine. They kill far too many people across all age groups—one person every twelve minutes, according to the National Highway Traffic Safety Administration—yet I believe that a fair number of these deaths could be prevented, with the proper tactics.
The most common way to be killed, as a driver, is by another car that hits yours from the left, on the driver’s side, having run a red light or traveling at high speed. It’s typically a T-bone or broadside crash, and often the driver who dies is not the one at fault.
The problem, and we will see this again in the nutrition chapters, is that we have this need to turn everything into a kind of religious war over which is the One True Church. Some experts insist that strength training is superior to cardio, while an equal number assert the opposite. The debate is as endless as it is pointless, sacrificing science on the altar of advocacy. The problem is that we are looking at these hugely important domains of life—exercise, but also nutrition—through a far too narrow lens. It’s not about which side of the gym you prefer. It’s so much more essential than that.
And if exercise is not a part of your life at the moment, you are not alone—77 percent of the US population is like you. Now is the time to change that. Right now. Even a little bit of daily activity is much better than nothing. Going from zero weekly exercise to just ninety minutes per week can reduce your risk of dying from all causes by 14 percent. It’s very hard to find a drug that can do that.
Of course, there are almost certainly confounders here, just as with all observational study, including that of nutrition. But at least five factors increase my confidence in at least the partial causality of this relationship. First, the magnitude of the effect size is very large. Second, the data are consistent and reproducible across many studies of disparate populations. Third, there is a dose-dependent response (the fitter you are, the longer you live). Fourth, there is great biologic plausibility to this effect, via the known mechanisms of action of exercise on lifespan and healthspan. And fifth, virtually all experimental data on exercise in humans suggest that it supports improved health.
The Centenarian Decathlon is a framework I use to organize my patients’ physical aspirations for the later decades of their lives, especially their Marginal Decade. I know, it’s a somewhat morbid topic, thinking about our own physical decline. But not thinking about it won’t make it any less inevitable.
I often test my own lactate while I am working out this way, using a small handheld lactate monitor, to make sure my pacing is correct. The goal is to keep lactate levels constant, ideally between 1.7 and 2.0 millimoles. This is the zone 2 threshold for most people.
How much zone 2 training you need depends on who you are. Someone who is just being introduced to this type of training will derive enormous benefit from even two 30-minute sessions per week to start with. Based on multiple discussions with San Millán and other exercise physiologists, it seems that about three hours per week of zone 2, or four 45-minute sessions, is the minimum required for most people to derive a benefit and make improvements, once you get over the initial hump of trying it for the first time. (People who are training for major endurance events, such as running a marathon, obviously need to do more than this.) I am so persuaded of the benefits of zone 2 that it has become a cornerstone of my training plan. Four times a week, I will spend about an hour riding my stationary bike at my zone 2 threshold.
I push my patients to train for as high a VO2 max as possible, so that they can maintain a high level of physical function as they age. Ideally, I want them to target the “elite” range for their age and sex (roughly the top 2 percent). If they achieve that level, I say good job—now let’s reach for the elite level for your sex, but two decades younger. This may seem like an extreme goal, but I like to aim high, in case you haven’t noticed.
Keep in mind, increasing your VO2 max by any amount is going to improve your life, not only in terms of how long you live but also how well you live, today and in the future. Improving your VO2 max from the very bottom quartile to the quartile above (i.e., below average) is associated with almost a 50 percent reduction in all-cause mortality
Where HIIT intervals are very short, typically measured in seconds, VO2 max intervals are a bit longer, ranging from three to eight minutes—and a notch less intense. I do these workouts on my road bike, mounted to a stationary trainer, or on a rowing machine, but running on a treadmill (or a track) could also work. The tried-and-true formula for these intervals is to go four minutes at the maximum pace you can sustain for this amount of time—not an all-out sprint, but still a very hard effort. Then ride or jog four minutes easy, which should be enough time for your heart rate to come back down to below about one hundred beats per minute. Repeat this four to six times and cool down.
The mortality from a hip or femur fracture is staggering once you hit about the age of sixty-five. It varies by study, but ranges from 15 to 36 percent in one year—meaning that up to one-third of people over sixty-five who fracture their hip are dead within a year. Even if a person does not die from the injury, the setback can be the functional equivalent of death in terms of how much muscle mass and, hence, physical capacity is lost during the period of bed rest (recall how quickly people over sixty-five lose muscle mass when bedridden).
I think of strength training as a form of retirement saving. Just as we want to retire with enough money saved up to sustain us for the rest of our lives, we want to reach older age with enough of a “reserve” of muscle (and bone density) to protect us from injury and allow us to continue to pursue the activities that we enjoy. It is much better to save and invest and plan ahead, letting your wealth build gradually over decades, than to scramble to try to scrape together an individual retirement account in your late fifties and hope and pray that the stock market gods help you out. Like investing, strength training is also cumulative, its benefits compounding. The more of a reserve you build up, early on, the better off you will be over the long term.
I’ve always been a fan of carrying heavy objects with my hands. As a teenager working on a construction site over the summers, I always volunteered to haul tools and materials across the site, and today I still incorporate some kind of carrying, typically with dumbbells, kettlebells, or sandbags, into most of my workouts. I’ve also become semiobsessed with an activity called rucking, which basically means hiking or walking at a fast pace with a loaded pack on your back. Three or four days a week, I’ll spend an hour rucking around my neighborhood, up and down hills, typically climbing and descending several hundred feet over the course of three or four miles. The fifty- to sixty-pound pack on my back makes it quite challenging, so I’m strengthening my legs and my trunk while also getting in a solid cardiovascular session. The best part is that I never take my phone on these outings; it’s just me, in nature, or maybe with a friend or a family member or a houseguest (for whom rucking is mandatory; I keep two extra rucksacks in the garage).
As great as rucking is, it’s not the only thing I rely on to build my strength. Fundamentally I structure my training around exercises that improve the following:
- Grip strength, how hard you can grip with your hands, which involves everything from your hands to your lats (the large muscles on your back). Almost all actions begin with the grip.
- Attention to both concentric and eccentric loading for all movements, meaning when our muscles are shortening (concentric) and when they are lengthening (eccentric). In other words, we need to be able to lift the weight up and put it back down, slowly and with control. Rucking down hills is a great way to work on eccentric strength, because it forces you to put on the “brakes.”
- Pulling motions, at all angles from overhead to in front of you, which also requires grip strength (e.g., pull-ups and rows).
- Hip-hinging movements, such as the deadlift and squat, but also step-ups, hip-thrusters, and countless single-leg variants of exercises that strengthen the legs, glutes, and lower back.
You grab the bar and just hang there, supporting your body weight. This is a simple but sneakily difficult exercise that also helps strengthen the critically important scapular (shoulder) stabilizer muscles
stability lets us create the most force in the safest manner possible, connecting our body’s different muscle groups with much less risk of injury to our joints, our soft tissue, and especially our vulnerable spine. The goal is to be strong, fluid, flexible, and agile as you move through your world.
On the one hand, we have made-for-clickbait epidemiological “studies” that make absurd claims, such as that eating an ounce of tree nuts each day will lower your cancer risk by exactly 18 percent (not making this up). On the other, we have clinical trials that tend almost without exception to be flawed. Thanks to the poor quality of the science, we actually don’t know that much about how what we eat affects our health. That creates a tremendous opportunity for a multitude of would-be nutrition gurus and self-proclaimed experts to insist, loudly, that only they know the true and righteous diet. There are forty thousand diet books on Amazon; they can’t all be right.
Low-fat, vegan, carnivore, Paleo, low-carb, or Atkins—every diet has its zealous warriors who will proclaim the superiority of their way of eating over all others until their dying breath, despite a total lack of conclusive evidence.
The Bradford Hill criteria are (1) strength of the association (i.e., effect size), (2) consistency (i.e., reproducibility), (3) specificity (i.e., is it an observation of disease in a very specific population at a specific site, with no other likely explanation?), (4) temporality (i.e., does the cause precede the effect?), (5) dose response (i.e., does the effect get stronger with a higher dose?), (6) plausibility (i.e., does it make sense?), (7) coherence (i.e., does it agree with data from controlled experiments in animals?), (8) experiment (i.e. is there experimental evidence to back up the findings?), and (9) analogy (i.e., the effect of similar factors may be considered).
This is called continuous glucose monitoring, or CGM, and it has become a very important part of my armamentarium in recent years.
Rice and oatmeal are surprisingly glycemic (meaning they cause a sharp rise in glucose levels), despite not being particularly refined; more surprising is that brown rice is only slightly less glycemic than long-grain white rice.
Fructose does not get measured by CGM, but because fructose is almost always consumed in combination with glucose, fructose-heavy foods will still likely cause blood-glucose spikes.
aerobic exercise seems most efficacious at removing glucose from circulation, while high-intensity exercise and strength training tend to increase glucose transiently, because the liver is sending more glucose into the circulation to fuel the muscles. Don’t be alarmed by glucose spikes when you are exercising.
Nonstarchy veggies such as spinach or broccoli have virtually no impact on blood sugar. Have at them.
Foods high in protein and fat (e.g., eggs, beef short ribs) have virtually no effect on blood sugar (assuming the short ribs are not coated in sweet sauce), but large amounts of lean protein (e.g., chicken breast) will elevate glucose slightly.
The first thing you need to know about protein is that the standard recommendations for daily consumption are a joke. Right now the US recommended dietary allowance (RDA) for protein is 0.8 g/kg of body weight. This may reflect how much protein we need to stay alive, but it is a far cry from what we need to thrive. There is ample evidence showing that we require more than this—and that consuming less leads to worse outcomes. More than one study has found that elderly people consuming that RDA of protein (0.8 g/kg/day) end up losing muscle mass, even in as short a period as two weeks. It’s simply not enough.
How much protein do we actually need? It varies from person to person. In my patients I typically set 1.6 g/kg/day as the minimum, which is twice the RDA. The ideal amount can vary from person to person, but the data suggest that for active people with normal kidney function, one gram per pound of body weight per day (or 2.2 g/kg/day) is a good place to start—nearly triple the minimal recommendation.
Do you need to eat meat, fish, and dairy to get sufficient protein? No. But if you choose to get all your protein from plants, you need to understand two things. First, the protein found in plants is there for the benefit of the plant, which means it is largely tied up in indigestible fiber, and therefore less bioavailable to the person eating it. Because much of the plant’s protein is tied to its roots, leaves, and other structures, only about 60 to 70 percent of what you consume is contributing to your needs, according to Don Layman, professor emeritus of food science and human nutrition at the University of Illinois Urbana-Champaign, and an expert on protein. Some of this can be overcome by cooking the plants, but that still leaves us with the second issue. The distribution of amino acids is not the same as in animal protein. In particular, plant protein has less of the essential amino acids methionine, lysine, and tryptophan, potentially leading to reduced protein synthesis. Taken together, these two factors tell us that the overall quality of protein derived from plants is significantly lower than that from animal products.
While carbohydrates are primarily a source of fuel and amino acids are primarily building blocks, fats are both. They are very efficient fuel for oxidation (think: slow-burning logs) and also the building blocks for many of our hormones (in the form of cholesterol) and cell membranes. Eating the right mix of fats can help maintain metabolic balance, but it is also important for the health of our brain, much of which is composed of fatty acids.
If there is one type of food that I would eliminate from everyone’s diet if I could, it would be fructose-sweetened drinks, including both sodas and fruit juices, which deliver too much fructose, too quickly, to a gut and liver that much prefer to process fructose slowly. Just eat fruit and let nature provide the right amount of fiber and water.
Paul is an expert in trauma, and he saw that I displayed all the behavioral signs: anger, detachment, obsessiveness, a need to achieve that was fueled by insecurity.
One framework that the therapists at the Bridge work with, and that I found helpful, is called the Trauma Tree. The idea behind it is that certain undesirable behaviors that we manifest as adults, such as addiction and uncontrolled anger, are actually adaptations to the various types of trauma we suffered in childhood. So while we only see the manifestation of the tree above the ground, the trunk and branches, we need to look underground, at the roots, to understand the tree completely. But the roots are often very well hidden, as they were with me. Trauma generally falls into five categories: (1) abuse (physical or sexual, but also emotional or spiritual); (2) neglect; (3) abandonment; (4) enmeshment (the blurring of boundaries between adults and children); and (5) witnessing tragic events. Most of the things that wound children fit into these five categories.
Just as an aside, a 2019 study provides an elegant demonstration of the principle that setbacks can be net positive. The researchers looked at junior scientists who had applied for NIH grants and separated them into two groups: One group had scored just above the threshold for funding, while the other had scored just below the funding line, meaning their grants were not funded. While the near-miss group were more likely to drop out of science in the immediate aftermath, those who stuck with it eventually outperformed their peers who had received funding on their first try. The early setback had not impaired their careers but may have had an opposite effect.
The most important thing about childhood trauma is not the event itself but the way the child adapts to it. Children are remarkably resilient, and wounded children become adaptive children. The problems begin when these adaptive children grow up to become maladaptive, dysfunctional adults. This dysfunction is represented by the four branches of the trauma tree: (1) addiction, not only to vices such as drugs, alcohol, and gambling, but also to socially acceptable things such as work, exercise, and perfectionism (check); (2) codependency, or excessive psychological reliance on another person; (3) habituated survival strategies, such as a propensity to anger and rage (check); (4) attachment disorders, difficulty forming and maintaining connections or meaningful relationships with others (check). These branches are often fairly obvious and easy to spot; the tricky part is digging down to the roots and beginning to disentangle them. All of this is highly individual; everyone responds and adapts to trauma in a unique way. And it’s not as if there is some sort of pill that can make someone’s trauma, or their adaptations to it, simply go away. It requires hard work—and, as I would come to understand, it can also take a very long time.
“I need to be great,” he said, “in order to feel like I’m not worthless.”
DBT, developed in the 1990s by Marsha Linehan. Based on the principles of cognitive behavioral therapy, which seeks to teach patients new ways of thinking about or acting on their problems, DBT was developed to help individuals with more serious and potentially dangerous issues, such as an inability to regulate their emotions and a propensity to harm themselves or even attempt suicide. These people are lumped into something called borderline personality disorder, which is a bit of a catch-all diagnosis, but DBT has also been found to be helpful in patients with less dramatic and dangerous emotional health issues, a category that encompasses many more of us.
I had long subscribed to a kind of Silicon Valley approach to longevity and health, believing that it is possible to hack our biology, and hack it, and hack it, until we become these perfect little humanoids who can live to be 120 years old. I used to be all about that, constantly tinkering and experimenting with new fasting protocols or sleep gadgets to maximize my own longevity. Everything in my life needed to be optimized. And longevity was basically an engineering problem. Or so I thought.
What I eventually realized, after this long and very painful journey, is that longevity is meaningless if your life sucks. Or if your relationships suck. None of it matters if your wife hates you. None of it matters if you are a shitty father, or if you are consumed by anger or addiction. Your résumé doesn’t really matter, either, when it comes time for your eulogy.
My obsession with longevity was really about my fear of dying. And something about having children was making my obsession with longevity ever more frenetic. I was running away from dying as fast as I could. Yet at the same time, ironically, I was also avoiding actually living. My tactics might have succeeded in my living longer, with optimal glucose regulation and ideal lipoprotein levels, but my strategy was unquestionably accumulating more regrets. My physical and cognitive health were great, but my emotional health was tanking.