Outlive by Peter Attia - Summary and Notes

Tuesday. September 12, 2023 - 168 mins

Summary

Peter Attia’s book covers a lot of ground in the latest research to improving our health span which Peter defines as “how well you live”.

Peter emphasizes the benefits of zone-2 training and how it be benefitial to our overall health. And similarly dives deep into other topics such as VO2 max, continous glucose monitoring and making stability a priority.

This book lays out the fundamentals of building a strong foundation of health (whether it be physical or emotional)

Favorite Quotes and Chapter Notes

I went through my notes and captured key quotes from all chapters below.

P.S. – Highly recommend Readwise if you want to get the most out of your reading.

Chapter 1: The Long Game: From Fast Death to Slow Death

The odds are overwhelming that you will die as a result of one of the chronic diseases of aging that I call the 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.
Longevity has two components. The first is how long you live, your chronological lifespan, but the second and equally important part is how well you live—the quality of your years. This is called healthspan, and it is what Tithonus forgot to ask for.
None of our treatments for late-stage lung cancer has reduced mortality by nearly as much as the worldwide reduction in smoking that has occurred over the last two decades, thanks in part to widespread smoking bans. This simple preventive measure(not smoking) has saved more lives than any late-stage intervention that medicine has devised.
Millions of people are suffering from a little-known and underdiagnosed liver condition that is a potential precursor to type 2 diabetes. Yet people at the early stages of this metabolic derangement will often return blood test results in the“normal” range. Unfortunately, in today’s unhealthy society,“normal” or“average” is not the same as“optimal.”
The metabolic derangement that leads to type 2 diabetes also helps foster and promote heart disease, cancer, and Alzheimer’s disease. Addressing our metabolic health can lower the risk of each of the Horsemen.
Almost all“diets” are similar: they may help some people but prove useless for most. Instead of arguing about diets, we will focus on nutritional biochemistry—how the combinations of nutrients that you eat affect your own metabolism and physiology, and how to use data and technology to come up with the best eating pattern for you.
One macronutrient, in particular, demands more of our attention than most people realize: not carbs, not fat, but protein becomes critically important as we age.
Exercise is by far the most potent longevity“drug.” No other intervention does nearly as much to prolong our lifespan and preserve our cognitive and physical function. But most people don’t do nearly enough—and exercising the wrong way can do as much harm as good.
Finally, as I learned the hard way, striving for physical health and longevity is meaningless if we ignore our emotional health. Emotional suffering can decimate our health on all fronts, and it must be addressed.

Chapter 2: Medicine 3.0: Rethinking Medicine for the Age of Chronic Disease

Medicine 2.0 arrived in the mid-nineteenth century with the advent of the germ theory of disease, which supplanted the idea that most illness was spread by“miasmas,” or bad air. This led to improved sanitary practices by physicians and ultimately the development of antibiotics.
The shift from Medicine 1.0 to Medicine 2.0 was prompted in part by new technologies such as the microscope, but it was more about a new way of thinking. The foundation was laid back in 1628, when Sir Francis Bacon first articulated what we now know as the scientific method. This represented a major philosophical shift, from observing and guessing to observing, and then forming a hypothesis, which as Richard Feynman pointed out is basically a fancy word for a guess.
This graph shows how little real mortality rates have improved since 1900, once you remove the top eight contagious/infectious diseases, which were largely controlled by the advent of antibiotics in the early twentieth century.
First, Medicine 3.0 places a far greater emphasis on prevention than treatment.
Second, Medicine 3.0 considers the patient as a unique individual.
The third philosophical shift has to do with our attitude toward risk. In Medicine 3.0, our starting point is the honest assessment, and acceptance, of risk—including the risk of doing nothing.
The fourth and perhaps largest shift is that where Medicine 2.0 focuses largely on lifespan, and is almost entirely geared toward staving off death, Medicine 3.0 pays far more attention to maintaining healthspan, the quality of life.
Similarly, there’s no billing code for putting a patient on a comprehensive exercise program designed to maintain her muscle mass and sense of balance while building her resistance to injury. But if she falls and breaks her hip, then her surgery and physical therapy will be covered. Nearly all the money flows to treatment rather than prevention—and when I say“prevention,” I mean prevention of human suffering.
Which brings us to perhaps the most important difference between Medicine 2.0 and Medicine 3.0. In Medicine 2.0, you are a passenger on the ship, being carried along somewhat passively. Medicine 3.0 demands much more from you, the patient: You must be well informed, medically literate to a reasonable degree, clear-eyed about your goals, and cognizant of the true nature of risk. You must be willing to change ingrained habits, accept new challenges, and venture outside of your comfort zone if necessary.

Chapter 3: Objective, Strategy, Tactics: A Road Map for Reading This Book

Strategy without tactics is the slowest route to victory. Tactics without strategy is the noise before defeat. —SUN TZU
I ask all my patients to sketch out an alternative future for themselves. What do you want to be doing in your later decades? What is your plan for the rest of your life?
Our tactics in Medicine 3.0 fall into five broad domains: exercise, nutrition, sleep, emotional health, and exogenous molecules, meaning drugs, hormones, or supplements.
So we will break down this thing called exercise into its most important components: strength, stability, aerobic efficiency, and peak aerobic capacity. Increasing your limits in each of these areas is necessary if you are hoping to reach your limit of lifespan and healthspan.
This is another area where my thinking has changed over time. I used to prioritize nutrition over everything else, but I now consider exercise to be the most potent longevity“drug” in our arsenal, in terms of lifespan and healthspan.
“Isn’t it ironic that your entire professional life is predicated around trying to make people live longer,” she mused,“yet you’re putting no energy into being less miserable, into suffering less emotionally?” She continued:“Why would you want to live longer if you’re so unhappy?” Her logic was undeniable, and it changed my whole approach to longevity.

Chapter 4: Centenarians: The Older You Get, the Healthier You Have Been

Those who live to their 110th birthday qualify for the ultra-elite cadre of“supercentenarians,” the world’s smallest age group, with only about three hundred members worldwide at any given time(although the number fluctuates). Just to give you a sense of how exclusive this club is, for every supercentenarian in the world at this writing, there are about nine billionaires.
This is part of why I place so much importance on taking a detailed family history from my patients: I need to know when your relatives died and why. What are your likely“icebergs,” genetically speaking?
The crucial distinction, the essential distinction, is that they tend to develop these diseases much later in life than the rest of us—if they develop them at all. We’re not talking about two or three or even five years later; we’re talking decades. According to research by Thomas Perls of Boston University and his colleagues, who run the New England Centenarian Study, one in five people in the general population will have received some type of cancer diagnosis by age seventy-two. Among centenarians, that one-in-five threshold is not reached until age one hundred, nearly three decades later.
Curiously, despite the fact that female centenarians outnumber males by at least four to one, the men generally scored higher on both cognitive and functional tests. This might seem paradoxical at first, since women clearly live longer than men, on average. Perls believes there is a kind of selection process at work, because men are more susceptible to heart attacks and strokes beginning in middle age, while women delay their vulnerability by a decade or two and die less often from these conditions. This tends to weed the frailer individuals out of the male population, so that only those men who are in relatively robust health even make it to their hundredth birthday, while women tend to be able to survive for longer with age-related disease and disability. Perls describes this as“a double-edged sword,” in that women live longer but tend to be in poorer health.“The men tend to be in better shape,” he has said.(The authors didn’t measure this, but my hunch is that it may have something to do with men having more muscle mass, on average, which is highly correlated to longer lifespan and better function, as we’ll discuss further in the chapters on exercise.)
What’s even more surprising is that Perls’s group has also found that the supercentenarians and the“semisupercentenarians”(ages 105 to 109) actually tend to be in even better health than garden-variety hundred-year-olds. These are the super survivors, and at those advanced ages, lifespan and healthspan are pretty much the same. As Perls and his colleagues put it in a paper title,“The Older You Get, the Healthier You Have Been.”
That said, a handful of potential longevity genes have emerged in various studies, and it turns out that some of them are possibly relevant to our strategy. One of the most potent individual genes yet discovered is related to cholesterol metabolism, glucose metabolism—and Alzheimer’s disease risk. You may have heard of this gene, which is called APOE, because of its known effect on Alzheimer’s disease risk. It codes for a protein called APOE(apolipoprotein E) that is involved in cholesterol transport and processing, and it has three variants: e2, e3, and e4. Of these, e3 is the most common by far, but having one or two copies of the e4 variant seems to multiply one’s risk of developing Alzheimer’s disease by a factor of between two and twelve. This is why I test all my patients for their APOE genotype, as we’ll discuss in chapter 9. The e2 variant of APOE, on the other hand, seems to protect its carriers against dementia—and it also turns out to be very highly associated with longevity.
We will explore the function of APOE in more detail in chapter 9, but it is likely relevant to our strategy on multiple levels. First and most obviously, it appears to play a role in delaying(or not delaying) the onset of Alzheimer’s disease, depending on the variant. This is likely not a coincidence, because as we’ll see, APOE plays an important role in shuttling cholesterol around the body, particularly in the brain; one’s APOE variant also has a large influence on glucose metabolism. Its potent correlation with longevity suggests that we should focus our efforts on cognitive health and pay special attention to issues around cholesterol and lipoproteins(the particles that carry cholesterol, which we’ll discuss in chapter 7), as well as glucose metabolism(chapter 6).
it suggests that even on this genetic level there may be no magic bullet; even for centenarians, longevity may be a game of inches, where relatively small interventions, with cumulative effect, could help us replicate the centenarians’ longer lifespan and healthspan.
One other possible longevity gene that has emerged, in multiple studies of centenarians worldwide, also provides some possible clues to inform our strategy. These are variants in a particular gene called FOXO3 that seem to be directly relevant to human longevity.
When FOXO3 is activated, it in turn activates genes that generally keep our cells healthier. It seems to play an important role in preventing cells from becoming cancerous as well. Here’s where we start to see some hope, because FOXO3 can be activated or suppressed by our own behaviors. For example, when we are slightly deprived of nutrients, or when we are exercising, FOXO3 tends to be more activated, which is what we want.

Chapter 5: Eat Less, Live Longer: The Science of Hunger and Health

Ultimately, he and others discovered that rapamycin acted directly on a very important intracellular protein complex called mTOR(pronounced“em-tor”), for“mechanistic target of rapamycin.”Why do we care about mTOR? Because this mechanism turns out to be one of the most important mediators of longevity at the cellular level. Not only that, but it is highly“conserved,” meaning it is found in virtually all forms of life, ranging from yeast to flies to worms and right on up to us humans. In biology,“conserved” means that something has been passed on via natural selection, across multiple species and classes of organisms—a sign that evolution has deemed it to be very important.
The job of mTOR is basically to balance an organism’s need to grow and reproduce against the availability of nutrients. When food is plentiful, mTOR is activated and the cell(or the organism) goes into growth mode, producing new proteins and undergoing cell division, as with the ultimate goal of reproduction. When nutrients are scarce, mTOR is suppressed and cells go into a kind of“recycling” mode, breaking down cellular components and generally cleaning house. Cell division and growth slow down or stop, and reproduction is put on hold to allow the organism to conserve energy.

Chapter 6: The Crisis of Abundance: Can Our Ancient Genes Cope with Our Modern Diet?

Avoidable human misery is more often caused not so much by stupidity as by ignorance, particularly our ignorance about ourselves. —CARL SAGAN
The liver is a highly resilient organ, almost miraculously so. It may be the most regenerative organ in the human body. When a healthy person donates a portion of their liver, both donor and recipient end up with an almost full-sized, fully functional liver within about eight weeks of the surgery, and the majority of that growth takes place in just the first two weeks. In other words, your liver can recover from fairly extensive damage, up to and including partial removal. But if NASH is not kept in check or reversed, the damage and the scarring may progress into cirrhosis.
Type 2 diabetes is technically a distinct disease, defined very clearly by glucose metrics, but I view it as simply the last stop on a railway line passing through several other stations, including hyperinsulinemia, prediabetes, and NAFLD/NASH. If you find yourself anywhere on this train line, even in the early stages of NAFLD, you are likely also en route to one or more of the other three Horsemen diseases(cardiovascular disease, cancer, and Alzheimer’s disease).
The upshot is that it’s not only obesity that drives bad health outcomes; it’s metabolic dysfunction.
Think of fat as acting like a kind of metabolic buffer zone, absorbing excess energy and storing it safely until it is needed. If we eat extra doughnuts, those calories are stored in our subcutaneous fat; when we go on, say, a long hike or swim, some of that fat is then released for use by the muscles. This fat flux goes on continually, and as long as you haven’t exceeded your own fat storage capacity, things are pretty much fine.
Individual fat-storage capacity seems to be influenced by genetic factors. This is a generalization, but people of Asian descent(for example), tend to have much lower capacity to store fat, on average, than Caucasians. There are other factors at play here as well, but this explains in part why some people can be obese but metabolically healthy, while others can appear“skinny” while still walking around with three or more markers of metabolic syndrome. It’s these people who are most at risk, according to research by Mitch Lazar at the University of Pennsylvania, because a“thin” person may simply have a much lower capacity to safely store fat. All other things being equal, someone who carries a bit of body fat may also have greater fat-storage capacity, and thus more metabolic leeway than someone who appears to be more lean.
It doesn’t take much visceral fat to cause problems. Let’s say you are a forty-year-old man who weighs two hundred pounds. If you have 20 percent body fat, making you more or less average(50th percentile) for your age and sex, that means you are carrying 40 pounds of fat throughout your body. Even if just 4.5 pounds of that is visceral fat, you would be considered at exceptionally high risk for cardiovascular disease and type 2 diabetes, in the top 5 percent of risk for your age and sex. This is why I insist my patients undergo a DEXA scan annually—and I am far more interested in their visceral fat than their total body fat.
Insulin resistance is a term that we hear a lot, but what does it really mean? Technically, it means that cells, initially muscle cells, have stopped listening to insulin’s signals, but another way to visualize it is to imagine the cell as a balloon being blown up with air. Eventually, the balloon expands to the point where it gets more difficult to force more air inside. You have to blow harder and harder. This is where insulin comes in, to help facilitate the process of blowing air into the balloon. The pancreas begins to secrete even more insulin, to try to remove excess glucose from the bloodstream and cram it into cells. For the time being it works, and blood glucose levels remain normal, but eventually you reach a limit where the“balloon”(cells) cannot accept any more“air”(glucose). This is when the trouble shows up on a standard blood test, as fasting blood glucose begins to rise. This means you have high insulin levels and high blood glucose, and your cells are shutting the gates to glucose entry. If things continue in this way, then the pancreas becomes fatigued and less able to mount an insulin response. This is made worse by, you guessed it, the fat now residing in the pancreas itself. You can see the vicious spiral forming here: fat spillover helps initiate insulin resistance, which results in the accumulation of still more fat, eventually impairing our ability to store calories as anything other than fat.
There are many other hormones involved in the production and distribution of fat, including testosterone, estrogen, hormone-sensitive lipase[*3] and cortisol. Cortisol is especially potent, with a double-edged effect of depleting subcutaneous fat(which is generally beneficial) and replacing it with more harmful visceral fat. This is one reason why stress levels and sleep, both of which affect cortisol release, are pertinent to metabolism. But insulin seems to be the most potent as far as promoting fat accumulation because it acts as kind of a one-way gate, allowing fat to enter the cell while impairing the release of energy from fat cells(via a process called lipolysis). Insulin is all about fat storage, not fat utilization.
Lots of people like to demonize fructose, especially in the form of high-fructose corn syrup, without really understanding why it’s supposed to be so harmful. The story is complicated but fascinating. The key factor here is that fructose is metabolized in a manner different from other sugars. When we metabolize fructose, along with certain other types of foods, it produces large amounts of uric acid, which is best known as a cause of gout but which has also been associated with elevated blood pressure.
The story they uncovered was that, millions of years ago, our primate ancestors migrated north from Africa into what is now Europe. Back then, Europe was lush and semitropical, but as the climate slowly cooled, the forest changed. Deciduous trees and open meadows replaced the tropical forest, and the fruit trees on which the apes depended for food began to disappear, especially the fig trees, a staple of their diets. Even worse, the apes now had to endure a new and uncomfortably cold season, which we know as“winter.” In order to survive, these apes now needed to be able to store some of the calories they did eat as fat. But storing fat did not come naturally to them because they had evolved in Africa, where food was always available. Thus, their metabolism did not prioritize fat storage. At some point, our primate ancestors underwent a random genetic mutation that effectively switched on their ability to turn fructose into fat: the gene for the uricase enzyme was“silenced,” or lost. Now, when these apes consumed fructose, they generated lots of uric acid, which caused them to store many more of those fructose calories as fat. This newfound ability to store fat enabled them to survive in the colder climate. They could spend the summer gorging themselves on fruit, fattening up for the winter. These same ape species, or their evolutionary successors, migrated back down into Africa, where over time they evolved into hominids and then Homo sapiens—while also passing their uricase-silencing mutation down to us humans. This, in turn, helped enable humans to spread far and wide across the globe, because we could store energy to help us survive cold weather and seasons without abundant food.
I test my patients’ levels of uric acid, not only because high levels may promote fat storage but also because it is linked to high blood pressure. High uric acid is an early warning sign that we need to address a patient’s metabolic health, their diet, or both.
The mechanisms are a bit complicated, but the bottom line is that even though it is rich in energy, fructose basically tricks our metabolism into thinking that we are depleting energy—and need to take in still more food and store more energy as fat.[*5] On a more macro level, consuming large quantities of liquid fructose simply overwhelms the ability of the gut to handle it; the excess is shunted to the liver, where many of those calories are likely to end up as fat. I’ve seen patients work themselves into NAFLD by drinking too many“healthy” fruit smoothies, for the same reason: they are taking in too much fructose, too quickly. Thus, the almost infinite availability of liquid fructose in our already high-calorie modern diet sets us up for metabolic failure if we’re not careful(and especially if we are not physically active).
This means keeping watch for the earliest signs of trouble. In my patients, I monitor several biomarkers related to metabolism, keeping a watchful eye for things like elevated uric acid, elevated homocysteine, chronic inflammation, and even mildly elevated ALT liver enzymes. Lipoproteins, which we will discuss in detail in the next chapter, are also important, especially triglycerides; I watch the ratio of triglycerides to HDL cholesterol(it should be less than 2:1 or better yet, less than 1:1), as well as levels of VLDL, a lipoprotein that carries triglycerides—all of which may show up many years before a patient would meet the textbook definition of metabolic syndrome. These biomarkers help give us a clearer picture of a patient’s overall metabolic health than HbA1c, which is not very specific by itself. But the first thing I look for, the canary in the coal mine of metabolic disorder, is elevated insulin. As we’ve seen, the body’s first response to incipient insulin resistance is to produce more insulin. Think back to our analogy with the balloon: as it gets harder to get air(glucose) into the balloon(the cell), we have to blow harder and harder(i.e., produce more insulin). At first, this appears to be successful: the body is still able to maintain glucose homeostasis, a steady blood glucose level. But insulin, especially postprandial insulin, is already on the rise. One test that I like to give patients is the oral glucose tolerance test, or OGTT, where the patient swallows ten ounces of a sickly-sweet, almost undrinkable beverage called Glucola that contains seventy-five grams of pure glucose, or about twice as much sugar as in a regular Coca-Cola.[*6] We then measure the patient’s glucose and their insulin, every thirty minutes over the next two hours. Typically, their blood glucose levels will rise, followed by a peak in insulin, but then the glucose will steadily decrease as insulin does its job and removes it from circulation. On the surface, this is fine: insulin has done its job and brought glucose under control. But the insulin in someone at the early stages of insulin resistance will rise very dramatically in the first thirty minutes and then remain elevated, or even rise further, over the next hour. This postprandial insulin spike is one of the biggest early warning signs that all is not well.
Studies have found that insulin resistance itself is associated with huge increases in one’s risk of cancer(up to twelvefold), Alzheimer’s disease(fivefold), and death from cardiovascular disease(almost sixfold)—all of which underscores why addressing, and ideally preventing, metabolic dysfunction is a cornerstone of my approach to longevity.
It is beyond backwards that we do not treat hyperinsulinemia like a bona fide endocrine disorder of its own. I would argue that doing so might have a greater impact on human health and longevity than any other target of therapy. In the next three chapters, we will explore the three other major diseases of aging—cardiovascular disease, cancer, and neurodegenerative diseases—all of which are fueled in some way by metabolic dysfunction. It will hopefully become clear to you, as it is to me, that the logical first step in our quest to delay death is to get our metabolic house in order. The good news is that we have tremendous agency over this. Changing how we exercise, what we eat, and how we sleep(see Part III) can completely turn the tables in our favor. The bad news is that these things require effort to escape the default modern environment that has conspired against our ancient(and formerly helpful) fat-storing genes, by overfeeding, undermoving, and undersleeping us all.

Chapter 7: The Ticker: Confronting—and Preventing—Heart Disease, the Deadliest Killer on the Planet

Globally, heart disease and stroke(or cerebrovascular disease), which I lump together under the single heading of atherosclerotic cardiovascular disease, or ASCVD, represent the leading cause of death, killing an estimated 2,300 people every day in the United States, according to the CDC—more than any other cause, including cancer. It’s not just men who are at risk: American women are up to ten times more likely to die from atherosclerotic disease than from breast cancer(not a typo: one in three versus one in thirty).
The scan was calibrated to detect calcification in my coronary arteries, a sign of advanced atherosclerosis. The results showed that I had a calcium“score” of 6. That sounds low, and in absolute terms it was; someone with severe disease could return a score well over 1,000. But for someone age thirty-six, it should have been zero. My score of 6 meant that I had more calcium in my coronary arteries than 75 to 90 percent of people my age. As I dug deeper into the pathology of this disease, I was dismayed to learn that it was already fairly late in the game. A calcium score is treated as a predictor of future risk, which it is, but it is also a measure of historical and existing damage. And I was already off the charts. I was only in my midthirties, but I had the arteries of a fifty-five-year-old.
While heart disease is the most prevalent age-related condition, it is also more easily prevented than either cancer or Alzheimer’s disease.
In addition to transporting oxygen and nutrients to our tissues and carrying away waste, our blood traffics cholesterol molecules between cells. It’s practically a dirty word, cholesterol. Your doctor will probably utter it with a frown, because as everyone knows, cholesterol is evil stuff. Well, some of it is—you know, the LDL or“bad” cholesterol, which is inevitably counterpoised against the HDL, or“good” cholesterol. I practically need to be restrained when I hear these terms, because they’re so meaningless. And your“total cholesterol,” the first number that people offer up when we’re talking about heart disease, is only slightly more relevant to your cardiovascular risk than the color of your eyes.
When an HDL transfers its“good cholesterol” to an LDL particle, does that cholesterol suddenly become“bad”? The answer is no—because it’s not the cholesterol per se that causes problems but the nature of the particle in which it’s transported. Each lipoprotein particle is enwrapped by one or more large molecules, called apolipoproteins, that provide structure, stability, and, most importantly solubility to the particle. HDL particles are wrapped in a type of molecule called apolipoprotein A(or apoA), while LDL is encased in apolipoprotein B(or apoB). This distinction may seem trivial, but it goes to the very root cause of atherosclerotic disease: every single lipoprotein that contributes to atherosclerosis—not only LDL but several others[*1]—carries this apoB protein signature.
Another major misconception about heart disease is that it is somehow caused by the cholesterol that we eat in our diet.
It has remained in nutritional purgatory for decades, even after reams of research papers showing that dietary cholesterol(and particularly egg consumption) may not have much to do with heart disease at all. Eating lots of saturated fat can increase levels of atherosclerosis-causing lipoproteins in blood, but most of the actual cholesterol that we consume in our food ends up being excreted out our backsides. The vast majority of the cholesterol in our circulation is actually produced by our own cells.
The final myth that we need to confront is the notion that cardiovascular disease primarily strikes“old” people and that therefore we don’t need to worry much about prevention in patients who are in their twenties and thirties and forties. Not true.
This is what HDL particles generally do: particles tagged with apoA(HDL) can cross the endothelial barrier easily in both directions, in and out. LDL particles and other particles with the apoB protein are far more prone to getting stuck inside. This is what actually makes HDL particles potentially“good” and LDL particles potentially“bad”—not the cholesterol, but the particles that carry it. The trouble starts when LDL particles stick in the arterial wall and subsequently become oxidized, meaning the cholesterol(and phospholipid) molecules they contain come into contact with a highly reactive molecule known as a reactive oxygen species, or ROS, the cause of oxidative stress. It’s the oxidation of the lipids on the LDL that kicks off the entire atherosclerotic cascade.
So to gauge the true extent of your risk, we have to know how many of these apoB particles are circulating in your bloodstream. That number is much more relevant than the total quantity of cholesterol that these particles are carrying.
The fatty streak is a precursor of an atherosclerotic plaque, and if you are reading this and are older than fifteen or so, there is a good chance you already have some of these lurking in your arteries. Yes, I said“fifteen” and not“fifty”—this is a lifelong process and it starts very early.
very much if anything about your overall risk profile. Risk does seem to decline as HDL-C rises to around the 80th percentile. But simply raising HDL cholesterol concentrations by brute force, with specialized drugs, has not been shown to reduce cardiovascular risk at all. The key seems to be to increase the functionality of the particles—but as yet we have no way to do that(or measure it).
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 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.)
It turned out that the culprit was a little-known but very deadly type of particle called Lp(a)(pronounced“el-pee-little-A”). This hot mess of a lipoprotein is formed when a garden-variety LDL particle is fused with another, rarer type of protein called apolipoprotein(a), or apo(a) for short(not to be confused with apolipoprotein A or apoA, the protein that marks HDL particles). The apo(a) wraps loosely around the LDL particle, with multiple looping amino acid segments called“kringles,” so named because their structure resembles the ring-shaped Danish pastry by that name. The kringles are what make Lp(a) so dangerous: as the LDL particle passes through the bloodstream, they scoop up bits of oxidized lipid molecules and carry them along.
This is not an atypical scenario: when a patient comes to me and says their father or grandfather or aunt, or all three, died of“premature” heart disease, elevated Lp(a) is the first thing I look for. It is the most prevalent hereditary risk factor for heart disease, and its danger is amplified by the fact that it is still largely flying under the radar of Medicine 2.0, although that is beginning to change.
This is why, if you have a history of premature heart attacks in your family, you should definitely ask for an Lp(a) test. We test every single patient for Lp(a) during their first blood draw. Because elevated Lp(a) is largely genetic, the test need only be done once(and cardiovascular disease guidelines are beginning to advise a once-a-lifetime test for it anyway).
How to Reduce Cardiovascular Risk
When I look at a patient’s blood panel for the first time, my eyes immediately dart to two numbers: apoB and Lp(a). I look at the other numbers, too, but these two tell me the most when it comes to predicting their risk of ASCVD.
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.
Many doctors, and in fact many of you reading this, might be shocked to see such a low LDL-C target: 10 to 20 mg/dL? Most guidelines consider lowering LDL-C to 70 mg/dL to be“aggressive,” even for secondary prevention in high-risk patients, such as those who have already had a heart attack. It’s also natural to ask whether such extremely low levels of LDL-C and apoB are safe, given the ubiquity and importance of cholesterol in the human body. But consider the following: infants, who presumably require the most cholesterol, in order to meet the enormous demands of their rapidly growing central nervous system, have similarly low levels of circulating cholesterol, without any developmental impairment. Why? Because the total amount of cholesterol contained in all our lipoproteins—not just LDL, but also HDL and VLDL—represents only about 10 to 15 percent of our body’s total pool of cholesterol. So the concern is unwarranted, as demonstrated by scores of studies showing no ill effects from extremely low LDL concentrations. This is my starting point with any patient, whether they are like Anahad(with one prominent risk factor) or like me(lots of smaller risk factors). Our first order of business is to reduce the burden of apoB particles, primarily LDLs but also VLDLs, which can be dangerous in their own right. And do so dramatically, not marginally or incrementally. We want it as low as possible, sooner rather than later. We must also pay attention to other markers of risk, notably those associated with metabolic health, such as insulin, visceral fat, and homocysteine, an amino acid that in high concentrations[*7] is strongly associated with increased risk of heart attack, stroke, and dementia.
You’ll note that I don’t pay much attention to HDL-C, because while having very low HDL-C is associated with higher risk, it does not appear to be causal.
my first step in controlling my own cardiovascular risk was to begin to change my own diet, so as to lower my triglycerides(a contributor to apoB when they are high, as mine were), but more importantly to manage my insulin levels. I needed to get my metabolic house in order. I should note that my own solution at the time, a ketogenic diet, might not work for everyone, nor is it a diet to which I continue to adhere. In my clinical experience, about a third to half of people who consume high amounts of saturated fats(which sometimes goes hand in hand with a ketogenic diet) will experience a dramatic increase in apoB particles, which we obviously don’t want.[*8] Monounsaturated fats, found in high quantities in extra virgin olive oil, macadamia nuts, and avocados(among other foods), do not have this effect, so I tend to push my patients to consume more of these, up to about 60 percent of total fat intake. The point is not necessarily to limit fat overall but to shift to fats that promote a better lipid profile.
risk is proportional to apoB exposure over time. The sooner we lower apoB exposure, thus lowering risk, the more the benefits compound over time—and the greater our overall risk reduction.
Brief Overview of Lipid-Lowering Medications
While there are seven statins on the market, I tend to start with rosuvastatin(Crestor) and only pivot from that if there is some negative effect from the drug(e.g., a symptom or biomarker). My goal is aggressive: as rationalized by Peter Libby, I want to knock someone’s apoB concentration down to 20 or 30 mg/dL, about where it would be for a child. For people who can’t tolerate statins, I like to use a newer drug, called bempedoic acid(Nexletol), which manipulates a different pathway to accomplish much the same end: inhibiting cholesterol synthesis as a way to force the liver to increase LDLR and therefore LDL clearance.
Triglycerides also contribute to the apoB particle burden, because they are largely transported in VLDLs. Our dietary interventions are aimed at reducing triglycerides, but in cases where nutritional changes are insufficient, and in cases where genetics render dietary interventions useless, fibrates are the drug of choice. Ethyl eicosapentaenoic acid(Vascepa), a drug derived from fish oil and consisting of four grams of pharmaceutical-grade eicosapentaenoic acid(EPA), also has FDA approval to reduce LDL in patients with elevated triglycerides.

Chapter 8: The Runaway Cell: New Ways to Address the Killer That Is Cancer

database—cancer is the second leading cause of death in the United States, right behind heart disease. Together, these two conditions account for almost one in every two American deaths.
three-part strategy for dealing with cancer. Our first and most obvious wish is to avoid getting cancer at all, like the centenarians—in other words, prevention. But cancer prevention is tricky, because we do not yet fully understand what drives the initiation and progression of the disease with the same resolution that we have for atherosclerosis. Further, plain bad luck seems to play a major role in this largely stochastic process. But we do have some clues,
Next is the use of newer and smarter treatments targeting cancer’s manifold weaknesses, including the insatiable metabolic hunger of fast-growing cancer cells and their vulnerability to new immune-based therapies,
Third, and perhaps most importantly, we need to try to detect cancer as early as possible so that our treatments can be deployed more effectively. I advocate early, aggressive, and broad screening for my patients—such as colonoscopy(or other colorectal cancer screening) at age forty, as opposed to the standard recommendation of forty-five or fifty—because the evidence is overwhelming that it’s much easier to deal with most cancers in their early stages. I am also cautiously optimistic about pairing these tried-and-true staples of cancer screening with emerging methods, such as“liquid biopsies,” which can detect trace amounts of cancer-cell DNA via a simple blood test.
Cancer cells are different from normal cells in two important ways. Contrary to popular belief, cancer cells don’t grow faster than their noncancerous counterparts; they just don’t stop growing when they are supposed to.
The second property that defines cancer cells is their ability to travel from one part of the body to a distant site where they should not be. This is called metastasis, and it is what enables a cancerous cell in the breast to spread to the lung. This spreading is what turns a cancer from a local, manageable problem to a fatal, systemic disease.
The American Cancer Society reports that excess weight is a leading risk factor for both cancer cases and deaths, second only to smoking. Globally, about 12 to 13 percent of all cancer cases are thought to be attributable to obesity.
What I am saying is that we don’t want to be anywhere on that spectrum of insulin resistance to type 2 diabetes, where our cancer risk is clearly elevated. To me, this is the low-hanging fruit of cancer prevention, right up there with quitting smoking. Getting our metabolic health in order is essential to our anticancer strategy.
Sandra was a very motivated patient. From the day of her diagnosis, she had become obsessed with doing anything possible to stack the odds in her favor. She devoured everything she could read on the impact of nutrition on cancer, and she had concluded that a diet that reduced insulin and IGF-1 would aid in her treatment. So she worked out a regimen that consisted primarily of leafy vegetables, olive oil, avocados, nuts, and modest amounts of protein, mostly from fish, eggs, and poultry. The diet was just as notable for what it did not contain: added sugar and refined carbohydrates. All along, she underwent frequent blood tests to make sure her insulin and IGF-1 levels stayed low, which they did. Over the next few years, every other woman who was enrolled at her trial site had died. Every single one. The patients had been on state-of-the-art chemotherapy plus the PI3K inhibitor, yet their metastatic breast cancer had still overtaken them.
This study and the Mukherjee-Cantley study we discussed earlier also point toward another important takeaway from this chapter, which is that there is rarely only one way to treat a cancer successfully. As Keith Flaherty, a medical oncologist and the director of developmental therapeutics at Massachusetts General Hospital, explained to me, the best strategy to target cancer is likely by targeting multiple vulnerabilities of the disease at one time, or in sequence. By stacking different therapies, such as combining a PI3K inhibitor with a ketogenic diet, we can attack cancer on multiple fronts, while also minimizing the likelihood of the cancer developing resistance(via mutations) to any single treatment.
About a third of cancers can be treated with immunotherapy, and of those patients, just one-quarter will actually benefit(i.e., survive). That means that only 8 percent of potential cancer deaths could be prevented by immunotherapy,
The final and perhaps most important tool in our anticancer arsenal is early, aggressive screening. This remains a controversial topic, but the evidence is overwhelming that catching cancer early is almost always net beneficial.
Even so, mainstream guidelines have been waving people away from some types of early screening, such as mammography in women and blood testing for PSA, prostate-specific antigen, in men. In part this has to do with cost, and in part this has to do with the risk of false positives that may lead to unnecessary or even dangerous treatment(entailing further costs). Both are valid issues, but let’s set aside the cost issue and focus on the false-positive problem.
So it is foolish to rely on just one test, not only for breast cancer but in many other areas as well. We need to think in terms of stacking test modalities—incorporating ultrasound and MRI in addition to mammography, for example, when looking for breast cancer. With multiple tests, our resolution improves and fewer unnecessary procedures will be performed.
This is what makes a colonoscopy such a powerful tool. The endoscopist is able not only to spot potentially cancerous growths before they become dangerous but also to intervene on the spot, using instruments on the colonoscope to remove polyps for later examination. It combines screening and surgery into one procedure. It’s an amazing tool.
there is ample evidence out there that age fifty may be too old for a first screening, even in patients with average risk factors(that is, no family history of colon cancer and no personal history of inflammatory bowel disease). About 70 percent of people who are diagnosed with CRC before the age of fifty have no family history or hereditary conditions linked to the disease. In 2020, some 3,640 Americans died from colorectal cancer before they turned fifty—and given the slow-moving nature of the disease, it’s likely that many of those who died later than that already had the disease on their fiftieth birthday. This is why the American Cancer Society updated its guidelines in 2018, lowering the age to forty-five for people at average risk. In my practice, we go further, typically encouraging average-risk individuals to get a colonoscopy by age forty—and even sooner if anything in their history suggests they may be at higher risk. We then repeat the procedure as often as every two to three years, depending on the findings from the previous colonoscopy.
Why do I generally recommend a colonoscopy before the guidelines do? Mostly because, of all the major cancers, colorectal cancer is one of the easiest to detect, with the greatest payoff in terms of risk reduction. It remains one of the top five deadliest cancers in the United States, behind lung(#1) and breast/prostate(#2 for women/men), and just ahead of pancreas(#4) and liver(#5) cancers.
Of all the Horsemen, cancer is probably the hardest to prevent. It is probably also the one where bad luck in various forms plays the greatest role, such as in the form of accumulated somatic mutations. The only modifiable risks that really stand out in the data are smoking, insulin resistance, and obesity(all to be avoided)—and maybe pollution(air, water, etc.), but the data here are less clear.

Chapter 9: Chasing Memory: Understanding Alzheimer’s Disease and Other Neurodegenerative Diseases

there are a few things that I immediately scan for when I get a new patient’s results back. Among them is their level of Lp(a), the high-risk lipoprotein that we talked about in chapter 7, along with their apoB concentration. A third thing that I always check is their APOE genotype, the gene related to Alzheimer’s disease risk
Can Neurodegenerative Disease Be Prevented?
While female Alzheimer’s patients outnumber men by two to one, the reverse holds true for Lewy body dementia and Parkinson’s, both of which are twice as prevalent in men. Yet Parkinson’s also appears to progress more rapidly in women than in men, for reasons that are not clear.
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.
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 evidence suggests that tasks or activities that present more varied challenges, requiring more nimble thinking and processing, are more productive at building and maintaining cognitive reserve. Simply doing a crossword puzzle every day, on the other hand, seems only to make people better at doing crossword puzzles. The same goes for movement reserve: dancing appears to be more effective than walking at delaying symptoms of Parkinson’s disease, possibly because it involves more complex movement.
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 are computers that are bigger and faster, but no machine yet made by man can match the brain’s ability to intuit and learn, much less feel or create. No computer possesses anything approaching the multidimensionality of the human self. Where a computer is powered by electricity, the beautiful machine that is the human brain depends on a steady supply of glucose and oxygen, delivered via a huge and delicate network of blood vessels.
On top of this, brain cells metabolize glucose in a different way from the rest of the body; they do not depend on insulin, instead absorbing circulating glucose directly, via transporters that essentially open a gate in the cell membrane. This enables the brain to take top priority to fuel itself when blood glucose levels are low. If we lack new sources of glucose, the brain’s preferred fuel, the liver converts our fat into ketone bodies, as an alternative energy source that can sustain us for a very long time, depending on the extent of our fat stores.(Unlike muscle or liver, the brain itself does not store energy.) When our fat runs out, we will begin to consume our own muscle tissue, then our other organs, and even bone, all in order to keep the brain running at all costs. The brain is the last thing to shut off.
Having type 2 diabetes doubles or triples your risk of developing Alzheimer’s disease, about the same as having one copy of the APOE e4 gene.
e4 itself could help drive the very same metabolic dysfunction that also increases risk of dementia. At the same time, it appears to intensify the damage done to the brain by metabolic dysfunction. Researchers have found that in high-glucose environments, the aberrant form of the APOE protein encoded by APOE e4 works to block insulin receptors in the brain, forming sticky clumps or aggregates that prevent neurons from taking in energy.
I actually think we know more about preventing Alzheimer’s than we do about preventing cancer. Our primary tool for preventing cancer is to not smoke and to keep our metabolic health on track, but that’s a very broad-brush approach that only takes us so far. We still need to screen aggressively and hope we somehow manage to find any cancers that do develop before it’s too late. With Alzheimer’s disease, we have a much larger preventive tool kit at our disposal, and much better diagnostic methods as well. It’s relatively easy to spot cognitive decline in its early stages, if we’re looking carefully. And we’re learning more about genetic factors as well, including those that at least partially offset high-risk genes like APOE e4.
Our goal is to improve glucose metabolism, inflammation, and oxidative stress. One possible recommendation for someone like her would be to switch to a Mediterranean-style diet, relying on more monounsaturated fats and fewer refined carbohydrates, in addition to regular consumption of fatty fish. 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.
The single most powerful item in our preventive tool kit is exercise, which has a two-pronged impact on Alzheimer’s disease risk: it helps maintain glucose homeostasis, and it improves the health of our vasculature. So along with changing Stephanie’s diet, we put her back on a regular exercise program, focusing on steady endurance exercise to improve her mitochondrial efficiency. This had a side benefit in that it helped manage her off-the-charts high cortisol levels, due to stress; stress and anxiety-related risk seem more significant in females.
And there appeared to be no upper limit or“plateau” to this relationship; the greater someone’s grip strength, the lower their risk of dementia.
I now tell patients that exercise is, full stop and hands down, the best tool we have in the neurodegeneration prevention tool kit.
Another surprising intervention that may help reduce systemic inflammation, and possibly Alzheimer’s disease risk, is brushing and flossing one’s teeth.(You heard me: Floss.) There is a growing body of research linking oral health, particularly the state of one’s gum tissue, with overall health.
better oral health correlates strongly with better overall health, particularly in terms of cardiovascular disease risk, so I pay much more attention to flossing and gum health than I used to.)
Broadly, our strategy should be based on the following principles:
WHAT’S GOOD FOR THE HEART IS GOOD FOR THE BRAIN. That is, vascular health(meaning low apoB, low inflammation, and low oxidative stress) is crucial to brain health.
WHAT’S GOOD FOR THE LIVER(AND PANCREAS) IS GOOD FOR THE BRAIN. Metabolic health is crucial to brain health.
TIME IS KEY. We need to think about prevention early, and the more the deck is stacked against you genetically, the harder you need to work and the sooner you need to start. As with cardiovascular disease, we need to play a very long game.
OUR MOST POWERFUL TOOL FOR PREVENTING COGNITIVE DECLINE IS EXERCISE. We’ve talked a lot about diet and metabolism, but exercise appears to act in multiple ways(vascular, metabolic) to preserve brain health;

Chapter 11: Exercise: The Most Powerful Longevity Drug

There are reams of data supporting the notion that even a fairly minimal amount of exercise can lengthen your life by several years. It delays the onset of chronic diseases, pretty much across the board, but it is also amazingly effective at extending and improving healthspan.
So if you adopt only one new set of habits based on reading this book, it must be in the realm of exercise. If you currently exercise, you will likely want to rethink and modify your program. 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.
Let’s start with cardiorespiratory or aerobic fitness. This means how efficiently your body can deliver oxygen to your muscles, and how efficiently your muscles can extract that oxygen, enabling you to run(or walk) or cycle or swim long distances. It also comes into play in daily life, manifesting as physical stamina. The more aerobically fit you are, the more energy you will have for whatever you enjoy doing—even if your favorite activity is shopping. It turns out that peak aerobic cardiorespiratory fitness, measured in terms of VO2 max, is perhaps the single most powerful marker for longevity. VO2 max represents the maximum rate at which a person can utilize oxygen. This is measured, naturally, while a person is exercising at essentially their upper limit of effort.(If you’ve ever had this test done, you will know just how unpleasant it is.) The more oxygen your body is able to use, the higher your VO2 max.
The fitter I am, the more oxygen I can consume to make ATP, and the faster I can run up that hill. Eventually, I will reach the point at which I just can’t produce any more energy via oxygen-dependent pathways, and I’ll be forced to switch over to less efficient, less sustainable ways of producing power, such as those used in sprinting. The amount of oxygen that I am using at this level of effort represents my VO2 max.
An average forty-five-year-old man will have a VO2 max around 40 ml/kg/min, while an elite endurance athlete will likely score in the high 60s and above. An unfit person in their thirties or forties, on the other hand, might score only in the high 20s on a VO2 max test, according to Mike Joyner, an exercise physiologist and researcher at the Mayo Clinic. They simply won’t be able to run up that hill at all.[*2] The higher someone’s VO2 max, the more oxygen they can consume to make ATP, and the faster they can ride or run—in short, the more they can do.
A 2018 study in JAMA that followed more than 120,000 people found that higher VO2 max(measured via a treadmill test) was associated with lower mortality across the board.
Consider this: A person who smokes has a 40 percent greater risk of all-cause mortality(that is, risk of dying at any moment) than someone who does not smoke, representing a hazard ratio or(HR) of 1.40. This study found that someone of below-average VO2 max for their age and sex(that is, between the 25th and 50th percentiles) is at double the risk of all-cause mortality compared to someone in the top quartile(75th to 97.6th percentiles). Thus, poor cardiorespiratory fitness carries a greater relative risk of death than smoking. That’s only the beginning. Someone in the bottom quartile of VO2 max for their age group(i.e., the least fit 25 percent) is nearly four times likelier to die than someone in the top quartile—and five times likelier to die than a person with elite-level(top 2.3 percent) VO2 max. That’s stunning. These benefits are not limited to the very fittest people either; even just climbing from the bottom 25 percent into the 25th to 50th percentile(e.g., least fit to below average) means you have cut your risk of death nearly in half, according to this study.
The strong association between cardiorespiratory fitness and longevity has long been known. It might surprise you, as it did me, to learn that muscle may be almost as powerfully correlated with living longer. A ten-year observational study of roughly 4,500 subjects ages fifty and older found that those with low muscle mass were at 40 to 50 percent greater risk of mortality than controls, over the study period. Further analysis revealed that it’s not the mere muscle mass that matters but the strength of those muscles, their ability to generate force.
Strength may even trump cardiorespiratory fitness, at least one study suggests. Researchers following a group of approximately 1,500 men over forty with hypertension, for an average of about eighteen years, found that even if a man was in the bottom half of cardiorespiratory fitness, his risk of all-cause mortality was still almost 48 percent lower if he was in the top third of the group in terms of strength versus the bottom third.[*4]
exercise strengthens the heart and helps maintain the circulatory system. As we’ll see later in this chapter, it also improves the health of the mitochondria, the crucial little organelles that produce energy in our cells(among other things). That, in turn, improves our ability to metabolize both glucose and fat. Having more muscle mass and stronger muscles helps support and protect the body—and also maintains metabolic health, because those muscles consume energy efficiently.
When we are exercising, our muscles generate molecules known as cytokines that send signals to other parts of our bodies, helping to strengthen our immune system and stimulate the growth of new muscle and stronger bones. Endurance exercise such as running or cycling helps generate another potent molecule called brain-derived neurotrophic factor, or BDNF, that improves the health and function of the hippocampus, a part of the brain that plays an essential role in memory. Exercise helps keep the brain vasculature healthy, and it may also help preserve brain volume.
But both physical activity levels and muscle mass decline steeply after about age sixty-five, and then even more steeply after about seventy-five. It’s as if people just fall off a cliff sometime in their mid-seventies.
Continued muscle loss and inactivity literally puts our lives at risk. Seniors with the least muscle mass(also known as lean mass) are at the greatest risk of dying from all causes. One Chilean study looked at about one thousand men and four hundred women, with an average age of seventy-four at enrollment. The researchers divided the subjects into quartiles, based on their appendicular lean mass index(technically, the muscle mass of their extremities, arms and legs, normalized to height), and followed them over time. After twelve years, approximately 50 percent of those in the lowest quartile were dead, compared to only 20 percent of those in the highest quartile for lean mass. While we can’t establish causality here, the strength and reproducibility of findings like this suggest this is more than just a correlation. Muscle helps us survive old age.
Having more muscle mass on your exoskeleton appears to protect you from all kinds of trouble, even adverse outcomes following surgery—but most important, it is highly correlated with a lower risk of falling, a leading but oft-ignored cause of death and disability in the elderly. As figure 10 reveals, falls are by far the leading cause of accidental deaths in those ages sixty-five and older—and this is without even counting the people who die three or six or twelve months after their nonfatal but still serious fall pushed them into a long and painful decline. Eight hundred thousand older people are hospitalized for falls each year, according to the CDC.
We can avoid it with the help of this powerful“drug” called exercise that miraculously extends lifespan and improves healthspan. The difference is that it requires much more work and knowledge than simply taking a pill. But the more effort you’re willing to put in now, the more benefit you’ll reap in the future. This is why I place such an emphasis on weight training—and doing it now, no matter your age.
Think of the Centenarian Decathlon as the ten most important physical tasks you will want to be able to do for the rest of your life. Some of the items on the list resemble actual athletic events, while some are closer to activities of daily living, and still others might reflect your own personal interests. I find it useful because it helps us visualize, with great precision, exactly what kind of fitness we need to build and maintain as we get older. It creates a template for our training. I start by presenting my patients with a long list of physical tasks that might include some of the following: Hike 1.5 miles on a hilly trail. Get up off the floor under your own power, using a maximum of one arm for support. Pick up a young child from the floor. Carry two five-pound bags of groceries for five blocks. Lift a twenty-pound suitcase into the overhead compartment of a plane. Balance on one leg for thirty seconds, eyes open.(Bonus points: eyes closed, fifteen seconds.) Have sex. Climb four flights of stairs in three minutes. Open a jar. Do thirty consecutive jump-rope skips. The full list is much longer, with more than fifty different items, but you get the idea.
To lift that twenty-pound suitcase overhead when you are older means doing so with forty or fifty pounds now. To be able to climb four flights of stairs in your eighties means you should be able to pretty much sprint up those same stairs today. In every case, you need to be doing much more now, to armor yourself against the natural and precipitous decline in strength and aerobic capacity that you will undergo as you age.
My version of the Decathlon is tailored to my own particular interests, such as swimming and archery. It’s also fairly aggressive, I admit, reflecting the importance of a high level of fitness in my life. So I would probably add in some of the following events: Swim half a mile in twenty minutes. Walk with a thirty-pound dumbbell in each hand for one minute. Draw back and fire a fifty-pound compound bow. Do five pull-ups. Climb ninety steps in two minutes(VO2 max = 32). Dead-hang for one minute. Drive a race car within 5 to 8 percent of the pace I can do so today. Hike with a twenty-pound backpack for an hour. Carry my own luggage. Walk up a steep hill.
In the end, most people’s Centenarian Decathlons will probably overlap to a degree. Someone who enjoys stand-up paddleboarding, for example, would perhaps choose“events” focused around building core and cross-body strength. But she will likely be training the same muscle groups as I am doing for archery, and maintaining a similar degree of stamina and balance.

Chapter 12: Training 101: How to Prepare for the Centenarian Decathlon

The three dimensions in which we want to optimize our fitness are aerobic endurance and efficiency(aka cardio), strength, and stability.
When we say“cardio,” we are talking about not one thing, but a physiologic continuum, ranging from an easy walk to an all-out sprint. The various levels of intensity all count as cardio but are fueled by multiple different energy systems. For our purposes, we are interested in two particular regions of this continuum: long, steady endurance work, such as jogging or cycling or swimming, where we are training in what physiologists call zone 2, and maximal aerobic efforts, where VO2 max comes into play.
I consider stability to be just as important as aerobic fitness and strength. It’s a bit hard to define, but I think of stability as the solid foundation that enables us to do everything else that we do, without getting injured. Stability makes us bulletproof.
Aerobic Efficiency: Zone 2
Most people think that one of the primary benefits of exercise, if not the primary benefit, is that it“burns calories.” And it does, but we are more interested in a finer distinction—not calories, but fuels. How we utilize different fuels, glucose and fatty acids, is critical not only to our fitness but also to our metabolic and overall health. Aerobic exercise, done in a very specific way, improves our ability to utilize glucose and especially fat as fuel.
The key here are the mitochondria, those tiny little intracellular organelles that produce much of our energy. These cellular“engines” can burn both glucose and fat, and thus they are fundamental to our metabolic health. Healthy mitochondria are also important to maintaining the health of our brain, and to controlling potential bad actors like oxidative stress and inflammation. I am convinced that it is impossible to be healthy without also having healthy mitochondria, which is why I place a great deal of emphasis on long, steady endurance training in zone 2. Zone 2 is one of five levels of intensity used by coaches and trainers in endurance sports to structure their athletes’ training programs.
Typically, zone 1 is a walk in the park and zone 5(or 6, or 7) is an all-out sprint. Zone 2 is more or less the same in all training models: going at a speed slow enough that one can still maintain a conversation but fast enough that the conversation might be a little strained. It translates to aerobic activity at a pace somewhere between easy and moderate.
In San Millán’s view, healthy mitochondria are key to both athletic performance and metabolic health. Our mitochondria can convert both glucose and fatty acids to energy—but while glucose can be metabolized in multiple different ways, fatty acids can be converted to energy only in the mitochondria. Typically, someone working at a lower relative intensity will be burning more fat, while at higher intensities they would rely more on glucose. The healthier and more efficient your mitochondria, the greater your ability to utilize fat, which is by far the body’s most efficient and abundant fuel source. This ability to use both fuels, fat and glucose, is called“metabolic flexibility,” and it is what we want: in chapters 6 and 7, we saw how the relentless accumulation and spillover of fat drives conditions such as diabetes and cardiovascular disease. Healthy mitochondria(fostered by zone 2 training) help us keep this fat accumulation in check.
A few years ago, San Millán and his colleague George Brooks published a fascinating study that helps illustrate this point. They compared three groups of subjects: professional cyclists, moderately active healthy males, and sedentary men who met the criteria for the metabolic syndrome, meaning essentially that they were insulin resistant. They had each group ride a stationary bicycle at a given level of intensity relative to their fitness(about 80 percent of their maximum heart rate), while the scientists analyzed the amount of oxygen they consumed and the CO2 they exhaled in order to determine how efficiently they produced power—and what primary fuels they were using. The differences they found were striking. The professional cyclists could zoom along, producing a huge amount of power while still burning primarily fat. But the subjects with metabolic syndrome relied almost entirely on glucose for their fuel source, even from the first pedal stroke. They had virtually zero ability to tap into their fat stores, meaning they were metabolically inflexible: able to use only glucose but not fat. Obviously, these two groups—professional athletes and sedentary, unhealthy people—were as dissimilar as could be. San Millán’s insight was that the sedentary subjects needed to be training in a manner similar to the Tour de France–bound cyclists he worked with. A professional cyclist might spend thirty to thirty-five hours a week training on his or her bike, and 80 percent of that time in zone 2. For an athlete, this builds a foundation for all their other, more intense training.(The catch is that a professional rider’s zone 2 output feels like zone 5 for most people.)
As fundamental as zone 2 training is for professional cyclists, however, San Millán believes that it’s even more important for nonathletes, for two reasons. First, it builds a base of endurance for anything else you do in life, whether that is riding your bike in a one-hundred-mile century ride or playing with your kids or grandkids. The other reason is that he believes it plays a crucial role in preventing chronic disease by improving the health and efficiency of your mitochondria, which is why training aerobic endurance and efficiency(i.e., zone 2 work) is the first element of my Centenarian Decathlon training program. When we are exercising in zone 2, most of the work is being done by our type 1, or“slow-twitch,” muscle fibers. These are extremely dense with mitochondria and thus well-suited for slow-paced, efficient endurance work. We can go for a long time without feeling fatigued. If we pick up the pace, we begin to recruit more type 2(“fast-twitch”) muscle fibers, which are less efficient but more forceful. They also generate more lactate in the process, because of the way they create ATP. Lactate itself is not bad; trained athletes are able to recycle it as a type of fuel. The problem is that lactate becomes lactic acid when paired with hydrogen ions, which is what causes that acute burning you feel in your muscles[*1] during a hard effort.
In technical terms, San Millán describes zone 2 as the maximum level of effort that we can maintain without accumulating lactate. We still produce it, but we’re able to match production with clearance. The more efficient our mitochondrial“engine,” the more rapidly we can clear lactate, and the greater effort we can sustain while remaining in zone 2. If we are“feeling the burn” in this type of workout, then we are likely going too hard, creating more lactate than we can eliminate.
Because I am a numbers guy and I love biomarkers and feedback, 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. If I’m working too hard, lactate levels will rise, so I’ll slow down.(It’s sometimes tempting to go too hard in zone 2, because the workout feels relatively“easy” on good days.) I make a point of this because lactate is literally what defines zone 2. It’s all about keeping lactate levels steady in this range, and the effort sustainable. If you don’t happen to have a portable lactate meter on hand, like most people, there are other ways to estimate your zone 2 range that are reasonably accurate. If you know your maximum heart rate—not estimated, but your actual maximum, the highest number you’ve ever seen on a heart rate monitor—your zone 2 will correspond to between approximately 70 and 85 percent of that peak number, depending on your fitness levels. That’s a big range, so when starting people out, I prefer they rely on their rate of perceived exertion, or RPE, also known as the“talk test.” How hard are you working? How easy is it to speak? If you’re at the top of zone 2, you should be able to talk but not particularly interested in holding a conversation. If you can’t speak in complete sentences at all, you’re likely into zone 3, which means you’re going too hard, but if you can comfortably converse, you’re likely in zone 1, which is too easy.
Zone 2 output is highly variable, depending on one’s fitness. In San Millán and Brooks’s study, the professional cyclists produced about three hundred watts of power in zone 2, while the sedentary, metabolically unhealthy subjects could generate only about one hundred watts at the same relative level of intensity. That’s a huge difference. If we express this output in terms of watts per kilogram of body weight, the difference becomes even more stark: The seventy-kilogram cyclists put out more than four watts per kilogram of body weight, while the one-hundred-plus kilogram sedentary subjects could only manage about one watt per kilogram. This pronounced difference comes back to the fact that the unhealthy subjects’ mitochondria—their engine(s)—were much less efficient than those of the athletes, so they very quickly switched over from aerobic respiration, burning fat and glucose in the mitochondria with oxygen, to the much less efficient glycolysis, an energy-producing pathway that consumes only glucose and produces loads of lactate(similar to the way cancer cells produce energy, via the Warburg effect). Once we start producing energy this way, lactate accumulates and our effort quickly becomes unsustainable. There are other(fortunately rare) genetic diseases that target the mitochondria and produce far more severe sequelae, but in terms of mass-acquired chronic conditions, type 2 diabetes does a real number on the mitochondria, and San Millán’s data very elegantly demonstrate the disability that it creates.
Even when we are at rest, our lactate levels tell us much about our metabolic health. People with obesity or other metabolic problems will tend to have much higher resting lactate levels, a clear sign that their mitochondria are not functioning optimally, because they are already working too hard just to maintain baseline energy levels. This means that they are relying almost totally on glucose(or glycogen) for all their energy needs—and that they are totally unable to access their fat stores. It seems unjust, but the people who most need to burn their fat, the people with the most of it, are unable to unlock virtually any of that fat to use as energy, while the lean, well-trained professional athletes are able to do so easily because they possess greater metabolic flexibility(and healthier mitochondria).[*2]
Mitochondrial health becomes especially important as we grow older, because one of the most significant hallmarks of aging is a decline in the number and quality of our mitochondria. But the decline is not necessarily a one-way street. Mitochondria are incredibly plastic, and when we do aerobic exercise, it stimulates the creation of many new and more efficient mitochondria through a process called mitochondrial biogenesis, while eliminating ones that have become dysfunctional via a recycling process called mitophagy
A person who exercises frequently in zone 2 is improving their mitochondria with every run, swim, or bike ride. But if you don’t use them, you lose them.
This in turn explains why exercise, especially in zone 2, can be so effective in managing both type 1 and type 2 diabetes: It enables the body to essentially bypass insulin resistance in the muscles to draw down blood glucose levels.
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.
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.
One way to track your progression in zone 2 is to measure your output in watts at this level of intensity.(Many stationary bikes can measure your wattage as you ride.) You take your average wattage output for a zone 2 session and divide it by your weight to get your watts per kilogram, which is the number we care about.
These are rough benchmarks, but someone who is very fit will be able to produce 3 watts/kg, while professional cyclists put out 4 watts/kg and up. It’s not the number that matters, but how much you are improving over time.
I think of zone 2 as akin to building a foundation for a house. Most people will never see it, but it is nevertheless important work that helps support virtually everything else we do, in our exercise regimen and in our lives.
Besides improving mitochondrial health and glucose uptake and metabolic flexibility, and all those other good things, zone 2 training also increases your VO2 max somewhat. But if you really want to raise your VO2 max, you need to train this zone more specifically. Typically, for patients who are new to exercising, we introduce VO2 max training after about five or six months of steady zone 2 work.
One reason why I emphasize this so much is that this measure of peak aerobic capacity is powerfully correlated with longevity, as we saw in chapter 11. I have all my patients undergo VO2 max testing and then train to improve their score. Even if you are not competing in high-level endurance sports, your VO2 max is an important number that you can and should know.
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,
Now, here’s another way to look at it: In your sixties, you will have achieved the aerobic fitness of an average man in his fifties, a decade younger than you. If you can get it still higher, to 38 or 39, you will be the aerobic equivalent of an average thirty-something. This means you will have bought yourself a phase shift, like we talked about with the centenarians: you now have the fitness of someone decades younger than you.
Even if we are not out to set world records, the way we train VO2 max is pretty similar to the way elite athletes do it: by supplementing our zone 2 work with one or two VO2 max workouts per week. 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.[*4]
You want to make sure that you get as close to fully recovered as possible before beginning the next set. If you fail to recover sufficiently between sets, you will not be able to reach your peak effort in the working sets and you’ll consequently miss the desired adaptation. Also, be sure to give yourself enough time to warm up and then cool down from this intense effort.
a single workout per week in this zone will generally suffice. You’ll pretty quickly find that it boosts your performance across the rest of your exercise program as well—and, more importantly, in the rest of your life.
My point is that if you really stop to consider the kind of aerobic fitness that most people actually need in the course of their lives, it basically boils down to being really good at going slow for a long time, but also able to go hard and fast when needed. Training and maintaining a high level of aerobic fitness, and doing it now, is essential to preserving this range of function in your later years.
we lose muscle strength about two to three times more quickly than we lose muscle mass. And we lose power(strength x speed) two to three times faster than we lose strength. This is because the biggest single change in the aging muscle is the atrophy of our fast twitch or type 2 muscle fibers. Ergo, our training must be geared towards improving these with heavy resistance training. Daily life and zone 2 endurance work may be enough to prevent atrophy of type 1 fibers—but unless you are working against significant resistance, your type 2 muscle fibers will wither away.
Another metric that we track closely in our patients is their bone density(technically, bone mineral density or BMD). We measure BMD in every patient, every year, looking at both of their hips and their lumbar spine using DEXA. This also measures body fat and lean mass, so it’s a useful tool across all of the body-composition domains that we care about.
The fact is that bone density diminishes on a parallel trajectory to muscle mass, peaking as early as our late twenties before beginning a slow, steady decline. For women, this decline happens much more quickly once they hit menopause, if they are not on HRT(yet another reason we heavily favor HRT), because estrogen is essential for bone strength—in both men and women.
The takeaway for readers here is that your BMD is important, demanding at least as much attention as muscle mass, so you should at least check your BMD every few years.
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.
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.
A far more important measure of strength, I’ve concluded, is how much heavy stuff you can carry. I say this on the basis of my intuition but also research into hunter-gatherers and human evolution. Carrying is our superpower as a species. It’s one reason why we have thumbs, as well as long legs(and arms). No other animal is capable of carrying large objects from one place to another with any efficiency.
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).
One thing I specifically focus on when rucking is the hills. Going uphill gives me a chance to push my VO2 max energy system; first-time ruckers are amazed at how taxing it is to walk up a 15 percent grade with even twenty pounds on your back—and then walk back down.(A good goal is to be able to carry one-quarter to one-third of your body weight once you develop enough strength and stamina.
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.
there is an enormous body of literature linking better grip strength in midlife and beyond to decreased risk of overall mortality.[*5] The data are as robust as for VO2 max and muscle mass, in fact. Many studies suggest that grip strength—literally, how hard you can squeeze something with one hand—predicts how long you are likely to live, while low grip strength in the elderly is considered to be a symptom of sarcopenia, the age-related muscle atrophy we just discussed.
Training grip strength is not overly complicated. One of my favorite ways to do it is the classic farmer’s carry, where you walk for a minute or so with a loaded hex bar or a dumbbell or kettlebell in each hand.(Bonus points: Hold the kettlebell up vertically, keeping your wrist perfectly straight and elbow cocked at ninety degrees, as though you were carrying it through a crowded room.) One of the standards we ask of our male patients is that they can carry half their body weight in each hand(so full body weight in total) for at least one minute, and for our female patients we push for 75 percent of that weight. This is, obviously, a lofty goal—please don’t try to do it on your next visit to the gym. Some of our patients need as much as a year of training before they can even attempt this test.
farmer’s carry is pretty straightforward(weight in each hand, arms at sides, walk). The most important tip is to keep your shoulder blades down and back, not pulled up or hunched forward. If you are new to strength training, start with light weights, even as low as ten to fifteen pounds, and work up from there.
Another way to test your grip is by dead-hanging from a pull-up bar for as long as you can.(This is not an everyday exercise; rather, it’s a once-in-a-while test set.) 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, which we will talk about in the next chapter. Here we like to see men hang for at least two minutes and women for at least ninety seconds at the age of forty.(We reduce the goal slightly for each decade past forty.)
No discussion of strength is complete without mentioning concentric and especially eccentric loading. Again, eccentric loading means loading the muscle as it is lengthening, such as when you lower a bicep curl. It’s more intuitive when lifting something to focus on the concentric phase, such as curling the dumbbell with your biceps. This is the strength of a muscle getting shorter. One of the tests we have our patients perform is stepping onto and off an eighteen-inch block and taking three full seconds to reach the ground
In life, especially as we age, eccentric strength is where many people falter. Eccentric strength in the quads is what gives us the control we need when we are moving down an incline or walking down a set of stairs. It’s really important to keep us safe from falls and from orthopedic injuries. When we can eccentrically load our muscles, it also prevents our joints from taking excess stress, especially our knees.
Training eccentric strength is relatively simple. Big picture, it means focusing on the“down” phase of lifts ranging from pull-ups or pull-downs to deadlifts to rows; rucking downhill, carrying a weighted pack, is a great way to build both eccentric strength as well as spatial awareness and control, which are important parts of stability training
Pulling motions are how we exert our will on the world, whether we are hoisting a bag of groceries out of the car trunk or climbing El Capitan. It is an anchor movement. In the gym, it typically takes the form of rows, where you’re pulling the weight toward your body, or pull-ups.
Hip-hinging under high axial load, as with a heavy deadlift or squat, should be approached with care because of the risk of injury to the spine. This is why we have our patients work up to weighted hip-hinging very slowly, typically beginning with single-leg step-ups(see description below) and split-stance Romanian deadlift, either without weights or with only very light weights held in the hands.

Chapter 13: The Gospel of Stability: Relearning How to Move to Prevent Injury

That is, older people tend to exercise less, or not at all, because they simply can’t. They have hurt themselves in some way, at some point in their lives, and they just never got back on the horse. So they continued to decline.
According to the CDC, more than 27 percent of Americans over the age of forty-five report suffering from chronic pain, and about 10 to 12 percent say that pain has limited their activities on“most days or every day” during the previous six months.
the research and my own experience, support my first commandment of fitness: First, do thyself no harm. How do we do this? I think stability is the key ingredient. But it also requires a change in our mindset. We have to break out of the mentality that we must crush all our workouts every single time we go to the gym—doing the most reps, with the heaviest weights, day after day.
Stability is tricky to define precisely, but we intuitively know what it is. A technical definition might be: stability is the subconscious ability to harness, decelerate, or stop force. A stable person can react to internal or external stimuli to adjust position and muscular tension appropriately without a tremendous amount of conscious thought.
Stability training begins at the most basic level, with the breath. Breathing is about much more than simple gas exchange or even cardiorespiratory fitness. We exhale and inhale more than twenty thousand times per day, and the way in which we do so has tremendous influence on how we move our body, and even our mental state. How we breathe, as Beth puts it, is who we are.
One simple test that we ask of everyone, early on, looks like this: lie on your back, with one hand on your belly and the other on your chest, and just breathe normally, without putting any effort or thought into it. Notice which hand is rising and falling—is it the one on your chest, or your belly, or both(or neither)? Some people tend to flare their ribs and expand the chest on the inhale, while the belly is flat or even goes down. This creates tightness in the upper body and midline, and if the ribs stay flared, it’s difficult to achieve a full exhalation. Others breathe primarily“into” the belly, which tilts the pelvis forward. Still others are compressed, meaning they have difficulty moving air in and out altogether, because they cannot expand the rib cage with each inhalation. Beth identifies three types of breathing styles and associated phenotypes, which she jokingly calls“Mr. Stay Puft,” the“Sad Guy,” and the“Yogini”—each corresponding to a different set of stability strategies:
Mr. Stay Puft HYPERINFLATED. This person is an upper-chest breather who tends to pull up into spinal extension for both respiration and stability.
All of the above makes them quite susceptible to lower back pain, as well as tightness in their calves and hips.
Sad Guy COMPRESSED. Everything about them is sort of scrunched down and tight.
Yogini UNCONTROLLED. These folks have extreme passive range of motion(i.e., flexibility)—and extremely limited ability to control it.
Sometimes they have very high anxiety, and possibly also a breathing pattern disorder.
The way in which we breathe reflects how we interact with the world.“Making sure that your breath can be wide and three-dimensional and easy is vital for creating good, efficient, coordinated movement,” Beth says. Beth likes to start with an exercise that builds awareness of the breath and strengthens the diaphragm, which not only is important to breathing but is an important stabilizer in the body. She has the patient lie on their back with legs up on a bench or chair, and asks them to inhale as quietly as possible, with the least amount of movement possible. An ideal inhalation expands the entire rib cage—front, sides, and back—while the belly expands at the same time, allowing the respiratory and pelvic diaphragm to descend. The telltale is that it is quiet. A noisy inhale looks and feels more dramatic, as the neck, chest, or belly will move first, and the diaphragm cannot descend freely, making it more difficult to get air in. Now, exhale fully through pursed lips for maximum compression and air resistance, to strengthen the diaphragm. Blow all that air out, fully emptying yourself before your shoulders round or your face or jaw gets tense. Very soon, you will see how a full exhale prepares you for a good inhale, and vice versa. Repeat the process for five breaths and do two to three sets. Be sure to pause after each exhale for at least two counts to hold the isometric contraction—this is key, in DNS.
In DNS, you learn to think of the abdomen as a cylinder, surrounded by a wall of muscle, with the diaphragm on top and the pelvic floor below. When the cylinder is inflated, what you’re feeling is called intra-abdominal pressure, or IAP. It’s critical to true core activation and foundational to DNS training. Learning to fully pressurize the cylinder, by creating IAP, is important to safe movement because the cylinder effectively stabilizes the spine. Here’s another quick exercise to help you understand how to create IAP: breathe all the way in, so you feel as if you are inflating the cylinder on all sides and pulling air all the way down into your pelvic floor, the bottom of the cylinder. You’re not actually“breathing” there, in the sense that air is actually entering your pelvis; you’re seeking maximal lung expansion, which in turn sort of pushes your diaphragm down. With every inhale, focus on expanding the cylinder around its whole diameter and not merely raising the belly. If you do this correctly, you will feel the entire circumference of your shorts expand evenly around your waist, even in the back, not just in the front. When you exhale, the diaphragm comes back up, and the ribs should rotate inward again as your waistband contracts. This inhale develops tension, and as you exhale, pushing out air, you keep that muscular tension all around your cylinder wall. This intra-abdominal pressure is the basic foundation for everything that we do in stability training—a deadlift, squats, anything. It’s as if you have a plastic bottle: with the cap off, you can crush the bottle in one hand; with the cap on, there is too much pressure(i.e., stability) and the bottle can’t be crushed. I practice this 360-degree abdominal breathing every day, not only in the gym but also while I am at my desk.[*2]
Your“type” also indicates how you should work out, to some extent. The Stay Puft people tend to need more grounding through the feet and more work with weight in front of them so as to pull their shoulders and hips into a more neutral position. Beth typically has someone like me hold a weight in front of my body, a few inches in front of the sternum. This forces my center of mass back, more over my hips. Try it with a light dumbbell or even a milk carton, and you’ll see what I mean. It’s a subtle but noticeable change of position. With the Sad Guys and Gals, Beth tends to work more on cross-body rotation, having them swing the arms across the body to open up the chest and shoulders. She is cautious about loading the back and shoulders, preferring to begin with body weight exercises and split-leg work, such as a walking lunge with a reach, either across the body or to the ceiling, on each step. For the Yoginis, Beth recommends doing“closed-chain” exercises such as push-ups, using the floor or wall for support, as well as using exercise machines with a well-defined and limited range of motion, given their lack of joint control. Machines are important for these folks, and also for people who have not lifted much or at all, because machines keep their movements within safe boundaries. For the Yoginis, as well as for newbies in general, it’s important to become more aware of where they are in space, and where they are relative to their range of motion.
If the road to stability begins with the breath, it travels through the feet—the most fundamental point of contact between our bodies and the world. Our feet are literally the foundation for any movement we might make.
Going back to my race car analogy, our feet are like the tires, the only point of contact between the car and the road. The force of the engine, the stability and stiffness of the chassis, the skill of the driver—all of it is useless if the tires are not firmly gripping the track surface. I would argue that our feet are even more important to us than tires are to a car, as they also play a crucial role in dampening force before it reaches the knees, the hips, and the back(at least a car has suspension rods for that). Failing to pay attention to your feet, as most of us do, is like buying a McLaren Senna(my dream car) and then going to Walmart and getting the cheapest tires you can find. That’s what spending years in mushy shoes does to us.
To help reacquaint us with our feet, Beth Lewis likes to put me, and our patients, through a routine she calls“toe yoga.” Toe yoga(which I hate, by the way) is a series of exercises intended to improve the dexterity and intrinsic strength of our toes, as well as our ability to control them with our mind. Toe strength may not be something you think about when you go to the gym, but it should be: Our toes are crucial to walking, running, lifting, and, most importantly, decelerating or lowering. The big toe especially is necessary for the push-off in every stride. Lack of big-toe extension can cause gait dysfunction and can even be a limiting factor in getting up off the floor unassisted as we age. If toe strength is compromised, everything up the chain is more vulnerable—ankle, knee, hip, spine. Toe yoga is a lot harder than it sounds, which is why I’ve posted a video demonstration of this and other exercises at www.peterattiamd.com/outlive/videos.
One key test in our movement assessment is to have our patients stand with one foot in front of the other and try to balance. Now close your eyes and see how long you can hold the position. Ten seconds is a respectable time; in fact, the ability to balance on one leg at ages fifty and older has been correlated with future longevity, just like grip strength.(Pro tip: balancing becomes a lot easier if you first focus on grounding your feet, as described above.)
The structure we most want to protect—and a major focus of stability training in general—is the spine.
The spine has three parts: lumbar(lower back), thoracic(midback), and cervical(neck) spine. Radiologists see so much degeneration in the cervical spine, brought on by years of hunching forward to look at phones, that they have a name for it:“tech neck.” This is why it’s important to(a) put down the phone, and(b) try to develop some proprioceptive awareness around your spine, so that you really understand what extension(bending back) and flexion(bending forward) feel like, at the level of each single vertebra. The easiest way to start this process is to get on your hands and knees and go through an extremely slowed-down, controlled Cat/Cow sequence, similar to the basic yoga poses of the same names.[*4] The difference is that you have to really, really slow down, moving so slowly and deliberately from one end of your spine to the other that you can feel each individual vertebra changing position, all the way from your tailbone up to your neck, until your spine is bent like a sway-backed cow. Then reverse the movement, tilting your pelvis forward and bending your spine one vertebra at a time until your back is arched again, like a really scared cat.(Note: Inhale on Cow, exhale on Cat.)
But because there are so many different muscular attachments in the shoulder(no fewer than seventeen), it is much more vulnerable than the hip as I learned in my boxing and swimming careers. Beth taught me a simple exercise to help understand the importance of scapular positioning and control, a movement known as Scapular CARs, for controlled articular rotations: Stand with your feet shoulder-width apart and place a medium to light resistance band under your feet, one handle in each hand(a very light dumbbell also works). Keeping your arms at your sides, raise your shoulder blades, and then squeeze them back and together; this is retraction, which is where we want them to be when under load. Then drop them down your back. Finally, bring them forward to the starting point. We start out moving in squares like this, but the goal is to learn enough control that we can move our scapulae in smooth circles. A large part of what we’re working on in stability training is this kind of neuromuscular control, reestablishing the connection between our brain and key muscle groups and joints.
Because we are not“training” grip in our daily lives, we must be deliberate in our workouts, focusing on initiating movement with the hands and utilizing all the fingers with our upper body movements. Adding carries to your training is a great way to train grip, but it is important always to be mindful of what your fingers are doing and how force is being transmitted through them. One way that Beth likes to illustrate the importance of this is via a basic bicep curl with a(light) dumbbell. First, try the curl with your wrist bent slightly backward, just a bit out of line with your forearm. Now try the same bicep curl with your wrist straight. Which one felt stronger and more powerful? Which one felt like the fingers were more involved? It’s about building awareness of the importance of your fingers, as the last link in the chain.
One more note: Trainers can be useful for some purposes, such as basic instruction, accountability, and motivation, but we discourage patients from becoming overly reliant on trainers to tell them exactly what to do every single time they work out. I liken this to learning to swim in a wetsuit. Initially, a wetsuit can help give someone confidence because of the additional flotation it provides. But over the longer term, a wetsuit robs you of the need to figure out your balance in the water. Balance is the real challenge with swimming, because our center of mass is way off from our center of volume, causing our hips to sink. Good swimmers learn to overcome this imbalance with training. But if you never take off the wetsuit, you will never learn how to fix this problem.
I would urge you to film yourself working out from time to time, to compare what you think you are doing to what you are actually doing with your body. I do this daily—my phone on the tripod is one of my most valuable pieces of equipment in the gym. I film my ten most important sets each day and watch the video between sets, to compare what I see to what I think I was doing. Over time, that gap has been narrowing.
Hip-Hinging 101: How to Do a Step-Up
I see that a lot among my own patients: they trade health for wealth. Then they reach a certain age and realize they are on a bad path. This was Barry: After spending basically fifty years sitting in a chair, he retired and it dawned on him that he was in terrible shape. Not only was his physical capacity very limited, but he was in almost constant pain. He was then closing in on eighty years old and looking at some painful years ahead—a bad Marginal Decade. He began to wonder: Why had he worked so hard? In the state he was in, retirement no longer seemed very appealing.
(For a video demonstration of the Barry Get-Up, please visit www.peterattiamd.com/outlive/videos.) Everyone should be able to do it.
Back when I used to fly every week, I tried a clever trick that Michael Rintala showed me: put two tennis balls in an athletic sock about four to six inches apart, and position them just about at the level of my kidneys, or where my thoracic spine meets my lumbar spine. Then, with every breath I try to make sure I expand fully enough to feel the tennis balls on both sides. The idea is that it cues your breathing. When I did this, I could get off a five-hour flight and feel as if I had not been sitting for longer than about five minutes.(It also kept my seatmates from talking to me when I was trying to work.) It’s worth trying on a long flight or drive.
If you really want to go all in on toe yoga, get a set of“toe spacers,” which help restore the toes to a more natural, spread position, particularly in people with bunions or other shoe-related issues.

Chapter 14: Nutrition 3.0: You Say Potato, I Say “Nutritional Biochemistry”

It’s not about telling you what to eat; it’s about figuring out what works for your body and your goals—and, just as important, what you can stick to.
What problem are we trying to solve here? What is our goal with Nutrition 3.0? I think it boils down to the simple questions that we posited in chapter 10: Are you undernourished, or overnourished? Are you undermuscled, or adequately muscled? Are you metabolically healthy or not?
When my patients are undernourished, it’s typically because they are not taking in enough protein to sustain muscle mass, which as we saw in the previous chapters is a crucial determinant of both lifespan and healthspan. So any dietary intervention that compromises muscle, or lean body mass, is a nonstarter—for both the under-and overnourished groups.
Nutrition is relatively simple, actually. It boils down to a few basic rules: don’t eat too many calories, or too few; consume sufficient protein and essential fats; obtain the vitamins and minerals you need; and avoid pathogens like E. coli and toxins like mercury or lead. Beyond that, we know relatively little with complete certainty. Read that sentence again, please. Directionally, a lot of the old cliché expressions are probably right: If your great-grandmother would not recognize it, you’re probably better off not eating it. If you bought it on the perimeter of the grocery store, it’s probably better than if you bought it in the middle of the store. Plants are very good to eat. Animal protein is“safe” to eat. We evolved as omnivores; ergo, most of us can probably find excellent health as omnivores.
The problem is that epidemiology is incapable of distinguishing between correlation and causation. This, aided and abetted by bad journalism, creates confusion.
Bad epidemiology so dominates our public discussion of nutrition that it has inspired a backlash by skeptics such as John Ioannidis of the Stanford Prevention Research Center, a crusader against bad science in all its forms. His basic argument is that food is so complex, made up of thousands of chemical compounds in millions of possible combinations that interact with human physiology in so many ways—in other words, nutritional biochemistry—that epidemiology is simply not up to the task of disentangling the effect of any individual nutrient or food. In an interview with the CBC, the normally soft-spoken Ioannidis was brutally direct:“Nutritional epidemiology is a scandal,” he said.“It should just go into the waste bin.” The true weakness of epidemiology, at least as a tool to extract reliable, causal information about human nutrition, is that such studies are almost always hopelessly confounded. The factors that determine our food choices and eating habits are unfathomably complex. They include genetics, social influences, economic factors, education, metabolic health, marketing, religion, and everything in between—and they are almost impossible to disentangle from the biochemical effects of the foods themselves.
the people who are still drinking in older age tend to do so because they are healthy, and not the other way around.
The group receiving the olive oil had about a one-third lower incidence(31 percent) of stroke, heart attack, and death than the low-fat group, and the mixed-nuts group showed a similar reduced risk(28 percent).
To me, perhaps the most vexing issue with diet and nutrition studies is the degree of variation between individuals that is found but often obscured.

Chapter 15: Putting Nutritional Biochemistry into Practice: How to Find the Right Eating Pattern for You

The elements that constitute the SAD are almost as devastating to most people as tobacco when consumed in large quantities, as intended: added sugar, highly refined carbohydrates with low fiber content, processed oils, and other very densely caloric foods. I should note that this does not mean all“processed” foods are bad. Almost everything we eat, aside from fresh vegetables, is processed to some degree. For example, cheese is a processed food, invented as a way to preserve milk, which would otherwise spoil quickly without refrigeration. What we’re really talking about, when we talk about the SAD, is junk food.
the SAD foils our key objectives with regard to nutrition: it induces us to eat more than we need to, becoming overnourished, while its preponderance of low-quality, ultraprocessed ingredients tends to displace other nutrients that we need, such as protein, to maintain optimal health. The SAD disrupts the body’s metabolic equilibrium. It places enormous strain on our ability to control our blood glucose levels, and causes us to store fat when we should be utilizing it.
Once you strip away the labels and the ideology, almost all diets rely on at least one of the following three strategies to accomplish this: CALORIC RESTRICTION, or CR: eating less in total, but without attention to what is being eaten or when it’s being eaten DIETARY RESTRICTION, or DR: eating less of some particular element(s) within the diet(e.g., meat, sugar, fats) TIME RESTRICTION, or TR: restricting eating to certain times, up to and including multiday fasting
From the standpoint of pure efficacy, CR or caloric restriction is the winner, hands down.
One not uncommon scenario that we see with TR is that a person loses weight on the scale, but their body composition alters for the worse: they lose lean mass(muscle) while their body fat stays the same or even increases.
One slight advantage is that calorie counting is agnostic to food choices; you can eat whatever you want so long as you stay within your daily allowance. But if you make too many poor decisions, you will be very hungry, so buyer beware. You can lose weight on a restricted-calorie diet consisting only of Snickers bars, but you will feel much better if you opt for steamed broccoli and chicken breasts instead.
Taken together, then, what do these two monkey studies have to tell us about nutritional biochemistry? Avoiding diabetes and related metabolic dysfunction—especially by eliminating or reducing junk food—is very important to longevity. There appears to be a strong link between calories and cancer, the leading cause of death in the control monkeys in both studies. The CR monkeys had a 50 percent lower incidence of cancer. The quality of the food you eat could be as important as the quantity. If you’re eating the SAD, then you should eat much less of it. Conversely, if your diet is high quality to begin with, and you are metabolically healthy, then only a slight degree of caloric restriction—or simply not eating to excess—can still be beneficial.
I think this last point is key. These two studies suggest that if you are eating a higher-quality diet—and are metabolically healthy to begin with—then severe caloric restriction may not even be necessary.
Interestingly, the post facto analyses also revealed that the NIH control monkeys naturally consumed about 10 percent fewer calories per day than the Wisconsin controls, likely because their higher-quality diet left them feeling less hungry. The researchers speculated that even this very slight degree of caloric reduction may have been significant—certainly, it supports our thesis that it is better to avoid being overnourished.
The monkeys teach us that if you are metabolically healthy and not overnourished, like the NIH animals, then avoiding a crap diet may be all you need.
DR: The Nutritional Biochemistry“Diet”
Even if done correctly and strictly, DR can still result in overnutrition. If you cut out carbohydrates altogether but overdo it on the Wagyu steaks and bacon, you will fairly easily find yourself in a state of caloric excess. The key is to pick a strategy to which you can adhere but that also helps achieve your goals. This takes patience, some willpower, and a willingness to experiment.
A more significant issue with DR is that everyone’s metabolism is different. Some people will lose tremendous amounts of weight and improve their metabolic markers on a low-carbohydrate or ketogenic diet, while others will actually gain weight and see their lipid markers go haywire—on the exact same diet. Conversely, some people might lose weight on a low-fat diet, while others will gain weight.
A ketogenic diet means restricting carbohydrates to such an extent that the body begins metabolizing fat into“ketone bodies” that the muscles and brain can utilize as fuel.
I’ve had more than one patient for whom a ketogenic diet has completely failed. They didn’t lose weight, and their liver enzymes and other biomarkers failed to improve. Or they found it impossible to sustain.
The real art to dietary restriction, Nutrition 3.0–style, is not picking which evil foods we’re eliminating. Rather, it’s finding the best mix of macronutrients for our patient—coming up with an eating pattern that helps them achieve their goals, in a way that they can sustain. This is a tricky balancing act, and it requires us(once again) to forget about labels and viewpoints and drill down into nutritional biochemistry. The way we do this is by manipulating our four macronutrients: alcohol, carbohydrates, protein, and fat. How well do you tolerate carbohydrates? How much protein do you require? What sorts of fats suit you best? How many calories do you require each day? What is the optimal combination for you?
Alcohol
alcohol should be considered as its own category of macronutrient because it is so widely consumed, it has such potent effects on our metabolism, and it is so calorically dense at 7 kcal/g(closer to the 9 kcal/g of fat than the 4 kcal/g of both protein and carbohydrate).
Alcohol serves no nutritional or health purpose but is a purely hedonic pleasure that needs to be managed. It’s especially disruptive for people who are overnourished, for three reasons: it’s an“empty” calorie source that offers zero nutrition value; the oxidation of ethanol delays fat oxidation, which is the exact opposite of what we want if we’re trying to lose fat mass; and drinking alcohol very often leads to mindless eating.
I also believe that drinking alcohol is a net negative for longevity. Ethanol is a potent carcinogen, and chronic drinking has strong associations with Alzheimer’s disease, mainly via its negative effect on sleep, but possibly via additional mechanisms. Like fructose, alcohol is preferentially metabolized in the liver, with well-known long-term consequences in those who drink to excess. Last, it loosens inhibitions around other kinds of food consumption; give me a few drinks, and the next thing you know I’m elbow-deep in the Pringles can as I pace around the pantry looking for my next snack.
I strongly urge my patients to limit alcohol to fewer than seven servings per week, and ideally no more than two on any given day, and I manage to do a pretty good job adhering to this rule myself.
Carbohydrates
Carbohydrates are our primary energy source. In digestion, most carbohydrates are broken down to glucose, which is consumed by all cells to create energy in the form of ATP. Excess glucose, beyond what we need immediately, can be stored in the liver or muscles as glycogen for near-term use or socked away in adipose tissue(or other places) as fat. This decision is made with the help of the hormone insulin, which surges in response to the increase in blood glucose.
We already know that it’s not good to consume excessive calories. In the form of carbohydrates, those extra calories can cause a multitude of problems, from NAFLD to insulin resistance to type 2 diabetes, as we saw in chapter 6. We know that elevated blood glucose, over a long enough period of time, amplifies the risk of all the Horsemen.
Each person will respond differently to an influx of glucose. Too much glucose(or carbohydrate) for one person might be barely enough for another.
Now we have a tool to help us understand our own individual carbohydrate tolerance and how we respond to specific foods. This is called continuous glucose monitoring, or CGM, and it has become a very important part of my armamentarium in recent years.[*2]
The power of CGM is that it enables us to view a person’s response to carbohydrate consumption in real time and make changes rapidly to flatten the curve and lower the average. Real-time blood glucose serves as a decent proxy for the insulin response, which we also look to minimize. And, last, I find that it is much more accurate, and more actionable, than HbA1c, the traditional blood test used to estimate average blood glucose over time.
Typically, my healthy patients need to use CGM only for a month or two before they begin to understand what foods are spiking their glucose(and insulin) and how to adjust their eating pattern to obtain a more stable glucose curve. Once they have this knowledge, many of them no longer need CGM. It’s a worthwhile investment.
When I’ve put my patients on CGM, I’ve observed that there are two distinct phases to the process. The first is the insight phase, where you learn how different foods, exercise, sleep(especially lack thereof), and stress affect your glucose readings in real time. The benefit of this information can’t be overstated. Almost always, patients are stunned to see how some of their favorite foods send their glucose soaring, then crashing back to earth. This leads to the second phase, which is what I call the behavior phase. Here you mostly know how your glucose is going to respond to that bag of potato chips, and that knowledge is what prevents you from mindlessly eating it. I’ve found that CGM powerfully activates the Hawthorne effect, the long-observed phenomenon whereby people modify their behavior when they are being watched.
Typically, the first month or so of using CGM is dominated by insights. Thereafter, it’s really dominated by behavior modification. But both are quite powerful, and even after my patients stop using CGM, I find that the Hawthorne effect persists, because they know what that bag of potato chips will do to their glucose levels.
The real beauty of CGM is that it allows me to titrate a patient’s diet while remaining flexible. No longer do we need to try to hit some arbitrary target for carbohydrate or fat intake and hope for the best. Instead, we can observe in real time how their body handles the food they are eating. Is their average blood glucose a little bit high? Are they“spiking” above 160 mg/dL more often than I would like? Or could they perhaps tolerate a little bit more carbohydrate in their diet? Not everyone needs to restrict carbohydrates; some people can handle more than others, and some have a hard time sticking to severe carbohydrate restriction. Overall, I like to keep average glucose at or below 100 mg/dL, with a standard deviation of less than 15 mg/dL.[*5] These are aggressive goals: 100 mg/dL corresponds to an HbA1c of 5.1 percent, which is quite low. But I believe that the reward, in terms of lower risk of mortality and disease, is well worth it given the ample evidence in nondiabetics and diabetics alike.
The SAD sends most people’s CGM readings through the roof, as all the sugar and processed carbohydrates dump into the bloodstream at once, provoking a strong insulin response, which is what we don’t want. But seemingly“healthy” meals, for example certain kinds of vegetarian tacos, can also send glucose levels soaring in some people but not others. It also depends on when those carbs are eaten. If you eat 150 grams of carbohydrates as a serving of rice and beans in one sitting, that has a different effect than eating the same amount of rice and beans spread out over the day(and, obviously, much different from ingesting 150 grams of carbs in the form of Frosted MiniWheats). Also, everyone tends to be more insulin sensitive in the morning than in the evening, so it makes sense to front-load our carb consumption earlier in the day.
One thing CGM pretty quickly teaches you is that your carbohydrate tolerance is heavily influenced by other factors, especially your activity level and sleep. An ultraendurance athlete, someone who is training for long rides or swims or runs, can eat many more grams of carbs per day because they are blowing through those carbs every time they train—and they are also vastly increasing their ability to dispose of glucose via the muscles and their more-efficient mitochondria.[*6]
From years of experience with my own CGM and that of my patients, it still amazes me how much even one night of horrible sleep cripples our ability to dispose of glucose the next day.
Another surprising thing I’ve learned thanks to CGM is about what happens to a patient’s glucose levels during the night. If she goes to bed at, say, 80 mg/dL, but then her glucose ramps up to 110 for most of the night, that tells me that she is likely dealing with psychological stress. Stress prompts an elevation in cortisol, which in turn stimulates the liver to drip more glucose into circulation.
This doesn’t need to be an exercise in deprivation: one patient of mine gleefully confessed that his CGM, which he had only reluctantly agreed to wear, had given him a“superpower” to cheat. By eating certain“forbidden” types of carbohydrates only at certain times, either mixed with other foods or after exercising, he had figured out how he could hit his average glucose goals while still enjoying all the foods he loved.
If you scarf a large baked potato before working out, it will leave much less of a footprint on your daily glucose profile than if you eat it right before bedtime.
Lessons from Continuous Glucose Monitoring
Not all carbs are created equal. The more refined the carb(think dinner roll, potato chips), the faster and higher the glucose spike. Less processed carbohydrates and those with more fiber, on the other hand, blunt the glucose impact. I try to eat more than fifty grams of fiber per day.
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.
Timing, duration, and intensity of exercise matter a lot. In general, 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.
A good versus bad night of sleep makes a world of difference in terms of glucose control. All things equal, it appears that sleeping just five to six hours(versus eight hours) accounts for about a 10 to 20 mg/dL(that’s a lot!) jump in peak glucose response, and about 5 to 10 mg/dL in overall levels.
Stress, presumably, via cortisol and other stress hormones, has a surprising impact on blood glucose, even while one is fasting or restricting carbohydrates. It’s difficult to quantify, but the effect is most visible during sleep or periods long after meals.
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. Protein shakes, especially if low in fat, have a more pronounced effect(particularly if they contain sugar, obviously).
Stacking the above insights—in both directions, positive or negative—is very powerful. So if you’re stressed out, sleeping poorly, and unable to make time to exercise, be as careful as possible with what you eat.
Perhaps the most important insight of them all? Simply tracking my glucose has a positive impact on my eating behavior. I’ve come to appreciate the fact that CGM creates its own Hawthorne effect, a phenomenon where study subjects change their behavior because they are being observed. It makes me think twice when I see the bag of chocolate-covered raisins in the pantry, or anything else that might raise my blood glucose levels.
Protein
One clue lies in the name, which is derived from the Greek word proteios, meaning“primary.” Protein and amino acids are the essential building blocks of life.
Unlike carbs and fat, protein is not a primary source of energy. We do not rely on it in order to make ATP,[*8] nor do we store it the way we store fat(in fat cells) or glucose(as glycogen). If you consume more protein than you can synthesize into lean mass, you will simply excrete the excess in your urine as urea. Protein is all about structure. The twenty amino acids that make up proteins are the building blocks for our muscles, our enzymes, and many of the most important hormones in our body. They go into everything from growing and maintaining our hair, skin, and nails to helping form the antibodies in our immune system. On top of this, we must obtain nine of the twenty amino acids that we require from our diet, because we can’t synthesize them.
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.
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. So if someone weighs 180 pounds, they need to consume a minimum of 130 grams of protein per day, and ideally closer to 180 grams, especially if they are trying to add muscle mass. This is a lot of protein to eat, and the added challenge is that it should not be taken in one sitting but rather spread out over the day to avoid losing amino acids to oxidation(i.e., using them to produce energy when we want them to be available for muscle protein synthesis). The literature suggests that the ideal way to achieve this is by consuming four servings of protein per day, each at ~0.25 g/lb of body weight. A six-ounce serving of chicken, fish, or meat will provide about 40 to 45 grams(at about 7 grams of actual protein per ounce of meat), so our hypothetical 180-pound person should eat four such servings a day.
Most people don’t need to worry about consuming too much protein. It would require an overwhelming effort to eat more than 3.7 g/kg/day(or ~1.7 g/lb of body weight), defined as the safe upper limit of protein consumption(too much stress on the kidneys, for one).
There is some evidence that older people might require more protein because of the anabolic resistance that develops with age—that is, their greater difficulty in gaining muscle.
Older people in particular should try to keep track of their lean mass, such as via a body-composition-measuring scale(or better yet, DEXA scan), and adjust their protein intake upwards if lean mass declines. For me and my patients, this works out to four servings, as described, with at least one of them being a whey protein shake.(It’s very difficult for me to consume four actual meals. Typically, I will consume a protein shake, a high-protein snack, and two protein meals.)
Now, a word on plant protein. 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. The same is true of protein supplements. Whey protein isolate(from dairy) is richer in available amino acids than soy protein isolate. So if you forgo protein from animal sources, you need to do the math on your protein quality score.
Layman suggests focusing on a handful of important amino acids, such as leucine, lycine, and methionine. Focus on the absolute amount of these amino acids found in each meal, and be sure to get about three to four grams per day of leucine and lycine and at least one gram per day of methionine for maintenance of lean mass. If you are trying to increase lean mass, you’ll need even more leucine, closer to two to three grams per serving, four times per day.
Multiple studies suggest that the more protein we consume, in general, the better.
You could make the case that protein is a performance-enhancing macronutrient. Other studies have found that boosting protein intake even moderately above the RDA can slow the progressive loss of muscle mass in older people, including patients with heart failure and cachexia(wasting). Adding thirty grams of milk protein to the diet of frail elderly people, in another study, significantly improved their physical performance.
Beyond its role in building muscle, protein may have beneficial effects on our metabolism.
Eating protein also helps us feel satiated, inhibiting the release of the hunger-inducing hormone ghrelin, so we eat fewer calories overall.
In case my point here isn’t clear enough, let me restate it: don’t ignore protein. It’s the one macronutrient that is absolutely essential to our goals. There’s no minimum requirement for carbohydrates or fats(in practical terms), but if you shortchange protein, you will most certainly pay a price, particularly as you age.
Fat
Fats have long had a bad rap, on two counts: their high caloric content(9 kcal/g) and their role in raising LDL cholesterol and thus heart disease risk. Like carbohydrates, fats are often labeled“good” or“bad” on the basis of one’s tribal or political stripes; in actuality, of course, it’s not that black and white.
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. On a practical level, dietary fat also tends to leave one feeling more satiated than many types of carbohydrates, especially when combined with protein.
There are(broadly) three types of fats: saturated fatty acids(SFA), monounsaturated fatty acids(MUFA), and polyunsaturated fatty acids(PUFA).[*9]
The key thing to remember—and somehow this is almost always overlooked—is that virtually no food belongs to just one group of fats. Olive oil and safflower oil might be as close as you can get to a pure monounsaturated fat, while palm and coconut oil might be as close as you can get to a pure saturated fat, but all foods that contain fats typically contain all three categories of fat: PUFA, MUFA, and SFA.
The default fat state of most of my patients(i.e., their baseline fat consumption when they come to me) works out to about 30–40 percent each of MUFA and SFA, and 20–30 percent PUFA—and within that PUFA group, they are generally consuming about six to ten times more omega-6 than omega-3s and usually scant amounts of EPA and DHA. From our empirical observations and what I consider the most relevant literature, which is less than perfect, we try to boost MUFA closer to 50–55 percent, while cutting SFA down to 15–20 percent and adjusting total PUFA to fill the gap. We also boost EPA and DHA, those fatty acids that are likely important to brain and cardiovascular health, with marine fat sources and/or supplementation.
Putting all these changes into practice typically means eating more olive oil and avocados and nuts, cutting back on(but not necessarily eliminating) things like butter and lard, and reducing the omega-6-rich corn, soybean, and sunflower oils—while also looking for ways to increase high-omega-3 marine PUFAs from sources such as salmon and anchovies.[*12]
But once again, this is where the SAD, our modern food environment, comes in to complicate things. A hundred years ago, our ancestors would have gotten all their fat from animals, in the form of butter, lard, and tallow, and/or fruits, such as olives, coconuts, and avocados. They would have done so mostly by consuming these foods in their relatively natural state, and achieving a reasonable balance of fatty acids would have come fairly easily. Over the course of the twentieth century, advances in food-processing technology enabled us to chemically and mechanically extract oil from vegetables and seeds that otherwise would have been impossible to get. These new technologies suddenly allowed vast quantities of oils high in polyunsaturated fats, such as corn and cottonseed oil(aka linoleic acid, a PUFA), to flood into the food supply. Our per capita consumption of soybean oil, for example, has increased over a thousand-fold since 1909; meanwhile, studies have found that levels of linoleic acid found in human fat tissue have also increased, by 136 percent over the last half century. This industrial fat revolution also helped create trans fats, listed on ingredient labels as“partially hydrogenated vegetable oils”(think: margarine), which in turn helped enable the proliferation of the SAD, in part because they allowed foods to remain shelf stable for longer periods.
It is tempting to indict this massive proliferation of soybean and other seed oils as the dietary bad guy responsible for our obesity and metabolic syndrome epidemic. Anything that goes up by a thousand-fold in the same few decades in which our health goes to hell in a handbasket can’t be good, right? Even just a few years ago, I used to think this was the case. But the closer and closer I look at the data, the less and less sure I am that we can say much in this regard. In fact, the most comprehensive review of this topic, Polyunsaturated Fatty Acids for the Primary and Secondary Prevention of Cardiovascular Disease, published by the Cochrane Collaboration in 2018—a 422-page summation of all relevant literature from forty-nine studies, randomizing over twenty-four thousand patients—drew the following conclusion:“Increasing PUFA probably makes little or no difference(neither benefit nor harm) to our risk of death, and may make little or no difference to our risk of dying from cardiovascular disease. However, increasing PUFA probably slightly reduces our risk of heart disease events and of combined heart and stroke events(moderate-quality evidence).”
I could go on, but I think you get the point. The data are very unclear on this question, at least at the population level. As we discussed in the introduction to Medicine 3.0 and earlier in this chapter, any hope of using broad insights from evidence-based medicine is bound to fail when it comes to nutrition, because such population-level data cannot provide much value at the individual level when the effect sizes are so small, as they clearly are here. All Medicine 2.0 has to offer is broad contours: MUFA seems to be the“best” fat of the bunch(based on PREDIMED and the Lyon Heart study), and after that the meta-analyses suggest PUFA has a slight advantage over SFA. But beyond that, we are on our own.
Medicine 2.0 says this proves that nobody should eat saturated fats, period. Medicine 3.0 takes these data and says,“While it is obviously not good that our patient’s apoB has gone up this much, it now presents us with a choice: Should we consider medication to lower their apoB, or reduce their intake of saturated fats? Or both?”
In the final analysis, I tell my patients that on the basis of the least bad, least ambiguous data available, MUFAs are probably the fat that should make up most of our dietary fat mix, which means extra virgin olive oil and high-MUFA vegetable oils. After that, it’s kind of a toss-up, and the actual ratio of SFA and PUFA probably comes down to individual factors such as lipid response and measured inflammation. Finally, unless they are eating a lot of fatty fish, filling their coffers with marine omega-3 PUFA, they almost always need to take EPA and DHA supplements in capsule or oil form.
TR: The Case for(and Against) Fasting
There is no denying that some good things happen when we are not eating. Insulin drops dramatically because there are no incoming calories to trigger an insulin response. The liver is emptied of fat in fairly short order. Over time, within three days or so, the body enters a state called“starvation ketosis,” where fat stores are mobilized to fulfill the need for energy—yet at the same time, as I often noticed when I was undergoing regular lengthy fasts, hunger virtually disappears. This paradoxical phenomenon is likely due to the ultrahigh levels of ketones that this state produces, which tamp down feelings of hunger.
Fasting over long periods also turns down mTOR, the pro-growth and pro-aging pathway we discussed in chapter 5. This would also be desirable, one might think, at least for some tissues. At the same time, lack of nutrients accelerates autophagy, the cellular“recycling” process that helps our cells become more resilient, and it activates FOXO, the cellular repair genes that may help centenarians live so long. In short, fasting triggers many of the physiological and cellular mechanisms that we want to see. So why don’t I recommend it to all my patients?
Because my thinking about fasting has evolved considerably, I feel that I need to address the topic here. I still think it can be useful sometimes, in some patients—typically the ones with the most severe metabolic dysfunction—but I am less persuaded that it is the panacea that some believe it to be.
another meal at 2 p.m., and nothing thereafter. There are an almost infinite number of variations on this, but the trick is that it works only provided you make the feeding window small enough. The standard 16/8(sixteen hours of fasting, eight hours to eat) is barely enough for most people, but it can work. Usually a narrower window, such as 18/6 or 20/4, is needed to eke out enough of a caloric deficit.
In my experience, most people find this to be the easiest way to reduce their caloric intake, by focusing on when they are eating rather than how much and/or what they are eating. But I am not convinced that short-term time-restricted feeding has much of a benefit beyond this.
The original 16/8 model came from a study conducted in mice. This study found that mice fed in only eight hours out of the day, and fasted for the other sixteen, were healthier than mice fed continuously. The time-restricted mice gained less weight than the mice that ate whenever they wanted, even though the two groups consumed the same number of calories. This study gave birth to the eight-hour diet fad, but somehow people lost sight of the fact that this is a big extrapolation from research in mice. Because a mouse lives for only about two to three years—and will die after just forty-eight hours without food—a sixteen-hour fast for a mouse is akin to a multiday fast for a human. It’s just not a valid comparison. Human trials of this eating pattern have failed to find much of a benefit.
One other study did find that shifting the eating window to early in the day, from 8 a.m. to 2 p.m., actually did result in lower twenty-four-hour glucose levels, reduced glucose excursions, and lower insulin levels compared to controls. So perhaps an early-day feeding window could be effective, but in my view sixteen hours without food simply isn’t long enough to activate autophagy or inhibit chronic mTOR elevation, or engage any of the other longer-term benefits of fasting that we would want to obtain.
Another drawback is that you are virtually guaranteed to miss your protein target with this approach(see“Protein,” above). This means that a person who needs to gain lean body mass(i.e., undernourished or undermuscled), should either abandon this approach completely or consume a pure protein source outside their feeding window(which more or less defeats the purpose of time-restricted feeding). Also, it’s very easy to fall into the trap of overindulgence during your feeding window and mindlessly consume, say, a half gallon of ice cream in one sitting. Taken together, this combo of too little protein and too many calories can have the exact opposite effect we want: gaining fat and losing lean body mass. In my clinical experience, this result is quite common.
As I said, I will sometimes put certain patients on a time-restricted eating pattern because I’ve found it helps them reduce their overall caloric intake with minimal hunger. But it’s more of a disciplinary measure than a diet. Setting time limits around food consumption helps foil a key feature of the SAD, which is that it’s difficult to stop eating it. Time-restricted feeding is a way of putting the brakes on snacking and late-night meals—the type of mindless eating-just-to-eat that the Japanese call kuchisabishii, for“lonely mouth.” But beyond that, I don’t think it’s particularly useful.
Therefore, I am inclined to agree with lead investigator James Betts:“If you are following a fasting diet, it is worth thinking about whether prolonged fasting periods [are] actually making it harder to maintain muscle mass and physical activity levels, which are known to be very important factors for long-term health.” As a result of this and other research, I have become convinced that frequent, prolonged fasting may be neither necessary nor wise for most patients.
My rule of thumb for any eating pattern, in fact, is that you must eat enough to maintain lean mass(muscle) and long-term activity patterns. That is part of what makes any diet sustainable. If we are going to use a powerful tool like fasting, we must do so carefully and deliberately.
Fasting had effectively reset or rebooted his crashed metabolism in a way that no other dietary intervention was able to achieve. Because it has such deleterious effects on muscle mass, I only use it in hard-to-fix patients like Tom. Tom was so overweight to begin with that he could tolerate the loss of muscle because he was losing so much fat at the same time. But most people can’t safely lose muscle mass, so fasting is a tool that we can only really use in extremis, when there are no other viable options.
I once believed that diet and nutrition could cure almost all ills, but I no longer feel that strongly about it. Nutritional biochemistry is an important component of our tactics, but it is not the only path to longevity, or even the most powerful one. I see it more as a rescue tactic, particularly for patients like Eduardo and Tom, with really severe metabolic problems such as NAFLD and type 2 diabetes. It is also essential for older people who need to build or maintain muscle mass. But its power to leverage increased lifespan and healthspan is more limited. Bad nutrition can hurt us more than good nutrition can help us. If you’re already metabolically healthy, nutritional interventions can only do so much.
zone 2 aerobic training can have a huge impact on our ability to dispose of glucose safely, and also on our ability to access energy we have stored as fat. And the more muscle mass we have, the more capacity we have to use and store excess glucose, and utilize stored fat.
(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.)
In the meantime, you can approximate your own CGM with a simple drugstore glucose monitor, simply by taking a reading every hour on the hour and plotting out the results(noting mealtimes and snacks, as well). It’s also enlightening to take glucose measurements before and after a meal, at thirty-minute intervals up to two hours postprandial, and to observe how different foods and combinations of foods affect your glucose“curve.”
Similar results have been found in multiple other studies, although it remains unclear whether protein supplementation helps to improve muscle strength as well as muscle mass.

Chapter 16: The Awakening: How to Learn to Love Sleep, the Best Medicine for Your Brain

If sleep is so unimportant, he asked, then why hasn’t evolution gotten rid of it?
This, he argued, demonstrates precisely why sleep is so important. Why would evolution allow us to spend up to a third of our lives in a state of unconsciousness, where we could easily be killed or eaten? He pressed the issue: Don’t you think natural selection would have eliminated the need to sleep hundreds of millions of years ago—unless, somehow, it was absolutely essential?
studies have found that people who sleep less chronically tend to have older-looking, flabbier skin than people their same age who sleep more.
Sleep researcher Eve van Cauter of the University of Chicago subjected healthy young people to severely restricted sleep, just 4.5 hours a night, and found that after four days they had the elevated insulin levels of obese middle-aged diabetics and, worse yet, approximately a 50 percent reduction in their capacity for glucose disposal. This turns out to be one of the most consistent findings in all of sleep research. No fewer than nine different studies have found that sleep deprivation increases insulin resistance by up to a third. Very rarely in medicine do we see such consistent findings, with experimental evidence confirming the epidemiology so powerfully, so it’s worth paying attention.
But it cuts both ways: long sleep is also a sign of problems. People who sleep eleven hours or more nightly have a nearly 50 percent higher risk of all-cause mortality, likely because long sleep = poor quality sleep, but it may also reflect an underlying illness.
Follow-up studies by van Cauter’s group have found that short-sleeping subjects ate about three hundred extra calories’ worth of food the following day, compared with when they were well rested. Taken together, this all adds up to a perfect recipe for the beginnings of NAFLD and insulin resistance.
The MR data confirmed the observational findings, that sleeping less than six hours a night was associated with about a 20 percent higher risk of a heart attack.
Sleep and the Brain
Both REM and deep NREM sleep(which we’ll call“deep sleep” for convenience) are crucial to learning and memory, but in different ways. Deep sleep is when the brain clears out its cache of short-term memories in the hippocampus and selects the important ones for long-term storage in the cortex, helping us to store and reinforce our most important memories of the day. Researchers have observed a direct, linear relationship between how much deep sleep we get in a given night and how well we will perform on a memory test the next day.
When we are young, REM sleep is important in helping our brains grow and develop. Even while we are asleep, our brain is forming new connections, expanding our neural network; this is why younger people spend more time in REM. In adulthood, our REM sleep time tends to plateau, but it remains important, especially for creativity and problem solving.
By generating seemingly random associations between facts and memories, and by sorting out the promising connections from the meaningless ones, the brain can often come up with solutions to problems that stumped us the previous day. Research has also found that REM sleep is especially helpful with what is called procedural memory, learning new ways of moving the body, for athletes and for musicians.
Another very important function of REM sleep is to help us process our emotional memories, helping separate our emotions from the memory of the negative(or positive) experience that triggered those emotions. This is why, if we go to bed upset about something, it almost always seems better in the morning. We remember the event but(eventually) forget the pain that accompanied it. Without this break for emotional healing, we would live in a state of constant anxiety, every memory triggering a renewed surge of the emotions around that event. If this sounds like PTSD, you are correct: studies of combat veterans found that they are less able to separate memories from emotions, precisely due to their lack of REM sleep. It turned out that the veterans put out high levels of noradrenaline, the fight-or-flight hormone that effectively prevented their brains from relaxing enough to enter REM.[*2]
Perhaps most intriguing, REM sleep helps us maintain our emotional awareness. When we are deprived of REM, studies have found, we have a more difficult time reading others’ facial expressions. REM-deprived study subjects interpreted even friendly or neutral expressions as menacing. This is not trivial: our ability to function as social animals[*3] depends on our ability to understand and navigate the feelings of others. In short, REM sleep seems to protect our emotional equilibrium, while helping us process memories and information.
Deep sleep, on the other hand, seems to be essential to the very health of our brain as an organ. A few years ago, researchers in Rochester discovered that while we are in deep sleep, the brain activates a kind of internal waste disposal system that allows cerebrospinal fluid to flood in between the neurons and sweep away intercellular junk; while this happens, the neurons themselves pull back to allow this to happen, the way city residents are sometimes required to move their cars to allow street sweepers to pass through.
Clearly, sleep and cognitive health are deeply intertwined; this is why one of the pillars of Alzheimer’s disease prevention, particularly for our high-risk patients, is improving their sleep. It is not enough merely to spend time in bed; good-quality sleep is essential to long-term brain health. This is the crucial distinction. Sleep that is irregular, or fragmented, or not deep enough will not allow the brain to enjoy any of these benefits.
Unfortunately, our ability to obtain deep sleep declines with age, beginning as soon as our late twenties or early thirties, but worsening as we enter middle age. It’s not entirely clear how much this decline in sleep quality is due to growing older itself, versus the increased likelihood of health conditions that result in poor sleep as we age.
More research points to the forties and sixties as the decades of life when deep sleep is especially important for the prevention of Alzheimer’s disease. People who have slept less during those decades seem to be at higher risk of developing dementia later on. Thus, good sleep in middle age appears to be especially important for maintaining cognitive health.
One drug that we do find helpful for assisting with sleep is trazodone, a fairly old anti-depressant(approved in 1981) that never really took off. At the doses used to treat depression, two hundred to three hundred milligrams per day, it had the unwanted side effect of causing users to fall asleep. But one man’s trash is another man’s treasure. That side effect is what we want in a sleep medication, especially if it also improves sleep architecture, which is exactly what trazodone does—and most other sleep meds do not.[*4]
(We have also had good results with the supplement ashwagandha.)
Like so much else in biology, this has a possible basis in evolution: if all members of a clan or a tribe adhered to the exact same sleep schedule, the entire group would be vulnerable to predators and enemies for several hours every night.
Another way to help cultivate sleep pressure is via exercise, particularly sustained endurance exercise(e.g., zone 2), ideally not within two or three hours of bedtime. My patients often find that a thirty-minute zone 2 session can do wonders for their ability to fall asleep. Even better is exercise that entails some exposure to sunlight(i.e., outdoors). While blue light late in the evening can interfere with sleep, a half-hour dose of strong daylight, during the day, helps keep our circadian cycle on track, setting us up for a good night of sleep.
How to Improve Your Sleep
But the more of these you can check off, the better your odds of a good night of sleep.
Don’t drink any alcohol, period—and if you absolutely, positively must, limit yourself to one drink before about 6 p.m. Alcohol probably impairs sleep quality more than any other factor we can control. Don’t confuse the drowsiness it produces with quality sleep.
Don’t eat anything less than three hours before bedtime—and ideally longer. It’s best to go to bed with just a little bit of hunger(although being ravenous can be distracting.)
Abstain from stimulating electronics, beginning two hours before bed. Try to avoid anything involving a screen if you’re having trouble falling asleep. If you must, use a setting that reduces the blue light from your screen.
For at least one hour before bed, if not more, avoid doing anything that is anxiety-producing or stimulating, such as reading work email or, God help you, checking social media. These get the ruminative, worry-prone areas of our brain humming, which is not what you want.
For folks who have access, spend time in a sauna or hot tub prior to bed. Once you get into the cool bed, your lowering body temperature will signal to your brain that it’s time to sleep.(A hot bath or shower works too.)
The room should be cool, ideally in the midsixties. The bed should be cool too. Use a“cool” mattress or one of the many bed-cooling devices out there. These are also great tools for couples who prefer different temperatures at night, since both sides of the mattress can be controlled individually.
Darken the room completely. Make it dark enough that you can’t see your hand in front of your face with your eyes open, if possible. If that is not achievable, use an eye shade. I use a silky one called Alaska Bear that costs about $8 and works better than the fancier versions I’ve tried.
Give yourself enough time to sleep—what sleep scientists call a sleep opportunity. This means going to bed at least eight hours before you need to wake up, preferably nine.
Fix your wake-up time—and don’t deviate from it, even on weekends. If you need flexibility, you can vary your bedtime, but make it a priority to budget for at least eight hours in bed each night.
Don’t obsess over your sleep, especially if you’re having problems. If you need an alarm clock, make sure it’s turned away from you so you can’t see the numbers. Clock-watching makes it harder to fall asleep. And if you find yourself worrying about poor sleep scores, give yourself a break from your sleep tracker.
It’s not just a matter of getting enough sleep; the timing also matters. Studies have looked at winning percentages of teams in the NBA/NFL/NHL, and there is a clear circadian disadvantage for teams who have to travel westward(Roy and Forest, 2018).
What’s interesting is that REM sleep appeared relatively late in the game of evolution; all animals display NREM sleep, but only birds and nonaquatic mammals experience REM, although recent studies suggest that a REM sleep–like state may exist in nonavian reptiles.(Aquatic mammals need to surface periodically to breathe, so they do not enter deep sleep.)

Chapter 17: Work in Progress: The High Price of Ignoring Emotional Health

This is why I’ve come to believe that emotional health may represent the most important component of healthspan. Nothing else about longevity is really worth much without some degree of happiness, fulfillment, and connection to others. And misery and unhappiness can also destroy your physical health, just as surely as cancer, heart disease, neurodegenerative disease, and orthopedic injury.
Even just living alone, or feeling lonely, is linked to a much higher risk of mortality. While most issues around emotional health are not age dependent, this is the one emotional health“risk factor” that does seem to grow worse with increasing age.
It took me a while to recognize this, but feeling connected and having healthy relationships with others, and with oneself, is as imperative as maintaining efficient glucose metabolism or an optimal lipoprotein profile. It is just as important to get your emotional house in order as it is to have a colonoscopy or an Lp(a) test, if not more so. It’s just a lot more complicated.
It’s a two-way street between emotional and physical health. In my own practice, I witness firsthand how many of my patients’ physical and longevity issues are rooted in, or exacerbated by, their emotional health. I see it on a daily basis. It is harder to motivate a patient who is feeling depressed to go and start an exercise program; someone who is overstressed at work and miserable in their personal life may not see the point of early cancer screening or monitoring their blood glucose levels. So they drift along, as their emotional misery drags their physical health down along with it.
The words of my therapist, Esther Perel, rang in my head practically every day:“Why would you want to live longer if you’re so unhappy?”
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.
Trauma is a pretty loaded word, and the therapists at the Bridge were careful to explain that there can be“big-T” trauma or“little-t” traumas. Being a victim of rape would qualify as a big-T trauma, while having an alcoholic parent might subject a child to a host of little-t traumas. But in large enough doses over a long enough time, little-t traumas can shape a person’s life just as much as one major terrible event.
But I also want to make an important distinction between trauma and adversity. They are not the same. I am not suggesting that it is ideal for children to grow up without experiencing any adversity at all, which sometimes seems to be a primary goal of modern parenting. Many stressors can be beneficial, while others are not. There is no bright line between trauma and adversity; terrible as it was, my own experience had made me stronger in some ways. Julie’s question is a pretty good litmus test: Would I want my child to experience it? If my daughter finished dead last in a cross-country race(for example), and didn’t get a medal, that would be okay. Sure, she might feel upset in the moment, but it could also motivate her to train harder and give her a better appreciation for the joy of placing in the top three one day. What would not be okay is if I had then screamed at her, in front of the other runners, for getting beaten by the shortest kid on the team.
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.
Our Medicine 3.0 thesis is that if we address our emotional health, and do so early on, we will have a better chance of avoiding clinical mental health issues such as depression and chronic anxiety—and our overall health will benefit as well. But there is rarely a simple cure or a quick fix, any more than we have a quick fix for cancer or metabolic disease. Addressing emotional health takes just as much constant effort and daily practice as maintaining other aspects of our physical health by creating an exercise routine, following a nutritional program, adhering to sleep rituals, and so on. The key is to be as proactive as possible, so that we can continue to thrive in all domains of healthspan, throughout the later decades of our lives.
At the Bridge, I learned that children don’t respond to a parent’s anger in a logical way. If they see me screaming at a driver who just cut me off, they internalize that rage as though it were directed to them. Second, trauma is generational, although not necessarily linear. Children of alcoholics are not inevitably destined to become alcoholics themselves, but one way or another, trauma finds its way down the line. As Terry had written:“Family pathology rolls from generation to generation like a fire in the woods taking down everything in its path until one person, in one generation, has the courage to turn and face the flames. That person brings peace to his ancestors and spares the children that follow.” I wanted to be that person.
One skill I worked on that is a bit more complicated is called“reframing.” Reframing is basically the ability to look at a given situation from someone else’s point of view—literally reframing it. This is an incredibly difficult thing for most of us to do, as David Foster Wallace explained in his now famous 2005 commencement address to the graduating class at Kenyon College,“This Is Water”: Everything in my own immediate experience supports my deep belief that I am the absolute center of the universe; the realest, most vivid and important person in existence. We rarely think about this sort of natural, basic self-centeredness because it’s so socially repulsive. But it’s pretty much the same for all of us. It is our default setting, hard-wired into our motherboards at birth. Think about it: there is no experience you have had that you are not the absolute center of. The world as you experience it is there in front of YOU or behind YOU, to the left or right of YOU, on YOUR TV or YOUR monitor. And so on. Other people’s thoughts and feelings have to be communicated to you somehow, but your own are so immediate, urgent, real.
Easier described than accomplished, reframing entails taking a step back from a situation and then asking yourself, What does this situation look like through the other person’s eyes? How do they see it? And why is your time, your convenience, or your agenda any more important than theirs?
Somewhere along the line, in a random airport on a long work trip, I had picked up David Brooks’s book The Road to Character. On the plane, I read the part where Brooks makes a key distinction between“résumé virtues,” meaning the accomplishments that we list on our CV, our degrees and fellowships and jobs, versus“eulogy virtues,” the things that our friends and family will say about us when we are gone. And it shook me. For my entire life, I had been accumulating mostly résumé virtues. I had plenty of those. But I had also recently attended a funeral for a woman about my age who had died of cancer, and I was struck by how lovingly and movingly her family had spoken about her—with hardly a mention of her impressive professional or educational success. What mattered to them was the person she had been and the things she had done for others, most of all her children. Would anyone be speaking that way about me when it was my turn in the casket? I doubted it. And I decided that that had to change.
Jacob Riis, the great Danish American journalist and social reformer:“When nothing seems to help, I go back and look at a stonecutter hammering away at his rock perhaps a hundred times without as much as a crack showing in it. Yet at the hundred-and-first blow it will split in two, and I know it was not the last blow that did it, but all that had gone before.”
dialectical behavior therapy, or 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.
One thing I like about DBT is that it is backed up by evidence: clinical trials have found it to be effective in helping suicidal and self-harming patients stop their dangerous behavior. Another thing that draws me to DBT is that it is skills-based, not just theoretical. Practicing DBT means literally working through a workbook with a DBT therapist, doing exercises every day. I’m better at doing than thinking sometimes. The practice of DBT is predicated on learning to execute concrete skills, repetitively, under stress, that aim to break the chain reaction of negative stimulus → negative emotion → negative thought → negative action.
DBT consists of four pillars joined by one overarching theme. The overarching theme is mindfulness, which gives you the ability to work through the other four: emotional regulation(getting control over our emotions), distress tolerance(our ability to handle emotional stressors), interpersonal effectiveness(how well we make our needs and feelings known to others), and self-management(taking care of ourselves, beginning with basic tasks like getting up in time to go to work or school).
DBT is rooted in mindfulness, which is one of those mushy buzzwords that I’d always despised until I began to understand it was a really effective tool to create distance between my thoughts and myself, to wedge even a sliver of space between some stimulus and my knee-jerk response. I needed that.
It’s not complete detachment in the sense that we’re checking out, but we want to create enough of a gap between stimulus and response so that we are not simply reacting reflexively to things that happen, like a driver who cuts us off in traffic or angry or distressing thoughts that we might have.
One obvious way this applies is in how we think about ourselves. What does our inner dialogue sound like? Is it kind and forgiving and wise, or is it harsh and judgmental, like my inner Bobby Knight? One of the most powerful exercises I learned was to simply listen to my self-talk. I would record voice memos to myself on my phone, after I did anything that could produce self-judgment, such as archery or driving my race-car simulator, or even just cooking dinner, and send each one to my therapist. My instinct in these situations was typically to scream at myself for failing somehow. My therapist at PCS told me to imagine instead that my best friend had performed exactly as I had done. How would I speak to him? Would I berate him the way I often berated myself? Of course not. This was a slightly different take on reframing, forcing me to step outside myself and really see the disconnect between my“mistakes”(minor) and the way I talked to myself about those mistakes(brutal). I did this multiple times a day, every single day, for about four months; you can imagine how much space it took up on my phone. Over time, my inner Bobby Knight became fainter and fainter, and today it’s almost hard for me to remember what that voice used to sound like.
One simple tactic that I use to cope with mounting emotional distress is inducing an abrupt sensory change—typically, by throwing ice water on my face or, if I’m really struggling, taking a cold shower or stepping into an ice bath. This simple intervention stimulates an important cranial nerve, the vagus nerve, which causes our heart rate and respiratory rate to slow and switches us into a calm, parasympathetic mode(and out of our fight-or-flight sympathetic mode). Interventions like these are often enough to help refocus and think about a situation more calmly and constructively. Another technique I have grown very fond of is slow, deep breathing: four seconds to inhale, six seconds to exhale. Repeat. As the breath goes, the nervous system follows.
One tactic that I’ve found especially helpful is called opposite action—that is, if I feel like doing one thing(generally, not a helpful or positive thing), I’ll force myself instead to do the exact opposite. By doing so, I also change the underlying emotions.
This small lesson, which I have implemented countless times since, taught me something very important: changing the behavior can change the mood. You do not need to wait for your mood to improve to make a behavior change. This is also why cognitive therapies alone sometimes come up short; simply thinking about problems might not help if our thinking itself is disordered.
Exercise is another important component of my overall emotional health program, particularly my practice of rucking, discussed in chapter 12. I find that spending time moving in nature, simply enjoying the feeling of the wind in my face and the smell of the budding spring leaves(and a heavily loaded pack on my back) helps me cultivate what Ryan Holiday calls“stillness,” the ability to remain calm and focused amid all the distractions that our world offers and that we create for ourselves. When my family comes along, it’s important bonding time. When I’m alone, rucking serves as a mindfulness practice, a kind of walking meditation. No phone, no music, no podcasts. Just the sounds of nature, and of my heavy breathing. This is another example of how action can lead us into a better mental state. And as Michael Easter pointed out to me, there is actual research suggesting that exposing oneself to the fractal geometric patterns in nature can reduce physiological stress, and that these effects show up on an EEG.
The most important“tactic” by far is my regular weekly therapy session
Each session begins with a physical checkin: How am I feeling? How have I slept(a big one)? Am I in physical pain? Am I in conflict? Then we dissect and discuss the events and issues of the week in minute detail. No topic is too insignificant. If, for example, I found myself getting really upset at a TV show or movie, this might be worth exploring. But we also tackle big-picture issues, the ones that propelled me into crisis in the first place. I complement my therapy sessions by writing in my journal, a place where I can practice articulating my emotions and understanding them, holding nothing back. I feel strongly that there is no substitute for this kind of work with a trained therapist.
There’s a quote from Paulo Coelho that I think about often:“Maybe the journey isn’t so much about becoming anything,” he writes.“Maybe it’s about unbecoming everything that isn’t really you, so you can be who you were meant to be in the first place.”

Epilogue

It took five years, two stints in inpatient treatment centers, and the near loss of my marriage and my kids to change my mind. 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.
the most important ingredient in the whole longevity equation is the why. Why do we want to live longer? For what? For whom?