This was one of my favourite reads of the year, and is the most useful book I’ve come across on living a longer, healthier life.
The 4-Hour Body is the health-related book whose content has stuck with me the longest, and I think Outlive will be another book like this.
There are four main reasons why most people’s health deteriorates, and this book both introduces you to each of these, and presents the most up-to-date research on how to reverse or prevent each from happening.
Health is the single most important thing in our lives; the value of the book is worth 100x the cost.
Note: the following are the ultra-summarized action items I laid out for myself after reading the book. Some things will apply to everyone, some may not. You can scroll down to view the summarized book notes below.
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.
There are four main points to Medicine 3.0:
In this book, we will apply this three-part approach to longevity: objective → strategy → tactics.
I think about healthspan and its deterioration in terms of three categories, or vectors. The first vector of deterioration is cognitive decline.
The second vector of deterioration is the decline and eventual loss of function of our physical body.
No matter how ambitious your goals are for your later years, I suggest that you familiarize yourself with something called the “activities of daily living,” a checklist used to assess the health and functionality of elderly people.
The third and final category of deterioration, I believe, has to do with emotional health. Unlike the others, this one is largely independent of age; it can afflict outwardly healthy young people in their twenties, or it can creep up on you in middle age, as it did with me.
The other key point is that lifespan and healthspan are not independent variables; they are tightly intertwined.
Medicine 2.0 relies on two types of tactics, broadly speaking: procedures (e.g., surgery) and medications. 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.
A small but growing number of people, including me and a handful of my patients, already take rapamycin off-label for its potential geroprotective benefits. I can’t speak for everyone, but taking it cyclically does appear to reduce unwanted side effects, in my experience.
The FDA has given the green light for a clinical trial of another drug with potential longevity benefits, the diabetes medication metformin. This trial is called TAME (Targeting Aging with Metformin), and it came about in a very different way. Metformin has been taken by millions of people for years. Over time, researchers noticed (and studies appeared to confirm) that patients on metformin appeared to have a lower incidence of cancer than the general population.
I insist my patients undergo a DEXA scan annually—and I am far more interested in their visceral fat than their total body fat.
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.
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.
Fully half of all major adverse cardiovascular events in men (and a third of those in women), such as heart attack, stroke, or any procedure involving a stent or a graft, occur before the age of sixty-five. In men, one-quarter of all events occur before age fifty-four.
If you look at the coronary arteries with a CT scan at this very early stage, you will likely miss this if you’re looking only for calcium buildup. (You have a better chance of spotting this level of damage if using a more advanced type of CT scan, called a CT angiogram, which I much prefer to a garden-variety calcium scan[*4] because it can also identify the noncalcified or “soft” plaque that precedes calcification.)
Back then, nearly fifteen years ago, the apoB test (simply, measuring the concentration of apoB-tagged particles) was not commonly done. Since then, evidence has piled up pointing to apoB as far more predictive of cardiovascular disease than simply LDL-C, the standard “bad cholesterol” measure. According to an analysis published in JAMA Cardiology in 2021, each standard-deviation increase in apoB raises the risk of myocardial infarction by 38 percent in patients without a history of cardiac events or a diagnosis of cardiovascular disease (i.e., primary prevention). That’s a powerful correlation. Yet even now, the American Heart Association guidelines still favor LDL-C testing instead of apoB. I have all my patients tested for apoB regularly, and you should ask for the same test the next time you see your doctor. (Don’t be waved off by nonsensical arguments about “cost”: It’s about twenty to thirty dollars.)
Once you establish the central importance of apoB, the next question becomes, By how much does one need to lower it (or its proxy LDL-C) to achieve meaningful risk reduction? The various treatment guidelines specify target ranges for LDL-C, typically 100 mg/dL for patients at normal risk, or 70 mg/dL for high-risk individuals. In my view, this is still far too high. Simply put, I think you can’t lower apoB and LDL-C too much, provided there are no side effects from treatment. You want it as low as possible.
As Peter Libby, one of the leading authorities on cardiovascular disease, and colleagues wrote in Nature Reviews in 2019, “Atherosclerosis probably would not occur [emphasis mine] in the absence of LDL-C concentrations in excess of physiological needs (on the order of 10 to 20 mg/dL).” Furthermore, the authors wrote: “If the entire population maintained LDL concentrations akin to those of a neonate (or to those of adults of most other animal species), atherosclerosis might well be an orphan disease.”
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.
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.
But for many patients, if not for most, lowering apoB to the levels we aim for—the physiologic levels found in children—cannot be accomplished with diet alone, so we need to use nutritional interventions in tandem with drugs. Here we are fortunate because we have more preventive options in our armamentarium than we do for cancer or neurodegenerative disease. Statins are far and away the most prescribed class of drugs for lipid management, but there are several other options that might be right for a given individual, and often we need to combine classes of drugs, so it’s not uncommon for a patient to take two lipid-lowering drugs that operate via distinct mechanisms. These are typically thought of as “cholesterol-lowering” medications, but I think we are better served to think about them in terms of increasing apoB clearance, enhancing the body’s ability to get apoBs out of circulation. That’s really our goal. Mostly this is done by amplifying the activity of LDL receptors (LDLR) in the liver, which absorb cholesterol from the bloodstream.
The problem we face is that once cancer is established, we lack highly effective treatments for it. Our toolbox is limited.
This experience informs our 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.
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.
Over dinner, I shared a story about a case where a PI3K-inhibiting drug treatment had been enhanced by a kind of metabolic therapy.
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.
Other types of dietary interventions have been found to help improve the effectiveness of chemotherapy, while limiting its collateral damage to healthy tissues. Work by Valter Longo of the University of Southern California and others has found that fasting, or a fasting-like diet, increases the ability of normal cells to resist chemotherapy, while rendering cancer cells more vulnerable to the treatment.
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.
In short, the problem is not the tests themselves but how we use them. Prostate cancer screening provides an even better example. It’s no longer as simple as “Your PSA number is X or higher, and therefore we must biopsy your prostate, a painful procedure with many unpleasant possible side effects.” Now we know to look at other parameters, such as PSA velocity (the speed at which PSA has been changing over time), PSA density (PSA value normalized to the volume of the prostate gland), and free PSA (comparing the amount of PSA that is bound versus unbound to carrier proteins in the blood). When those factors are taken into account, PSA becomes a much better indicator of prostate cancer 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. If a sessile (flat) polyp is found, for example, we’re inclined to do it sooner than if the endoscopist finds nothing at all. Two or three years might seem like a very short window of time to repeat such an involved procedure, but colon cancer has been documented to appear within the span of as little as six months to two years after a normal colonoscopy. Better safe than sorry.
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.
MRI has a distinct advantage over CT in that it does not produce any ionizing radiation but still provides good resolution. One newer technique that can enhance the ability of a screening MRI to differentiate between a cancer and noncancer is something called diffusion-weighted imaging with background subtraction, or DWI for short.
I tell patients, if you’re going to have a whole-body screening MRI, there is a good chance we’ll be chasing down an insignificant thyroid (or other) nodule in exchange for getting such a good look at your other organs. As a result of this, about a quarter of my patients, understandably, elect not to undergo such screening. Which brings me to the next tool in the cancer screening tool kit, a tool that can complement the high sensitivity / low specificity problem of imaging tests.
I am cautiously optimistic about the emergence of so-called “liquid biopsies” that seek to detect the presence of cancers via a blood test.[*11] These are used in two settings: to detect recurrences of cancer in patients following treatment and to screen for cancers in otherwise healthy patients, a fast-moving and exciting field called multicancer early detection.
Some researchers are beginning to develop ways to use blood tests to screen for cancer generally, in otherwise healthy people.
One company leading the charge with this type of assay is called Grail, a subsidiary of the genetic-sequencing company Illumina. The Grail test, known as Galleri, looks at methylation patterns of the cell-free DNA, which are basically chemical changes to the DNA molecules that suggest the presence of cancer. Using very-high-throughput screening and a massive AI engine, the Galleri test can glean two crucial pieces of information from this sample of blood: Is cancer present? And if so, where is it? From what part of the body did it most likely originate?
*9 For those seeking more detailed guidance, this is what I wrote (Attia 2020a) in a blog post on CRC screening a few years ago: “Before you get your first colonoscopy, there are [a] few things you can do that may improve your risk-to-benefit ratio. You should ask what your endoscopist’s adenoma detection rate (ADR) is. The ADR is the proportion of individuals undergoing a colonoscopy who have one or more adenomas (or colon polyps) detected. The benchmarks for ADR are greater than 30% in men and greater than 20% in women. You should also ask your endoscopist how many perforations he or she has caused, specifically, as well as any other serious complications, like major intestinal bleeding episodes (in a routine screening setting). Another question you should ask is what is your endoscopist’s withdrawal time, defined as the amount of time spent viewing as the colonoscope is withdrawn during a colonoscopy. A longer withdrawal time suggests a more thorough inspection. A 6-minute withdrawal time is currently the standard of care.”
I rely as much as one can on biomarkers, so we run a comprehensive array of tests, but 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 that we mentioned in chapter 4.
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.
This is why an important first step with any patient who may have cognitive issues is to subject them to a grueling battery of tests.
There is a parallel concept known as “movement reserve” that becomes relevant with Parkinson’s disease. People with better movement patterns, and a longer history of moving their bodies, such as trained or frequent athletes, tend to resist or slow the progression of the disease as compared to sedentary people. This is also why movement and exercise, not merely aerobic exercise but also more complex activities like boxing workouts, are a primary treatment/prevention strategy for Parkinson’s. Exercise is the only intervention shown to delay the progression of Parkinson’s.
The 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 Preventive Plan
I actually think we know more about preventing Alzheimer’s than we do about preventing cancer.
Because metabolism plays such an outsize role with at-risk e4 patients like Stephanie, our first step is to address any metabolic issues they may have. 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. Higher doses of DHA may be required because of e4-induced metabolic changes and dysfunction of the blood-brain barrier. This is also one area where a ketogenic diet may offer a real functional advantage: when someone is in ketosis, their brain relies on a mix of ketones and glucose for fuel. Studies in Alzheimer’s patients find that while their brains become less able to utilize glucose, their ability to metabolize ketones does not decline. So it may make sense to try to diversify the brain’s fuel source from only glucose to both glucose and ketones. A systematic review of randomized controlled trials found that ketogenic therapies improved general cognition and memory in subjects with mild cognitive impairment and early-stage Alzheimer’s disease. Think of it as a flex-fuel strategy.
In Stephanie’s case, she cut out not only added sugar and highly refined carbohydrates but also alcohol. The precise role of alcohol in relation to Alzheimer’s disease remains somewhat controversial: some evidence suggests that alcohol may be slightly protective against Alzheimer’s, while other evidence shows that heavier drinking is itself a risk factor for the disease, and e4 carriers may be more susceptible to alcohol’s deleterious effects. I’m inclined to err on the side of caution, and so is Stephanie.
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. As we’ll see in chapter 11, endurance exercise produces factors that directly target regions of the brain responsible for cognition and memory. It also helps lower inflammation and oxidative stress.
Strength training is likely just as important. A study looking at nearly half a million patients in the United Kingdom found that grip strength, an excellent proxy for overall strength, was strongly and inversely associated with the incidence of dementia (see figure 8).
Sleep is also a very powerful tool against Alzheimer’s disease, as we’ll see in chapter 16. Sleep is when our brain heals itself; while we are in deep sleep our brains are essentially “cleaning house,” sweeping away intracellular waste that can build up between our neurons. Sleep disruptions and poor sleep are potential drivers of increased risk of dementia. If poor sleep is accompanied by high stress and elevated cortisol levels, as in Stephanie’s case, that acts almost as a multiplier of risk, as it contributes to insulin resistance and damaging the hippocampus at the same time.
Another somewhat surprising risk factor that has emerged is hearing loss. Studies have found that hearing loss is clearly associated with Alzheimer’s disease, but it’s not a direct symptom. Rather, it seems hearing loss may be causally linked to cognitive decline, because folks with hearing loss tend to pull back and withdraw from interactions with others.
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.
One other somewhat recent addition to my thinking on dementia (and ASCVD while we’re at it) prevention is the use of dry saunas.
The best interpretation I can draw from the literature suggests that at least four sessions per week, of at least twenty minutes per session, at 179 degrees Fahrenheit (82 degrees Celsius) or hotter seems to be the sweet spot to reduce the risk of Alzheimer’s by about 65 percent (and the risk of ASCVD by 50 percent).
Other potential interventions that have shown some promise in studies include lowering homocysteine with B vitamins, while optimizing omega-3 fatty acids. Higher vitamin D levels have been correlated with better memory in e4/e4 patients but it’s difficult to know from the current literature if this means supplementing with vitamin D will reduce risk of AD. And as mentioned earlier, hormone replacement therapy for women during the transition from perimenopause to menopause seems promising, especially for women with at least one copy of e4.
Broadly, our strategy should be based on the following principles:
Our two most complex tactical domains are nutrition and exercise, and I find that most people need to make changes in both—rarely just one or the other. When I evaluate new patients, I’m always asking three key questions:
It turns out that peak aerobic cardiorespiratory fitness, measured in terms of VO2 max, is perhaps the single most powerful marker for longevity.
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.
The data demonstrating the effectiveness of exercise on lifespan are as close to irrefutable as one can find in all human biology. Yet if anything, I think exercise is even more effective at preserving healthspan than extending lifespan.
Therefore, I will find a way to lift heavy weights in some way, shape, or form four times per week, no matter what else I am doing or where I might be traveling.
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.
Aerobic Efficiency: Zone 2
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.
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 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.
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.
How much zone 2 training you need depends on who you are. Someone who is just being introduced to this type of training will derive enormous benefit from even two 30-minute sessions per week to start with. Based on multiple discussions with San Millán and other exercise physiologists, it seems that about three hours per week of zone 2, or four 45-minute sessions, is the minimum required for most people to derive a benefit and make improvements, once you get over the initial hump of trying it for the first time. (People who are training for major endurance events, such as running a marathon, obviously need to do more than this.) I am so persuaded of the benefits of zone 2 that it has become a cornerstone of my training plan. Four times a week, I will spend about an hour riding my stationary bike at my zone 2 threshold.
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. So if you weigh 60 kilos (about 132 pounds) and can generate 125 watts in zone 2, that works out to a bit more than 2 watts/kg, which is about what one would expect from a reasonably fit person.
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.
Zone 2 can be a bit boring on its own, so I typically use the time to listen to podcasts or audiobooks, or just think about issues that I’m working on.
Maximum Aerobic Output: VO2 Max
If zone 2 represents a steady state, where you are kind of cruising along at a sustainable pace, VO2 max efforts are almost the opposite. This is a much higher level of intensity—a hard, minutes-long effort, but still well short of an all-out sprint.
I push my patients to train for as high a VO2 max as possible, so that they can maintain a high level of physical function as they age. Ideally, I want them to target the “elite” range for their age and sex (roughly the top 2 percent). If they achieve that level, I say good job—now let’s reach for the elite level for your sex, but two decades younger. This may seem like an extreme goal, but I like to aim high, in case you haven’t noticed.
Studies suggest that your VO2 max will decline by roughly 10 percent per decade—and up to 15 percent per decade after the age of fifty.
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.
You want to make sure that you get as close to fully recovered as possible before beginning the next set.
In practice, I’ve found that my ideal VO2 max pace works out to about 33 percent more power than my zone 2 pace, if I’m doing four-on/four-off intervals. So if your zone 2 pace represents an output of 150 watts, your VO2 max training pace should be about 200 watts for four minutes, followed by four minutes of rest. Better yet, if you know your functional threshold power (FTP), which is the highest power you can sustain for sixty minutes, you should target 120 percent of this for three-minute intervals and 106 percent of this for eight-minute intervals and adjust for everything in between.
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.
Why do we care so much? Just as with muscle, it comes down to protection. We want to slow this decline, armoring ourselves against injury and physical frailty. The mortality from a hip or femur fracture is staggering once you hit about the age of sixty-five.
When we detect low or rapidly declining BMD in a middle-aged person, we use the following four strategies:
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.
A far more important measure of strength, I’ve concluded, is how much heavy stuff you can carry.
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:
I focus on these four foundational elements of strength because they are the most relevant to our Centenarian Decathlon—and also to living a fulfilling and active life in our later decades. If you can grip strongly, you can open a jar with ease. If you can pull, you can carry groceries and lift heavy objects. If you can do a hip-hinge correctly, you can get up out of a chair with no problem. You’re setting yourself up to age well. It’s not about how much weight you can deadlift now, but how well you will function in twenty or thirty or forty years.
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.
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.)
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 (next chapter). It also helps protect against knee pain. You don’t need to do this for every rep of every set. Sometimes you just want to focus on moving the weight quickly or moving a heavier load, but make sure at some point in each workout that you are taking the time to cue the eccentric phase of your lifts.
Next is pulling, which is closely related to grip strength. 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. A rowing machine, something I love to use for VO2 max training, is another simple and effective way to work on pulling strength.
The final foundational element of strength is hip-hinging, which is what it sounds like: You bend at the hips—not the spine—to harness your body’s largest muscles, the gluteus maximus and the hamstrings. (I repeat: Do not bend your spine.) It is a very powerful move that is essential to life. Whether you are launching off an Olympic ski jump, picking up a lucky penny off the sidewalk, or simply getting up out of a chair, you are hip-hinging.
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.
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.
If you’d like to know more after you’ve read this chapter, I suggest visiting the websites for DNS (www.rehabps.com) and the Postural Restoration Institute (PRI) (www.posturalrestoration.com), the two leading exponents of what I’m talking about here. Stability is an integral part of my training program. Twice a week, I spend an hour doing dedicated stability training, based on the principles of DNS, PRI, and other practices, with ten to fifteen minutes per day on the other days.
Stability training begins at the most basic level, with the breath.
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.
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.
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 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. First, Beth tells her students to think of their feet as having four corners, each of which needs to be rooted firmly on the ground at all times, like the legs of a chair. As you stand there, try to feel each “corner” of each foot pressing into the ground: the base of your big toe, the base of your pinky toe, the inside and outside of your heel. This is easy, and revelatory; when was the last time you felt that grounded?
Try to lift all ten toes off the ground and spread them as wide as you can. Now try to put just your big toe back on the floor, while keeping your other toes lifted. Trickier than you’d think, right? Now do the opposite: keep four toes on the floor and lift only your big toe. Then lift all five toes, and try to drop them one by one, starting with your big toe. (You get the idea.)[*3]
Now when I squat, or do any standing lift, my first step is to ground my feet, to be aware of all four “corners,” and distribute weight equally. (Also important: I prefer to lift barefoot or in minimal shoes, with little to no cushioning in the soles because it allows me feel the full surface of my feet at all times.)
Feet are also crucial to balance, another important element of stability. 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.)
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.
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:
I used to think that diet and nutrition were the one path to perfect health. Years of experience, with myself and my patients, have led me to temper my expectations a bit. Nutritional interventions can be powerful tools with which to restore someone’s metabolic equilibrium and reduce risk of chronic disease. But can they extend and improve lifespan and healthspan, almost magically, the way exercise does? I’m no longer convinced that they can.
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.
CR: Calories Matter
Taken together, then, what do these two monkey studies have to tell us about nutritional biochemistry?
DR: The Nutritional Biochemistry “Diet”
The advantage of DR is that it is highly individualized; you can impose varying degrees of restriction, depending on your needs. For example, you could decide to eliminate all sugar-sweetened beverages, and that would be a great first step (and a relatively easy one). You could go a step further and quit drinking sweet fruit juices as well. You could quit eating other foods with added sugar. Or you could go as far as reducing or eliminating carbohydrates in general.
A major risk with DR is that you can still easily end up overnourished if you are not deliberate about it. People tend to (erroneously) assume you can’t eat too much if you’re just restricting fill-in-the-blank (e.g., carbohydrates).
My personal bottom line: if you drink, try to be mindful about it. You’ll enjoy it more and suffer fewer consequences.
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.
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.
I am confident that such studies will show a benefit, if done correctly, because there are already ample data showing how important it is to keep blood glucose low and stable. A 2011 study looking at twenty thousand people, mostly without type 2 diabetes, found that their risk of mortality increased monotonically with their average blood glucose levels (measured via HbA1c). The higher their blood glucose, the greater their risk of death—even in the nondiabetic range of blood glucose. Another study in 2019 looked at the degree of variation in subjects’ blood glucose levels and found that the people in the highest quartile of glucose variability had a 2.67 times greater risk of mortality than those in the lowest (most stable) quartile.
From these studies, it seems quite clear that we want to lower average blood glucose and reduce the amount of variability from day to day and hour to hour. CGM is a tool that can help us achieve that. We use it in healthy people in order to help them stay healthy. That shouldn’t be controversial.
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. (The Hawthorne effect is also what makes it difficult to study what people actually eat, for the same reason.)
The real beauty of CGM is that it allows me to titrate a patient’s diet while remaining flexible.
Overall, I like to keep average glucose at or below 100 mg/dL, with a standard deviation of less than 15 mg/dL.
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] Also, sleep disruption or reduction dramatically impairs glucose homeostasis over time.
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.
Lessons from Continuous Glucose Monitoring
In the years that I have used CGM, I have gleaned the following insights—some of which may seem obvious, but the power of confirmation cannot be ignored:
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.
How much protein do we actually need? It varies from person to person. In my patients I typically set 1.6 g/kg/day as the minimum, which is twice the RDA. The ideal amount can vary from person to person, but the data suggest that for active people with normal kidney function, one gram per pound of body weight per day (or 2.2 g/kg/day) is a good place to start—nearly triple the minimal recommendation.
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.
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.)
There are (broadly) three types of fats: saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA).[*9] The differences between these have to do with differences in their chemical structure;
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. Even a ribeye steak contains a lot of monounsaturated fats.
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. We titrate the level of EPA and DHA in our patients’ diets by measuring the amount of each found in the membranes of their red blood cells (RBC), using a specialized but readily available blood test.[*11] Our target depends on a person’s APOE genotype and other risk factors for neurodegenerative and cardiovascular disease, but for most patients the range we look for is between 8 and 12 percent of RBC membrane composed of EPA and DHA.
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.
Medicine 3.0 asks, what is the “best” mix of fats for our patient? I use an expanded lipid panel to keep track of how changes in fatty acid consumption may affect my patients’ cholesterol synthesis and reabsorption, and their overall lipid and inflammatory response.
TR: The Case for (and Against) Fasting
Fasting, or time-restricted (TR) eating (regulating when you eat), presents us with a tactical conundrum. On the one hand, it is a powerful tool for accomplishing some of our goals, large and small. On the other, fasting has some potentially serious downsides that limit its usefulness. While intermittent fasting and eating “windows” have become popular and even trendy in recent years, I’ve grown skeptical of their effectiveness. And frequent longer-term fasting has enough negatives attached to it that I am reluctant to use it in all but the most metabolically sick patients. The jury is still out on the utility of infrequent (e.g., yearly) prolonged fasts. Overall, I’ve come to believe that fasting-based interventions must be utilized carefully and with precision.
Most important, you must create an environment for yourself that is conducive to sleeping well. The first requirement for good sleep is darkness. Light is the enemy of sleep, full stop. Thus, you want to make your bedroom itself as dark as possible—installing room-darkening curtains if you live somewhere with a lot of outdoor evening light, and removing all light sources in the bedroom, even down to electronic equipment like TVs and cable boxes and such. Their little pinpoint LEDs are more than bright enough to keep you from sleeping well. Digital clocks are especially deadly, not only because of their bright numerals but also because if you wake up and see that it’s 3:31 a.m., you might start worrying about your 7 a.m. flight and never fall back asleep.
The devices we stare at before bed—phones, laptops, video games—are even worse for our sleep. Not only do they bombard us with more blue light, but they also activate our minds in ways that impede our ability to sleep.
Another very important environmental factor is temperature. Many people associate sleep with warmth, but in fact the opposite is true: One of the signal events as we are falling asleep is that our body temperature drops by about one degree Celsius. To help that happen, try to keep your bedroom cool—around sixty-five degrees Fahrenheit seems to be optimal. A warm bath before bed may actually help with this process, not only because the bath itself is relaxing but also because when we get out of the bath and climb into our cool bed, our core temperature drops, which signals to our brain that it is time to fall asleep. (There are also a variety of cooling mattresses and mattress toppers out there that could help people who like to sleep cool.)
Our internal “environment” is just as important to good sleep. The first thing I tell my patients who are having difficulty sleeping is to cut back on alcohol—or better yet, give it up entirely.
Someone who metabolizes caffeine slowly should probably stop at one or two cups, before noon.
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).
It is also important to mentally prepare ourselves for sleeping. For me, this means avoiding anything that might create stress or anxiety, such as reading work emails or especially checking the news.
How to Improve Your Sleep
The following are some rules or suggestions that I try to follow to help me sleep better. These are not magic bullets but are mostly about creating better conditions for sleeping and letting your brain and body do the rest. The closer you can come to these operating conditions, the better your sleep will be. Of course, I’m not suggesting that it’s necessary to do all these things—in general, it’s best not to obsess over sleep. But the more of these you can check off, the better your odds of a good night of sleep.
Even just living alone, or feeling lonely, is linked to a much higher risk of mortality.
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.
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.
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.
Looking back on all this, one of the most important lessons that I learned is that the type of change I describe in this chapter is not possible unless we are equipped with a set of effective tools and sensors with which to monitor, maintain, and restore our emotional equilibrium. These tools and sensors are not innate; for most of us, they must be learned, and refined, and practiced daily. And neither are they quick fixes.
Two benefits of mindfulness:
Listen to your self-talk. Imagine instead that your best friend had performed exactly the same way. How would you speak to them?
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.
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.
It is also important to note that DBT is not a passive modality. It requires conscious thought and action on a daily basis. 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.
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.
The most important “tactic” by far is my regular weekly therapy session (down from three or four per week when I left PCS). This is not optional. Each session begins with a physical check-in: 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.
If you take nothing else from my story, take this: If I can change, you can change. All of this has to begin with the simple belief that real change is possible. That’s the most important step.
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. None of it matters if your wife hates you. None of it matters if you are a shitty father, or if you are consumed by anger or addiction. Your résumé doesn’t really matter, either, when it comes time for your eulogy.
All these need to be addressed if your life is to be worth prolonging—because the most important ingredient in the whole longevity equation is the why. Why do we want to live longer? For what? For whom?
“I think people get old when they stop thinking about the future,” Ric told me. “If you want to find someone’s true age, listen to them. If they talk about the past and they talk about all the things that happened that they did, they’ve gotten old. If they think about their dreams, their aspirations, what they’re still looking forward to—they’re young.”
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