Outlive - Raw Notes

Chapter 1 The author is a cancer surgeon who became disillusioned with his profession. The problem he saw was that by the time the patients got to him, often they’re pretty much dead anyway. With some intervention, they could give the patient a few months more of life. That felt like he was putting out fires that have already caused a lot of damage, when the focus should be on preventing the fires.

He outlined the four major causes of “slow” deaths:

• Cardiovascular disease
• Diabetes
• Cancer
• Neurodegenerative diseases

The current medical system diagnoses all of these too late in the game to really save the person. For example, when someone is just below the threshold of diabetes, they declare him as pre-diabetic and sometimes put him on drugs and vaguely monitor the situation for a year. He doesn’t think such a treatment is adequate, and by the time they’re pre-diabetic, it’s pretty late. Perhaps they’ll be able to prevent the person from becoming diabetic, but the person is already broken.

So he switched his career to focus on the preventive aspect. He highlights some of the ingredients he thinks are necessary:

• Diet: with an emphasis on protein as one gets older
• Exercise
• Mental health Chapter 2

He believes that modern medicine is very poor at risk analysis. It is biased against taking risks that could potentially harm one aspect of life while vastly benefiting other aspects. He gives the example of a large-scale study on hormone replacement therapy: it was found that it led to a 24% increase in breast cancer. But the breast cancer rates were so low to begin with that the absolute increase in the population was merely 0.1%. However, because 24% sounds like a large number, the hormone replacement therapy regimen was suspended. As a result, many people suffered from the lack of hormone replacement therapy.

Modern medicine is good at treating the cause of the fast death: things like infectious diseases. But he makes a compelling case that it’s pretty poor at treating slow deaths like cancer, diabetes, and cardiovascular disease. He has a plot where he shows that in the last 70 years, if you take the mortality rate and subtract the deaths due to the 8 leading causes of infectious disease, then the mortality rate is relatively flat. This is an indicator that modern medicine hasn’t made much progress on the slow deaths.

Not many studies go beyond 10 years, but the development of these diseases spans decades. Therefore, taking the results of the studies that span less than 10 years is really focusing on the tail end of the disease, where it probably has significantly progressed in the body.

He’s a strong believer in personalized medicine.

He also feels there’s not enough of a focus on the quality of life as opposed to merely extending the lifespan.

Most of healthcare spending goes towards treatment instead of prevention. As an example, insurance companies rarely pay for preventive behavior. But once you’re diagnosed with diabetes, they’ll pay a huge amount for the diabetes treatment because they need to be invested. Chapter 3 It’s common to spend your 70s with a significantly degraded quality of life. Both mental and physical problems can overtake your well-being. And then you die.

Everyone should think about what they want to do in their later life, including their 70s and 80s. That gives you a target for what you want to plan for.

Let’s assume you live in a world with no modern medicine. You will start to decline at a certain age, and the decline will just continue and continue until you die. With modern medicine, you’re still declining at the same rate, except when you’re very close to the bottom of your quality of life. The medical system then kicks in and extends your lifespan by a little bit. The problem with this approach is that prior to that intervention, you already had significantly degraded mental and physical well-being.

The author’s goal is to intervene much earlier and ensure that both physically and mentally your well-being can continue, and the decline, albeit fairly sharp, happens at a much later age.

There are three categories of deterioration: cognitive decline, physical decline, and emotional health.

Ask yourself what you want to be doing in your 60s and 70s. If you start listing physically strenuous activities like tennis, then ask yourself whether you can even do those now. If you cannot, then you are fairly ill-prepared to be able to do it at a later age when everything is working against you.

The tactics in what he calls medicine 3.0 fall into five domains:

1. Exercise
2. Nutrition
3. Sleep
4. Emotional health
5. Exogenous molecules (drugs, hormones, and supplements).

For exercise, the components are strength, stability, aerobic efficiency, and peak aerobic capacity. You have to increase your limits in all of these. Exercise is the most important of the five domains.

For nutrition, the first order effect is focusing on the amount of calories you take into your body. You have to figure out what the appropriate amount is for yourself.

Sleep is very important. Good sleep is necessary for repairing physiological problems.

Modern medicine relies heavily on randomized studies. Unfortunately, such studies are hard, if not impossible, to perform over several decades. Take a hundred or a thousand individuals at a very young age, split them into different categories, and apply different regimens over four decades to see the results. Even if you could, you have to control for all the other factors that may interfere, and it’s simply not practical. So the author relies on doing the best with the amount of data and evidence we can gather.

He identified five sources of information that are evidence-based. The first source is studying centenarians. The next source is studying animals. While it’s true that many studies involving animals don’t replicate in humans, if there are studies that consistently work across several animals and several species, there’s a good chance it’s applicable to humans as well.

The next source of information is pretty much everything we know about the four major causes of slow death: diabetes, neurodegenerative diseases, cardiovascular disease, and cancer.

The next source of information is whatever we know about drugs and supplements, as well as exercise.

The last source of information is a method of analysis called Mendelian randomization. The way it works is that if you take a lot of individuals and look at their genes, there’s a fair amount of variation amongst them. In one sense, that can be treated as a sort of randomized trial because the variations are random. An example given of this is the existence of studies that seem to imply a lower LDL cholesterol level correlated with a higher cancer risk. However, when you apply Mendelian randomization, you find out that they really are uncorrelated. Chapter 4

Centenarians live longer primarily because of their genes. The interesting thing about them is that they tend to appear and be physically and mentally younger than their peers at most stages of their life. So at 70 years old, they are in better health than most 70-year-olds. The diseases of slow death appear much later in their life. So not only are they simply living longer, they’re living better for decades longer than the average person.

By the age of 75, 20% of the general population will have received some type of cancer diagnosis. Centenarians at age 100 reach that threshold of 1 in 5 with a cancer diagnosis. Similarly, at 75, 25% of the general population have been diagnosed with some kind of cardiovascular disease, which occurs at age 92 for centenarians. Bone loss or osteoporosis occurs 16 years later for them than for the general population. Similar numbers exist for stroke, dementia, and hypertension.

This doesn’t hold true merely for the physical aspect, but for the mental aspect as well. If you take a typical assessment of physical and cognitive function for older individuals, they perform very well up to a fairly late age.

So while the general population spends their last decade suffering and being a patient in the medical system, centenarians often live their last decade fairly well and only have a very steep decline at the very end. This is called compression of morbidity.

Female centenarians outnumber male ones by a factor of four. However, the male ones typically score higher, both cognitively and on functional tests. As a general rule, women live longer than men, but older men perform better on these tests than older women. This might be a statistical quirk in that if a male has lived past a certain point, then you have filtered out a lot of the weaker males. In general, it seems that women can live longer while being sick than men can. Given the same age, a larger proportion of males are well compared to the proportion of females. This may be simply due to men having a larger muscle mass, which is fairly important as you age.

It is important to evaluate your family history. How long did your parents and their parents live? What kinds of diseases did they suffer from? How did they die? If they got cancer, when did they get it? You need to know how you are genetically predisposed so that you can make a strategy that counters that predisposition.

When researchers tried to identify a particular gene or gene variant that leads to longevity in these centenarians, they came up almost empty-handed. The reason is that natural selection is relevant only in terms of passing the genes on. So once you have children, it doesn’t matter that you have genes that’ll kill you in your 50s, because you most likely have had children by that point. Natural selection will not eliminate those genes from the population. Think Darwin Awards criteria.

That’s why most slowly lethal genes continue to survive in the population: they’re not going to kill you before you have children.

Centenarians live long because of a combination of a whole bunch of genes.

Still, they have identified some relevant genes. One of them is called APOE: it affects your risk for getting Alzheimer’s. It has three variants: e2, e3, and e4. Having one or two copies of the e4 variant significantly increases your risk of developing Alzheimer’s by a factor of somewhere between 2 and 12. It’s recommended you look up whether you have this variant. e2, on the other hand, appears to protect from dementia, and it’s highly correlated with longevity. Generally, people who have at least one e2 and no e4 are 30% more likely to reach extreme old age, which is 97 for men and 100 for women, compared to people with the standard e3 variant. Those with two copies of e4 are 81% less likely to live that long.

Another relevant gene and its variant is called FOXO3. When Fox03 is activated, it activates other genes that keep cells healthier. It likely plays a role in preventing cells from becoming cancerous. The interesting thing about it is that it can be activated or suppressed by behavior. When we are slightly deprived of nutrients, or we are exercising, Fox03 tends to be more activated, which is what we want.

It’s possible gene expression can be influenced by behaviors and environment. A 2007 study showed that older people who took on a regular exercise program shifted to a more youthful pattern of gene expression after six months.

Likely, centenarians can get away with a lot of bad behavior like drinking, smoking, and lack of exercise because their genes already do much for them that exercise gives us. The point being that if you exercise, your body behaves similarly to those centenarians who have those genes - or at least, that’s the hope.

One of the problems with the current medical methods is that it treats these conditions independently. We treat diabetes as if it’s unrelated to cancer or Alzheimer’s. But diabetes is a major risk factor for both. According to a University of Illinois Chicago researcher, the underlying risk factor for almost everything that goes wrong with us as we grow older is intertwined and interrelated. It doesn’t make sense to study these conditions in isolation. Chapter 5 Rapamycin is a chemical that is used to treat transplant patients because it suppresses the immune system. However, it has a lot of other uses. It’s a fairly powerful antifungal. It’s often used to fight kidney cancer.

The way it works is it slows down the process of cellular growth and division. It activates the part of the cell that is responsible for cleaning things up. Essentially, it makes cells feel as if they’re being deprived of a lot of nutrition, and the cells, as a result, become less wasteful and more efficient. They start cleaning up the mess within their own cells.

It extends the lifespan of mice. This has been well tested across the world in several studies. No other molecule has been shown to extend the lifespan of a mammal. It has been tested on genetically diverse animals, and the results have been consistent.

As an aside, resveratrol does not extend the lifespan regardless of what was reported earlier, nor does nicotinamide riboside.

There’s a general principle that goes back to ancient times: the notion that if you eat less, you’ll actually live longer. Specifically, without malnutrition. The idea is that you get all the nourishment, all the important vitamins and minerals, and so on, but find a diet that gives it to you with a smaller amount of calories.

This has been studied often, and the results are relatively consistent. The lifespan of animals like mice and rats increases. It’s been shown to be true across several species, including yeast, worms, flies, fish, hamsters, dogs, and spiders. In fact, perhaps the only exception is houseflies.

Now, this is not a good strategy to live your life. While it may be true that it will extend your lifespan, it leaves you vulnerable to several infectious diseases. There’s no point in dying of a preventable cause just so that you can try to avoid the slow death. However, stating this gives an idea of why caloric restriction works.

Part of why it works is that it has the same effect on the cells as rapamycin does. It inhibits cell growth. It makes cells become more fuel efficient and stress resistant and triggers autophagy, which means self-eating, which involves recycling.

Autophagy is essential to life. If it stops completely, the organism dies because it is no longer recycling the trash from the cell. As we get older, autophagy declines. Impaired autophagy is associated with ailments like neurodegeneration and osteoarthritis.

One of the reasons rapamycin hasn’t been approved for general public use is because of its immunosuppressing properties. However, recently it was discovered that a rapamycin analogue called Everolimus actually enhances the immune response. It is now believed that rapamycin is actually not a suppressant but a modulator. When taken in small quantities, it actually improves the immune system, but in large quantities it suppresses it. These are relatively new studies, so I’m not sure if future studies will support this. There is an ongoing study being done on giving dogs rapamycin to see if it extends their lifespan. The study will end in 2026.

There is another ongoing study being done on the potential longevity benefits of the diabetes medication Metformin. Metformin has been taken by many over several years, and researchers have started noticing that people on Metformin appear to have a lower incidence of cancer compared to the general population. One fairly large analysis showed that diabetics on Metformin actually live longer than non-diabetics. None of these has shown that Metformin actually makes people live longer, and that’s what the current clinical trial is hoping to investigate. Chapter 6 Consuming a lot of sugar can seriously damage the liver, leading to what’s called non-alcoholic steatohepatitis, or NASH. More than one in four people on this planet have it to some degree, or its precursor, known as non-alcoholic fatty liver disease.

Sometimes doctors do a blood test called alanine aminotransferase, or ALT for short. When the level is a little high, it is an indicator that something is wrong with the liver. The author, however, disputes what value is considered normal. Given that, as time goes by, these numbers seem to increase in the population, leading to a new normal. But normal doesn’t mean healthy.

Both NASH and non-alcoholic fatty liver disease are reversible. You have to remove the fat from the liver, and the most common mechanism to do that is weight loss. The inflammation goes away and the liver returns to normal. But if NASH is not kept in check or reversed, it may progress to cirrhosis. This happens to about 11% of patients with NASH. Once you have cirrhosis, it is difficult to reverse. You will most likely die from it unless you receive a liver transplant.

If you find yourself with non-alcoholic fatty liver disease, you’re likely on the path to one or more of the three horsemen: cardiovascular disease, cancer, and Alzheimer’s.

The author talks about metabolic dysfunction and how it should not be confused with obesity. So what is metabolic syndrome? Consider the following five criteria:

1. High blood pressure (>130/85)
2. High triglycerides (>150 mg/dL)
3. Low HDL (<40 mg/dL for men)
4. Central adiposity (Waist circumference > 40in for men)
5. Elevated fasting glucose (>110mg/dL)

If you meet at least three of these criteria, then you have metabolic syndrome. It’s believed about 120 million Americans have it and 90% of the population ticks at least one of these boxes. Note that obesity is merely one of the criteria and is not required for metabolic syndrome. In fact, about one-third of obese people are actually metabolically healthy, and 20 to 40% of non-obese adults are metabolically unhealthy by some of those measures. So don’t think that just because you are not overweight that everything is okay.

As an example, Americans that are of normal weight but metabolically unhealthy have more than triple the risk of all-cause mortality and/or cardiovascular events than metabolically healthy normal weight individuals. Meanwhile, the metabolically healthy but obese subjects are not at significantly increased risk.

Consider what happens when you eat food like carbohydrates: The carbohydrates could be converted into glycogen and available for use in the near term as needed, to be converted into glucose. 75% of the glycogen ends up in muscle and the rest goes to the liver. An adult male can store about 1600 calories worth of glycogen, which is about two hours of vigorous endurance. That’s why if you’re running a marathon, you do need to replenish.

One of the liver’s important jobs is to convert stored glycogen into glucose and release it to the bloodstream to maintain the glucose level. Another place energy is stored is fat. So how does the body know where to store the energy? Insulin is key in that mechanism. It is responsible for helping shuttle glucose to where it’s needed. If you’re typically sedentary, you do not need to use your glycogen rapidly. So the excess energy often ends up in fat cells.

Now, ideally, it will store it in subcutaneous fat, which is a relatively safe place. There was a study done on mice that were insulin resistant. They surgically implanted fat tissue into them to make them even more fat, and it immediately resolved their metabolic dysfunction. The new fat used the excess glucose and stored it safely.

Fat is a form of long-term energy storage. It is converted into energy as needed. However, if you keep consuming calories beyond your needs, your subcutaneous fat cells will eventually fill up. When that capacity is reached, the energy has to go somewhere. The body will find other places to deposit fat.

It will start dumping it in the blood in the form of excess triglycerides, and into your liver, contributing to non-alcoholic fatty liver disease. It also deposits fat into your muscle tissue, which contributes to insulin resistance, and around your heart and pancreas. All of these are bad places for fat to accumulate. This is called visceral fat.

Individuals vary in the amount of fat that can be stored in subcutaneous fat. Generally, people of certain descent have a lower capacity and are likely more at risk. This explains why some people can be obese but still metabolically healthy. Their genes allow them to store more fat or more energy in the subcutaneous fat. And that’s why certain skinny people are more at risk: they have a lower capacity to store fat, so even small excesses can lead to visceral fat.

Define how much visceral fat you have. You recommend undergoing a DEXA scan annually.

When fat finds its way into your muscle, insulin resistance starts. One key indicator is inactivity. If a person is not physically active, they are not consuming energy through their muscles, and the fat spillover-driven insulin resistance develops a lot quicker.

When they do a glucose test and you have high values, it means you have both high insulin levels as well as high glucose. If it continues this way, then the pancreas becomes fatigued. But if there’s fat around your pancreas, that exacerbates the situation.

Cortisol is particularly nasty because it depletes your subcutaneous fat and replaces it with visceral fat. This is why stress levels and sleep, both of which affect cortisol, are fairly important to metabolism. Insulin, though, is all about fat storage, not fat utilization. When the insulin in your body is chronically elevated, problems arise. One of the symptoms is weight gain.

Type 2 diabetes is a relatively modern disease. It was very rare in the past and only occurred amongst relatively wealthy folks. One in nine has Type 2 diabetes, including 29% of adults over 65. More than a third meet the criteria for pre-diabetes. If you add it up, that means almost half the population either has it or is on the path to get it.

Although diabetes ranks low in terms of the leading causes of death, it is actually something that puts you at greater risk for more common diseases like cardiovascular disease, cancer, Alzheimer’s, and other dementias.

We simply did not evolve for the modern lifestyle of low activity and highly available food. Fructose, in particular, is a powerful driver for metabolic dysfunction if consumed to excess. It is metabolized differently from other sugars. It produces a large amount of uric acid, but it’s also a driver for fat gain, even though it may be low in calories. Humans lack the ability to clear uric acid the way other animals do. From an evolutionary perspective, this was actually beneficial because it assisted in storing energy into fat, which would often be needed in colder climates.

He believes fructose is okay when consumed in a manner that the ancestors did, which is eating fruit directly as opposed to concentrated fruit juice. He’s not particularly against high fructose corn syrup because it’s almost the same proportion as regular sugar. Food high in chemicals called purines, such as certain meats, cheese, anchovies, and beers, also generate uric acid. Because of that, he often tests his patients’ levels of uric acid. High uric acid is an early sign of metabolic distress.

Glucose is metabolized very differently from fructose. When the cell breaks down glucose, it must expend a certain amount of adenosine triphosphate in order to make more. This expenditure is regulated by an enzyme. Metabolizing fructose, though, a different enzyme takes over and that enzyme does not regulate the expenditure of adenosine triphosphate. So, those levels in a cell drop rapidly, which makes the cell think it’s still hungry. So, fructose tricks the metabolism into thinking that we are depleting energy and we need to take in more food and store it as fat.

If you drink a large amount of fruit juice, more than the gut has the ability to handle, the excess energy is sent to the liver where much of it is stored as fat. Patients can get non-alcoholic fatty liver disease by drinking too many healthy fruit smoothies.

As mentioned a while ago, you need to satisfy three out of the five conditions or criteria to be considered to have metabolic syndrome. The author is questioning why one has to wait until three of them are satisfied. He also looks at lipoproteins and triglycerides. He watches the ratio of triglycerides to HDL. But the most important thing he looks for is elevated insulin levels.

The problem with glucose tests is it’s possible to have fairly elevated insulin levels and a normal glucose. But that’s actually a sign of a pancreas in distress. It shouldn’t need to generate that much insulin. So the test he uses for his patients is called an oral glucose tolerance test, where the patient consumes a very sweet drink that contains 75 grams of glucose. They then measure the patient’s glucose and insulin every 30 minutes for two hours. The blood glucose levels should rise, followed by a peak in insulin. Then the glucose will decrease as insulin does its job. But if someone is in the early stage of insulin resistance, the insulin will rise dramatically in the first 30 minutes and then remain elevated over the next hour. That’s a warning sign.

Having high insulin levels is not merely an indicator of diabetes. Insulin resistance is associated with a huge risk in cancer, up to 12-fold. A 5-fold increased risk in Alzheimer’s and a 6-fold increased risk from cardiovascular diseases.

If any other hormone were to go out of balance, like thyroid or cortisol, doctors act swiftly to rectify this condition. But when it comes to insulin, we tend to wait till it’s quite late. Chapter 7

(Note: I didn’t audit the speech recognition output for typos below).

The first presentation of a heart attack can often be sudden death. It isn’t always preceded by some kind of pain or shortness of breath.

Heart attacks are fatal roughly one-third of the time.

Cardiovascular diseases are the Number 1 cause of death globally.

The author underwent a CT scan of his heart intended to detect calcification in the coronary arteries during his 30s, which resulted in a score of six - quite low. Although severe cases may score over a thousand, a score of zero is expected for someone in their 30s. His score placed him in the 75th to 90th percentile for his age, suggesting he had the arteries of a 55-year-old. However, as his overall score was still low, most physicians would dismiss it and not consider treatment.

He was overweight and borderline insulin-resistant, but his LDL scores were good.

Heart disease is easier to prevent than cancer or Alzheimer’s. He feels it should not be the leading cause of death but perhaps further down on the list.

He is against looking at the total cholesterol figure. He thinks it has very little relevance to cardiovascular risk. Cholesterol is essential to life, and it is produced in the body. While it is produced in many places, 20% of the supply is found in the liver, which acts as a repository. The liver shifts it out to cells as needed and receives it back.

Cholesterol is part of the fat family. It’s not water-soluble, so it needs to be carried around by special particles called lipoproteins. LDLs are called “low” because they carry more lipids. HDLs carry more protein in relation to fat and are therefore more dense. HDL carriers and LDL carriers frequently exchange cargo between themselves, so it’s silly to label one as good and the other as bad.

What causes problems isn’t the LDL or HDL itself, but the molecule that wraps them and carries them around. LDLs are encased in a apollipoprotein, also known as apoB, and that’s what causes problems related to heart disease. The key thing to note is that LDL is not the only entity that is carried by these proteins. So even if your LDL is low, you may still be carrying a huge amount of these proteins around.

So don’t measure the amount of LDL you have, but the amount of these proteins that you’re carrying around.

Most of the cholesterol we consume is excreted from the body. Sure, some of it might be retained and may contribute to the problem, but the bulk of the cholesterol that causes problems in the body is generated by the body.

Apparently, in 2015, the US government dietary guidelines changed to state that cholesterol is not a nutrient of sufficient concern for over-consumption.

Heart disease is not just a concern for the elderly. For men, half of the major adverse cardiovascular events - such as heart attacks, strokes, or procedures involving a stent or graft - occur before the age of 65. A quarter of them occur before the age of 54. For women, about a third of these events occur under the age of 65.

The events leading up to heart disease have been developing in your body for years. It’s a slow-moving but sneaky disease. Some scientists believe that the processes are set into motion in late adolescence, perhaps during our teen years, and the risk builds up from there. Autopsies on teenagers and 20-year-olds who died for other reasons already showed damage in their arteries.

HDL can reverse some of the damage that LDL-carrying proteins do. They provide other benefits to the body as well. However, having a high HDL has not been well studied, and it’s not clear how beneficial or harmful it is. It is said that risk seems to decline as HDL rises to about the 80th percentile, but artificially raising HDL by brute force using drugs has not shown any impact on vascular disease.

Regular CT scans for calcium are fuzzy, and damage that is visible is often overlooked. A better type of CT scan is called the CT angiogram, which does have a slightly higher dose of radiation, but it’s better at identifying the plaque that precedes calcification. Experts often see patients who had a normal calcium score of zero from the regular CT scan, but the angiogram showed high-risk plaque.

Prior to calcification, the plaque may not be visible in a CT scan. You have to wait till it calcifies for a regular CT scan to show it. Calcification is an attempt by the body to repair damage, but it is also an indicator of actual damage. If you have a positive calcium score, there’s a good chance you have undetected plaque elsewhere in your body.

Uncalcified plaque may result in the formation of a clot. That’s why he worries more about non-calcified plaques than the calcified ones. Most plaques grow silently without causing any problem to your body until they hit the critical size, and even then, you may only feel it when you do vigorous activity.

There is now a test for measuring the amount of those harmful LDL-carrying proteins in the body. The test is not commonly done, but according to one analysis, each standard deviation increase in that protein raises the risk of myocardial infarction by 38% in patients who don’t have a history of cardiac events. He has all his patients tested with that test regularly. He suggests asking the doctor for that test the next time you see them. The underlying cost is only about $20 to $30.

He is very focused on lowering that number. The goal is to get it as low as possible, as early as possible.

Some people have a deadly type of particle called LP(a). It provides some good use to the body, but it has the same harm as the LDL-carrying protein and is, in fact, a lot more harmful. It speeds up the formation of arterial plaques.

When you have a patient that says their father, grandfather, or aunt died of premature heart disease, the first thing to look for in that patient is LP(a). It is the most prevalent hereditary risk factor for heart disease.

Most people have a small concentration of this particle, but certain people have up to 100 times more. It’s largely genetic. Roughly 20% to 30% of the US population has a high concentration. As an example, generally, if you’re of African descent, you have a higher concentration. The test for this is mostly genetic, so it needs to be done only once.

Exercise and dietary changes help prevent the damage that LDL-carrying proteins do, but they have no impact on LP(a). There is a class of drugs called PCSK9 inhibitors, which lower those protein concentrations and do seem to reduce LP(a) levels by roughly 30%. As of yet, there’s no evidence that it actually reduces events like heart attacks.

The only approach for those people is to try to reduce the protein levels overall.

So, APOB and LP(a) are the top two things he looks for in his patients.

Say you have a high APOP number. What is the approach to reducing it, and how low do you need to go? Treatment guidelines specify a target range for LDL: 100 milligrams per deciliter for patients with normal risk and less than 70 milligrams per deciliter for high-risk individuals. He thinks these numbers are way too high. He believes the goal is to get these numbers down as low as possible without incurring any side effects from the treatment.

One of the leading authorities on cardiovascular disease states that if it could be brought down to 10 to 20 milligrams per deciliter, it would probably eliminate most heart events.

Even though cholesterol is vitally needed for the body, he thinks it’s okay to go that low given that babies have levels that low and they need a lot of cholesterol and they do just fine. There have been a whole bunch of studies showing no ill effects from extremely low LDL concentrations.

The other markers or factors that he looks at are insulin, visceral fat, homocysteine.

He more or less ignores HDL. Having a very low HDL is associated with higher risk, but he doesn’t think it’s causal. He has seen that drugs that raise HDL do not reduce risk.

If one is smoking or has high blood pressure, that is the first thing to aim to fix. When it comes to diet, the focus is on lowering triglycerides, which are contributors to those proteins, and managing insulin levels. He solved his problem with a ketogenic diet but doesn’t generally recommend it because it’s often high in saturated fat, which will dramatically increase the numbers of those proteins. Monounsaturated fats don’t have this effect, so he encourages his patients to consume more of those, aiming for it to be about 60% of their total fat intake.

Getting to the low levels that he aims for cannot be done with diet alone. For that, you need to add drugs into the mix. Things like statins, which are his first choice. Statins inhibit the synthesis of cholesterol. They also seem to have an anti-inflammatory effect. About 5% of patients have side effects with statins, particularly muscle pain, so they’re not for everyone. A smaller subset of patients taking statins experience a higher risk for type 2 diabetes. Another small fraction have some liver problems. For both of these, the side effects are rapidly reversed when they stop taking statins. His approach is to put people on statins and closely monitor them, keeping them on the medication if there are no side effects.

The damage related to heart disease starts at a fairly young age and should be treated from a fairly young age. When you treat it at an older age, a lot of the damage has already been done. It doesn’t make sense to wait until you’re close to having a heart attack to treat it.

He got his scan done at age 36 and went on aggressive mitigation. He got himself scanned multiple times, including at age 50, and subsequent scans have shown no further damage.

Most studies focus on a five-year horizon when it comes to statins. You found one study that looked at a 30-year horizon, and it suggested that for every seven people who are on statin at an early age, you’d save one life.

He makes the analogy with smoking and lung cancer: we know that these proteins are causative, not merely correlated. We know the damage is being done to the arteries, and, over time, this will eventually cause an event. Similarly, smoking causes damage to the lungs and contributes to potentially getting lung cancer. Yet, we’re very clear that people should not smoke right from the start. We don’t wait for sufficient damage to be done to their lungs to tell them to stop smoking and say that it’s okay to smoke prior to that threshold being met. Why should we have a different attitude towards heart disease?

When it comes to statins, he starts with rosuvastatin, also known as Crestor, and he changes only if there is a negative effect from that drug. If they can’t tolerate statins, he uses a newer drug called Bempidoic Acid, also known as Nexlitol. Another drug is Ezetimibe, also known as Zetia. And there’s also PCSK9 inhibitors.

Statins do not reduce LP(a), but PCSK9 inhibitors do. He also tries to lower triglycerides using dietary intervention. Such interventions don’t always work for various reasons, including genetic reasons. In those cases, he recommends fibrates as a drug to consume. There’s also Vascepa, which is derived from fish oil and has been approved to reduce LDL in patients with elevated triglycerides. Chapter 8 He begins with the story of someone who had been treated to remove a stomach tumor years ago. At that time, it had metastasized and shown up in the liver. Normally, people with such a condition will not survive long, yet he survived over a decade. When the doctors checked, his cancer in the liver had gone. Somehow, his immune system managed to eradicate it after the removal of the stomach tumor.

The doctor who observed this decided to focus on immunotherapy for cancer.

It’s very rare for the immune system to suddenly manage to attack and destroy metastasized tumors. There are very few known cases of it. Is there something special in those patients that we can learn from?

Cancer continues to claim the lives of Americans at almost the same rate as it did 50 years ago. Unfortunately, significant progress in reducing cancer mortality rates has been limited.

We have made progress with leukemia. For adults, the 10-year survival rate has doubled between 1975 and 2000, going from 23% to 44%.

Usually, by the time cancer is detected, it has likely been progressing for years, if not decades.

Surgery is of limited value if the cancer has metastasized. Metastatic cancers can be slowed by chemotherapy, but they almost always come back and are usually more resistant to treatment when they do.

We are fairly poor at early detection.

The solution is threefold:

1. Try to avoid getting cancer.
2. Use newer and smarter treatments to target the cancer’s weakness.
3. Improve cancer detection.

Cancerous cells don’t grow faster than other cells. What differentiates them is that they simply continue to grow where other cells stop dividing.

Typically, cancer will kill you only after metastasis. If it remains in one organ, it usually doesn’t kill. Unfortunately, only 5% to 8% of U.S. cancer research funding goes into studying metastasis. We’re not good at detecting when it will metastasize. The focus has been more on treatment rather than understanding.

Chemotherapy drugs attack cells that replicate rapidly, which tend to be cancerous cells. However, we also have some regular cells that normally replicate rapidly, such as those in the stomach and hair follicles. That’s why digestion issues and hair loss are common among chemotherapy patients.

And chemotherapy can be brutal. Christopher Hitchens said that he would lie for days, trying in vain to postpone the moment when he would have to swallow. Every time he swallowed, it was incredibly painful. It seemed he did not think the treatment was worth it.

One of the problems is that the immune system doesn’t see cancerous cells as the enemy. There’s something about cancerous cells that tells the immune system that they’re totally normal.

In the 1920s, a German physiologist observed something unique about cancer cells: they had a huge appetite for glucose, consuming it about 40 times the rate of healthy tissues. However, they used anaerobic respiration instead of aerobic respiration, which is less efficient. One way to detect tumors is to look for locations in the body with an abnormally high glucose concentration.

It turns out that producing energy inefficiently is actually a side effect; the goal isn’t merely to produce energy. While aerobic respiration typically produces only energy, anaerobic respiration generates other materials, which cancerous cells utilize to grow and build cells rapidly.

Obesity and type 2 diabetes increase the risk of many types of cancers, including esophageal, liver, and pancreatic. Excess weight is a leading risk factor for cancer cases, second only to smoking. About 12% to 13% of all cancer cases are thought to be attributed to obesity. Type 2 diabetes increases the risk of certain cancers by as much as double in some cases, like pancreatic and endometrial cancers. Extreme obesity is associated with a 52% greater risk of death from all cancers in men and 62% in women.

Some researchers believe insulin acts as a cancer enabler, accelerating its growth. They suspect lowering insulin levels could slow the growth of some cancers and reduce cancer risk. Laboratory animals on a calorically restricted diet develop cancer at far lower rates than control animals. So for them, getting metabolic health in order is essential for anti-cancer prevention, particularly by lowering insulin levels.

Some cancer drugs actually increase insulin levels, which works against the goal to eradicate cancer.

He talked about one trial where several cancer patients were given PI3K inhibiting drug treatments. There was one particular patient who also underwent an advanced kind of metabolic therapy. She worked aggressively to maintain a diet rich in leafy vegetables, olive oils, avocados, nuts, and small amounts of protein, eliminating sugar and refined carbohydrates. She underwent frequent blood tests to ensure her insulin and IGF-1 levels remained low. Over the next few years, all the other women in the trial died. She was the only survivor.

The transcript is already neat and doesn’t require additional edits. Here’s a clean version just for confirmation: Subsequently, they did a study on mice, giving them a combination of a ketogenic diet and PI3K inhibitors. It showed improved response to treatment.

Another study showed that fasting or a fasting-like diet increases the ability of normal cells to resist chemotherapy, while cancer cells become more vulnerable to the treatment. They found that there are no major adverse events in chemotherapy treatments and that fasting occasionally improves the quality of life for patients. This goes against traditional practice where they try to get patients to eat high-calorie and even high-sugar diets. More studies need to be done.

No single treatment is particularly or universally effective, but a combination of different treatments, he suspects, increases the chances of successful outcomes.

The goal of immunotherapy is to get the immune system to identify the cancerous cells as foreign or to remove the mechanisms by which those cells manage to hide from the immune system.

There is an immunotherapy treatment called CAR T-cell therapy. It has been proven successful against B-cell lymphoma but not other cancers. It works because we can live without B-cells, allowing it to obliterate all those cells.

James Allison discovered another immunotherapy treatment, which he tested on cancer-prone mice, resulting in a 100% success rate. All the mice that received the treatment survived, while those that were not treated succumbed to the disease. The significance of the findings was clear without the need for statistical analysis. This breakthrough led to the development of two checkpoint-inhibiting drugs: Urvoi and Keytruda. These drugs can be quite effective, as evidenced by cases like Jimmy Carter, who was treated for metastatic melanoma, and another patient whose cancer had spread to the pancreas. Although the second patient was cured, the treatment destroyed the pancreas, resulting in type 1 diabetes. Despite this, it was still considered a positive outcome.

This type of treatment only benefits about 8% of people with cancer because only a third of cancers can be treated with immunotherapy, and of those, only about a quarter benefit from this particular treatment. It’s also fairly expensive.

There is another treatment called adoptive cell therapy (ACT). The idea is that cancer cells at some point grow more rapidly than the immune system has the ability to attack. So there’s a way to essentially drastically boost the amount of cells responsible for attacking them in the immune system. It’s a very expensive and labor-intensive procedure as well. However, he points out that in the long run, chemotherapy is also very expensive given that it usually has remissions.

He points out that immune-based cancer treatments, when they work, work really well. With traditional chemotherapy, remission is common. But when patients respond to immunotherapy and go into complete remission, they stay that way more or less. Between 80 and 90% of patients who went into remission from immunotherapy remain disease-free 15 years out.

The 10-year survival rate for patients with metastatic cancer is virtually the same now as it was 50 years ago: zero. So the focus really needs to be on early cancer detection before there’s a chance of metastasizing.

When cancers are detected early in stage 1, survival rates skyrocket. He believes that early detection is really the best hope for reducing cancer mortality.

We’re not good at detecting most cancers in the early stage. There are reliable screening methods for only five of them: lung, breast, prostate, colorectal, and cervical. Even then, there’s debate on how soon you should start screening because of the risk of unnecessary procedures and false positives. He feels the focus should be on reducing false positives.

Any given test may not be that accurate or may give too many false positives. So one approach is stacking different tests. If multiple tests point in the same direction, then the chances of detecting a real tumor are high.

He recommends colorectal cancer screenings earlier than the official guidelines. He also recommends doing them more frequently. The reason is colorectal cancers are one of the easiest to detect and have the greatest payoff in risk reduction. It’s one of the top five deadliest cancers, but it is the one that we are most capable of detecting early. It grows in an accessible location - the colon - and can be seen without any need for imaging techniques or surgical biopsies. He doesn’t think much of stool-based tests and believes nothing compares to a colonoscopy. He suggests average-risk individuals get a colonoscopy at age 40, and sooner if they are at higher risk, and repeat the procedure every two to three years, depending on the findings of the previous colonoscopy.

15% of people who get lung cancer have never smoked. In non-smokers, lung cancer ranks as the seventh deadliest cancer. There are low-dose CT scans for lung cancer screenings, and they’re recommended currently for smokers and former smokers, but he thinks they should be recommended to the whole population.

MRI has an advantage over CT scans in that it doesn’t produce radioactive particles but still has decent resolution. There’s a special type of MRI called diffusion-weighted imaging, or DWI for short. The idea is to look at water movement in and around the tissue at different points in time, very close to each other. If it’s held or trapped, then it could indicate the presence of a tightly packed cluster of cells. At the moment, DWI works best in the brain.

DWI has a fairly high false positive rate. So it’s best when combined with other tests.

He tells people that a whole-body screening MRI has a good chance they’ll be chasing down an insignificant thyroid or other nodule in exchange for getting a good look at the organs. Because if there’s a quarter of his patients, he’d like them not to undergo those screenings.

There’s a new category of tests called liquid biopsies that try to detect cancer via blood tests. They’re usually used to detect recurrence in cancer patients and to screen cancers in otherwise healthy patients.

The idea is this: because cancer cells are growing constantly, they tend to shed cellular matter, including bits of tumor DNA, into the circulation. So, a blood test will try to detect the so-called cell-free DNA. The issue is that the concentration is very low. In early stage cancer, perhaps 0.01% to 0.001% of cell-free DNA actually comes from the cancer. So, even if the test detects a lot of cell-free DNA, the vast majority of it has nothing to do with the tumor. Improvements are needed in these types of detections.

There is another type of test called the GRIL test, also referred to as the gallery test. Along with AI, the aim of this test is to determine if a person has cancer and, if so, where it is located. The test has a much higher resolution than radiographic tests such as MRI or mammograms. This allows it to detect tumors that are much smaller, which can only happen when they are above a certain size with the gallery test.

One other benefit of liquid-based tests is that they not only detect the presence of a tumor, but also identify the type of tumor and its stage.

Overall, cancer is probably the hardest thing to treat and the greatest barrier to living a long life. The first rule is don’t get cancer because treatment is relatively poor. If you do get cancer, the second rule is to catch it as soon as possible. Chapter 9

The gene related to Alzheimer’s disease is the APOE genotype. If you have the E4 allele, you have a higher risk of Alzheimer’s disease. If you have two copies of the E4 allele, it means your risk is 12 times greater than that of someone with two copies of the common E3 allele. If you have the E2 version, you have a reduced risk: 10% reduced for someone with E2/E3 and about 20% for E2/E2.

Generally, scientists don’t know much about how and why it begins, how to slow or prevent it. There’s also no way to treat it once symptoms begin.

The other main neurodegenerative diseases are Lewy body dementia and Parkinson’s disease. Lewy body dementia is primarily a dementing disorder affecting cognition, while Parkinson’s mostly affects movement, although there is a bit of cognitive decline. In the US, 6 million people are diagnosed with Alzheimer’s, 1.4 million with Lewy body dementia, and 1 million with Parkinson’s. Parkinson’s, though, is the fastest growing neurodegenerative disease. Less common are ALS and Huntington’s disease.

At the moment, the only way is to try to prevent it.

He notes there are E4:E4 carrying centenarians without any signs of dementia. They probably have other genes that protect them from E4. And plenty of normal E3:E3 carriers will still go on to develop Alzheimer’s.

Alzheimer’s patients have a large buildup of plaque in the brain. It’s a peptide called amyloid beta. For a long time, and even now, many believe that amyloid beta is the cause of Alzheimer’s disease.

Lab mice has been engineered to generate amyloid beta, which has difficulty performing cognitive tasks that are normally easy. Amyloid also triggers the aggregation of another protein called tau, which leads to inflammation and eventually brain shrinkage.

There are a bunch of genetic mutations that promote very rapid amyloid beta accumulation, pretty much guaranteeing that someone will develop the disease often at a fairly young age. Families carrying these mutations experience very early onset of Alzheimer’s, often developing in their 30s and 40s. These mutations are rare, but they occur in 10% of early onset Alzheimer’s cases and about 1% of all cases.

For a long time, it was believed that if you could eliminate the amyloid, then you could halt or even reverse the progression of the disease. However, several drugs have been developed that target amyloid beta in one way or another. Even when they succeed in clearing amyloid or slowing its production, it has shown no effect on the progression of the disease. Every single one failed. So then they considered giving these drugs very early on, before Alzheimer’s symptoms have even developed. This has been tested in large and well-publicized clinical trials involving people with a mutation that more or less guarantees early-onset Alzheimer’s. Again, the trial showed failure. Still, there are other hypotheses currently being tested along similar grounds, so the jury is still out.

There was a widely cited 2006 study that gave a lot of strength to the amyloid theory, and it is now believed that the data had been falsified.

Autopsies have shown that more than 25% of cognitively normal people had large deposits of amyloid in their brains when they died, some of them with the same degree of plaque buildup as patients who died with severe dementia. These people were normal with no cognitive symptoms. This has been known since the ‘60s. Some argue that these patients actually did have Alzheimer’s, but the symptoms had not manifested.

On the flip side, there have been recent studies showing that some patients have all the symptoms of Alzheimer’s, including significant cognitive decline, with little to no amyloid in their brains. Three patients with mild to moderate dementia had no evidence of amyloid in their brains. Other studies have found only a weak correlation between the degree of amyloid and the severity of the disease.

So it seems amyloid-beta plaques are neither necessary nor sufficient for Alzheimer’s.

The researcher who originally identified amyloid in Alzheimer’s found it in a patient who had died in her 50s and showed significant cognitive decline. Regular Alzheimer’s patients usually show symptoms after the age of 65, so he was likely looking at an extreme case. In fact, genetic tests have been performed on the patient’s tissue to show that she did have the genes for early Alzheimer’s.

Having the APOE4 variant not only increases your risk for Alzheimer’s but also for Lewy body dementia, as well as Parkinson’s disease.

There have been studies in Europe showing that interventions around nutrition, physical activity, and cognitive training help maintain cognitive function and prevent decline amongst a group of at-risk older adults. The author didn’t make it clear if they had already been diagnosed with Alzheimer’s or if these were everyday adults.

Having the APOE E4 genotype means you’re at higher risk if you’re Caucasian and female. Generally, Africans have a higher overall Alzheimer’s risk, but a lower risk if they have the E4 gene. Alzheimer’s is twice as common in women than in men, and this is not simply because they live longer. In China, Parkinson’s is twice as prevalent in men. However, if Parkinson’s appears in a female, it usually progresses more rapidly.

Most cognitive tasks can involve several parts of the brain. Often, if one part becomes weaker, other parts become stronger to compensate. This can make it harder to identify Alzheimer’s early because no cognitive decline is visible. At the same time, having more of these networks and subnetworks to provide redundancy actually makes the body more resistant to cognitive decline. It has been shown to help some patients resist the symptoms of Alzheimer’s, delaying their manifestation.

Similarly with Parkinson’s, people with better movement patterns, such as trained athletes, tend to resist or slow the progression of the disease compared to sedentary people. It’s not just movement and exercise, but also more complex activities like boxing workouts, which serve as primary treatments and prevention for Parkinson’s. So far, exercise is the only intervention shown to delay the progress of Parkinson’s.

People who die of Alzheimer’s often show a marked calcification of the blood vessels and capillaries that feed the brain. It is believed to be a consequence of neurodegeneration and not a cause. However, there have been experiments where the amount of blood flowing to rats’ brains was restricted, and eventually, those rats developed symptoms very similar to those of Alzheimer’s, like memory loss. Restoring blood flow would halt or reverse the damage to some extent, but it seemed to be more severe and lasting in older animals than younger ones. So, a robust blood flow seems critical to maintaining brain health.

The brain uses up 20% of our total energy expenditure. It metabolizes glucose differently from the rest of the body. It doesn’t rely on insulin; instead, it absorbs circulating glucose directly.

So one theory is that Alzheimer’s is really a result of long-term reduction in blood flow to the brain. Alzheimer’s is more likely to be diagnosed in patients who have suffered a stroke. People with a history of cardiovascular disease are at a higher risk of developing Alzheimer’s. There’s a linear relationship between cognitive decline and increased intimal media thickness in the carotid artery. Cerebral blood flow declines naturally during the aging process.

There is a connection between Alzheimer’s and metabolic dysfunction. Having type 2 diabetes doubles or triples your risk of developing Alzheimer’s. That’s about the same as having one copy of the APOE E4 gene. Insulin resistance alone is enough to elevate one’s risk. Insulin plays a key role in memory function. Spraying insulin directly into the subject’s noses quickly improves cognitive performance and memory, even in people who have already been diagnosed with Alzheimer’s.

People with the E4 allele appear to have defects in both cholesterol transport and glucose metabolism. Interestingly enough, for most of human history, the majority of people were E4/E4. It was the original human allele. The E3 mutation showed up about 200,000 years ago, and E2 in the last 10,000 years. Having E4 may have been helpful in surviving in environments with high levels of infectious disease. Children carrying that allele are more resistant to diarrhea and have stronger cognitive development. It promotes inflammation, which can be beneficial in situations like fighting infections, but harmful in the context of modern life.

People with the E4 allele show dramatic blood glucose spikes after eating carbohydrate-rich foods. Thus, people with E4 are at a higher risk of metabolic dysfunction.

So his first step is to address any metabolic issues someone may have. High doses of DHA may be required for E4 individuals. The ketogenic diet may offer a significant advantage when you are in ketosis. The brain relies on a mix of ketones and glucose for fuel. Alzheimer’s patients have difficulty getting their brain to utilize glucose, but metabolizing ketones does not decline. So it makes sense to divert the brain’s fuel from glucose to both glucose and ketones. Some studies have shown a benefit of this diet in early-stage Alzheimer’s.

The most important item is exercise, both because it helps maintain glucose homeostasis and because it improves the health of the vasculature. 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 may be as important. A study looking at nearly half a million patients in the UK found that grip strength, which is a great proxy for overall strength, was strongly and inversely associated with the incidence of dementia. People in the lowest quartile of grip strength had a 72% higher incidence of dementia compared to those in the top quartile. The association held up even after adjusting for confounding variables.

Sleep is a very powerful tool against Alzheimer’s. It is when the brain heals itself, particularly in deep sleep. Sleep disruption and poor sleep drive an increased risk of dementia. When you combine poor sleep with high stress and elevated cortisol levels, it acts as a multiplier of risk because it contributes to insulin resistance. Excessive cortisol due to stress impairs the release of melatonin.

Hearing loss may be causally associated with Alzheimer’s. Hearing loss is linked to cognitive decline because people with hearing loss tend to withdraw from interactions with others. When the brain is deprived of inputs, such as auditory inputs, it withers.

Good gum health - which means brushing and flossing - could be a preventive factor as well. A microbe that commonly causes gum disease is responsible for large increases of having shown up in the brains of patients with Alzheimer’s. We don’t know yet whether the bacteria causes dementia. Additionally, oral health correlates strongly with better health overall, especially when it comes to cardiovascular diseases.

He’s also beginning to think that dry saunas are relevant. It’s early to say, but he is recommending four sessions a week, of at least 20 minutes a session, at 82 degrees Celsius or hotter. It seems to reduce the risk of Alzheimer’s by about 65% and cardiovascular disease by 50%.

Other interventions that have shown promise are B vitamins and omega-3 fatty acids. Higher vitamin D levels have been correlated with better memory in E4/E4 patients, but it has not yet been shown whether supplementing with vitamin D reduces the risk of Alzheimer’s disease.

1. What’s good for the heart is good for the brain.
2. What’s good for the liver and pancreas is good for the brain.
3. Prevention has to start early.
4. The most powerful tool for preventing cognitive decline is exercise.

Chapter 10

There are five things to focus on:

1. Exercise.
2. Diet.
3. Sleep.
4. Emotional health.
5. Drugs and supplements.

When it comes to car accidents, the majority of deaths do not occur on the highway. They occur when there’s alcohol involved or excessive speed. One of the high-risk factors of getting killed while driving is a car slamming you on the driver’s side. This can happen when you are crossing an intersection, and a car hits you from the left. So it’s a good idea to always check the left side when you’re crossing an intersection, even if you have the right of way.

When he sees new patients, he asks three key questions:

1. Are they overnourished or undernourished?
2. Are they undermuscled or adequately muscled?
3. Are they metabolically healthy or not?

If a person is overnourished, the goal is to lose weight, but you don’t want to lose muscle along with it. So you can’t treat these three independently of one another.

He doesn’t advocate for any specific school of thought or ideology like keto or low-fat diets. Likewise, he doesn’t encourage choosing aerobic training at the expense of strength training or vice versa. The best advice will vary from individual to individual, and he is open to changing his mind on these topics as time goes on.

Chapter 11 He cautions against following the “One True Church” and advises to avoid religious wars over which exercise and nutrition diets to follow. The debate is pointless.

Exercise has the greatest power to determine how you will live out the rest of your life. 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. It’s very effective at extending and improving healthspan. It reverses physical decline, but it also reverses cognitive decline as well. It is believed to improve emotional health, although that’s harder to measure.

If you build only one set of new habits based on this book, it has to be exercise.

Going from zero exercise to just 90 minutes a week reduces your risk of dying from all causes by 14%. You’re not going to find a drug as effective as that.

Lots of studies have shown that regular exercisers live as much as a decade longer than sedentary people. Not only do they live longer, but they usually have better health and less morbidity from causes related to metabolic dysfunction.

The benefit of aerobic exercises is enhancing the body’s ability to deliver oxygen to your muscles efficiently. It also increases your stamina. The more aerobically fit you are, the more energy you’ll have for whatever you enjoy doing, even if it’s shopping.

The more oxygen your body is able to use, the higher your VO2 max.

The average 45-year-old will have a VO2 max around 40 milliliters per kilogram per minute, while an elite endurance athlete will score in the high 60s and above. An unfit person in their 30s or 40s might score only in the high 20s. They simply won’t be able to run up that hill at all.

A 2018 study followed more than 120,000 people and found that higher VO2 max was associated with lower mortality across the board. The fittest people had the lowest mortality rates. A person who smokes has a 40% greater risk of all-cause mortality than someone who doesn’t smoke. However, someone with a low average VO2 max, between the 25th and 50th percentiles, is at double the risk of all-cause mortality compared to someone in the top quartile. Thus, poor cardiorespiratory fitness carries a greater relative risk of dying than smoking.

Someone in the bottom quartile of VO2 Max, which is less than the 25th percentile, is nearly four times more likely to die than someone in the top quartile, and five times more likely to die than a person at the elite level, which is the top 2.3%. Even just climbing from the bottom 25th percentile into the 25th to 50th percentile means you cut your risk of death nearly in half.

A large-scale study was conducted involving 750,000 veterans aged 30 to 95. The research found almost the same results: a person in the least fit 20% had a 4.09 times greater risk of dying than someone in the top 2% of their age and sex category. Even someone in the 40th to 60th percentile is still at more than double the risk of mortality compared to the fittest group.

There are confounding factors such as nutrition, but he wants to note that the magnitude of the effect is very large. The data is consistent and reproducible across studies with different populations. There is a dose-dependent response, meaning the fitter you are, the longer you live. The biology of the effect is well understood, and there’s a lot of experimental data on this.

Furthermore, researchers have not seen any upper limit to the benefit. Simply put, the fitter you are, the longer you tend to live. It doesn’t saturate at any point.

Now let’s talk about muscles. A 10-year study of about 4,500 subjects ages 50 and older found that those with low muscle mass were at a 40 to 50% greater risk of mortality than the controls over the study period. It’s not just the muscle mass that matters, but the strength of those muscles - their ability to generate force. Just having large biceps in the gym is not that relevant. They have to be strong, meaning the ability to create a large force.

There is some data supporting the notion that strength may be even more important than cardio fitness. A researcher followed a group of about 1,500 men over 40 years old with hypertension for about 18 years. They found that even if a man was in the bottom half of cardiorespiratory fitness, his risk of all-cause mortality was still 38% lower if he was in the top third of the group in terms of strength versus the bottom third.

John Ioanidis conducted a literature study and found that in numerous randomized clinical trials, exercise-based intervention performed as well as or better than multiple classes of pharmaceutical drugs at reducing mortality from heart disease, diabetes, and stroke.

Exercise helps keep the brain vasculature healthy and may also help preserve brain volume. He thinks it’s relevant to preventing the development of Alzheimer’s. The evidence regarding the impact on lifespan is less concrete, but he strongly believes that, in fact, even if exercise were to reduce your lifespan by a year, it would be worth it.

By the time you hit 80 years old, you will have lost eight kilograms of muscle from your peak. But people who maintain higher activity levels lose much less muscle, more like three to four kilograms on average.

A Chilean study looked at about 1,000 men and 400 women, with an average age of 74. They were divided into quartiles based on their lean mass index, which is a proxy for their muscle mass, and followed them over time. After 12 years, 50% of those in the lowest quartile were dead compared to only 20% in the highest quartile.

Having more muscle mass is highly correlated with a lower risk of falling. Deaths due to falls at age 65 and older increase significantly. This doesn’t even account for those who die three, six, or twelve months after their fall. Approximately 800,000 older people are hospitalized for falls each year. When you get beyond the age of 75, the risk of dying due to a fall rises significantly compared to age 65, and it increases dramatically if you’re 85 or older.

Never think you’re too old to start. His mother didn’t begin lifting weights until she was 67, and it has dramatically improved her life. It can significantly improve mobility and physical functions of obese people or those recovering from cancer, even if they are elderly and frail.

He cautions against doing only one type of exercise, even if you take it to extreme levels. He used to do extreme cycling, and that gave him a fairly high VO2 max, but it did not improve his strength, flexibility, or stability. He was a one-dimensional athlete. If he continued with cycling, he probably would have suffered serious injuries due to that imbalance.

Instead, he uses the analogy of the decathlon. He called it the centenarian decathlon. The idea is to pick the 10 most important physical tasks you want to be able to do for the rest of your life. Here’s an example:

1. Hike one and a half miles on a hilly trail.
2. Get up off the floor under your own power, using a maximum of one arm for support.
3. Pick up a young child from the floor.
4. Carry two five-pound bags of groceries for five blocks.
5. Lift a 20-pound suitcase into the overhead compartment of the plane.
6. Balance on one leg for 30 seconds with eyes open.
7. Have sex.
8. Climb four flights of stairs in three minutes.
9. Open a jar.
10. Do 30 consecutive jump rope skips.

You can probably do all of these things at age 40. But keep in mind that over the next 30 to 40 years, your muscle strength will decline by 8 to 17% per decade. So if you want to pick up a 30-pound kid when you’re 80 years old, you actually need to be able to lift about 50 to 55 pounds right now. Make that your target.

Perhaps that hike requires a VO2 max of roughly 30 milliliters per kilogram per minute. And that may be the max you have right now. But that VO2 is going to drop as you get older. So you need to have a higher than 30 VO2 max right now to be able to continue doing that when you’re in your 80s.

Lifting that 20-pound suitcase when you’re 80 probably means you should be able to do it for a 40 or 50-pound one right now.

If you want to climb a flight of stairs in your 80s, that means you should be able to sprint up those stairs today.

So set up an exercise program that targets these 10 items.

And of course, there’s no need to limit it to just 10.

Big items that are wide across the range and not focusing on just one thing like arm strength. But pick things that you enjoy. This list is personalized to you.

So stop pointlessly or aimlessly exercising just because that’s what you feel you have to do. Don’t think in terms of exercise; think in terms of training with the specific purpose of being able to do these things when you’re 80 years old.

Chapter 12 There are three aspects of exercise that you need to focus on: cardio, strength, and stability.

Stability is about being able to do what you want to do without getting injured. You can be fairly strong but not stable.

Don’t focus too much on burning calories, but instead focus on the fuels that are being burned. The primary fuels are glucose and fatty acids. When you do aerobic exercise well, it improves your ability to utilize glucose and especially fat as fuel.

He thinks it’s impossible to be healthy without having healthy mitochondria, and that’s why he emphasizes long, steady endurance training in Zone 2. Different fitness coaches define Zone 2 differently. Some focus on heart rate, others on power output. Typically, Zone 1 is a walk in the park, and Zone 5 is an all-out sprint. Zone 2 tends to be 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 is a little strained. It’s between easy and moderate.

Zone 2 is important in building endurance.

Healthy mitochondria are important for both athletic performance and metabolic health. They convert both glucose and fatty acids to energy. Glucose can be converted to energy in multiple different ways, but fatty acids can only be converted using mitochondria. Normally, working at a lower relative intensity will burn more fat, while high intensity will burn more glucose. The healthier your mitochondria, the greater their ability to utilize fat. Fat is the body’s most efficient and abundant fuel source. The ability to use both fuels, fat and glucose, is called metabolic flexibility. Healthy mitochondria can help keep fat accumulation in check.

One researcher took three groups of subjects: professional cyclists, moderately active healthy males, and sedentary men, and had them ride stationary bikes at about 80% of their maximum heart rate. They measured the amount of oxygen they consumed and the carbon dioxide they exhaled to determine how efficiently they produced power. The professional cyclists could produce a huge amount of power while still burning primarily fat. Those with metabolic syndrome relied almost entirely on glucose for their fuel source, right from their first pedal stroke. Their ability to tap into their fat stores was pretty much zero. They were metabolically inflexible, able to use only glucose and not fat.

When exercising in zone 2, most of the work is being done by slow-twitch muscle fibers. They’re very dense with mitochondria, allowing us to go for a long time without feeling fatigued. If you want to go faster, you recruit more type 2 or fast-twitch muscle fibers, which are less efficient but more forceful. They also generate lactate in the process. Lactate can be useful for certain uses. It is what causes the burning sensation in your muscles during hard effort.

The goal of zone 2 is to maintain a maximum level of effort without accumulating lactate. Although we’ll still produce lactate, we’re able to match the production with clearance. Usually, if you’re feeling the burn in this type of workout, you’re going too hard and creating more lactate than you can eliminate.

You can get a lactate monitor and use it while working out. The goal is to keep the lactate levels consistent, usually between 1.7 and 2.0 millimoles. That’s a Zone 2 threshold for most people. If the lactate levels go up, then you need to slow down.

Another way to estimate your Zone 2 range is to know your maximum heart rate and work out at approximately 70 to 85 percent of that peak number, depending on your fitness level. That’s a wide range, so you might as well just use the talk test. If you’re having trouble speaking in complete sentences, you’re likely in Zone 3.

The fitter you are, the more energy you can produce while still staying in Zone 2. This is because you have more efficient mitochondria.

As you get older, there is a decline in the number and quality of mitochondria. However, doing aerobic exercise stimulates the creation of new and more efficient mitochondria while eliminating dysfunctional ones. So when you run frequently in zone 2, you’re improving the mitochondria. And if you don’t use them, you lose them.

Additionally, muscle is the largest glycogen storage sink in the body. The more mitochondria you use, the more you increase the capacity for disposing of glycogen rather than having it end up as fat.

If you exercise in zone 2, you can help manage the symptoms of type 1 and type 2 diabetes. He has one patient with type 1 diabetes who mostly keeps his glucose in check by walking briskly for 6-10 miles a day. As a result, he drastically reduced the amount of insulin injections he needs.

The nice thing about Zone 2 is how accessible it is. It’s not very intense, so find an activity you like and ramp it up to Zone 2.

If you are just starting to train, you’ll get a lot of benefit from even two 30-minute sessions a week. The optimal number is probably three hours a week, which could be four 45-minute sessions after you get past the initial hump of trying it for the first time. So, four 45-minute sessions a week is the target you should go for. He thinks that’s the minimum.

To track your progress in zone 2, measure your output in watts, particularly watts per kilogram. A number of stationary bikes let you measure this as you ride. 2 watts per kilogram is good for a reasonably fit person, 3 watts is a good target, and professionals aim for 4 watts. Don’t focus too much on the absolute number; instead, focus on how it improves over time.

VO2max is a measure of the maximum aerobic output. Think about those standing desks with treadmills. It’s a measure of the maximum rate of oxygen consumption.

Zone 2 training can increase your VO2max a little bit, but if you really want to raise it, you need to train this zone more specifically. For patients who are new to exercising, VO2max training is introduced after about five or six months of steady Zone 2 work.

The measure of peak aerobic capacity is strongly correlated with longevity. There are many places you can conduct this test, including some large fitness chains. It’s very unpleasant. Patients are made to do the test at least once a year. Their results are then compared, normalized by weight, to the population by age and sex.

There is a vast difference between the VO2 max of a sedentary person and someone in the top 10 or top 5 percentile. But also note that there’s a dramatic drop in your VO2 max as you age. As an example, a 35-year-old man with average fitness should be able to run at a 10-minute mile pace. But by age 70, only the very fit 5 percent of people will be able to do it.

He tells his patients to target the top 2% of their age and gender. If they can manage to reach it, he then tells them to target it for two decades younger.

Your VO2 max will decline by roughly 10% per decade, and after the age of 50, by about 15% per decade. So having an above-average VO2 max right now just won’t cut it. If you are 50 years old and you have 32 milliliters per kilogram per minute, you can expect to be closer to 21. That’s a significant decline in function. It’s the difference between walking easily up a flight of stairs versus struggling to even walk on an inclined surface.

Note that increasing your VO2 max doesn’t just provide benefits for the future; it will significantly improve your quality of life even today. Improving your VO2 max from the bottom quartile to the quartile above is associated with almost a 50% reduction in all-cause mortality. If you go below 18 for men, your ability to live on your own is at risk.

How much can you increase VO2 max? The conventional wisdom is that for elderly subjects, you can improve aerobic capacity by about 13% over 8 to 10 weeks and 17% after 6 months to a year. Optimistically, it’s possible to achieve even more as long as you stay committed to the regimen. Don’t think of it as something you do for two months, but rather for at least two years.

One study found that boosting allergy subjects’ VO2 max by 6, or about 25%, was equivalent to subtracting 12 years from their age. If you’re a man in your 60s and you’re starting with a VO2 max of 30, you’re more or less average for your age group. If you can boost that to 35, you’ll be in the top 25% of your age group, which means you’ll have achieved the aerobic fitness of a man in his 50s.

No matter how old you are, your VO2 max can increase. He suggests supplementing Zone 2 work with 1 or 2 VO2 max workouts per week. A VO2 interval is from 3 to 8 minutes. You can also run on a treadmill, a stationary bike, or a rowing machine. The prescription is to go 4 minutes at the maximum pace you can sustain for this amount of time. You have enough time for your heart rate to come back down to below about 100 beats per minute. Repeat this 4 to 6 times and then cool down. Make sure you are as close to fully recovered before you begin the next set. Give yourself enough time to warm up and cool down.

You’re not going to need to operate at peak VO2 much in your life, but it’s good to have that reserve when you need it.

An 80-year-old man will have about 40% less muscle tissue than he did at 25. However, muscle mass is not the most important metric. Strength is more important. You lose strength two to three times more quickly than you lose muscle mass. Furthermore, if you look at power - which is strength multiplied by speed - you lose that two to three times faster than you lose strength.

The single biggest change in muscle is the atrophy of the type 2 muscle fibers - the fast-twitch ones. Zone 2 endurance and daily life routines prevent the atrophy of type 1 fibers. However, you need to do resistance training to keep your type 2 fibers from withering away.

Even if you are doing strength training diligently, a short period of inactivity, such as recovering from a fall or a broken bone, can erase many of those gains. If it lasts longer than a few days, you could end up in a steep decline that you’ll never fully recover from. When you’re 67, 10 days of bed rest results in a loss of 3.3 pounds of muscle mass.

If you end up in what’s called sarcopenia or frailty, gaining muscle is pretty difficult. A study looked at 62 frail seniors with an average age of 78. They engaged in a program of strength training, and even after six months, half of the subjects did not gain any muscle mass. Fortunately, they didn’t lose any. But the point is, if you let yourself get to such a weak condition at an old age, it’s hard to gain mass.

He measures bone mineral density (BMD) for every patient once a year. It is a measure of body fat and lean mass.

Once you are about 65 years old, having a hip or femur fracture is very serious. About 15 to 35% will be dead within a year. Even if they don’t die, the resulting loss of muscle mass is debilitating.

When he detects a rapidly declining BMD in a middle-aged person, he focuses on:

1. Optimizing nutrition, focusing on protein and total energy needs
2. Strength training with heavy load-bearing activity
3. Hormone replacement therapy, if indicated
4. Drugs to increase BMD if needed

Often, he can solve the problems with the first two. The point, though, is BMD is very important. You should focus on it as much as muscle mass. Check it at least once every few years.

certainly want to start building strength early to ensure a healthier and more active life as you age. Just like saving money over time allows for a comfortable retirement, building strength gradually over the years can lead to better health outcomes and an improved quality of life. Integrating strength training into your routine while you’re young sets a solid foundation for the future.

He’s not concerned about large biceps or how much he can bench press. A better measure of strength is how much heavy stuff you can carry. If you look at hunter-gatherers, carrying was one of their main tasks. No other animal naturally carries as much as humans do. Animals like horses have been bred and trained to do it. It’s not their natural state.

He often carries heavy objects with his hands, be they dumbbells or sandbags. He tries to incorporate them into his workout. He also does what’s called rucking, which is hiking or walking at a fast pace with a loaded backpack on your back. Three to four days a week, he’ll spend an hour rucking around the neighborhood, going up and downhill for three to four miles with a 50 to 60-pound pack on his back. He’s getting both cardio and muscle benefits.

A good goal is to be able to carry a quarter to a third of your body weight once you develop enough strength and stamina.

1. Grip strength
2. Concentric loading for all your movements. Concentric is when the muscles are shortening and eccentric is when they are lengthening. Think of it as being able to both lift the weight up and put it back down slowly with control. Rucking downhill works on eccentric strength.
3. Pulling motions, such as pull-ups and rows.
4. Hip hinging movements, such as deadlifts and squats, but also step-ups, hip thrusters, and so on.

These are the four elements of strength that he focuses on because they have strong correlations with daily activities:

There is a lot of literature linking better grip strength in midlife and beyond to a decreased risk of overall mortality. The data is as robust as it is for VO2 max and muscle mass.

Our grip strength has been declining for adults over the last few decades. Someone in their mid-30s had more grip strength 30 years ago than someone in their mid-30s does today.

One way to train for grip strength is to do the farmer’s carry, where you walk for a minute or so with a heavy weight like a dumbbell or a kettlebell in each hand. He describes certain ways of carrying that I didn’t bother noting down here.

He asks his male patients if they can carry half their body weight in each hand for at least one minute. Obviously, most cannot. His patients need as much as a year of training before they can even attempt to do this test, so don’t try it out on your own.

He urges new patients to begin with far less weight than they are used to carrying because they need to learn their form first. Still, a farmer’s carry is pretty easy to do. You have a weight in each hand, arms at your sides, and you walk. You keep your shoulder blades down and back, not pulled up or hunched forward. Start with 10 to 15 pounds and work up from there.

Another way to test your grip strength is by dead-hanging from a pull-up bar for as long as you can. Don’t do this on a daily basis, just once in a while. Grab the bar and hang there, supporting your whole body weight. It is recommended that men aim to hang for at least 2 minutes at the age of 40. This goal can be reduced for each decade past 40.

For concentric and eccentric loading, one of the tests he does is have patients step onto and off an 18-inch block, taking three full seconds to reach the ground. Stepping up is usually easy, but people struggle with a controlled three-second descent. As you age, eccentric strength is where you are more likely to falter. This is the strength needed to move down an incline or walk down a set of stairs, and it’s very important to maintain it to prevent falling. It also puts less strain on the knees if you have that strength.

Eccentric strength training is relatively easy. Focus on the down phase of lifts ranging from pull-ups or pull-downs to deadlifts to rows. Walking downhill, carrying a weighted backpack is a great way to build both eccentric strength as well as spatial awareness and control. It also helps protect against knee pain. You don’t need to do this for every rep of every set. Just make sure that at some point in your workout, you’re taking the time to cue the eccentric phase of your lifts.

Pulling is closely related to grip strength. Pulling is how we do most of our work in this world, such as carrying grocery bags. In the gym, it’s usually done in the form of rows, pull-ups, or on rowing machines.

Hip hinging involves bending at the hips while ensuring the spine remains straight. It’s an essential movement for daily activities, such as picking up items from the sidewalk or getting out of a chair. Although you can hip hinge with a heavy load, there’s a risk of spine injury. Therefore, he advises his patients to progress slowly to weighted hip hinging, typically starting with single-leg step-ups and split stance Romanian deadlifts without weights or with very light weights. These exercises can be difficult to describe accurately, and it’s best to have a trainer guide you through them.

He seems to suggest that before engaging in any form of heavy strength training, or at least training with heavy weights, you should first focus on improving your stability.

Chapter 13

In this chapter, he talks about stability.

Even if you keep exercising into old age, it’s unlikely that you will have the muscles that the book implies you need. The reason is, at some point you’re going to get injured due to your strength training, and as was shown in a previous chapter, that can be debilitating when you’re older. Many people don’t recover from those injuries at old age. The solution to this is to ensure you have good stability as you exercise.

The idea is this: When you are working with very heavy weights, the energy expelled from the motion has to go somewhere. If your form is not correct, that excess energy will go off into joints where it shouldn’t. Joints that can’t handle that much energy. Over time, that will lead to damage of the joints.

Submitted to old age, the author in his 20s experienced a back injury due to excessive exercise. There wasn’t a triggering event; it manifested suddenly. It was a long and difficult recovery. He had trouble even brushing his teeth and needed other people to care for him. Imagine how bad that would be in your 60s.

Back pain alone results in a cost of $635 billion when you combine both the medical costs and the loss in productivity.

Let go of the mentality of trying to crush it every time you go to the gym. If you’re struggling to get through your workout, then you’re likely resorting to your body’s own cheats, which will ensure that you complete the exercise using inappropriate means.

Injuries like ACL tears, although they occur suddenly, have usually been building up for a while.

He learned proper stability from Beth Lewis. I won’t write all the details that he mentioned in the book. He does provide some websites related to Beth Lewis’ practice that may be useful for future reference.

He talks about Dynamic Neuromuscular Stabilization, or DNS for short. It is based on the simplest, most natural movements we make when we are babies. The theory is that the sequence of movements that young children undergo on their way to learning how to walk is part of a program of neuromuscular development. As we go through that sequence, our brains learn to control our bodies and develop ideal patterns of movement. A study in the ‘60s showed that kids who did not go through those stages had movement problems throughout their lives. Kids with cerebral palsy are such kids. But when they’re put through a training program to ensure they go through that sequence, they are able to control their motion as they grow older. Normal people, as they grow up, also lose the natural, healthy movement patterns due to things like the modern lifestyle.

The author discovered that he had been doing a squat wrong all along, and he’s a fairly fit person.

For his patients, he doesn’t emphasize strength training, including exercises like dead hangs and weighted step-ups, until he has established a base level of stability. It’s too risky, and it’s worth taking extra time to build this foundation. It may delay the whole project by several months. Since everyone has different issues related to stability, it’s not possible to give a one-size-fits-all prescription.

Twice a week, he spends an hour just on stability training, and he spends 10 to 15 minutes each day on it as well.

At the most basic level, one has to learn how to breathe properly. Breathing improperly puts your body at greater risk for things like back injuries.

Next, he talks about feet and how they make contact with the floor. When doing exercises, it’s critical that your feet are properly positioned. He says you should be able to feel all four corners and ensure that they are gripping the floor better.

He then talks about the spine. And then the shoulders. And then the hands.

He doesn’t let his patients work with heavy loads until they work on stability principles for at least six months. He’s not a big fan of trainers. He thinks they’re useful for basic instruction, accountability, and motivation, but discourages his patients from being overly reliant on them and having them present every time they work out. So, use trainers to learn the basics and motivate yourself, but do most of the exercises on your own. He puts his phone on a tripod and films himself doing the exercises so he can evaluate what he is doing.

Chapter 14 Don’t get too attached to any particular fad diet like low fat, Atkins, or Keto. A given diet may be good for you, but not for someone else. So it’s not to say that doing keto is bad, but don’t go for it just because it works well for someone else.

The science behind nutritional studies is indeed flawed, especially when it comes to epidemiological studies. Due to the significant uncertainty present in all these studies, there tend to be numerous strong advocates and self-proclaimed gurus. It’s best to disregard their claims.

Focus on the following three:

1. Whether you’re undernourished or overnourished.
2. Whether you’re undermuscled or adequately muscled.
3. Whether you’re metabolically healthy or not.

Generally, he is trying to get patients to lose weight without losing muscle mass by lowering the calories, increasing protein intake, and adding exercise.

For him, any dietary intervention that compromises muscle or lean body mass is a non-starter, whether you’re undernourished or overnourished.

He strongly feels that diet and nutrition are very important for things like metabolic health and reducing the risk of chronic disease. However, he doesn’t think they come close to having the same effect as exercise does for longevity.

Eating to correct poor health and eating to maintain good health are very different. Just like wearing a cast to fix a broken bone is beneficial, but wearing a cast when healthy can be damaging. It’s important to differentiate between these two approaches.

What we know is that you need to eat the right amount of calories, not too many and not too few. You need to have enough protein and essential fats, get the appropriate amount of vitamins and minerals, and avoid pathogens like E. coli and toxins like mercury. Beyond that, we know very little.

He is a believer in not eating things your great-grandmother wouldn’t recognize. He thinks plants are very good, and animals should also be eaten since we are omnivores.

Epidemiological studies have been very effective for non-nutrition related diseases because the strength of the result is quite strong, or rather it has a strong effect. However, epidemiological studies cannot distinguish between correlation and causation. The effects they show for nutrition are not very powerful, so they are likely dominated by confounding factors.

The correlation between eating red and processed meats and colorectal cancer is such that it raises your risk of colon cancer by 17%. This is a fairly weak association. Someone who smokes cigarettes is 10 to 25 times more likely to get lung cancer. A 17% increase is negligible. There are very few epidemiological studies showing a risk of even a 50% increase in cancer in relation to food.

Then there’s the issue of self-reported questionnaires: sometimes asking what you ate over the last month, as if you can reliably remember what you ate two weeks ago.

There was a great study done on mice. The researcher split the mice into three groups, with the only differentiator being the amount of food they were given. One group was a low-calorie group, another medium-calorie, and the third, a high-calorie group. The last group, the mice were allowed to eat as much as they wanted. What they found is that the low-calorie mice lived the longest, followed by the medium-calorie, and the high-calorie mice lived the shortest on average. But then, the researcher focused purely on the high-calorie group and found that those who ate less died quicker than those who ate more. If you look at just this small subgroup, it seems that eating less is correlated with a greater risk of mortality, and eating more isn’t. But in reality, they were eating less because they had some underlying health condition. And so that’s the risk with a lot of these studies. They’re not looking at the general population, but often looking at a population that’s already at risk, for example, the elderly. Often, the result is just a reflection of their underlying health, not on the treatment they’re being given.

A well-known study published in JAMA showed that when you account for all the confounding factors, alcohol is always a negative. Having a glass of red wine a day does not improve your health at all.

I’ll compare the rigor of the studies for the new medicine. It can take a decade or two to collect enough data to show whether a particular medicine is having an impact. And this is where the data is good: we know when and how often the medicine was administered. Now, I’ll compare that with studies related to diet, where the data is so much worse and potentially the strength of the results is a lot weaker.

There have been a few large-scale, very expensive studies that have gathered good data. For example, one study tracked 50,000 women over eight years and cost $750 million. They found no statistically significant difference between the low-fat and controlled diet groups regarding breast cancer, colorectal cancer, cardiovascular disease, and overall mortality. So, if such a powerful study shows no effect, how much more expensive does it need to be to find even a weak effect?

He is a proponent of the Mediterranean diet. A large Spanish study showed that giving a group a weekly gift of a liter of olive oil and another group a certain quantity of nuts every week, with a control group simply instructed to eat a low-fat diet with no nuts or excess fat, followed 7,500 people for six years. However, it was halted after four and a half years because the control group was dying at a significantly higher rate than the other two groups, and it was deemed unethical to continue the study. The group that received the olive oil had a one-third lower incidence of stroke and heart attack, while the mixed nut group had a 28% reduced risk.

Keep in mind that all three groups had serious risk factors like diabetes, smoking, hypertension, and so on. So it’s not necessarily true that a Mediterranean diet will help a reasonably healthy person.

Chapter 15 Our current diet evolved from the following principles: 1. producing enough food to feed almost everyone; 2. doing it inexpensively; 3. preserving the food so it can be stored and transported; and 4. making it highly palatable.

When you optimize for these four, you get the diet we currently have. The problem with it is that it’s a relatively harmful diet. The goal had not been to do harm, but it is a side effect.

The farther we go away from this diet, the better off we’ll be. That’s why many diets tend to restrict a particular aspect of this diet.

All diets fall into one of the following three categories:

1. Caloric restriction, which is eating less in total, but not being too particular about what you’re eating.
2. Dietary restriction, which is eating less of a particular category, like low fat, low sugar, low meat.
3. Time restriction, which is eating only at certain times or for a certain duration of a day or a week.

Caloric restriction is the most efficient one. It’s what bodybuilders use to lose weight while maintaining muscle mass, and it’s also the most flexible. The difficulty lies in doing it properly. You have to track every single thing you eat, and if you cheat on it enough, it just doesn’t work. Most people have trouble sticking to it.

Dietary restriction is the most common diet. It only works if the food you’re restricting is both plentiful and significant enough that eliminating it will create a caloric deficit. A no-lettuce diet, for example, is not going to do you any good.

Time-restricted diets are also known as intermittent fasting. It’s the easiest but can easily backfire if you overeat. Many have had the experience of gaining weight on a one-meal-a-day plan because their meal was loaded with calories. The other problem with this diet is that it’s hard to get enough protein because our body can absorb only a certain amount of protein at a time. If you are restricting eating to only a few hours a day, it’s almost a given you’re not getting enough protein.

It was mentioned in a previous chapter that most studies show that for most animals, a low-calorie diet is highly correlated with longevity. So how well does this apply to humans?

A study was done on rhesus monkeys that were fed a reduced-calorie diet for over 20 years, and they lived significantly longer than a control group that was allowed to eat freely. The low calorie group had about 25% less calories than the control group.

The calorie-restricted group was healthier by many other measures, such as insulin sensitivity and a higher level of gray matter.

But there was another long-term study done with monkeys. The study began in the 80s and was published in 2012. One group of monkeys was fed about 25 to 30% less than the other. In this study, the calorically restricted monkeys did not live longer than the controls. There was no statistical significance between the two groups.

There were differences between the two studies, though. In the first study, the control group was fed highly processed food. In the second study, their food was a lot more natural. In the latter study, their food contained about 4% sugar. In the former study, it contained almost 30% sugar by weight.

And it showed. In the first study, the unrestricted group had a very high percentage developing insulin resistance and pre-diabetes. In the second study, only one in seven became diabetic. In the first study, the control monkeys were much more likely to die from cardiovascular reasons than cancer.

So perhaps what this is showing is that if you have a pretty poor diet, caloric restriction is good for you. But if you have a healthy diet, then it’s not particularly relevant.

In fact, it was one of the goals of the first study to mimic the human diet. It wasn’t a flaw in their study that they were giving highly processed food.

Having significant caloric restriction does have its downsides. It can weaken the immune system and put you at greater risk for muscle loss.

His belief is that if you’re metabolically healthy and not overnourished, then all you really have to do is avoid a poor diet and not eat too much.

For diet restriction, the challenge is figuring out what to restrict.

The advantage of this diet is that it is highly individualized. You can impose various degrees of restriction depending on your needs. You can figure out what is causing problems for you and just address that.

Cutting out carbs can be very effective because it also reduces your appetite. However, it’s challenging to maintain. Cutting out fat may work or may not, depending on what you eat as an alternative. If you fill your diet with low-fat but high-carb junk food, you’re going to gain weight and perhaps still be hungry.

Additionally, you still need to ensure that you’re getting enough nutrition. For example, cutting out a lot of proteins is a bad idea because it will lead to muscle loss. Replacing carbohydrates with lots of saturated fats can significantly increase your risk of cardiovascular disease.

Another problem with dietary restriction is that everyone’s metabolism is different. For some people, going on a low-carb or ketogenic diet results in a significant loss of weight as well as improving metabolic markers. For others, they may actually gain weight and a lot of their markers can get worse on exactly the same diet.

He’s had patients reverse Type 2 diabetes by going on a ketogenic diet, and he’s had patients where it significantly worsened their diabetes.

Carbohydrates are a primary energy source. Carbs are broken down to glucose. Excess glucose beyond what is needed is stored in the liver or muscles as glycogen or stored in adipose tissue as fat. An accompanying rise of insulin may have negative effects. Everyone responds differently to an influx of glucose. Too much glucose for one person may be less than sufficient for another.

He is a strong advocate of continuous glucose monitoring. Coupled with apps, you can get a lot of good data out of them, and it’s really powerful to see the impact of eating foods like potato chips or donuts on your insulin and glucose levels.

He thinks it’s much more accurate and actionable than HbA1c. At the moment, it’s available only by prescription. Adults should have it.

He says you can obtain one from several online metabolic health startups. They’re not cheap; it costs about $120 a month. But he finds that if you’re healthy, you tend to need to use it only for 1 to 3 months to understand the effect of glucose and how you can adjust your diet to optimize for glucose and insulin. After that, his patients generally stop using the continuous glucose monitoring.

Not only is having high glucose a greater risk for death, but it’s been shown that people with the highest quartile of glucose variability had a higher risk of mortality compared to the lowest quartile. So, not only is the absolute amount of glucose important, but the variability is crucial too. Continuous glucose monitoring can help you understand this. Even if your glucose levels are always healthy, try to reduce that variability with diet.

Stress also leads to spikes in your glucose level.

He’s found in his patients that after they adjust their behaviors based on continuous glucose monitoring, they generally are able to maintain those behaviors even after they stop the monitoring.

The obvious benefit of continuous glucose monitoring is that you can customize it to the patient. You can see that for some patients, certain carbs or certain levels of carbs are actually beneficial. For others, it is detrimental. You don’t have to guess; you are getting almost immediate feedback. Not everybody needs to restrict carbohydrates. Some can handle it more than others. He tries to keep the average glucose at or below 100 milligrams per deciliter with a standard deviation of less than 15 milligrams per deciliter. These are aggressive goals. They correspond to an HbA1c of 5.1%, which is fairly low. He thinks a high standard deviation means a higher variance and more insulin is required to get the glucose under control.

Continuous glucose monitoring will teach you that tolerance for carbohydrates is heavily influenced by factors such as your activity level and your sleep. Sleep disruption or reduction can significantly impair glucose homeostasis over time. It has been observed that even one night of bad sleep can cripple the ability to dispose of glucose the following day.

He has seen patients go to bed at 80 milligrams per deciliter and then see the glucose ramp up to 110 for most of the night. This is a sign of psychological stress. Stress prompts the elevation in cortisol, which stimulates the liver to release more glucose into circulation. It means that the person has to address their stress level and sleep quality.

Continuous glucose monitoring can allow one to cheat. One patient has learned to eat certain forbidden types of carbohydrates only at certain times without affecting his average glucose level. He found out that if he ate them right after exercising, the body handled them very well. This way, he was able to still enjoy the foods he liked without putting himself at risk.

Still, don’t be over-reliant and continue glucose monitoring. You also need to consider all your other biomarkers, such as your weight, body composition, lean mass to fat mass ratio, and so on.

Some of the things he’s learned from his own diet include that fiber tends to blunt the glucose impact. He aims for 50 grams or more of fiber per day.

Another discovery is that brown rice is only slightly less glycemic than white rice.

Keep in mind that fructose is not measured by continuous glucose monitoring. However, it’s generally consumed in combination with glucose, so that’s why he sees fructose-heavy food still causing glucose spikes.

The timing, duration, and intensity of exercise matter a lot. Aerobic exercise, in particular, seems efficient at removing glucose from circulation. Intense exercise and strength training tend to increase glucose briefly, so don’t be alarmed by glucose spikes when you are exercising. This is actually a good thing.

The effect of stress on glucose is mostly visible by your glucose levels while sleeping, or in periods long after meals.

Non-starchy vegetables like spinach or broccoli have no impact on blood sugar, so you can eat a lot of them.

Foods that are high in protein and fats, such as eggs and certain parts of beef, have virtually no effect on blood sugar. Large amounts of lean protein like chicken breast will elevate glucose slightly. A lot of protein shakes can have a strong effect on glucose, especially if they contain sugar.

He then switches to talking about proteins.

He thinks the standard recommendations for protein in the US are pretty low. It’s 0.8 grams per kilogram of body weight. This is what we need to stay alive, but not to thrive. There are a lot of studies showing we probably need more. Multiple studies show that elderly people who consume this amount end up losing muscle mass, even in as little as two weeks.

The amount of protein you need varies from person to person. He targets 1.6 grams per kilogram of weight as a minimum. The ideal will vary for each individual. He suggests that for people with normal kidney function, one gram per pound of body weight is a good starting point.

The challenge with eating so much protein is that you cannot do it all at once. There’s a limit to how much your body can process at a time, so you need to spread it out during the day. Studies show that the ideal way is to have four servings of protein per day, each at 0.25 grams per pound of body weight.

The upper limit for safe is 3.7 grams per kilogram of body weight. He says you shouldn’t even worry about this because it’s very hard to achieve such a high level of protein intake.

He thinks older people probably need more protein for body weight because they have greater difficulty in gaining muscle. Finding out the ideal amount for you is through trial and error. You have to monitor your muscle mass, and if you find you’re losing it, then you need to eat more proteins.

He makes at least one of the four protein servings a protein shake or a high-protein snack. Often, one serving will be a protein shake, another a high-protein snack, and the other two will be through regular foods.

If you insist on getting all your proteins through plants, keep in mind that the body is not efficient in digesting them. You may only get 62% or 70% of the proteins that you’re consuming. If you cook the plants, the percentage goes up a little. Additionally, the types of proteins in plants are not as good as what you would get from animal products. You also have to be careful about protein supplements. Whey protein isolate is richer in amino acids than soy protein isolate. You can go into great detail about how to calculate things if you’re interested in a protein-only diet, or rather a plant-only protein diet.

A large study with over 2,000 elderly subjects found that those who ate the most protein, about 18% of their calorie intake, retained more of their muscle mass over three years than those in the lowest quintile, which was 10% of calories. The difference was that the low protein group lost 40% more muscle than the high protein group.

He then switches to talking about fat.

Eating the right mix of fats can help maintain metabolic balance, but it’s also important for the health of our brain, which is composed of fatty acids. Also, dietary fat tends to leave one feeling more satiated than many types of carbohydrates, especially when you combine the fat with protein.

There are three types of fat: Saturated, monounsaturated, and polyunsaturated. Polyunsaturated fats can also be divided into omega-6 and omega-3 variants. Omega-3 can be subdivided into marine and non-marine sources. Salmon and other oily seafood are marine sources, while nuts and flaxseed are non-marine sources.

It’s very hard to find natural food that is primarily just one of these. Most fats in nature are a mixture of these three. Olive oil and safflower oil are the closest you can get to monounsaturated fat, and palm and coconut oils are the closest you can get to saturated fat.

The important thing is to get the right mixture of each kind of fat.

His target for patients is to make monounsaturated fats closer to 50% to 55%; saturated fats, 15% to 20%; and polyunsaturated fats for the remaining percentage. Within polyunsaturated fats, he prioritizes the marine ones because they’re important for brain and cardiovascular health. Compared to the usual diet, this means an increase in monounsaturated fatty acids and a decrease in saturated fatty acids.

In practice, this means eating more olive oil, avocados, and nuts, cutting back on but not eliminating butter, reducing omega-6 rich corn, soybean, and sunflower oils, and finding ways to increase high omega-3 foods such as salmon and anchovies.

Studies have shown that reducing saturated fat reduces the risk of combined cardiovascular events by 17%. However, the same study found little or no effect on all-cause mortality or even cardiovascular mortality. They also did not observe an effect on cancer mortality, cancer diagnosis, diabetes diagnosis, HDL, triglycerides, blood pressure, LDL, and BMI.

He cites similar confusing studies with regards to saturated and unsaturated fats. The studies are mixed or show no effect.

He uses an expanded lipid panel to keep track of how changes in fatty acid consumption affect his patients’ cholesterol, synthesis, and reabsorption. Subtle changes in fat intake, particularly with saturated fats, have shown a significant difference in some people and not in others. So there’s no single answer that will apply to everyone.

Unless his patients are already eating a lot of foods like salmon, he suggests supplements.

He next talks about time restriction. He’s become skeptical of its effectiveness. Frequent long-term fasting has plenty of negatives. And so the question is more about infrequent fasts.

In the short term, fasting has numerous benefits. However, the scientific literature on fasting is still relatively weak.

He thinks limiting eating to eight hours a day is not sufficient. It’s fairly easy to get a caloric excess in eight hours.

The primary study demonstrating the benefits of a 16/8 fasting diet was conducted on mice. The researcher believes it’s not applicable to humans because mice have a much shorter lifespan, so a 16-hour fast for them equates to a fast lasting multiple days for humans.

There have been several studies on humans about the 16/8 diet, and most find minimal or no benefit. For example, there wasn’t weight loss, and the metabolic health did not improve. One study showed that shifting the window from 8 a.m. to 2 p.m. did result in lower 24-hour glucose levels and lower insulin compared to controls. However, some feel that 16 hours without food isn’t long enough for the body to activate the processes that promote longevity.

There are other types of fasting that have shown benefits, like alternate day fasting. However, one of the problems is the loss of muscle mass. In general, it is believed that frequent prolonged fasting is not a good idea; the downsides outweigh the positives. Occasionally, there are patients for whom it can be a great benefit.

Chapter 16

He talks about how he, as a doctor, was against reducing the maximum number of hours a resident would work per week down to 80 from 110. He thought it would make everyone soft. Yet another data point on how long work hours for doctors is not tied to patient care, but machismo.

Chronic sleep deprivation is more likely to kill you than acute sleep deprivation. Many studies have found associations between insufficient sleep, defined as less than seven hours a night on average, and adverse health outcomes such as an increased susceptibility to colds and dying from a heart attack. Poor sleep increases one’s propensity for metabolic dysfunction up to and including type 2 diabetes, and it can really mess up the body’s hormonal balance.

Good sleep is important for the brain. Not just quantity, but quality matters. It’s critical to cognitive function, memory, and emotional balance. There’s evidence that sleeping well is essential to cognition at any age and staves off Alzheimer’s.

Now, a lot of these studies are admittedly observational studies, which are often criticized when it comes to nutrition. However, more stock is put in these because there literally is only one variable in question: sleep. Arguably, there are still multiple variables, including the duration as well as the quality.

He used to be against the idea of sleep impacting health significantly. His belief was that five to six hours was more than enough, and that for some people, even less is fine. If you don’t feel tired, then you don’t need more sleep. Simple. Then someone posed a question to him: if sleep is so non-essential, why is it pervasive across all species, and why hasn’t evolution rooted it out? Because sleep is actually fairly risky. It leaves you vulnerable to predators.

He looked into it and found that the claim was pretty much true. All higher-functioning animals sleep.

Most of the research indicates that you need seven and a half to eight and a half hours of adequate sleep.

Keep in mind that people are good at adapting to inadequate sleep, so the effects of sleeping less may not be apparent to them for a while.

A single night of bad sleep can make you perform markedly worse physically. Your endurance drops, your VO2 max drops, and even your 1 rep max strength drops. Your ability to perspire is impaired, and you are more likely to be injured. A 2014 study found that young athletes who spent less than six hours per night sleeping were more than two and a half times more likely to experience an injury compared to those who slept eight hours or more.

A study involving Stanford basketball players showed that they were instructed to strive for 10 hours of sleep a day, with or without naps, and to avoid alcohol and caffeine. After five weeks, their shooting accuracy improved by 9%, and their sprint times also got faster.

A physician for Navy SEALs once analyzed their blood tests and was shocked to find that these people in their 20s had hormone levels and inflammatory markers of men several decades older than them. It was because their training exercises and missions often began at odd hours of the night and required them to stay awake for 24 hours or longer.

Even in the short term, sleep deprivation can cause profound insulin resistance. One study subjected young people to a severely restricted sleep of just four and a half hours a night and found that after four days, they had the elevated insulin levels of obese middle-aged diabetics and a 50% reduction in their capacity for glucose disposal. This is actually a fairly consistent finding in all of sleep research. Nine different studies have found that sleep deprivation increases insulin resistance by up to a third.

Studies consistently show that there’s a relationship between sleep duration and risk of type 2 diabetes and metabolic syndrome. It cuts both ways. Having too much sleep is also a sign of problems. People who sleep 11 hours or more have a nearly 50% higher risk of all-cause mortality, possibly because the long sleep is an indicator of poor-quality sleep.

Risk association between poor or short sleep and hypertension: 17%. Cardiovascular: 16%. Coronary heart: 26%. Obesity: 38%.

He thinks stress levels are the link between poor sleep and metabolic health. Higher stress levels make you sleep poorly, and at the same time, poor sleep can make you more stressed the following day. It’s a positive feedback loop. Stress increases your fight-or-flight response as well as inducing cortisol. A higher overnight glucose shown on continuous glucose monitoring is almost always a sign of excessive cortisol, which is exacerbated by late-night eating and drinking.

Sleeping just four to five hours a night suppresses leptin, which is a hormone that signals to us that we are full, and increases the hunger hormone. When you sleep poorly, you’re more likely to eat high-calorie and high-sugar foods and overeat. Studies showed that short sleeping subjects consumed about 300 extra calories of food the following day compared to when they were well-rested.

Inadequate sleep over long periods is associated with an increased risk of cardiac events. This may again have to do with stress and how it affects the blood circulation system. It’s harder to study, but two studies have shown about a 6 to 26 percent increase in cardiovascular disease. Causality is not clear, but one study used Mendelian randomization, which seems to link low sleep to these events. It showed that sleeping less than six hours a night was associated with about a 20 percent higher risk of heart attack. Sleeping 6-9 hours a night was associated with a reduction in risk, even among individuals who are genetically predisposed to coronary heart disease.

Sleep plays a major role in brain health, particularly as you get older - not just in terms of your daily cognitive function, but also in terms of long-term cognitive health.

Poor sleep used to be considered one of the first symptoms of Alzheimer’s. But now, a number of researchers believe it could also be a potential cause of Alzheimer’s and dementia.

He goes into a lot of detail about the different phases of sleep, REM, and non-REM sleep.

Deep sleep is when the brain clears out short-term memories and selects important ones for long-term storage. Researchers have seen a direct linear relationship between how much deep sleep we get in a given night and how well we perform on a memory test the next day.

Rent, sleep is important in helping us process our emotional memories and separating the emotions from the memory of the positive or negative experience. This is why if you go to bed upset at something, it’s common in the morning that you remember the event but don’t feel particularly upset about it. People who have PTSD often have trouble separating those two because they tend to have much less REM sleep.

During deep sleep, the brain activates an internal waste disposal system that allows cerebrospinal fluid to flood in between the neurons and sweep away intercellular junk. If you do not get enough sleep, then amyloid and tau build up amongst neurons. Studies have shown that people who sleep less than seven hours a night over decades tend to have a lot more amyloid beta and tau built up in their brains. This can become a vicious cycle. If someone has Alzheimer’s disease, they’re likely to experience sleep disturbances. And those sleep disturbances, in turn, help create the conditions that allow Alzheimer’s to progress.

It’s been shown that good sleep quality in older adults is associated with a lower risk of developing mild cognitive impairment and Alzheimer’s. Successfully treating sleep disturbances may delay the onset of mild cognitive impairment by about 11 years, according to one study.

When he has patients that are at a higher risk of Alzheimer’s, he prioritizes good quality sleep for them.

Unfortunately, as you get older, it’s more difficult to get deep sleep. It’s not clear if this is simply due to age or due to other health conditions that arise. Research shows that your 40s and your 60s are the decades in life where deep sleep is particularly important in the prevention of Alzheimer’s. People who sleep less during those decades seem to be at a higher risk of developing dementia.

There are a number of FDA-approved sleep medications on the market. He discusses them and points out how they don’t really help or may make things worse. He highlights a few that might show promise. When he has patients come in, a number of them are using these medications. Some of them take them once a month, only for travel, but some more frequently. One drug that he thinks may be useful is Trazodone, which is an antidepressant but has a side effect of improving sleep. He thinks taking a lower dosage would help with quality sleep, about 15 milligrams or even less. The optimal amount depends on the individual.

He’s also seen good results with the supplement ashwagandha.

He’s in favor of using sleep trackers to give you an idea of how well you’re sleeping. They measure things like heart rate, heart rate variability, movement, breathing rate, and so on. They’re used to estimate sleep duration and stages and do so with somewhat good accuracy. He’s cautious about not being overly focused on the final score you get. He even has to tell some patients to stop using it for a few months because being obsessed with those scores makes it harder to get good sleep.

You should make a long-term assessment of your sleep quality over the last month. He recommends the Pittsburgh Sleep Quality Index, a four-page questionnaire that you can find online.

Another screening tool he recommends is the Insomnia Severity Index.

People may differ widely in their chronotypes, which is a fancy way of saying that some people are morning people and some people are not morning people. People have different cycles, and the relationship seems genetic. Some individuals are predisposed to leaping out of bed in the morning, while others naturally wake up and go to sleep later, reaching their peak in the afternoon.

You need to check for sleep apnea. If you can’t do a formal sleep lab or at-home test, there’s a questionnaire called STOP-BANG that correlates very strongly with a formal apnea test.

Create an environment for yourself that is conducive to sleeping well. You need darkness. Light is the enemy of sleep. Even the small LED lights from devices are enough to disrupt sleep.

Try to eliminate blue light as the time comes closer to sleep. Blue light tends to block the natural release of melatonin.

A couple of hours before you go to bed, start turning off unnecessary lights in the house.

Phones, laptops, and video games before sleeping can negatively affect your sleep. They emit a lot of blue light and also stimulate your mind. One large study showed that using these interactive devices right before bed resulted in more difficulty falling asleep compared to passive devices, such as TV, music players, and books. It is interesting to note that watching TV before bed doesn’t seem to affect sleep as negatively, while playing video games and scrolling through social media does.

He recommends staying away from computers that fold for at least an hour before bedtime and not keeping them near your bed.

Another important factor is temperature. He recommends keeping your bedroom at about 65 degrees Fahrenheit for sleeping. A warm bath before bed actually helps you fall asleep, particularly as you transition into the cold room. He suggests cooling mattresses and mattress toppers to help you feel cool. If you have a partner that doesn’t want it so cool, get one of the mattresses that lets you set each half of the bed to its own temperature.

Avoid caffeine. Caffeine merely disrupts your ability to sleep. It doesn’t improve your awareness or reflexes. People are genetically predisposed; some can process caffeine and not be as impacted, while others are severely affected by it. You can do genetic tests, like 23andMe, to see what type of caffeine-related gene you have.

He talks about the concept of sleep pressure, which is basically setting up the environment and your body to promote sleep. Taking a nap during the day can sometimes relieve that sleep pressure, making it harder to fall asleep at night. Another way to cultivate sleep pressure is through exercise, particularly zone two exercise, but not within two or three hours of bedtime. His patients find that doing a 30-minute zone two session does wonders for their ability to fall asleep. Exercising with some exposure to sunlight also helps.

Avoid anything at night that may create stress or anxiety, such as work emails, news, and social media.

He recommends not eating anything less than three hours before bedtime. He thinks spending time in a sauna or hot tub prior to bed increases your chance of falling asleep. When you get into a cool bed, your lowering body temperature will signal to your brain that it’s time to sleep. He thinks the room should be dark enough that you cannot see your hand in front of you. If you cannot get it that dark, he recommends an eye shade. He uses one called Alaska Bear. It costs eight dollars. Focus on going to bed early enough that you get at least eight hours of sleep. If you know you have to wake up at a certain time and you’re going to bed such that you cannot get eight hours of sleep, then everything else in this chapter becomes irrelevant. He thinks having a fixed wake-up time, even during weekends, will make it easier to get good quality sleep. Definitely don’t worry about apps for sleep scores and those trackers.

In the off chance that you have insomnia, don’t lie awake trying to go back to sleep. Get up, go to another room, and do something relaxing, like reading a book until you feel sleepy again. Whatever you do, make sure it doesn’t serve a particular purpose. So don’t do a hobby project, pay bills, etc. Don’t try to be productive.

Equally importantly, don’t assume you have insomnia if you are simply a night person. If after this you still have insomnia, then he recommends cognitive behavioral therapy for insomnia.

Chapter 17 This chapter is about emotional health. Much of it is related to their own experiences.

Mental health affects lifespan in many ways. At one extreme, it can cut life short via suicide. In other cases, it leads to depression, which often results in physical self-neglect. It can contribute to alcoholism, increase the risk of type 2 diabetes, and so on. Trying to live a long life without addressing emotional health is incomplete.

Feeling connected and having healthy relationships with both others and with yourself is as important as the physical aspects described in the book.

One key thing a therapist asked him was, “Why would you want to live longer if you’re so unhappy?”

Trauma generally falls into five categories:

1. Abuse
   1. Neglect
      1. Abandonment
      2. Enmeshment, which is a blurring of boundaries between adults and children
         1. Witnessing tragic events.

Sometimes seemingly small things happen to children, but they are small only when viewed from an adult’s perspective. To a child, it can trigger life-and-death-type responses. The feeling of powerlessness was a large source of his pain.

He makes a distinction between trauma and adversity and points out that the line between them is blurry. Certain types of troubles can make one stronger and better. Setbacks are not necessarily a bad thing. As he says, the most important aspect of childhood trauma is not the event itself, but the way the child adapts to it. Children are resilient and often become adaptive children. Unfortunately, when these adaptive children grow up, they might become maladaptive, dysfunctional adults. He identifies four ways this manifests itself:

1. Acceptable things like work, exercise, and perfectionism.
   1. Codependency or excessive psychological reliance on another person.
      1. Survival strategies such as the propensity for anger and rage.
      2. Attachment disorders, difficulty forming and maintaining connections, and meaningful relationships with others.

Mental health and emotional health are not the same thing. Mental health encompasses disease-like states such as schizophrenia and clinical depression. They’re difficult to treat, but they have recognizable symptoms.

Emotional health, which includes mental health, is a lot broader. It has more to do with how we regulate emotions and manage interpersonal relationships.

Men often mask depression and channel their emotions more towards anger.

He quotes an author who said, “90% of male rage is helplessness, masquerading as frustration.”

It’s probably important to hide your anger and rage from children. Even if you never direct the anger and rage at them, merely observing you behave that way can have a very negative effect on them.

He definitely had trouble expressing his emotions.

He had to change how he dealt with day-to-day problems and frustrations. He needed to learn different behaviors and different ways of thinking about them. He worked on reframing, which is looking at the situation from someone else’s point of view. Whenever in conflict with another person or when you find someone else’s behavior towards you irritating, consider how it is from their perspective.

He calls out the difference between resume virtues and eulogy virtues. Resume virtues are the accomplishments that you list on your resume: degrees, etc. Eulogy virtues are what people will say about you when you are gone. He had spent most of his life focusing on resume virtues and little on eulogy virtues.

He had a strong streak of perfectionism. When he would fail, he would really berate himself. As one of his own patients said, “I need to be great in order to feel like I’m not worthless.” He needed to change how he reacted to minor missteps in his own performance. He had to change his attitude toward himself. As the common adage goes, you would never treat a close friend the way you treat yourself.

He asks himself, “Who cares how well you perform if you’re so utterly miserable?”

He focused on dialectical behavior therapy, or DBT for short. It was developed to help individuals with more serious and potentially dangerous issues, but he felt it’s useful for regular people as well. It is backed up by evidence and clinical trials. The other positive thing about it is that it is skill-based and not just theoretical. You literally are working through a workbook with a therapist doing exercises every day. He is a believer that behavior changes the internal aspects as much as the other way around. Don’t just try to reason your way or think your way out of a problem. Simply changing, forcing yourself to change behavior, can change you. He talks quite a bit about it.

Every person has to figure out his or her own problems and have a customized way to manage them. He cannot give advice that will work for everyone.

He points out that often a lot of the problems we have in life are due to the narrative we have around them. With physical ailments, it doesn’t cause as much emotional harm. The thing is, you can control the narrative in your head. As Buddha said: your worst enemy cannot harm you as much as your own guarded thoughts. Seneca said: we suffer more often in imagination than in reality. Hamlet noted: there’s nothing either good or bad, but thinking makes it so.

He focused a lot on his internal dialogue and keeping track of it. I didn’t make notes of all of it.

Another tactic he used when experiencing mounting emotional stress was to induce an abrupt sensory change, often by throwing ice water in his face or, even worse, taking a cold shower or stepping into an ice bath. This stimulates an important cranial nerve - the vagus nerve - which causes the heart rate and respiratory rate to slow down and switches the body into a calm mode, out of the fight-or-flight sympathetic mode. Another technique is slow, deep breathing: four seconds to inhale, six seconds to exhale, and repeat.

Another tactic is called the opposite action. Whenever he feels like doing something that generally is not helpful or positive, he forces himself to do the exact opposite. This is where behavior can lead to underlying change. Walking in nature with the phone off really helps as well. Learning to forgive yourself for missteps is another important strategy.

An important quote from someone else: “I think people get old when they stop thinking about the future. If you want to find someone’s true age, listen to them. If they talk about the past and 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, then they’re young.”