PDF Summary:How Not to Age, by Michael Greger

Aging is complex, involving hundreds of biological processes—but many of these processes can be slowed through dietary and lifestyle choices. In How Not to Age, Dr. Michael Greger examines the science behind aging, exploring how cellular mechanisms like AMPK activation, mitochondrial function, and DNA methylation influence how quickly we age. He explains how specific dietary patterns, particularly plant-based eating, can activate longevity pathways and suppress age-accelerating processes.

Greger outlines practical interventions for extending your healthspan—the period of life spent in good health. He discusses calorie restriction, protein modulation, and the role of specific nutrients in slowing biological aging. The guide also addresses common pitfalls, including unproven anti-aging supplements and dietary factors that accelerate cognitive decline. Throughout, Greger emphasizes that the most powerful tool for healthy aging is a whole-food, plant-based diet combined with other lifestyle modifications.

(continued)...

(Shortform note: The reason that different amounts and types of protein affect IGF-1 levels is that they change the mix of amino acids and hormones that reach the liver, which in turn affects how strongly growth hormone stimulates the liver to produce IGF-1. When you eat a lot of protein, especially from animal sources, your body gets a surge of certain amino acids that signal the liver to ramp up IGF-1 production. This is because animal proteins are rich in specific amino acids like leucine and methionine, which are potent stimulators of IGF-1 synthesis. On the other hand, plant proteins tend to have a different amino acid profile that doesn't trigger the same response in the liver, leading to lower IGF-1 levels.)

The rise in IGF-1 after consuming dairy might result from absorbing IGF-1 that is already in milk. Proteins found in dairy can also lead to increased IGF-1 production. The different impacts of animal versus protein from plants result from differing amino acid profiles. The liver produces a protein that binds to sequester excess IGF-1 in the blood. Reducing animal protein intake for just eleven days can lower IGF-1 levels by 20% and raise IGF-1 binding protein levels by 50%. A study found that after following a plant-based diet for less than two weeks, the blood of study subjects suppressed cancer growth 30% better than before. The cancer-suppressing effect was so powerful that it delayed, halted, and even turned back the advancement of non-aggressive prostate cancer in its early stages. Biopsies indicated reduced activity of essential cancer-related genes.

Is IGF-1 in Milk Absorbed by the Human Body?

While researchers have found that IGF-1 is present in cow’s milk, a scientific paper published in 1990 concluded that it’s unlikely that IGF-1 in milk is absorbed by the human body. The authors of the research article argue that IGF-1 is a protein, and proteins are broken down by the digestive system. They also point out that IGF-1 is present in human breast milk, and if it were absorbed by the body, it would cause infants to grow at an abnormally fast rate. However, the authors of the paper don’t address the possibility that IGF-1 in milk could be absorbed by the body in small amounts. While this might not be enough to cause infants to grow at an abnormally fast rate, it could still be enough to increase the risk of cancer.

Strategies for Improving Your Healthspan

Greger suggests that reducing caloric intake could help increase both lifespan and the period of life spent in good health. This involves decreasing calorie consumption without malnutrition. It's been demonstrated to lengthen the lives of yeast, fruit flies, worms, rats, and mice. It also helps animals live healthier lives by averting or slowing down autoimmune conditions, cancer, heart issues, eye disorders, neurodegeneration, and issues with the kidneys. Caloric restriction might extend lifespan due to a deceleration of metabolism, which reduces oxidative stress caused by free radicals. It may also boost AMPK and autophagy, which eliminates malformed proteins, harmed cell structures, and aging cells.

(Shortform note: The idea of reducing caloric intake without malnutrition is considered the most important experiment in the field of aging science. According to Brian K. Kennedy et al., this experiment demonstrated that the biological rate of aging is malleable and that modifying these pathways can delay the co-occurrence of multiple chronic diseases of late life. This experiment inspired the National Institutes of Health to launch the “geroscience” program, which aims to target the biology of aging itself rather than treating individual age-related diseases. The authors argue that this approach could be more effective in preventing or postponing a wide range of age-related diseases.)

However, the impacts of caloric restriction on lifespan vary between strains of the same species, and it’s unclear whether the results can be extrapolated to humans. Some researchers argue that the advantages of restricting calories are due to obesity reducing lifespan, rather than the calorie restriction increasing lifespan. In most studies, the animals assigned to the control condition can eat freely, which causes them to become obese. In humans, adults who remain extremely obese over their lifetimes have their lifespan reduced by a minimum of seven years and their healthspan by nineteen years. Restricting calories would benefit them, but it’s unclear if a person who maintains a healthy weight would gain any advantage from reducing calories more.

(Shortform note: If you’re not obese, the mixed evidence on calorie restriction may make it difficult to decide how much to restrict your calories. One way to approach this is to avoid long-term calorie restriction and instead focus on maintaining a healthy relationship with food. If you’re already at a comfortable weight, you may not need to restrict your calories further. Instead, you can focus on eating in a way that feels good to you and supports your overall well-being. This might mean allowing yourself to enjoy a variety of foods without feeling guilty or anxious about your choices. By prioritizing your mental and emotional health, you can create a sustainable approach to eating that supports your long-term health and happiness.)

In humans, severe calorie restriction is linked to reduced lifespan. Anorexics have a mortality rate roughly tenfold that of the general population. However, people who practice calorie restriction for extended periods seem to be very healthy.

(Shortform note: The “very healthy” profile of people who practice calorie restriction for extended periods may not apply to everyone. For example, frail or underweight older adults may not benefit from calorie restriction, as it can exacerbate muscle and bone loss.)

Greger also suggests that NAD+ boosters could promote longevity and a longer healthspan. These are supplements that boost NAD+ concentrations in the body. NAD+ is a molecule that contributes to many cellular processes, including energy production and DNA repair. Research indicates that NAD+ boosters can increase longevity and healthy years in rodents. Treated mice had increased physical activity and endurance, improved vision, and strengthened bones, while delaying, avoiding, or counteracting muscle atrophy, hearing loss, ovarian aging, and cognitive decline.

(Shortform note: While NAD+ boosters may have potential benefits for longevity, researchers have raised concerns about their long-term safety. Some academic papers and research articles have suggested that NAD+ boosters could potentially promote the survival and growth of pre-cancerous or cancerous cells. This is because many cancer cells have a high demand for NAD+ to support their rapid growth and metabolism. By increasing NAD+ levels, these supplements could theoretically provide cancer cells with the resources they need to thrive.)

There is evidence of advantages for almost every organ system, including enhanced functioning of the arteries, brain, heart, immune system, kidneys, liver, and muscles. Other animals may also live longer due to NAD+ boosters, likely because they enhance sirtuin activity that's reliant on NAD+. Yeast cells were used to demonstrate this longevity effect over two decades ago. Overexpressing the genes responsible for NAD+ synthesis prolonged replicative lifespans by as much as 60 percent. NAD+-enhancing substances can lengthen the longevity of the microscopic worm C. elegans by up to 16 percent. In mice, one NAD+ booster increased lifespan by a less dramatic 5 percent, but it was achieved even when supplementation began later in life, which is atypical for longevity treatments. The major concern is if any of these impacts on lifespan or healthspan apply to humans.

NAD+ Boosters May Not Improve Human Health

Since the publication of How Not to Age, researchers have continued to investigate the effects of NAD+ boosters on human health. In an academic paper published in 2023, researchers reviewed the results of 15 clinical trials that tested the effects of NAD+ boosters on human health. The researchers found that NAD+ boosters consistently increased NAD+ levels in the blood, but they didn’t find any clear evidence that NAD+ boosters improved any clinically relevant outcomes. In other words, NAD+ boosters may increase NAD+ levels in the blood, but there’s no evidence that this increase in NAD+ levels has any meaningful effect on human health.

Let’s take a closer look at Greger’s foundational principles for healthspan extension and practical lifestyle changes.

Foundational Principles for Healthspan Extension

Greger states that living healthfully through your eating habits and way of life can prevent early death and physical limitations. The primary contributor to mortality for Americans is our diet. The typical diet in America is killing us. Most untimely fatalities and disabilities can be avoided with a nutritious diet and healthy habits. Diet is the top factor affecting our lifespan. The ideal eating plan mainly consists of unrefined plants.

Diet Is the Leading Cause of Death and Disability in the US

A 2018 study found that diet was the leading cause of death and disability in the US, accounting for more than 500,000 premature deaths and 11 million disability-adjusted life years (DALYs) lost annually. The study used a comparative risk assessment model to estimate the impact of 17 dietary factors on mortality and DALYs, finding that suboptimal intake of fruits, vegetables, whole grains, nuts, and seeds was responsible for the largest proportion of diet-related deaths and DALYs. The researchers concluded that improving diet quality could have a greater impact on reducing mortality and disability than any other single modifiable risk factor.

Let’s explore these foundational principles in greater depth.

Scientific Principles of Extending Your Healthy Years

Greger states that following a plant-centered diet can extend your healthspan. This diet minimizes the consumption of processed and animal-derived foods while maximizing the intake of unrefined plant-based foods, such as fruits, vegetables, whole grains, legumes, mushrooms, nuts, seeds, herbs, and spices. Eating a plant-based diet is linked to a reduced chance of getting cardiovascular disease, less likelihood of mortality from cardiovascular disease, and a decreased risk of death from any cause. The more you eat plant-based foods and consume fewer animal foods, the healthier and longer your life will be.

(Shortform note: In The Big Fat Surprise, journalist Nina Teicholz challenges the prevailing notion that plant-based diets are superior for health and longevity. She argues that the demonization of animal fats, particularly saturated fats, is based on flawed science and misinterpretation of data. Teicholz presents evidence from traditional diets and modern clinical trials suggesting that animal fats can be part of a healthy diet and may even contribute to longevity. She contends that the push for plant-based diets has led to increased consumption of processed foods and vegetable oils, which may have unintended negative health consequences.)

Replacing only 3% of the animal protein in your daily diet with plant protein is linked to reducing overall mortality rates by 10% for men and women alike. Replacing 3% of your daily calories from egg protein with plant protein is associated with a 20% lower mortality in men and women. Swapping merely 1% of calories from protein sourced from animals to protein from plants notably reduces deficit accumulation. For people of various ethnicities, legumes are the top dietary factor in predicting survival in old age. They contain high amounts of iron, zinc, and protein, while having naturally low levels of sodium and saturated fat.

(Shortform note: Deficit accumulation is a term used in geriatric research to describe the process of accumulating health deficits as people age. These deficits can include symptoms, diseases, disabilities, and functional impairments. The concept was introduced by Alexander Mitnitski, Anatoli Mogilner, and Kenneth Rockwood in 2001. They proposed that aging could be measured by counting the number of health deficits a person has, creating a “frailty index.” This index is calculated by dividing the number of deficits present by the total number of deficits considered. For example, if 40 possible deficits are assessed and a person has 10 of them, their frailty index would be 0.25. The frailty index has been shown to predict adverse outcomes such as disability, hospitalization, and mortality.)

They contain no cholesterol and are full of nutrients found in plants, such as fiber, vitamin B9, and potassium. Legumes may reduce cholesterol, blood pressure, and inflammation indicators. They also help regulate blood glucose and reduce insulin levels. However, legumes aren’t all the same, so you should strive for variety. The compounds in soybeans, chickpeas, lentils, and beans have only 7% overlap. To emulate those who live the longest, healthiest lives, Greger recommends following the Blue Zones Food Guidelines: 1) Make your diet 95-100% plant-based. 2) Consume fewer processed foods. 3) Consume one to two daily servings of chickpeas, lentils, split peas, or beans. 4) Consume primarily water. 5) Snack on nuts. 6) Consume fish sparingly. 7) Remove eggs from your diet. 8) Slash sugar. 9) Cut down on dairy. 10) Retreat from meat.

How to Stick to the Blue Zones Food Guidelines

To help you follow these guidelines, consider keeping a daily checklist of the 10 guidelines and marking which ones you met. Then, write down one small change you can make to improve tomorrow. This simple self-monitoring technique can help you stay on track with your new eating habits. Research shows that people who keep food diaries are more likely to stick to their dietary goals and make healthier choices. By tracking your progress and identifying areas for improvement, you can gradually adopt the Blue Zones Food Guidelines and work toward a longer, healthier life.

Avoiding Pitfalls in the Pursuit of Longevity

Greger warns against unproven anti-aging treatments and supplements. The business around anti-aging is a multi-billion dollar enterprise that often preys on people’s desire to stay young. Many treatments and dietary aids are marketed as miracle cures without scientific evidence to back them up. Certain treatments could even be harmful.

For example, human growth hormone is sometimes promoted as a method to counter aging, but there’s no evidence it slows aging. In fact, it might elevate cancer risk and shorten lifespan. Another example is DHEA, a hormone that decreases with age. DHEA supplements are marketed as anti-aging remedies, but studies show they're no more effective than placebo pills. Certain DHEA products don't even contain any DHEA at all.

HGH and DHEA as Anti-Aging Treatments

A 2006 investigation found that HGH and DHEA were being marketed as anti-aging treatments without any requirement to track long-term outcomes in otherwise healthy older adults. The investigation found that HGH was being promoted as a way to counteract the natural decline in growth hormone levels that occurs with age. However, there was no evidence that HGH could actually slow aging or improve health in older adults. In fact, some studies suggested that HGH might increase the risk of cancer and other health problems. Similarly, DHEA was being marketed as an anti-aging remedy because its levels also decline with age. But research showed that DHEA supplements were no more effective than placebos at improving health or slowing aging. Some DHEA products didn't even contain any actual DHEA.

Practical Lifestyle Interventions

Greger explains that embracing a health-focused way of living can substantially reduce the likelihood of getting long-term illnesses and dying early. A healthy lifestyle includes not smoking, maintaining a healthy weight, exercising for 30 minutes a day, and eating a healthy diet. Such a lifestyle can lower the likelihood of diabetes by 90%, having a myocardial infarction by 80%, suffering a stroke by 50%, and getting cancer by 33%. It can additionally lower the likelihood of death by 40% over the coming four years and postpone the onset of chronic illnesses by 10 years.

(Shortform note: The evidence supporting the benefits of a healthy lifestyle is robust and comes from large-scale, long-term studies. For example, a study of over 120,000 adults found that those who maintained a healthy weight, exercised regularly, ate a nutritious diet, and didn’t smoke had a 90% lower risk of diabetes, 80% lower risk of heart attack, 50% lower risk of stroke, and 33% lower risk of cancer compared to those with unhealthy lifestyles. These findings held true even after accounting for other factors like age, family history, and socioeconomic status. The studies used a scoring system that combined all four lifestyle factors, showing that the more healthy habits people adopted, the lower their risk of chronic diseases and early death.)

People who don’t smoke, don’t have diabetes, aren’t obese, don’t have high blood pressure, and aren’t sedentary have a 95% chance of living to age 90. People who have these risk factors have less than a 5% chance of reaching age 90. Even people over 75 can live 18 months longer without being disabled by choosing a healthier way of living.

(Shortform note: The statistics Greger cites here are likely an exaggeration of the data. In a 2018 study, Yanping Li, Dong D. Wang, and Frank B. Hu found that people who didn’t smoke, weren’t obese, exercised regularly, ate a healthy diet, and drank alcohol in moderation lived 12 to 14 years longer than people who didn’t have these five low-risk factors. However, the probability of living to age 90 is likely not as high as 95% for people who don’t have these risk factors and not as low as 5% for people who do.)

Let’s take a closer look at the positive and negative lifestyle interventions that Greger recommends.

Positive Lifestyle Interventions

Greger states that a diet made up of unprocessed plant-based foods can promote longevity and reduce disease risk. This plant-based eating plan omits refined carbohydrates, white potatoes, alcoholic beverages, as well as additional sugar and oils.

(Shortform note: The term “unprocessed plant-based foods” can be confusing. In general, it refers to foods that are close to their natural state, such as fruits, vegetables, whole grains, and legumes.)

A whole-food, plant-based diet can help you lose body fat and reduce your likelihood of developing fat around the belly, hypertension, high blood glucose, metabolic syndrome, elevated cholesterol, high triglycerides, depression, anxiety, and mental distress. It can also reduce your risk of non-cancerous breast conditions and breast cancer. Additionally, this diet may extend your lifespan. Eating a daily intake of five portions of fruits and vegetables can help you live three years longer than someone who doesn’t eat any fruits and vegetables. Eating plant foods can help you live longer even if you start eating them in your 70s. This diet can also reduce your exposure to industrial pollutants that accumulate in the food chain and cause illness and aging.

The Origins of the Whole-Food, Plant-Based Diet

The idea that a whole-food, plant-based diet can extend your lifespan originated in the 1950s, when researchers began studying the health of Seventh-day Adventists, a religious group that promotes a vegetarian diet. In Diet, Life Expectancy, and Chronic Disease, Gary Fraser explains that these studies found that Adventists had lower rates of heart disease, cancer, and other chronic illnesses compared to the general population. The Adventists’ diet, which emphasizes whole grains, legumes, fruits, nuts, and vegetables, was linked to these health benefits. The studies also found that Adventists who ate more fruits and vegetables lived longer than those who ate fewer plant foods.

Negative Lifestyle Interventions

Greger warns that consuming large amounts of saturated fat is linked to cognitive decline and dementia. Saturated fat might make Alzheimer's more likely by compromising the blood-brain barrier. It might also result in poorer memory and faster cognitive deterioration. The Harvard Women's Health Study found that the women with the most saturated fat in their diet were 60 to 70 percent more likely to experience cognitive decline as time went on, while the women with the lowest consumption had brain function equivalent to women six years younger.

(Shortform note: The Harvard Women’s Health Study is an offshoot of the Nurses’ Health Study, which began in the 1970s to track the health of over 120,000 nurses. The study was originally designed to investigate the causes of cardiovascular disease and cancer in women. Over time, researchers added questions about diet and cognitive function to the study. This allowed them to track how women’s eating habits in midlife affected their memory and thinking skills as they aged.)

Research has shown that consuming more saturated fat correlates with a 40% higher chance of cognitive issues, a 46% increased likelihood of Alzheimer's, and over double the risk of dementia overall. A new review determined that the relationship between eating saturated fat and Alzheimer’s seems definitive and harmful. Saturated fat may raise dementia risk through various indirect means, such as causing insulin resistance, hypertension, inflammation, or clogged cerebral arteries.

(Shortform note: As early as 2003, researchers were already warning that saturated fat could be a risk factor for Alzheimer’s. In an academic paper, they reported that a study of over 800 people in Chicago found that those who ate the most saturated fat were more likely to develop Alzheimer’s disease. The researchers also found that trans fats were linked to a higher risk of Alzheimer’s. This study was one of the first to suggest that certain types of fat in our diet could contribute to Alzheimer’s disease later in life.)

It could also cause the brain's blood vessels to become more permeable. The barrier's permeability can be measured by administering a dye intravenously and observing its leakage into the brain through an MRI scan. People with Alzheimer’s or vascular dementia usually have more permeable brain vessels compared to peers their age. These conditions can degrade the blood-brain barrier, although the permeability seems to come before the dementia. Leakage rates increase in mild cognitive impairment and cerebral small vessel disease, which are precursor syndromes to Alzheimer's disease and vascular dementia. In healthy people, blood-brain barrier permeability generally increases as they get older, especially in brain areas that are more susceptible to aging, implying that barrier disruption might contribute to typical cognitive decline. Having excess weight or obesity in midlife was linked to reduced blood-brain barrier functionality 24 years later.

(Shortform note: The dye used in this procedure is a contrast agent, a substance that enhances the visibility of internal structures in medical imaging. In this case, the contrast agent is gadolinium, a rare earth metal that is commonly used in MRI scans. Gadolinium is injected into the bloodstream, and its movement through the body is tracked using MRI. The authors explain that the MRI scan measures the time-dependent changes in signal intensity in brain tissue and blood vessels. By analyzing these changes, researchers can calculate a parameter called the transfer constant (Ktrans), which reflects the rate at which the contrast agent moves from the blood vessels into the brain tissue. An increase in Ktrans indicates a more permeable blood-brain barrier, as the contrast agent is able to leak into the brain tissue more easily.)

From a dietary perspective, cholesterol, with or without saturated fat, can increase how permeable the blood-brain barrier is. In mice, saturated fat can lead to blood-brain barrier dysfunction that is 30 times worse, and dietary cholesterol can cause it to worsen sevenfold; a cholesterol-lowering drug can prevent both effects. This could be doubly harmful because consuming saturated fat can elevate the creation of amyloid precursor protein from the gut, which becomes amyloid beta in mice, and also raise its release into the bloodstream. Just one meal rich in saturated dairy fat can result in a sevenfold rise in blood amyloid protein levels. Together with a permeable blood-brain barrier, this might account for the increased plaques seen in animals fed fat.

(Shortform note: The effects of cholesterol and saturated fat on the blood-brain barrier and amyloid protein levels in humans may not be as dramatic as in animal studies. According to biomedical researchers, the human brain produces its own cholesterol, and the blood-brain barrier prevents cholesterol from entering the brain from the bloodstream. This means that changes in blood cholesterol levels from a single meal are unlikely to have a significant impact on the brain’s cholesterol levels or the integrity of the blood-brain barrier. However, in people with certain health conditions, such as diabetes or high blood pressure, the blood-brain barrier may be more permeable, potentially allowing more cholesterol to enter the brain.)

In the anti-inflammatory section of his book, Greger discusses numerous studies demonstrating that only a few days on a high-fat, ketogenic diet can dull cognitive function, potentially taking weeks to bounce back from. A meal high in saturated fat can negatively affect people's cognitive abilities in just five hours. This may stem from inflammation in the brain.

(Shortform note: Neuropsychologist Robert Krikorian and his colleagues have argued that ketogenic diets can improve cognitive function. In a research article, they describe a study in which they found that a diet that induces ketosis can improve memory in older adults with mild cognitive impairment. This suggests that, at least in some cases, a ketogenic diet can enhance cognitive function rather than dulling it.)

When laboratory animals consume saturated fat, it permeates the blood-brain barrier, builds up in the brain's core, and causes inflammation. The initial research on animals employed diets based on lard, but butterfat seems to produce similar results. The situation can also be replicated in a petri dish. When neurons are exposed in vitro to the primary saturated fat common in the typical American diet (largely sourced from dairy and meat), it can rapidly trigger inflammation. The positive thing is that this can be reversed. When the animal subjects returned to their typical low-fat diet, their brain inflammation disappeared.

(Shortform note: While the laboratory animals’ brain inflammation disappeared when they returned to their typical low-fat diet, researchers have found that low-fat diets can have negative effects on the brain. In a study of older adults, those who followed a low-fat diet had worse cognitive outcomes than those who followed a Mediterranean diet. The researchers suggest that this may be because the low-fat diet didn’t include enough unsaturated fats, which are important for brain health. This research suggests that replacing saturated fat with unsaturated fat may be more beneficial for brain health than simply reducing fat intake.)

In randomized crossover trials, researchers covertly increased the saturated fat intake of study participants and saw that it causes negative alterations in inflammation, mood, brain function, and resting metabolic rate, and even seems to reduce the drive to exercise. Participants' physical activity levels dropped by 12–15% when consuming high-saturated-fat diets compared to those with reduced saturated fat. Remember that the researchers employed palm oil, a plant-derived saturated fat included in some processed foods like vegan spreads and cheese substitutes. Therefore, an anti-inflammatory eating plan emphasizes plants overall; it particularly focuses on whole, unprocessed plants.

(Shortform note: In a randomized crossover trial, each participant receives the different diet conditions in a random order, allowing researchers to compare the effects within the same person. This design helps control for individual differences and provides more reliable results.)

Apart from oxidized cholesterol and saturated fat, what other factors in meat might explain why people who eat it have up to triple the risk of dementia compared to vegetarians? In the Glycation section, Greger discusses how the presence of AGEs in meat that is baked, broiled, grilled, fried, or roasted contributes to cognitive decline as people age, as well as brain shrinkage, mild cognitive impairment, and the onset and worsening of Alzheimer's disease.

(Shortform note: If you run a hospital or care home kitchen, you could use this information to set a daily “AGE budget” for your patients or residents. In a research article, researchers provide a table of the AGE content of various foods and suggest that you could set a limit of 15,000 AGE units per day. For example, a 3.5-ounce serving of broiled beef contains 6,674 AGE units, so you could limit your patients to two servings of beef per day.)

Pollutants, including those that are chlorinated, might be contributing factors as well. In older Americans, there's a connection between DDT, its derivative DDE, and a higher likelihood of faster cognitive decline, along with Alzheimer's severity and diagnosis. These toxins remain in our bodies since they continue to be found in our food supply. Specimens from grocery stores throughout the U.S. showed fish, various meats, eggs, and dairy had dioxin and PCB concentrations five to ten times higher than the plant-based foods.

(Shortform note: The widespread presence of chlorinated pollutants in the U.S. food supply and in older Americans’ bodies is a legacy of decades of intensive use of organochlorine pesticides and industrial chemicals. DDT, dioxins, and PCBs were heavily used in agriculture and industry from the 1940s through the 1970s, when their environmental and health impacts became undeniable. These chemicals are extremely persistent, with half-lives measured in decades, and they accumulate up the food chain. This means that people born before the 1970s were exposed to much higher levels throughout their lives than those born after widespread bans and restrictions were implemented.)

Recently, researchers have suggested endotoxins as a mechanism explaining the connection between cognitive impairment and saturated fat. Essentially, two methods exist to reduce endotoxin spikes post-meal. One method is to limit initial intake. However, if you consume meat, including fiber-rich foods can mitigate the endotoxin spike. Eating a McDonald's Sausage and Egg McMuffin alongside a cereal rich in fiber notably decreased endotoxin levels in the bloodstream relative to eating just the McMuffin. The fiber also decreased the linked oxidative stress, which plainly demonstrates a significant impact on the meal's metabolic and inflammatory processes.

(Shortform note: Endotoxins are fragments of bacterial cell walls that can enter the bloodstream after a high-fat meal. These fragments, known as lipopolysaccharides (LPS), are components of the outer membrane of certain bacteria. When these LPS molecules cross from the gut into the bloodstream, they trigger an immune response, leading to widespread inflammation throughout the body. This process, called metabolic endotoxemia, has been linked to the development of obesity and insulin resistance. The authors explain that even small amounts of these endotoxins can activate the body's innate immune system, causing chronic, low-grade inflammation that disrupts normal metabolic functions.)

The primary recognized risk factor for cognitive decline is aging, but it seems 40 percent of dementia cases are tied to modifiable risk factors that we can influence. In addition to enhancing our eating habits, we can lower the risk of dementia by avoiding head injuries, stopping smoking or staying away from it, steering clear of secondhand smoke and other air pollutants, moderating alcohol consumption, getting enough sleep, managing weight, and maintaining physical activity. Sports are linked to up to 30% of traumatic brain injuries. This might explain why ex-professional soccer players seem to have a fivefold increased likelihood of dying from Alzheimer's compared to similar counterparts, particularly those in field roles where they often perform more "headers."

The Impact of Risk Factors Varies by Age

If you can’t optimize every risk factor, focus on the ones that have the greatest impact for your age group. For example, a 2020 study found that hearing loss, depression, and social isolation were the most significant modifiable risk factors for dementia in people over 55. For those under 55, diabetes, excessive alcohol consumption, and smoking were the most important factors. The study also found that the impact of these risk factors varied by age. For example, diabetes was a stronger risk factor for dementia in people under 55 than in those over 55. This suggests that interventions to prevent dementia may need to be tailored to different age groups.

Greger also warns that consuming alcohol could raise the likelihood of developing certain cancers. Alcohol is detoxified in the body into acetic acid, which activates AMPK. However, before it is fully converted, a harmful compound called acetaldehyde is formed; it’s a known carcinogen. This could explain why alcohol is thought to raise the likelihood of several types of cancer, including breast and colorectal, even in light drinkers.

(Shortform note: The link between acetaldehyde and cancer risk is supported by studies of people with a genetic mutation that causes them to accumulate more acetaldehyde when they drink alcohol. These people have a much higher risk of cancer, even if they drink only a small amount of alcohol. This suggests that acetaldehyde is a key factor in the cancer-causing effects of alcohol.)