The Link Is Unmistakable
Tell people that biology and the environment cause obesity and they are offered the one thing we have to avoid: an excuse.
Andrew Lansley, British Secretary of State for Health1
Aging—the slow decline in vitality and ability—affects us all. Yet while people move through time at a constant rate, not everyone ages at the same rate during the same amount of time lived. Some individuals deteriorate (age) much faster than others. While we cannot affect the passage of time, we can affect our passage through time—we can make intelligent choices to maximize health and slow the decay so that we grow older with greater vitality and retained abilities.
When we know what accelerates aging, we can make intelligent choices to minimize or avoid harmful factors and embrace actions that promote vitality and youthfulness. So what factors accelerate aging and loss of vitality, and what actions can we take to maintain our abilities to the highest extent possible?
One of the major factors in accelerated aging is oxidative stress, which is the damage to DNA, proteins, lipids, and other body tissues caused by oxygen-containing molecules. Cut an apple and leave it on the counter for an hour and what happens? It browns; this is oxidation—oxygen molecules binding with and damaging the fruit. Oxidation damages the body’s tissues and accelerates aging. This is why we hear so much about antioxidants—factors that scavenge the oxidizing molecules and protect us from oxidative damage.
Inflammation
In this book I use the term inflammation or inflammatory cascade when describing various factors that accelerate aging. In fact, it is through the inflammatory pathway of the body that most of the negative health factors cause accelerated aging and increase our risk of dementia. Whatever increases inflammation will accelerate aging and raise dementia risk, while whatever decreases inflammation will slow aging and lower dementia risk.
So what do I mean by inflammation?
Inflammation is when the body responds to attacks (either by injury, infection, or disease) by mobilizing its forces to neutralize and resolve the attack, thus restoring the body to normal function. The body’s inflammatory response is exquisitely complex with many cells (white blood cells—neutrophils, monocytes, eosinophils, mast cells), proteins, and other factors (chemokines, cytokines, adhesion molecules, oxygen-containing molecules, etc.) working in orchestrated cascades to resolve threats, bring healing, and restore normal function. We have all experienced this when we have had a cold or some other infection. These inflammatory factors, which are designed to neutralize threats to the body, impact the body in other ways as well and cause symptoms such as malaise, fatigue, concentration problems, loss of appetite, and achiness—symptoms we often experience when fighting a sickness. When all things go as designed such inflammation is limited to the level of the threat and resolves when the injury is healed or the infection cleared.
However, sometimes things go wrong and the body’s inflammatory system stays turned on. This can happen in the aftermath of an infection or injury and can contribute to chronic fatigue, autoimmune disorders, and chronic pain states. The body can also turn on this inflammatory cascade in response to certain foods, toxins, pollutants, or other ingested substances as we shall soon discover.
Finally, the body can also gear up its inflammatory response in reaction to perceived threats. This means chronic anxiety, worry, conflict, and stress can turn on this system and increase within the body the concentration of circulating molecules that are designed to damage (oxidize) invading viruses and bacteria. But when we are under chronic worry and stress, the concentration of these molecules increases without any foreign invaders for them to attack. So instead they begin damaging healthy cells within our bodies. This is inflammation—elevation and activation of immune cells, chemokines, cytokines, adhesion molecules, and oxygen-containing molecules—which causes widespread problems in our bodies, including accelerated aging, and, as we will see in chapter 14, directly contributes to the development of dementia.
So what are the factors that increase oxidative damage to our brains? In Part 2 we will explore three factors that increase oxidation and accelerate aging—obesity, sugar, and toxic substances.
Obesity
Perhaps the most significant factor that increases oxidative damage to our bodies and accelerates aging is obesity! Excessive fat tissue produces reactive oxygen species (ROS), which are molecules that contain oxygen capable of interacting with our body tissues and causing damage. Further, excess fat reduces the body’s antioxidant enzymes, undermining our body’s ability to eliminate these toxic molecules.2 Obesity increases oxidative stress.3
At age seventy an obese person’s brain has 8 percent less brain volume and appears sixteen years older than a normal-weight person’s brain of the same age. Also, at age seventy an overweight person’s brain has 4 percent less brain volume and appears eight years older than a normal-weight person’s brain of the same age.4
Obesity in America is rampant: more than 40 percent of men and 42 percent of women between the ages of fifty-five and sixty-four are obese; between ages sixty-five and seventy-four, over 36 percent of men and 35 percent of women are obese. That is well more than one in three. If we include those who are overweight, the numbers are staggering: after age fifty-five approximately 80 percent of men and 70 percent of women are either overweight or obese!5
Historically, people viewed obesity as a simple matter of calories consumed versus calories burned—if people ate more calories than they burned, they got obese. While this is true as the final common denominator, many factors other than the amount of food ingested impact the body’s energy balance. In other words, obesity is quite complex with a multiplicity of factors contributing to alterations in the body’s ability to absorb and utilize energy.
Sleep and Obesity
Studies have shown that sleep deprivation can alter the body’s hormones that impact metabolism, thus altering its ability to burn energy reserves (fat) and increasing the risk of obesity.6 According to the Centers for Disease Control (CDC), fifty to seventy million Americans have some type of sleep disorder.7 A 2009 multistate CDC survey of over seventy thousand adults found that more than 35 percent of people slept fewer than seven hours per night.8 And according to a Sleep in America Poll conducted on behalf of the National Sleep Foundation, approximately 20 percent of Americans get fewer than six hours of sleep per night.9 Sleep deprivation is a serious problem and alters normal body energy use, contributing to obesity, which contributes to increased oxidative stress. In chapter 9 we will explore in greater detail the importance of sleep for healthy brain function and factors that interfere with normal sleep.
Soybeans and Obesity
Over the last one hundred years dietary patterns in many westernized countries have changed. In the United States there has been a significant shift in the percentages of dietary oils ingested—away from healthy oils to more obesity-promoting fats. Historically, the human diet contained no more than 1 percent of the oil linoleic acid (LA), which is an omega-6 fatty acid found in a variety of foods but highly concentrated in soybean oil. Over the past century the United States’ dietary intake of LA has increased from 1 percent to 8 percent of daily caloric intake. Soybean oil is used in most margarines and shortenings as well as in mayonnaise, salad dressing, frozen foods, imitation dairy, various meat products, and commercial baking goods.
Recent research has demonstrated that LA is a precursor to two brain-derived marijuana-like compounds called endocannabinoids. These compounds are active in the brain region that controls appetite, caloric intake, and satiety. Increasing activity in this brain region triggers increased appetite and is associated with increasing obesity.10
Remarkably, in animal studies conducted to evaluate the impact of increasing LA in the diet, animals fed diets composed of 35 percent fat and 8 percent LA had significantly greater obesity than animals fed 60 percent fat diets and only 1 percent LA. This indicates that the LA trigger of endocannabinoid receptors mediates obesity. Even if one lowers the amount of total fat in the diet, if the diet retains a high percentage of LA, obesity risk increases.
However, supplementing the 8 percent LA diet with 1 percent omega-3 fatty acids from fish oil (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) reversed the elevations of endocannabinoids and decreased both food consumption and obesity.
Further, insulin levels were not altered in either group, meaning the obesity was occurring before diabetic metabolic dysregulation occurred and was not caused by insulin resistance or driven by carbohydrate intake.
Soybean oil (not to be confused with soybean protein) is about 50 percent LA by weight and is the single greatest contributor to the increase in LA in the American diet over the last century. Combine this increased consumption of LA with the reduction in EPA and DHA through either less fish consumed or increased farm-raised fish (which are generally devoid of EPA and DHA), and we have a dietary setup for increased obesity. This dietary change corresponds with the increased prevalence of obesity seen in the United States.
A diet low in EPA and DHA and high in LA is associated with not only increased obesity but also increased risk for mental health–related problems, including psychosis, mood disorders, and dementia.11 Therefore, reducing LA, primarily by reducing soy intake and increasing EPA and DHA in the diet, has been shown to be healthy for the brain. Other sources of LA include safflower, sunflower, and sesame oil, as well as Brazil nuts and pine nuts. Alternative oils low in LA include canola (21 percent), olive (10 percent), palm (10 percent), and coconut (2 percent).
Foods high in omega-3s (EPA and DHA) include wild sardines, salmon, mackerel, tuna, and trout. Freshwater fish have significantly less EPA and DHA than cold-water ocean fish. EPA and DHA are not produced in plants, with the exception of some sea algae and seaweed. Therefore, vegans are encouraged to find a seaweed supplement high in EPA and DHA. Flax seed is high in omega-3 (ALA) but is poorly converted in the body to the form the brain needs, with approximately 8 percent converted to EPA and less than 1 percent converted to DHA. Therefore, flax seed supplement is not recommended as a substitute for EPA and DHA.12
Genetically Modified Foods and Obesity
Another factor impacting obesity rates today may be genetically modified foods. I first became concerned about genetically modified foods when studies began to emerge demonstrating that we are impacted not only by the fats, proteins, and carbohydrates of the foods we eat but also by the genetic material of consumed foods. Whatever food we eat contains the DNA and RNA of that plant or animal, and its genetic material is also absorbed into our bodies. Science now demonstrates that ingested genetic material can alter how our genes are expressed. One study found that small pieces of RNA from ingested rice alter the human gene that codes for how LDL cholesterol is processed.13 This means the genetic material from the foods we eat can alter how our genes are expressed.
With this thought in mind, I became troubled by the amount of genetically modified food in our food supply and the serious lack of evidence demonstrating that it is safe and does not cause genetic modifications damaging to our health. A recent animal study in Norway lends support to my concern. Rats that were fed genetically modified food grew fatter than rats fed nongenetically modified food. This occurred whether the rats ate the genetically modified corn directly or ate fish that were fed genetically modified corn. Professor Åshild Krogdahl of the Norwegian School of Veterinary Science rightly asks, “If the same effect applies to humans, how would it impact on people eating this type of corn over a number of years, or even eating meat from animals feeding on this corn?”14 While the exact reasons for these differences in weight have not been determined, altered gene expression is one possibility.
Until much more research is done to prove the health safety of genetically modified foods, the wisest course of action is to select organic, non-GMO foods whenever possible. This may be difficult to achieve in the United States where as much as 75 percent of the food in supermarkets contains genetically modified ingredients. The law passed in 2016 requiring the labeling of GMO-containing foods allows manufacturers to comply by placing a QR code on the packaging that, when scanned by a smartphone, would take the consumer to a website informing them of the GMO content. I would encourage those concerned to speak with your supermarket managers and request they do this research and clearly label items for sale in their stores as GMO-free items.
Gut Bacteria and Obesity
Other research has documented that obese people and thin people have different types of bacteria living in their stomachs and intestines, and these differences can contribute to obesity.15 Obese people had fewer bacteria called Bacteroidetes and greater amounts of Firmicutes as compared to lean people.16 Further research demonstrated that diet impacts the balance of microbes living in our guts. When dietary changes were made that resulted in weight loss, Bacteroidetes increased and Firmicutes decreased in the gut.17 Typically, fiber in plants is indigestible to humans, which means the energy in such material (like cellulose) is not absorbed by humans and doesn’t contribute to caloric intake. However, studies have demonstrated that bacteria living in the gut can metabolize fiber and contribute as much as 10 percent of daily caloric intake. This may be why some obese people don’t lose weight even when eating foods low in calories but high in fiber.18 This means that addressing obesity isn’t as simple as merely calculating the number of calories consumed versus those burned but includes the impact that the bacteria living in one’s bowels are having. Are the gut bacteria converting typically inaccessible consumed calories (cellulose) into absorbable calories? The evidence strongly suggests the answer is yes.
Our food choices do change the gut flora and these changes occur quickly. One recent study found that people on a plant-based diet who began eating animal products (eggs, milk, cheese, meat) experienced changes in gut bacteria within one day.19 And the bacterial changes with the animal-based diet were associated with greater risk for inflammatory diseases.20 Foods high in plant fiber (legumes, fruit, broccoli, etc.) increase the growth in good bacteria that promote weight loss, whereas foods high in sugar and animal fats promote bacteria that increase inflammation and oxidation.21 Interestingly, this may be one of the reasons gastric bypass surgery often results in weight loss. Studies have shown that one factor in the weight loss associated with gastric bypass surgery is not simply a reduction in calories consumed but also the marked change in gut flora that the surgery triggers.22
The bottom line on obesity in this regard is that it isn’t just the total calories consumed that matters but also the types of foods consumed, which alter gut bacteria. Animal-based foods increase the bacteria that contributes to obesity, whereas plant-based foods that are high in fiber increase the bacteria that promotes weight loss. Reducing animal products and increasing plant-based food choices is one action you can take to reduce obesity risk.
Not All Body Fat Is Equal
The body has two populations of adipose, or fat: white and brown. White fat is associated with obesity and is very difficult to mobilize and remove from our bodies. Brown fat is involved in regulating body temperature and thus actively burns calories. While white fat cells contain only fat, brown fat cells in addition to the fat also contain iron-rich mitochondria and more capillaries to provide oxygen for energy use. As we age, we tend to lose brown fat from our bodies; this may contribute to the midlife spread, the typical increase in body fat that happens in our fifties. Recent research has demonstrated that diet, gut bacteria, and inflammation and the immune response to it directly impact the amount of brown fat in our bodies and thus whether we are obese or remain thin throughout life.
Researchers at Harvard and Conway Institute at University College Dublin have demonstrated that an immune cell, invariant natural killer T (iNKT), is integral in activating the small protein fibroblast growth factor-21 (FGF-21). This protein, when available, triggers the body to convert white fat into brown fat and results in increased energy production from the fat cells, which raises body temperature and basic metabolic rate and brings about significant weight loss. Blood samples from obese individuals showed reduced iNKT cells. But obese individuals who lost weight after bariatric surgery showed increased iNKT cells. Similarly, in animal studies when the animals were placed on a high-fat diet, they lost their iNKT cells and gained weight, but when the diet was returned to normal the iNKT cells increased and weight loss occurred. When iNKT cells were removed from normal mice and injected into obese iNKT-deficient mice, the obese mice lost weight, had improved insulin sensitivity, and improved triglycerides—all indicators of improvement in metabolic profile. Finally, the researchers tested a lipid (alpha-galactosylceramide [aGC]) known to activate the iNKT cells and discovered that a single dose of this lipid resulted in reversal of diabetes, marked weight loss, and lowering of blood lipid levels.23 Though not currently available as a treatment, hopefully it soon will be.
What is interesting is that as people become obese, the iNKT cells are lost and the ability to produce brown fat is reduced. Contributing factors to the reduction of the iNKT cells are diets high in fat and sugars and low in dietary fiber, the Western diet. One potential mechanism for this was recently discovered and has to do with the bacteria living in our gut. As we just discussed, the bacteria living in our gut can impact our caloric absorption. But recent research has demonstrated that one type of bacteria, Bacteroides, also produces the glycosphingolipid α-galactosylceramide (α-GalCerBf), which is structurally related to aGC and has been shown to be an activator of our iNKT cells in both vitro and vivo studies.24 This means that a plant-based diet rich in fiber and low in animal fats will cause growth of good bacteria (Bacteroides), which produce a protein that will activate our iNKT cells, which in turn will produce a protein that will trigger white fat to turn to brown fat—increasing our metabolism, burning fat, and reducing obesity.
Genetic Expression and Obesity
On a similar note, as we discussed in chapter 2, research has found that during fetal development environmental factors can impact gene expression that regulates how efficiently one absorbs energy from food. During WWII in the Netherlands there was a severe food shortage. People averaged about five hundred calories of food intake per day, including pregnant women.
Children born to women during this food shortage grew up with higher rates of obesity, diabetes mellitus, and metabolic problems than their siblings born to the same parents when food was more plentiful. Researchers have identified that the severe food shortage altered the expression of a specific gene (IGF2) associated with energy absorption from food. This particular gene was altered in a way that caused increased expression and resulted in what scientists believe is the ability of these individuals to extract more calories from the same food as compared to others where this gene is less active.25
For some, then, obesity has little to do with their lifestyle or food choices but with the epigenetics governing metabolism genes. Understanding this may provide psychological relief and reduce guilt, blame, and shame cycles, which only activate stress pathways and thus contribute to increased inflammation and undermine the ability to lose weight. Additionally, persons who may be obese due to such epigenetic changes may have tried various diet or lifestyle programs with minimal results and have become discouraged and given up—thinking, Why bother?—and resigned themselves to eating whatever they want. This would be a terrible mistake because it isn’t just obesity itself that is the problem but also the increased inflammation throughout the body that causes the negative brain changes. Lifestyle choices that reduce inflammation will reduce the damage and add protection to the brain—even if the person remains overweight.
Therefore, if you are struggling with excessive body fat and have tried lifestyle changes to lose weight but have experienced only limited success, don’t fall into the trap of believing that your choices don’t matter—they do! Choosing to make healthy lifestyle choices, including walking daily (see chap. 8), regular, normal sleep cycles (see chap. 9), anti-inflammatory diet (see chap. 6), mental rest and relaxation (see chap. 10), and formulating healthy belief systems (see chap. 11), will reduce inflammatory stress, improve brain function and cognitive performance, and reduce dementia risk even if the total body weight doesn’t change!
Infections and Obesity
Another factor that can increase inflammation is infections, and certain viral infections have been shown to contribute to obesity. Adenoviruses are a family of viruses that infect humans, causing the common cold and stomach, eye, and bladder infections. One particular adenovirus (Ad-36) has been shown to cause obesity in humans.26 The exact mechanism is unknown but is potentially related to increased inflammation.
Inflammation and Obesity
Finally, inflammation causes insulin resistance, which results in the body increasing the amount of insulin circulating in the blood. Insulin not only regulates the body’s glucose levels but also signals fat cells to create more fat and to stop adipose cells from breaking down stored fat to be burned off. In order to burn stored fat rather than create more fat, the signal sent by insulin to fat cells must be reduced. An interesting animal study revealed that knocking out the insulin receptor in fat cells resulted in the animals losing up to 70 percent of their body fat in three months, despite eating 55 percent more food per gram of body weight—and they lived 18 percent longer than animals without the insulin receptor knocked out.27 The weight-loss strategy of lowering insulin is the core principle behind the various high-fat, low-carb weight-loss programs. If one reduces carbs, then one reduces the production of insulin and thereby promotes weight loss. Such diets focus exclusively on weight loss, not on aging and slowing the loss of vitality and retaining abilities. So while it is true that reducing obesity is beneficial to slowing aging, one can still have accelerated aging with a normal body weight if inflammation is not reduced. A highly inflammatory diet with normal body weight is not the best approach to slowing the aging process.
Anything that increases inflammation will contribute to insulin resistance and promote obesity. Highly processed foods, junk food, and fast food contribute to obesity not only because of the high concentration of calories but also because these foods are highly inflammatory foods. Thus, they increase glucose while simultaneously contributing to insulin resistance. And of course, once obesity occurs the adipose tissue itself creates inflammatory factors, contributing to further insulin resistance and increasing production of fat stores—a downward spiral.
While excessive body fat increases production of oxidizing molecules and reduces the antioxidant enzymes in the body, it isn’t merely the body fat itself but also the constellation of other lifestyle factors that typically accompany and contribute to obesity that are the real problem when it comes to aging. Obese people generally don’t exercise as much as thin people, thereby reducing exercise-induced neurotrophins (proteins that act like fertilizer in the brain to keep neurons healthy and increase the production of new neurons and neuron-to-neuron connections, which improve learning and slow cognitive decline). Also, those with excessive body fat typically eat unhealthier diets, with foods that are inflammatory in nature, and often have sleep problems, which accelerate cognitive decline.
The point of all of this is that obese individuals have accelerated brain decline and increased risks of dementia because of multiple negative factors working together. Even if one doesn’t lose weight but addresses the other negative factors, the damaging toll on the brain will be reduced. Therefore, an obese person who gets normal sleep, walks thirty minutes daily, eats a healthy anti-inflammatory diet, gets regular mental rest, and manages life stress well will reduce the negative impact of obesity on their brains, slow cognitive decline, and have better memory and cognitive performance.
LEARNING POINTS
ACTION PLAN: THINGS TO DO