The Immune Miracle – Chapter 3 – Stress and Your Immune System

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

 

Chapter 3

Stress and Your Immune System

We know that during periods of increased stress, there is often also an increase in the incidence of certain chronic “immune-related” conditions, such as asthma, allergies, and rheumatoid arthritis, as well as of gastrointestinal ailments such as irritable bowel syndrome (IBS) and Crohn’s disease. This is quite interesting, because each of these conditions is considered to have an autoimmune component to it—meaning that one’s own immune system has gone a bit haywire and has started to attack one’s own tissues. In these cases, doctors often prescribe synthetic versions of cortisol (your body’s primary stress hormone) as a way to suppress an overactive immune system, and it works quite well—but only for a short period of time. The problem with using synthetic cortisol as a medication, however, is that too much of the stuff, or even a modest amount for too long, leads to the very same tissue breakdown and metabolic disturbances present during chronic stress.

Medical researchers have known for more than sixty years that chronic or repeated bouts of stress will lead to a shrinking of the thymus gland (one of the key immune tissues in the body) and to a general suppression of immune-system strength via an inhibition of white-blood-cell production and activity. Cortisol suppresses the ability of white blood cells to secrete chemical messengers (interleukins and interferons), so the different varieties of immune-system cells are unable to communicate with each other in order to effectively fight off infections. Finally, and most remarkably, is the fact that cortisol can actually act as a signal to many immune-system cells to simply shut off and stop working (that is, the cells die).

Now, why would stress and cortisol have all of these detrimental effects on the immune system? You would think that during times of stress, the body would want to increase its resistance to invading pathogens (bacteria and viruses) rather than decrease this vital protection—but this is clearly not what happens. To answer this question, we need to consider the timing of the stress response, where we see that immune function is actually stimulated by stress for a short period of time (a few minutes). This short blast of immune-system stimulation appears to be used by the body to “wake up” existing immune-system cells, as well as to “clear out” cells that fail to work properly due to normal cell aging.

This is all very good: now, you have a short-term stressor that has ramped up immune-system activity and you’re ready to fight off the invading bugs. The problem occurs when a prolonged stress response sends these finely regulated systems into complete chaos. During periods of chronic stress, cortisol levels remain elevated and immune-system integrity begins to suffer. Not only do the chronically stimulated immune-system cells start to break down (losing their ability to fight off invading pathogens), in some cases, they can start unleashing their destructive properties on the body’s own tissues, resulting in a variety of allergies, as well as in autoimmune diseases such as multiple sclerosis, lupus, fibromyalgia, and rheumatoid arthritis.

Confused yet? If not, then you should be, because most of the world’s top immunologists and stress physiologists are baffled by the fact that stress increases immune-system function on the one hand, but then turns around and dismantles one of our most important protective systems on the other. One of the proposed reasons for this “Jekyll and Hyde” effect of cortisol has to do with the fact that, while a stimulated immune system is good on a short-term basis, undergoing this stimulation long-term may actually lead to autoimmune diseases (wherein the immune system attacks the body’s own tissues).

It makes good sense for cortisol to stimulate immune-system activity during stress, and when cortisol levels return to normal (after the stress is over) for overall immune-system activity to do so, too. Unfortunately, our modern high-stress lifestyles don’t allow cortisol levels to return to normal. Consequently, one of the body’s “safety valves” comes into play, whereby chronic exposure to cortisol causes the immune-system cells to break down, thus preventing autoimmune diseases, but also reducing our ability to ward off future infections and increasing our risk for many diseases.

Speaking of autoimmune diseases, it is important to make the point that glucocorticoid drugs (powerful synthetic versions of our cortisol stress hormone) are routinely used by physicians to combat autoimmune diseases. If we think of autoimmune diseases as conditions wherein an overactive immune system attacks our joints (rheumatoid arthritis) or nerve cells (multiple sclerosis) or connective tissue (lupus), then it is logical to knock down this overzealous immune system with a huge dose of cortisol (glucocorticoids). In this way, cortisol can be thought of as our “friend” by suppressing immune-system activity. However, cortisol can also be thought of as our “enemy” because of the memory problems, muscle loss, weight gain, and other side effects experienced by patients injected with high doses of glucocorticoids. Unfortunately during times of stress, these very same autoimmune diseases tend to flare up—which is confusing, because the stress-induced rise in cortisol would be expected to reduce immune-system activity and actually help control the diseases. Again, it probably comes down to timing, with short-term stress causing a temporary stimulation of immune activity and, thus, an increase in the symptoms of the autoimmune condition.

Studies in both animals and humans have noted a reduction by as much as 50% in levels of immune-system cells called natural killer cells following exposure to various forms of stress. Natural killer cells (NK cells) typically function within the immune system to identify viruses and cancer cells. In one study of breast cancer patients, the level of emotional stress caused by the initial cancer diagnosis was directly related to NK cell activity. In these women, a higher stress level predicted a reduced ability of NK cells to destroy cancer cells as well as a poorer response to interventions aimed at improving NK cell activity. From animal studies, we know that cortisol not only suppresses the number and activity of NK cells, but also promotes the synthesis of new blood vessels in tumors (a process called angiogenesis) and accelerates the growth of certain kinds of tumors. The bottom line here may be that chronic stress can accelerate the growth of cancer cells in the body as well as block the body’s ability to battle the disease.

Heightened stress levels have also been linked to adverse effects on the balance of intestinal microflora, which are known to respond to changes in both diet and stress level. These beneficial bacteria live in our intestinal tract, and while they are intimately involved with optimal gastrointestinal function, they also play a vital role in helping to support immune function. In a study of fighter pilots preparing for simulated battle (definitely a stressful event), distinct reductions were noted in the numbers of “good” bacteria (lactobacilli and bifidobacteria), along with a corresponding increase in the numbers of “bad” bacteria (E. coli, enterobacteria, and clostridia). The outcome for these pilots was, predictably, a sharp increase in their reported incidence of sore throats, headaches, colds, diarrhea, and upset stomachs.

In some stress-management clinics, the primary determinants of whether or not a person will get sick include:

-The number of major life events in the past year (divorce, death in the family, change in job or location, etc.)

-A psychological perception that daily demands exceed coping resources and/or support system

-Current emotional state

Of this short list of three “sickness determinants,” researchers have found that the overall degree of psychological stress is strongly related, in a dose-response fashion, to URTIs (upper-respiratory-tract infections) and other breakdowns in immune-system integrity (such as gastrointestinal health). This means the more stressed you are, the more likely you are to get sick.

Numerous studies in animals and humans have shown that both acute and chronic stress increases susceptibility to infectious diseases. In particular, the risk of upper-respiratory-tract infections (URTIs) is sharply increased, so that people who are under the greatest stress (or who deal with it poorly) are the ones who most often get sick. Students catch colds during exam week; accountants get sore throats in April, when they’re filing dozens of last-minute tax returns.

Swedish researchers have found chronic stress to increase the occurrence of yeast infections, a consequence likely due to the overall suppression of immune-system activity from chronic stress. Brazilian researchers have linked elevated stress levels to both depression and suppressed immune function, and have suggested that chronic stress may contribute to the development of certain forms of cancer. In a series of experiments, results show that various cellular and molecular aspects of the immune system are impaired during chronic stress and depression, yielding, for example, high levels of cortisol and inflammatory cytokines, and reduced the numbers and activity of T cells and NK cells: the specific immune-cell types responsible for immune surveillance of cancer tumors.

We have known for many years that some forms of cancer are related to increased levels of psychological stress. Researchers from the University of Wisconsin Medical School have recently shown that breast cancer patients have a flattened cortisol rhythm (resulting in an elevated 24-hour exposure to cortisol) that predicts a shorter survival time.

So, after all this discussion about the suppression of immune-system function by stress, who do you think gets sick most often? What demographic group, among all others, suffers from the highest incidence of stress-related disease?

*          Wealthy investment bankers? No.

*          Stressed-out college students? No.

*          Single mothers working two jobs and driving beat-up junkers? Yes!

The most direct example of the chronically elevated human stress response can be observed every day in the lives of a large part of the American (and worldwide) population. These are the folks who are driving a junker car (and hoping it makes it) to their second job. They are hoping the money from that second paycheck will last until the end of the month when the bills are due. They are not the people whom you see commiserating with each other about their terrible jobs on sitcoms. It is the constant unrelenting stress of making ends meet, job instability, sleep deprivation, poor diet, lack of outlets for stress, and overall lack of control that combine to increase the risk of disease by a factor of five to ten!

Unfortunately, none of the information or recommendations that follow in The Immune Miracle will alleviate the actual stressors encountered by the “working poor” or by the “working middle class” (wherever you choose to draw the economic line)—but much of what follows can be used to reduce the damage wreaked by stress on our immune systems. Further, by countering the stress-induced immune system dysfunction, we can protect our health and improve our daily feelings of vigor and well-being.

The Immune Miracle – Chapter 2 – Immune System Overview

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

 

Chapter 2

Immune System Overview

We typically think of the immune system in two parts – the “innate” and the “acquired” (adaptive) immune systems. After the “barriers” to pathogens, such as our skin and the mucous membranes surrounding our airways and intestinal linings, the innate immune system is our primary, fast-acting line of defense against invading bacteria and viruses, environmental toxins, and even against damaged cells, including cancer cells. The adaptive immune system is what most people think of when they consider the immune system, because it’s the part of our immune system that “learns” to protect us from specific diseases such as measles and chicken pox. Our adaptive immune system enables us to develop these diseases just once (or be vaccinated against them), because the adaptive system has learned to recognize and destroy that particular virus if we ever encounter it again. The specificity of the adaptive immune system is amazing and is crucial for our survival; yet, it suffers from being a delayed response (several days or weeks for optimal development) and requires action from the innate immune system to be initiated.

As mentioned in the Introduction, our immune systems are comprised of a complex network of multiple parts communicating and interacting with each other. In addition to the skin and mucous membranes that “block” infections, we also have acidic and enzymatic secretions in the stomach and in our the tear ducts of our eyes that can destroy viruses and bacteria before they gain entry into the body. The innate immune system also encompasses a group of serum proteins called the “complement” system that can directly kill or dissolve pathogens or “tag” them for destruction by certain immune cells (called macrophages, they can engulf and destroy pathogens by a process called phagocytosis).

Cells of the innate immune system include Macrophages, Neutrophils, and Natural Killer (NK) cells. Macrophages perform day-to-day functions as “garbage collectors” and “handy men,” cleaning up damaged cells and cellular debris; its not glamorous work, but it’s vital to our well-being and optimal function. However, as soon as we encounter a bacteria, our macrophages quickly turn from garbage-men to Superman and leap into action to fight the invaders.

As they fight bacteria, macrophages send out hormone-like messengers called cytokines that alert other immune system cells such as neutrophils to join the fight. Within a very short period of time, cytokine signaling induces a full-blown “inflammatory” reaction that “walls off” or “quarantines” the infectious invaders and sends out the alert to the rest of the immune system – and it’s the innate immune system that’s responsible for the initial reaction and the ultimate coordination of the different immune system cells.

Primed Versus Stimulated

You can see how important it is to keep your innate immune system properly “primed” for rapid action, but we also want that activity to be “smart” – so we attack only the “bad guys” (infectious pathogens) and not the “good guys” (our own healthy tissues). One way research has shown effective to actively prime our innate immune system for rapid and intelligent activity is through exposure to yeast.

The health benefits of yeast have been known for many years, but it was only in the 1960’s that scientists were able to identify the natural compounds in the cell walls of yeast, called “whole-gluco-polysaccharides” (WGP) as the components responsible for improved immune system function. When we eat yeast (as in bread or beer), the WGP particles are actively absorbed and transported from the small intestine to the immune system by macrophage cells. WGPs are absorbed through a particular region of the small intestine known as Peyer’s patches, an area which immunologists have shown to be comprised of a specialized concentration of epithelial cells that act to alert the body when a pathogen is present in the system.

After transport and signaling via the Peyer’s patches, the WGPs are engulfed (phagocytized) by macrophages and broken down into active fragments that interact with specialized receptors (called “CR3” receptors) on neutrophils and NK cells – causing these cells to become “primed” and ready for action. This priming effect is very different from typical approaches to “stimulating” immune system activity, because while a “stimulated” cell is immediately turned on and starts looking for something to attack, a “primed” cell is only in “standby” mode: it does not turn on its “attack” mode until it encounters a true pathogen. The priming effect is possible because the CR3 receptor has two binding sites – so when WGP occupies one site, the neutrophil “gets ready” – and when a virus occupies the other site, the neutrophil is immediately stimulated to destroy it.

The main source of WGPs in the human diet is from brewer’s or baker’s yeast (Saccharomyces cerevisiae), but purified yeast extracts containing specialized WGP particles are also available as dietary supplements. In supplements, WGP particles may be generically referred to as “beta-glucan” (see Chapter 6). However, there can be important molecular differences between different types of WGP particles – and even the slightest structural difference can affect bioactivity at a cellular level. For example, one form of WGP (a type with a 1-3/1-6 branching structure) has been shown to increase levels of two cytokines in the blood (INF-y and TNF-a), both of which play an important role in regulating the body’s immune response. But, an equally important finding was that this type of WGP does not cause any increase in another cytokine (IL-1), which can cause the symptoms of fever, chills, and muscle aches that are associated with active infections and often with other immune “stimulating” supplements. Using WGPs as daily dietary supplements (250-500mg/day) can be an effective and safe approach to actively nourishing and priming your immune system for optimal health and well-being. In fact, results from a 1999 study published in the American Journal of Clinical Nutrition showed that even consuming huge doses of WGP (15 grams per day or 30-60 times the recommended daily dosage) resulted in no adverse effects.

Obesity Infection?

It turns out that comparing the “spread” of obesity to an “epidemic” like the flu may not be very far off the mark. There is a growing body of scientific evidence that obesity might actually be caused by an infectious virus known as Adenovirus 36 (AD36). Researchers at several universities have shown that AD36 infection is related to a higher rate of fat storage in adipocytes (fat cells) – an effect thought to be due to the ability of the AD36 virus to “turn on” certain genes involved in fat production and storage. In laboratory studies of isolated fat cells, the AD36 virus has been shown to infect immature fat cells (called pre-adipocytes) and stimulate them to develop faster than normal as well as grow in both number and size.

It’s interesting that rates of AD36 infection in obese individuals are more than double those of the non-obese. In a recent study of AD36 infection among obese children (ages 8-18), researchers from the San Diego School of Medicine and the University of California found that the majority (78%) of children who tested positive for AD36 infection were obese – weighing an average of 35-50 pounds more than non-infected children.

AD36 is currently the only virus linked directly to human obesity; and, it raises the tantalizing idea that improving our immune system function may help protect us from the fat-storage effects of AD36 – and possibly, even help those who are already infected.

Inflammation and Immunity

The word “inflammation” is derived from the Latin “inflammare”—meaning to “set on fire”—because an injury or infection is typically red, warm, and painful. Think of pain and inflammation as different sides of the same coin: they coincide with each other, but are driven by different—yet related—biochemical factors.

Pain and inflammation are normal body processes. Without them, you would literally not be able to survive for very long. Pain is a signal to your body that damage is occurring, and you need to stop doing whatever is causing that damage. Inflammation is a process controlled by the immune system that protects your body from invading bacteria and viruses, but this process also serves to regulate heart function, blood flow, and many vital functions. Maintaining a normal balance of pain signals and inflammation is critical to good health and vigor; it is the link between having a properly primed immune system (high vigor, abundant energy, and a good mood) or a poorly functioning immune system (a daily struggle with pain, fatigue, and depression).

When this balance becomes disrupted, you experience more inflammation and increased pain along with less flexibility and reduced mobility. When you have too much inflammation, this process—which is supposed to be protecting you—actually causes more and more damage. For example, an overactive inflammatory response is known to stimulate bone breakdown (leading to osteoporosis), interfere with cartilage repair (leading to a worsening of arthritis), and accelerate muscle breakdown (leading to flare-ups of fibromyalgia). Inflammation is also involved in emotional balance and brain function. So, when your body experiences too much inflammation, you simply don’t feel happy. Instead you feel mentally exhausted and burned out—obviously, the opposite of vigor.

Your doctor may also give your unbalanced inflammation another kind of label—one that ends in “-itis.” In medical terminology, “-itis” is used to denote inflammation. Therefore, you may have arthritis (inflammation of the joint—“arthros” is Latin for joint), tendonitis (inflammation of the tendon), or fasciitis (inflammation of the fascia—the tough layer of connective tissue over muscles, tendons, and ligaments that can become inflamed following excessive exercise or with lower-back pain and fibromyalgia).

Normal Inflammation vs. Chronic Inflammation

As mentioned earlier, the normal process of inflammation helps dismantle and recycle older tissues that have become damaged or worn out or that simply need repair (remember those macrophage garbage-men). This process of normal and balanced inflammation is called “turnover,” and it occurs when older tissue is replaced with newer tissue. Before the age of thirty or so, this normal turnover process is perfectly balanced—for every bit of tissue that is damaged and removed, another similar (or greater) bit is put in its place. This means that, under ordinary circumstances, you’re always making your tissue stronger and more resilient. After about age thirty, however, the immune system can lose some of its precision, and the turnover process becomes somewhat less efficient year after year. This causes a very slight loss of healthy tissue—you continue to break down and to remove some tissue, but the amount of healthy tissue added back to replace it is just a bit less than it should be. As you age, the turnover process becomes less and less efficient, and your body’s ability to heal itself from injury and protect itself from infection is reduced. This imbalance in tissue turnover and the “normal inflammation” process is the primary cause of the loss of flexibility, vigor, and the various “-itis” diseases that people tend to encounter as they get older.

With aging, these normal repair mechanisms start to dwindle; and, ironically, the very inflammatory process that has been helping “turn over” older tissue into healthy new tissue can completely turn on you. That leads to problems with pain, mobility, and flexibility. The same process of inflammation that naturally governs your body’s repair and protection starts to accelerate tissue breakdown and impede that repair. The end result, as you may have already started to experience, is that your tissues literally begin to fall apart. Cartilage degrades; muscles lose tone; ligaments and tendons creak; bones become brittle; energy and mood falter, and vigor is sapped.

Let’s keep in mind that not all inflammation is bad. As you’ve just learned, inflammation is part of the normal healing and turnover process for any tissue. But, when you experience too much inflammation or “chronic” inflammation, things go awry. With chronic inflammation, healing is suppressed, and tissue destruction is accelerated. Your body simply cannot heal itself or stop the damage when inflammation gets out of control. To illustrate this point, think about the ocean crashing against a protective seawall. The seawall represents your tissues, and the ocean is your inflammatory process. Over time, that wall will become weakened and broken by the crashing waves; it will need to be repaired to return to optimal functioning. If the pace of repair fails to keep up with the pace of destruction, then the seawall fails, and the ocean comes rushing in (leading to tissue destruction and dysfunction). You need to maintain the integrity of the seawall (your tissue) by keeping up with repair and maintenance—but, you can’t do that if the ocean is continually crashing down on you.

A plethora of scientific and medical evidence demonstrates how to use diet, exercise, and supplementation to “calm” the ocean (reduce damage caused by excessive inflammation) and to accelerate tissue repair (keep that seawall intact). It is all a question of balance. You want to maintain a normal level of inflammation so you can then maintain a normal pace of tissue turnover and, thus, retain healthy tissue, flexibility, and mobility. As soon as you get too much inflammation—that is, chronic inflammation—even by a small amount, you see a bit more tissue deterioration, leading to a little more inflammation and still more tissue breakdown. Once this vicious cycle of inflammation/damage has begun, it can be very difficult to stop—unless you have a comprehensive plan to control inflammation via multiple health practices.

Chronic Inflammation—The World on Fire

Like the seawall metaphor above, it may help you to think of chronic inflammation as you would a fire in an apartment building. Let’s say you live in a twenty-story apartment building, which represents your body. Then, a fire (inflammation) breaks out on the fifteenth floor, causing destruction (tissue damage) to that entire floor. But your penthouse apartment on the twentieth floor is fine. To put out the fire, you call in the firefighters (immune cells), which may cause a bit more damage by tearing down some walls and spraying water (cytokines, the signaling substance secreted by immune system cells)—all in an effort to solve the bigger problem of putting out the fire. Let’s now say that the fifteenth floor is a complete loss, while other floors suffer some repairable damage (water damage on the fourteenth floor, smoke damage on the sixteenth floor). The repair process begins on all three floors, with carpenters, painters, and other “builders” brought in to repair the damage. On floors fourteen and sixteen, where the damage is less severe, the repair process might be complete within a few weeks; but on the fifteenth floor, where the fire was concentrated and the damage was most severe, the repair process may take a year.

Your body also has an entire team of “builder” cells in each and every tissue. In cartilage, these “builders” are called chondrocytes; in bone, they are called osteoblasts; in muscles, they are myocytes; in skin and some other tissues, they are fibroblasts—the list goes on and on. In your own tissues, you can have the equivalent of a raging fire and firefighting (tissue damage and inflammation). But if you’re not able to shut off this process—that is, if your level of inflammation is thrown off by something—your body is then in a continual state of destruction and pain. You’ll never be able to get to the rebuilding and repair stages unless you can shut off this process of chronic inflammation.

How Normal Inflammation Becomes Chronic

When a tissue is damaged—whether from infection, trauma, or unbalanced turnover—it releases signaling chemicals called “cytokines.” These cytokines are like flare guns, sending up a call for help that signals surrounding cells to jump into action to stop (wall off) and repair the damage. The cytokines also call immune-system cells (white blood cells) into the area to help clean up the damaged tissue. You have no doubt experienced the blood rush that leads to the recognizable redness, warmth, and swelling common to many injuries. As the white blood cells rush in to the damaged area, they release more and more of their own inflammatory chemicals. This blast of inflammation is intended to cause even more tissue destruction as a way to either kill bacteria and viruses or to take away damaged tissue and set the stage for repair efforts to begin. As you can imagine, this part of the inflammatory process is supposed to be short-term. If it were to continue without shutting down, you’d simply destroy your own tissue without ever rebuilding healthy tissue in its place. Unfortunately, this “never-shut-down” scenario precisely describes the chronic inflammation and constant state of tissue destruction with which millions of Americans live their lives every day.

A number of mechanisms are in place to shut down the process of inflammation, including the naturally short half-life of cytokines and other inflammatory molecules, and the production of anti-inflammatory cytokines (with such names as TGF-beta and IL-10). Unfortunately, immune-system cells can remain in a state of chronic inflammation if the “cell-damage” signals keep coming from free-radical damage (which can be controlled via antioxidant nutrients found in brightly colored fruits & vegetables), from cortisol-induced tissue breakdown (resulting from chronic stress), or if signals to “shut down” the inflammatory process are not “heard” by target cells (as in the case of cells damaged by problems with blood-sugar levels).

Unfortunately, chronic inflammation is not confined to the tissue in which it starts. Cytokines—such as IL-6, IL-8, and TNF-alpha—are able to leave the original site of inflammation. They can then travel in the blood to spread inflammatory signals through the blood vessels and into every tissue in the body (leading to metabolic diseases, such as obesity, diabetes, and depression, and to structural/damage diseases, such as Alzheimer’s, Parkinson’s, and arthritis). Because most cytokine molecules are produced by immune-system cells (specifically by macrophages, neutrophils, and NK cells of the innate immune system), numerous drug companies attempt to control chronic inflammation by suppressing immune function. The problem, of course, is that wholesale suppression of immune function also limits your body’s ability to protect you from actual pathogens—so you’re “protected” from chronic inflammation, but become more susceptible to infections and certain cancers. Not a great trade-off!

Chronic Inflammation and Chronic Diseases

Chronic inflammation is not just a problem that affects the way you feel on a daily basis or the level of vigor you experience. It also contributes to the development of serious health conditions, including four that we will briefly discuss in this section: heart disease, cancer, obesity, and diabetes.

Heart Disease

Researchers may know the most about the adverse effects of chronic inflammation when it comes to heart disease. Until about ten years ago, most cardiologists and other health experts believed that heart disease was a simple “plumbing” problem, with too much cholesterol being the culprit that clogged up blood vessels and led to heart attacks. Unfortunately, the cause of heart attacks was found to be a little more complicated: population studies showed that at least half of all heart attacks occurred in people with perfectly normal cholesterol levels. What scientists know now is that oxidative damage (by free radicals) is what allows cholesterol to become “sticky” in the first place and start plugging blood-vessel linings with plaque deposits. Chronic inflammation, therefore, seems to be the “trigger” what causes those deposits to rupture and create a blockage in the heart, leading to a heart attack. The degree of chronic inflammation throughout the body can be measured by blood levels of a protein called “C-Reactive Protein” (CRP). CRP is produced in the liver, with levels rising in direct proportion to inflammatory signals in the body. During times of active infection (acute inflammation), CRP levels may rise by a factor of one thousand to fifty thousand in response to the increased production of cytokines, such as IL-6, from macrophages. A CRP value of 3.0 mg/L is associated with a tripling of heart-attack risk, while people with very low CRP levels (below 0.5 mg/L) rarely have any sign of inflammatory heart disease. You may have to push for it, but you can have your CRP levels tested the next time you’re at the doctor’s office.

Cancer

For more than one hundred years, researchers have known that cancerous tumors tend to arise from and cluster at sites of chronic inflammation. Stated another way, sites of chronic inflammation seem to attract and promote the growth of cancer. Part of this effect might have to do with the fact that sites with more inflammation will also have more oxidative free-radical damage; so, DNA damage and subsequent “mistakes” during repair may result in more mutations and a higher chance for cancer development. Another factor may be that a higher concentration of inflammatory cytokines attracts a greater number of immune cells, which “think” they’re being called to the site of an infection and, thus, create even more damage as they try to “kill” a nonexistent pathogen. So here is evidence of the ultimate conundrum: your immune cells, which normally protect you against cancer, may actually be co-opted by excessive inflammatory signals into actually stimulating further cancer growth. If there were ever a reason to be interested in maintaining a properly primed immune system, it is for the reduced risk of cancer it may confer.

Obesity and Diabetes

Earlier in this chapter, I wrote about the growing body of research suggesting that a viral infection (AD36) may be linked to increased rates of obesity. But, some researchers are not convinced whether the infection comes first (causing increased fat storage and obesity) or the obesity comes first (leading to an inflammatory state that interferes with normal immune function and allows AD36 infection).

Obesity is defined as an excess of adipose (fat) tissue, with adipose tissue producing a range of inflammatory cytokines (adipokines, adiponectin, leptin, resistin, TNF-alpha, IL-6, IL-1, and many others). Adiponectin and leptin are the most abundant adipokines and are considered key signaling compounds in regulating inflammation within fat cells and throughout the body. Adiponectin levels are markedly decreased in obesity, diabetes, and heart disease and are thought to contribute direct anti-inflammatory effects. Leptin, on the other hand, is considered a highly pro-inflammatory and pro-atherogenic cytokine that is associated with elevated body fat levels and reduced insulin sensitivity. The ratio between adiponectin and leptin has been proposed by some researchers as a useful index of heart-disease risk in patients with obesity and diabetes. Leptin acts directly on the hypothalamus region of the brain to regulate food intake and energy expenditure. Leptin is a general “satiety” signal that tells the brain that “enough” fat is stored. The amount of leptin produced is proportional to the amount of body fat stored; so, when you lose body fat, your leptin levels fall and your hunger increases to drive you to eat in order to “replace” the lost fat. On the other hand, adiponectin increases fat oxidation and improves the activity of insulin to regulate blood-sugar levels.

Through the action of cytokines/adipokines, fat tissue can be directly influenced by the overall inflammatory state of the body; but, through the action of cytokines/adipokines on the brain, fat tissue can also influence inflammation throughout the entire body. Aside from the adipokine signaling mentioned above, another important source of chronic inflammation associated with abdominal obesity is the constant activation of the innate immune system. As they grow, changes in cell-surface proteins on adipose tissue can allow swollen abdominal fat cells to resemble bacterial cells or tumor cells in certain ways. This effect attracts cells from the innate immune system (macrophages, neutrophils, and NK cells), which attempt to destroy the “tumor” (your own fat cells) with their normal bursts of free radicals and cytokines. Unfortunately, rather than killing off your fat (if only it were that simple!), this immune system attack merely damages your fat cells; this, in turn, sets off the expected normal cycle of injury/inflammation/repair that any of your body cells would undergo. The really bad news is that the end result is yet a higher level of inflammation and oxidation—and a growth of fat stores through a variety of metabolic signals.

Control Inflammation—Naturally—For Superior Immune Function and More Vigor

The immune system responds to and creates oxidative “free radicals” and responds to and creates inflammatory cytokines. “Normal” inflammation exists to protect us from invading pathogens (viruses, bacteria, and even uncontrolled cell growth that could lead to cancerous tumors). Sometimes, however, the walling-off and destroying process of the immune system’s inflammatory response doesn’t shut off the way it is supposed to: immune-system cells, such as macrophages (which fight bacteria), neutrophils (which fight viruses), and natural killer cells (which fight tumors), respond to free radicals as if they were toxins. A small amount of free radical signaling is a “good thing” for immune cells, keeping them vigilant to defend us against “real” pathogens. But when free radical exposure becomes excessive, immune cells release a wide array of pro-inflammatory cytokines, such as interleukins (IL-1, IL-6, TNF-alpha), to “wall off” tissues from further free radical damage. And that can lead to chronic inflammation as well as a cascade of diseases, including heart disease, obesity, diabetes, Alzheimer’s, and certain cancers.

Unfortunately, the Western lifestyle is a perfect recipe for increasing chronic inflammation, with its high intake of sugar, refined carbohydrates, and saturated fats. Such a diet, combined with low levels of fiber, infrequent exercise, and sleep deprivation, make it more likely that inflammation becomes too high—and stays that way.

Thousands of years ago, ancient herbal practitioners were prescribing all-natural foods and herbal extracts for controlling pain and inflammation. What these traditional healers did not realize at the time, but what we now know thanks to advances in nutritional biochemistry, is that these natural anti-inflammatory nutrients were effective at controlling inflammation and improving immune system function in many ways simultaneously. This balanced approach is associated not only with a greater degree of overall effectiveness, but also with a restoration of normal tissue function and fewer side effects. As is so often the case, however, the drug industry has tried to synthetically copy the extraordinary healing properties and powers of natural medicine—only to create more suffering, injury, and even death. Fortunately, those herbs and natural products cannot be “owned” by the drug companies, thus keeping them widely available to anyone who wants to enjoy the safe and effective benefits of controlling pain and inflammation naturally.

The obvious dilemma when it comes to selecting a natural option for inflammatory balance and pain relief is that you want something that is safe, natural, fast-acting, and long-lasting. It is a tall order to get all four “wants” in a single item—but a growing number of products offer a suitable range of options (mostly by combining the most effective ingredients into a single multi-faceted product solution).

Now that I’ve presented the idea that herbs and natural products can combat inflammation, pain, and immune dysfunction, you may be wondering what, exactly, you need to ingest in order to address these health issues. Let me stop you right there for a moment. To get the real benefits from natural products and traditional healing wisdom, you have to break out of the mind-set that tells you taking one pill or that one drug will cure your ills with a “quick fix.” This mind-set is pervasive in modern society, and countless ads and commercials constantly reinforce it. So, before considering specific natural strategies for controlling inflammation, the first thing you need to do is to be willing to change the mind-set that says you can take a pill and forget the problem. You may also need to change your lifestyle and recognize the importance of being an active participant in developing your health and wellness, instead of a passive recipient of a prescription from a physician. Many of you reading this are undoubtedly aware of the benefits of changing your mind-set and lifestyle in order to embrace a view of health that’s more comprehensive and multi-faceted than the typical Western medical approach. Nevertheless, it bears repeating, because even people who appreciate traditional medicine can fall back into thinking that one “superfood” or one “special” herb will solve a health problem as quickly and efficiently as a pill from the pharmacist.

Having said that, here are a few specific, natural options that you can pursue to control inflammation and get your immune system function back on an even keel:

Exercise—Numerous studies confirm that moderate exercise reduces inflammation as well as the production of C-reactive protein, which plays a role in heart disease. A study from researchers at the Emory University School of Medicine in Atlanta that was published in the Archives of Internal Medicine (2002) found that the more frequently you exercise, the lower your overall level of inflammation, and the more robust your immune response. The study looked at nearly four thousand U.S. adults ages forty and older and found that exercising approximately five times per week was associated with almost a 40% reduction in overall inflammation.

Sleep—Sleep is crucial to your health and vigor in countless ways, including helping to corral chronic inflammation. In a study published in the Archives of Internal Medicine (2006), researchers from the UCLA School of Medicine found that even a single night of disrupted sleep increases levels of inflammation throughout the body by two to three times compared to a normal night’s sleep.

Herbs and Supplements—As you’ll read in greater detail in Chapter 5, there are a great many safe and effective dietary supplements for reducing inflammation and bolstering immune function naturally. For instance, ginger, turmeric, boswellia, papain, and bromelain are all derived from nature and have long been used in traditional Indian medicine to treat arthritis and other inflammatory conditions, as well as to ward off infections and heal injuries.

To sum up: The human immune system is an exquisite network of active cells, cytokines, and multiple interacting defenses. The walling-off aspect of the inflammatory process is an ideal response for keeping viruses or bacteria from moving into other parts of your body. However, free radical–generated inflammation encourages immune cells to fight “yourself” in a vicious cycle of oxidation/inflammation, which ends up creating more problems and eventually leads to a lower state of vigor. Coming chapters discuss a variety of natural options for priming optimal immune system activity, controlling inflammation, and improving vigor and overall well-being.

The Immune Miracle – Chapter 1 – Immunity and Disease

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

 

Chapter 1

Immunity and Disease

First – let’s make sure we’re all on the same page with a proper definition of the “Immune System.” An immune system is a network of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism’s own healthy cells and tissues in order to function properly.

The key part of that definition is the word “network,” because a properly-functioning immune system encompasses “barriers” such as skin and membranes that block the entry of pathogens into our bodies, as well as a vast array of cells, enzymes, hormones, and other aspects of biochemistry that serve as signals and messengers to identify and destroy invaders. If any part of this complex and coordinated network breaks down, we’re more susceptible to infections, more likely to catch a cold, and even more likely to develop cancer.

The last time we experienced flu pandemic occurred more than forty years ago (1968) – but many experts feel that we’re very close to experiencing an even worse pandemic in the very near future. Whether its the risk of a swine flu epidemic (H1N1) or an avian (bird) flu epidemic (H5N1), our risk for a global flu pandemic has risen steadily over the years for many reasons – including the ease of international travel, the emergence of drug-resistant and rapidly mutating virus strains, and the presence of greater numbers of environmental toxins and stressors in today’s world.

Every year in the United States, influenza results in more than 200,000 hospitalizations and nearly 40,000 deaths (representing more than $10 billion in medical costs). Since nobody wants to get sick – never mind not wanting to be hospitalized or dead – the entire category of “immune support” products is enjoying a significant level of sales growth. Americans spend more than $300 million on non-prescription cold remedies every year. BUT, most of these products tend to base their claims of “immune support” on levels of nutrients such as vitamins A & C and minerals such as zinc & selenium. While these nutrients are certainly needed at proper levels for normal immune system function, they are unlikely to do much of anything towards truly bolstering the immune system when it’s challenged by a pathogen such as influenza or other viruses.

Let’s look at some of the more ridiculous products claiming immune “boosting” capabilities lately. There is the popular Airborne dietary supplement (“formulated by a teacher!”) that paid $30 million to settle a false claims lawsuit, though it remains on the market with similar “boost immune function” claims. Another well-known product Crystal Light drink mix (owned by Kraft) claimed it would help “maintain a healthy immune system” based on a dusting of vitamins A, C, & E, and Green Giant Immunity Boost (a blend of broccoli, carrots, and peppers from General Mills). There are dozens of other silly examples – but how is a consumer to know which (if any) of these foods or dietary supplements really holds any promise for truly helping them to maintain immune function when they need it the most (such as when exposed to a virus, when under stress, or when our defenses are depleted)?

Immunity and Vigor

It’s pretty logical to understand that if your immune system is suppressed in some way, it’s less likely to protect you from pathogens, and you’re more likely to get sick. What many people do NOT understand is that a properly-functioning immune system is also associated with a general feeling of well-being; conversely, a suppressed immune system is one of the primary reasons for feeling fatigued and depressed. Chapter 3 covers the relationship between chronic stress, cortisol (a stress hormone), immune suppression, and low vigor in greater detail.

Vigor is a term from psychology research that measures a combination of physical energy, mental acuity, and emotional well-being (vigor is the opposite of “burnout” or physical and mental exhaustion). When your vigor is low, you not only lack energy and may even be depressed, you also lack the necessary motivation to get up and accomplish the things that you’d like to do. When your immune system is suppressed, your vigor is low — BUT, when you bring your immune system back to optimal levels of functioning, your vigor improves… and you feel great again. This “priming” of immune system activity is covered in detail in Chapter 4.

There are basically three “tiers” to consider when it comes to effective immune system support: Protect – Prime – Promote.

Protect

This first tier is where you do whatever you can to protect yourself from exposure to pathogens. Steps like eating a healthy diet, supplementing with a balanced multivitamin, consuming enough antioxidants, consuming yogurt as a source of pre- and pro-biotics (beneficial bacteria), frequent hand-washing, getting enough sleep, and avoiding or reducing stress all come into play. For example, overexposure to stressful events or sleep loss increases cortisol (the stress hormone) in our bodies; this will dramatically suppress immune system function – as will underexposure to dietary antioxidants (A, C, E, carotenoids, flavonoids, etc).

Prime

It’s important to eat a healthy diet, rich in brightly colored fruits & vegetables and yogurt for its immune-active pre- and pro-biotics (beneficial bacteria). Yet, we also must consider bolstering (or “priming,” but NOT “stimulating”) immune vigilance. Especially during periods of elevated stress (environmental, emotional, physical), the immune system needs to maintain its primary function of protecting the body from harmful invaders. Numerous human research trials of several “immune support” types of dietary supplements have shown that “priming” key immune system cells (macrophages, neutrophils, and natural killer cells), helps them to quickly identify, ward off, and defeat foreign challenges. Research studies show that people with properly primed immune systems have fewer cold/flu symptoms and better indices of well-being, vigor, energy, and mood. The more stress you’re under, the more you can expect your immune system also to be “stressed” (and suppressed), the more likely you are to benefit from a daily regimen of immune system priming.

Promote

This is your last resort – after you’ve tried the first two tiers and you’re down for the count with an established infection (i.e. you have a cold or the flu). The best approach to temporarily promoting or stimulating immune system activity above normal levels is to start consuming higher levels of vitamin C at the first sign of a sore throat or related cold symptom. You can drink more orange juice, eat lots of strawberries, or get an inexpensive chewable vitamin C tablet — and shoot for an intake of 500mg every 3-4 hours (up to 3,000mg/day for 4-7 days). This simple, safe, and inexpensive approach is a good way to help your immune system get a jump on the infection; it might reduce your symptoms by a couple of days.

Avoid Antibiotics and Immune Stimulants

If you can help it – DO NOT assume that you need an antibiotic drug to treat your symptoms (antibiotics only work against bacterial infections, NOT against viral infections like colds or the flu). As many as HALF of the 100 million antibiotic prescriptions written each year are given to people who have viral upper respiratory infections. This is a leading cause for the development of antibiotic-resistant organisms like E. Coli H157 and MRSA (methicillin-resistant Staphylococcus aureus)! Also consider that side effects of antibiotics (such as allergic reactions) result in more than 140,000 emergency room visits annually. Think of antibiotics this way: you probably do not need one; they only work on bacterial infections, and they are highly likely to make you sick (or at least give you diarrhea due to destruction of beneficial gut bacteria). Skip them unless you’re on your deathbed.

The vast majority of the herbal immune “boosters” on the market are plant extracts containing a combination of polysaccharides that “irritate” the immune system into action. This is a clumsy approach that may certainly “ramp up” immune activity – but it’s is really an old-fashioned shotgun approach that makes little sense when we can scientifically prime our immune activity when we need it (vs. when we don’t want it). Supplements such as Arabinogalactan (Larch tree extract), Echinacea, Ginseng, and some medicinal mushroom extracts (Reishi, Maitake, AHCC, etc.) all show evidence for reducing the duration and severity of URTIs (upper respiratory tract infections). However, direct-stimulation of immune activity is an approach that you only want to employ infrequently, because too-frequent stimulation of immune activity is likely to lead to allergies (ragweed, seasonal), autoimmune diseases such as celiac disease, thyroiditis, lupus, rheumatoid arthritis, and multiple sclerosis, and other problems associated with over-activity of the immune system (such as chronic inflammatory conditions).

Summary

The immune system is one of the most complex body networks – but, maintaining its proper balance and optimal function doesn’t have to be complicated. Protect your immune function with a healthy diet (antioxidants from fruits/veggies and probiotics from yogurt). Maintain balanced immune function, especially during times of stress with proper Priming, and Promote immune activity above normal only as a last resort (and then only for a short period of time).

The chapters that follow in The Immune Miracle will take you step-by-step toward an understanding of how the immune system works, how stress interferes with immune function and leads to low vigor, and how a properly primed immune system can protect you from disease while helping you to feel better than you’ve ever felt before.

The Immune Miracle – Introduction

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

 

Introduction

Every year, near “back to school” time, people start thinking about their immune systems. Right around that same time, I also get bombarded with questions about “stimulating” or “maintaining” immune system health. Maybe it’s because when kids go back to school, they’re exposed to germs from the other kids and they tend to get sick more often. It might also have something to do with the media reports of swine flu or bird flu that tend to air every year in the Fall. And it might just be because we’re heading into the beginning of the cold/flu season, which can run from early October to as late as April.

The sudden interest every year in “boosting” our immune system function in order to ward off or overcome a cold or the flu always makes me shake my head in dismay. Why? Because keeping our immune system strong should be something that we think about EVERY day of the year – not just when we have a “problem” such as an active cold, flu, or other infection. Just as we maintain optimal health by thinking about our daily nutrition, our daily exercise, or our daily amount of sleep, we should think about nourishing our immune systems every single day. By keeping our immune system properly “primed” for activity, we not only improve its ability to fight off viruses, bacteria, and even cancer – but we also help ourselves feel better, enjoy higher levels of energy, better mood, and improved vigor (mental/physical well-being).

Chapter 1 provides a brief discussion about immunity and disease– and what it means to “prime” versus “stimulate” our immune system function so we can optimize day-to-day immune protection. The Chapters that follow will delve into greater detail about how the immune system functions (Chapter 2), how stress can suppress immune function (Chapter 3), why priming your immune system is important for optimal functioning (Chapter 4), how to eat and supplement your diet for proper immune system nourishment (Chapter 5), and how a natural yeast extract may be the future of immune system support (Chapter 6).

The Immune Miracle

Reminder of the video class that I did recently on ways to strengthen your immune system – posted HERE on YouTube.

With all the cornea virus news, I thought it might be a good idea to repost the text of my 2012 book about supporting immune strength – The Immune Miracle.

The paperback is available for $14.95 from Amazon HERE – it’s a quick 80-page read.

I hope everyone finds this information to be informative and helpful during this crazy time!

I will post the text of the book chapter-by-chapter – here is what is covered in each post…

 

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

Table of Contents

Introduction

Chapter 1 – Immunity and Disease

Chapter 2 – Immune System Overview

Chapter 3 – Stress and Your Immune System

Chapter 4 – Priming Your Immune System

Chapter 5 – Eating for Immunity

Chapter 6 – Priming: The Next Frontier of Immune Support

References

Why Bill Gates is Investing in the Microbiome

Drugs From Bugs: Why Gates, Zuck And Benioff Think The Next Blockbusters Will Come From Inside Your Gut

This was a terrific story in the March 31, 2020 issue of Forbes Magazine – also appearing online on Feb 7, 2020.

As you’ll see, this article focuses primarily on how numerous biotech and Pharma companies are exploiting the microbiome to develop synthetic drugs. Not necessarily a “bad” thing – but what if you could naturally modulate your microbiome environment with personalized nutrition regimens and target dietary supplements?

Our group has already shown how targeted nutrition interventions (e.g. probiotics, prebiotics, etc) can improve microbiome balance (American College of Nutrition 2017); may enhance post-exercise recovery and sports performance (American College of Sport Medicine 2018); reduce stress and enhance mood (Functional Foods for Health & Disease Journal 2019); and optimize metabolism for glucose/weight control (Functional Foods for Health & Disease Journal 2020).

Read the original Forbes article here = https://www.forbes.com/sites/susanadams/2020/02/07/drugs-from-bugs-why-gates-zuck-and-benioff-think-the-next-blockbusters-will-come-from-inside-your-gut/ and see my highlighted version and notes below…

Sharp pains shot through the patient’s stomach, and he had constant diarrhea. Seven rounds of antibiotics over 18 months had only made him feel worse. A previously healthy man in his 20s who wishes to remain anonymous, he had contracted a recurring case of Clostridium difficile, or C. diff, after having his gallbladder removed in 2012. Hospital patients are prone to C. diff since antibiotic treatment for other maladies decimates the infection-fighting capacity of what scientists call the gut microbiome, the trillions of cells that move through the human digestive system. “It didn’t just affect my gut,” he says. “I was exhausted all the time. I had really bad brain fog. I couldn’t concentrate.” Doctalbott Note = the microbiome has been linked to effects on both physical health and mental wellness.

Desperate, he researched possible therapies and discovered articles about fecal transplants wiping out the infection. But his gastroenterologist refused to perform the procedure. So he took matters into his own hands. He asked his roommate to supply a stool sample, bought an enema kit from CVS, pulsed the mixture in a blender, strained it through a coffee filter and pumped it into his gut. As though a wizard had cast a spell, he made a full recovery within days. Doctalbott Note = having seen the benefits of microbiome optimization firsthand in thousands of people, it often seems like “magic” because of the widespread health benefits that emerge.

Welcome to the most promising new frontier in medicine: poop. By focusing on what’s coming out of patients’ rear ends, a growing body of scientific research over the last 15 years has highlighted the crucial role the microbiome plays in human health. That new understanding could lead to breakthrough treatments for a huge range of illnesses, from obvious ones like digestive ailments and food allergies to surprising ones like cancer and autism. A microbiome-derived drug is already in the works to prevent childhood asthma. Doctalbott Note = some of the most promising microbiome interventions involve “mental wellness” benefits for depression, anxiety, stress, and other effects that you can FEEL relatively quickly.

“It’s only in the past 15 years that we’ve come to understand the incredible diversity of the microbiome. It’s almost like a rainforest inside our bodies. There are 100 times more bacterial genes than human genes,” says Smith

Put crudely, the idea is to use gut bugs as drugs. Doctalbott Note = but why not utilize this “internal pharmacy” to naturally produce our own “drugs” on-demand when we need them? More than 50,000 scientific papers in the last five years have explored the microbiome’s effects. Various kinds of gut bacteria appear to stimulate or suppress immune responses in the body, while others seem to fight off disease-causing microbes. A groundswell of cutting-edge research has the potential to deliver a burst of new therapies that will vastly reduce human suffering—and generate huge paydays for the field’s pioneers.

When scientists transferred gut microbiome cells from obese mice into lean ones, the recipients gained weight. In one study, melanoma patients with the most diverse microbiomes had the best response to immunotherapy. And mice injected with gut bacteria from marathon runners ran longer distances. A new drug for obesity alone could be worth more than $20 billion.

So far, the most compelling microbiome-derived therapy is a live fecal transplant for C. diff, which strikes half a million Americans annually, killing 15,000. In 2013, the New England Journal of Medicine published a paper that caught the scientific community by surprise and jump-started investment in microbiome drug development. In a randomized trial, 94% of recurrent C. diff patients recovered after receiving fecal transplants. To put that in context, cancer drugs with efficacy rates as low as 10% have been approved by the FDA.

“I don’t think there’s any other field of medicine today that holds as much promise for the future of medicine as the microbiome,” says Olle.

Billions of dollars are pouring into microbiome medicine. Gbola Amusa, a medical doctor and partner at Chardan, a health care–focused investment bank in New York, pegs the total amount invested since 2014 at more than $5 billion. Techie billionaires including Bill Gates, Salesforce founder Marc Benioff and Silicon Valley venture capitalist Vinod Khosla are funding microbiome startups, and Gates, Benioff and Mark Zuckerberg have all made donations to support microbiome research at institutions including Stanford, Washington University in St. Louis and the University of California, San Francisco.

The race is on for FDA approval of the first drug made from gut bacteria. But the science is young and unproven. At Oppenheimer in New York, Mark Breidenbach says investor enthusiasm in microbiome companies is on a downswing because “there is no consensus about what the microbiome can do.”

Amusa is more bullish. “The science is turning,” he says. “When it comes through with proof, these biotech companies will be worth not hundreds of millions of dollars, but billions.”

Somerville, Massachusetts–based Finch Therapeutics is one of the most promising startups developing microbiome drugs. Cofounder Mark Smith, 33, was a microbiology grad student at MIT when the 20-something C. diff patient begged him for help. “I had to tell him, I’m a microbiologist, not a doctor,” Smith says.

The patient’s ordeal motivated Smith to create OpenBiome, the equivalent of a public blood bank for human feces, while Smith was still at MIT in 2013. The Cambridge, Massachusetts, nonprofit, the first of its kind in the world, has since supplied stool for more than 53,000 transplants in 1,200 hospitals and clinics.

Inspired by the demand for transplants, Smith cofounded for-profit Finch (named for the diverse group of finches Charles Darwin discovered in the Galápagos Islands) in 2016 to develop an FDA-approved C. diff pill. Currently, most doctors perform fecal transplants through a colonoscopy, which can cost as much as $5,000. The procedure is not FDA-approved or reliably covered by insurance.

Smith and his 80 employees occupy two floors in an industrial park that formerly housed administrative offices and storage space for the Harvard Art Museums. Tall and slender with piercing blue eyes, he welcomes the inevitable jokes that come with being a human-feces entrepreneur. On Halloween he wore a poop-emoji costume (“I was a pooper trooper”) to the office, where the copiers have names like Squatty Potty and Magic Stool Bus.

But he has raised serious capital. Venture funds have put in $130 million, and Finch has a partnership with Tokyo-based pharma giant Takeda to develop drugs for ulcerative colitis and Crohn’s disease, which together have 10 million sufferers worldwide. Finch is also working on an autism drug.

“It’s only in the  past 15 years that we’ve come to understand the incredible diversity of the microbiome. It’s almost  like a rainforest inside our bodies. There are 100  times more bacterial genes than human genes.

Traditionally, scientists start with data gathered through experiments on mice. Finch is taking a “human-first” approach, skipping the rodents and analyzing the stool of human patients who have recovered after receiving fecal transplants. “We’re looking at what works in patients and figuring out how to make our drugs from the top down,” Smith says. “It’s called reverse translation.”

For one of its C. diff drugs, Finch is extracting what Smith describes as the “full spectrum” of bacteria in a human stool sample from a carefully screened healthy donor, freeze-drying it and delivering the equivalent of a fecal transplant in a single pill. It’s also working on simpler drugs made from five to 10 key bacteria. It expects results from its first Phase 2 trial (which demonstrates efficacy) of the full-spectrum C. diff capsule by the end of the second quarter of 2020.

“Even if only a few of the microbiome therapies scientists are working on come to fruition,” Smith says, “it will have a huge impact on public health.”

Another MIT Ph.D., Bernat Olle, 40, is running Vedanta Biosciences, a nine-year-old Cambridge, Massachusetts–based microbiome drug developer with $112 million in funding, including $10 million from the Bill & Melinda Gates Foundation. The Gates investment supports preclinical research at Vedanta aimed at developing a gut bacteria–derived drug that would prevent child malnutrition in the developing world. Nearly 200 million children under age 5 suffer from either wasting or stunting, resulting in at least 1.5 million deaths a year. “Malnourished children struggle to gain weight even when fed enough,” Olle says. “Emerging research suggests that this is because their gut microbiota develop abnormally, and that beneficial gut bacterial strains may help correct this imbalance.”

“I don’t think there’s any other field of medicine today  that holds as much promise for the future of medicine as the microbiome.” Bernat Olle, cofounder and CEO of Vedanta Biosciences.

Vedanta also has two partnerships with big pharmaceutical companies, including Bristol-Myers Squibb, to develop drugs aimed at boosting the effectiveness of immunotherapy to treat melanoma and colorectal and gastric cancers. Like Finch, Vedanta is developing a drug to treat recurrent C. diff.

Inside Vedanta’s maze of labs and storage rooms is an oversized freezer containing fecal matter from 275 donors on four continents, including an indigenous tribe in Papua New Guinea. Vedanta is isolating and then testing bacteria from each sample in the hope of determining which strains make the most effective drugs.

A wiry Catalan immigrant with close-cropped salt-and-pepper hair who bicycles to work, Olle came to the U.S. in 2002 to study chemical engineering at MIT, where he focused on the emerging science of using live organisms like bacteria to produce drugs. In 2007, after earning both an MIT doctorate and an MBA from the Sloan School, he joined PureTech Health, a Boston biotech firm.

In 2010 PureTech backed him in launching Vedanta with five cofounders, all scientists, including big names such as Kenya Honda, a microbiology professor at Keio University medical school in Tokyo. Honda had published a groundbreaking paper on the connection between gut bacteria and regulatory T cells, known to prevent inflammatory diseases. “Think of them as the U.N. peace forces of the intestine,” Olle says. “Honda’s work suggested that the cells encoded in human DNA are influenced by the bacteria that live within you.”

“This work has forced me to rethink what it means to be human,” Olle says. “We are not just the product of the Homo sapiens genome.”

Every gold rush attracts its share of charlatans and claim jumpers. More than a half-dozen startups are using the microbiome as a marketing buzzword to sell stool-analysis tests. The kits, which require the consumer to mail a small sample to a lab, purport to convey valuable personalized health data and nutrition advice. That despite a consensus among scientists that it’s not yet possible to draw useful dietary recommendations from a person’s poop. To avoid hostile oversight by the FDA, the kit sellers are careful to make no specific claims about diagnosing or treating particular diseases.

Four years ago, former InfoSpace billionaire Naveen Jain, 60, launched Bellevue, Washington–based Viome, which sells a $119 “gut intelligence test” online. After analyzing a pea-sized stool sample, it sends customers a customized 60-page report with dietary recommendations “aimed at balancing your overall microbiome.” It might recommend, for instance, increasing consumption of “superfoods” like alfalfa sprouts and anchovies or avoiding green beans and kombucha. Jain says Viome has sold more than 100,000 kits and banked more than $15 million in revenue last year. Doctalbott Note = 60-pages?!?! I’m not sure most people actually want that level of information overload – it’s not usable information. What if you had a simple “overall score” and a few understandable and actionable targets that you could easily, quickly and inexpensively track over time? I think a LOT of people might be interested in that. 

“Viome’s claims are not supported by any scientific literature,” says Jonathan Eisen, a medical microbiology professor who directs microbiome research at the University of California, Davis. “What they’re saying is, in fact, deceptive.” A dozen former Viome staffers say they believe the company was selling a product of dubious value. Six of those ex-staffers describe the food recommendations as “pseudoscience.”

“Anyone who says this doesn’t understand how our science works and how we make recommendations,” Jain counters. “It’s not my job to convince everyone; it’s my job to continue to help make the world a better place.”

A nonstop talker prone to enthusiastic, stream-of-consciousness self-promotion, Jain immigrated to the U.S. from India in 1982 and worked at Microsoft from 1989 until 1996, when he founded InfoSpace, also in Bellevue, which delivered internet content to early cellphones. His net worth ballooned to $8 billion, then crashed to $220 million when the first internet bubble burst. A flood of shareholder suits followed, and the InfoSpace board fired him as CEO in late 2002. Before he left InfoSpace, he bought a $13 million stucco mansion on the shores of Lake Washington not far from Jeff Bezos’ and Bill Gates’ pads.

Despite having no background in science or medicine, Jain has managed to raise $75 million from investors including Benioff and Khosla. Both declined to comment on their microbiome investments. But Alex Morgan, a Khosla Ventures principal with an M.D. and Ph.D. from Stanford, suggests Khosla’s decision to back Viome has nothing to do with nutritional advice. Instead, he says, the firm invested because Viome hired a team of scientists from the U.S. Department of Energy’s Los Alamos National Laboratory. In addition, Viome had made a deal with the lab to license a valuable tech platform that has a unique ability to sequence the biochemical activity in microorganisms.

“The goal is to scientifically show that it’s not voodoo stuff or a placebo,” says Jain

So even if Jain is selling snake oil, Viome might have significant value. Indeed, British pharma giant GlaxoSmithKline struck a royalty deal with Viome in November 2019 to use its tech to help develop microbiome-derived vaccines. Jain’s investors could make out handsomely.

At Caltech in Pasadena, California, microbiologist Sarkis Mazmanian, 47, is considered one of the foremost gurus of microbiome research. In 2012 the MacArthur Foundation gave him a $500,000 “genius” grant for his work on the microbiome’s role in disease. Since then, he’s been exploring one of the most intriguing connections in human health: the “gut-brain axis.” The working thesis is that the bugs in your belly have a direct impact on your neurological health, which has profound implications for autism, Parkinson’s and Alzheimer’s. Doctalbott Note = our group has made more than a dozen peer-reviewed scientific presentations showing how natural microbiome modulation dramatically improves psychological mood states including depression, tension, stress, burnout, and fatigue.

In 2008, two years after joining the Caltech faculty, Mazmanian published a cover story in Nature that documented his successful treatment of inflammatory bowel disease in mice with human gut bacteria. A Caltech colleague, Paul Patterson, who was researching autism in mice, saw a possible connection to the digestive problems suffered by as many as 60% of children with autism.

Together they started testing whether human gut bacteria could induce and ameliorate autism-like symptoms in mice. In the midst of their early work, Patterson was diagnosed with fatal brain cancer. In a hospital room at UCLA where Patterson was awaiting surgery in May 2014, Mazmanian signed papers giving Patterson a stake in a company that would develop drugs from their experiments. “I wanted Paul to get the recognition of his contribution,” says Mazmanian. Patterson died the following month.

In a trailblazing study,  he transferred gut bacteria from humans with autism into sterile mice who then exhibited autism-like  behaviors. “The most rigorous clinicians and investors,” he says, “realize this is a long journey we’re on.”

Mazmanian is carrying on their research in his sub-basement lab at Caltech, where 1,000 germ-free mice, delivered by Caesarean section in sterile conditions to ensure they are bacteria-free, live inside plastic-encased rectangular bubbles. Grad students douse the animals’ food with various gut microbes to test which bacteria promote tremors and motor problems in mice that correlate with Parkinson’s symptoms in humans.

In 2016, David Donabedian, a chemistry Ph.D. who was then a partner at Longwood Fund, a Boston venture capital firm, volunteered to raise the money and research power to move Mazmanian’s biotech venture forward. The company, Waltham, Massachusetts–based Axial Biotherapeutics, has $55 million in backing and 30 employees. Under Donabedian as CEO, Axial is in the early stages of developing synthetic drugs made of small molecules it hopes will absorb the particular gut-bacteria byproducts (called “metabolites”) that appear to exacerbate autism symptoms. It’s also working on a drug to treat the digestive problems suffered by many people with Parkinson’s. Doctalbott Note = again, lot’s of people are likely to prefer a natural approach to optimizing their microbiome metabolism – and we can do that!

In the U.S., more than a million people suffer from autism, and there are no drugs to treat it; an additional million have Parkinson’s. What would be the value of an FDA-approved drug for either condition? “I can’t give you a market size,” says Donabedian. “But if either one hits, it will be huge.”

Chris Howerton, a biotechnology analyst at Jefferies, a New York investment bank, is less shy. “If every single microbiome paper turns into a proven therapy, it could impact the drug markets for most major categories of disease, which together were worth $350 billion in 2018 in the U.S. alone,” he says. “The breadth of the microbiome’s potential application is really tantalizing.” Doctalbott Note = AGREED!

ADHD in Adults

An excellent article in today’s Wall Street Journal about ADHD in older adults – a diagnosis that lots of people have considered solely a problem for “kids and teens” – but is increasingly being seen as a massive problem for productivity and achievement (and general well-being) in middle-aged and older adults.

I personally use two different mood/focus herbal products to improve mood, enhance focus, and boost stress resilience. Every morning, I use Mood+ and most afternoons I use Kid’s Mood+  (both from Amare Global and both of which I formulated).

Each supplement works in different ways to keep me on track mentally and creatively, especially during stressful periods (which seems like “always” these days).

See the original WSJ article here (behind pay wall for subscribers) = https://www.wsj.com/articles/an-unexpected-new-diagnosis-in-older-adults-adhd-11582558978

See my highlighted notes below…

An Unexpected New Diagnosis in Older Adults: ADHD

For years, ADHD has been considered a disorder of kids and younger adults. Now, doctors are realizing older people have it too—and it’s sometimes mistaken for dementia.

Many seniors get diagnosed with conditions like dementia or heart disease.

Not Timothy McMichael. At the age of 60, he was diagnosed with a condition most often associated with school children: attention-deficit hyperactivity disorder. He started taking a low dose of a stimulant about a year-and-a-half ago and says his attentiveness and concentration at work have never been better. (DocTalbott note = why would you take an addictive synthetic stimulant if you could get superior benefits naturally – probably because you simply did not know any better?)

“I’ve been fairly successful in my life and career, and did not think of ADHD as an adult thing,” says Mr. McMichael, a 61-year-old Leonardtown, Md., resident and engineer for the Department of Defense. “But I had spent the last 40 years coming up with coping mechanisms.”

Like many older people diagnosed with ADHD for the first time, Mr. McMichael didn’t consider the condition until his then-11-year-old son went through the diagnosis and treatment process about five years ago. He recognized many of the symptoms and struggles of his son and raised the issue with his son’s psychiatrist, David Goodman.

Dr. Goodman, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine, sees patients between the ages of 15 and 85. He has a particular interest in ADHD patients who are over 50 and have never been diagnosed.

Until just a few years ago, older adults were hardly ever diagnosed with ADHD. But as awareness of the condition among younger people has surged, doctors are beginning to make the diagnosis more often in seniors as well. (DocTalbott note = an prescribing more and more addictive synthetic stimulants – again, probably because they simply do not know any better?)

Doctors don’t believe the actual prevalence of the condition among seniors has increased, or that they are developing the condition as they age. Instead, doctors suspect many seniors have lived their whole lives with ADHD, and only now are getting diagnosed. Many found ways to manage their symptoms in earlier stages of life, but hit a new hurdle as they aged that prompted a flare-up—or simply recognized the symptoms after a younger relative’s diagnosis.

People with ADHD experience symptoms of inattention, disorganization and hyperactivity. Often hyperactivity diminishes with age, but challenges with attention and organization don’t.

Research on ADHD in seniors is nascent, but one study estimated the prevalence rate in people over 50 at 3%. That compares with about 8% in U.S. children and about 4.5% in adults under age 45. Some studies have found that about half of the children diagnosed with ADHD no longer meet diagnostic criteria by the time they reach adulthood.

One challenge to diagnosing ADHD in seniors is that symptoms look similar to age-related ailments. Cognitive difficulties in older people are often attributed to memory impairments or early signs of dementia, says Dr. Goodman. For women in their early 50s, such complaints are often attributed to perimenopause, the time before a woman reaches menopause.

Treatment presents another hurdle. The most common ADHD treatment among younger people is stimulants. But those are riskier in older adults because they can raise heart rate and blood pressure, so they need to be monitored closely.

Kathleen Nadeau, founder and clinical director of the Chesapeake Center, an ADHD, learning and behavioral health clinic based in Bethesda, Md., says she has seen three typical patterns for a diagnosis in seniors. Some patients were in treatment for another condition, like depression, and their psychiatrist suggested they get evaluated for ADHD. Another group had a relative or friend diagnosed. A third had a change in their life that increased the demands on them and they couldn’t cope.

She says ADHD symptoms rise and fall in people depending on how stressful their circumstances are. (DocTalbott note = which REALLY screams out for a natural solution that both improves focus AND bolsters stress resilience – which is not what the synthetic stimulants do – and which can actually increase feeling of stress) “If you don’t have to work or raise children anymore, it may look like you have less ADHD, but you actually have less demands,” says Dr. Nadeau. “If you’re put back in a situation you may have similar difficulties. This doesn’t go away and people still need help” at older ages.

Lenard Adler, director of the adult ADHD program at NYU Langone Health, says more people over the age of 60 are coming in with ADHD symptoms. Of the older patients he’s treated, some found him after other psychiatrists were unwilling to treat them, he says. One patient had a history of hypertension and cardiac problems. He was able to successfully treat the patient with a long-acting amphetamine.

Dr. Alder says it’s important to distinguish between memory and ADHD issues in seniors. “We’re dealing with a population that may have some age-related memory decline,” he says.

In some cases, patients may mistakenly be diagnosed with mild cognitive impairment, often a precursor to dementia. But other times families may be looking for any diagnosis besides cognitive decline. One family brought in their loved one hoping it was ADHD and not dementia. The patient, says Dr. Adler, was “having a substantial cognitive decline and it obviously was dementia. So it can go both ways. It’s important to get the diagnosis right.”

Doctors say that age-related memory impairments come on later in life and are primarily memory deficits, while ADHD symptoms start in childhood or early adolescence and revolve around inattention. While neuropsychological tests can’t distinguish between the two, certain cognitive impairments are associated with pre-dementia, such as difficulty remembering a word or getting lost while driving a familiar route.

Treatment of ADHD in older adults is similar to that of younger patients. Treatment can combine prescription stimulants with non-medication approaches such as cognitive behavioral therapy and organizational skill work. A study published last year showed that CBT was an effective treatment for older ADHD patients. (DocTalbott note = and why not also try a natural approach like saffron – see a short clip about it from ABC7 in Los Angeles = http://blog.amare.com/health-benefits-of-saffron-in-amares-kids-mood/)

Dr. Goodman says most ADHD studies of stimulants don’t include seniors because of greater risks with heart rate and blood pressure. There is also a risk of developing insomnia, agitation and psychosis.

Dr. Goodman’s experience in treating some 800 seniors over the past three decades has shown few side effects, he says. He says diagnostic accuracy is crucial in seniors before prescribing any medications. “Dosing is thoughtfully slow while monitoring improving cognitive symptoms, side effects and blood pressure,” he says.

Sandra Kooij, an associate professor of psychiatry at Amsterdam University Medical Center, studies ADHD in seniors in the Netherlands. At her clinic they have treated about 150 seniors age 55 and older with stimulants, in addition to psychoeducation and cognitive behavioral therapy, for ADHD.

Dr. Kooij says they are analyzing the treatment and side effects for a study they hope to publish later this year. Overall efficacy has been similar to younger adults, and the medications were well tolerated with appropriate management of cardiovascular risks, she says. Patients were also treated for conditions like anxiety and depression that often present in ADHD patients, and sometimes occur as side effects of stimulants. (DocTalbott note = great – so now the stimulant used to “treat” ADHD leads to depression/anxiety that has to be “treated” with antidepressants and anti-anxiety drugs – so you get another set of symptoms and side effects – brilliant!) 

Seniors that have lived with ADHD all their lives and don’t feel impaired shouldn’t be treated, she notes. “Only people who feel impaired by their symptoms should be treated,” she says.

Joan Friess, a 76-year-old who lives in a senior community in Coconut Creek, Fla., was diagnosed with a precursor to Alzheimer’s disease about five years ago and started taking medication for it, says her son, Steve Friess, a freelance writer who lives in Ann Arbor, Mich.

But Ms. Friess never believed the neurologist who diagnosed her, both mother and son say. She is an advanced bridge and mahjong player and sings with an elite choir with no problem.

After her husband died and she moved to a different part of Florida, she decided to see a different neurologist.

Mr. Friess talked to the neurologist, who asked him if his mother’s behavior was different than most of her life. “I said, ‘No, not really,’ ” he recalls. “She was always losing things and a bit forgetful.”

The neurologist did some brain scans. Comparing them with previous scans, she said she saw nothing to indicate Alzheimer’s disease or dementia. Instead, she diagnosed Ms. Friess with ADHD.

Ms. Friess says she was relieved to confirm what she knew all along. “My husband thought I was forgetting things, but I knew there was nothing wrong with me,” she says.

Mr. Michael, the Department of Defense engineer, says even though he’s had a successful career, he can’t help but wonder how earlier treatment might have helped him. He says even his colleagues noticed his improved performance at work. “I’m much more focused on individual tasks,” he says. “I’m more efficient in how I use my day. I think my life absolutely would have been a lot easier had I known.”

Hawaii Health Professionals – Gut/Heart/Brain Axis for Mental Wellness Seminar

Had a wonderful SOLD OUT seminar last night in Honolulu to educate a diverse audience of health professionals about the role of the microbiome, gut-brain-axis, and heart-brain-axis in optimizing mental wellness.

We live-streamed to Facebook and you can also see the video at YouTube.

Slides are here = Hawaii Health Pro 021820 Gut Heart Brain Mental Wellness

 

Gut-Brain-Axis Optimization for Peak Performance – Interview with NeuroPeak Pro

Here is a interview that I did with the great Joe Martinez at NeuroPeak Pro.

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Hunger Buster Smoothies

Heading into the end of January – I can HEAR your stomach growling!

This is the time of year when a lot of people start to fall OFF their New Year’s resolutions to lose weight and get in shape – and a BIG reason for that fall off is because you’re HUNGRY!

I visited KUTV’s Fresh Living on Thursday (Jan 23) to talk about foods that can help reduce appetite – you can see the segment HERE.

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Both of my Hunger Buster Smoothies include specific foods that are known to enhance SATIETY (reducing overall appetite and increasing feelings of fullness for longer).

Each of these foods is high in a phytonutrient called Falcarinol – it’s a naturally-occurring plant compound that helps to protect vegetables and herbs from insects – so in some ways it’s like the plant’s own natural insecticide.

Among the highest falcarinol-containing foods are carrots, parsley, celery, fennel, and mint.

In small amounts, falcarinol protects plants from bugs, but it also inhibits important appetite centers in the brain (CB1 receptors) – so we feel less hungry and more full for longer – which is exactly what many of us need to help us stay on that healthy eating plan.

Here are two of my go-to simple smoothie recipes – they only take a couple minutes to blend together.

The first one is really more of a morning Green Detox Juice – and the second is a more substantial Chocolate Mint Protein Shake.

Green Detox Juice

  • 1 stalk celery
  • 1 stalk fennel
  • 1/2 apple
  • 1 handful fresh parsley
  • 1 pinch each of paprika and salt
    • Blend together with 1 cup of cold water and handful of ice cubes

Chocolate Mint Protein Shake

  • 1 cup milk (of your choice) and a handful of ice cubes
  • 2 scoops Amare GBX Protein (Chocolate)
  • 1 carrot
  • 2 fresh mint leaves
    • Blend together with 1 cup of milk (of your choice) and a handful of ice cubes