From Sarah Ramey’s book, The Lady’s Handbook for Her Mysterious Illness:
Functional medicine, I learned, is about the root cause of chronic illness. It is a special, standardized training that is starting to be offered around the country to supplement medical school for doctors and other health practitioners, focusing on the systems of the body. It isn’t antisurgery, antitechnology, or antimedication, but the foundational teaching is that diet, lifestyle, and attitude are the cornerstones of health and that when it comes to chronic disease, you must start there. Specifically with a blood-sugar stabilizing, a microbiome-friendly diet, and a lifestyle that safeguards sleep, relaxation, exercise, and human connection as top priorities for a baseline of normal vitality. And the reasons for these recommendations are biochemical, not touchy-feely. None of this is taught in medical school.
Dr. [Mark] Hyman also explained—and this was what sold me—that the model he was proposing was not to be confused with what the public understands as “integrative medicine.” He explained that integrative medicine has come to be a catchall term that can mean integrating almost anything alternative into the traditional medical model. In contrast, functional medicine isn’t about giving the patient a goody bag of acupuncture, massage, vitamin D, and a quartz crystal as a complement to their Prozac and their statins.
It is a very specific, standardized method for testing, treating, and stabilizing the four main systems that have been identified as the drivers of our modern, chronic illnesses. These four areas of focus are: The Gut. The Liver. The Immune System. The Endocrine System.
The Gut, he explained, is extremely complicated. In modern times, because of a huge uptick in sugar consumption, chemical production, and antibiotic overuse, we are dealing with a very unhappy microbiome—and this situation is increasingly understood in functional medicine to be one of the direct and missing links to autoimmunity, and to the mystery illnesses as a whole.
The Liver, he went on, isn’t doing very well in these modern times, either. Eighty thousand new chemicals have been introduced into the environment in the last century, placing an enormous and unprecedented burden on our detoxification processes. While not all chemicals are dangerous, and it is important not to become chemophobic, it is definitely true that a growing number of chemicals and pesticides are either known or suspected to have a negative effect on human health. And when the liver has too much work to do, it is unable to properly metabolize all the things floating around, such as hormones, biotoxins, certain chemicals, and any waste or debris. In some cases, these substances then recirculate in the bloodstream and may be flagged as antigens, stimulating the immune system, causing inflammation. In others, the recirculated toxins can get deposited in the tissues, which has also been associated with fibromyalgia, multiple chemical sensitivity, and food allergies. And in other patients, unmetabolized hormones and xenoestrogens can cause endocrine disruption.
The Immune System, he continued, and the many problems associated with immune dysregulation, is still not very well understood, as there are so many types of antigens, so many points of entry, and so much genetic and environmental variation from patient to patient. However, an overstimulated, dysregulated immune system has clearly been shown to be at the heart of autoimmunity and many of the WOMI [Women of Mysterious Illness] problems.
The focus for any patient dealing with these problems is thus to do everything in her power to reduce antigenic flow, and to cool the varying types of inflammation as naturally as possible via an anti-inflammatory diet and anti-inflammatory herbs. Many of the common steroidal anti-inflammatories used by a traditional doctor, particularly for autoimmunity, can cause major side effects—and most important, they do not address the source of the fire.
Finally, he added, the Endocrine System is extremely complicated as well. We tend to think of stress as a metaphor, but the stress response is biochemically quite real. Both stress and unstable blood sugar call on the adrenal glands to secrete cortisol to mobilize glucose from the cells when insulin has been tapped for too long. This constant call for cortisol disrupts the delicate conversation between the brain and the target glands. And as mentioned, some chemicals can disrupt the hormonal conversation in the body, as well. And when any of these conversations are thrown off for prolonged periods of time, you will start to see polycystic ovary syndrome, endometriosis, fibroids, hypothyroidism, painful periods, low sex drive, and infertility—aka the hormonal mysterious illnesses, aka HOMIs.
…For functional medicine practitioners, he explained that there is one test that matters a little bit more than all the rest. You must, he explained, test the HPA axis. Or, the hypothalamic-pituitary-adrenal axis. Adrenals? I thought when I first saw this. I had read about them, and knew the basics. The adrenal glands are a pair of small glands that sit on top of the kidneys. They are part of the endocrine system, and they are the glands that secrete glucocorticoids (predominantly cortisol) and adrenaline in your body. Your hypothalamus and pituitary are the glands that tell the adrenals when to do so, and how much.
And the adrenal glands’ most famous function is the fight-or-flight response. When faced with danger, the body immediately begins to secrete both adrenaline and cortisol, a series of chemical reactions that help you fight, freeze, or take flight. The adrenals, the hypothalamus, and the pituitary function as your stress mediators. Sure, sure, I thought. “Stress.” I already knew that. Yoga. Pranayama. Meditation. Wind chimes. Got it. So at first I thought this guy might have a touch of Very Large Ear Syndrome, focusing too much on only one part of the elephant. Oh really, Dr. Tests? I’d like to hear why the adrenals are so important? Ahead of, say, the gut?
He went on to explain that the HPA axis controls a rhythmic, hormonal conversation that is happening in the body all the time. The hypothalamus scans the body, decides if the adrenals need to secrete any hormones; if they do, it sends the message to the pituitary, which talks to the adrenals, and voilà: secretion. Cortisol. ACTH. Adrenaline. In a normal state, cortisol and adrenaline are called on throughout the day to buffer and address any small stresses that come up. The system can also go into high gear, built to help you cope with occasional major stress or trauma, as well.
And most people have usually heard the following explanation of stress: back in the day, our big stressors would have been the chance grizzly bear, an unexpected saber-toothed tiger, drought, famine, winter, and so on. Modern life has protected us from many of these more dramatic stressors of the wild, but of course we have replaced them with our own new stresses. Modern people experience two different types of traumas—big T and little t. Big T traumas include things like rape, domestic abuse, combat, the unexpected death of a spouse, acrimonious divorces, major infections, head injuries, and accidents. And then there are traumas with a little t. Losing a job, a bad breakup, and a move to a new city are some little t examples. All of the above are called “external stressors.” They all activate the HPA axis, and the production of the stress hormones, especially cortisol. This comprises most of our normal understanding of “stress.”
However, big T and little t stressors aren’t the only triggers for cortisol production. When you eat a high-glycemic meal, blood sugar goes up, insulin moves the glucose to the cells, blood sugar then drops—and the drop causes cortisol and other glucocorticoids to be secreted to bring blood sugar back up to baseline. The same is true for chronically high blood sugar, as in diabetes. When sugar does drop, it is cortisol that comes in to stabilize things. And in the West, we consume a famously high-glycemic, low-fiber diet—read: a lot of blood sugar spikes and drops throughout the day, calling on small amounts of cortisol, insulin, and leptin all day, every day. This is a very modern phenomenon. And this same constant biochemical call for small amounts of cortisol will be triggered if you maintain low blood sugar all day, as in the woman who eats a few almonds for breakfast, salad for lunch, and salad for dinner, and keeps herself going all day with Diet Coke, Provigil, and coffee.
Disordered eating, low blood sugar, smart drugs, and caffeine all register as stress, and all stimulate cortisol production. Another trigger is sleep deprivation. Reducing sleep by even one hour—and certainly two, three, or four hours short of the recommended eight—primes the amygdala (the fear center) to be much more reactive the next day. Fear activates the HPA axis. Another trigger is inflammation. Infections, food sensitivities (especially to gluten), inflammatory foods, toxins, mold, heavy metals, and inflammatory diseases—all inflammation is registered as stress in the body and all inflammation will rev the HPA axis. Another trigger is pain. Unremitting pain is extremely stressful, and to this one I can attest. All of these—unstable blood sugar, sleep deprivation, infections, inflammation, pain—are called “internal stressors.” They activate the HPA axis without much conscious input.
Then finally, in the last category are the everyday stresses and issues that generally constitute the rest of our common, cultural understanding of stress. We know what these are: horrible bosses, traffic jams, social media, deadlines, debt, constant connection to technology, bringing work home, negative news, toxic relationships, body-image problems, and so on. We have a lot of this in our culture. And, of course, we all already know about this kind of stress and that we should be “less stressed.” These kinds of everyday issues are especially problematic for those of us of the HSP [highly sensitive people] persuasion—these problems are known to cause significantly more distress for us, just because of our wiring. We jangle easily, and it is such a jangly world. And this common, culturally understood category of stress is counted as both internal and external. Much of it is happening outside of you, but some of the stress response is largely within one’s control. It is called “perceived stress” because life is not actually in danger, and there is no real need to fight, or take flight. With work, these things can be dealt with personally. One can change one’s environment to be less stressful, or change the quality of one’s response. Serenity now, and so on. But if we look at this list, we see something very important:
Horrible bosses and bad body image are not our only stressors. Having an infection is not a matter of perception, or serenity. The HPA axis can be thought of as home to a small red emergency button. Negativity, your boss, deadlines, and social media can all certainly push that button—but problems with the diet, gut dysbiosis, sleep, infections, toxins, and food sensitivities can also be pressing that same red button, even more frequently, well below the threshold of consciousness. It is not a very different concept from the constant antigen activation of the immune system. It’s happening, but you’re not aware that it’s happening. And this really matters.
While most of these factors are not new—sugar, gluten, stress, dysbiosis—what is new is the sheer volume at which they exist in modern society. All of the stressors listed above are a pretty good description of the new normal. Our encounters with these things are not chance—they’re constant.
The average American consumes roughly sixty-six pounds of sugar annually—orders of magnitude more than the amount of sugar an average American consumed just a hundred years ago. Not only is that a lot more sugar—it is a lot more cortisol. The average American gets two hours less sleep than the average American did a hundred years ago. That has many consequences, and one of them is a more reactive amygdala, and thus more cortisol. Infections have always been around, but since we have succeeded so profoundly with treating acute infections—saving millions and millions and millions of lives—chronic use of antibiotics have also opened the doorway to chronic infections, resistant infections, and most importantly (in combination with a high-sugar diet): gut dysbiosis. This is a major, major new stressor—and most people have never even heard the word “dysbiosis.”
But it doesn’t end there. As mentioned before, the average American has been exposed to eighty thousand new chemicals in the environment over the last century, and the number continues to grow. While a little contact is okay, or even a moderate amount, an onslaught is not okay. And it’s not just the big bad wolves like pesticides and BPAs; there are also toxins in our medications, our baby wipes, our makeup, our mattresses, and our new clothes. There are toxins everywhere. This creates a real burden on the body. Cortisol. Food sensitivities, especially to gluten (to everyone’s dismay), have become extremely widespread. More about this later on, but for now just understand this: when the IgA (immunoglobulin A) immune response is activated in response to gliadin proteins in the bloodstream, so is the stress response.
And, as we hear every day in our news feeds (omnipresent news feeds, mostly bad news, which also compounds the problem), we now live in a relentlessly go, go, go world, full of screens, and late nights, and folks who don’t quite know how to turn off. Stress. Cortisol. As a people, we tap that emergency button all day, every day, and we don’t know it. Thus the development of a problem with the red button is perhaps fairly predictable. The HPA axis is not an unbreakable machine, it is a delicate system in the body. While it is resilient, it isn’t immortal. It can handle stress just fine—just not constant stress, from every direction, all the time.
It makes sense that it might get confused. We’re not supposed to have constant stress, from every direction, all the time. And this confusion is thought, by Dr. Tests and others, to lead to a phenomenon known as dysregulated cortisol. This is sometimes called “adrenal fatigue,” but we aren’t going to call it that. For one, just like its friends gluten and dysbiosis, that phrase is already extremely fraught in the medical community, and not taken seriously. It is also linguistically misleading, as the adrenals themselves are not fatigued or damaged—it’s the HPA conversation that has broken down.
Either way, you and I are going to leave “adrenal fatigue” behind for now. From here on out, we’re going to go with the terms used by researchers—cortisol dysregulation and HPA axis dysregulation. But all of the above, of course, are the exact same thing. HPA axis dysregulation is quite real. There are thousands of studies on this phenomenon. While the exact mechanisms are not fully understood, we do have a sense of the basics. After a very long time of being activated—all day, every day—the brain’s hippocampus appears to shrink, and because the hippocampus affects the HPA axis, this means that the HPA axis stops being able to produce cortisol in its healthy, predictable ski slope of a diurnal pattern.
According to Dr. Tests, a healthy person is meant to wake up with between twenty and twenty-five units of cortisol flooded into their system, which is what gives you a boost in the morning to hit the ground running. This slowly tapers off throughout the morning, and throughout the day—with small bumps at both lunch and dinnertime, tapering off to nearly zero at bedtime, which is part of what makes you feel sleepy. Of cortisol’s many functions in the body, the main one is that it is in charge of how your body makes and how your body uses energy. Graphed, the daily pattern looks like an elegant ski slope, with some moguls at the end.
But when this cycle is disrupted, the body begins to produce the wrong amounts of cortisol at the wrong times. This dysregulation will get worse as time goes on if whatever is overstimulating the axis is not changed or removed—that is, if behavior is not modified or the stressor is not eliminated. That is, over time the problem does not remain static, it evolves. It is dynamic. It has stages.
In Stage 1, the person begins to produce too much cortisol—instead of a smooth ski slope production of cortisol, there is a surge in the morning, followed by a slight crash in midmorning, and then again in the late afternoon. Symptoms associated with Stage 1 are mild: slight fatigue, skin problems, mild hormonal problems, and possibly more bowel complaints than the next guy. Nothing serious.
In Stage 2, cortisol starts to be sky-high in the morning, but the subsequent crashes throughout the day are much steeper and require a lot more propping up with sugar and caffeine. At this point, cortisol also starts to go up in the evenings, before bedtime—producing a kind of second wind, and insomnia. This results in less sleep, and thus more cortisol dysregulation. Now she starts to see real problems—because excess cortisol, as with any hormonal imbalance, starts to disrupt the whole endocrine system. For example, cortisol dysregulation is known to lead directly to sex-hormone dysregulation. Dr. Sara Gottfried has written about this extensively. For just one example, cortisol takes precedence when it comes to engaging the receptors on any cell. So if there is a flood of cortisol, researchers have found that cortisol will hog the receptor sites in the body. This means other sex hormones can’t engage at the receptor sites and therefore will continue to float around unused. If the brain gets the message that estrogen never got to the cell, then the body produces more estrogen, even though there is already plenty. Over time this can lead to estrogen dominance, which is highly correlated with PCOS, infertility, and endometriosis. This is just one example of an extremely long list of possible hormonal fallouts. Excess cortisol has been shown capable of affecting many other hormones—for example, testosterone, DHEA—and it can especially slow down the thyroid, and this is thought to be one of the main contributors to subclinical hypothyroid problems. This is a lot, but this is not all. Dr. Tests explained that when cortisol goes up, immunity is suppressed. So when cortisol dysregulation is chronic, immunity is chronically suppressed.
If I could gracefully write in all caps here, I would. When the stress response is activated, the body favors systems that are essential for survival—it sends blood to the large muscles for flight, dilates the pupils, and increases heart rate. It draws blood and energy away from less essential parts of the body—for example, the immune system and the digestive system. If faced with a lion, your body is appropriately less concerned in the moment with digestion, or warding off the common cold. But if there isn’t actually a lion—if you are just in this very common, very modern state of being stressed, sugar-addicted, caffeine-addled, wired, and tired, and have measurably high cortisol, you can be sure your immunity is likely not in a state of excellence, and you won’t have nearly as many troops defending the gates.
So now—not only are you feeling stressed, tired, and wired, with trouble sleeping, as well as worrisome hormonal and metabolic problems (like night sweats, hot flashes, cold feet)(at age twenty-six), but you also seem to be picking up every flu, every cold, and every sore throat. If someone is going to pick up a nasty virus on vacation, it is pretty reliably going to be you. This brings us to Stage 3. Stage 3, come to find, is almost always precipitated by a trauma. For this person who has been muddling along at Stage 2, perhaps for a very long time—not really sick, but not really well either—when a car hits them head-on out of nowhere, or there is a huge, rancorous divorce, or a nasty virus hits, or they get bitten by an infected tick—this person’s stress response is no longer able to react properly.
This person switches suddenly from producing very high amounts of cortisol to extremely low amounts of cortisol. They fall precipitously off a cliff—but it is an invisible cliff, and an invisible fall. The exact mechanism that causes this switch is not totally understood, though it is known that the state of chronic stress damages or causes the hippocampus to shrink, which in layman’s terms “screws the pooch” for further, appropriate cortisol production. Clinicians who understand this problem and regularly measure cortisol patterns in their patients all report the same phenomenon. Once the patient has been in Stage 2 for long enough, and a trauma is introduced, she is almost inevitably moved to this next level, which is a state of low cortisol. The adrenals and the hypothalamus and the pituitary still work just fine, but their ability to converse with one another properly has broken down.
Now in the morning, the patient wakes up with well below the average units of cortisol—and accordingly hits the ground dragging. While excess cortisol has its problems, low cortisol is a much bigger issue. This low level stays low throughout the day, and she feels like complete hell all the time—she quite literally doesn’t have enough of the hormone that is in charge of how her body makes and uses energy. Her sex hormones are all out of whack, she can’t conceive, her thyroid is slowing down, and she has a very low sex drive. Because her digestion is so poor, her mitochondria are not getting the nutrients they need to produce cellular energy, causing even more fatigue. This is all creating more anxiety, more stress, a more depressed immune system, and she gets sick all the time. Starting to ring any bells? But most important of all: When cortisol goes down, according to Dr. Tests, the hormone DHEA goes down—and the hormone DHEA is directly connected to how much secretory IgA, or mucosal immunity, is produced in the gut.
Eighty percent of our immune system resides in the gut, and so when cortisol goes down, it brings intestinal mucosal immunity down with it. Thus: this person who is already saddled with so many health problems suddenly has a deficit of immune troops in her gut. Out of sight and out of mind, these troops have been defending and protecting her all her life from the inside out, stationed at the walls and ramparts of her intestinal lining. But when DHEA goes down, these soldiers are slowly put to sleep, one battalion at a time. This is not good. She needs those troops. And so now, the real unraveling begins.
Now this Stage 3 person may be struggling with a serious infection like Lyme or Epstein-Barr, or a head injury from an accident, or the ongoing stress of a divorce—in addition to very low cortisol production and poor mitochondrial function, as well as all manner of hormonal problems (all of which, especially aggregated, is extremely stressful in and of itself)—now they also have a very unusual state of low mucosal immunity in the gut. And so now, when this person with suppressed secretory IgA takes antibiotics for her sore throat, her own immunity is not there in full force to help her restore the proper flora in the gut. She needs those ground troops to keep pathogens at bay, which gives the good bugs time to repopulate.
Now, when the gut doesn’t reboot, and becomes colonized by too many of the bad guys, and not enough good guys, real and intractable dysbiosis commences, and the reactive inflammation in the gut starts to rage (a different branch of the immune system that is very much not suppressed)—all of which is exacerbated by poor diet, continuing stress, insomnia, and the enormous stress of being sick and addled. Here, in this swampy environment, in addition to everything else, this type of person can almost certainly say goodbye to healthy intestinal function, and hello to our least favorite syndrome, leaky gut syndrome.
And once that gate is open, the inflammatory, antigenic hellions are no longer confined to the gut and may roam freely throughout the body, like Orcs released from Mordor. And by now, we know what that does. The exact immune issue(s) she develops will likely depend on her genetic weak links. Lupus, MS, food sensitivities, mast cell activation syndrome—these are all immune problems. But as you can see, those intestinal gates don’t just poof open on their own—and it doesn’t happen to everyone who takes antibiotics.
The upstream problem in the brain and the resulting hormonal problem set the stage, and make the entire thing much more difficult to heal. Thus, in this type of patient, no matter how many heroic interventions she undertakes to battle this dysbiosis and inflammation—no matter how much she tries to suppress symptoms, detoxify, take probiotics, and affirm herself—trying to staunch the many, many, many, many, many symptoms that will follow—even if she tries to heal the gut lining—if nothing is being done about the HPA axis dysfunction, especially if she has progressed into Stage 3: She cannot get better. Glass ceiling, thy name is stress.
And because cortisol dysregulation is not considered real or important, it is thus a problem her regular doctors cannot or will not measure, and she herself cannot articulate. It is invisible. And it is related to her state of mind. But also to the state of her diet. And also to the uncontrollable bad things that happen in life. And also to the state of her sleep. And also to the state of her gut. And also to any infections she might have. Or head injuries. Or pain. It is not her fault. She is a product of her environment. And unfortunately, a broken HPA axis is not “fixable.” The hormonal pattern and the brain itself have to be retrained, and rehabilitated, and all the major stressors, internal and external, must be removed.
This is the beginning of an explanation as to why hormonal issues, adrenal issues, immune issues, and gut issues have anything to do with each other. I knew they did, but only in an observational way, not in a scientific way. It is the chronic state of compromised intestinal immunity which opens the gut up for any number of infections, general dysbiosis, and a leaky gut. This is directly related to cortisol.
Furthermore, as overall immunity goes down, the person is then open to ALL manner of infections (for example, Epstein-Barr, Lyme, Strongyloides)—that they are then unable to kick. It is a porous state of being. She is a sponge. ~ So, to recap: The gut is often the biggest, most hulking problem, and the gateway to many of the worst of the symptoms—but according to Dr. Tests and a whole lot of others, it isn’t the keystone. For most people, the keystone is upstream. The keystone is cortisol. Or, more accurately, the keystone is stress. Which is kind of bad news. Because Stress is probably the concept that all of us, including myself, treat with the lowest, most piddling regard. ~
“Stress.” Like energy, it is so amorphous and below consciousness most of the time, that “stress” is something we “know” is a “problem,” but we take almost no meaningful steps to “address.” Stress resides in the air quote part of our consciousness, along with other things we “should” do. Even in the alternative world, many people think that to address stress—or even to treat severe cortisol dysregulation—you just do yoga, or go on a retreat, or take some Gaia adrenal herbs, backstroking through a calming pool of lavender and unicorns, and that’s that. But in the functional medicine model, stress is measurable and central. Cortisol, as Dr. Gottfried says, is “the little hinge that swings big doors.” So first, it turns out, you have to test it properly. These tests will continue to evolve, but currently a four-point salivary test or a urine test is done throughout the day to measure how much cortisol you are producing at given points during the day. The test you would do at a regular doctor’s office for cortisol is a single blood test—but knowing what we know now about the dysregulatory pattern, you can see that a single blood test is insufficient. You need to see what the pattern looks like throughout the day. You need to know where you are on the spectrum of dysregulation. Then you and a practitioner need to investigate what is causing that stress for you specifically—so you can take the appropriate steps to slowly reverse the cycle. And this does take time, which no one likes to hear.
You need to search out all the ways you are pushing the red button—a high-sugar diet, stealth infections, gut infections, food sensitivities, a moldy home, poor sleep, or particularly bad relationships to other people, or to yourself. This is where trauma therapy definitely could play a role. Because if your main stressor is psychological—which it certainly could be—then that is what needs to be addressed. It’s just that often a psychological trauma is not the only stress, let alone the primary stress. And no matter what, you need to keep testing (you know, as with any major illness) to see how you’re progressing and to make sure you know when you’re getting better. This testing piece is extremely important. You don’t want, for example, to stop as soon as you feel a tiny bit better, go join a political campaign with eighteen-hour workdays, only to spiral again into the abyss. (For example.)
Finally, once all underlying factors have been removed or remediated, then you need to retrain your nervous system—teaching it to move from defaulting to fight-or-flight mode (the sympathetic nervous system) to defaulting to “rest and digest” mode (the parasympathetic nervous system). This is where all of the things we are familiar with come in—yoga, meditation, acupuncture, brain retraining, tapping, trauma therapy, vagus nerve stimulation, and positive thinking. But in the functional medicine model that must—must—come after you’ve stabilized the foundation of a blood sugar–stabilizing diet, healed the gut, if necessary, sussed out any infections or heavy metals, and addressed any environmental issues in the home, like mold. You can’t meditate yourself out of mercury poisoning. The tricky bit is, you have to be doing this in a systematic, logical, monitored environment. That’s the issue. You can’t swing from acupuncture to a vegan diet to a paleo diet to a twenty-one-day fast like a wild monkey—while simultaneously drinking loads of whiskey, or still consuming gluten, or still running around trying to achieve huge goals, save the world, save the women, or trying to take care of everyone but yourself. You have to fully reset. And you have to do it in the right ways, with a good guide.
Otherwise, the bathtub stopper isn’t in place, and you just keep pouring everything—time, energy, herbs, money, hopes, dreams—down the drain. A familiar story. And you can see how hard this would be for someone who is already in an incredible amount of pain, not getting the proper care, not believed, and not given any of the right information to help herself. She is in perpetual flight. And as this WOMI spirals down and down and down, the whole thing compounds on itself, because the endless descent into darkness is nothing if not stressful. It is truly a vicious cycle. ~
And of course the issue is not just cortisol. Cortisol is simply the mascot, the metaphor, the surrogate, the rep. The deeper issue, the much more serious issue, is stress. Stress defined anew. Looking at this family of diseases as the aggregate of too much stress, both internal and external, both physical and emotional, over many, many, many years—with the understanding that stress has a real, physiologic, quantifiable, and cumulative impact on the body—almost all of the disparate research that exists around these topics starts to make sense. The literature shows that ongoing stress can damage or change: Mitochondria, the powerhouse of the cell that produces our cellular energy. DNA, switching disease genes on or off based on the cellular environment. Cell receptor sites, making it difficult to get certain basic nutrients like calcium in and out of cells. The autonomic system. The immune system.
…Then there are discussions to be had about the wide range of experimental treatments coming down the pike—and a functional medicine doctor is a good person to have this discussion with. Fecal transplants look like they might hit the market soon, which could be exciting, or at the very least, interesting. Some practices are trying more tech-based treatments that help rewire the hypervigilant brain, such as transcranial magnetic stimulation (TMS) or vagus nerve stimulation (VNS). Some are hoping to come at the same problem with a psychogenic approach—for example, using psilocybin, a psychedelic being studied primarily at Johns Hopkins. More and more people are being checked and treated for having a range of different issues in the spine—from spinal fluid leak, to craniocervical instability, to spinal stenosis—which turn out to be fairly common in WOMIs, and a few prominent patients with ME/CFS have gotten radically better from those spinal procedures. Others are anticipating a medication called larazotide, which is being developed and may help with regulating zonulin, which would speed up the healing of a leaky gut. There is a drug called rituximab, which depletes B cell formation, used sometimes for patients with autoimmune diseases and some CFS patients. There is a drug called Mestinon, shown to be useful in POTS, and possibly mast cell activation syndrome. There is a new drug called Ampligen, which shows some promise for immunomodulation. There is a drug many ME/CFS patients feel hopeful about called suramin, which is a drug that may turn off what Dr. Robert Naviaux at UC Davis calls the cell danger response, as well as a new drug being studied called Cortene, which addresses the maladaptive response in the limbic system. There are medications for those of us who have POTS to increase our blood volume, such as fludrocortisone. Some are using ketamine infusions and inhalers and creams for severe pain and depression. And then of course there is the ubiquitous antidepressant, which certainly can relieve some symptoms for some people….
…We just have to keep in mind the bigger picture. When we look at the things that are working, from dietary change to neural retraining to low-dose naltrexone to larazotide, these things always revolve around the same principles: Fixing dysbiosis and leaky gut. Correcting nutrient deficiencies. Retraining a hyperreactive brain, stuck in fight or flight. Lightening the toxic load. Treating infections. Regulating stress, metabolic, and sex hormones. Calming inflammation, histamine issues, and microglial inflammation. Supporting the mitochondria, and supporting the methylation pathways. And it is just not possible to address all of that for this hugely diverse patient population with one miracle drug or surgery. A wide battery of things got us here in the first place, and so while we all support radically increased research and funding for the drugs that will help us get better, faster, I believe we need to protect ourselves from the temptation of believing that one intervention is going to press reset and put things back to normal, for all of us, forever.
Functional medicine has a long way to go. I want to reiterate that all I’m recommending is learning about this model, not spending your life savings on it. If you can find a doctor in traditional medicine who is covered by insurance, will look for gut dysbiosis, knows how to treat MCAS and POTS, is well versed in chronic Lyme and ME/CFS and the whole WOMI spectrum—by all means, see that doctor. There are a few clinics around the country run by more traditional physicians who do….
As we keep our attention and our ingenuity and our dollars focused on the correct metrics, this model of medicine is going to become more accessible, more streamlined, and more affordable. I can easily imagine a not-too-distant future where a WOMI goes to the doctor, and straight out of the gate she gets a fecal transplant, a round of transcranial magnetic stimulation, and a single dose of suramin—and that being an immediate jump start on the way back to health.