Your immune system lives to protect you. Like an elite security detail, it guards your body’s perimeters and swiftly deals with troublemakers, such as minor pathogens and cancer cells. It uses a range of tools, including the inflammatory response and specialized immune cells that attack invaders. Once it has vanquished the enemy, the immune system settles back into a state of cool, calm surveillance.
Or at least that’s how it’s supposed to work.
Sometimes the immune system gets confused and attacks the body it’s meant to protect. This is called autoimmunity, or, literally, immunity to self.
Autoimmunity encompasses more than 100 known conditions, including type 1 diabetes, rheumatoid arthritis, lupus, multiple sclerosis, and inflammatory bowel disease. And the number of such diagnoses has continued to rise as healthcare providers have begun to recognize the prevalence of immune dysregulation.
“Twenty-five to 50 million Americans have some kind of disease characterized by dysregulation of the immune system,” says Leonard Calabrese, DO, director of the Cleveland Clinic’s R. J. Fasenmyer Center for Clinical Immunology. Symptoms can include joint pain, recurring fever, skin problems, fatigue, swollen glands, and gastrointestinal issues.
But diagnosing autoimmune conditions can be tough. There’s typically no single conclusive test, and many conditions mirror each other. A care provider may need to consider symptoms (which often fluctuate), blood markers, and other factors.
According to the Institute for Functional Medicine, latent or pre-autoimmune disease often exists for seven to 14 years before diagnosis.
The Challenge of Autoimmunity
Autoimmunity rates have been rising steadily for decades, and experts suspect that increasing exposure to environmental toxins may be to blame (more on this later). But the COVID-19 pandemic could be responsible for a massive influx of members to this club that no one wants to join.
The virus that causes COVID was dubbed the “autoimmune virus” in a 2020 article in Autoimmunity Reviews; the authors cited a strong association between the viral infection and the development of autoimmunity. Research shows that the novel coronavirus may activate preexisting “autoantibodies” — the immune proteins that target a person’s own tissues — as well as prompt the body to make new ones.
How can a virus cause the immune system to turn on itself? It apparently has to do with the delicate balance and regulation of this complicated system.
“How viruses interact with our immune system is at the forefront of understanding autoimmunity.”
“The immune system doesn’t work like a radio with a volume control,” explains functional-medicine internist Leo Galland, MD. “It’s more like an orchestra with many different sections that interact with each other. The interactions are dynamic and complex, and the outcome of a novel interaction can be hard to predict.”
Several factors can make us more likely to develop autoimmunity, and genes are one of them. “Some genetic polymorphisms put people more at risk,” says functional-medicine practitioner Keesha Ewers, PhD, ARNP, FNPc, MSN, author of Solving the Autoimmune Puzzle. Polymorphisms on the major histocompatibility complex (MHC) genes that code proteins for the adaptive immune system, for example, can create greater susceptibility.
But a genetic proclivity doesn’t guarantee autoimmunity. “Genes are the cards you’re dealt at birth, but it’s how you play your cards that determines how your genes function throughout your life,” explains Calabrese.
Autoimmune conditions require five basic ingredients, according to pediatric gastroenterologist Alessio Fasano, MD: genetics, environmental triggers, loss of gut-barrier function, a belligerent immune system, and an imbalanced microbiome (dysbiosis).
For instance, if you have a genetic intolerance to gluten, eat a gluten-heavy diet, and develop a leaky gut, “your immune system is already angry,” says Ewers. A baseline state of chronic inflammation sets the stage for an environmental trigger, such as a virus or parasite, to activate a dysregulated immune response.
Traditional approaches to treating autoimmunity involve medications that suppress symptoms without addressing root causes, so many people with one autoimmune condition soon develop others. One study found that a single autoimmune diagnosis increases the likelihood of a second (or third) diagnosis by up to 34 percent.
By contrast, addressing the root causes of a dysfunctional immune response makes it less likely that the immune system will expand its attack in other areas of the body, forgoing the need for ever more band-aids that simply suppress symptoms.
One study found that a single autoimmune diagnosis increases the likelihood of a second (or third) diagnosis by up to 34 percent.
Although the presence of autoantibodies is usually a critical indicator in diagnosing autoimmune conditions, not everyone who has detectable autoantibodies has active autoimmune disease. Those with autoantibodies but no autoimmune symptoms are considered to have “pre-autoimmunity.”
Yet because the internal environment is a key influence on autoantibodies’ behavior, certain precautions can enable these people to remain symptom-free. “Some of the most common autoantibodies we produce only create damage when there’s also systemic inflammation,” explains Galland.
The exact provocations for autoimmunity are still poorly understood. Stress, which includes toxic relationships and thought patterns, is a known trigger, says Ewers. But so are many pathogens, such as the bacteria that cause Lyme disease, and viruses such as Epstein-Barr, herpes, human papillomavirus (HPV), and coronaviruses such as SARS-CoV-2.
Ewers suspects that environmental toxins such as cigarette smoke, pesticides, allergens, and molds can potentially activate autoimmunity. She also focuses on estrogen-mimicking chemicals, including bisphenol A (BPA), which is found in plastic, canned foods, and personal-care products. These chemicals can disrupt the modulation of inflammatory proteins called cytokines, which may be one reason women appear to be more susceptible than men to autoimmunity, representing nearly 80 percent of all cases.
It sounds like a hodgepodge, but these suspected triggers are more alike than they seem. Calabrese notes that they are all part of the body’s “exposome,” or the sum total of its exposure to environmental stressors.
“The exposome is everything from pollution and chemicals in food and water to how we eat, exercise, sleep, and handle stress,” he explains. Researchers are just starting to understand the exposome’s role in autoimmunity.
The Virus Question
Viruses outnumber everything on the planet. Some we catch, like SARS-CoV-2 or HPV; others have been incorporated into the human genome and bestow benefits such as disease resistance or starch digestion.
As journalist Moises Velasquez-Manoff writes in An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases, viruses we catch help with training and balancing the adaptive immune system, providing external stimuli that may help prevent autoimmunity.
But viruses have also long been suspected as autoimmune triggers. Epstein-Barr (best known for causing mononucleosis) has been linked to lupus, and influenza can trigger a blood-clotting disorder called autoimmune thrombocytopenia. Chikungunya, a mosquito-borne virus, can cause chronic inflammatory rheumatic diseases.
Now SARS-CoV-2 appears to trigger its own autoimmune cascade, which is revitalizing researchers’ urgency to understand the role of viruses in these conditions. “How viruses interact with our immune system is at the forefront of understanding autoimmunity,” says Calabrese.
Many COVID victims die not from the virus itself but from an overactive immune response to it, characterized by the “cytokine storm.”
One of the most potent effects of SARS-CoV-2 is on the human immune system. Many COVID victims die not from the virus itself but from an overactive immune response to it, characterized by the “cytokine storm.” (Cytokines are inflammatory immune proteins that, in large quantities, can destroy the body’s tissues and organs.) And many who survive COVID seem to generate copious amounts of autoantibodies — the proteins that target the body’s own tissues.
“The question is, What are those autoantibodies doing?” says Calabrese. “Are they predisposing people to inflammation and autoimmunity? Are they contributing to the pathogenesis of long COVID?”
There are multiple theories on how SARS-CoV-2 may be triggering the autoimmune symptoms (including brain fog, fatigue, headaches, dizziness, joint pain, fever, and mood disorders) that have come to be associated with long COVID. The first theory is called molecular mimicry, in which viral proteins that resemble proteins in the body spur the creation of antibodies that attack the body’s own cells.
Another possibility is that inflammation from the infection primes the immune system to mistake the spilled contents of destroyed cells as foreign and create autoantibodies against these cellular pieces.
Again, the health of the gut seems to play an important role. “People with COVID-19 have changes in the gut microbiome of a type that fosters inflammatory reactions,” says Galland. “The bacteria that provoke more inflammation grow, and anti-inflammatory bacteria are suppressed in the GI tract.”
(For more on how mRNA COVID vaccines may resolve some autoimmune symptoms, see “Long-Haul-COVID Recovery and Vaccines”.)
Repairing the Terrain
One of the greatest challenges with autoimmune conditions is that they can affect multiple body systems. A 2020 study in the Journal of Autoimmunity examined how autoimmune processes may account for the widespread damage caused by some COVID infections, including inflammation of the heart and circulatory system. Circulatory damage can lead to loss of oxygen in the body’s tissues; this in turn slows the function of mitochondria, the energy-producing powerhouses in our cells.
“Immune cells require energy to work properly,” says Galland. “If you have a smart TV and the remote’s battery starts to die, the TV starts doing screwy things. When the power source diminishes, it’s not just that everything gets dim — it gets wacky. That’s the impact of mitochondrial damage on the immune system.”
While researchers still have much more to learn about long COVID, functional-medicine practitioners are already reaching for proven strategies that have helped people manage other autoimmune conditions. There is no one-size-fits-all protocol, but some basic principles apply.
“I go to individualization — what’s at the root?” asks Ewers. “Why was this terrain susceptible to this virus, and what form did it take? Then the treatment protocol matches those things.”
Keep reading to learn about the main tenets of a functional-medicine approach to treating autoimmunity.
The Functional-Medicine Approach to Treating Autoimmunity
An Anti-Inflammatory Diet
An anti-inflammatory diet is one of the most important tools for managing autoimmune conditions. “Many predisposing factors to poor outcomes [from autoimmunity] come from chronic inflammation, and a largely plant-based diet is a great start toward lowering inflammation,” says Calabrese.
Several special diets have proven to be helpful for people with autoimmune disease, including the Wahls Protocol, Autoimmune Protocol, and variations on the paleo diet. While they vary in their specifics, they share an emphasis on fresh, whole, unprocessed foods; plenty of colorful vegetables; abundant fermented foods; bone broth; and healthy fats. They also minimize sugar, processed carbs, alcohol, dairy, and caffeine.
Ewers recommends working with a functional-medicine provider to identify specific food sensitivities, absorption issues, or nutrient deficiencies. Using diet to manage inflammation and support circulation and mitochondrial function can make a huge difference in autoimmune symptoms and quality of life.
The gut microbiome plays a crucial role in immune function. “The microbiome controls so much of how the immune system responds to invaders,” says Ewers. A comprehensive stool analysis can help identify imbalances in the microbiome, such as a lack of beneficial bacteria or an overabundance of harmful microbes, parasites, or yeast.
“We see similarities between long COVID and chronic fatigue syndrome in the microbiome,” says Galland. For long COVID, he recommends supplementing with specific bacteria strains, such as Bifidobacterium longum BB536 and a form of Bacillus subtilis, which may help stabilize and reorganize the gut microbiome. Studies show that eating avocados and chickpeas may also support the growth of anti-inflammatory bacteria, he notes. (For more on microbiome health, see “Your Microbiome: The Ecosystem Inside“.)
Sleep helps restore the immune system. Insufficient sleep (less than seven or eight hours per night) has been linked to the production of inflammatory cytokines. But many people with autoimmune conditions have disturbed sleep patterns; they may suffer from profound fatigue and struggle to regularly sleep through the night.
Working with a functional-medicine provider to integrate sleep-hygiene techniques, such as ritualized sleep–wake cycles, environmental and dietary modifications, and (potentially) melatonin therapy, can help restore healing and supportive sleep patterns. (For more on sleep, see “Sleep It Off“.)
Exercise is key for healthy immune function. Multiple studies have shown that moderate exercise offers benefits for patients with autoimmune conditions — including improvements in joint mobility, mood, cognitive ability, energy, and quality of life. If you’ve received a diagnosis recently or are easing into exercise after being sedentary, start with gentle, moderate movement as you build up strength and stamina, and be sure to consult with your provider.
There is no singular supplement protocol that will achieve the same results in everyone with autoimmunity. Most functional-medicine providers make supplement recommendations based on a person’s specific test results and symptoms. Still, these are some of the most common supplements used to support better health and function for a variety of autoimmune conditions, including long COVID, and each one has a range of salutary effects.
- Vitamin D3: Insufficient vitamin D is associated with a number of autoimmune diseases. Raising low levels may help mitigate disease severity and progression and help repair a leaky gut.
- Curcumin: This potent anti-inflammatory chemical is found naturally in turmeric.
- Resveratrol: A polyphenol found in peanuts, berries, and red grapes, resveratrol may help reduce the production of autoantibodies, among other immunomodulating effects.
- Fish oil: This oil contains EPA and DHA, anti-inflammatory omega-3 fatty acids that Ewers says help with healthy gene expression.
- NAC: Short for “N-acetyl-L-cysteine,” NAC helps the body make the antioxidant glutathione, which protects against cellular damage and supports immune health. Combining NAC with niacin can help support mitochondrial function, says Galland.
- CoQ10: Naturally produced by the body and also available in supplement form, this antioxidant supports circulation and mitochondrial function.
Psychoneuroimmunology is a burgeoning area of immune science based on the insight that the central nervous system and immune system are intertwined. “The brain and the immune system are one organ,” explains Calabrese.
To manage the stress of autoimmunity itself, Ewers believes we may also need to look directly at the “autoimmune mindset” — a sense of being at war with oneself.
“People are always looking to be done,” notes Ewers. “The expectation is that we kill the yeast in our gut, get our hormones balanced, and the body should shape up.”
But people with autoimmune conditions need to accept that creating health is a long-term process that involves all the layers of our being — physical, energetic, mental, emotional, and spiritual. “There are no quick fixes or tricks for immune health,” notes Calabrese. “It’s a process.”
Autoimmune patients need to treat their bodies with unconditional love. . . . Praise them when they get it right, and when things go wrong, offer some help and support.
We can use tools like mindfulness meditation, which has shown a capacity to lower inflammation and tamp down inflammatory genes. Mind–body techniques such as yoga, tai chi, and qigong can reduce autoimmune activity. But overall, the recovery process requires patience and lots of self-love.
“When we have expectations that aren’t being met, that’s one thing that sets the immune system off the worst,” says Ewers. She believes autoimmune patients need to treat their bodies with unconditional love, the way we would children who are learning a new skill: Praise them when they get it right, and when things go wrong, offer some help and support.
“It’s about getting into a collaborative instead of a combative relationship with yourself.”
This article originally appeared as “Autoimmunity Now” in the January/February 2022 issue of Experience Life.