The Inflammation Gap

My patient’s lungs were filled with blood, and he lay intubated in an ICU bed. His kidneys were failing, too. The cause of his illness was not a mystery: He had been previously diagnosed with an autoimmune disease that, in many cases, leads to severe organ damage, and he clearly needed the same treatment he’d received before, a drug that suppresses the immune system. With it, he started to improve in days. At a follow-up visit, I suggested re-dosing the medication in a few months, to prevent future episodes of life-threatening inflammation. That word caught his attention. “What caused it?” he asked. “The inflammation, I mean.” He and his wife exchanged uncertain glances as I explained that doctors don’t know what sets off most autoimmune inflammatory diseases: It’s likely a complex interplay between genetics, environment, and bad luck. But we do know how to treat them. At the next visit, his wife asked me about the potential causes of chronic inflammation that she’d read about online—tick bites, heavy-metal exposures, nutritional deficiencies—as well as anti-inflammatory treatments including herbal supplements, acupuncture, and energy healing. I began to worry that framing the conversation around inflammation—a word that clearly meant one thing to me and quite another to this couple—had been a mistake. Doctors caring for patients with autoimmune diseases have long thought of inflammation in precise terms: Cells of the immune system lodge in tissues and release messenger molecules, called cytokines, that rev up the body’s response to a perceived insult. In recent years, scientists have been able to identify many cytokines and create targeted therapies for a host of disabling, sometimes fatal, diseases. At the same time, popular culture has latched on to the concept of inflammation and made it a catch-all term for “something amiss in the body”—a bête noire for wellness gurus, health influencers, and the “Make America Healthy Again” movement. A YouTube or TikTok search for chronic inflammation might lead to Josh Farris, also known as “The Gut Guy,” who argues that rubber-soled shoes prevent us from connecting to the earth and force the body to steal energy from other cells, causing “an inflammation loop cycle.” The MAHA report, which the White House released in May, suggests that ultra-processed foods and the overuse of medications may be contributing to chronic inflammation in children. Even as conventional treatments for autoimmune diseases have become more effective than ever, alternative treatments, including nutritional supplements, breathing exercises, hyperbaric oxygen chambers, and cold plunges in frigid water, have proliferated. Andrew Weil is perhaps the person most responsible for inserting the phrase anti-inflammatory into the American lexicon. Weil, a Harvard Medical School graduate who completed his internship before deciding to explore nontraditional medical practices, told me that his views on inflammation are simple and have not changed over the decades. According to Weil, acute inflammation is a natural, protective response to injury or infection and is an important part of healing. Chronic inflammation is a low-level, persistent activation of the immune system that can damage the body over time and is linked to ailments such as cardiovascular disease, neurodegenerative diseases, cancer, and autoimmune conditions. Weil argues that following his anti-inflammatory food pyramid and taking up practices such as meditation, yoga, and tai chi can help prevent and treat these diseases of chronic inflammation. To support his claims, Weil cites population studies showing that people who maintain a diet high in fruits, vegetables, and whole grains have lower rates of heart disease, diabetes, and some cancers than those who don’t consume these products. He also points to studies showing that certain foods and spices, including turmeric and ginger, can inhibit key regulators of the immune system, reducing cytokine production. When I asked Weil about proof that these interventions work, based on randomized clinical trials, he told me that he believes such studies are not necessary when an intervention is unlikely to cause harm. “I grade evidence on a sliding scale,” he said. Weil’s anti-inflammatory message has germinated across the internet in tweets, podcasts, and YouTube Shorts. The result is a hodgepodge of myths and theories about how to address the issue that go well beyond advice to just eat well and meditate. Juice cleanses are fashionable in certain anti-inflammatory circles, even though they can cause electrolyte imbalances. A popular notion on TikTok is that hidden parasites are a common cause of chronic inflammation and that ingesting wormwood—a bitter herb that can lead to liver injury—will rid the body of this problem. Other videos encourage viewers to ingest water laced with borax, a powdery substance found in laundry detergent, in order to reduce inflammation and joint pain. Most claims made by health gurus and social-media influencers are exaggerated. “If it sounds too good to be true, it is,” Richard Panush, a rheumatologist and emeritus professor at the University of Southern California, who has studied alternative therapies for autoimmune diseases, told me. Some of their recommendations are outright dangerous. Still, these ideas are clearly enticing to patients feeling beaten down by chronic disease. One recent study showed that, among people with an autoimmune condition, more than 80 percent have tried some form of complementary and alternative medicine. In my experience, most patients gravitate toward interventions on the milder end of the spectrum, such as acupuncture and herbal remedies, but even these can be problematic if taken to the extreme. One patient of mine told me that, at a certain point, he was consuming 60 supplements a day, putting him at risk of adverse interactions with his prescription medications. In decades past, alternative therapies may not have seemed so outlandish compared with  conventional therapies, which often had significant side effects and limited efficacy. Now, though, doctors like me can prescribe treatments that turn many debilitating diseases into manageable conditions. People with rheumatoid arthritis can be treated with one or two medications and expect to experience disability-free lives with few to no symptoms. Surgeons used to routinely remove the colons of individuals with ulcerative colitis, but an injection or infusion of medication every few weeks can put those patients in remission. The key to these advances has been the development of certain biologics that target key pathways in the immune system and selectively block the activity of pro-inflammatory cytokines. Dozens of FDA-approved biologics are now available to patients for diseases including psoriasis, Crohn’s, and multiple sclerosis. The future is even more promising with therapies like CAR T cells, which are genetically modified “living drugs” that have had remarkable success in clinical trials, particularly for lupus. This is not to say that conventional therapies come without costs. Using a medication meant to suppress the immune system has an inherent trade-off: Autoimmunity may be better controlled, but the risk of infection increases. The list price for some biologics can reach $7,000 a month, and patients receiving infusible medications must arrange travel plans around the timing of their therapy. Alternative health might be appealing for another reason. Because doctors cannot give a simple explanation as to why most autoimmune conditions developed in the first place,  patients may look elsewhere for insights and solutions. Some autoimmune diseases also can remit on their own for reasons that remain unclear, implying that not every patient may require lifelong therapy. For doctors, though, taking the wait-and-watch approach feels risky when the stakes are high: Not treating a disease, in the hopes that it’ll resolve naturally, could leave someone with, say, joint erosions or renal failure. “I frequently tell patients, ‘I’m overtreating you’ because we can’t predict if your disease will cause irreversible damage,” Philip Seo, a rheumatologist at Johns Hopkins University, told me. “We can’t go back in time.” Conversations with patients about if and when to start medication have always been complex, but online lore about inflammation, coupled with declining confidence in doctors since the coronavirus pandemic, have made such discussions more fraught. “It comes down to trust,” Panush, the rheumatologist who researches alternative therapies, told me, “which I’m afraid doctors are losing from patients who have adopted a different belief system than their own.” I saw that happen with my own ICU patient, whose condition had been so dire. He and his family were willing to accept immune-suppressing therapy when he was critically ill, but his calculus changed once he was doing better. I tried to provide clear recommendations while making him and his wife feel heard, but it seemed like we were talking past each other. Eventually, he stopped showing up for appointments. I called multiple times to check in, but there was no answer. A year later, I learned that he had died. His obituary didn’t mention his autoimmune disease, the most likely cause of his death. Instead, it said he had died from agricultural and industrial pollution.