Acetylcysteine

While social media continues to circulate claims linking acetaminophen to autism in children, medical experts say those fears distract from a far more serious and proven danger: overdose. Acetaminophen, found in Tylenol and many cold and flu remedies, is one of the leading causes of emergency room visits, hospitalizations, and acute liver failure in the United States.Social media and news feeds are filled with unverified claims about a possible connection between acetaminophen and autism in children. But medical experts say the far more serious and well-documented concern is something else entirely: overdose from the widely used pain and fever medication. Acetaminophen poisoning is one of the leading causes of hospitalization and death related to non-prescription drugs in the United States, according to Kennon Heard, MD, PhD, a professor in the CU Anschutz Department of Emergency Medicine and the department's section chief of medical toxicology. Each year, an estimated 56,000 people visit emergency departments because of acetaminophen poisoning, and about 2,600 are hospitalized. The drug is responsible for nearly half of all acute liver failure cases in the U.S. and roughly 20% of liver transplants nationwide. Heard has studied acetaminophen poisoning for more than 25 years. He is now helping to lead a long-term clinical trial that is testing a potential new way to reduce liver damage in severe overdose cases. The experimental approach uses a medication typically given to patients poisoned by antifreeze. Heard says CU and Denver Health, which is home to the Rocky Mountain Poison & Drug Safety center, have played a central role in this research for decades. "have been the center of the acetaminophen research universe for the past 40 years. There's been a long history of this type of work being done here, and it's great to be a part of it." Why Acetaminophen Overdoses Happen Acetaminophen is the main ingredient in Tylenol and many store-brand pain relievers used for mild to moderate pain and low-grade fever. It is also included in a wide range of over-the-counter products for colds, flu, sinus symptoms, and menstrual discomfort. The medication has been used safely for decades when taken according to instructions. Problems arise when people exceed recommended doses, either by taking too much at once or by repeatedly taking more than advised over time. "There are cases where people accidentally take too much acetaminophen," Heard says. "Or maybe they have a really bad toothache, and they think if two is good, four is better, eight is even better, and so on. Or it's someone who's taking multiple repeated overdoses. Those are the people who get into trouble." Overdoses are also frequently linked to suicide and self-harm, Heard notes. "The No. 1 rule at the Poison Center is that if it's available, people will take it, and a lot of people have Tylenol in their medicine chest." Limits of the Standard Antidote For decades, doctors have relied on a drug called acetylcysteine as an effective antidote for acetaminophen overdose. When given early, it can prevent serious liver damage. Its effectiveness drops sharply, however, if treatment begins more than eight hours after the overdose. "The problem is that many patients don't present with acetaminophen poisoning until after they have liver injury, at which point the acetylcysteine is less effective, and in some cases doesn't really work at all," Heard says. Testing an Antifreeze Antidote The current clinical trial led by Heard and his colleagues is focused on fomepizole, a drug approved to treat poisoning from ethylene glycol and methanol, substances commonly found in antifreeze. Exposure can occur accidentally, and in some cases people with alcohol use disorder have consumed antifreeze as a substitute for alcohol. Fomepizole works by blocking enzymes known as alcohol dehydrogenase, stopping the body from converting ethylene glycol and methanol into toxic byproducts. Heard says interest in using fomepizole for acetaminophen overdose dates back to the 1990s, when he was training in medical toxicology. Evidence came from individual patient case reports and animal studies, particularly in severe overdose cases. More recently, research has shown that doctors are increasingly using fomepizole off-label to treat serious acetaminophen poisoning. Richard Dart, MD, PhD, a professor of emergency medicine and Heard's longtime mentor, ultimately suggested formally testing the drug in a clinical trial. Dart has served as director of Rocky Mountain Poison & Drug Safety since 1992. A Proof of Concept Clinical Trial The ongoing phase II trial is designed to determine whether adding fomepizole to standard acetylcysteine treatment can reduce liver damage in patients at high risk after acetaminophen overdose. It is considered a "proof of concept" study to see whether the combination shows enough promise to justify larger trials. Participants are randomly assigned to receive either both medications or acetylcysteine alone. The study is double-blind, meaning neither the patients nor the researchers know which treatment each participant receives until the trial ends. "We'll compare the amount of liver damage, as measured by their liver enzymes, to see whether the fomepizole provides an added protective benefit beyond the standard treatment," Heard says. Patients are currently being enrolled at Denver Health, UCHealth University of Colorado Hospital, Children's Hospital Colorado, and several additional sites. Enrollment has been slow due to the challenge of finding patients who meet the study criteria, but researchers hope to enroll about 40 participants within 12 to 18 months. If the findings are positive, Heard expects the research to move into a larger trial that would examine longer-term outcomes, including survival and the need for liver transplants. A Caution for Medicine Cabinets Everywhere "The message that I would want to get out," Heard says, is that people should carefully read medication labels, avoid exceeding recommended doses, and recognize that acetaminophen may be present in multiple products at home. "We've started to recognize that the number of people who die from an accidental overdose is pretty close to the number of people who deliberately take an overdose," he says. Heard's collaborators on the study include Dart and Andrew Monte, MD, PhD, also a professor of emergency medicine.

Long COVID affects an estimated 65 million people worldwide and can damage the brain, heart, blood vessels, and immune system long after infection. Researchers now link symptoms to lingering virus, inflammation, micro-clots, and disrupted energy metabolism. While structured rehab and pacing can improve quality of life, a growing list of experimental treatments—from antivirals and metformin to microbiome therapies and biologics—shows early promise. Clear answers, however, are still limited by small studies and the lack of large, definitive trials.Long COVID is defined as symptoms that last at least two months after an initial SARS-CoV-2 infection, with no other clear medical explanation. An estimated 65 million people worldwide are now affected, yet there are still no approved, evidence-based treatments. Researchers are working to better understand what drives the condition and to test a wide range of possible therapies, from structured rehabilitation programs to antivirals, blood thinners, anti-inflammatory drugs, supplements, and new biologic treatments. Scientists believe long COVID is fueled by several overlapping biological problems. These include lingering virus in the body, ongoing low-level inflammation marked by elevated IL-1β, IL-6, and TNF-α, and the formation of tiny blood clots caused by interactions between the viral spike protein and fibrinogen. Other contributing factors include auto-immunity, disruptions in gut bacteria, and impaired mitochondrial function. Together, these processes can damage multiple organs, leading to blood vessel dysfunction, heart inflammation, neuro-inflammation, small-fiber neuropathy, ME/CFS-like fatigue, menstrual changes, problems with blood sugar regulation, and kidney or liver injury. Rehabilitation and Non-Drug Approaches For people with mild symptoms in the early stages, non-drug treatments remain the first option. Clinical trials show that online, group-based physical and mental rehabilitation programs can improve quality of life. Breathing exercises and inspiratory-muscle training have also been shown to boost heart and lung fitness. Additional strategies may include pacing daily activities, cognitive and speech therapy, smell retraining, and dietary counseling. However, exercise that is not carefully supervised can worsen inflammation. For this reason, activity programs need to be gradual and adjusted based on symptoms. Antivirals and Early Treatment Effects Antiviral drugs taken during the initial COVID-19 infection appear to slightly reduce the risk of developing long COVID. In Japan, ensitrelvir lowered long-COVID rates by 25% among out-patients. In high-risk individuals, nirmatrelvir/ritonavir and molnupiravir were linked to about a 25% reduction in risk, while favipiravir showed little benefit. Researchers are also studying monoclonal antibodies that target the spike protein for possible effects on neuro-toxicity, although phase-3 trial results are not yet available. Medications Targeting Specific Symptoms Some treatments focus on particular complications such as clotting, autonomic nervous system problems, and immune imbalance. Low-dose naltrexone has been shown to reduce fatigue and lower platelet aggregation. Apheresis can remove micro-clots and auto-antibodies from the blood, but it is expensive and its benefits tend to be short-lived. Other medications are being tested for symptom relief. β-blockers are used to treat postural-tachycardia syndrome. Famotidine, intravenous immunoglobulin, SGLT-2 inhibitors, and GLP-1 agonists are under investigation for neurological, immune-related, heart, and kidney symptoms. Targeting Inflammation at Its Source Reducing inflammation early appears to be one of the most active areas of research. When started within seven days of infection, metformin lowered the risk of long COVID by 41%, likely by reducing mTOR signaling. Plant-based supplements containing quercetin, curcumin, and piperine improved fatigue compared with placebo. Other approaches include sulphur-thermal-water inhalation and enzymatically liberated salmon oil, both of which lowered CRP levels and helped restore the lung's protective barrier. Baricitinib and rapamycin, which act on JAK and mTOR pathways, are now entering multi-centre trials aimed at interrupting widespread STAT3-driven inflammation. Gut Health, Supplements, and Energy Metabolism Adjusting the gut microbiome may also help. The synbiotic SIM01 eased overall symptoms after six months. Small randomized trials suggest that high doses of vitamins C and D, coenzyme Q10, magnesium, and creatine-glucose blends can improve cellular energy production and blood vessel function. Early-stage studies also report benefits from N-acetyl-cysteine and the amino-acid blend AXA1125, both of which improved mitochondrial respiration and reduced fatigue. Experimental Biologics and Emerging Therapies New biologic treatments are exploring the role of fibrin-driven neuro-inflammation. A humanized antibody that blocks the inflammatory region of fibrinogen is currently in phase-1 trials after animal studies showed protection against neuronal loss. Another experimental therapy, the DNA aptamer BC007, removes G-protein-coupled-receptor auto-antibodies and reversed fatigue and poor capillary blood flow in a single patient, though larger trials are still needed. Other non-drug approaches have shown potential. Hyperbaric oxygen therapy improved cognition, sleep, and pain in a six-month randomized trial. Case series of acupuncture reported reductions in brain-fog and joint pain. Vaccines and Long COVID Outcomes Vaccination provides limited protection against long COVID after breakthrough infections, lowering risk by about 15 to 41%. Among people who already had long COVID symptoms, outcomes after a booster were mixed. About 17% improved, 21% worsened, and 62% saw no change. Where the Science Stands Now Although many potential treatments are showing early promise, most evidence still comes from small or open-label studies that rely on indirect outcome measures. Large, adaptive randomized trials with consistent definitions and biomarker-based patient grouping are urgently needed. Until clearer answers emerge, experts support a flexible, team-based approach that includes early antiviral use, carefully graded exercise, targeted anti-thrombotic and anti-inflammatory treatments, gut microbiome support, and personalized rehabilitation. This strategy reflects the diverse, multi-system nature of long COVID while researchers continue searching for definitive, mechanism-based cures.