Herxheimer Reaction in Chronic Fatigue Syndrome (ME/CFS)
What is the Herxheimer Reaction?
The Herxheimer reaction, also known as a Jarisch-Herxheimer reaction, is a temporary worsening of symptoms that occurs when harmful pathogens are rapidly killed off in the body. This can happen during treatment with antibiotics, antivirals, antifungals, or even certain supplements. As these pathogens die, they release toxins (endotoxin), causing an immune response and an increase in cellular inflammation (cytokines) that leads to varied symptoms.
This reaction was first discovered in 1900 by 2 German researchers studying Syphilis. The reaction is now recognized as a common occurrence when treating bacterial, viral, or fungal infections with medications. Yet, it is still poorly understood.
This reaction is often referred to as a "healing crisis" or detox reaction because, despite the discomfort, it is seen as a sign that the treatment is working to eliminate the underlying infection. The reaction typically lasts from a few hours to a few days and eventually subsides as the body handles the initial reaction. It should not be confused with an adverse reaction or allergic reaction.
Symptoms of Herxing
A drop in systolic blood pressure (top number)
Severe musculoskeletal and joint pain (often uncontrolled with analgesics)
Migraines
Sore throat
Severe bloating and intestinal cramps
Extreme fatigue
Sweating and chills
Nausea
Brain Fog
How Can You Tell if It’s a Herxheimer Reaction?
While there’s no specific test to diagnose a Herxheimer reaction, there are some key indicators:
Timing: Symptoms usually worsen shortly after starting or increasing the dosage of a treatment, often within hours or a few days.
Short Duration: A Herxheimer reaction usually lasts a few hours to a few days and then subsides as the body clears the die-off products.
It’s important to rule out other causes, such as medication side effects or a true allergic reaction, which could also lead to symptom flare-ups. In some instances and with healthcare access, C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) can be assessed to determine if a Herx reaction has occurred. These markers can rise during an inflammatory response but are not necessarily specific to the Herxheimer reaction.
Supplements That Cause a Herxheimer Reaction
While the Herxheimer reaction is best known in medical settings, many report experiencing it when using supplements that target pathogens or those that affect immune function. For example, supplements like monolaurin, which has antiviral properties, and L-lysine, often used as part of an antiviral protocol, may trigger a reaction in people with chronic infections.
When these supplements target persistent pathogens, such as viruses associated with ME/CFS they can cause a temporary worsening of symptoms due to the same die-off process that occurs with prescription treatments.
Similarly, herbs for bacteria or fungal infections commonly trigger a Herx reaction. Herbs specific to yeast such as oregano, thyme, peppermint, and goldenseal are common culprits. Berberine compounds against certain bacteria are also commonly used. Some probiotic agents may also cause a Herx reaction as bacteria die-off and release endotoxin the digestive tract.
It’s important to start supplements gradually and monitor for any Herxheimer-like reactions.
The Herxheimer Reaction and ME/CFS
People with ME/CFS, a condition defined by chronic viral infections and immune dysfunction, are more susceptible to experiencing a Herxheimer reaction. Those with the highest pathogen load, logically, can expect to experience the worst Herx reactions. Some pathogens that play a role in ME/CFS include:
Epstein-Barr Virus (EBV): A herpes family virus most commonly linked to chronic fatigue and viral reactivation in people with ME/CFS.
Human Herpesvirus 6 (HHV-6): Another herpesvirus that has been studied in connection with ME/CFS.
Cytomegalovirus (CMV): Some patients with ME/CFS have chronic CMV infections, which can trigger immune reactions.
Candida Albicans: systemic or chronic Candida infection (yeast infection) is common to ME/CFS patients. As antifungals (prescription or herbs) kill off the Candida organisms, toxins like acetaldehyde are released, potentially causing flu-like symptoms, headaches, and fatigue.
Mycoplasma: Mycoplasma pneumonae is common in ME/CFS with a Herxheimer reaction triggered during treatment with antibiotics or antimicrobial herbs.
Lyme: Spirochete bacteria like Lyme have a unique structure and are known for releasing toxic molecules as they are killed. Lyme disease is known to trigger a Herxheimer reaction in about 15-30% of those who are treated with antibiotics like doxycycline or amoxicillin. The die-off of the bacteria releases endotoxins, which lead to a temporary worsening of symptoms.
When antiviral treatments or immune-supportive supplements are introduced, the body may respond by attacking these pathogens, causing a temporary symptom flare-up. This is particularly relevant for ME/CFS patients using protocols aimed at treating underlying viral infections.
How to Manage a Herxheimer Reaction: The Basics
If you experience a Herxheimer reaction, there are ways to ease the symptoms and help your body cope with the extra inflammatory burden. While it’s not always possible to completely avoid the reaction, the following basic tips can help reduce discomfort:
Start Slowly: When introducing a new supplement or medication that may kill off pathogens or provoke the immune system, start with a lower dose and gradually increase it. It can be helpful to take capsules apart and split the contents to get a lower dose. Tablets should be cut into smaller pieces. Liquids should be taken in smaller volumes. This allows your body to adjust and reduces the likelihood of a severe reaction.
Stay Hydrated: Drinking plenty of water helps flush out endotoxins and other byproducts of pathogen breakdown. Drinking plenty of water and ensuring regular bowel movements also help support your body’s natural detox pathways. Adding electrolytes or herbal teas can also help support your system.
Rest and Reduce Stress: Rest is crucial when going through a healing crisis. Reducing physical and emotional stress allows your body to recover. Relaxation techniques can also help.
Be smart and anticipate the reaction any time you introduce a new treatment. It is also important to stick with it! Don’t let the Herx reaction prevent you from continuing on a protocol set out by your doctor. In time, it will pass, especially if you take care to reduce the effects.
How to Manage a Herxheimer Reaction: Supplements
Support Liver Detox Pathways: Supplements like NAC (N-acetyl cysteine) and milk thistle may help support your liver and digestive system in processing toxins released by pathogen die-off. Activated charcoal can bind to toxins in the gut, aiding their removal.
Manage Inflammation: Remember, the Herx reaction occurs because of increasing inflammatory cytokines. It follows that potent and bioavailable anti-inflammatory supplements like curcumin, glutathione, and/or sulforaphane may help reduce inflammation during a Herxheimer reaction.
Words of Caution
Some healthcare providers and patients may over-attribute symptom flare-ups to the Herxheimer reaction when the worsening of symptoms could be due to other issues, such as the progression of the illness. If the worsening continues after you stop taking the new treatment, something else is going on that is not a Herx reaction.
Also, be wary of practitioners who insist that the expensive protocol they have you on is working and that it will be worse before it gets better. Yes, you may feel worse before you get better. However, that worsening should be short-lived, not weeks or months. If worsening occurs for an extended period, something else is going on and should be thoroughly investigated, and reassessed, and the treatment plan should be adjusted accordingly.
It is important to understand what the Herxheimer reaction is and what to expect. A little common sense and critical thinking also go a long way. By understanding how this reaction occurs and taking steps to mitigate it, individuals can manage the temporary worsening of symptoms and continue their treatment journey with more comfort. They will also be wiser to avoid over-prescribing of supplements and unnecessary detoxes.
References
Belum GR, Belum VR, Chaitanya Arudra SK, Reddy BS. The Jarisch-Herxheimer reaction: revisited. Travel Med Infect Dis. 2013;11(4):231-237. doi:10.1016/j.tmaid.2013.04.001
Jaiswal N, Kumar A. Candida die-off: Adverse effect and neutralization with phytotherapy approaches. Toxicon. 2024;237:107555. doi:10.1016/j.toxicon.2023.107555
Straub RK, Powers CM. Chronic Fatigue Syndrome: A Case Report Highlighting Diagnosing and Treatment Challenges and the Possibility of Jarisch-Herxheimer Reactions If High Infectious Loads Are Present. Healthcare (Basel). 2021;9(11):1537. Published 2021 Nov 10. doi:10.3390/healthcare9111537
