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Home / Herxheimer Die-off Reaction & Cytokines / If you feel worse after herbal anti-microbials or prescriptive antibiotics to treat Lyme are started it is likely you are having a Herxheimer die-off reaction. A die-off reaction, also called a Herxheimer reaction, can occur when treating the Lyme germ, some co-infections, and yeast. It occurs as bacteria or yeast die during antibiotic treatment. It is common to have Herxheimer die-off reactions when starting herbal anti-microbials or antibiotics when treating Lyme. These reactions can also occur when new antibiotics are introduced into a treatment. Fortunately there are a number of good natural medicines that you can take to stop or limit Herxheimer reactions. In this article I review how these reactions occur, the various supplements I use with my patients to successfully limit the reactions, and my recommended dosing of each supplement. In a die-off reaction, there is a release of toxins, proteins, and oxidizing agents that results in an increase in inflammatory cytokines such as tumor necrosis factor alpha, interleukin-6, and interleukin-8.




The symptoms of a die-off reaction are generally a worsening of the underlying symptoms of Lyme disease and its associated infections. A majority of Lyme disease symptoms are actually excess inflammatory cytokine symptoms. So in a die-off reaction there is a worsening of many Lyme disease symptoms including: fatigue, brain-fog, muscle and nerve pain, chills and sweats, and/or memory and thinking. Cytokines: The Good and The Bad Good: Cytokines are proteins made by various types of white blood cells to fight infections. They perform a number of functions that include: making antibodies work more effectively, increasing active white blood cells to fight infections, recruiting white blood cells to the location of an infection, turning on white blood cells to fight infections, and decreasing viral and bacterial replication. Bad: Too many cytokines: suppress the immune system, decrease hormone production from organs like the thyroid and the adrenal glands,




increase fatigue and tiredness, decrease the function of various organs throughout the body resulting in many other symptoms and medical problems. Cytokines: How They are Made Cytokines are made when immune cells are stimulated by germs, oxidizing agents, cytokines, toxins, and other agents. Once the immune cells are stimulated an intracellular messenger called NF-kB causes genetic programming for the production of cytokines and the turning on of white blood cells to fight infections. Within the white blood cell cytokines are then produced in chemical reactions which require enzymes called kinases. Cytokines in Lyme: What’s the Problem? Cytokines are good, right? Well yes and no. In the right amount they promote healing. In excess, they are harmful. The problem in chronic Lyme and associated diseases is that they are made in excess. This occurs even more so in a Herxheimer die-off reaction. How to treat a Herxheimer Die-Off Reaction To treat Herxheimer die-off reactions there are a number of interventions to:




I think it is the best option for someone with chronic Lyme …The Jarisch-Herxheimer reaction was originally noted in 1895 by Dr. Jarisch who worked with Syphyllis (a spirochete) patients.  In the 21st century, we observe Herxheimer reactions in tick-borne illnesses such as Lyme Disease, also caused by a spirochete.  A Herxheimer reaction (Herx) typically occurs hours to days after antimicrobial administration and is thought to be the result of endotoxins released into the bloodstream by dying spirochetes.  The body’s immune system then responds to the endotoxins and the concurrent release of cytokines (i.e., tumor necrosis factor, interleukin 6, and interleukin 8) which are chemical messenger molecules of the immune system producing exaggerated symptoms lasting 3 days up to several weeks. Dr. Marra doses antibiotics specifically for the individual patient so that the Herxheimer reaction on a scale of 1-10, is about a 5.  This is her own technique, and she feels that severe Herxheimer reactions over prolonged periods of time may cause tissue damage from the excessive release of endotoxins and cytokines. 




Tissues become friable as the result of chronic inflammation, not unlike what happens when a sponge is repeatedly used and the surface area becomes frayed.  Dr. Marra is not convinced that this kind of tissue damage is reversible which is why she chooses to take the route of treatment that she does.  However, many other physicians choose to treat more aggressively and seem to have good results. This is simply her own treatment preference. The general description of a Herxheimer reaction is a temporary increase in symptoms but may also include the development of completely new symptoms.  More specifically, the most common complaints of a Herx reaction are increased joint and muscle pain, headaches, chills, night sweats, fever (usually low grade), extreme fatigue, and brain fog or lack of mental clarity, drop in blood pressure, hives, or a rash of some sort.  Worth noting here is that a rash or hives can sometimes be mistaken for an allergic reaction.  It is up to the treating physician to determine this, but with close, experienced observation and the use of Benadryl, Alka Seltzer Gold, Quercitin, warm lemon water and vitamin C (see Herx management), unnecessary premature cessation of antibiotics may be prevented.  




In more severe cases of Herxheimer reactions, a reduction in the antibiotic dosage or cessation of the antimicrobials may be required. The timing of a Herx reaction is very individualistic and can occur within days to weeks after the onset of antibiotic treatment.  In some patients, a Herxheimer reaction occurs only once or twice, or not at all throughout treatment.  It is clear however, that as you move through the treatment and the spirochetal load becomes decreased, the Herx reactions become less and less severe.  Herxheimer reactions can also occur in cycles (usually 4 week cycles) and may be affected by the lunar cycle.  This is anecdotal but it is an interesting observation in some people. About 70-80% of people undergoing Lyme Disease treatment with antibiotics experience some sort of Herxheimer reaction.  It is thought by a number of physicians and scientists that these people have difficulty in detoxification processes, and that perhaps there may be a defect in one of the detox pathways in the liver.