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Herxheimer Die-Off Reaction: Inflammation Run Amok

  • natural medicines:  curcumin, quercetin, ecklonia cava, alpha lipoic acid, n-acetyl cystiene, ume plum, glutathione
  • pharmaceutical medicines:  none that are safe and effective

"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.

     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,
  • cause pain,
  • decrease hormone production from organs like the thyroid and the adrenal glands,
  • disturb sleep,
  • decrease brain function, 
  • increase fatigue and tiredness, 
  • waste muscles,
  • cause depression, and
  • decrease the function of various organs throughout the body resulting in many other symptoms and medical problems.

Cytokines: How They are Made

     Cyokines 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:

  • lower oxidizing agents,
  • decrease NF-kB genetic programming of cells,
  • block kinase enzymes,
  • block inflammatory prostaglandins triggered by cytokines,
  • promote liver detoxification, and
  • lower blood acid levels.

     Based on the work of Martin Pall, PhD, it is critcal to lower oxidizing agents that trigger cytokine production. Ecklonia cava extract derived from sea weed is a potent oral anti-oxidant which seems to have greater affect than other ones. In addition to this, alpha lipoic acid (ALA), n-acetyl cysteine (NAC), and glutathione are helpful. Oral glutathione is poorly absorbed, so this is best in an IV form through a physicians office. Glutathione, and its precursor building blocks of ALA and NAC, also support liver removal of toxins. In addition to working with these antioxidants, the antioxidants quercetin and curcumin decrease NF-kB induced genetic signals to produce cytokines and block the production of inflammation prostaglandins. Quercetin also blocks kinase enzymes required in the production of cytokines. Blocking kinases with quercetin interferes with the cytokine production line. Prostaglandins are inflammation and pain chemicals that are triggered by inflammatory cytokines. Ume plum concentrate helps remove toxins and changes acid levels (alkaline) in a way that improves die-off reaction symptoms.

My Recommendations

     Step 1: The Beginning of Treatment to Prevent Herxheimer Die-off Reactions.

     Use a good multivitamin that includes alpha lipoic acid n-acetyl cysteine, antioxidants, and other micronutrients that decrease oxidizing agents and supports liver detoxification. My favorite multivitamin for this is the Energy Enfusion. If you cannot tolerate this or have whey protein allergies then use Mediclear. Also use curcumin.
  • Curcumin. Meriva 500 (Thorne) 500mg, 1 pill 3 times a day.
  • Multivitamin. Energy Enfusion (Integrative Therapeutics) 1 scoop daily or Mediclear (Thorne) 2 scoops daily.

     Step 2: Moderate Herxheimer Die-off Reactions.

     For more severe cases add ecklonia cava to the curcumin and consider adding quercetin. You can use all three. If this is not effective then add ume plum concentrate.  This combination works to block the cytokine production line and decreases oxidizing agents that trigger production. These treatments can take 1-2 weeks for maximum effect.

  • Quercetin.  Quercetone (Thorne) 2 pills 3 times a day.
  • Ecklonia Cava.  Fibroboost (Allergy Research) 2 pills 2 to 3 times a day.
  • Ume Plum Concentrate.  Ume Plum Balls (Eden)  suck on 2-3 balls 3 to 5 times a day.

If Fibroboost is not tolerated, or if Lyme disease and die-off symptoms have nerve pain or numbness,  then work with one or a combination of the following anti-oxidants. 

  • Alpha Lipoic Acid.  Super Lipoic Acid (Seroyal/Genestra) 1 pill 2 times a day.
  • N-Acetyl Cysteine.  Cysteplus (Thorne) 1 pill 3 times a day.

     Step 3: Severe Herxheimer Die-off Reactions.

     For severe die-offs use IV glutathione as a potent antioxidant and to support liver detoxification. This is administered in an integrative medicine physician's office. Do not use oral forms because they are not well absorbed. 

  • Glutathione IV 1200mg to 2500mg 2 times a week for a minimum of four treatments. If it helps but there are still improvements with the last treatment, consider weakly treatments until improvements plateau. You will likely feel more tired after the first treatment.

You Do Not Have to Feel This Way.




To purchase the other recommended supplements go to our store: Lyme Disease Supplements and More.


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     This discussion is hosted by Marty Ross MD and Tara Brooke ND.