Clinical Approaches to Herxheimer Reactions

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Lyme disease is one of the fastest growing insect-borne infectious diseases in the United States. ^[1] The majority of infections occur following a bite from a deer tick carrying Borrelia burgdorferi, or one of its subspecies. Acute Lyme disease is often treated relatively easily when caught early, but newer research suggests that Lyme disease may also become persistent or chronic in some individuals.

For these individuals with persistent Lyme disease, side effects of treatment can occasionally be much more debilitating than the symptoms of the disease itself. This is because a common occurrence with Lyme treatment is the Jarisch-Herxheimer or “Herx” reaction, where the patient experiences flu-like symptoms such as fatigue, muscle aches, fever, joint pain, tachycardia and more. ^[2] When spirochetes like Borrelia burgdorferi are killed, they release toxins into the circulation, eliciting a strong immune response that’s responsible for these adverse symptoms. These reactions can be incredibly uncomfortable and even debilitating for many, leaving some patients to wonder whether treatment is worth it. Mitigating these side effects can be so important in these cases. Fortunately, research suggests that there are some nutritional approaches that can be very effective for those suffering from Herxheimer reactions.

For these individuals with persistent Lyme disease, side effects of treatment can occasionally be much more debilitating than the symptoms of the disease itself.

 

The role of Inflammation in Jarisch-Herxheimer Reactions

Studies suggest that quelling inflammation can have a beneficial effect for “Herx” patients. Most spirochetes, such as Borrelia borgderferi, elicit only mild or moderate inflammation when left untreated. However, after antibiotic treatment, spirochetes are rendered more susceptible to neutrophil phagocytosis, provoking a much stronger inflammatory response. There is also an increase in pro-inflammatory cytokine release following antibiotic treatment of spirochetes.[3] These inflammatory mechanisms are responsible for some of the sensations associated with a herx reaction.

Curcumin

Turmeric (Curcuma longa), and its extract commonly referred to as curcumin, is a potent anti-inflammatory agent. It is perhaps the most well-known and studied herbal anti-inflammatory agent and for good reason. It is known to reduce pro-inflammatory cytokines such as interleukin (IL) -1, IL-6, and tumor necrosis factor α (TNFα)[4], that are perceived to be responsible for many of the symptoms associated with “herx” reactions. Curcumin has also demonstrated a benefit against additional pro-inflammatory cytokines such as NF-kB, cyclooxygenase-2 (COX-2), lipoxygenase (LOX) and inducible nitric oxide synthase (iNOS).^[5] Likely due to its anti-inflammatory properties, curcumin has been shown to greatly reduce symptoms of joint and muscle pain, which can be some of the most debilitating for patients experiencing Herxheimer reactions.[6]^,[7]

curcumin has been shown to greatly reduce symptoms of joint and muscle pain, which can be some of the most debilitating for patients experiencing Herxheimer reactions.

Boswellia serrata

Boswellia is another potent anti-inflammatory herb that has been used for centuries in traditional forms of medicine around the world. It is one of the most valued herbs in ayurvedic medicine, historically used for ailments associated with chronic inflammation, and touted for its pain relieving and antipyretic, or fever reducing, effects.[8]  Boswellic acids, the active constituents of Boswellia serrata, have been shown to inhibit inflammatory leukotriene synthesis without disrupting glycosaminoglycan (GAG) synthesis. Common non-steroidal anti-inflammatory drugs (NSAIDS) are known to degrade GAGs, leading to joint damage and increased pain levels over time.[9] This specificity associated with Boswellia allows it to be a great option for symptom relief in those experiencing painful Herxheimer reactions.

Bicarbonates

Sodium bicarbonate and potassium bicarbonate are common clinical tools to minimize inflammation and reduce symptoms associated with Herxheimer reactions. A study by Biolo et al. found that supplementation with potassium bicarbonate greatly increased glutathione, our body’s master antioxidant, levels suggesting that potassium bicarbonate could be protective against oxidative damage.[10] The researchers also observed a change in their participants’ fatty acid ratios, with the group receiving potassium bicarbonate exhibiting a more favorable n-3-to-n-6 polyunsaturated fatty acid (PUFA) ratio. This suggests a more anti-inflammatory versus pro-inflammatory pattern with potassium bicarbonate supplementation. Research also suggests that sodium bicarbonate can downregulate inflammation via the vagus nerve.[11] Because both bicarbonate formulas have anti-inflammatory effects through different mechanisms and pathways, they are often used in conjunction for management of inflammation during Herxheimer reactions.

Gastrointestinal Binders

Gastrointestinal binders are often used to improve the elimination of the toxin byproducts released during the dying off of spirochetal organisms. This can lessen the perceived symptoms while decreasing their duration as well. Activated charcoal is among the most well-known for its ability to bind and absorb toxins. It is even commonly used in emergency medicine following the ingestion of a poisonous substance.[12] Activated charcoal is known to bind and remove endotoxin which is a major contributor to Herxheimer symptoms due to its inhibition of detox pathways.[13]

Another relevant binding agent is chitosan, which acts by preventing the absorption of lipids by binding to bile salts and removing toxins secreted in the bile.[14] It has also proven to be an effective binder of endotoxin.[15] In a clinical trial with Lyme patients, chitosan was shown to reduce multiple symptoms associated with a Herxheimer reaction, including pain, sleep disturbances, and mood alterations.[16]

With an increase in the incidence of Lyme diagnoses, it is important for clinicians and patients alike to have a healthy understanding when it comes to Jarisch-Herxheimer reactions. Reducing inflammation and supporting removal of toxins released by treatment are among the most effective methods cited in the literature to improve patient comfort and, ideally, improve all outcomes of treatment by increasing patient compliance.

Click here to see References

[1] Kugeler KJ, et al. Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010–2018. Emerging Infectious Diseases. 2021;27(2):616-9.

[2] Dhakal A, Sbar E. Jarisch Herxheimer Reaction [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan 2021 May 4 [cited 2021 Jul 12]. Available from: https://pubmed.ncbi.nlm.nih.gov/32491752/

[3] Butler T. The Jarisch-Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis. Am J Trop Med Hyg. 2017;96(1):46-52. doi:10.4269/ajtmh.16-0434

[4]White CM, et al. Oral turmeric/curcumin effects on inflammatory markers in chronic inflammatory diseases: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019 Aug;146:104280.

[5] Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr. 2006 Jan-Feb;30(1):45-51.

[6] Sun J, Chen F, Braun C, et al. Role of curcumin in the management of pathological pain. Phytomedicine. 2018;48:129-140. doi:10.1016/j.phymed.2018.04.045

[7] Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016;19(8):717-729. doi:10.1089/jmf.2016.3705

[8] Siddiqui MZ. Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci. 2011;73(3):255-261. doi:10.4103/0250-474X.93507

[9] Brandt KD, Palmowski MJ. Effect of salicylates and other non-steroidal anti-inflammatory drugs on articular cartilage. Am J Med. 1984;77:65–9.

[10] Biolo G, Di Girolamo FG, Heer M, et al. Alkalinization with potassium bicarbonate improves glutathione status and protein kinetics in young volunteers during 21-day bed rest. Clin Nutr. 2019;38(2):652-659. doi:10.1016/j.clnu.2018.04.006

[11] Ray SC, Baban B, Tucker MA, et al. Oral NaHCO₃ Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells. J Immunol. 2018;200(10):3568-3586. doi:10.4049/jimmunol.1701605

[12] American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol. 1999;37(6):731-51.

[13]  Du X, et al. Effect of activated charcoal on endotoxin adsorption. Part I. An in vitro study. Biomater Artif Cells Artif Organs. 1987;15(1):229-35.

[14] Gallaher CM, et al. Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr. 2000 Nov;130(11):2753-9.

[15] Davydova V, et al. Interaction of bacterial endotoxins with chitosan. Effect of endotoxin structure, chitosan molecular mass, and ionic strength of the solution on the formation of the complex. Biochemistry (Mosc). 2000 Sep;65(9):1082-90.

[16] Allergy Research Group. Detoxification with Nanomolecular Chitosan Found Helpful for Lyme Patients in Small Clinical Trial. FOCUS Newsletter. July 2007;9-10.

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