Many clinicians may shy away from treating Lyme disease patients. This may be because very few had an immersed internship, or they knew, likely from a personal or close family member's experience, that working with Lyme disease was a personal passion they would pursue until unable any more. So, how do we step into the world of Lyme and work with this patient population and all its complications? An understanding of the challenges that can make this infectious disease so chronic helps us to recognize what tools from our holistic toolbox may be useful in not only the eradication of this infection, but also for palliating the symptoms with which our patients may suffer.
Lyme disease specifically refers to the tick-borne infection typically caused by one of three pathogenic species of the spirochete Borrelia burgdorferi sensu lato.1 Of these, in the United States, B. burgdorferi is the most common, while B. afzelii and B. garinii have been observed more in Europe as well as Asia. Many new species and variants within this family continue to be recognized.2 However, B. burgdorferi, or one of these others, is not the only pathogenic agent which a tick may transmit. Common co-infections include microbes from the families of Bartonella, Ehrlichia, Anaplasma, and Babesia,3,4 which not only lead to symptoms associated with their presence but also can increase Lyme disease severity and have their own distinct challenges in the process of eradication.5 The various diagnostic tests on the marketplace, and their advantages or pitfalls, are beyond the scope of this article and are a complex discussion as well.
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The Borrelia spirochete not only often travels with a companion, but itself can take many forms in the body. It is able to defend itself by switching to a cystic form or existing within a biofilm-like colony, as well as by differentially expressing proteins and genes that enable survival in the host.6-8 By doing such, it is not only able to avoid immune system clearance, it also is able to avoid detection.9,10 Because of this switching, we will see not only resistance to antibiotics, but also botanicals, necessitating an ongoing process of switching our therapies, often through a long course of treatment.
Given these issues, the interventions selected for the treatment of Lyme disease must consider the broad array of pathogens that may exist, the protective nature of biofilms that prevent eradication, and support to encourage a necessary, yet balanced, immune system response. With the vast array of symptoms which are debilitating for many, support for symptom palliation, ideally in a manner that does not suppress but rather further encourages healing, also is necessary.
Artemisia annua, also known as sweet wormwood, or Qinghao, has a long history of use as an antimicrobial agent.11,12 The primary compound derived from this plant is artemisinin, also known as Qinghaosu.13 However, additional bioactive substances found in its oil include camphor, germacrene D, artemisia ketone and 1,8 cineole.14
A. annua has broad-spectrum action as an antiparasitic, antibacterial, antifungal, and antiviral agent. A. annua and its derivatives, particularly artemisinin, have been shown to be active against Babesia, as well as cytomegalovirus, herpes simplex virus, Epstein-Barr virus, and Toxoplasmosis gondii – each of these being additional common causes of persistent, chronic infections that burden the immune system.15-18 Action has also been demonstrated against Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, E. coli UPEC, Haemophilus influenzae, Helicobacter pylori, Pseudomonas aeruginosa, Campylobacter jejuni, Clostridium perfringens, and Candida spp.,19-22 many of which may exist as pathogens or at unbalanced levels in the often immune-compromised Lyme patient. Artemisinin also may impact biofilms, which make some of these pathogens resistant to treatment.23,24
In a recent study of patients experiencing short-term memory deficits associated with Lyme disease, oral treatment with artesunate, a water-soluble artemisinin derivative, was shown to significantly reduce the short-term memory difficulties.25 Although the memory issues may occur due to central nervous system infection with Borrelia spp., this symptom also may be attributable to a Babesia co-infection. Regardless of the infectious etiology, this recent finding is noteworthy and may translate to clinical improvements.
Grapefruit seed extract, although the subject of some controversy due to the possible contamination of products with benzethonium chloride and triclosan,26,27 also may be helpful in the treatment of Lyme disease, due to its demonstrated action against both the motile and cystic forms of B. burgdorferi.28,29 It has been reported to have no significant adverse effects, including on the population of healthy Lactobacillus spp. or Bifidobacterium spp. in the gut.30
Many botanicals have evidence of supporting immune system function; of these, one which is of importance in the treatment of Lyme disease is cat's claw (Uncaria tomentosa), also known in Spanish as uña de gato. Cat's claw is ideally suited in the Lyme setting, as in addition to its immune-supportive actions, it has been shown to have anti-inflammatory, anti-arthritic, and antioxidant effects, and supports cognitive function. Cat's claw has been shown to enhance proliferation of both T helper and B lymphocytes,31,32 also increasing lymphocyte viability and survival. In the setting of rheumatoid arthritis, cat's claw has been shown to significantly reduce the number of painful and swollen joints.33 In osteoarthritis, similar benefits have been seen, with a significant improvement in pain associated with activity, as well as medical and patient symptom assessment scores.34 Potent antioxidant activity, including the protection of membrane lipids from peroxidation, has been demonstrated in multiple in vitro studies, along with a strong level of inhibition of tumor necrosis factor (TNF)-α, a primary pro-inflammatory cytokine associated with the acute immune system response.35,36
Cat's claw also has the potential to improve some of the cognitive symptoms seen with Lyme disease and its common co-infections. In multiple animal models, cat's claw has been demonstrated to have a neuroprotective effect and improve memory,37,38 possibly attributable to its antioxidant action or altered glutaminergic signaling.39
Reducing Biofilms and Taming the Inflammatory Response
Lactoferrin, a glycoprotein found in milk and at much higher concentrations in colostrum, has long been recognized for the role it plays in protecting infants from infection as well as supporting normal immune system function.40 It has been shown to have antimicrobial activity against parasites, bacteria, fungi, and viruses,41 and supports the body's protective response to tick-borne pathogens. Lactoferrin has been shown to have an inhibitory effect on bacterial biofilms,42 including that of B. burgdorferi.43 Lactoferrin also has been shown to inhibit the growth of Babesia spp., one of the common co-infections.44
Lactoferrin's immunomodulating effects support symptom reduction and an improved systemic response. Many Lyme patients not only experience symptoms due to the active infection in their body; but when treatment commences, a reaction referred to as "die-off," or formally, a Jarisch-Herxheimer reaction, may occur. Specifically, a Jarisch-Herxheimer reaction is the symptoms that transpire due to the uncontrolled release of endotoxin (also known as lipopolysaccharide or LPS), as well as endotoxin-like products, during lysis of the broad spectrum of bacteria which many natural and pharmaceutical antibiotics impact.45 These products of bacterial die-off not only stimulate a further immune response and inflammation, they also can adversely affect organ and systemic function, sometimes critically, in patients with Lyme disease.46,47 Lactoferrin has been shown to neutralize endotoxin,48 also directly inhibiting the endotoxin-induced immune system response.49,50 Lactoferrin has also been shown in several studies to decrease levels of TNF-α.51 In animal models, the administration of supplemental lactoferrin prior to endotoxin shock dramatically reduced mortality and increased overall wellness.52,53
Chitosan is a biopolymer derived from chitin, a component of the shell of crustaceans that is used in a variety of biological applications including as a vaccine adjuvant. Chitosan also is used in an array of applications as a chelator.54,55 It has been shown to have the ability to bind and remove a variety of toxins including polychlorinated biphenyls, phthalates, bisphenol A, mold toxins, and heavy metals.56-59 It also has an ability to chelate and remove the heavy metals manganese and zinc.60,61 Manganese and zinc are two minerals that are essential for the lifecycle and metabolic needs of B. burgdorferi, also serving as central regulators of many of its virulence genes.62,63
Chitosan has been shown to have an antimicrobial effect via disrupting biofilms associated with Streptococcus mutans and C. albicans, particularly when the chitosan is of low molecular weight.64,65 Chitosan also has the ability to bind endotoxin66,67 and has been shown specifically, in the setting of Lyme, to reduce symptoms attributed to the Jarisch-Herxheimer reaction.68 In the gut, chitosan has been shown to have a prebiotic effect, promoting the growth of Bifidobacterium spp. and Lactobacillus spp., which are predominant healthy flora that also support the reduction of inflammation and a normal immune response.69-71
Support for Cellular Function
One possible contributor to the fatigue that is experienced with Lyme disease, and with other chronic infections for that matter, is altered cellular function due to oxidative stress and damage. In Lyme borreliosis patients, classified by the CDC definition of Lyme disease and not being treated by antibiotics, significantly low levels of cytosolic ionized calcium, indicative of interrupted cellular communication, and significantly higher levels of mitochondrial superoxide, indicative of oxidative stress and damage within the cell, have been shown.72 Additionally, B. burgdorferi has been shown to sequester cysteine, the rate-limiting amino acid for glutathione production, for its growth.73 This may further impair cellular function and detoxification, leaving the cell even more susceptible to oxidative damage particularly if additional insults occur. It is not uncommon that we see patients with Lyme disease easily fall ill when exposed to mold or heavy metals; the reduced ability for the cells to detoxify and carry on normal function may be a significant contributor.
Lipid replacement therapy, that is, oral supplementation with glycerolphospholipids, which are the main component of cellular membranes, is one strategy to support normal cellular function and repair. To further enhance this, critical antioxidants such as coenzyme Q10 (CoQ10) and reduced nicotinamide adenine dinucleotide (NADH) are also often provided as well. The combination therapy of glycerolphospholipids, CoQ10, NADH, and additional ingredients to support cellular function, such as L-carnitine, has been studied in the setting of intractable chronic fatigue and chronic Lyme disease, diagnosed by symptoms and positive Western blog analysis. After two months of daily supplemental support, fatigue, as well as all subcategories of fatigue including cognitive function and mood, were significantly improved (P<0.0001).74 Trendlines also showed significant and consistent downward trends in the data, indicating that symptoms would have further improved with time. Additional studies utilizing glycerolphospholipids as a monotherapy or in combination with additional nutrients have shown positive outcomes in similar settings of chronic fatigue, also leading to improvement in mitochondrial function.75,76
Although the challenges associated with supporting patients whose health has been compromised by a tick-borne infection do have many complexities, therapies such as these, or a combination thereof, offer a starting point that clinicians can trust, due to evidence in in vitro, animal, and human clinical studies that support their use. Other botanical and nutritional substances, as well as energetic medicine and physical modalities, also are often necessary for complete recovery; but for some, therapies such as these discussed herein may be adequate to encourage the body to respond and recover.
Carrie Decker is a certified naturopathic doctor, graduating with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Dr. Decker sees patients at her office in Portland, Oregon, as well as remotely, with a focus on gastrointestinal disease, mood imbalances, eating disorders, autoimmune disease, and chronic fatigue. Prior to becoming a naturopathic physician, Dr. Decker was an engineer and obtained graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectively. Dr. Decker continues to enjoy academic research and writing and uses these skills to support integrative medicine education as a writer and contributor to various resources. Dr. Decker supports Allergy Research Group as a member of their education and product development team.