Botanical Medicines For Lyme And Coinfections

of the information discussed in this ebook is based on the three scientific studies referenced in the bibliography. These studies were conducted by a team of scientists and medical doctors, including CCFM’s

and President Sunjya Schweig. The studies will be referenced throughout the text.

Chapter 1: Introduction

TICKBORNE DISEASE AND TREATMENT OVERVIEW

The Borrelia bacteria is a marvel in its ability to evade the immune system and persist as a stealth infection. These bacteria have essentially been around forever from an evolutionary point of view. They know us and they have watched us evolve. Therefore it’s no surprise that they are incredibly smart and unbelievably good at evading our immune systems and persisting.

As with any disease or illness, the optimal functional medicine approach to working with tickborne disease patients works to restore optimal functioning and balance across all body systems. The treatment of tickborne disease is complex and can take a long time. Each body system needs to be addressed and balance restored.

There are enormous challenges in effectively treating patients with tickborne infections. Each patient can be infected with different bugs and different strains, and the effects that they experience can be unique to each person's body. Testing is extremely problematic, owing in large part to the stealth nature of the pathogens and their ability to evade the immune system and get out of the bloodstream. Patients are frequently very well-read and well-informed and are often

trying different treatments on their own and or in collaboration with multiple practitioners. Importantly, many tickborne disease patients are already utilizing botanical medicines.

The optimal functional medicine approach to working with tickborne disease patients works to restore optimal functioning and balance across all body systems.

Complex Manifestations

Many different body systems can be affected. While some people experience symptoms from their initial infection, others may struggle years later with new impairments.

Varied Symptoms

Tickborne diseases affect all body systems and therefore present with a variety of symptoms. Some of the most common include joint pain, brain fog, neurological challenges, fatigue, and muscle weakness.

Chapter 2: Persister Cells

UNDERSTANDING PERSISTER CELLS

Impacted Daily Life

Many who were healthy before tickborne illness can no longer function normally or exercise due to debilitating fatigue. A significant number of people cannot return to work full-time.

Many doctors and researchers believe that persister cells are one of the most important reasons why patients fail treatment or relapse following treatment and improvement. Persister cells are dormant, non-dividing cells that have multi-drug tolerance and survive treatment by all known antimicrobials. They can exist in different morphological forms and are often found within biofilm colonies. Biofilms are protected from the immune system by a barrier called exopolymer matrices. A combination of protection from the immune system coupled with antibiotic multidrug tolerance makes these infections incredibly difficult to eradicate. We now know that the persister phenomenon has been found in almost all bacteria, including human, animal, and plant pathogens such as Lyme.

It is important to note the differences between antibiotic tolerance, persistence, and resistance:

• Antibiotic Tolerant Cell: An antibiotic tolerant cell is a cell that survives treatment with an antibiotic, without carrying a resistance factor, and that can regrow after removal of the antibiotic. Tolerance factors enable bacteria to survive a treatment that would kill more susceptible bacteria. These tolerance factors can be environmental or genetic.

• Antibiotic Persistence: Antibiotic persistence is a population-level phenomenon that frequently involves a biphasic killing curve with the presence of two subpopulations, consisting of cells that are killed quickly by the antibiotic and tolerant cells that may survive. By definition, the term antibiotic persistence is always connected with a heterogeneous population, in which a part of the population consists of tolerant cells.

• Antibiotic Resistance: Antibiotic resistance occurs when certain groups of bacteria adapt to antibiotics or medicines over time. Although many of the bacteria are killed by the antibiotic, a small group may survive and develop the ability to stop the effect of the antibiotic, pump the antibiotic out of the cell, or mutate so that the antibiotic no longer works.

Persistent infections are usually multifactorial and involve mechanisms evolved by different pathogens to evade the immune system.

PERSISTER CELLS AND TICKBORNE DISEASE

So how does this play out clinically with a Lyme patient?

The patient is prescribed an antibiotic or a combination of antibiotics that, hopefully, over time kills all of the active replicating spirochetes (Lyme bacteria). Some or all of the patient's symptoms improve and so the antibiotic cocktail is stopped. Because the bacteria were able to form antibiotic-tolerant cells, once the antibiotics are discontinued the bacteria can begin replication again and cause a symptom relapse. This scenario demonstrates why many Lyme patients and practitioners experience frustration with Lyme treatment — antibiotics can work very well but then patients can experience a relapse of symptoms when they stop the antibiotics. There is also

emerging evidence that antibiotic tolerance can progress to antibiotic resistance so these mechanisms may be overlapping. Again, resistance is not persistence but persistence may promote resistance.

Chapter 3: Botanical Medicine for Tickborne Disease

BOTANICAL MEDICINE FOR THE TREATMENT OF PERSISTER CELLS

Botanical medicine can be an effective treatment of persister cells through mechanisms that kill the cells, break down biofilms, and help to improve immune system function and response. Let’s dive a little deeper into some of the key botanical medicines used to treat tickborne diseases.

BOTANICALS

Cryptolepis sanguinolenta

All three studies have found this plant to be effective against Lyme, Babesia, and Bartonella. This was a very exciting and groundbreaking finding. Cryptolepis is generally well-tolerated with few side effects during its long-term use in China and India. Given its traditional use against malaria, it has been used in the Lyme treatment community for Babesia, because of the fact that Babesia is

a malaria-like organism. Cryptolepis has been previously noted to be a powerful general antibacterial herb, and our research is the first to show activity against Borrelia and Bartonella Previous studies have shown Cryptolepis to have anti-inflammatory, antimicrobial, anti-amoebic, anti-cancer, and antimalarial properties.

Polygonum cuspidatum

Polygonum cuspidatum extracts showed good inhibitory effects against all three organisms. The polyphenol resveratrol is one of its main active constituents and previous in vitro testing has documented that resveratrol exhibited activity against log-phase spirochetes of Borrelia burgdorferi and Borrelia garinii, minimal activity against Borrelia round bodies, and no significant activity against Borrelia associated biofilms.

Polygonum cuspidatum has been found to have minimal toxicity in animal and human studies. While only a limited number of human studies have been conducted using Polygonum cuspidatum as a whole herb, the available data shows a significant reduction in inflammation and oxidative stress following oral administration.

Polygonum cuspidatum contains over 60 active constituents with varying degrees of bioavailability and wide-ranging mechanisms of action. Resveratrol is the most studied constituent and has been shown to help treat cardiovascular disease, certain cancers, high blood pressure, high triglycerides, high cholesterol, endothelial cell function, metabolic syndrome, weight loss, and cognitive performance. It has also been documented to have antimicrobial, antitumor, neuroprotective, and anti-inflammatory activity. Gastrointestinal upset and diarrhea can occur but resolves with decreasing or stopping the intake. While few studies have been performed in humans, a 2010 review found that it is well-absorbed and rapidly metabolized.

Artemisia annua

Our first and second studies found Artemisia to be active against Lyme and Babesia. The first study also found Artemisia annua to exhibit excellent activity against stationary phase B. burgdorferi

The Chinese herb, Artemisia annua (Sweet wormwood or Qing Hao) has been used for the treatment of malaria for centuries and the Chinese scientist who isolated its most famous active constituent, artemisinin, was awarded the Nobel Prize in 2015 in recognition of artemisinin’s role in reducing malaria-associated morbidity and mortality Artemisinin-based compounds have become pivotal in malaria treatment as they can reduce malarial parasite load more rapidly than other known antimalarial drugs and are effective against all stages of Plasmodium spp.

Past studies have shown Artemisia to hold good activity against Borrelia burgdorferi, and our second study supplements this finding, showing impressive inhibitory effects against B. duncani

Some gastrointestinal upset including mild nausea, vomiting (rarer), and abdominal pain can occur at higher doses. The use of whole plant extracts instead of single constituents offers potential advantages including providing multiple mechanisms of action and synergistic effects that can reduce the risk of developing microbial resistance.

Importantly, Artemisia can induce its own metabolism so we recommend pulse dosing. For example, four days on and three days off, or one week on and one week off

Scutellaria baicalensis (Chinese skullcap)

Our first and second studies found Scutellaria baicalensis to be effective against Lyme and Babesia. Scutellaria baicalensis has been widely used as a medicinal plant in China for thousands of years for the treatment of diarrhea, dysentery, hypertension, hemorrhage, insomnia, inflammation, and respiratory infections

Over forty different compounds have been isolated from Scutellaria baicalensis and the antimicrobial activity is hypothesized to be due to flavonoids, volatile oils, terpenoids, and polysaccharides

Previous studies have demonstrated that a Scutellaria baicalensis extract and one of its primary bioactive constituents, baicalein, exhibited in vitro activity against various morphologic forms of Borrelia burgdorferi and Borrelia garinii Scutellaria baicalensis and its constituents have been shown to have neuroprotective, antioxidant, and anti-inflammatory effects. Interestingly, it is also an important herbal medicine that has been found helpful for the prevention and treatment of COVID-19.

Juglans nigra

Our first and second studies found Juglans nigra to have high activity against Lyme and B. henselae Juglans nigra and its constituents have been shown to have antioxidant, antibacterial, antitumor, and chemoprotective effects. Previous in vitro testing has documented that Juglans nigra exhibited bacteriostatic activity against log-phase spirochetes of B. burgdorferi and B. garinii and bactericidal activity against Borrelia round bodies.

Juglans nigra is well-tolerated and side effects are uncommon. Clinical studies are lacking on Juglans nigra as a whole herb, however, data from two active constituents indicate a systemic effect in humans.

The most well-studied active constituent is epigallocatechin gallate (EGCG) which has been documented to have significant benefits for multiple diseases including hyperlipidemia, metabolic syndrome, acne, breast cancer, and upper respiratory infections. In some individuals, it can cause gastrointestinal disturbance and induce changes in skin pigmentation. There can be some allergic cross-reactivity in those allergic to tree nuts or walnuts, as well as cases of dermatitis reported in humans.

Uncaria tomentosa (Cat’s Claw)

Uncaria tomentosa was found to be effective in our first study against B. burgdorferi. It has documented neuroprotective effects in preclinical studies, and preliminary human studies have shown improved quality of life in individuals with cancer, enhanced DNA repair, and symptom improvement in individuals with rheumatoid arthritis and osteoarthritis. Uncaria tomentosa has been found to be safe and to have minimal side effects in a variety of animal and human studies.

Chapter 4: Foundational Support

Conventional healthcare often fails to identify and provide the right care for tickborne diseases like Lyme disease and coinfections.

A functional medicine approach to Lyme disease evaluates and addresses all interconnected body systems. In addition to diagnosing and treating core infections, we correct immune dysfunction, inflammation, hormone imbalances, and other metabolic disorders to help you recover.

With multi-faceted treatments, we can support a healthy immune response to create the best chance of putting tickborne diseases into remission.

NUTRITION

It is key to focus on targeted nutritional interventions to reduce inflammation and support the immune system. This helps the body recover and enables other Lyme treatments to work better.

GUT HEALTH

Gut health plays a crucial role in recovering from Lyme disease, and for optimal success, we need to focus on supporting and healing the gut. Lyme disease and coinfections can result in gut inflammation, immune dysregulation, and autoimmune activation. Without a deep focus on gut health, we see less than optimal responses to treatments and an increased risk of relapse. The flip side is true as well, we can leverage gut healing to help you recover more quickly and robustly from tickborne illnesses.

NEUROPLASTICITY AND EMOTIONAL HEALING

It is also vital to leverage neuroplasticity and emotional healing. Many people with complex chronic illnesses live in a state of stress, trauma, and limbic system activation. The tickborne illness medical journey can be traumatic given the complexity, difficulty with proper diagnosis and treatment, and the disputed nature of the illness. Emotional healing and brain retraining are key components of recovery. The goal is to work to calm down the amygdala and fight-flight state, allowing the body and brain to reset.

EXERCISE AND MOVEMENT

Exercise and movement are key for endorphins, lymph flow, detoxification, and much more. But due to the varied symptoms of each person with a tickborne disease, it has to be individualized to avoid the push crash phenomenon.

SLEEP

Adequate, good-quality sleep is vital to healing, brain function, immune function, inflammation control, gut health, repair, detox, and more. See Dr. Schweig’s podcast with Dhru Purohit for a deep dive into sleep.

HORMONE BALANCING

People with tickborne diseases frequently suffer from dysregulation in hormones, such as adrenal, thyroid, and sex hormones. Rebalancing hormones can be an intricate process but can help significantly with mood, energy, sleep, and immune system function.

TREATING MOLD TOXICITY

Exposure to mold interferes with immune health in many people, including those with tickborne disease. Mold toxicity can mimic or exacerbate Lyme and coinfections and must be addressed before deep healing can occur.

ANTIMICROBIALS

Conventional medical treatment often relies solely on pharmaceutical antimicrobials like antibiotics to treat Lyme disease. Of course, it is possible to use a broader tool kit, with a combination of pharmaceuticals, botanicals, and other natural antimicrobials. This can give you deeper healing while minimizing damage to your gut.

Conclusion

Since traditional antibiotic approaches fail to resolve all symptoms in a subset of patients treated for Lyme disease, there is a need for identifying antimicrobial agents that are effective against actively growing and persister microcolonies of Lyme, Babesia, and Bartonella. Herbal medicines are an important and powerful part of tickborne infection protocols as well as broader antimicrobial protocols.

It is important to emphasize that the studies referenced in this ebook were all done in the lab. It is important to consider the potential limitations of the in vitro model given that it exists outside of the biological organism. The in vitro model can provide information on direct antimicrobial activity, and while this can be part of the function of botanical and natural medicines, it can also function via additional diverse pathways. For example, botanical medicines can exert effects via

anti-inflammatory/anti-cytokine activity, immune system regulation/augmentation, adaptogenic stimulation of cellular, and organismal defense systems, and biofilm disruption to name a few.

In these activities, the mechanisms of the medicines rely on complex interplay and interaction between different body systems, which can only occur within the living organism. Because the in vitro model is unable to provide information with regard to alternative pathways through which natural botanical medicines act, it is important that future in vivo studies in animals and humans be performed to investigate the activity and efficacy of botanical and natural medicines against Borrelia and other tickborne diseases.

If you have just noticed a tick bite, it’s crucial to get an immediate and accurate diagnosis, but this is challenging due to a lack of accurate diagnostics. Our team understands the complexities and nuances of the diagnosis and treatment of persistent and late-stage Lyme disease and tickborne coinfections.

The California Center for Functional Medicine is at the forefront of functional medicine treatment for Lyme disease. We have helped thousands of patients across the U.S. recover from Lyme and other tickborne illnesses. If you are suffering, we can help.

Bibliography

1. Feng J, Leone J, Schweig S, Zhang Y. Evaluation of Natural and Botanical Medicines for Activity Against Growing and Non-growing Forms of B. burgdorferi. Front Med (Lausanne). 2020 Feb 21;7:6. doi: 10.3389/fmed.2020.00006. PMID: 32154254; PMCID: PMC7050641.

2. Ma, Xiao1; Leone, Jacob2; Schweig, Sunjya3; Zhang, Ying4. Botanical Medicines With Activity Against Stationary Phase Bartonella henselae. Infectious Microbes & Diseases

3(3):p 158-167, September 2021. | DOI: 10.1097/IM9.0000000000000069

3. Zhang Y, Alvarez-Manzo H, Leone J, Schweig S, Zhang Y. Botanical Medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia Demonstrate Inhibitory Activity Against Babesia duncani. Front Cell Infect Microbiol. 2021 Mar 8;11:624745. doi: 10.3389/fcimb.2021.624745. PMID: 33763384; PMCID: PMC7982592.