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The Effect of Cryptolepis on Tick-Borne Infections

Updated: May 18, 2022

Introduction

In 2019, there were 50,865 new cases of tick-borne diseases, up from 48,610 in 2016 (Centers for Disease Control and Prevention [CDC], 2021). Despite Lyme disease being the most prevalent of all tick-borne infections, an individual may contract many other infections from a tick bite, causing many individuals to experience Lyme and multiple co-infections simultaneously (CDC, 2021; Zhang et al., 2021). Infected individuals each experience a unique set of symptoms, frequently being misdiagnosed and mistreated for years before discovering that chronic infections are at the root of the individual’s health struggles (Feng et al., 2020; Ma et al., 2021; Zhang et al., 2021). There has been a steady incline of tick-borne disease cases in the past few decades, not only throughout the United States but also across the globe (CDC, 2021; Zhang et al., 2021). This paper will focus on the treatment options, specifically concerning the use of Cryptolepis sanguinolenta as an herbal antimicrobial for patients managing acute and chronic tick-borne infections.

General Overview

Cryptolepis sanguinolenta, Cryptolepis for short, is a thin-stemmed shrub that grows in West Africa (Buhner & Nathan, 2015; Cryptolepis Root Extract, n.d.). It is commonly used for patients treated with an integrative approach who have persistent or chronic tick-borne infections (Buhner & Nathan, 2015). Babesiosis is a parasitic infection like malaria; therefore, it attacks red blood cells and responds similarly to the same treatments as malaria (Zhang et al., 2021). According to Buhner & Nathan (2015), there have been no reports of adverse events correlated with Cryptolepis when used in its complete form. Cryptolepine is the principal alkaloid of Cryptolepis and is cytotoxic when used, as many isolated constituents made into pharmaceuticals do (Buhner & Nathan, 2015). Cryptolepine is cytotoxic because it interrupts DNA, inserting itself between the two helixes’, inhibiting cellular division, making it an effective cancer treatment (Buhner & Nathan, 2015). Cryptolepis, in its complete form, has not been found to cause cytotoxicity in humans (Buhner & Nathan, 2015). The average cost of a high-quality Cryptolepis is $13-15 per liquid ounce (Cryptolepis, n.d.; Cryptolepis Root Extract, n.d.). Each ounce typically lasts about a month, depending on the dosing and how much is recommended (Cryptolepis, n.d.; Cryptolepis Root Extract, n.d.).

Selection Rationale

Cryptolepis was selected for review due to the continual increase of tick-borne infection cases in the United States, increasing its relevance to the clinical setting (CDC, 2021).

Search History

Research performed on the effects of Cryptolepis on tick-borne infections was done through the following process on January 23, 2022. The search conducted used the databases of PubMed, select books, and specific webpages for the pricing details of Cryptolepis. A search for related articles was conducted manually to identify literature discussing the effects of Cryptolepis on tick-borne infections. The investigation was limited to articles and books less than ten years old and written in English. Key terms identified to aid the search were Lyme, Borrelia, Babesia, Bartonella, coinfections, treatment, chronic Lyme, persistent Lyme, and Cryptolepis.

Search results and data collected included one book on tick-borne infections with defined herbal protocols by Buhner & Nathan (2015) and three laboratory-performed control studies (Feng et al., 2020; Ma et al., 2021; Zhang et al., 2021). Furthermore, two web pages from Green Dragon Botanicals and Woodland Essence with pricing options for Cryptolepis were utilized to compare the cost (Cryptolepis, n.d.; Cryptolepis Root Extract, n.d.). Lastly, one webpage from the CDC (2021) was used to obtain epidemiological data significance. Inclusion criteria included treating a tick-borne infection, epidemiological significance, and botanical activity evaluation. The primary objective of the analysis was to identify how effective Cryptolepis is when treating tick-borne infections. All sources collected were compared to Oxford's level of evidence to ensure the data collected was high quality. These resources are the foundation of this literature review.

Literature Review

In the book Healing Lyme by Bruhner & Nathan (2015), the authors describe the use of Cryptolepis on Babesia, potential adverse side effects, interactions, and dosing. Bruhner & Nathan (2015) explain why Cryptolepis is best taken in its whole form versus the isolated state as cryptolepine, known to be toxic to cells. The adverse reactions noted are elevated alkaline phosphatase (ALP) levels and negative effects on pregnant mice (Bruhner & Nathan, 2015). The potential chemical interactions are with central nervous system depressants and hypnosedatives; the authors deny any patient reports of adverse effects experienced when those medications are mixed with Cryptolepis (Bruhner & Nathan, 2015). Suggested dosing for acute Babesiosis is one liquid teaspoon to one tablespoon of a 1:5 plant to solvent ratio three times a day for five days, to be repeated once again in 14 days (Bruhner & Nathan, 2015).

The strengths of Bruhner & Nathan (2015) are that the authors include great detail as to what the indicated uses and dosing of Cryptolepis are for practitioners using this with patients, doing so clearly and concisely. Despite being very clear about how Cryptolepis is appropriately used, Bruhner & Nathan (2015) do not detail what studies they are referring to when making their claims and statements of efficacy; this directly affects the strength of their statements.

The Centers for Disease Control and Prevention (CDC) (2021) provides epidemiological data indicating that tick-borne infections are a growing public health concern. According to the CDC, the total reported tick-borne infection rates in the United States (US) went from 48,610 in 2016 to 50,865 in 2019. The CDC (2021) provides strong evidence displaying the gradual incline of confirmed tick-borne infections within the US. Some limitations of this data include cases not reported and misdiagnosed individuals, potentially skewing the data down.

To compare the pricing of Cryptolepis, the webpages of Green Dragon Botanicals and Woodland Essence were utilized. Green Dragon Botanicals sells Cryptolepis for $15 per fluid ounce, whereas Woodland Essence sells it for $13.20 per fluid ounce; how long each ounce lasts depends on the dosing (Cryptolepis, n.d.; Cryptolepis Root Extract, n.d.). Green Dragon Botanicals’ ingredients include Cryptolepis root extract from Ghana with a 1:5 plant to solvent ratio, organic grain alcohol (55-60%), water, and organic vegetable glycerin (Cryptolepis, n.d.). Woodland Essence’s ingredients include Dried Cryptolepis root from Africa with a 1:5 plant to solvent ratio, organic non-GMO cane alcohol (60-65%), 5% organic apple cider vinegar, and pure Adirondack water (Cryptolepis Root Extract, n.d.). Details of how the Cryptolepis plant is harvested from Africa and its medicinal benefits, dosing, and uses are provided (Cryptolepis Root Extract, n.d.). Woodland Essence additionally lists a safety warning, indicating that the tincture is not used during pregnancy (Cryptolepis Root Extract, n.d.).

Strengths of Green Dragon Botanicals and Woodland Essence include providing adequate amounts of supportive data detailing what carrier ingredients they use in their Cryptolepis tinctures (Cryptolepis, n.d.; Cryptolepis Root Extract, n.d.). They additionally provide adequate sourcing details of where the Cryptolepis is harvested from. Despite these noted strengths, Green Dragon Botanicals and Woodland Essence do not list their resources to back their claims of how Cryptolepis can medicinally support clients using their products; including this would add strength to their statements and increase their credibility.

Feng et al. (2020) performed a controlled study in a lab intending to evaluate the significance of Cryptolepis amongst other botanicals on Borrelia burgdorferi (B. burgdorferi), the Lyme disease-causing bacteria. The researchers conducted this study by culturing the B. burgdorferi strain B31 in a BSK-H medium with 6% rabbit serum; the cultures were then incubated in 50mL sterile cone-shaped tubes in an incubator at 33°C with 5% CO2 without antibiotics (Feng et al., 2020). The primary selection criteria for the botanicals included having a significant anti-borrelial effect noted in previous studies, good safety ratings, high bio-availability, positive clinical effects reported from patients and practitioners, and has an ability to break the biofilm and cross the blood-brain barrier (Feng et al., 2020).

The botanical medicines studied by Feng et al. (2020) were provided in 30, 60, and 90% alcohol; additionally, the alcohol was separately tested as a control. B. burgdorferi B31 was cultured unshaken for seven days in an incubator at 33°C and 5% CO2 as stationary phase cultures, about 10^7-8 spirochetes/mL (Feng et al., 2020). The stocks and control solvents were added to 100 microliters of the B. burgdorferi stationary phase culture in 96-well plates to test the efficacy of Cryptolepis against stationary strains (Feng et al., 2020). The botanicals were tested in different strengths and compared to antibiotic controls including daptomycin, doxycycline, and cefuroxime; all tests were run three times to ensure accuracy in the concluding results (Feng et al., 2020).

The researchers discovered that 0.25-1% Cryptolepis left only dead and aggregated B. burgdorferi cells, with 47-63% residual rates. In contrast, doxycycline and cefuroxime had 65-74% residual rates (Feng et al., 2020). In conclusion, Feng et al. (2020) state that Cryptolepis was found to have anti-inflammatory, antibacterial, anti-fungal, anti-amoebic, and anti-malarial properties, being highly effective against B. burgdorferi with a Minimum Inhibitory Concentration (MIC) rate of 0.03-0.06% and 0.25-0.5%. Furthermore, Cryptolepis was well tolerated on average, with very few side effects noted; doses up to 500mg/kg are further reported to be well-tolerated and safe (Feng et al., 2020).

The strengths of Feng et al. (2020) are that they provide strong evidence from their lab testing performed indicating that Cryptolepis is an effective anti-borrelia agent, having higher efficacy than the antibiotics per their reported residual rates. The study’s limitations by Feng et al. (2020) include that it was performed in a lab in a controlled environment and not on participants. The botanicals studied were added directly to the Borrelia cultures in the lab versus when taken by an individual; the active ingredients will have to penetrate layers of the body before it reaches the targeted microorganism. This will cause the study to yield different efficacy rates of the botanicals being applied to cultures in the lab compared to those administered to an individual with tick-borne infections.

Ma et al. (2021) performed a controlled lab study that reviews the efficacy of Cryptolepis against Bartonella henselae. Bartonella is the bacterium most commonly known for cat scratch disease and is a common tick-borne infection (Ma et al., 2021). Bartonella is a stealth infection that can evade the immune system and conventional antibiotics, negatively affecting the infected individual persistently (Ma et al., 2021). The researchers in Ma et al. (2021) aimed to improve the current treatment of Bartonella with the use of botanical herbs and identify botanicals that had meaningful activity against stationary phase Bartonella; they did so by using antibiotics and alcohol controls to compare the efficacy of botanical extracts including Cryptolepis. Ma et al. (2021) studied the application of the Cryptolepis at 0.5 and 1% to Bartonella cultures that were five days old in a 96-well plate, comparing it to the results of FDA-approved antibiotics typically used to treat Bartonella. The antibiotics were found to have high activity against growing Bartonella but not stationary Bartonella, leading to persistent infections (Ma et al., 2021). Cryptolepis was found to have the ability to eliminate all stationary phase Bartonella cells within seven days at 0.83mg/mL and 1.25mg/mL in drug-exposed time-kill assays (Ma et al., 2021).

Ma et al. (2021) state that Cryptolepis left a low percentage of viable Bartonella cells compared to other botanicals and antibiotics, with a P-value <0.05. Furthermore, they discuss the finding of a P-value >0.05 for the antimicrobial activity of fluorescence microscopy, solvents, and alcohol use compared to the drug-free control, indicating that they did not significantly impact the Bartonella samples (Ma et al., 2021). In conclusion, it was discovered that after a five-day incubation period at 37°C and 5% CO2 unshaken, Cryptolepis 3.33mg/mL (1%) and 1.67mg/mL (0.5%) in 30, 60, and 90% alcohol extract had residual rates of 8-47% (Ma et al., 2021). These results were better than the residual rates of the antibiotics, alcohol, solvent, and drug-free control results of 6-82% (Ma et al., 2021). The writers further review the findings that Cryptolepis is safe at doses below 500mg/kg; how this is known is not specified. Other studies have also discussed possible reproductive toxicity effects in more significant amounts (Ma et al., 2021). Overall, the researchers note that there is hope for improving the efficacy of treating Bartonella with Cryptolepis (Ma et al., 2021).

Ma et al. (2021)'s strengths include providing statistical solid evidence backing their statements on Cryptolepis, control factors such as the carrier ingredients, and their effects on Bartonella. They also thoroughly discuss how the testing was performed in detail. The weaknesses and limitations of Ma et al. (2021) are similar to that of Feng et al. (2020). Their findings are based on experiments in highly controlled environments rather than on infected individuals. Therefore, the results obtained do not fully reflect the accuracy of efficacy when treating an infected individual.

Zhang et al. (2021) performed a controlled lab study discussing the efficacy of Cryptolypis on Babesia, a tick-borne parasitic infection affecting red blood cells. Zhang et al. (2021) note that up to 23% of patients with Babesia also have Lyme disease, resulting in a complicated medical case with a myriad of symptoms and increased duration of illness. The authors discuss how the current treatment for Babesia is insufficient, as 72% of individuals experience adverse side effects such as ringing in the ears, vertigo, upset stomach, and relapsing symptoms after pharmaceutical treatment was complete (Zhang et al., 2021). Babesia is noted to have excellent resistance to pharmaceutical medicines such as atovaquone and azithromycin (Zhang et al., 2021). The researchers used a centrifuge and triple-washed whole hamster blood resuspended at a concentration of 50% hematocrit in Puck’s saline glucose buffer with 20G of glucose per Liter, storing it at 4°C less than when it was obtained (Zhang et al., 2021). Strains of Babesia duncani were obtained and cultured in a 24-well plate using an HaRGM medium and 2.5% hematocrit of hamster erythrocytes at 37°C with 5% CO2 and 95% humidity for three to four days (Zhang et al., 2021).

The researchers investigated a total of 46 botanical medicines, including Cryptolepis sanguinolenta; they were added to ethanol controls of 30, 60, and 90% strengths to 96-well plates that contained the infected hamster blood, ultimately making a complete concentration of 0.01% (Zhang et al., 2021). The treated cultures were placed in an incubator for three days with environmental controls described above. After three days it was determined that Cryptolepis in 60 and 90% ethanol extracts were 70-80% effective against Babesia; the study methods were repeated three times to ensure accuracy (Zhang et al., 2021). Overall, the researchers concluded that Cryptolepis has low cost, low toxicity, good pharmacokinetic properties, and long-standing research history documenting its safety and efficacy (Zhang et al., 2021).

The strengths of Zhang et al. (2021) include that they provided sufficient details on how the study was performed, leading to their conclusion. The researchers adequately relayed the inhibition rates of all the botanicals studied; however, they did not list the inhibition rates of the carriers and controls. Therefore, Zhang et al. (2021) did not display how the carriers affected the Babesis cultures compared to the botanical efficacy rates.

Conclusion

Cryptolepis has been shown to have the potential to be a treatment option for individuals with chronic and acute tick-borne infections (Bruhner & Nathan, 2015; Feng et al., 2020; Ma et al., 2021; Zhang et al., 2021). Cryptolepis has been studied for many years in the lab, and has been noted to be a safe, effective, and cost-friendly option for those being treated for tick-borne infections (Bruhner & Nathan, 2015; Cryptolepis, n.d.; Cryptolepis Root Extract, n.d.; Feng et al., 2020; Ma et al., 2021; Zhang et al., 2021). In a review of the collective limitations noted above with the consideration of many studies suggesting that further research is needed to solidify its validity and efficacy for clinical use, the effectiveness of Cryptolepis on an individual requires other studies to be completed (Bruhner & Nathan, 2015; Feng et al., 2020; Ma et al., 2021; Zhang et al., 2021). Overall, integrating Cryptolepsis into the care plan for an individual with tick-borne infections may possibly be considered as an adjunct therapy, hoping to optimize their outcomes and chances of having a higher quality of life while living with chronic tick-borne infections.

Resources

  • Buhner, S. H., & Nathan, N. (2015). Healing Lyme: Natural healing of Lyme borreliosis and the coinfections chlamydia and Spotted Fever Rickettsioses (pp. 394-396). Raven Press.

  • Centers for Disease Control and Prevention. (2021, October 6). Tickborne Disease Surveillance Data Summary. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/ticks/data-summary/index.html

  • Cryptolepis. Green Dragon Botanicals. (n.d.). Retrieved from https://greendragonbotanicals.com/products/cryptolepis

  • Cryptolepis Root Extract. Woodland Essence. (n.d.). Retrieved from https://woodlandessence.com/products/cryptolepis-root-extract?variant=2175884754968

  • Feng, J., Leone, J., Schweig, S., & Zhang, Y. (2020). Evaluation of Natural and Botanical Medicines for Activity Against Growing and Non-growing Forms of B. burgdorferi. Frontiers in medicine, 7, 6. https://doi.org/10.3389/fmed.2020.00006

  • Ma, X., Leone, J., Schweig, S., & Zhang, Y. (2021). Botanical medicines with activity against Stationary phase Bartonella henselae. Infectious Microbes and Diseases, 3(3), 158–167. https://doi.org/10.1097/im9.0000000000000069

  • Zhang, Y., Alvarez-Manzo, H., Leone, J., Schweig, S., & Zhang, Y. (2021). Botanical Medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia Demonstrate Inhibitory Activity Against Babesia duncani. Frontiers in cellular and infection microbiology, 11, 624745. https://doi.org/10.3389/fcimb.2021.624745

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