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New study on Borrelia and botanicals: lessons on good research design

A new study published last week examined the anti-borrelial activity of several botanical extracts against doxycycline and cefuroxime in vitro. This study was well designed and helps advance the conversation on Lyme disease and potential herbal treatments. More importantly, there are important lessons for research groups.

From the abstract:

In the present study, we investigated the antimicrobial effects of 12 commonly used botanical medicines and three other natural antimicrobial agents for potential anti-Borrelia burgdorferi activity in vitro. Among them, 7 natural product extracts at 1% were found to have good activity against the stationary phase B. burgdorferi culture compared to the control antibiotics doxycycline and cefuroxime. These active botanicals include Cryptolepis sanguinolenta, Juglans nigra (Black walnut), Polygonum cuspidatum (Japanese knotweed), Artemisia annua (Sweet wormwood), Uncaria tomentosa (Cat’s claw), Cistus incanus, and Scutellaria baicalensis (Chinese skullcap). In contrast, Stevia rebaudiana, Andrographis paniculata, Grapefruit seed extract, colloidal silver, monolaurin, and antimicrobial peptide LL37 had little or no activity against stationary phase B. burgdorferi.

The minimum inhibitory concentration (MIC) values of Artemisia annua, Juglans nigra, and Uncaria tomentosa were quite high for growing B. burgdorferi, despite their strong activity against the non-growing stationary phase B. burgdorferi. On the other hand, the top two active herbs, Cryptolepis sanguinolenta and Polygonum cuspidatum, showed strong activity against both growing B. burgdorferi (MIC = 0.03–0.06% and 0.25–0.5%, respectively) and non-growing stationary phase B. burgdorferi. In subculture studies, only 1% Cryptolepis sanguinolenta extract caused complete eradication, while doxycycline and cefuroxime and other active herbs could not eradicate B. burgdorferi stationary phase cells as many spirochetes were visible after 21-day subculture.

Applications to herbal practice

In terms of observed antibacterial activity, Japanese knotweed and cryptolepsis are stand outs. Those MICs are notable. Japanese knotweed is particularly attractive due to its ubiquity and classification as an invasive plant in many places. It also has a decent history of use and appears to be very well tolerated. The lack of activity from Andrographis is no enormous surprise, as many herbalists have considered to be more of an immune stimulant in these situations.

I love that these are standard herbal tinctures that most people could make. (Though Heron Botanicals tinctures are exquisite and I use them in my practice!) I am less enthused about costly proprietary-process products like Byron White and Nutramedix–they are simply not accessible to most people, especially for a long course of treatment.

I’m glad they included Stevia extracts in their sample set. The effects observed in the widely-shared 2015 study were not reproducible in this study. It’s notable that there were no ethanol controls utilized in the 2015 paper (which the authors cite here). Ethanol controls are critically important to use when studying ethanol-containing extracts, as ethanol is stressful to cells and highly bioactive in its own right.

Design considerations for researchers

Ultimately, the research team did several things very well here:

  • collaborated with clinicians and practitioners who have ‘boots on the ground’ and hands-on experience with patients,
  • consulted with those who know and understand the study materials (in this case, qualified and trained herbalists),
  • sourced quality materials from reputable suppliers for the study (from Heron Botanicals, Mountain Rose Herbs, Friends of the Trees, and Pacific Botanicals),
  • compared the botanical samples against standard treatments (doxycycline and cefuroxime).

This, in a nutshell, is good research and experimental design. You’re always designing it for people (in this case, people with chronic Lyme disease). What do they need? What are their questions? Are the preparations, doses, and other study parameters in the study remotely reasonable?

This is some of the thinking I bring into my own work in research settings. In the life sciences, it’s easy to lose touch and speak to those in your own field. This study is relevant in the discipline as well as practitioners and patients because the research team kept them in mind. Lyme is still a wicked problem, but there are many people working on it.

The full text of the article is available free of charge, and is well worth the read.

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

About Author

Renée A. Davis MA RH is a designer and educator in botanical and mycological medicine. Her training began at the Pratt Institute of Art and Design in New York City and concluded in biomedical sciences at the University of Washington. She currently directs research and development for a nutraceutical mushroom company in the Pacific Northwest.

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