As many of us have discovered during the COVID pandemic shutdown, living like a hermit is no fun. Yet,  as we venture outdoors for a little diversion and exercise, it’s important to protect ourselves from ticks. However, there are a lot of repellents I will not use because of our cats, fish and bees.

Now, it looks like there may be new options for protection coming our way.

In July, the US Environmental Protection Agency (EPA) approved a natural compound known as nootkatone, for use in insecticides and pesticides.

Nootkatone is derived from nature and has been found to effectively repel and kill ticks. It is also safe for domesticated animals, birds, bees, butterflies, and the environment.

This paves the way for manufacturers to start developing nootkatone-based products for public use. Before these new products become available to the public, however, each of them must first go through safety testing and FDA approvals.

What is nootkatone?

Nootkatone is a botanical extract found in minute amounts in the essential oils of the Alaska yellow cedar tree, alpinia plants, bitter cardamon and the skin of citrus fruits—especially grapefruit.

For millions of years, plants and trees have produced natural compounds to protect themselves from threats such as termites and mold. Nootkatone is one of these natural compounds. It is also what gives each of these plants/trees its distinctive smell.

Your grandmother’s cedar chest is a good example of the scent and the natural ability of cedar to repel moths and other insects from woolen clothes.

Nootkatone is non-toxic and has been commonly used as a fragrance in colognes and perfumes, and as a flavoring in foods and drinks for decades. “If you drink Fresca or Squirt, you’ve drunk nootkatone,” the CDC’s Ben Beard told the NY Times.

Now we know, nootkatone not only tastes and smells good but it also repels and kill ticks, mosquitoes, fleas, cockroaches, termites and bed bugs. Because nootkatone is non-toxic to humans, birds and animals, this may be the first bug-killing product that can be broadly used without harming the environment.

Thomas Mather, of the TickEncounter Resource Center, tells me, “We’re excited that EPA has approved nootkatone for vector control. In 2014, we tested an earlier formulation of the product for blacklegged tick control and found that it was one of only a few natural products that actually killed more than 50% of the ticks in our tests.”

Tick control

Tick-borne diseases continue to spread throughout the United States. Yet, so far, there have been few governmental efforts to control them.

Lars Eisen, Ph.D., with the CDC’s Division of Vector-Borne Disease, wrote in 2010, “Mosquito control is a community responsibility; tick control is an individual homeowner responsibility. This may explain why currently in the United States, several thousand people are dedicated to mosquito control, whereas only a few dozen are dedicated to public-health related tick control.”

Little has changed in the last 10 years.

In 2000, the CDC filed a patent for “Compounds For Pest Control, and Methods for Their Use” after finding that nootkatone compounds were effective in killing ticks, mosquitoes and a variety of other pests.

[Specifically, the CDC patented the compounds that employ the “eremophilane sesquiterpenes” structure. This is a sub-class of “terpenes” that are derived from the essential oils of certain plants and trees known for their strong odor which naturally repels pests.]

Yet, here we are, 20 years later and ticks are still causing 8 out of every 10 cases of vector-borne (mosquito and tick) diseases reported to the CDC, with most of those being Lyme disease.

Kirby C. Stafford III, Ph.D., of the Connecticut Agricultural Experiment Station and colleagues conducted research utilizing nootkatone from 2003-2010.  (Dr. Stafford and Dr. Eisen are members of the Tick-Borne Disease Working Group sub-committee on “Tick, Biology, Ecology and Control.” I am also a member and I thank them both for generously sharing their research.)

The way it’s formulated matters a great deal

Stafford’s research team found that nootkatone’s ability to kill ticks varies significantly, depending on how the compound is prepared and applied. Nootkatone that is formulated in a way that protects it from UV light is long lasting, effectively kills ticks and doesn’t damage plants.

In addition, they found that high-pressure perimeter spraying (versus backpack spraying) is more effective at getting into the leaf litter providing up to 28 days of protection from ticks— including nymphs.

Stafford’s team has found nootkatone to be effective against the blacklegged tick (Ixodes scapularis, pacificus), and three additional species: the brown dog tick (Rhipicephalus sanguineus Latreille); the American dog tick (Dermacentor variabilis); and lone star tick (Amblyomma americanum).

These ticks are responsible for spreading at least 18 different disease-causing pathogens to humans including: anaplasmosis, babesiosis, Bourbon virus, ehrlichiosis, Lyme disease, relapsing fever borreliosis, rickettsiosis, Rocky Mountain spotted fever, Powassan virus and more.

When will it be available?

In 2000, the CDC discovered that the pest killing compounds called nootkatol, epinootkatol, nootkatone and nootkatene can be isolated from natural sources, semi-synthesized from naturally occurring compounds or completely synthesized.

Unfortunately, the price of these pure essential oils has made it too expensive to use on a broad scale—until now.

In 2017, the CDC entered into an agreement with the biotech company Evolva to further develop nootkatone specifically. Since then, Evolva has developed a fermentation method allowing it to mass produce the ingredient in a 99% pure nature-identical form. (This means it is chemically synthesized and chemically equivalent, rather than a 100% pure extract.)

Because nootkatone is also being developed to control the mosquitoes that cause dengue, Zika, chikungunya and West Nile viruses, Evolva has received more funding than if it had been just for ticks.

For instance in 2016, the CDC received $350 million for Zika with 5,100 reported cases (4,000 of them travel-related). That same year, the CDC received $11 million for Lyme disease which affected an estimated 437,000 Americans.

According to Alexandra Dapolito Dunn, of the EPA, nootkatone has the potential to be used in future insect repellents and pesticides that will protect people from disease.

In many areas of the United States, Dunn said, mosquitoes have become resistant to currently available pesticides. “A new active ingredient in our toolbox will help vector-control programs.”

The CDC also predicts that products using nootkatone could be commercially available as early as 2022.

Great potential

Experiments have also shown that soap containing nootkatone can wash ticks off of mice.

Imagine if nootkatone were formulated into simple, safe, and inexpensive personal care products like soaps, lotions, and shampoos. Imagine not having to look for tiny nymphal ticks (smaller than a pinhead) on you and your children after every outdoor activity.

This past weekend, my Facebook page was flooded with pictures of friends and family hiking, camping and enjoying the outdoors. I wondered if they’d taken precautions against ticks. Wouldn’t it be great if you and your kids could simply jump in the shower and easily wash away any tiny ticks that happened to be hitching a ride?

LymeSci is written by Lonnie Marcum, a Licensed Physical Therapist and mother of a daughter with Lyme. In 2019-2020, she served on a subcommittee of the federal Tick-Borne Disease Working Group. Follow her on Twitter: @LonnieRhea  Email her at: lmarcum@lymedisease.org .

References

Anuja Bharadwaj, Kirby C. Stafford, III, Robert W. Behle (2012) Efficacy and Environmental Persistence of Nootkatone for the Control of the Blacklegged Tick (Acari: Ixodidae) in Residential Landscapes, Journal of Medical Entomology, 49(5): 1035–1044. DOI: https://doi.org/10.1603/ME11251

Behle RW, Flor-Weiler LB, Bharadwaj A, Stafford KC 3rd. (2011) A formulation to encapsulate nootkatone for tick control. J Med Entomol. 48(6):1120-1127. DOI: https://doi.org/10.1603/ME10282

Bezerra Rodrigues Dantas L, Silva ALM, da Silva Júnior CP, et al. (2020) Nootkatone Inhibits Acute and Chronic Inflammatory Responses in Mice. Molecules. 25(9):2181. DOI: 10.3390/molecules25092181

Dietrich G, Dolan MC, Peralta-Cruz J, et al. (2006)  Repellent activity of fractioned compounds from Chamaecyparis nootkatensis essential oil against nymphal Ixodes scapularis (Acari: Ixodidae). J Med Entomol.  DOI: https://doi.org/10.1093/jmedent/43.5.957

Dolan MC, Jordan RA, Schulze TL, et al. (2009) Ability of two natural products, nootkatone and carvacrol, to suppress Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) in a Lyme disease endemic area of New Jersey. J Econ Entomol. 102(6):2316-2324. DOI: 10.1603/029.102.0638

Eisen L. (2020) Stemming the Rising Tide of Human-Biting Ticks and Tickborne Diseases, United States. Emerging Infectious Diseases. 26(4):641-647. DOI:10.3201/eid2604.191629.

EPA | Nootkatone Now Registered by EPA

EVOLVA |  Evolva receives US EPA registration for nootkatone, a next-generation protection against vector-borne diseases spread by insects

Flor-Weiler LB, Behle RW, Stafford KC 3rd. (2011) Susceptibility of four tick species, Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, and Rhipicephalus sanguineus (Acari: Ixodidae), to nootkatone from essential oil of grapefruit. J Med Entomol. 48(2):322-326. doi:10.1603/me10148

Galisteo Pretel, A., Pérez Del Pulgar, H., Olmeda, A. S., Gonzalez-Coloma, A., Barrero, A. F., & Quílez Del Moral, J. F. (2019). Novel Insect Antifeedant and Ixodicidal Nootkatone Derivatives. Biomolecules, 9(11), 742. https://doi.org/10.3390/biom9110742

Jordan RA, Schulze TL, Dolan MC. (2012) Efficacy of Plant-Derived and Synthetic Compounds on Clothing as Repellents Against Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) Journal of Medical Entomology. 49 (1): 101–106. DOI: 10.1603/me10241

Jordan RA, Dolan MC, Piesman J, Schulze TL. (2011) Suppression of Host-Seeking Ixodes Scapularis and Amblyomma Americanum (Acari: Ixodidae) Nymphs After Dual Applications of Plant-Derived Acaricides in New Jersey, Journal of Economic Entomology. 104(2):659–664. DOI: https://doi.org/10.1603/EC10340

Karchesy JJ, Kelsey RG, González-Hernández MP. (2018) Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology. J Chem Ecol. DOI: 10.1007/s10886-018-0956-y

McAllister JC, Adams MF. (2010) Mode of action for natural products isolated from essential oils of two trees is different from available mosquito adulticides. J Med Entomol. 47(6):1123-1126.  DOI: 10.1603/me10098

Morley R, Minceva M. Trapping multiple dual mode liquid-liquid chromatography: Preparative separation of nootkatone from a natural product extract. J Chromatogr A. 2020;1625:461272.

DOI: 10.1016/j.chroma.2020.461272

Panella NA, Dolan MC, Karchesy JJ, et al. (2005) Use of novel compounds for pest control: insecticidal and acaricidal activity of essential oil components from heartwood of Alaska yellow cedar. J Med Entomol. 42(3):352-358. DOI: 10.1093/jmedent/42.3.352

Schulze TL, Jordan RA, Dolan MC. (2011) Experimental use of two standard tick collection methods to evaluate the relative effectiveness of several plant-derived and synthetic repellents against Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae). J Econ Entomol.104(6):2062-2067. DOI: 10.1603/ec10421