Rosemary – Safe or Toxic?

Rosemary – Safe or Toxic?

Author: Katt Crouch

It is a commonly held belief by pet owners that Rosemary is toxic to their pets – but is it really? Something that few people are aware of is that there are actually two different forms of Rosemary used in pet food products – Rosemary Oil, and Rosemary Extract. Rosemary Oil and Extract are very similar, and are both used as food preservatives; however, they are slightly different substances with slightly different properties.

Rosemary Oil is an essential oil (EO). It is extracted from the rosemary plant via a process known as distillation. The oil consists of primarily alpha-pinene, bornyl acetate, and verbenone, with some amount of 1,8-cineole, borneol, camphor, camphene, and limonene (Boutekediiret et. al, 1999; Irmak et al., 2010; Kadri et al., 2011; Pintore et al., 2002). Rosemary Oil is believed by many to be neurotoxic in dogs, yet a very extensive literature search revealed no research linking Rosemary Oil to neurotoxicity. In fact, despite several hours of searching, only one research paper was found indicating any toxicity of Rosemary Oil. This paper (Maistro et al., 2010) found oral application of Rosemary essential oil to cause significant increases in DNA damage in mice.

One research team (Burkhard et al., 1999) underwent a case study of three healthy patients who experienced seizures after the use of therapeutic oils. While many online articles and published journal articles reference this paper, there are in fact no direct indications in the paper whatsoever that rosemary causes seizures beyond one reference to a French article. In fact, the Burkhard et al. (1999) case study did not study the effects of rosemary oil at all – the 3 cases of plant-induced seizures included 2 cases involving sage essential oil, and one case involving eucalyptus, pine, and thyme. The only indication in the study that rosemary may cause seizures is the single reference to the single French article, which Burkhard et al. (1999) claim shows rosemary oil to be epileptogenic (seizure causing). A very extensive search of the literature pulled up nothing to directly indicate that Rosemary causes seizures, but did reveal several articles that briefly mention Rosemary Oil as a “known epileptogenic.” However, upon closer inspection EVERY single one of those studies used Burkhard et al (1999) as their only reference for this information. It was one big, unproductive, uninformative loop! As I was unable to obtain access to the French journal, I decided to go directly to the source. Burkhard et al’s (1999) article suggested that the Epileptogenic (seizure causing) compounds of Rosemary Oil were Cineole and Camphor. So I did a search for those instead…

After some digging I was finally able to get some results. Indeed, there are multiple studies that indicate Cineole and Camphor can induce seizures in both humans and animals (Culic et al., 2009; Gazdag et al., 2009; Khine et al., 2009; WHO, 2011). The World Health Organization (2011) even indicated that medications containing turpenic derivatives (such as camphor) have a risk of “introducing neurological disorders, especially convulsions,” in young children and should not be used in children under 30 months or with a history of epilepsy or fever-induced seizures.

Rosemary Extract is a slightly different substance from Rosemary Oil. It consists of carnosic acid, carnosol, and rosmarinic acid. Rosemary Extract however, still contains very similar amounts of Camphor and Cineole to the amounts found in Rosemary Oil. The extract is made by a slightly different process from the distillation used to make oils. (European Commission, 2005; Genena et al., 2008; Moreno et al., 2006; Sensorans et al., 2000; Thorsen, Hildebrandt, 2003; Tschiggerl, Bucar, 2010).

What you really want to know though, is IS Rosemary Extract neurotoxic as so many people believe? I have searched high and low for evidence of this and have not managed to find a single article reporting neurotoxic effects of Rosemary Extract, nor did I find anything regarding Rosemary Extract and seizures. The only link to these effects is the fact that the extract, like the oil, contains Camphor and Cineole.

Some studies found that the use of oral Rosemary Extract in rodents led to a decreased sperm count in males (Joshi et al., 2011; Nusier et al., 2007). Another study found that Rosemary Extract may lead to an “anti-implantation effect,” meaning that some fertilized eggs in females could not implant in the uterus, but stated that after implantation the extract did not adversely affect the fetus (Lemonica et al., 1996). While these results may sound alarming to some there are two key factors that you must keep in mind. The first is, most ferret owners are unable and/or do not intend to breed their ferrets, so a decrease in fertility is largely irrelevant. Secondly, the doses of Rosemary Extract used in these studies were far beyond the amounts that you would find in pet food products.

A study of the toxicity of Rosemary Extract in rats found that the extract was only acutely toxic at doses above 2,000 mg (2 grams) of extract per kilogram of body weight (2g/kg was tolerated by the rats with NO adverse effects) (Anadon et al., 2008). One kilogram is equal to 2.2lb – close to the average weight of a domestic ferret. If you look at any pet food product label that contains Rosemary Extract you will see that it is one of the last ingredients on the list, as it is used primarily as a preservative. When reading pet food labels, the ingredients are listed in descending order of content by weight. The last ingredients are, by weight, present in the smallest amounts in foods. Thus, Rosemary Extract is present in only very small amounts in pet food products.

On the OTHER hand…. In my searching I came across several studies of the benefits of Rosemary Extract. Multiple studies found that Rosemary Extract had hepatoprotective effects – meaning that it protected the liver from damage (Amin et al., 2005; Hasani- Ranjbar et al., 2009; Ramadan et al., 2013). Other studies found that the Extract helped to combat diabetes, high cholesterol, and moderates weight gain (even when fed a fatty diet) (Bakirel et al., 2008; Ibarra et al., 2011; Ramadan et al., 2013; Tu et al., 2013; Vaquero et al., 2013). Some researchers found that Rosemary Extract may help to protect against ulcers (Amaral et al., 2013). One study showed that in rats, Rosemary Extract helped to protect major organs in aged animals (Posadas et al., 2009). Rosemary Extract and Oil are both also known to have great antimicrobial properties (prevents bacterial growth), and are considered powerful antioxidants – which is precisely why they are used as preservatives in foods (Carvalho et al., 2005; European Commission, 2005; Genena et al., 2008; Hasani-Ranibar et al., 2009; Kadri et al., 2011; Mangena et al., 1999; Moreno et al., 2006; Ortuno et al., 2014; Pintore et al., 2002; Vicente et al., 2013).

In stark contrast to the common belief that Rosemary Extract is neurotoxic, I actually found several articles indicating that Rosemary Extract may be Neuroprotective (Aruoma et al., 2003; Azad et al., 2010; Kayashima et al., 2009; Park et al., 2010)! Yet another study indicated that Rosemary Extract may aid in preventing depression (Machado et al., 2009). Probably the most relevant to ferrets though, with their high propensity for developing cancers, are the several studies that I found showing that Rosemary Extract can help fight cancer. Studies found that Rosemary Extract can significantly slow tumor growth in various types of cancer, and may assist in making treatments for cancer more effective (Gonzalez-Vallinas, Molina, Vicente, Sanches-Martinez, et al., 2014; Gonzalez-Vallinas, Molina, Vicenta, Cueva, et al., 2013; Gonzalez-Vallinas, Molina, Vicenta, Zarza, et al., 2014; Petiwala et al., 2014; Vicente et al., 2013; Yi et al., 2011).

What does this mean for our pets? I cannot tell you what to feed or not feed your pets, all I can do is provide information. It is up to you to make an informed decision for your family members. I strongly encourage everyone to do their own research, but be careful what you read. Check sources and always go to the original studies whenever possible.

Rosemary Oil is an Essential Oil; EO’s are believed to be toxic to cats as they lack a liver enzyme (glucuronyltransferase), needed to break them down (Court et al, 2000). Most assume that as fellow obligate carnivores with similar metabolic physiology, this may also be true of ferrets. As the age-old rule goes, “Better safe than sorry.” It is typically not recommended to use any product containing EO’s in, on, or around cats or ferrets. In addition to its potential danger as an EO, the study indicating that Rosemary Oil may increase DNA mutations in cells (which could increase risk of developing cancer) raises some concerns about the safety of the oil (Maistro et al., 2010), particularly in a species that is already very cancer-prone.

Rosemary Oil and Rosemary Extract both contain a portion of Camphor, and of Cineole, which have been found to cause seizures when ingested at toxic levels and are particularly dangerous to the very young, the very old, and those with pre-existing seizure disorders (Culic  et al., 2009; Gazdag et al., 2009; Khine et al., 2009; WHO, 2011). While Camphor and Cineole are present in significant amounts in both the oil and the extract, they are still only a portion of the complete substance. They are then further diluted by other ingredients when the extract or oil is added to food substances. The relative amount of Camphor and Cineole in the food when all is said and done, is very low. It is easy to think “but if it can cause problems I don’t want ANY of it,” but keep in mind that almost all supplements and medications are toxic in the right dose. In small amounts many substances can be beneficial (or at the very least harmless); however, these same substances given in larger doses can be extremely toxic. Rosemary Extract requires a high dose to reach toxicity. The chance of ever ingesting a high enough dose from a pet food product to reach toxicity is extremely low.

Rosemary Extract may have many wonderful benefits, from ulcer protection, to organ and neuro protection, to cancer fighting properties. This, combined with the very low toxicity of the Extract makes it difficult to suggest going out of your way to avoid products containing Rosemary Extract. It may be best to avoid using it in breeding animals however, due to its possible effects on fertility (though again, the studies used a greatly higher dose than that found in pet foods).

In summary, Rosemary Oil is an Essential Oil, and thus should be avoided with cats and ferrets and additionally, may have some DNA damaging effects. Rosemary Extract however, is of very low toxicity and may provide some health benefits to our furry little friends. Both substances contain Camphor and Cineole, which can cause seizures at toxic doses, but the relative amount of these substances in pet products is low and unlikely to even approach toxic levels.

 

 

References

Al-Ereitia, M., Abu-Amerb, K., Sena, P. (1999). Pharmacology of rosemary (rosmarinus officinalis linn.) and its therapeutic potentials. Indian Journal of Experimental Biology. 37: 124-131.

Amaral, G., Rodrigues, N., Carvalho, N., Barcelos, R., Dobrachinski, F., de Lima Portella, R., da Silva, M., Lugokenski, T., Dias, G., da Luz, S., Boligon, A., Athayde, M., Villetti, M., Soares, F., Fachinetto, R. (2013). Protective action of ethanolic extract of rosmarinus officinalis l. in gastric ulcer prevention induced by ethanol in rats. Food and Chemical Toxicology. 55: 48-55.

Amin, A., Hamza, A. (2005). 77 (3). Hepatoprotective effects of hibiscus, rosmarinus, and salvia on azathioprine-induced toxicity in rats. Life Sciences. 77 (3): 266-278.

Anadon, A., Martinez-Larranaga, M., Martinez, M., Ares, I., Garcia-Risco, M., Sensorans, F., Reglero, G. (2008). Acute oral safety study or rosemary extracts in pets. Journal of Food Protection. 71 (4) 790-795.

Aruoma, O., Bahorun, T. Jen, L. (2003). Neuroprotection by bioactive components in medicinal and food plant extracts. Mutation Research. 544: 203-215.

Azad, N., Rasoolijazi, H., Taghi Joghataie, M., Soleimani, S. (2010). Neuroproective effects of carnosic acid in an experimental model of alzheimer’s disease in rats. Cell Journal. 13 (1): 39-44.

Bakirel, T., Bakirel, U., Keles, O., Ulgen, S., Yardibi, H. (2008). In vivo assessment of antidiabetic and antioxidant activities of rosemary (rosmarinus officinalis) in alloxan-diabetic rabbits. Journal of Ethnopharmacology. 116 (1) 64-73.

Boutekedjiret, C., Bentahar, F., Belabbes, R., Bessiere, J. (2003). Extraction of rosemary essential oil by steam distillation and hydrodistillation. Flavour and Fragrance Journal. 18: 481-484.

Burkhard, P., Burkhardt, K., Haenggeli, C., Landis, T. (1999). Plant-induced seizures: Reappearance of an old problem. J Neruol. 246: 667-670.

Carvalho Jr, R., Moura, L., Rosa, P., Meireles, M.A. (2005). Supercritical fluid extraction from rosemary (rosmarinus officinalis): Kinetic data, extract’s global yield, composition, and antioxidant activity. The Journal of Supercritical Fluids. 35 (3) 197-204.

Court, M., Greenblatt, D. (2000). Molecular genetic basis for deficient acetaminophen glucoronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics. 10 (4): 355-369.

Culic, M., Kekovic, G., Grbic, G., Martac, L., Sokovic, M., Podgorac, J., Sekulic, S. (2009). Wavelet and fractal anaylsis of rat brain activity in seizures evoked by camphor essential oil and 1,8-cineole. Gen Physiol Biophys. 28: 33-40.

European Commission. (2005). Evaluation report of the community reference laboratory feed additives authorisation on the method(s) of analysis for rosemary extract liquid. European Commission Directorate-General Joint Research Center; Institute for Reference Materials and Measurements. Belgium.

Gazdag, G., Bitter, I., Ungvari, G., Baran, B., Fink, M. (2009). Laszlo meduma’s pilot studies with camphor inductions of seizures. Journal of ECT. 25 (1): 3-11.

Genena, A., Hense, H., Smania Junior, A., Souza, S. (2008). Rosemary (rosmarinis officinalis) – a study of the composition, antioxidant and antimicrobial activities of extracts obtained with supercritical carbon dioxide. Clenc Technol Altment.28 (2): 463-469.

Gonzales-Vallinas, M., Molina, S., Vicente, G., Sanches-Martinez, R., Vargas, T., Garcia-Risco, M., Fornari, T., Reglero, G., Ramirez de Molina, A. (2014). Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells. Electrophoresis. 35 (11): 1719-1727.

Gonzalez-Vallinas, M., Molina, S., Vicenta, G., Cueva, A., Vargas, T., Santoyo, S., Garcia-Risco, M., Fornari, T., Reglero, G., Ramirez de Molina, A. (2013). Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells. Pharmacological Research. 72: 61-68.

Gonzalez-Vallinas, M., Molina, S., Vicenta, G., Zarza, V., Martin-Hernandez, R., Garcia-Risco, M., Fornari, T., Reglero, G., Ramirez de Molina, A. (2014). Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of rosemary diterpenes in colon and pancreatic cancer. PLoS One. 9 (6): e98556.

Hasani-Ranjbar, S., Larikani, B., Abdollahi, M. (2009). A systematic review of the potential herbal sources of future drugs effective in oxidant-related-diseases. Inflammation & Allergy – Drug Targets. 8: 2-10.

Ibarra, A., Cases, J., Roller, M., Chiralt-Boix, A., Coussaert, A., Ripoll C. (2011). Carnosic acid-rich rosemary (rosmarinus officinalis) leaf extract limits weight-gain and improves cholesterol levels and glycaemia in mice on a high-fat diet. Br J Nutr. 106 (8): 1182-1189.

Irmak, S., Solakyildirim, K., Hesenov, A., Erbatur, O. (2010). Study on the stability of supercritical fluid extracted rosemary (rosmarinus officinalis l) essential oil. Journal of Analytical Chemistry. 65 (9): 899-906.

Joshi, S., Sharma A., Chaturvedi, M. (2011). Antifertility potential of some medicinal plants in males: An overview. International Journal of Pharmacy and Pharmaceutical Sciences. 3 (5): 204-217.

Kadri, A., Zarai, Z., Chobba, I., Bekir, A., Gharsallah, N., Damak, M., Gdoura, R. (2011). Chemical constituents and antioxidant properties of rosmarinus officinalis l. essential oil cultivated from the south-western tunisia. Journal of Medicinal Plants Research. 5 (28) 6502-6508.

Kayashima, T., Matsubara, K. (2012). Antiangiogenic effect of carnosic acidand carnosol, neuroprotective compounds in rosemary leaves. Biosci Biothecnol Biochem. 76 (1): 115-119.

Khine, H., Weiss, D., Graber, N., Hoffman, R., Esteban-Cruciani, N., Avner, J. (2009). A cluster of children with seizures caused by camphor poisoning. Pediatrics. 123 (5) 1269-1272.

Lemonica, I., Damasceno, D., di-Stasi, L. (1996). Study of the embryotoxic effects of an extract of rosemary (rosmarinus officinalis l.). Braz J Med Biol Res. 29 (2): 223-227.

Machado, D., Bettio, L., Cunha, M., Capra, J., Dalmarco, J., Pizzolatti, M., Rodrigues, A. (2009). Antidepressant-like effect of the extract of rosmarinus officinalis in mice: Involvement of the monoaminergic system. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 33: 642-650.

Maistro, E., Mota, S., Lima, E., Bernardes, B., Goulart, F. (2010). Genotoxicity and mutagenicity of rosmarinis officinalis (labiatae) essential oil in mammalian cells in vivo. Genetics and Molecular Research. 9 (4) 2113-2122.

Mangena, T., Muyima, N. (1999). Comparative evaluation of the antimicrobial activities of essential oils of Artemisia afra, pteronia incana, and rosmarinus officinalis on selected bacteria and yeast strains. Letters in Applied Microbiology. 28: 291-296.

Moreno, S., Scheyer, T., Romano, C., Vojnov, A. (2006). Antioxidant and antimicrobial activities of rosemary extracts linked to their polyphenol composition. Free Radical Research. 40 (2): 223-231.

Nusier, M., Batauneh, H., Daradkah, H. (2007). Adverse effects of rosemary (rosmarinus officinalis l.) on reproductive function in adult male rats. Experimental Biology and Medicine.232 (6) 809-813.

Ortuno, J., Serrano, R., Jordan, M., Banon, S. (2014). Shelf life of meat from lambs given essential oil-free rosemary extract containing carnosic acid plus carnosol at 200 or 400 mg kg-1. Meat Science. 96: 1452-1459.

Park, S., Kim, S., Sapkota, K., Kim, S. (2010). Neuroproective effect of rosmarinus officinalis extract on human dopaminergic cell line, SH-SY5Y. Cellular and Molecular Neurobiology. 30 (5): 759-767.

Petiwala, S., Berhe, S., Li, G., Puthenveetil, A., Rahman, O., Nonn, L., Johnson, J. (2014). Rosemary (rosmarinus officinalis) extract modulates CHOP/GADD153 to promote androgen receptor degradation and decreases xenograft tumor growth. PLoS One. 9 (3): e89772.

Pintore, G., Usai, M., Bradesi, P., Juliano, C., Boatto, G., Tomi, F., Chessa, M., Cerri, R., Casanova, J. (2002). Chemical composition and antimicrobial activity of rosmarinus officinalis l. oils from Sardinia and Corsica. Flavour and Fragrance Journal. 17: 15-19.

Posadas, S., Caz, V., Largo, C., De la Gandara, B., Matallanas, B., Reglero, G., De Miguel, E. (2009). Protective effect of supercritical fluid rosemary extract, rosmarinus officinalis, on antioxidants of major organs of aged rats. Experimental Gerontology. 44: 383-389.

Ramadan, K., Khalil, O., Danial, E., Alnahdi, H., Ayaz, N. (2013). Hypoglycemic and hepatoprotective activity of rosmarinus officinalis extract in diabetic rats. Journal of Physiology and Biochemistry. 69 (4): 779-783.

Sensorans, F., Ibanez, E., Cavero, S., Tabera, J., Reglero, G. (2000). Liquid chromatographic-mass spectrometric analysis of supercritical-fluid extracts of rosemary plants. Journal of Chromatography A. 870 (1-2), 491-499.

Thorsen, M., Hildebrandt, K. (2003). Quantitative determination of phenolic diterpenes in rosemary extracts: Aspects of accurate quantification. Journal of Chromatography A. 995 (1-2), 119-125.

Tschiggerl, C., Bucar, F. (2010). Investigation of the volatile fraction of rosemary infusion extracts. Scientia Pharmaceutica. 78 (3): 483-492.

Tu, Z., Moss-Pierce, T., Ford, P., Jiang, T. (2013). Rosemary (rosmarinus officinalis l.) extract regulates glucose and lipid metabolism by activating AMPK and PPAR pathways in HepG2 cells. J Argic Food Chem. 61 (11) 2803-10.

Vaquero, M., Yanez-Gascon, M., Villalba, R., Larrosa, M., Fromentin, E., Ibarra, A., Roller, M., Tomas-Barberan, F., de Gea, J., Garcia-Conesa, M. (2012). Inhibition of gastric lipase as a mechanism for body weight and plasma lipids reduction in zucker rats fed a rosemary extract rich in carnosic acid. PLoS One. 7 (6): e39773.

Vicente, G., Molina S., Gonzales-Vallinas, M., Garcia-Risco, M., Fornari, T., Reglero, G., Ramirez de Molina, A. (2013). Supercritical rosemary extracts, their antioxidant activity, and effect on hepatic tumor progression. The Journal of Supercritical Fluids. 79: 101-108.

World Health Organization (2011). WHO Drug Information Volume 24 Issue 4 Page 359. Geneva: Switzerland.

Yi, W., Wetzstein, H. (2011). Anti-tumorigenic activity of five culinary and medicinal herbs grown under greenhouse conditions and their combination effects. Journal of the Science of Food and Agriculture. 91 (10): 1849-1854.