There is substantial reference to historic use of Oil of Oregano from Hippocrates (500BC), Discordes (1st century AD) and Paracelsus (AD 16th century). Oregani herba also has an official monograph in the European Pharmacopoeia since 2005. Due to its phenomenal healing properties it made its way out of the eclectic texts and to the laboratories of a variety of researchers. Studies have shown that Oil of Oregano is hepato-protective as well as geno-protective, it has been shown to be effective against enteric parasites and is effective as a general antimicrobial agent, in fact Oil of Oregano has been shown to be effective against MRSA where other antibiotics have failed. The antimicrobial and antioxidant activities of Oil of Oregano are quite well known, however studies have also shown that it has numerous other properties. These include anti-tumour, anti-platelet, anti-inflammatory, anti-spasmodic, anti-elastase, and analgesic effects; furthermore recent investigations have shown that it also has anti-depressant activities. Unfortunately the majority of the research has been done using animal models and there is lack of human data.
The Natural Health Product Directorate (NHPD) has estimated the minimum lethal dose of carvacrol, the active constituent of Oil of Oregano to be 2.7 mg/kg body weight/day which is equivalent to 189 mg for an average adult. This dose has been extrapolated from LD50=100 mg/kg b.w. in rabbits, referenced in the Merk Index (1976), based on toxicity data from Kochmann (1931). However on closer inspection of this archaic publication it appears that the study is weak, for example the investigation primarily focuses on chlorcarvacrol, and the effects of carvacrol are secondary, what's more not all the study animals are administered carvacrol.
The lethal dose of chlorcarvacrol in mice given subcutaneously was 1500 mg/kg, higher than that of rabbits (>300 mg/kg), and it appears that carvacrol was not administered to mice. In addition the lethal dose when given orally to dogs is 5000-10000 mg/kg, much higher than 750-1000 mg/kg in rabbits; again data for carvacrol is not included. It would be interesting to know why rabbit and cats were given carvacrol, especially when dogs and mice tolerated a higher dose of chlorcarvacrol. It could be possible that administration was carried out, but no toxicity was observed. From this data however it would be reasonable to argue that the lethal dose of carvacrol in mice and dogs would most likely be higher than the 100 mg/kg seen in rabbits. The other factors to consider is the lack of information regarding the animals, number of animals, where they were acquired, housing standards adhered to, general health and age at dosing. All these factors are required in current publications to be considered acceptable. In addition control data is absent and there is lack of methodology.
In mice chlorcarvacrol at 1000 mg/kg in a 2% oily solution given subcutaneously does not appear to cause any adverse reactions; however they do at a higher dose of 1500 mg. These doses are still higher than the lethal dose in rabbits. Why was carvacrol not given to mice for comparison and why was there no oral administration of chlorcarvacrol?
The doses given to rabbits were prepared in two ways, dissolution in oil, for oral and subcutaneous administration and emulsification with gum; there are no other details about the specifics of the preparation and no mention of whether carvacrol was prepared in the same way. The authors state that with oral administration of 750 mg half the animals died whereas with higher doses of 1000 mg/kg all the animals died. Does this not question whether there may be additional factors influencing the rabbits reaction to chlorcarvacrol? For example, were they all healthy? Were they all the same age? In addition higher doses of 3000 mg/kg dissolved in olive oil given subcutaneously did not cause any lethality. They also found that animals given higher doses of chlorocarvacrol orally had low levels of protein in their urine, loss of appetite and weight loss and at autopsy irritation of the gastrointestinal tract and fatty livers were observed. In order to complete this picture animal weights should have been given as well as a numerical indication of the protein as well as the proportion of animals this occurred in, i.e. was it all of the animals that died? There is also mention of differences in pathological changes in the oral preparations, but are not addressed completely. The only negative side effect of subcutaneous administration mentioned is that there was weight loss in animals given higher doses of 1000 mg/kg, which was regained within a week, with animals often gaining more weight. The proportion of animals and weights are not given. What is striking is the difference in the effect of route of administration and the authors suggest that it may be related to the irritation of the gastrointestinal tract.
In the cat and dog no subcutaneous administration of chlorcarvacrol was carried out and the same oral preparations were administered as in the rabbit. In cats sub-lethal doses of 500-750 mg/kg did not result in toxic effects and the weight and height remained the same. At the lethal doses of 1000 mg/kg similar symptoms to the rabbit were observed. It appears that dogs tolerated the doses better reaching lethal doses at 5000-10000 mg/kg; it is unfortunate that carvacrol was not administered for comparison. Small dogs were given 250 mg/kg, 500 mg/kg and 1000 mg/kg chlorcarvacol in 10% oily solution and at the two lower doses there was a slight loss of body weight and at the higher doses there was substantial weight loss and vomiting in about 20% of animals (translation is unclear, there could be weight loss in 20% of animals, or vomiting in 20% animals), the urine however was free of protein. Weights are not given and again there are no controls, it is also unclear whether this was a separate experiment using 'small dogs' different from the dogs used to calculate LD50.
What is interesting is that the authors mention using a 24.5 kg dog for a 23 day trial, where it was given 1000 mg chlorcarvacol with its feed. In this animal no toxic symptoms were observed. Moreover a similar experiment was carried out with the administration of carvacrol with the same results and no specifications of this experiment are given. In this study carvacrol was administered to cats and rabbits, there are no particulars on the experiment, just that the pathological-anatomical changes are consistent with those observed after chlorcarvacrol. There are no particulars of the experiments just that after oral administration of 100 mg/kg death occurs 23-26 days later. This raises questions about the mechanism of action in these animals and how they process it. The delayed lethality should be addressed.
Due to the lack of human data NHPD is limiting the daily dose of carvacrol based on the LD50 value from the Kochmann study. However together with its traditional use general use today, with no reports of adverse reactions, should be evidence for its safe use in itself. Furthermore in Turkey Oregano Water is sold in supermarkets which contains 0.01% oil comprising 70-80% carvacrol, and it is reported that some people consume as much as 1 liter of this extremely bitter distilled water of oregano a day without any adverse effects. Industry members now have a choice of either accepting the limit or 'pushing back' and asking for further assessment of carvacrol. As it stands NHPD are assessing applications with carvacrol within the accepted limit but will be refusing applications outside this limit unless further evidence is presented that can be used to reassess the maximum lethal dose in humans.
