Juniperus – Juniper Oil (Juniperi aetheroleum)
|Latin name of the genus:||Juniperus|
|Latin name of herbal substance:||Juniperi aetheroleum|
|Botanical name of plant:||Juniperus communis l.|
|English common name of herbal substance:||Juniper oil|
Latin name of the genus: Juniperus
Latin name of herbal substance: Juniperi aetheroleum
Botanical name of plant: Juniperus communis L.
English common name of herbal substance: Juniper Oil
- 1. Introduction
- 2. Historical data on medicinal use
- 3. Non-Clinical Data
- 3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- 3.4. Overall conclusions on non-clinical data
- 4. Clinical Data
- 4.1. Clinical Pharmacology
- 4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.2. Clinical Efficacy
- 4.2.1. Dose response studies
- 4.2.2. Clinical studies (case studies and clinical trials)
- 4.2.3. Clinical studies in special populations (e.g. elderly and children)
- 4.3. Overall conclusions on clinical pharmacology and efficacy
- 5. Clinical Safety/Pharmacovigilance
- 6. Overall conclusions
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Herbal substance(s) Not applicable.
The essential oil is obtained by steam distillation from the ripe,
Juniper berries (Juniperi
The plant has its origin in northern Europe and mountain areas. The herbal substance is imported among others from Italy, from the countries on the Adriatic coast and from Albania. Leaves are needles occurring in whorls of three on the branches. The
Four subspecies of Juniperus communis occurre in Europe: ssp. alpine (NEILR.) CELAK; ssp. communis; ssp. hemisphaerica (J. et C. PRESL), ssp. nana (Willd.) Syme (Hänsel et al. 1993).
Other species of Juniper mentioned in the literature are Juniperus oxycedrus, Juniperus phoenicea and Juniperus virginiana. Their oils are used as fragrance ingredients in cosmetics (Anonymous, 2001).
The ESCOP monograph refers to the cone berries from Greek plant material as containing high levels of essential oil. The cone berries may not contain less than 10 ml/kg of essential oil. The amount of essential oil can be up to 3%. The essential oil of Juniper cone berries contains about 105 constituents (ESCOP, 2003).
The following constituents were identified:
The composition of the essential oil varies depending upon the source but consists mainly of monoterpene hydrocarbons, principally monoterpenes (about 58% of the essential oil) (ESCOP 2003):
The qualitative composition of the oil is constant, but as already mentioned, the percentage of the components analysed with
bornylacetate (0.4 %) (range Ph.Eur. less than 2.0%)
Additionally the Ph.Eur. limits the concentration of
Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
1.2. Information about products on the market in the Member States
Regulatory status overview
MA: Marketing Authorisation TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration Other: If known, it should be specified or otherwise add ’Not Known’
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.
Details about preparations
1 This wording was from the substance/indication list established by a German expert commission for the traditional medicinal products (with respect to the earlier German legislation). It was the strategy to have a reduced indication.
2. Historical data on medicinal use
2.1. Information on period of medicinal use in the Community
Leclerc (1966) mentions case studies in the treatment of rheumatoid arthritis with a preparation of 8 g essential oil mixed with 4 g diethylether, to be taken in a dose of 10 drops a day.
The Extra Pharmacopoeia Martindale (Todd, 1967) refers to the British Pharmaceutical Codex of 1949 when mentioning the essential oil of Juniper, as the oil distilled from the dried ripe fruits of Juniperus communis. According to this source juniper oil is carminative and antiseptic and has been used in flatulence and colics. During excretion it irritates the
In Germany, Juniper oil is registered as an authorized preparation since 1976.
Soft capsules are used internally against dyspeptic complaints with minor abdominal cramps, flatulence and feeling of fullness. This indication is considered as a well established use.
It is also traditionally used as a bath additive to promote the blood circulation of the skin.
Kommission E considers Juniper only for ‘Dyspeptische Beschwerden’ or dyspepsia as a general complaint (Kommission E, 1984).
According to the ESCOP monograph, Juniper has a widely documented use as a remedy to enhance the renal elimination of water and for dyspeptic complaints. For these indications the monograph refers to handbooks and not to original research (ESCOP, 2003).
Besides its diuretic action, sometimes Juniper is also used as a urinary antiseptic, an indication which is disputed. The activity should be mainly limited to water diuresis, mainly due to an irritative action of
Therapeutic indications for the essential oil of Juniperus are mostly related to diuresis and dyspepsia.
There is a lot of discussion about the safe use of Juniperus. Some sources refer to the hyperemic effect of terpenes in the essential oil fraction to explain the diuretic action. Their action should be based on hyperemia of the glomeruli which is considered as an irritative action. Experimental pharmacological and toxicological data will be important in a constructive therapeutic approach.
The indication for external use (promoting blood circulation in the skin) can be questioned as being too close to a health claim for cosmetics but no medicinal indication.
2.2. Information on traditional/current indications and specified substances/preparations
The dried herbal substance is used in a dose of 2 g with a maximum of 10 g per day. According to some authors, this posology corresponds to 20 and 100 mg essential oil, respectively (Hänsel et al. 1993; Barnes et al. 2007; Ph. Eur. 2008).
Dose regimens for essential oil of Juniperus can be derived from the posology of the Juniper berries
Other sources recommend a daily dose of 20 to 100 mg (Hänsel et al. 1993). According to the Extra Pharmacopoeia Martindale (Todd, 1967) the dose can be 50 to 200 mg. It is not specified whether this dose is meant as a single or a daily dose. Most probably the upper daily limit is 200 mg.
In Germany soft capsules with 100 mg essential oil are registered as an authorized preparation. Posology is limited to 100 mg or one capsule orally per day. A bath additive with 6.993 g oil/100 g (approx. 94.5 ml) is used 3 to 4 times weekly:
Juniperus preparations should not be used for more than 4 weeks without medical advice.
There are some discrepancies as far as the dose is concerned. Doses up to 200 mg are mentioned with no clear reference to the daily dose regimen. It is recommended to stick to the reported doses of registered preparations. Therefore
2.3. Specified strength/posology/route of administration/duration of use for relevant preparations and indications
See section 1.2 and 2.2.
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Although this assessment report is focused on Juniperi aetheroleum studies with Juniperi pseudo- fructus are also included. In several studies, the essential oil as well as extracts are included in the same experimental setting. As a consequence it is difficult to separate them.
MIC = minimal inhibitory concentration (= no growth)
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
There were no data found about absorption, distribution, metabolism, elimination, or pharmacokinetic interactions with other medicinal products.
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
Gavage of megadoses is mentioned in original literature sources: up to 5 or 30 g Juniperus oil for one rabbit (respectively Gmeiner 1904 and Senon 1844 cited by Schilcher & Heil 1994). Whereas the rabbits survived a dose of 15 g essential oil, a dose of 30 g killed all animals within 24 hours.
Acute toxicity of the essential oil intraperitoneally injected in mice resulted in a mean LD50 = 750 (range
746) mg/kg was reported for mice after intramuscular application. For
Cardiovascular and respiratory toxicity
The effect of Juniper oil (Juniper species not stated) on the cardiovascular and respiratory system was evaluated using 20 rabbits, anesthetized with urethane. When Juniper oil was administered intramuscularly as well as orally (concentrations 0.5%, 2.5% and 5% in corn oil: dose 1 mg/kg) a prolonged and slowly developing hypotonia occurred (Anonymous, 2001).
Undiluted Juniper berry oil did not induce skin irritation when applied to the backs of hairless mice and swine. Moderate skin irritation occurred after the oil was applied to intact or abraded skin of rabbits for 24 hours under occlusive patches.
No phototoxicity effects were reported when the oil was applied to the skin of hairless mice and swine (Anonymous, 2001).
Reproductive and developmental toxicology
Experiments with Juniperus extracts were performed in several animal species. Abortifacient activity of Juniper has been observed in rats after oral administration of a 50% ethanolic extract at 300 mg/kg. (Agrawal et al. 1980, cited in ESCOP 2003)
There are no data about reproductive and developmental toxicology of Juniper oil.
There are no genotoxicity data available for Juniperus communis or preparations thereof. In the tar of Juniperus oxycedrus (cade oil) benzpyrenes were found in the nanogram/g range, but this does not apply to Juniperus communis (Hänsel et al. 1993).
According to one source the chemical composition of Juniperus communis oil and Juniperus communis
3.4. Overall conclusions on
The earliest experimental evidence for a diuretic activity goes back more than 70 years. Rats were mostly used as subjects. The peroral way of administration corresponds to traditional use in humans. The extracts are mostly prepared from whole cone berries, but also the essential oil and
Price & Price (2007) consider the diuretic properties as basic for Juniper: “… the property of Juniperus communis upon which all are agreed is its diuretic effect …”.
In contrast with the traditionally claimed indication, there is no experimental evidence for use in dyspeptic complaints.
Other activities include an
Furthermore antioxidant and antitumoral activity is reported in some experimental in vitro models. Extrapolations of these activities remain speculative.
The complex phytochemistry of Juniper essential oil makes it difficult to conceive any representative pharmacokinetic study. As a consequence no data are available.
Most reports of toxicity refer to the essential oil or essential oil components. No data on carcinogenicity and genotoxicity exist.
4. Clinical Data
4.1. Clinical Pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
There are no data available on human pharmacodynamics.
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
There are no data available on human pharmacokinetics.
4.2. Clinical Efficacy
4.2.1. Dose response studies
4.2.2. Clinical studies (case studies and clinical trials)
4.2.3. Clinical studies in special populations (e.g. elderly and children)
4.3. Overall conclusions on clinical pharmacology and efficacy
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
No data available.
5.2. Patient exposure
There is a lack of systematically obtained subacute clinical safety and toxicity data for Juniper, creating the need for safety update reporting. Standard references give contradictory information, mostly based upon interpretation by the authors and not on clinical data.
Schilcher & Heil are not convinced of the renal toxicity of Juniperus oil because quite a lot of sources may just have copied the doubtful renal side effects (Schilcher & Heil, 1994; ESCOP, 2003).
Nevertheless the German Kommission E only considered dyspepsia as the only therapeutic indication. The use of essential oil is questioned by some authors (Bruneton, 1999). Herewith a quote supported by Duke (1988): “… this drug is no longer recommended for various kidney disorders by the medical profession. Since much safer and more effective diuretic and carminative drugs exist, the use of Juniper in folk medicine should also be abandoned …”. The author does not refer to case studies or causality reporting. Not all German sources limit the use of Juniper. Weiss & Fintelman (1999) consider the cone berries of Juniperus communis as valuable ‘aquaretica’. They include the following conditions for traditional use: unspecific dysuria, sensitive bladder (‘Reizblase’) and prophylaxis of relapsing urolithiasis and urinary infections.
In Belgium, only Juniperus sabina L. is prohibited to be used in food or food supplements. The cone berries of Juniperus communis L., Juniperus procera Hochst. and Juniperus virginiana L. are permitted, as notified ingredients of food supplements. Also the use of Juniperus oxycedrus L. is allowed (Anonymous, 1997).
5.3. Adverse events and serious adverse events and deaths
Most handbooks warn for renal damage when Juniperus communis preparations are used for their aquaretic properties.
Renal damage has been reported after long term use (several months). Overdosing with the essential oil leads to renal damage.
According to Semon (1844; cited by Schilcher & Heil 1994), Juniper oil increases the renal circulation and dose dependent damage can occur (stranguria, dysuria, hematuria and ischuria). The activity of Juniper oil was formerly compared with terpentine oil. Most probably the findings for terpentine oil were copied to Juniper oil without factual analysis. Also Potter (1898; cited by Schilcher & Heil, 1994) mentioned Juniper cone berries in his Materia Medica: “… may set up renal irritation, in large doses producing strangury, priapism; hematuria, suppression of the urine and uremic convulsions …”, a wording taken over by the German literature. Although the volatile oil is reported to be generally non- sensitising and
Two irritation reactions were observed in 2 of 20 subjects
Seizures and kidney damage have been reported in individuals who took more than 10 g of Juniper per day or who took high doses of Juniper for longer than 4 weeks. The way and form of administration is however not specified. Also the exact dose (“… more than 10 g …”) is not mentioned. The same source recommends a maximal daily dose of 10 g of dried Juniper cone berries. However the source is not scientifically documented
access on September 13 2010). If such reactions occur, they may be caused by contamination of the oil (Schilcher et al. 2007).
It can be questioned whether the oil of Juniper, blamed for its renal toxicity was contaminated with terpentine oil. Some sources even use the term ‘falsification’. By preference the concentration of α- and
Serious adverse events and deaths
5.4. Laboratory findings
No data available.
5.5. Safety in special populations and situations
The use of Juniperus communis is
Intrinsic (including elderly and children) /extrinsic factors
No data available.
There is limited evidence from preclinical studies that Juniper may influence glucose levels in diabetes. However, there will be no warning in the monograph, as the experimental data from different experiments are contradicting (ESCOP, 2003; Barnes et al. 2007).
Use in pregnancy and lactation
As the cone berries should not be used during pregnancy and lactation, use of essential oil in these conditions is also not recommended. It is generally accepted that Juniper should not be used by pregnant women as uretral contractions could occur (Duke 1988).
In case of prolonged use and overdose, urine will smell of violets. There may be renal irritation and pain in and near the kidney, strong diuresis, albuminuria, haematuria, purplish urine, gastrointestinal upsets, accelerated heartbeat and blood pressure. Rarely symptoms of central stimulation like convulsions occur as well as metrorrhagia and abortion (Wichtl, 1994; Duke, 1988).
No data available.
Withdrawal and rebound
No data available.
Effects on ability to drive or operate machinery or impairment of mental ability
No data available.
5.6. Overall conclusions on clinical safety
Issues of safety monitoring of the essential oil of Juniperus are related to:
the preparation: the effect depends on the concentration of compounds and thus on the solvents used and the way of extraction; as both the cone berries and the essential oil have a possible antioxidant effect, the original composition has to be considered;
the patients: apart from preclinical data on reproductive toxicology, little is known about possible groups at risk and interactions with other medication;
the physiological condition: it can be expected that the kidney will be the first target organ.
There seems to be confusion about the possible toxicity of Juniper oil and data obtained with terpentine oil. The findings reported by Semon (Semon 1844; cited by Schilcher & Heil 1994) have been copied several times without further analysis.
6. Overall conclusions
The traditional use of Juniperus communis aetheroleum and preparation thereof should be limited to the stimulation of renal water excretion and to dyspeptic disorders. The former is sustained by tradition and by experimental evidence, the latter only by tradition.
There is a need for systematic pharmacovigilance reporting in order to address the issue of subacute safety when using different preparations of Juniper.
Juniper essential oil is described in the European Pharmacopoeia. Adulteration and contamination remain possible: unripe berries should not be used. Essential oil should only be prepared from ripe berries, without any needles or wood from the tree. Contaminated oil can indeed affect the renal function, so quality should be proven. However, reports on cases of overdose or prolonged use are vague and of bad quality, not meeting the pharmacovigilance criteria. Pharmacokinetics of Juniper components are not known.
As genotoxicity has not been studied, a list entry cannot be granted.
The therapeutic indication for cutaneous use is close to a health claim for cosmetics and the status of a medicine in that context can be questioned. The therapeutic indications for oral use are far from life threatening and suitable for