Juniperus – Juniper berry (Juniperi pseudo-fructus)
|Latin name of the genus:||Juniperus|
|Latin name of herbal substance:||Juniperi pseudo-fructus|
|Botanical name of plant:||Juniperus communis l.|
|English common name of herbal substance:||Juniper berry|
Latin name of the genus: Juniperus
Latin name of herbal substance: Juniperi pseudo-fructus
Botanical name of plant: Juniperus communis L.
English common name of herbal substance: Juniper berry
- 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
- 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
The herbal substance is mentioned in the DAB 10, ÖAB 90, Ph. Fr. X, Ph. Helv. VII, British Herbal Pharmacopoeia 1983 and the European Pharmacopoeia 6.0. It is described as ‘dried ripe cone berry of Juniperus communis L.’. The plant part is described as 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 with three on the branches. The
There are 4 subspecies of Juniperus communis occurring in Europe: ssp. alpine (NEILR.) CELAK; ssp. communis; ssp. hemisphaerica (J. et C. PRESL), ssp. nana (Willd.) Syme (Hänsel et al. 1993). Adulteration is occasionally observed with fruits of other Juniperus species. Fruits from Juniperus oxycedrus L. (cade- or
Other species of Juniper mentioned in literature are Juniperus oxycedrus, Juniperus phoenicea and Juniperus virginiana. Their oils are used only as fragrance ingredients in cosmetics (Anonymous, 2001).
Composition of the cone berries has been described by Hänsel et al. (1993), Schilcher & Heil (1994), Bruneton (1999), Barnes et al. (2007), Duke (1988), in the ESCOP monograph (ESCOP, 2003), Martin et al. (2006) The cone berries contain between 0.5 and 3.42 % of essential oil. The content of essential oil may vary depending on the origin of the herbal substance (Banthorpe et al. 1973).
The ESCOP monograph refers to 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 in Juniperi
Monoterpenes (about 58% of the essential oil); the essential oil contains mainly
Diterpenic acids: isocommunic acid; labdane diterpenes
C12 terpenoid: geijerone
Tannins: proanthocyanidines (condensed), gallocatechin and epigallocatechin
Flavonoids: amentoflavone, quercitin, isoquercitrin, apigenin and various glucosides
Invert sugar (30%); glucose + fructose (about 30%) and pectin
Organic acids: malic acid, ascorbic acid, glucuronic acid
Juniper in: an amorphous substance isolated from decoctions (most probably a complex of sugars and tannins)
There is no consensus about the possible role of sugars, salts and saponins in the cone berries. The content of the cone berries varies with the origin and the ripening.
Herbal preparation(s) See above.
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.
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.
1.3. Search and assessment methodology
2. Historical data on medicinal use
2.1. Information on period of medicinal use in the Community
Historically, the cone berries were used in a diuretic wine recommended by Cato the Ancient in his book ‘De re rustica’. Leclerc (1966) mentions also 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 famous Oil of Haarlem or ‘Haarlemmer olie’ contains Juniper
Cone berries were traditionally used for dyspepsia (tincture and fluid extract), acute and chronic cystitis, arteriosclerosis, gout and inflammations. Furthermore, menstruation pain and bleeding, irritative cough, flu related bronchitis and diabetes are mentioned. Topical use is related to muscle pain and acute arthritic conditions (Hänsel et al. 1993; Barnes et al. 2007).
Babulka (2000) describes the use of medicinal herbs in Hungary. Juniperus communis is reported to be used for
Schulz (1929 cited by Schilcher & Heil, 1994) mentions the successful use of Juniper berry juice for treatment of nephritic hydrops. Whereas Klare (1927 cited by Schilcher & Heil, 1994) reports its use in case of paediatric tuberculosis. The first reports about the diuretic action in humans date from more than one century ago (Raphael, 1894 and Breitenstein, 1902, both cited by Schilcher & Heil, 1994). Most probably Raphael used 300 mg essential oil, two times daily during several months. Raphael considered the essential oil as a whole and not just one group of compounds, more particularly terpenes.
The German Commission E considered Juniper only for ‘Dyspeptische Beschwerden’ or dyspepsia as a general complaint (Commission E, 1984).
In France, Juniperi
(1) appetite stimulant; (2) renal evacuation of water; (3) diuretic adjuvant in case of minor urinary complications (Bruneton, 1999). In France, a toxicological dossier must be prepared for tinctures or extracts with an alcohol strength above 30% (V/V). No toxicological data have to be explicited for tinctures and extracts with an alcohol strength of 30% or lower (De Smet et al. 1993).
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 for 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
The cone berries are widely used as a flavouring component in spirits (e.g. gin, genever). They play a traditional culinary role as an ingredient of ‘choucroute’ (France). Juniper is listed by the Council of Europe as a natural source of food flavouring (fruit N2). Category N2 indicates that the cone berries can be added to foodstuffs in small quantities, with a possible limitation of an active principle (as yet unspecified) in the final product (Barnes et al. 2007).
The highest average maximum use level reported for the oils is 0.006% in alcoholic beverages and 0.01% for the extract of
In Belgium only Juniperus sabina L. cannot be used in food or food supplements. The cone berries of
Juniperus communis L., Juniperus procera Hochst. and Juniperus virginiana L. are allowed as notified ingredients of food supplements. Also the use of Juniperus oxycedrus L. is allowed (Anonymous, 1997).
Preparations made of Juniperi
The most frequently cited traditional use of Juniperi
There is a lot of discussion about the safe use of Juniperi
2.2. Information on traditional/current indications and specified substances/preparations
Use of herbal preparations
*Decoctions and infusions are traditionally used (Hänsel et al. 1993)
*Liquid extract with 25% ethanol (DER 1:1 W/V) (Hänsel et al. 1993; Barnes et al. 2007)
*Tincture with 45% ethanol (DER 1:5 W/V) (ESCOP, 2003; Barnes et al. 2007)
*Soft extract with water (DER
Although decoctions as well as infusions are traditionally used, most standard sources with information for therapeutic practice prefer infusions. All secondary sources referring to the liquid extract and the tincture cite the British Herbal Pharmacopoeia (1983) as a source. Most probably the preparations are used already more than 30 years in Europe. The British Herbal Pharmacopoeia 1996 contains a shortened version of Juniper berry and contains information taken from the British Herbal Pharmacopoeia 1971. As the 1996 edition is a shortened version, no details are given about preparations. In this edition, the British Herbal Pharmacopoeia 1983 is mentioned as the second consolidated edition comprising parts 1 (1976), 2 (1979) and 3 (1981). As a consequence, the information in the 1983 edition is from a date former than 1983.
2.3. Specified strength/posology/route of administration/duration of use for relevant preparations and indications
Route of administration
All preparations are used orally.
The dried herbal substance is used in a dose of 2 g with a maximum dose equivalent to 10 g per day. According to some authors, this posology corresponds with respectively 20 and 100 mg essential oil (Hänsel et al. 1993; Barnes et al. 2007; Ph. Eur. 2008).
In some traditions (Sebastian Kneipp) it is recommended to start on day 1 with 5 cone berries , increasing the number every day by 1 cone berry (well chewed) up to 15 cone berries, then decrease the number (1 per day less) to 5 cone berries. So the duration of the therapy is 21 days, the maximum daily dose 15 cone berries. In case of therapeutic result the duration should be limited to 3 weeks. It is not recommended to continue the treatment for more than 2 weeks if the symptoms persist (Anonymous, 2009).
Preparation of infusion (the concentration may vary according to the method of preparation):
2 to 3 g with 150 ml hot water, infusion time 10 minutes: to be drunk 3 to 4 times a day (Hänsel et al. 1993; ESCOP, 2003).
1:20 (W/V) with boiling water: 100 ml 3 times daily (Barnes et al. 2007).
The latter is more concentrated and most sources limit the single dose equivalent to 2 g. Therefore an amount of 2 g 2 to 3 times a day is preferred as recommended dose.
Powder: 2 to 8 g per day (Delfosse, 1998). It is not clear whether the use of powdered
Tincture (1:5 W/V in 45% ethanol):
Tinctura Juniperi (Codex Français): 5 to 15 g to be enhanced and tapered progressively (Van Hellemont, 1985). Data about the duration of use are missing. Also the original source is not specified. This preparation is not included into the monograph.
Liquid extract (1:1 W/V in 25% ethanol):
Duration of use
As the duration of use for self medication is concerned, Juniper preparations should not be used for more than 2 weeks if the symptoms persist or worsen. Traditional use of the
According to several sources infusions may contain a maximal dose of 10 g cone berries per day. This dose is subject to some considerations.
As several authors mention the same dose, they may have copied each other.
The approximate weight of 100 cone berries is 16 g (Schilcher & Heil, 1994). A dose of 10 g would correspond to approximately 60 cone berries. This amount seems quite high.
The content of essential oil in cone berries may vary from 0.5 to 3.42%. When the content of essential oil is high, a daily dose of 10 g corresponds to about 342 mg of essential oil, whereas a maximal daily dose of 100 mg is recommended according to several sources.
It can be hypothesised that, when making an infusion, the volatile components of Juniper pseudo- fructus will not be extracted at 100%.
Taking the cone berries as such, a maximum dose of 15 cone berries per day is recommended. By this way of administration, the cone berries are not taken with water.
As a result of these considerations, for use as an infusion, a maximal dose of 2 g taken 3 times daily can be considered as a safe margin as, even with a 100% extraction in case of a high content on essential oil, the amount will be lower than 100 mg per day.
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
i.v. = intravenous
MIC = minimal inhibitory concentration (= no growth)
p.o. = per oral
vs = versus
Assessor’s overall conclusions on pharmacology
The earliest experimental evidence for a diuretic activity goes back more than 70 years. Rats were mostly used as subjects. The p.o. way of administration corresponds to traditional use in humans. The extracts are mostly prepared from whole cone berries, but also the essential oil and
used. The diuretic activity cannot be characterized as only aquaretic, i.e. increasing the volume of water excreted by the kidneys, as several authors found also an increased excretion of an organic component (mainly chloride). In one study, the whole extract of the cone berries seemed to be more potent as compared to the essential oil, but in this study the rats were pretreated with antidiuretic hormone. It should be mentioned that the diuretic activity is not always consistent and obtained with relatively high doses if converted to human conditions (when recalculating the number of berries to be taken, this leads to more than 100 berries/day). There are no systematic investigations reported about the possible beneficial consequences of the diuretic activity. Only one study with total extract intravenously administered to anesthetised normotensive rats mentioned a lowering effect on blood pressure without any link to increased diuresis.
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.
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
No data were found about absorption, distribution, metabolism, elimination and pharmacokinetic interactions with other medicinal products.
Assessor’s overall conclusions on pharmacokinetics
No data are available. The complex phytochemistry of Juniper cone berries makes it difficult to conceive any representative pharmacokinetic study.
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
LD50 of a lyophilized water extract of Juniper
Acute toxicity was tested on 10 Wistar rats of a standardised 80% ethanolic extract of Juniper pseudo- fructus (2.5 g/kg) during 7 days. No side effects were reported. All animals survived. A dose of 3 g/kg induced hypothermia and mild diarrhoea in
Other sources mention an oral LD50 of the herbal substance or Juniperi
Reproductive and developmental toxicology
Doses of 300 and 500 mg (p.o.) of an of Juniperi communis
14, 15 and 16, to the rats which showed implantation. On day 18 the rats were again laparotomized in order to control abortifacient activity. The number of embryos developing was lower in the intervention group as compared to the rats receiving vehiculum only: in rats which showed implantation sites (pregnant), no pups could be delivered.
In another experiment, three of the rats without implants on day 10 were allowed to mate with males after 2 months of rest. Although mating was successful, no implantations were reported.
Based on the results of the preceding experiments, the investigations concluded that Juniperi communis
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 J. communis.
According to one source, the chemical composition of J. communis oil and J. communis
Assessor’s overall conclusions on toxicology
There is no serious concern about possible acute toxicity of the Juniperi
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
5.2. Patient exposure
Historically, the cone berries were used in a diuretic wine recommended by Cato the Ancient in his book ‘De re rustica’ (Leclerc, 1966). The use of Juniper cone berries can be considered as a century- long standing practice.
On the other hand, 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 Commission E only considered dyspepsia as the only therapeutic indication. The use of essential oil is questioned by some authors (Bruneton, 1999). 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.
Juniper berry oil was given GRAS (Generally Recognised as Safe) status by the Flavouring Extract Manufacturers Association (FEMA) in 1965 and is approved by the U.S. Food and Drug Administration for food use. Juniper berry was included in the Council of Europe list of substances, spices and seasonings deemed admissible for use with a possible limitation of the active principle in the final product (De Smet et al. 1993).
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. Although the monograph is conceived for the
Renal damage has been reported after
The most detailed study is made by Schilcher & Heil (1994) mentioning that ancient sources do not warn for renal complications in humans. Massive doses that were much higher than the
15 cone berries is 2500 mg. With a 1% content of essential oil, the oil equivalent will be 25 mg. There have been no adverse events mentioned after the use of broiled cone berries, although it must be specified that this preparation is a residual product of cone berries from which the essential oil has been removed (Schilcher & Heil, 1994).
According to Semon (1844; cited by Schilcher & Heil 1994), Juniperus oil increases the renal circulation and
Although the volatile oil is reported to be generally
Of 26 patients examined for suspect plant dermatitis, 14 showed positive patch test reactions to Juniper
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 Juniperi
Serious adverse events and deaths
5.4. Laboratory findings
No data are available.
5.5. Safety in special populations and situations
Safety in special populations and situations
The use of Juniperus communis is
Intrinsic (including elderly and children)/extrinsic factors
No data available. Because of the tighter dose margin, a restriction to adults is recommended.
There is limited evidence from preclinical studies that Juniper may influence glucose levels in diabetes (ESCOP, 2003; Barnes et al. 2007).
Use in pregnancy and lactation
There are no data available about use during pregnancy and lactation.
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; Barnes et al. 2007).
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
With the use of cone berries serious adverse events are improbable as the amount of substance to be ingested before problems occur will be high. Issues of safety monitoring are related to:
the preparation: the concentrating effect on the compounds depends upon the solvents and the way of extraction; as both the cone berries and the essential oil have a possible antioxidant affect, respecting the original composition is recommended
the patients: apart from preclinical data on reproductive toxicology, little is known about possible groups at risk and interactions with other medication
it can be expected that the kidney will be the first target organ
6. Overall conclusions
The traditional use of Juniperus communis
There is a need for systematic pharmacovigilance reporting in order to address the issue of subacute safety when using different preparations of Juniper.
Juniper berries as well as the essential oil are described in the European Pharmacopoeia. The macroscopic identification of the berries can be done easily. 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 questionable quality, not meeting the pharmacovigilance criteria. Pharmacokinetics of Juniper components are not known.
As genotoxicity and carcinogenicity are not studied, a list entry in the ‘Community list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products’ cannot be established.
The therapeutic indications do not relate to life threatening conditions and they are supported by traditional use evidence. There are more potent conventional medicines with known benefits based on