Community herbal monograph on
Juniperus communis
L.,
aetheroleum
To be specified for the individual finished product.
Well-established use
Traditional use
With regard to the registration application of
Article 16d(1) of Directive 2001/83/EC as
amended
Juniperus communis
L., aetheroleum
(juniper oil)
i) Herbal substance
Not applicable.
ii) Herbal preparations
Essential oil obtained by steam distillation from
the ripe, non-fermented berry cones.
Well-established use
Traditional use
Herbal preparation in liquid dosage forms for oral
and cutaneous use.
The pharmaceutical form should be described by
the European Pharmacopoeia full standard term.
1
The material complies with the Ph. Eur. monograph (ref.: 1/2008:1832).
2
The declaration of the active substance(s) for an individual finished product should be in accordance with relevant herbal
quality guidance.
Community herbal monograph on
Juniperus communis L.,
aetheroleum
EMA/HMPC/12402/2010
Page 2/6
4.1.
Therapeutic indications
Well-established use
Traditional use
Oral use
Indication 1)
Traditional herbal medicinal product to increase
the amount of urine to achieve flushing of the
urinary tract as an adjuvant in minor urinary tract
complaints.
Indication 2)
Traditional herbal medicinal product for
symptomatic relief of digestive disorders such as
dyspepsia and flatulence.
Cutaneous use
Indication 3)
Traditional herbal medicinal product as adjuvant
in the relief of minor muscular and articular pain.
The product is a traditional herbal medicinal
product for use in specified indications exclusively
based upon long-standing use.
4.2.
Posology and method of administration
Well-established use
Traditional use
Posology
Oral use
Adults and elderly
Average daily dose
60-100 mg juniper oil to be taken in 1-3 doses.
The use in children and adolescents under
18 years of age is not recommended (see section
4.4 ‘Special warnings and precautions for use’).
Cutaneous use
Adolescents, adults and elderly
Bath additive 3-4 times weekly 1-1.5 g juniper oil
in full bath for 10-20 minutes at 35-38°C.
The use in children under 12 years of age is not
recommended (see section 4.4 ‘Special warnings
and precautions for use’).
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Well-established use
Traditional use
Duration of use
If symptoms persist longer than 2 weeks during
the use of the medicinal product, a doctor or a
qualified health care practitioner should be
consulted.
Method of administration
Oral use.
Cutaneous use.
4.3.
Contraindications
Well-established use
Traditional use
Hypersensitivity to the active substance.
Indications 1) and 2)
Severe renal disease including infectious
interstitial nephritis, pyelitis and pyelonephritis.
Indication 1)
Conditions where reduced fluid intake is
recommended (e.g. severe cardiac diseases).
4.4.
Special warnings and precautions for use
Well-established use
Traditional use
If the symptoms worsen during the use of the
medicinal product, a doctor or a qualified health
care practitioner should be consulted.
Oral use
The use in children and adolescents under
18 years of age has not been established due to
lack of adequate data.
Indication 1)
Appropriate fluid intake is recommended.
If complaints or symptoms such as fever, dysuria,
spasms or blood in the urine occur during the use
of the medicinal product, a doctor or a qualified
health care professional should be consulted.
The use of this product is not recommended in
case of oedema due to limited heart and kidney
function.
Cutaneous use
Community herbal monograph on
Juniperus communis L.,
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EMA/HMPC/12402/2010
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Well-established use
Traditional use
The use in children under 12 years of age has not
been established due to lack of adequate data.
In cases of hypertension, a full bath should be
used with caution.
4.5.
Interactions with other medicinal products and other forms of
interaction
Well-established use
Traditional use
None reported.
4.6.
Pregnancy and lactation
Well-established use
Traditional use
Safety during pregnancy and lactation has not
been established. In the absence of sufficient
data, the use during pregnancy and lactation is
not recommended.
4.7.
Effects on ability to drive and use machines
Well-established use
Traditional use
No studies on the effect on the ability to drive and
use machines have been performed.
4.8.
Undesirable effects
Well-established use
Traditional use
Allergic skin reactions have been reported. The
frequency is not known.
If other adverse reactions not mentioned above
occur, a doctor or a qualified health care
practitioner should be consulted.
Well-established use
Traditional use
In case of prolonged oral use and overdose, urine
will smell of violets. There may be renal irritation
and kidney pain, strong diuresis, albuminuria,
haematuria, purplish urine, gastrointestinal
upsets, increased heartbeat and blood pressure.
Rarely symptoms of central stimulation like
Community herbal monograph on
Juniperus communis L.,
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EMA/HMPC/12402/2010
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Well-established use
Traditional use
convulsions occur as well as metrorrhagia and
abortion.
5.1.
Pharmacodynamic properties
Well-established use
Traditional use
Not required as per Article 16c (1)(a)(iii) of
Directive 2001/83/EC as amended.
There is limited evidence from non-clinical studies
that juniper may influence glucose levels in
diabetes.
5.2.
Pharmacokinetic properties
Well-established use
Traditional use
Not required as per Article 16c (1)(a)(iii) of
Directive 2001/83/EC as amended.
5.3.
Preclinical safety data
Well-established use
Traditional use
Not required as per Article 16c (1)(a)(iii) of
Directive 2001/83/EC as amended, unless
necessary for the safe use of the product.
Adequate tests on reproductive toxicity,
genotoxicity and carcinogenicity have not been
performed.
Well-established use
Traditional use
Not applicable.
25 November 2010
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Assessment Report
Table of contents
..........................................................................................
......................... 2
......................... 3
ations thereof . 3
...................... 6
9
...................... 9
/preparations ... 9
for relevant
.................... 10
....................... 10
subs s), herbal
.................... 10
herbal
.................... 12
)/herbal
.................... 12
....................... 13
....................... 14
.................... 14
s)/preparation(s)
.................... 14
/preparation(s)
.................... 14
.................... 14
.................... 14
.................... 14
.................... 14
.................... 14
....................... 14
.................... 14
5.2. Patient exposure .............................................................................................. 14
5.3. Adverse events and serious adverse events and deaths ......................................... 15
5.4. Laboratory findings .......................................................................................... 16
5.5. Safety in special populations and situations ......................................................... 16
5.6. Overall conclusions on clinical safety ................................................................... 17
6. Overall conclusions ..........................................................................................................17
Annex .................................................................................................................................. 17
Assessment report on Juniperus communis L., aetheroleum
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1. Introduction
1.1.
Description of the herbal substance(s), herbal preparation(s) or
thereof
Herbal substance(s)
Not applicable.
Herbal preparation(s)
The essential oil is obtained by steam distillation from the ripe, non-fermented
(
Juniper communis
L.). A suitable antioxidant may be a
berry cones of Juniper
dded (Ph. Eur. 2008; Hänsel
et al.
1993).
Juniper berries (
Juniperi pseudo-fructus
) are mentioned in the European Pharm
described as ‘dried ripe cone berry of
Juniperus communis
L’. Juniper belongs to th
Cupressaceae
, and the class of the
Gymnospermae
(Ph. Eur. 2008).
acopoeia 6.0. It is
e family of the
ope and mountain areas. The herbal substance is imported
among others from Italy, from the countries on the Adriatic coast and from Albania. Leaves are
e open on the apex with a
triradiate mark and depressions that indicate the sutures of the three scales. They are violet to black-
very hard, oblong,
needles occurring in whorls of three on the branches. The berry-like fruits ar
brown, often bluish pruinose and up to 10 mm in diameter. There are usually three,
triangular seeds (Bruneton, 1999; Wichtl 1994).
Four subspecies of
Juniperus communis
occurre in Europe: ssp.
alpine
(NEILR.) CEL
communis
; ssp.
hemisphaerica
(J. et C. PRESL), ssp.
nana
(Willd.) Syme (Hänsel
e
AK; ssp.
t al.
1993).
d 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 con
essential oil. The cone berries may not contain less t
essential oil can be up to 3%. The essential oil of Ju
taining high levels of
han 10 ml/kg of essential oil. The amount of
niper cone berries contains about 105 constituents
(ESCOP, 2003).
The following constituents were identified:
The composition of the essential oil varies dependin
monoterpene hydrocarbons, principally monoterpenes (a
g upon the source but consists mainly of
bout 58% of the essential oil) (ESCOP 2003):
α-pinene (24.1-55
.4%) (range Ph. Eur. 2008 = 20-50%)
β-pinene (2.1-6
.0%) (range Ph. Eur. 2008 = 1.0-12%)
β-myrcene (7.3-22.0%) (range Ph. Eur.2008 = 1.0-35%)
sabinene (1.4-28.8%) (range Ph. Eur. 2008 = less than 20%)
limonene (2.3-10.9%) (range Ph. Eur. 2008 = 2.0-12%)
terpinene-4-ol (0.7-17.0%) (range Ph. Eur. 2008 = 0.5-10%)
α-terpineol (up to 1.7%)
α-thujene (0.6-1.9%)
caryophyllene (1.3-2.3%) (Ph.Eur. 2008 for β–caryophyllene = less than 7.0%)
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
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combinations
The plant has its origin in northern Eur
Other species of
Juniper
mentione
CH
3
CH
2
CH
2
H
3
C
H
3
C
CH
3
CH
3
α-pinene
β-pinene
H
3
C
CH
3
sabinene
CH
2
CH
3
CH
3
CH
2
H
3
C
OH
CH
3
H
3
C
CH
3
H
2
C
CH
3
β-myrcene
limonene
Terpinen-4-ol
CH
3
H
3
C
CH
2
CH
3
β-caryophyllene
The qualitative compo
components analy
some other terpene
sition of the oil is constant, but as already mentioned, the percentage of the
sed with GC-MS may vary considerably. Apart from the terpenes mentioned above,
compounds occur in lower concentrations (essential oil from Italian origin) (Hänsel
et al
. 1993):
γ-muurolen (
7.6%)
humulen (2
.1%)
α-muurolen
(1.1%)
β-elemen (1%)
β-farnesen (0.9%)
α-cubeben (0.9%)
4-thujanol (0.8%)
α-cadinol (0.8%)
γ-cadinen (0.7%)
aromadendren (0.6%)
α-copaen (0.4%)
Assessment report on Juniperus communis L., aetheroleum
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bornylacetate (0.4 %) (range Ph.Eur. less than 2.0%)
camphen (0.3%)
campholena
ldehyd (0.2%)
p-cymene (0.2%)
verbenon (0.2%)
Additionally the Ph.Eur. limits the concentration of α–phellandrene to less than 1
.0%.
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.
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
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1.2.
Information about products on the market in the Member States
Regulato y status over
r
view
Member
State Regulat ry St
o
atus
Comments (not
ndatory field)
ma
Austria
MA
TRAD
Other TRAD
O
ther Specify: Prep
arations with
essential oil authorized
Belgium
MA
TRAD
Other TRAD
O
ther Specify:
Mixed preparations with
essential oil authorized
Bulgaria
MA
TRAD
Other TRAD
O
ther Specify: No i
nformation
Cyprus
MA
TRAD
Other TRAD
O
ther Specify: No
information
Czech Republic
MA
TRAD
Other TRAD
O
ther Specify: No
authorized or
registered preparations
Denmark
MA
TRAD
Other TRAD
O
ther Specify: Mixe
d preparations with
essential oil authorized
Estonia
MA
TRAD
Other TRAD
O
ther Specify: Onl
y food supplements
Finland
MA
TRAD
Other TRAD
O
ther Specify:
No authorized or
stered preparations
regi
France
MA
TRAD
Other TRAD
O
ther Specify:
No information
Germany
MA
TRAD
Other TRAD
Other Specify: Preparations with
essential oil authorized
Greece
MA
TRAD
Other TRAD
O
ther Specify: No a
uthorized or
registered preparations
Hungary
MA
TRAD
Other TRAD
O
ther Specify:
No information
Iceland
MA
TRAD
Other TRAD
O
ther Specify:
No information
Ireland
MA
TRAD
Other TRAD
O
ther Specify:
No information
Italy
MA
TRAD
Other TRAD
O
ther Specify: No a
uthorized or
registered preparations
Latvia
MA
TRAD
Other TRAD
O
ther Specify:
No information
Liechtenstein
MA
TRAD
Other TRAD
O
ther Specify:
No information
Lithuania
MA
TRAD
Other TRAD
O
ther Specify: No i
nformation
Luxemburg
MA
TRAD
Other TRAD
O
ther Specify:
No information
Malta
MA
TRAD
Other TRAD
Other Specify: No authorized or
eparations
registered pr
The Netherlands
MA
TRAD
Other TRAD
Other Specify: No information
Norway
MA
TRAD
Other TRAD
Other Specify:
No information
Poland
MA
TRAD
Other TRAD
Other Specify:
No information
Portugal
MA
TRAD
Other TRAD
Other Specify: No authorized or
registered preparations
Romania
MA
TRAD
Other TRAD
Other Specify: No authorized or
registered preparations
Slovak Republic
MA
TRAD
Other TRAD
Other Specify:
Mixed preparations with
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
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Member State Regulatory Status
Comments (not
datory field)
man
essential oil authorized
Slovenia
MA
TRAD
Other TRAD
O
ther Specify:
No authorized or
eparations
registered pr
Spain
MA
TRAD
Other TRAD
O
ther Specify:
No a
regi
uthorized or
stered preparations
Sweden
MA
TRAD
Other TRAD
Other Specify: No authorized or
registered preparations
United Kingdom
MA
TRAD
Other TRAD
Other Specify:
No information
MA: Marketing Authorisation
TRAD: Traditional Use Registration
ional Traditional systems of registration
Other: If known, it should be specified or otherwise add ’Not Known’
gulato
This re
ry overview is
not legally binding and does not ne
cessarily refle
ct the legal status of the
ucts in the MSs concerned.
Details about preparations
Country
Specifications
Classification
Austria
Juniper
oil
Soft gelatin capsules with 20 mg e
Increasing the amount of urine
Posology: 1 capsule 3 x daily
Numerous combination pr
Authorized product
> 1993
ssen
tial oil
oducts are on the market;
ou
indications: oral use – increase of the am
cutaneous use
nt of urine
;
: rheumatic complaints.
Belgium
essential oils or
substances from essential oils (eucalyptol,
gaultheria oil, cajaput oil, menthol,
Mentha
for upper respiratory tract affections.
Authorized
parations
eugenol,
piperita
oil)
pre
Denmark
1.
Aetheroleum Juniper
i
1g/100 gram Aetheroleum
menthae piperitae
2.
Combination product with peppermint oil,
aetheroleum carvi, eucalypti oil and fennel oil
Authorized
preparations
Estonia
All products containing
Juniper oil are
classified as non
medical products.
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Other TRAD: Other nat
prod
Juniper oil only combined with other
Germ
any
Juniper oil
-
Bath
Pharmaceutical form: bath ad
additive
Therapeutic indication: traditionall
promote the blood circulation of the skin
Posology: for use in adults and ad
1
Traditional
>
1976
oil
ditive, as bath
y used to
1
.
o scents over
2 years; if necessary 3-4 x weekly 15-20 ml
bath additive/full bath for 10-20 mi at 35-38°C;
g Juniper oil/100 g (approx. 94.5 ml) bath
le
:
n
6.993
additive.
was marketed since
1978 until the end of the nineties: Wacholderöl=
Juniperi
eroleum
10 g/100 ml. The indication was "
Linderung
abeschwerden, Bandscheibenbe
scs).
aeth
von Rheum
Not any longer on the
market.
schwerden
"
(mild symptoms of rheumatic diseases/di
Juniper oil
Soft
Dyspeptic complaints with minor abd
flatulence and
WEU
>
1976
ominal cramps,
feeling of fullness
For oral use in adults and adolescents > 12y
lood glucose level
Posology: 1 capsule with 100mg/day
Interaction: possible influence on b
in diabe
Side effects: Long-standing use
cause renal impairment
tics
and ov
erdose may
Juniper oil
There are combination products with terpentine oil and
Juniperi oleum
the indication of which is in the field of
rheumatic diseases.
Slovakia
Juniperi aetheroleum only combined with
Menthae
piperitae aetheroleum
;
Caryophylli aetheroleum
;
Eucalypti aetheroleum
Authorized preparation
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.
Assessment report on Juniperus communis L., aetheroleum
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Additional information
There is a monopreparation that
capsules
2.
Historical data on medicinal use
2.1.
Information on period of medicinal use in the Communit
y
Leclerc (1966) mentions case studies in the treatment of rheumatoid arthritis with
essential oil mixed with 4 g diethylether, to be taken in a dose of 10 drops a day.
a preparation of 8 g
The Extra Pharmacopoeia Martindale (Todd, 1967) refers to the British Pharmaceut
when mentioning the essential oil of Juniper, as the oil distilled from the dried ripe frui
communis
. Accordin
flatulence and colics. During excretion it irritates the genito-uri
the uterus. It has been used as a diuretic but it should not be employed during pregnanc
presence of renal disease.
ical Codex of 1949
ts of
Juniperus
g to this source juniper oil is carminative and antiseptic and has been used in
nary tract and may cause contraction of
y or in the
In Germany, Juniper oil is registered as an authorized preparation since
1976.
Soft capsules are used internally against dyspeptic complaints with minor abd
and feeling of fullness. Th
ominal cramps, flatulence
is indication is considered as a well established use.
It is also traditionally used as a bath additive to promote the blood circulation of th
e 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 rem
renal elimination of water and for dyspeptic complaints. F
handbooks and no
edy to enhance the
or these indications the monograph refers to
t to original research (ESCOP, 2003).
Besides its diuretic action, sometimes Juniper is also used as a urinary antiseptic, an
disputed. The activity should be mainly limited to water diuresis, mainly due to an i
terpinen-4-ol on the kidney tissue. More particularly, hypereamia of the glomerul
activity of the secretory epithelium (Wichtl 1994; Barnes
et al.
2
indication which is
rritative action of
i should stimulate the
007).
Assessor’s comments
Therapeutic indications for the essential oil of
Juniperus
are mostly related to diuresis and dyspepsia.
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
ia of the glomeruli which is considered as an irritative action. Experimental pharmacological
hyperem
and toxicological data will be important in a constructive therapeutic approach.
The indication for external use (p
close to a health claim for cosmetics but no medicinal indication.
romoting blood circulation in the skin) can be questioned as being too
2.2.
Information on traditional/current indications and specified
substances/preparations
Doses used
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
(
pseudo-fructus
). Some sources mention 2 to 4 drops per day (Van Hellemont 1985; Delfosse 1998).
Assessment report on Juniperus communis L., aetheroleum
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There is a lot of discussion about the safe use of
Other sources recommend a daily dose of 20 to 100 mg (Hänsel et al. 1993). Accor
Pharmacopoeia Martindale (Todd, 1967) the dose can be 50 to 200 mg.
ding to the Extra
It is not specified whether this
is 200 mg.
dose is meant as a single or a daily dose. Most probably the upper daily limit
In Germany soft capsules with 100 mg essential oil are registered as an authoriz
Pos
(approx. 94.5 ml) is used 3 to 4 times weekly: 15-20 ml bath additive/fu
38°C.
Juniperus preparations should not be used for more than 4 weeks without medical a
dvice.
Assessor’s comments
g are mentioned with
It is recommended to stick to the reported doses of
registered preparations. Therefore 60-100 mg per day is proposed to be taken in 1 to 3 single doses.
2.3.
Specified stren
for relevant prepara
gth/posology/route of administration/duration of use
tions and indications
See section 1.2 and 2.2.
3. Non-Clinical Data
the herbal
substance(s), herbal preparation(s) and relevant constituents thereof
Diuretic act
ivity
Although this essment report i
ncluded. In sever
tal setting. As a cons
ass
s focuse
d on
Jun
iperi aetheroleum
studies with
Ju
ll as extracts a
ate them.
niperi
pseudo-
fructus
are a
lso i
al studi
es, the essential oil as we
re included in the
same exper
imen
equ
ence it is difficult t
o separ
Species
Preparation &
intervention
Results
Comments
(references)
Rats receiving A
by i.p. doses of
0.004 IU/100 g
04 IU/100 g
00 g
.
19
DH
g
%
fusion of
Juniper
us; or (2)
us solution of
oil (with 0.2% of
ubilizer); or
(3) 0.01 solution of
terpinen-4-ol; or control
solution of (4) water or
water + 0.2% tween (rats
not receiving ADH)
body
eduction of
uresis:
- 6%/24 h with (1) and (2)
4 h w
Day 2 and 3:
diuresis:
+ 43-44% with (1)
(P<0.05)
No stimulation with the
other solutions.
These results are
not convincing for
the essential oil.
The activity may
be due to
hydrophilic
substances in the
infusion.
0.
0.4 IU/1
(Stanic
et al
98)
0.1%
- 30%/2
ith (3)
stimulation of
aqueo
Juniper
tween 20 sol
Rats
(Schilcher &
Leuschner 1997)
p.o.:
(1) Juniper oil
100 mg/kg/day
(2) Juniper oil
333 mg/kg/day
No significant diuresis.
Essential oil did
not give a positive
result.
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
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ed preparation.
ology is limited to 100 mg or one capsule orally per day. A bath additive with 6.993 g oil/100 g
ll bath for 10-20 min at 35-
There are some discrepancies as far as the dose is concerned. Doses up to 200 m
no clear reference to the daily dose regimen.
3.1.
Overview of available pharmacological data regarding
p.o.: 5 ml/100
weight of (1) 10
aqueous in
Day 1: r
di
Species
(references)
Prepa
interven
Results
Comments
Duration: 28 days
Rats
(Janku
et al.
19
Janku
et al.
196
s.c. injec
tion
r oil: 1
f diuresis a
(3) 78.4
7.1 / 157.6
+
n o
fter
Essential oil less
active than pure
compound
terpinene-4-ol.
57 ;
0)
(1) Junipe
(2
ml/kg
4 /24 h with
+
) NaCl solution
(3) Terpinene-4-o
0.1 ml/kg
l
7.1%
(1) 44.0
+
6.9 / 85.3
+
7
(2) 14
.3
+
4.1 / 43.8
+
4.6%
ADH = ant
i.p. = intrap
idiureti
c hormone (vasopres
neal
sin
)
p.o. = peroral
erito
s.c. = subcutaneous
Other activiti
es
Species
Preparations &
interventions
Results
Comments
(referenc
es)
Rats: carrageen
an p.o. administere
(1) Ethanol ext
of
Juniperi
d
ra
pseudo-fructus
(1:3) 100 mg/kg
(2) Indomethacin 5 mg/kg
:
ct (80%)
Reduction
(1) -60%
of
paw oedema:
Only one dose
tested: no dose
response
relationship
investigated.
used as a pro-
inflammatory agent
(2) -45%
(1) > (2) : P < 0.01
(Mascolo
et al.
1987)
Cell cultures
Extract of
Juniperi
pseudo-
DNA-replicat
ion of H
lated amnion
SV-1
No cytotoxcitiy
seen in a range of
1.5 to 7000 ng/ml
Activity may be
due to
desoxypodophyl-
lotoxin.
(Hänsel
et al.
1993;
Barnes
et al
fructus
prepared wi
isopropanol
th hot lowered in
iso
.
20
07)
cells.
Gram + and Gram –
bacteria, yeast,
i
Essential oil from Juniper
cone berries,
Gram + / -:
(V/V)
MIC: 8-70%
No comparator
tested. The
antibacterial
concentrations
vary considerably.
The highest
concentrations are
not relevant in a
therapeutic
context.
yeast-like fung ,
concentrations
as MIC
ex
pressed Fungicid
Candida: M
(V/V)
al ac
IC
tivity against
: 0.78-2%
yeasts and
dermatoph
(Pepeljnj
2005)
ytae
ak
et a
l.
Dermatophytes MIC: 0.39-
10% (V/V)
Microbial organisms
Staphylococcus
aureus
Escherichia coli
Enterobacter
aerogenes
Pseudomonas
aeruginosa
(Rossi
et al.
2000)
Essential oil distilled from
aerial parts of
J. communis
spp. alpine
Concentrations 0.03-2%
(V/V) in agar
Inhibition zones for
St.
aureus
and
E.coli
: controls
<
J.communis <
antibiotics
(ciprofloxacine, penicillin
G).
Concentrations
tested are within
acceptable limits.
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
Page 11/17
ration &
tion
Stimulatio
.6%
Species
Preparations &
ns
Results
Comments
(references)
interventio
Gram-negativ
gram-positiv
e and
Essential oil fract
distilled from con
ions
e berries
Diameter
component
antibiotics (
tetracycline
vancomy , clincamycine,
, ampicylline,
-30 µg).
No comparator for
fungi and
Candida
.
e
i and
Candida albicans
0
(Glisic
et al.
20 7)
Antioxidant activity:
rylhydrazi
Essential oil of ps
fructus
eudo-
Concentrati n-response
re
* DPPH:
o
Antioxidant activity
with specific sub-
strate: should not
be extrapolated.
Difenylpic
ne
(= DPPH)
lationship
niper fruit oil << vitamin
C < quercetin
Desoxyribose
degradation
(Emami
et al.
2007)
* Desoxyribose
Juniper fruit << querce
tin
HSV-1 = Herpes simplex virus 1
p.o. = perorally
MIC = minimal inhibitory concentration (= no growth)
3.2.
Overview of available pharmacokinetic data rega
substance(s), herbal preparation(s) and relevant cons
rding the herbal
tituents thereof
There wer
interactions with other medicinal products.
e no data found about absorption, distribution, metabolism, elimination, or pharmacokinetic
3.3.
Overview of available toxicological data regarding
substance(s)/herbal preparation(s) and constituents ther
the herbal
eof
Acute toxicity
Gavage of megadoses is mentioned in original literature sources: up to 5 or
rabbit (respectively Gmeiner 1
rabbits survived a dose of 15 g essential oil, a dose of 30 g killed all animals within
30 g Juniperus oil for one
904 and Senon 1844 cited by Schilcher & Heil 1994). Whereas the
24 hours.
in a mean LD
50
= 750
cted in guinea-pigs was
LD = 1200 (range 1170-1230) mg/kg (Anonymous 2001). A mean LD
50
of 700 (range 654-
g was reported for mice after intramuscular application. For guinea-pigs after subcutaneous
ous 2001).
50
746) mg/k
application a mean LD
50
of 1440 (range 1425-1455) mg/kg was reported (Anonym
Cardiovascular and respira
tory 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).
Skin irritation
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.
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
Page 12/17
inhibition zone
s (8.75 µg) >
gentamycin,
, erythromycin,
cine
streptomycin
penicilline: 6
bacteria, fung
Ju
Acute toxicity of the essential oil intraperitoneally injected in mice resulted
(range 685-815) mg/kg. Acute toxicity of the essential oil intraperitoneally inje
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 extrac
Juniper has been observed in rats after oral administration of a 50
(Agrawal
ts were performed in several animal species. Abortifacient activity of
% ethanolic extract at 300 mg/kg.
et al. 1980, cited in ESCOP 2003)
There are no data about reproductive and developmental toxicology of Juniper oil.
Genotoxicity
There are no genotoxicity data available for Juniperus communis or preparations th
Juniperus oxycedrus (cade oil) benzpyrenes were found in the nanogram/g range,
apply to Juniperus communis (Hänsel et al. 1993).
ereof. In the tar of
but this does not
n of Juniperus communis oil and Juniperus communis
terms of genotoxicity (Anonymous, 2001). However,
ce in composition between the oil and water extracts of Juniperi pseudo-fructus must be
3.4.
Overall conclusions on non-clinical data
Pharmacology
The earliest experimental evidence for a diuretic activity goes back more than 70
mostly used as subjects. The peroral way of administration corresponds to traditio
The extracts are mostly prepared from whole cone berries, but also the essential oil
are used. The diuretic activity cannot be characterized as only aquaretic, i.e. incr
water excreted by the kidneys, as sev
components (mainly chloride). In one study the whole extract of the cone berries s
potent as compared to the essential oil, but in th
hormone. It should be mentioned that the diuretic activity is not always consistent and obt
relatively high do
about the possible beneficial consequences of the diuretic activity. Only one study wi
intravenously administered to anesthetised normotensive rats mentioned a lowe
pressure without any link to increased diuresis.
years. Rats were
nal use in humans.
and terpinen-4-ol
easing the volume of
eral authors found also an increased excretion of anorganic
eemed to be more
is study the rats were pretreated with an antidiuretic
ained with
ses if converted to human conditions. There are no systematic investigations reported
th total extract
ring effect on blood
Price & Price (2007) consider the diuretic properties as basic for Juniper: “… the pr
communis
upon which all are agreed is its diuretic effect …”.
operty of
Juniperus
In contrast with the traditionally claimed indication, there is no experimental evidence for use in
dyspeptic complaints.
Other activities include an anti-inflammatory (
in vivo
and
in vitro
) effect, antimicrobial activity towards
some viruses (HSV-1), bacteria (
E. coli
and
S. aureus
) and
Candida albicans
. The antimicrobial and
anti-inflammatory activity may underpin the traditional claim of urinary infections, although the
concentrations used are not always physiologically relevant. Most of the experiments were carried out
with the essential oil or its components. However, extrapolation of
in vitro
results to
in vivo
conditions
remains difficult, due to partially high concentrations of oil used in the assays and the direct contact
with micro-organisms which may result in cytotoxic rather than antimicrobial effects.
Furthermore antioxidant and antitumoral activity is reported in some experimental
in vitro
models.
Extrapolations of these activities remain speculative.
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
Page 13/17
According to one source the chemical compositio
pseudo-fructus extract is considered as similar in
the differen
taken into consideration.
Pharmacokinetics
The complex phytochemistry of Juniper essential oil makes it difficult to conceive any representative
okinetic study. As a consequence no data are available.
Toxicology
Most reports of toxic
and genotoxicity exi
ity refer to the essential oil or essential oil components. No data on carcinogenicity
st.
4.
Clinical Data
4.1.
Clinical Pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal
constituents
There are no data available on human pharma
codynamics.
4.1.2.
Overview
substance(s)/preparation(s) includin
of pharmacokinetic data regarding the herbal
g data on relevant constituents
There are
no data available on human pharmacokinetics.
4.2.
Clinical Efficacy
4.2.1.
Dose response studies
Not available.
4.2.2.
Clinical studies (case studies and clinical tri
als)
Not availab
le.
4.2.3.
Clinical studies in special popu
lations (e.g. elderly and children)
Not available.
4.3.
Overall conclusions on clinical pharmacology and efficacy
Not applicable.
5.
Clinical Safety/Pharmaco
vigilance
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.
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
Page 14/17
pharmac
substance(s)/preparation(s) including data on relevant
Schilcher & Heil are not convinced of the renal toxicity of
Juniperus
oil because quite a lot of sources
P, 2003).
Nevertheless the German Kommission E only considered dyspepsia as the only th
The use of essential oil is questioned by some authors (Bruneton, 1999). Here
by Duke (1988): “
… this drug is no longer recommended for various kidney diso
profession. Since much safer and more effective diuretic and carminative drugs exist,
Juniper in folk medicine should also be abandoned …”.
The author does not ref
causality reporting. Not all
the cone berries of
Juniperus communis
as valuable ‘
aquaretica
’. They include th
for traditional use: unspecific dysuria, sensitive bladder (‘Reizblase’) and prophylax
urolithiasis and urinary infections.
erapeutic indication.
with a quote supported
rders by the medical
the use of
er to case studies or
German sources limit the use of Juniper. Weiss & Fintelman (1999) consider
e following conditions
is of relapsing
In Belgium, only
Juniperus sabina
L. is prohibited to be used in food or food supplements. The cone
irginiana
L. are permitted,
L. is allowed
97).
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). Overdo
oil leads to renal damage. Cramp-like pain and bleeding of the uterus has been menti
al.
1993).
sing with the essential
oned (Hänsel
et
According to Semon (1844; cited by Schilcher & Heil 1994), Juniper oil increases t
and dose dependent damage can occur (stranguria, dysuria, hematuria and isc
Juniper oil was formerly compared with terpentine oil. Most probably the findings fo
were copied to Juniper oil without factual analysis. A
mentioned Juniper cone berries in his
Materia Medica
: “
… may set up renal irrita
producing strangury, priapism; hematuria, suppression of the urine and uremic c
wording taken over by the German literature. Although the volatile oil is reporte
sensitising and non-phototoxic, dermal irritation has been recognized with Junipe
test reactions have been documented. The latter are attributed to the irritant natu
pseudo-fructus
extract. Burning, erythema, inflammation with blisters and oedem
after external application of the essential oil (Barnes
et
he renal circulation
huria). The activity of
r terpentine oil
lso Potter (1898; cited by Schilcher & Heil, 1994)
tion, in large doses
onvulsions …
”, a
d to be generally non-
r and positive patch
re of a
Juniperi
a have been reported
al.
2007).
r berry oil for 24
latum and tested
re applied, no skin
4 h produced two
irritation reactions in 20 subjects. On the other hand a 48 h closed patch test in humans tested with
5% oil in petrolatum produced no irritation and no irritation and sensitization or phototoxic reactions
were reported (De Smet
et al.
1993). In a study including 86 patients with allergic reactions Juniper
berry oil caused allergic reactions in 6 patients (Anonymous, 2001).
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 (
http://ezinearticles.com/?Juniper---Uses-and-Side-Effects&id=1071369
last
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
Page 15/17
may just have copied the doubtful renal side effects (Schilcher & Heil, 1994; ESCO
berries of
Juniperus communis
L.,
Juniperus procera
Hochst. and
Juniperus v
as notified ingredients of food supplements. Also the use of
Juniperus oxycedrus
(Anonymous, 19
Two irritation reactions were observed in 2 of 20 subjects patch-tested with Junipe
hours. No skin irritations occurred when 8% Juniper berry oil was mixed with petro
with closed patches for 48 hours. In another exposure test with the same mixtu
sensitization was seen (Anonymous, 2001). A patch test using full strength oil for 2
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
terpentine oil. Some sources even use the term ‘falsification’. By preference t
and β-pinene ideally should be low, whereas the conte
substance being considered as
irritation sh
contaminated with
he concentration of α-
nt of terpinene-4-ol should be high, the latter
an active compound. Moreover, for such essential oils, the renal
ould be minimal (Schilcher & Heil, 1994; ESCOP, 2003).
Serious adverse events and deat
hs
None reported.
5.4.
Laboratory findings
No data available.
5.5.
Safety in special populations and
situations
munis
is contra-indicated in case of inflammation of the kidney, nephritis and
pyelitis (Kommission E, 1984; De Smet
et al.
1993; ESCOP, 2003).
Intrinsic (including elderly and children) /extrinsic factors
No data available.
Drug interactions
ucose levels in diabetes.
However, there will be no warning in the monograph, as the experimental data from different
ents are contradicting (ESCOP, 2003; Barnes
et al.
2007).
experim
Use in pregnancy and lactation
of essential oil in these
conditions is also not recommended. It is generally accepted that Juniper should not be used by
men as uretral contractions could occur (Duke 1988).
pregnant wo
longed 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
stimulation like
ccur as well as metrorrhagia and abortion (Wichtl, 1994; Duke, 1988).
upsets, accelerated heartbeat and blood pressure. Rarely symptoms of central
convulsions o
Drug abuse
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.
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
Page 16/17
The use of
Juniperus com
There is limited evidence from preclinical studies that Juniper may influence gl
As the cone berries should not be used during pregnancy and lactation, use
In case of pro
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 concentr
used and the way of extraction; as both the cone berries and the essential oil have a poss
antioxidant effect, the original composition
ation of compounds and thus on the solvents
ible
has to be considered;
the patients: apart from preclinical data on reproductive toxicology, little
groups at risk and interactions with other medication;
is known about possible
the physiological condition: it can be e
xpected that the kidney will be the first target organ.
There seems to be confusion a
terpentine oil. The findings reporte
been copied several times without further analysis.
bout the possible toxicity of Juniper oil and data obtained with
d by Semon (Semon 1844; cited by Schilcher & Heil 1994) have
6.
Overall conclusions
The traditional use of
Juniperus communi
the stimulation of ren
tradition and by experimental evidence, the latter only by tradition.
s
aetheroleum
and preparation thereof should be limited to
al water excretion and to dyspeptic disorders. The former is sustained by
There is a need for systematic pharmacovigilance reporting in order to addres
safety when using different preparations of Juniper.
s the issue of subacute
Benefit-risk assessm
ent
Juniper essential oil is described in the European Pharm
remain possible: unripe berries should not be used. Essential oil should only be prep
berries, without any needles or wood from the tree. Contaminated oil can indeed
function, so quality should be proven. However, reports on cases of overdose or p
vague and of bad quality, not meeting the pharmacovigilance criteria. Pharmaco
components are not known.
acopoeia. Adulteration and contamination
ared from ripe
affect the renal
rolonged use are
kinetics of Juniper
As genotoxicity has not been studied, a list entry cannot be granted.
l use are far from life
ing and suitable for self-medication. They have to be considered within a traditional context.
There are more potent conventional medicines with known benefits based on well established use.
f risk may be: elderly, pregnant mothers and children. There are no reports on drug
interactions, but combining Juniper with diuretic compounds is not recommended. Although there is
some experimental evidence for a blood glucose lowering effect with extracts of Juniper cone berries,
the blood glucose lowering effect by the essential oil was not studied. There are also no reports on
clinical consequences of combining Juniper oil with blood glucose lowering medicines. No clinical trials
on Juniper oil are available; however, the European tradition is much older than 30 years.
Standard groups o
Annex
List of references
Assessment report on Juniperus communis L., aetheroleum
EMA/HMPC/12401/2010
Page 17/17
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 ora
threaten
Source: European Medicines Agency
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