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MONOGRAPH
FROM NATURAL STANDARD
Catherine Ulbricht, PharmD, Column Editor
Thyme (Thymus vulgaris L.), Thymol
Ethan Basch, MD, MPhil
Catherine Ulbricht, PharmD
Paul Hammerness, MD
Anja Bevins, PharmD
David Sollars, MAc, HMC
Ethan Basch is affiliated with the Natural Standard Research Collaboration.
Catherine Ulbricht is affiliated with the Massachusetts General Hospital. Paul
Hammerness is affiliated with the Harvard Medical School. Anja Bevins is affiliated
with Northeastern University. David Sollars is affiliated with the New England School
of Acupuncture. All are members of the Natural Standard Research Collaboration
(www.naturalstandard.com).
Address correspondence to: Catherine Ulbricht, PharmD, c/o Natural Standard, P.O.
Box 390709, Cambridge, MA 02139-0008 (E-mail: ulbricht@naturalstandard.com).
The information in this monograph is intended for informational purposes only, and
is meant to help users better understand health concerns. Information is based on re
-
view of scientific research data, historical practice patterns, and clinical experience.
This information should not be interpreted as specific medical advice. Users should
consult with a qualified healthcare provider for specific questions regarding therapies,
diagnosis and/or health conditions, prior to making therapeutic decisions.
Copyright 2003 Natural Standard Inc. Reprinted with permission.
Journal of Herbal Pharmacotherapy, Vol. 4(1) 2004
http://www.haworthpress.com/web/JHP
Digital Object Identifier: 10.1300/J157v04n01_07 49
ABSTRACT. An evidence-based systematic review including scien
-
tific evidence, expert opinion, folkloric precedent, history, pharmacol
-
ogy, kinetics/dynamics, interactions, adverse effects, toxicology, and
dosing.
[Article copies available for a fee from The Haworth Document Deliv
-
ery Service: 1-800-HAWORTH. E-mail address: <docdelivery@haworthpress.
com> Website: <http://www.HaworthPress.com>]
KEYWORDS. Thymus vulgaris L., thymol, Labiatae, Lamiaceae
SYNONYMS/COMMON NAMES/RELATED SUBSTANCES. Com
-
mon thyme, common garden thyme, English thyme, farigola, folia thymi,
French thyme, garden thyme, Gartenthymian, herba thymi, herba timi,
Labiatae (family), Lamiaceae (family), mother of thyme, red thyme,
rubbed thyme, serpyllium, shepherd’s thyme, Spanish thyme, ten, thick
leaf thyme, time, timo, thym, thyme aetheroleum, thyme oil, thymi
herba, Thymian, Thymus serpyllum, Thymus zygis L., wild thyme, white
thyme oil.
CLINICAL BOTTOM LINE/EFFECTIVENESS
Brief Background
Thyme has been used medicinally for thousands of years. Beyond its
common culinary application, it has been recommended for a myriad of
indications, based upon proposed antimicrobial, antitussive, spasmolytic
and antioxidant activity. To date there are no well-defined controlled
clinical trials to support thyme monotherapy for therapeutic use in hu-
mans.
Thymol, one of the constituents of thyme, is contained in antiseptic
mouthwashes, with limited clinical studies in the available literature to
corroborate its efficacy as a monotherapy in dental outcomes, such as
reductions in plaque formation, gingivitis and caries.
Although no well-defined clinical data exist, traditional health prac
-
tice patterns, expert opinion, and anecdote suggest that the herb is gen
-
erally well tolerated in common doses; the majority of adverse events
appear to be related to dermatologic or allergic reactions. The essential
oil of thyme should not be used orally since it has been associated with
toxic reactions ranging from nausea to respiratory arrest.
50 JOURNAL OF HERBAL PHARMACOTHERAPY
Scientific Evidence for Common/Studied Uses
Indication Evidence Grade
Alopecia areata C
Dental plaque C
Paronychia, onycholysis, antifungal C
Bronchitis, cough C
Inflammatory skin disorders C
Historical or Theoretical Indications
Which Lack Sufficient Evidence
Abscess, acne, appetite stimulant, anxiety, arthritis, asthma, burns,
cancer,
1
cellulitis, depression, gastritis, colic, cystitis, dermatitis, der-
matomyositis, diarrhea, diuresis, dysmenorrhea, dyspepsia, dyspnea,
eczema, edema, enuresis, epilepsy, fever, flatulence, flu, gas, gingivitis,
gout, H. pylori,
2
halitosis, headache, heartburn, hookworms, indiges-
tion, inflammation of the colon, insect bites, insomnia, intestinal para-
sites, laryngitis, lice, neuralgia, nightmares, obesity, pertussis, pruritis,
rheumatism, roundworms, scabies, scleroderma, sinusitis, sore throat,
spasms, sprains, stomach cramps, stomatitis, tonsillitis, urethritis, upper
respiratory tract infection, urinary tract infection, vaginal irritation,
warts, wound healing.
Expert Opinion and Folkloric Precedent
Thyme leaf is renowned for being a culinary spice and has also been
used cosmetically and medicinally.
Traditional uses of thyme include for coughs and upper respiratory
congestion; it continues to be one of the most commonly recommended
herbs in Europe for these indications. The German expert panel, the
Commission E, has approved thyme for symptoms of bronchitis, whoop
-
ing cough, and catarrh (inflammation of upper respiratory tract mucous
membranes).
Topically, thymol (a major constituent of thyme), has been used for
various bacterial infections. Recent studies of combination products in
-
cluding thymol, such as Listerine
®
, have shown antibacterial activity
when used as a mouthwash to reduce oral bacteria.
Monograph from Natural Standard 51
Experts have recommended the use of thymol in treatment of acti
-
nomycosis, onycholysis (separation or loosening of a fingernail or toe
-
nail from its nail bed), and paronychia (inflammation of the tissue
surrounding a fingernail or toenail) due to its antifungal properties. An
-
ecdotal reports of successful healing date to the 1960s,
3
although there
are no well-designed clinical studies to advise for human therapeutic
use.
Brief Safety Summary
Likely Safe: When thyme is used in amounts found in foods; thyme
was granted “generally recognized as safe status” (GRAS) status in the
United States.
Possibly Safe: When thyme is used orally or topically in recom-
mended amounts. It is often recommended not to exceed oral doses of
10 g dried leaf containing 0.03% phenol (calculated as thymol) per day.
Likely Unsafe: When thyme oil is used either orally or topically in a
non-diluted form.
DOSING/TOXICOLOGY
General
There is limited scientific evidence supporting any specific dose of
thyme. Listed doses are based primarily on historical practice. How-
ever, with natural products it is often not clear what the optimal doses
are to balance efficacy and safety. Preparation of products may vary
from manufacturer to manufacturer, and from batch to batch within one
manufacturer. Because it is often not clear what are the active compo
-
nents of a product, standardization may not be possible, and the clinical
effects of different brands may not be comparable.
Standardization
Standardized amounts of thyme oil may be found in commercial
products, such as topical cosmetic formulations or mouthwash.
4
Standardized extracts may contain 0.6-1.2% volatile oil and 0.5%
phenol content.
Common thyme contains a greater quantity of volatile oil (0.4-3.4%)
than Spanish thyme (0.7-1.38%).
52 JOURNAL OF HERBAL PHARMACOTHERAPY
Adult Dosing (18 Years and Older)
Oral
General: One to two grams of thyme extract taken daily in divided
doses has been used.
Tea: For upper respiratory tract infection/bronchitis symptoms, it has
been recommended to steep 1-2 grams of dried herb in 150 mL boiling
water for 10 minutes, strain, and drink several times daily as needed for
symptom alleviation. Safety and efficacy have not been proven.
Liquid Extract: Traditional doses for various ailments including up
-
per respiratory tract infection symptoms include 1-2 grams of extract in
fluid/one cup water up to three times daily; 20-40 drops liquid extract
(1:1 weight/volume fresh leaf or 1:4 dried leaf) three times daily in
juice; or 40 drops tincture (1:10 in 70% ethanol) up to three times daily.
Safety and efficacy have not been proven.
Oil: Two to three drops thyme oil on a sugar cube 2-3 times daily has
been used. Safety and efficacy have not been proven, and thyme oil is
considered to be highly toxic.
Combination with Primulae radis: In one study, 1 tablet of Bronchipret
®
containing 60 mg dried extract of Primulae radis and 160 mg dried ex-
tract of thyme was used, although the specific number of tablets and fre-
quency of administration were not clear.
5
Gargle/Mouthwash
For periodontal prophylaxis, it has been recommended to steep 5
grams dried leaf per 100 mL boiling water for 10 minutes and strain (5%
infusion). Thymol is a constituent in some combination mouthwash
products such as Listerine (demonstrated to be efficacious in the reduc
-
tion of oral bacteria).
Topical
Oil/Ointment: For alopecia areata, 2-3 drops of an essential oil com
-
bination (thyme, lavender, rosemary, and cedarwood added to grape
-
seed and jojoba oil) massaged into the scalp every night for seven
months has been studied.
6
For paronychia, 1 drop of 1-2% thymol in
chloroform to the affected area three times daily, or 1 drop of 4%
thymol in chloroform to a chronically affected area three times daily has
been used.
3
Diluted thyme oil has been applied as needed in 1-2% oint
-
Monograph from Natural Standard 53
ments for a variety of skin disorders. Safety and efficacy have not been
proven, and thyme oil is considered to be highly toxic.
Compress: As a compress for rheumatic diseases, bruises, and mis
-
cellaneous skin disorders, it has been recommended to steep 5 grams of
dried leaf per 100 mL boiling water for 10 minutes and strain. Safety
and efficacy have not been proven.
Pediatric Dosing (Younger Than 18 Years)
There is insufficient available evidence to recommend medicinal use of
thyme in children for any indication. For periodontal prophylaxis, a combi
-
nation product containing 1% chlorhexidine/thymol varnish (Cervitec
®
)
was tolerated in 110 healthy children, ages 8-10 years old, when taken 3
times within 2 weeks.
7
Toxicology
Anecdotally, it has been suggested not to exceed oral doses of 10
grams of dried leaf with 0.03% phenol (calculated as thymol) per day to
prevent toxicity.
Thyme oil is considered to be highly toxic. Signs of toxicity include
nausea, and based on animal studies may include tachypnea and hypo-
tension.
8
The LD
50
of the essential oil of thyme is 2.84 g/kg body weight in
rats.
9
Oral doses (0.5-3 g/kg body weight) of concentrated thyme ex-
tract (equivalent to 4.3-26 g/kg of thyme) decreased locomotor activity
and respiratory activity in mice.
10
Following 3 months oral administra-
tion of 0.9 g dried herb daily as an extract in 95% ethanol, mice experi
-
enced an increase in liver and testes weight; 30% of male animals and
10% of female and control animals died.
10
PRECAUTIONS/CONTRAINIDCATIONS
Allergy
Avoid if known allergy/hypersensitivity to members of the Lamiaceae
(mint) family or to any component of thyme.
Contact allergies to thyme or thyme oil have been reported by numer
-
ous sources, dating to the 1940s and 1950s. In a study of 100 patients
with contact allergies, 5% were attributed to thyme oil as an allergen
54 JOURNAL OF HERBAL PHARMACOTHERAPY
contained in wound dressings.
11
Several case reports have described al
-
lergic contact dermatitis and allergic alveolitis provoked by thyme and
thymol (a main component of thyme oil).
12-14
In one case report, pruritic
contact dermatitis was observed following topical application of the
combination antiseptic solution Listerine to a chronic parenchyma of
the toe; patch testing with single ingredients revealed selective allergic
hypersensitivity to thymol.
15
Cross-reactions to birch pollen, celery, oregano, and to other species
in the Lamiaceae/Labiatae (mint) family may occur, and have been re
-
ported in a 45-year-old man allergic to thyme with a history of IgE-me
-
diated rhinitis and asthma.
16
His reaction included nausea, emesis,
pruritis, angioedema, dysphagia, dysphonia, hypotension, and progres-
sive respiratory difficulty. The subject recovered with supportive therapy
including epinephrine, antihistamines and corticosteroids, and cross-re-
activity was confirmed using in vitro assays.
Adverse Effects
General: Based on historical use and clinical anecdote, thyme flower
and leaves appear to be safe in culinary and in limited medicinal use.
However, caution is warranted with the use of thyme oil, which should
not be taken orally and should be diluted for topical administration due
to potential toxic effects.
Neurologic/CNS: Headache and dizziness have been associated with
oral ingestion of thyme and thyme oil. Oral ingestion of thyme oil may
cause seizure and coma.
Ocular/Otic: Conjunctivitis has been reported in a farmer exposed to
thyme dust.
14
Dermatologic: Contact dermatologic reactions have been reported in
numerous sources, dating to the 1940s and 1950s. Spiewak et al. de
-
scribe occupational airborne contact dermatitis caused by thyme dust in
farmers exposed to dried thyme.
14
Allergic contact dermatitis was re
-
ported in a 70-year-old woman six weeks after initiation of 4% thymol
once daily to a chronic paronychia.
12
Topical application of Listerine
antiseptic solution to a chronic parenchyma of the toe by a 43-year-old
man resulted in contact dermatitis.
15
As an ingredient in toothpaste,
cases of inflamed lips and tongue have anecdotally been attributed to
thyme oil.
Pulmonary/Respiratory: Occupational asthma provoked by thyme
and confirmed by inhalation challenge has been described in a butcher.
17
Allergic alveolitis and rhinitis due to thyme dust exposure have been re
-
Monograph from Natural Standard 55
ported in farmers.
13,14
High doses of thyme or thyme oil have elicited
tachypnea in animals.
8
Oral ingestion of thyme oil may lead to respira
-
tory arrest (anecdotal).
Cardiovascular: Hypotension after ingestion of thyme seasoning
was seen in a 45-year-old man, possibly related to an allergic re
-
sponse.
16
Animal studies have reported both hypotension and increased
cardiac contractility.
8
Anecdotal reports suggest that bradycardia may
be associated with ingestion of thyme, and cardiac arrest may occur
with oral intake of thyme oil.
Gastrointestinal: Oral thyme and thyme oil may elicit heartburn,
nausea, vomiting, diarrhea, and gastrointestinal irritation (anecdotal).
Endocrine: An extract of Thymus serpyllum, a related species to Thy
-
mus vulgaris, has been shown to exert anti-thyrotropic effects in rats,
causing decline in thyroid stimulating hormone and prolactin.
18
Estradiol
and progesterone receptor-binding activity has been demonstrated in
vivo.
19
Endocrine effects of Thymus vulgaris in humans are unclear.
Genitourinary: Oral thyme has anecdotally been reported to exacer-
bate inflammation associated with urinary tract infections.
Musculoskeletal: Oral use of thyme or thyme oil has been associated
with muscle weakness in anecdotal reports, although details are limited.
Precautions/Warnings/Contraindications
Avoid if known allergy/hypersensitivity to members of the Lamiaceae
(mint) family or to any component of thyme.
Avoid oral ingestion or non-diluted topical application of thyme oil
due to potential toxicity.
Avoid topical preparations in areas of skin breakdown or injury, or in
atopic patients, due to multiple reports of contact dermatitis.
Use cautiously in patients with gastrointestinal irritation or peptic ul
-
cer disease due to anecdotal reports of gastrointestinal irritation.
Use cautiously in patients with thyroid disorders due to observed
anti-thyrotropic effects in animal research of the related species Thymus
serpyllum.
Pregnancy and Lactation
Thyme is not recommended in pregnancy or lactation, due to lack of
sufficient data. A 1975 review of plants as possible new anti-fertility
agents classified thyme as an emmenagogue and abortifacient.
20
56 JOURNAL OF HERBAL PHARMACOTHERAPY
INTERACTIONS
Thyme/Drug Interactions
Thyroid Replacement Therapy, Anti-Thyroid Agents: An extract of
Thymus serpyllum, a related species to Thymus vulgaris, has been
shown to exert anti-thyrotropic effects in rats, causing decline in thyroid
stimulating hormone and prolactin.
18
Therefore, in theory, thyme may
decrease levels of thyroid hormone, although this has not been system
-
atically studied or demonstrated in humans.
Estrogen, Progesterone: Thyme has demonstrated estradiol and pro-
gesterone receptor-binding activity in vivo,
19
although this has not been
systematically studied or demonstrated in humans.
5-fluorouracil (Topical): Topical thymol significantly enhanced
percutaneous absorption of 5-fluorouracil through porcine epidermis
compared to control.
21
Thyme/Herb/Supplement Interactions
Herbs with Estrogen or Progesterone Receptor Activity: Thyme has
demonstrated estradiol and progesterone receptor-binding activity in
vivo,
19
although this has not been systematically studied or demon-
strated in humans.
Thyme/Food Interactions
Insufficient available evidence.
Thyme/Lab Interactions
Thyroid Stimulating Hormone (TSH): TSH levels have been sup
-
pressed by administration of thyme extract in rats.
18
Effects in humans
are unknown.
Thyroid Hormones (T3, T4): Thyroid hormone levels have been re
-
ported to decrease after single intravenous injections of thyme extract in
rats.
18
Prolactin: Based on pre-clinical data, prolactin levels theoretically
may be decreased at high thyme doses.
18
Monograph from Natural Standard 57
MECHANISM OF ACTION
Pharmacology
Constituents: The key constituents of thyme include essential oils,
such as the phenols thymol and carvacrol, glycosides, flavonoids, p-cy
-
mene, borneol, linalool, alcohols, rosmarinic acid, saponins, tannins,
and terpenoids.
14,22,23
Four acetophenone glycosides have been isolated
from the butanol-soluble fraction of thyme extracts, with weak cytotoxic
and antioxidant effects in vitro.
24
Anti-Microbial Effects: Anti-microbial activities of thyme and thymol
have been reported in vitro.
4
Antibacterial efficacy has been noted
against several bacterial species, including Salmonella typhimurium,
Staphylococcus aureus, and Helicobacter pylori.
2,4,25-28
Activity against
cariogenic and periodontopathogenic bacteria such as Porphyromonas
gingivalis, Selenomonas artemidis, Streptococcus sobrinus, and Strep-
tococcus mutans has been reported, possibly related to membrane per-
foration and rapid efflux of intracellular components.
7,29
Thymol has
exhibited activity against some fungi and yeast including Aspergillus
parasiticus, Aspergillus flavus, and Candida albicans, and suppresses
fungal growth and aflatoxin synthesis at doses of 250 ppm in vitro.
4,30-33
Spasmolytic/Antitussive Effects: Spasmolytic and antitussive activity
has historically been attributed to thymol and carvacrol.
34
In animal
models, flavonoids in thyme appear to relax tracheal and ileal smooth
muscles via inhibition of acetylcholine and histamine receptors, or via
calcium channel antagonism.
22,23,35
In vitro, thyme extract and volatile
oil exert relaxing effects on tracheal and ileal smooth muscle by inhibit-
ing phasic contractions,
36,37
and may depend on the concentration of
flavone aglycones.
35
Antioxidant Effects: A biphenyl compound and a flavonoid isolated
from thyme have been reported to inhibit superoxide anion production
and to protect red blood cells against oxidative damage.
38
Rat and in vitro
studies have noted antioxidant properties of thyme oil and thymol.
39-42
Anti-Inflammatory Effects: Inhibition of prostaglandin synthesis by
thymol and carvacrol,
43
and in vivo inhibition of mouse macrophages
and complement activation have been reported.
44
Pharmacodynamics/Kinetics
There is limited available pharmacodynamic information for thyme,
its constituents or derivatives. In one study of thymol and carvacrol in
58 JOURNAL OF HERBAL PHARMACOTHERAPY
rats, urinary excretion of metabolites occurred rapidly; only small
amounts were excreted after 24 hours.
45
HISTORY
Thyme has been used historically for cosmetic, culinary and medici
-
nal purposes. Ancient Sumerian and Egyptian cultures employed thyme
for medicinal purposes and to embalm the dead. Romans burnt thyme to
deter dangerous animals, and used thyme to flavor cheese and alcoholic
beverages. Roman soldiers bathed in thyme, as this was believed to pro
-
vide vigor.
Thyme’s common name may be derived from a Greek word meaning
to fumigate, based on its use as incense, or may come from the Greek
word thymon, meaning courage. In Medieval times, women sometimes
embroidered a sprig of thyme on gifts for knights.
In modern times, thyme oil is commonly used in manufacturing as a
constituent of soaps, cosmetics, mouthwash and toothpaste. Red thyme
oil is used in perfumes.
EVIDENCE TABLE
Condition Study
Design
Author,
Year
N Statistically
Significant?
Quality of
Study
0-2 = poor
3-4 = good
5 = excellent
Magnitude
of Benefit
ARR NNT Comments
Alopecia
areata
Randomized
controlled
trial
Hay,
1999
86 Yes 2 Small NA NA Thyme used in
a combination oil.
Bronchitis Matched pair
comparison
Ernst,
1997
7783 NA NA NA NA NA Thyme used in
combination with
primula root
(Bronchipret
®
)
vs. synthetic
secretolytics.
Cough Randomized,
controlled,
double-blind
trial
Knols,
1994
60 No 2 NA NA NA Thyme compared
to bromhexine.
EVIDENCE DISCUSSION
Alopecia Areata
Summary: There is no available clinical evidence regarding the use
of thyme as a monotherapy for hair loss. Combination preparations of
Monograph from Natural Standard 59
essential oils including thyme have been evaluated, without definitive
results. Therefore, there is currently insufficient information to recom
-
mend for or against the use of topical thyme oil for alopecia areata.
Evidence: In a randomized double-blind trial, 86 subjects with alope
-
cia were assigned to massage a combination of essential oils (thyme,
rosemary, lavender, and cedarwood) or a placebo oil into the scalp
nightly.
6
After seven months, it was reported that 44% of the essential
oil group experienced new hair growth, compared to 15% of controls,
with statistical significance. However, measurement of affected areas
was only performed in 32 patients. Although this study was designed to
be double-blind, the oils were not identical in smell, and therefore dif
-
ferences could be discerned both by enrollees and evaluators. There was
a 32% attrition rate in the control group, without follow-up of dropouts.
Conceivably if patients experiencing hair growth dropped out of the
control group, this would skew results favorably towards the treatment
group.
Dental Plaque
Summary: One of thyme’s main constituents, thymol, has been found
in vitro to have activity against cariogenic and periodontopathogenic
bacteria such as Porphyromonas gingivalis, Selenomonas artemidis,
Streptococcus sobrinus, and Streptococcus mutans (possibly related to
membrane perforation and rapid efflux of intracellular components).
7,29
Thymol is included as one of several ingredient in antiseptic mouth-
washes such as Listerine. Clinical studies have reported efficacy of
Listerine in decreasing plaque formation and gingivitis, although hu
-
man evidence for thymol as a monotherapy mouthrinse is lacking.
Cervitec: A combination product of 1% chlorhexidine and 1% thymol
varnish (Cervitec) has been evaluated in the treatment of Streptococcus
mutans in plaque and saliva in 110 schoolchildren. Subjects were as
-
signed to receive this preparation over 2 years, and were compared to an
untreated reference group. Statistically significant reductions in bacte
-
rial colonization levels (at 1 month only) and in interdental plaque (at 1
and 3 months) were reported in treated children.
7
These results are of
limited clinical utility due to the open and uncontrolled nature of the
trial and the use of a combination product.
Listerine: Listerine antiseptic mouthrinse contains a combination of
essential oils, including eucalyptol, menthol, thymol, and methyl sal
-
icylate. Broad-spectrum antibiotic properties have been demonstrated
for Listerine
46
including against Streptococcus mutans
47
herpes sim
-
60 JOURNAL OF HERBAL PHARMACOTHERAPY
plex virus, and influenza A virus.
48
Listerine has been demonstrated in
several randomized, double-blind trials to be efficacious in the treat
-
ment of supragingival plaque and gingivitis when used twice daily for
up to six months.
49-52
•
Listerine mouthrinse has been reported to significantly reduce gin
-
givitis and plaque in several additional human studies,
53-55
and to
be less efficacious than Peridex
®
(chlorhexidine) against plaque,
56-58
but less likely than Peridex to cause stains or supragingival calcu
-
lus.
59
A 2001 human trial conducted by Pfizer (the manufacturer
of Listerine) reported Listerine mouthrinse plus a fluoride tooth
-
paste to be superior to Colgate Total dentrifice (toothpaste) for the
reduction of plaque and gingivitis in 316 individuals with plaque
after six months.
60
• There is early evidence that Listerine is able to penetrate dental
plaque biofilm and kill gram-positive organisms interproximally
(in the area most associated with periodontitis and dental caries,
heretofore thought to be cleansed primarily only via flossing).
61,62
• Adverse effects of Listerine have included case reports of allergic
contact dermatitis,
15
attributed to thymol, and cardiac asystole in
an alcoholic patient who ingested a large volume of Listerine.
63
Other uses of Listerine have included the removal of orally inhaled
corticosteroids following inhalation,
64
and wound-dressing fol-
lowing periodontal surgery.
65
Paronychia, Onycholysis, Antifungal
Summary: In vitro studies suggest that thyme essential oil and thymol
exert activity against a number of fungi including Aspergillus parasiticus
and Aspergillus flavus, and may completely suppress growth and afla
-
toxin synthesis. Topical thymol has been used traditionally in the treat
-
ment of paronychia and onycholysis. However, due to a lack of controlled
clinical trials, there is insufficient evidence to recommend for or against
thyme/thymol as a treatment for fungal infections.
Evidence: In the 1930s, Myers reported five cases of actinomycosis
successfully treated to resolution with thymol in oral doses, ranging
from 1 gram twice weekly up to 2 grams once daily.
66
Three of the five
patients received additional thymol as a 10-25% injection into the sinus
tract. A sixth patient received local thymol injection only and subse
-
quently died of fungemia. Adverse effects were not clearly reported,
and in light of the known toxicity of thymol, and the current availability
Monograph from Natural Standard 61
of other antifungal agents with demonstrated efficacy and more favor
-
able therapeutic indices, thymol may not be advisable for such cases.
Topical thymol has been used traditionally in the treatment of paro
-
nychia and onycholysis. In a 1965 review article in the Archives of Der
-
matology, Wilson suggested that one drop of 1% or 2% thymol in
chloroform can be used for acute paronychia, while chronic cases may
be treated with 4% thymol, applied three times daily.
3
The author noted
personal experience treating patients over 20 years with these formula
-
tions with good results and excellent tolerance.
Bronchitis, Cough
Summary: Thyme has traditionally been used for the treatment of re
-
spiratory conditions including cough and bronchitis. Animal studies
have identified spasmolytic properties of thyme constituents. The Ger-
man expert panel, the Commission E, has approved thyme for use in
bronchitis. However, due to a lack of data regarding thyme as a mono-
therapy for any specific respiratory indication, there is currently insuffi-
cient scientific evidence to recommend for or against thyme as a
treatment for bronchitis or coughs.
Evidence: Ernst et al. conducted a multi-center post-market surveil-
lance study comparing Bronchipret
®
(combination of thyme and primula
root) with other pharmaceutical options for acute bronchitis.
5
The study
was designed as a matched-pair comparison of 7,783 patients. Patients
received Bronchipret, “other herbals” pooled into one treatment group
(Bronchoforton-eucalyptus, peppermint, Hedelix-ivy extract, Prospan-
ivy extract, Sinupret-Rad. Gentianae, Flos Primulae cum calycibus,
Herba Rumicis, Flos Sambuci, Herba Verbenae, Soledum-extract of
thyme) or the synthetic agents N-Acetylcysteine (NAC) or Ambroxal.
Clinical outcomes of bronchitis and adverse reactions were documented.
Data were evaluated by comparing the treatment success of the test
medication and 3 control groups using ordinal regression. The authors
reported that the clinical effectiveness of Bronchipret was not less than
the synthetic drugs. There was a trend towards better results with
Bronchipret, particularly in adults. Bronchipret was associated with a
favorable adverse effects profile compared to controls. The authors
concluded a possible risk/benefit advantage of Bronchipret over these
controls for the management of acute bronchitis. This preliminary find
-
ing may merit follow-up with a prospective controlled trial with both a
placebo arm, and a control medication with established evidence of effi
-
cacy.
62 JOURNAL OF HERBAL PHARMACOTHERAPY
In a double blind, randomized trial, 60 patients with productive
cough as a result of an uncomplicated respiratory infection received ei
-
ther syrup of thyme or bromhexine for a period of 5 days.
67
Both groups
made similar gains from day zero to day five. The authors reported no
significant difference between the two groups based on self-reported
symptom relief. The study concluded that bromhexine may be no better
in alleviating coughing complaints than syrup of thyme. However, no
power calculation was conducted prior to the study, and it is conceiv
-
able that the sample size was too small to detect significant differences
between groups. Without a placebo arm, these results cannot be dis
-
criminated from the natural course of disease.
Inflammatory Skin Disorders
Summary: Historically, thyme has been used topically for a number
of dermatologic conditions. Although several case reports note possible
beneficial effects, controlled trial evidence of effectiveness for treating
dermatological disorders is conflicting. Due to lack of controlled trials,
there is insufficient evidence to recommend for or against thyme as
treatment for inflammatory disorders of the skin.
Evidence: Oral administration of large doses of thymol was reported
to resolve a case of dermatomyositis and a case of progressive sclero-
derma in a 1965 publication.
68
• A case study of two sisters with vulval lichen sclerosis reported
successful treatment of both patients with a topical cream contain-
ing thyme extract. There were no reported side effects.
69
• A randomized controlled clinical trial evaluated the effects of
aromatherapy with essential oils including thyme on a group of
children with atopic eczema. The essential oil mixture (containing
thyme, benzoin, boswellia, German chamomile, Litsea cubeba,
myrrh, spike lavender, and sweet marjoram oil) was massaged into
the scalp daily in conjunction with counseling by a therapist. No
significant difference in improvement was detected between the
treatment group (aromatherapy with massage) and control (mas
-
sage only).
70
PRODUCTS STUDIED
Brands Used in Statistically Significant Clinical Trials
Not applicable.
Monograph from Natural Standard 63
Combination Products
Listerine contains thymol, a phenolic constituent of thyme, as well as
other essential oils such as eucalyptol.
NOTE
There are up to 400 subspecies of thyme; common thyme (Thymus vulgaris) and
Spanish thyme (Thymus zygis) are often used interchangeably for medicinal purposes.
Not to be confused with calamint (Calamintha ascendens, basil thyme) or with Spanish
origanum oil (Thymus capitatus, Sicilian thyme, Spanish thyme).
REFERENCES
1. Aschhoff B. Retrospective study of Ukrain treatment in 203 patients with ad-
vanced-stage tumors. Drugs Exp Clin Res 2000;26(5-6):249-252.
2. Tabak M, Armon R, Potasman I, et al. In vitro inhibition of Helicobacter pylori
by extracts of thyme. J Appl Bacteriol 1996;80(6):667-672.
3. Wilson JW. Paronychia and onycholysis, etiology and therapy. Arch Dermatol
1965;92(6):726-730.
4. Manou I, Bouillard L, Devleeschouwer MJ, et al. Evaluation of the preservative
properties of Thymus vulgaris essential oil in topically applied formulations under a
challenge test. J Appl Microbiol 1998;84(3):368-376.
5. Ernst E, Marz R, Sieder C. A controlled multi-centre study of herbal versus syn-
thetic secretolytic drugs for acute bronchitis. Phytomedicine 1997;4:287-293.
6. Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy. Suc
-
cessful treatment for alopecia areata. Arch Dermatol 1998;134(11):1349-1352.
7. Twetman S, Petersson LG. Interdental caries incidence and progression in rela
-
tion to mutans streptococci suppression after chlorhexidine-thymol varnish treatments
in schoolchildren. Acta Odontol Scand 1999;57(3):144-148.
8. Kagramanov KM, et al. Effect of the essential oils of some thyme growing in
Azerbaidzhan on cardiovascular activity and respiration. Azerbaidzhanskii Meditsinskii
Zhurnal 1977;54(5):49-51.
9. Skramlik EV. Toxicity and toleration of volatile oils. Pharmazie 1959;14:
435-445.
10. Qureshi S, Shah AH, Al-Yahya MA, et al. Toxicity of Achillea fragrantissima
and Thymus vulgaris in mice. Fitoterapia 1991;62(4):319-323.
11. Le Roy R, Grosshans E, Foussereau J. [Investigation of contact allergies in 100
cases of ulcus cruris (author’s transl)]. Derm Beruf Umwelt 1981;29(6):168-170.
12. Lorenzi S, Placucci F, Vincenzi C, et al. Allergic contact dermatitis due to
thymol. Contact Dermatitis 1995;33(6):439-440.
13. Mackiewicz B, Skorska C, Dutkiewicz J, et al. Allergic alveolitis due to herb
dust exposure. Ann Agric Environ Med 1999;6(2):167-170.
64 JOURNAL OF HERBAL PHARMACOTHERAPY
14. Spiewak R, Skorska C, Dutkiewicz J. Occupational airborne contact dermatitis
caused by thyme dust. Contact Dermatitis 2001;44(4):235-239.
15. Fisher AA. Allergic contact dermatitis due to thymol in Listerine for treatment
of paronychia. Cutis 1989;43(6):531-532.
16. Benito M, Jorro G, Morales C, et al. Labiatae allergy: systemic reactions due to
ingestion of oregano and thyme. Ann Allergy Asthma Immunol 1996;76(5):416-418.
17. Lemiere C, Cartier A, Lehrer SB, et al. Occupational asthma caused by aromatic
herbs. Allergy 1996;51(9):647-649.
18. Sourgens H, Winterhoff H, Gumbinger HG, et al. Antihormonal effects of plant
extracts. TSH-and prolactin-suppressing properties of Lithospermum officinale and
other plants. Planta Med 1982;45(2):78-86.
19. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods,
herbs, and spices. Proc Soc Exp Biol Med 1998;217(3):369-378.
20. Farnsworth NR, Bingel AS, Cordell GA, et al. Potential value of plants as
sources of new antifertility agents I. J Pharm Sci 1975;64(4):535-598.
21. Gao S, Singh J. Mechanism of transdermal transport of 5-fluorouracil by
terpenes: carvone, 1,8-cineole, and thymol. Int J Pharmaceutics 1997;154:67-77.
22. Van den Broucke CO, Lemli JA. Action spasmolytique des flavones de
differentes especes de Thymus. Plantes Med Phytother 1983;16(4):310-317.
23. Van den Broucke CO, Lemli JA. Spasmolytic activity of the flavonoids from
Thymus vulgaris. Pharm Weekbl Sci 1983;5(1):9-14.
24. Wang M, Kikuzaki H, Lin CC, et al. Acetophenone glycosides from thyme
(Thymus vulgaris L.). J Agric Food Chem 1999;47(5):1911-1914.
25. Ramanoelina AR, Terrom GP, Bianchini JP, et al. [Antibacterial action of es-
sential oils extracted from Madagascar plants]. Arch Inst Pasteur Madagascar 1987;
53(1):217-226.
26. Juven BJ, Kanner J, Schved F, et al. Factors that interact with the antibacterial
action of thyme essential oil and its active constituents. J Appl Bacteriol 1994;76(6):
626-631.
27. Agnihotri S, Vaidya AD. A novel approach to study antibacterial properties of
volatile components of selected Indian medicinal herbs. Indian J Exp Biol 1996;
34(7):712-715.
28. Ceyhan N, Ugur A. Investigation of in vitro antimicrobial activity of honey. Riv
Biol 2001;94(2):363-371.
29. Shapiro S, Guggenheim B. The action of thymol on oral bacteria. Oral Microbiol
Immunol 1995;10(4):241-246.
30. Mahmoud AL. Antifungal action and antiaflatoxigenic properties of some es
-
sential oil constituents. Lett Appl Microbiol 1994;19(2):110-113.
31. Tantaoui-Elaraki A, Beraoud L. Inhibition of growth and aflatoxin production
in Aspergillus parasiticus by essential oils of selected plant materials. J Environ Pathol
Toxicol Oncol 1994;13(1):67-72.
32. Arras G, Usai M. Fungitoxic activity of 12 essential oils against four post
-
harvest citrus pathogens: chemical analysis of thymus capitatus oil and its effect in
subatmospheric pressure conditions. J Food Prot 2001;64(7):1025-1029.
33. Inouye S, Uchida K, Yamaguchi H. In-vitro and in-vivo anti-Trichophyton ac
-
tivity of essential oils by vapour contact. Mycoses 2001;44(3-4):99-107.
Monograph from Natural Standard 65
34. Van den Broucke CO. Chemical and pharmacological investigation on Thymi
herba and its liquid extracts. Planta Med 1980;39:253-254.
35. Van den Broucke CO, Lemli JA. Pharmacological and chemical investigation
of thyme liquid extracts. Planta Med 1981;41(2):129-135.
36. Reiter M, Brandt W. Relaxant effects on tracheal and ileal smooth muscles of
the guinea pig. Arzneimittelforschung 1985;35(1A):408-414.
37. Meister A, Bernhardt G, Christoffel V, et al. Antispasmodic activity of Thymus
vulgaris extract on the isolated guinea-pig trachea: discrimination between drug and
ethanol effects. Planta Med 1999;65(6):512-516.
38. Haraguchi H, Saito T, Ishikawa H, et al. Antiperoxidative components in Thy
-
mus vulgaris. Planta Med 1996;62(3):217-221.
39. Youdim KA, Deans SG. Dietary supplementation of thyme (Thymus vulgaris
L.) essential oil during the lifetime of the rat: its effects on the antioxidant status in
liver, kidney and heart tissues. Mech. Ageing Dev. 1999;109(3):163-175.
40. Youdim KA, Deans SG. Effect of thyme oil and thymol dietary supple
-
mentation on the antioxidant status and fatty acid composition of the ageing rat brain.
Br J Nutr 2000;83(1):87-93.
41. Aeschbach R, Loliger J, Scott BC, et al. Antioxidant actions of thymol,
carvacrol, 6-gingerol, zingerone and hydroxytyrosol. Food Chem Toxicol 1994;32(1):
31-36.
42. Takacsova M, Pribela A, Faktorova M. Study of the antioxidative effects of
thyme, sage, juniper and oregano. Nahrung 1995;39(3):241-243.
43. Wagner H, Wierer M, Bauer R. [In vitro inhibition of prostaglandin biosynthesis
by essential oils and phenolic compounds]. Planta Med 1986;(3):184-187.
44. Englberger W, Hadding U, Etschenberg E, et al. Rosmarinic acid: a new inhibi-
tor of complement C3-convertase with anti-inflammatory activity. Int J Immuno-
pharmacol 1988;10(6):729-737.
45. Austgulen LT, Solheim E, Scheline RR. Metabolism in rats of p-cymene deriva-
tives: carvacrol and thymol. Pharmacol Toxicol 1987;61(2):98-102.
46. Ross NM, Charles CH, Dills SS. Long-term effects of Listerine antiseptic on
dental plaque and gingivitis. J Clin Dentistry 1988;1(4):92-95.
47. Fine DH, Furgang D, Barnett ML, et al. Effect of an essential oil-containing an
-
tiseptic mouthrinse on plaque and salivary Streptococcus mutans levels. J Clin Periodontol
2000;27(3):157-161.
48. Dennison DK, Meredith GM, Shillitoe EJ, et al. The antiviral spectrum of
Listerine antiseptic. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79(4):
442-448.
49. Lamster IB. The effect of Listerine antiseptic on reduction of existing plaque
and gingivitis. Clin Prev Dent 1983;5:12-16.
50. Gordon JM, Lamster IB, Seiger MC. Efficacy of Listerine antiseptic in inhibit
-
ing the development of plaque and gingivitis. J Clin Periodontol 1985;12(8):697-704.
51. DePaola LG, Overholser CD, Meiller TF, et al. Chemotherapeutic inhibition of
supragingival dental plaque and gingivitis development. J Clin Periodontol 1989;
16(5):311-315.
52. Minah GE, DePaola LG, Overholser CD, et al. Effects of 6 months use of an an
-
tiseptic mouthrinse on supragingival dental plaque microflora. J Clin Periodontol
1989;16(6):347-352.
66 JOURNAL OF HERBAL PHARMACOTHERAPY
53. Brecx M, Brownstone E, MacDonald L, et al. Efficacy of Listerine, Meridol and
chlorhexidine mouthrinses as supplements to regular tooth cleaning measures. J Clin
Periodontol 1992;19(3):202-207.
54. Pitts G, Brogdon C, Hu L, et al. Mechanism of action of an antiseptic, anti-odor
mouthwash. J Dent Res 1983;62(6):738-742.
55. Nelson RF, Rodasti PC, Tichnor A, et al. Comparative study of four over-
the-counter mouthrinses claiming antiplaque and/or antigingivitis benefits. Clin Prev
Dent 1991;13(6):30-33.
56. Maruniak J, Clark WB, Walker CB, et al. The effect of 3 mouthrinses on plaque
and gingivitis development. J Clin Periodontol 1992;19(1):19-23.
57. McKenzie WT, Forgas L, Vernino AR, et al. Comparison of a 0.12% chlorhexidine
mouthrinse and an essential oil mouthrinse on oral health in institutionalized, mentally
handicapped adults: one-year results. J Periodontol 1992;63(3):187-193.
58. Brecx M, Netuschil L, Reichert B, et al. Efficacy of Listerine, Meridol and
chlorhexidine mouthrinses on plaque, gingivitis and plaque bacteria vitality. J Clin
Periodontol 1990;17(5):292-297.
59. Overholser CD, Meiller TF, DePaola LG, et al. Comparative effects of 2
chemotherapeutic mouthrinses on the development of supragingival dental plaque and
gingivitis. J Clin Periodontol 1990;17(8):575-579.
60. Charles CH, Sharma NC, Galustians HJ, et al. Comparative efficacy of an anti-
septic mouthrinse and an antiplaque/antigingivitis dentifrice. A six-month clinical
trial. J Am Dent Assoc 2001;132(5):670-675.
61. Pan P, Barnett ML, Coelho J, et al. Determination of the in situ bactericidal ac-
tivity of an essential oil mouthrinse using a vital stain method. J Clin Periodontol
2000;27(4):256-261.
62. Fine DH, Furgang D, Barnett ML. Comparative antimicrobial activities of anti-
septic mouthrinses against isogenic planktonic and biofilm forms of Actinobacillus
actinomycetemcomitans. J Clin Periodontol 2001;28(7):697-700.
63. Westermeyer RR, Terpolilli RN. Cardiac asystole after mouthwash ingestion: a
case report and review of the contents. Mil Med 2001;166(9):833-835.
64. Kelloway JS, Wyatt NN, Adlis S, et al. Does using a mouthwash instead of wa
-
ter improve the oropharyngeal removal of inhaled flovent (fluticasone propionate)?
Allergy Asthma Proc 2001;22(6):367-371.
65. Yukna RA, Broxson AW, Mayer ET, et al. Comparison of Listerine mouthwash
and periodontal dressing following periodontal flap surgery. I. Initial findings. Clin
Prev Dent 1986;8(4):14-19.
66. Myers HB. Thymol therapy in actinomycosis. JAMA 1937;108(22):1875.
67. Knols G, Stal PC, Van Ree JW. Productive coughing complaints: Sirupus
Thymi or Bromhexine? A double-blind randomized study. Huisarts en Wetenschap
1994;37:392-394.
68. Buccellato G. [Dermatomyositis cured by administration of para-methyl-iso
-
propyl-phenol (thymol)]. G Ital Dermatol Minerva Dermatol 1965;106(1):89-94.
69. Hagedorn M. [Genital vulvar lichen sclerosis in 2 siblings]. Zeitschrift fur
Hautkrankheiten 1989;64(9):810, 813-810, 814.
70. Anderson C, Lis-Balchin M, Kirk-Smith M. Evaluation of massage with essen
-
tial oils on childhood atopic eczema. Phytother Res 2000;14(6):452-456.
Monograph from Natural Standard 67