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Thyme ( Thymus vulgaris L.), Thymol

Authors:

Abstract

An evidence-based systematic review including scientific evidence, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
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).
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Monograph from Natural Standard 67
... It is considered as very resistant plants, which allows it to live under extreme climatic conditions concerning temperature and water supply [5]. It is considered as one of most popular plants that has in addition to its culinary uses in salads, or with sesame and sumac what we know locally as "Zaatar", many other uses as a way of traditional treatments that used for thousands of years, it well known for its antimicrobial [6], Antifungal [7], antiinflammatory [8], and antioxidant activity [9]. ...
... Table (8). Shows the revenues and net profit of one dunam thyme field during the six years of this project, and Table (9). ...
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Cultivation of medicinal and aromatic plants significantly contribute to affordable healthcare and livelihood security. This study aims to investigate the economic analysis of Syrian oregano ( Origanum syriacum ) production with total area of 1000 m ² , depending on some standard economic indicators. The results showed that the annual net profit constitutes 56% of the total annual revenues. Furthermore, the net present value after six years was a positive value, and the index of profitability was 2.71, which confirms the economic viability of this project. The internal rate of return (IRR) reached 90.67%, which is a good number compared to the bank interest rate. Although this project does not occupy large areas, (a small possession 500-2000 m ² is sufficient for its establishment), but it is able to achieve guaranteed profits within a short period. Therefore, Thyme cultivation should be expanded by providing small farmers the necessary technical support and drawing their attention to economic efficiency of such project.
... The reported oral LD50 of thymol in guinea pigs, rats, mice, cats, and rabbits is 880, 980, 640, 250, and 750 mg kg −1 , respectively, 11 while the recommended daily dose of thymol sulfate for humans is 93.75 mg kg −1 . 46 The LD50 is still among the most important measures in evaluating compound toxicity, with an inverse relationship, a fact that further supports the reported data on the high safety of thymol. 47 On the other hand, Rojas-Armas et al. reported that an 28-day oral toxicity assessment of thyme oil, containing about 37-55% thymol, 48,49 revealed that the no-observedadverse-effect level (NOAEL) is greater than 250 mg kg −1 day −1 , whereas thyme oil exhibited moderate oral toxicity with a dose of 500 mg kg −1 day −1 . ...
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In the present study, we aimed to delineate the neuroprotective potential of thymol (THY) against neurotoxicity and cognitive deterioration induced by thioacetamide (TAA) in an experimental model of hepatic encephalopathy (HE). Rats received TAA (100 mg kg-1, intraperitoneally injected, three times per week) for two weeks. THY (30 and 60 mg kg-1), and Vit E (100 mg k-1) were administered daily by oral gavage for 30 days after HE induction. Supplementation with THY significantly improved liver function, reduced serum ammonia level, and ameliorated the locomotor and cognitive deficits. THY effectively modulated the alteration in oxidative stress markers, neurotransmitters, and brain ATP content. Histopathology of liver and brain tissues showed that THY had ameliorated TAA-induced damage, astrocyte swelling and brain edema. Furthermore, THY downregulated NF-kB and upregulated GFAP protein expression. In addition, THY significantly promoted CREB and BDNF expression at both mRNA and protein levels, together with enhancing brain cAMP level. In conclusion, THY exerted hepato- and neuroprotective effects against HE by mitigating hepatotoxicity, hyperammonemia and brain ATP depletion via its antioxidant, anti-inflammatory effects in addition to activation of the CREB/BDNF signaling pathway.
... com). T. vulgaris is a herb widely used in the traditional and alternative system of medicine for curing cough, bronchitis, constipation, warts, alopecia, spam, inflammation and skin infection 4,9 . The leaf essential oil of Thymus vulgaris has been reported to have significant antimicrobial, anti-oxidant, antifungal and cytotoxic activities 7,10,11 . ...
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The essential oil of Thymus vulgaris is extensively used in the food, pharmaceuticals, cosmetic and fragrance industries. The present work was carried out to analyse the chemical constituents of T. vulgaris leaf essential oil of Western Himalayan (India) origin and study its antimicrobial, antioxidant and cytotoxic potential. The analysis of the essential oil through GC-MS led to the identification of a total of 27 compounds representing 99.11 % of the total oil showing carvacrol (45.53 %) as the predominant constituent followed by o-cymene (11.29 %), linalool (9.60 %), diethyl phthalate (8.48 %) and thymol (6.12 %). The antioxidant study of the essential oil through DPPH and FRAP assay exhibited IC50 value and EC50 value as 1.71±0.02 and 1.032 ± 0.01 μg/ml respectively. Essential oil revealed strong antibacterial activity against nine food spoiling pathogenic bacteria with MIC values ranging from 0.02 to 1.56 μg/ml. Cytotoxic study of essential oil revealed moderate cytotoxic activity as evaluated by MTT assay with IC50 value of 135.46 and 98.59 μg/mL respectively for HepG-2 and PC-3 cancerous cell lines. The present paper with confirmatory evidence of significant bioactivity of carvacrol-rich leaf essential oil of T. vulgaris from India ascertained its therapeutic value for health benefits.
... 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 [10]. Carvacrol and thymol are the two main phenols that constitute oregano and thyme essential oils, as well as the monoterpene hydrocarbons p-cymene and γ-terpinene [11]. ...
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The aim of this study was to investigate antibacterial effects of oregano and thyme essential oils on Listeria monocytogenes in fermented sausages and their effect on the sensory characteristics of these sausages. For testing purposes, sausages contaminated with L. monocytogenes were produced. Changes in the microbiological status of fermented sausages and physicochemical properties were monitored during ripening. Essential oils exhibited antibacterial activity against L. monocytogenes , and in the groups with a high concentration (0.6%) of oregano or thyme essential oils (KLO2 and KLT2), the number of L. monocytogenes was below the detection threshold on day 14 of ripening, with a stronger effect of oregano. In groups with 0.3% essential oil of oregano or thyme added, the number of L. monocytogenes was reduced to below the detection threshold on day 21 of ripening. During the ripening, the a w and pH of all test groups of fermented sausages decreased. Experimental sausages with 0.3% thyme essential oil had acceptable smell and taste, while in other experimental groups, sausage smell and taste were very intense, uncharacteristic and unacceptable.
... Due to their antispasmodic, antiseptic and antimicrobial properties, they are used for therapeutic purposes. T.vulgaris is a renowned herbal medication used in the treatment of dental plaque, alopecia, dermatophyte infections, inflammatory skin disorders, gastrointestinal distress, cough and bronchitis (Basch et al., 2004). ...
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A convincing number of investigations that indicate that thymol with other metabolites exhibited potent antimicrobial, antifungal, antibacterial, and antiparasitic properties prompted us to verify the antibacterial efficacy of four species and one interspecific hybrid of the Thymus genus collected in the western part of Ukraine against Staphylococcus aureus subsp. aureus (ATCC® 29213™) strain. Considering the points highlighted above and based on previous results obtained in our laboratory, in the current study, we decided to evaluate the antimicrobial efficacy of five ethanol extracts obtained from leaves of Thymus representatives against Staphylococcus aureus subsp. aureus (ATCC® 29213™) strain. Fresh leaves were washed, weighed, crushed, and homogenized in 96 % ethanol (in proportion 1:19) at room temperature. The extracts were then filtered and investigated for their antimicrobial activity. Antimicrobial activity was determined using the agar disk diffusion assay. The ethanol extracts obtained from leaves of Thymus plants showed different antibacterial activities against Staphylococcus aureus subsp. aureus (ATCC® 29213™) strain. The antibacterial activity of extracts was greatest for Th. serpyllum followed by Th. pannonicus followed by Th. pulegioides, Th. alpestris, and then by Th. x porcii. Since the antibacterial effectiveness of medicinal plants varies dramatically depending on the phytochemical characteristics of plant families and subfamilies, it is not surprising to note the difference in this efficacy even when using samples taken from the same plant, but from two different regions. The antimicrobial activity of the crude ethanol extracts obtained from leaves of Thymus plants may be attributed to specific compounds or a combination of compounds. The present study lays the basis for future research, to validate the possible use of Thymus species as a candidate in the treatment of infections caused by Staphylococcus aureusin medicine and veterinary.
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Introduction: We have reported that thymol and carvacrol can improve cognitive abilities in Alzheimer’s disease (AD) rat model. However, the mechanism of their action is not yet fully understood. Recently, our in vitro results suggested that PC12 cell death-induced by Aβ25-35 can be protected by thymol and carvacrol via PKC and ROS pathways. So, we hypothesize that the mechanisms of thymol and carvacrol in improving the learning impairment in AD rat model may be related to their effects on PKC. So, the activity of PKC and protein expression levels of PKCα was examined in the hippocampal cells of AD rat model. Methods: To examine thymol and carvacrol effects, we performed behavioral test in AD rat model induced by Aβ25–35 neurotoxicity. To access the underlying mechanism of protective effects, western blotting was performed with antibodies against PKCα. We also measured PKC activity assay by Elisa. Histopathological studies were carried out in hippocampus by hematoxylin & eosin (H&E). Results: It was shown that escape latency increased in Aβ-received rats compared to control group and thymol and carvacrol reversed this deficit. Furthermore, these compouds could enhance PKC activity, and increase the PKCα expression ratio. Moreover, H&E showed that Aβ caused shrinkage of the CA1 pyramidal neurons. However, thymol and carvacrol treatments could prevent this effect of Aβ peptides. Conclusions: This study suggests that Aβ results in memory decline and histochemical disturbances in hippocampus. Moreover, these results revealed that thymol and carvacrol could have protective effects on cognition in AD-like models via PKC activation.
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