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Efficacy, safety and tolerability of Tiger Balm® ointments: a systematic review

and a meta-analysis of prevalence

Article  in  Journal of Pharmacy & Pharmacognosy Research · January 2020

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 © 2020 Journal of Pharmacy & Pharmacognosy Research, 8 (1), 1-17, 2020
ISSN 0719-4250
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Review | Revisión

Efficacy, safety and tolerability of Tiger Balm® ointments: a

systematic review and a meta-analysis of prevalence
[Eficacia, seguridad y tolerabilidad de los ungüentos Tiger Balm®: una revisión sistemática y un metanálisis de
prevalencia]
Michele Antonelli1,2,3*, Davide Donelli1,3, Marco Valussi4
1Terme di Monticelli. via Basse 5, 43022, Monticelli Terme, Parma, Italy.
2Instituteof Public Health, Department of Medicine and Surgery, University of Parma, Parma, Italy.
3Servizio di Consulenza in Medicina Integrativa e Complementare (SCMIC), Reggio Emilia, Italy.
4European Herbal and Traditional Medicine Practitioners Association (EHTPA), Norwich, United Kingdom.

*E-mail: [email protected]

Abstract Resumen
Context: Tiger Balm® (TB®) ointments are multi-purpose branded Contexto: Los ungüentos Tiger Balm® (TB®) son remedios tópicos chinos
Chinese topical remedies, often used for pain relief and purchasable in de marca multipropósito, a menudo utilizados para aliviar el dolor y
many countries as over-the-counter medications. que se pueden comprar en muchos países como medicamentos de venta
Aims: To assess the efficacy, safety and tolerability of TB® ointments. libre.
Methods: Medline, Scopus, EMBASE, Cochrane Library, Web of Science, Objetivos: Evaluar la eficacia, seguridad y tolerabilidad de los ungüentos
Google Scholar, PEDro, and the Chinese Clinical Trial Registry were TB®.
systematically searched for relevant articles. The quality of included Métodos: Se realizaron búsquedas sistemáticas de artículos relevantes en
studies on the efficacy of TB® ointments was evaluated with dedicated Medline, Scopus, EMBASE, Cochrane Library, Web of Science, Google
NIH tools. Retrieved evidence was then summarized and critically Scholar, PEDro y el Registro de ensayos clínicos chinos. La calidad de
appraised. los estudios incluidos sobre la eficacia de los ungüentos TB® se evaluó
Results: After article screening and selection, 12 studies were finally con herramientas NIH dedicadas. La evidencia recuperada se resumió y
included in the present review (five on TB® ointments efficacy, whereas se evaluó críticamente.
seven on their safety and tolerability). Two cases of dermatitis and one Resultados: Después del tamizaje y selección del artículo, finalmente se
of cheilitis likely ascribable to the use of TB® ointments have been incluyeron 12 estudios en la presente revisión (cinco sobre la eficacia de
reported. Based on available studies, it might be estimated that around los ungüentos TB®, mientras que siete sobre su seguridad y tolerabi-
4% [95% CI, 3%-5%] of patients with history of contact skin allergy lidad). Se han informado dos casos de dermatitis y uno de queilitis
could be positive if patch tested with TB® ointments, therefore caution probablemente atribuibles al uso de ungüentos TB®. Según los estudios
is recommended in the use of TB® among these subjects. disponibles, se podría estimar que alrededor del 4% [IC 95%, 3% -5%] de
Conclusions: According to retrieved evidence, TB® ointments might be los pacientes con antecedentes de alergia cutánea por contacto podrían
useful for the management of pain due to tension headache, and they ser positivos si el parche se prueba con ungüentos TB®, por lo tanto, se
seem capable of increasing leg blood flow if combined with massage. recomienda precaución en el uso de TB® entre estos sujetos.
Considering available evidence on topical products with camphor, TB® Conclusiones: Según la evidencia recuperada, los ungüentos TB® podrían
ointments shouldn’t be used in children, as well as in pregnant or ser útiles para el tratamiento del dolor debido al dolor de cabeza por
lactating women. Chronic use, large amounts of balm, and the tensión, y parecen capaces de aumentar el flujo sanguíneo de las piernas
application on damaged skin must be avoided too. Further studies are si se combinan con un masaje. Teniendo en cuenta la evidencia
recommended. disponible sobre productos tópicos con alcanfor, los ungüentos TB® no
deben usarse en niños, así como en mujeres embarazadas o lactantes.
También se debe evitar el uso crónico, grandes cantidades de bálsamo y
la aplicación sobre la piel dañada. Se recomiendan más estudios.
Keywords: drug efficacy; drug safety; systematic review; traditional Palabras Clave: eficacia del fármaco; medicina tradicional china; revisión
Chinese medicine. sistemática; seguridad de drogas.

ARTICLE INFO
Received: July 27 30, 2019.
Received in revised form: October 9, 2019.
Accepted: October 12, 2019.
Available Online: October 17, 2019.
Declaration of interests: The authors declare no conflict of interest.
Funding: This research was not funded and did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

_____________________________________
Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

INTRODUCTION According to the definition of the National

Tiger Balm® (TB®) ointments are Chinese mul- Cancer Institute (NCI), Complementary and Al-
ti-purpose topical products, often used for pain ternative Medicines (CAM) are forms of treatment
relief and available in many countries as over-the- that are used in addition to (complementary) or
counter herbal remedies (The Tiger Balm Philoso- instead of (alternative) standard treatments, and
phy, 2014). TB® ointments are today produced by these practices are not generally considered stand-
an Asian company based in Singapore and they ard medical approaches (NCI Dictionary of Cancer
are claimed to be invented decades ago by a Chi- Terms, 2011). Therefore, TB® ointments, being a
nese herbalist named Aw Chu Kin (The Tiger Balm traditional herbal preparation, can be classified as
Philosophy, 2014). Their traditional uses include a CAM remedy (2011). Patients with pain, includ-
symptomatic relief for pain associated with mus- ing musculoskeletal pain (which appears to be one
cular ache, arthritis, and rheumatism (A. Aldulai- of the most important indications of TB® oint-
mi and Li, 2016). Moreover, in the East, TB® oint- ments), are reported to likely use CAM treatments
ments are applied on the chest as a balsam for res- (Artus et al., 2007; Tan et al., 2013). This tendency
piratory ailments like bronchial inflammation or has also been confirmed for patients already tak-
asthma (Fan, 2009). ing analgesic drugs (like opioids) for pain man-
agement (Fleming et al. 2007). In fact, in a survey
In the United Kingdom, two traditional oint- of 1259 CAM users with knee osteoarthritis, it was
ment formulations of TB® are Red TB® and White reported that 352 (28.0%) of them used topical
TB® (Shih et al., 2015). Red TB® is recommended agents like TB® ointments (Lapane et al., 2012). As
by the producer to soothe sore and aching mus- over-the counter products, TB® ointments can be
cles, and it is reported to contain camphor (11.0%), purchased by patients without any medical pre-
menthol (10.0%), clove oil (5.0%), cajuput oil scription. Moreover, TB® ointments are not only
(7.0%), as well as cinnamon oil, dementholized used by adults, but, in countries like Cambodia,
mint oil, yellow soft paraffin and hard paraffin even children and infants are reported to be given
(Tiger Balm Red, 2014). White TB® is recommend- this remedy for colicky pain or other pain-related
ed by the producer to relieve pain of tension head- problems (Johnson et al. 2017). Therefore, due to
aches, and it is reported to contain camphor their worldwide availability and use, it is im-
(11.0%), menthol (8.0%), clove oil (1.5%), cajuput portant to evaluate whether TB® ointments have
oil (13.0%), as well as dementholized mint oil, yel- some demonstrated therapeutic effects, and if they
low soft paraffin and hard paraffin (Tiger Balm can be considered a safe and well-tolerated reme-
White, 2014). Overall, according to disclosed in- dy in the light of existing scientific evidence on the
formation about composition of these two formu- topic.
lations, Red TB® has a higher concentration of
clove oil and menthol, a lower concentration of The aim of this systematic review is to assess
cajuput oil, and contains cinnamon oil (Tiger Balm the clinical efficacy, safety and tolerability of TB®
Red, 2014; Tiger Balm White, 2014). Red TB® has ointments.
been also analyzed with gas chromatographic
techniques by some researchers, showing a rela- MATERIAL AND METHODS
tive abundance of camphor and menthol, which The PRISMA guidelines were followed for the
should be considered the characteristic chemical present review (Moher et al., 2015).
markers of this herbal remedy (A. Aldulaimi and
Li, 2016). Some formulations other than Red or Eligibility and exclusion criteria (PICOS)
White TB® ointments (like the liquid TB® lini-
All studies investigating the clinical efficacy,
ment) have been reported to contain compounds
safety and tolerability of TB® ointments both in
like methyl salicylate (Davis, 2007).
healthy subjects and in patients with a diagnosed
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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

disease were included. Intervention was defined Table 1. Keywords and results of searches conducted in each
as the topical administration of TB® ointments, database.
applied over the skin with or without massage. All Database Keyword(s) Item(s) searched
studies were included regardless of compari-
PubMed “tiger balm” OR 8
son/control group type. All clinical outcomes “tiger balsam” OR
were considered, including any change in disease “tiger oil” OR “cam-
severity, physiological parameters, subjective phor balm” OR
symptoms, and reported quality of life. No lan- “menthol balm”
guage restrictions were applied during article se- Scopus “tiger balm” OR 23
lection process. “tiger balsam” OR
“camphor balm” OR
The following list summarizes the applied “menthol balm”
PICOS criteria for inclusion and exclusion of stud- EMBASE “tiger balm” OR 12
ies in the present review: “camphor balm” OR
“menthol balm”
• P (Population): healthy subjects or patients
with a diagnosed disease. Cochrane Library “tiger balm” 1
Web of Science “tiger balm” OR 5
• I (Intervention): topical administration of “camphor balm” OR
TB® ointments. “menthol balm”

• C (Comparison): any type of comparison Google Scholar “tiger balm” AND 474
(placebo, usual care, other treatments, or no "trial" 12
control). “camphor balm” 31
“menthol balm” 289
• O (Outcomes): any change in disease severi- “tiger oil” 30
ty, physiological parameters, subjective “tiger balsam”
symptoms, and reported quality of life.
Chinese Clinical “tiger balm” 0
• S (Study design): all types of study design. Trial Registry
PEDro “tiger balm” 1
Information sources
Medline via PubMed, Scopus, EMBASE, Study selection and data collection process
Cochrane Library, Web of Science, Google Scholar,
Study screening and selection was performed
PEDro, and the Chinese Clinical Trial Registry
by two authors independently. Afterwards, disa-
were systematically searched for relevant studies
greements were discussed until consensus was
investigating the clinical efficacy, safety and toler-
reached. Details of study selection and data collec-
ability of TB® ointments both in healthy subjects
tion process were summarized in a flowchart (Fig.
and in patients with a diagnosed disease.
1) (Moher et al. 2015). Data were manually extract-
Search ed from included articles, collected in tables and
then critically appraised. When data were missing,
Databases were searched up to February 2nd, authors were contacted by email to recover essen-
2019. The following search strategies were used tial information. The full-text version of an article
(see Table 1 for a brief summary of keywords and was retrieved in this way (Schattner and Rander-
results obtained after searching each database): son, 1996).

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 Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

Records identified through Records identified through

database searching database searching
(n = 886) (n = 886)
Identification

Identification
Databases: Databases:
Medline (n = 8), EMBASE (n = 12),
Medline (n = 8), EMBASE (n = 12),
Scopus (n = 23), Web of ScienceScopus (n = 23), Web of Science
(n = 5), Cochrane Library (n = 1),(n = 5), Cochrane Library (n = 1),
Google Scholar (n = 836), Chinese
Google Scholar (n = 836), Chinese
CTR (n = 0), PEDro (n = 1) CTR (n = 0), PEDro (n = 1)
Screening

Screening

Records screened Records excluded (duplicatesRecords

or excluded (duplicates or
Records screened
(n = 886) no relevant topic) (n = 850) no relevant topic) (n = 850)
(n = 886)
Eligibility

Full-text
Full-text articles assessed forFull-text articles assessed forarticles excluded, with
Eligibility

Full-text articles excluded, with

eligibility eligibility reasons (n = 24) reasons (n = 24)
(n = 36) (n = 36) - No investigation about efficacy, safety
- No investigation about efficacy, safety
and tolerability of Tiger Balm® (n = and
12) tolerability of Tiger Balm® (n = 12)

- Experiment with murine models -(n Experiment

= 1) with murine models (n = 1)
- Report of camphor toxicity after - Report of camphor toxicity after
accidental ingestion (n = 2) accidental ingestion (n = 2)
- No original study (n = 4) - No original study (n = 4)
Included

Studies included in
Included

- No retrievable
Studies included in full-text version (n- =No
5) retrievable full-text version (n = 5)
qualitative synthesis qualitative synthesis
(n = 12) (n = 12)

Figure 1. Flowchart describing article screening and selection of the review, adapted
from Moher et al., 2015.

Data items Risk of bias in individual studies and across

studies
Data items extracted from included reviews
were the following ones: characteristics of the A dedicated tool developed by the National In-
study population and intervention, comparison stitutes of Health (NIH) was used for the quality
type and analyzed outcomes, study design, the assessment of controlled intervention studies
overall results and the authors’ conclusions. (Study Quality Assessment Tools – NHLBI, 2018).

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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

The overall evaluation was based on the answers basis of available data.
to 14 questions, regarding the presence and meth-
Quality of evidence from case reports and case
ods of randomization, the treatment allocation
series describing potential side effects of TB® were
concealment, the blinding of study participants
assessed with another tool, recently developed by
and outcome assessors, the absence of significant
synthetizing and adapting to these study types
differences between groups at baseline, the attri-
several already existing evaluating criteria, includ-
tion and dropout rate, the adherence to interven-
ing the Newcastle Ottawa scale (Murad et al.,
tion protocol, the presence of confounding factors,
2018). This tool covers four domains (selection,
the use of valid and reliable measures, the re-
ascertainment, causality, and reporting), described
cruitment of a sufficient number of participants,
in eight items. The overall score ranges from 0 to 8,
and other potential sources of bias. Every question
with 8 representing the highest possible quality.
could be answered in three ways, either “yes”, or
“no”, or “other” (which indicates that data are not Results of the overall quality assessment were
reported, the answer cannot be determined, or the reported in a specific column of Tables 2 and 3.
question is not applicable). Studies were assessed
individually and their overall quality was scored Summary of measures and synthesis of results
as poor if 6 or less of the items were positive (an- Results were summarized in two tables: Table
swered with “yes”), fair if positive items ranged 2, reporting characteristics and quality of included
from 7 to 9, and good if at least 10 items were posi- studies analyzing the efficacy of TB® ointments,
tive. When items couldn’t be determined, were not and Tables 3 and 4, reporting information from the
applicable, or were not reported, the overall quali- most relevant case reports or case series, and ob-
ty was decided on the basis of available data. servational studies about the safety and tolerabil-
Another dedicated NIH tool was used for the ity of TB® ointments. Then, retrieved evidence
quality assessment of pre-post studies with no was discussed to obtain a critical qualitative syn-
control group (Study Quality Assessment Tools – thesis.
NHLBI, 2018). The overall evaluation was based Among included studies investigating TB®
on the answers to 12 questions, regarding the clari- ointments tolerability with patch tests (Bruze et al.,
ty of study objectives, eligibility criteria of partici- 1999), prevalence data from those ones involving
pants and tested intervention, the validity and patients (at least 20 subjects) with history of (or
reliability of outcome measures, the recruitment of with a suspected) allergic contact dermatitis to any
a sufficient number of participants, the blinding of substance other than TB® products were extracted.
study outcome assessors, the attrition and dropout A meta-analysis of prevalence was therefore per-
rate, the appropriateness of statistical methods formed, using the “MetaXL” software (version 5.3)
used to analyze data, and other potential sources (Barendregt et al., 2013). Prevalence was consid-
of bias. Every question could be answered in three ered as the ratio between the number of patients
ways, either “yes”, or “no”, or “other” (which in- who were positive when patch tested with TB®
dicates that data are not reported, the answer can- ointments and the total number of analyzed pa-
not be determined, or the question is not applica- tients. The inverse variance method was adopted
ble). Studies were assessed individually, and their to obtain individual study weight and pooled
overall quality was scored as poor if 4 or less of the prevalence. The double arcsine transformation was
items were positive (answered with “yes”), fair if applied, and preferred over the logit transfor-
positive items ranged from 5 to 7, and good if at mation, to stabilize the variance (Barendregt et al.,
least 8 items were positive. When items couldn’t 2013). Results of this analysis were reported in
be determined, were not applicable, or were not dedicated plots (Fig. 2).
reported, the overall quality was decided on the

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 Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

Table 2. Characteristics and quality of included studies on the efficacy of Tiger Balm®.

Reference Population Intervention Comparison(s) Outcome(s) Study Quality Main results (quotation) Authors'
design conclusions

Schattner & 57 patients with Application (rubbing) of TB® onto the Yes Headache severity RCT A Statistical analysis shower that Tiger Balm® is significantly Positive, in
Randerson, acute tension temple three times (at baseline, after 30 (paracetamol (scale 0-7) and relief different to placebo from 5 min to 2 h. Tiger Balm® and favor of the
1996 headache (22 males; min and 1 h). 1000 mg or (scale 0-4) measured paracetamol groups recorded a significant decline in headache efficacy of
age range: 18-60 placebo topical 5, 15, 30, 60, 120, and severity during the 3 h period, although Tiger Balm® was TB®.
years): TB® group treatment) 180 min after found to provide more rapid relief than paracetamol at 5 and
(n=22), placebo intervention. 15 min.
group (n=20), drug
group (n=22).

Case et al., 54 healthy subjects Application of TB® on the left cheek. Yes Measures of sensory RCT A [TB®] caused higher ratings of tingliness than numbing cream NA*
2013 (19 males, mean (moisturizing referral (touch- or moisturizer. The three conditions did not differ significantly
age: 20.9 ± 2.13): 3 cream or confusions, in participants’ estimated sensory acuity in the cream region.
groups (n=18 in anesthetic subjective tingliness, [TB®] and moisturizer did not differ significantly in the
each group). cream) and sensory acuity). number of touch-confusions observed.

Ljungfelt et 12 healthy subjects Massage with TB® and Frisco® liniment Yes (the same Blood flow in lower Cross- B Tiger Balm® with massage increased the skin blood flow by Positive, in
al., 1994 (4 males; age range: of lower limbs (TB® on one leg, Frisco® liniments limbs measured with over 20.4 ± 8.0 perfusion units, “immediately after”. The increase favor of the
16-48 years, mean on the other one). applied with a strain-gauge non- was significant for 40 min. Stick application of Tiger Balm® efficacy of
age: 26.4). stick) plethysmography RCT gave a slow increase in skin blood flow and was significant TB®.
and laser Doppler after 50 min. Massage with Tiger Balm® increased the calf
flowmetry. blood flow by 2.2 ± 0.8 mL/min/100 mL tissue “immediately
after”. The increased blood flow was significant even after 60
min. Stick application of Tiger Balm® did not influence the calf
blood flow.

Li et al., 2009 45 patients with Application of essential balm or TB®, or No VAS (pain) Pre- C The VAS score of pre-treatment was 6.45 ± 1.95 and it was Positive, in
headache caused by warm water on specific areas of the post US 1.43±0.65 after treatment. favor of the
cold (sex ratio and body, mostly using a spoon (chest, back, efficacy of
mean age: bilateral Taiyang (Ex-HN 5), Yintang massage with
unknown). (Ex-HN 3). or without
TB®.

Fan, 2009 38 patients with Application of essential balm or TB®, or No The patient’s Pre- C The average annual frequency of asthma attack prior to the Positive, in
bronchial asthma warm water on specific areas of the average frequency of post US scraping method was (2.3 ± 1.3) times, and (0.6±0.4) times after favor of the
(sex ratio: body, using a spoon (upper back, along asthma attack the scraping treatment. efficacy of
unknown; average the pathway of Bladder Meridian), (recorded once every massage with
age: 47.4 ± 8.3 every 10-20 days for 3 years. 6 months for 3 or without
years). years). TB®.

NA = Not Applicable, RCT = Randomized Controlled Trial, TB® = Tiger Balm®, US = Uncontrolled Study. Studies are listed according to their design, with priority for controlled trials. PICOS characteristics of each included study are briefly reported in the
table, as well as the quality of their evidence (A = good, B = fair, C = poor), and a quotation from original texts summarizing the main findings. Threshold for significance was considered at p<0.05. The last column reports the authors’ conclusions on the topic.
*The aim of this study was not to assess the therapeutic efficacy of TB®, but to use it as a control in order to comparatively test the effects of a lidocaine-based cream on sensory referral in healthy participants completing an experimental task.

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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

Table 3. Case reports about side effects of Tiger Balm®.

Reference Case N° Gender Age Health condition Anamnesis and additional information Quality

Leow et al., 1995 1 F 52 12-year history of recurrent cheilitis. History of using Tiger Balm®. Positive Patch Test. 4/8
Schliemann et al., 2011 2 M 48 Itching, erythema, and scaling on the History of using Tiger Balm®. Positive Patch Test. Evidence of hay fever and 6/8
forehead. mild atopic skin diathesis.
3 F 36 Severe contact dermatitis on the back. History of using Tiger Balm®. Positive Patch Test. No history of cosmetic or 6/8
fragrance allergy, and no atopy.
F = Female; M = Male. This table summarizes case reports about side effects of Tiger Balm®.

Table 4. Studies investigating the prevalence of contact allergy to Tiger Balm®.

Reference Type of TB® (% Time after record Number of Number of % (N of Characteristics of study population
of agent in of test results positive tested positive/tested
vehicle) subjects subjects subjects)

Anggraini et al., NA NA 1 1 100.0% Patients with allergic contact dermatitis and with a positive result for at least
2017 one allergen.
Lee & Lam, 1990 Red TB® 48 h 2 20 10.0% Patients with eczema or contact dermatitis due to substances other than TB®.
96 h 1 17 5.8%
Leow et al., 1995 White TB® (1%) NA 0 12 0.0% Patients with history of dermatitis of a likely contact origin, not related to the
usage of topical traditional Chinese medicaments and patients with a primary
White TB® (5%) 1 22 4.5% dermatitis under control.
White TB® (10%) 3 55 5.5%
Leow, 1997 NA NA 0 87 0.0% Subjects with no history of allergic contact dermatitis, probably healthy
(reported as “controls”).
Lim et al., 2007 White TB® (10%) 48-72-168 h 3 44 6.8% Patients with chronic venous (or mixed venous and arterial) leg ulcers.
Schliemann et al., Red TB® NA 7 18 38.9% Patients with concomitant reactions to other fragrances.
2011
Shih et al., 2015 Red TB® 48-72-96 h 42 1076 3.9% Patients with suspected allergic contact dermatitis.

White TB® 48-72-96 h 39 1076 3.6%

NA = Not Available, TB® = Tiger Balm®. This table summarizes data of studies investigating tested contact allergy to Tiger Balm®. Articles are alphabetically sorted according to the first author’s surname.

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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

Figure 2. Forest plots displaying pooled prevalence of positive Patch Test with Tiger Balm® among patients with skin allergic
diathesis.
(A) Overall pooled prevalence, regardless of Tiger Balm® formulation; (B) Pooled prevalence referred to Red Tiger Balm®; (C) Pooled prevalence
referred to White Tiger Balm®.

RESULTS in the review. Among them, five articles investi-

gated TB® ointments efficacy (Ljungfelt et al.,
After database searching, 886 articles were 1994; Schattner and Randerson, 1996; Fan, 2009; Li,
screened and twelve of them were finally included et al. 2009; Case et al., 2013), while seven of them

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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

reported information about their safety and toler- pain (p<0.05) (Li et al., 2009), and for bronchial
ability (Lee and Lam, 1990; Leow et al., 1995; Le- asthma, reporting a significant decrease in average
ow, 1997; Lim et al., 2007; Schliemann et al., 2011; annual frequency of asthma attacks (p<0.05) (Fan,
Shih et al., 2015; Anggraini et al., 2017), as dis- 2009). The quality of included studies, assessed
played in each table (Tables 2-4). Details of article with dedicated NIH tools, was rated as good for
screening and selection process was described in a two studies (Schattner and Randerson, 1996; Case
flowchart (Fig. 1). et al., 2013), fair for another one (Ljungfelt et al.,
1994), while poor for the remaining two (Fan, 2009;
Five articles investigated the therapeutic effica-
Li et al., 2009).
cy of TB® ointments and their physiological ef-
fects. In an included Randomized Controlled Trial Two articles described three cases of patients
(RCT), authors reported that the efficacy of TB® using TB® ointments and reporting adverse events
(unspecified formula, but probably White TB® probably ascribable to its skin application (Leow et
ointment) in relieving pain due to acute tension al., 1995; Schliemann et al., 2011). One article de-
headache was significantly better than a topical scribed a case report regarding a 48-year-old man
placebo remedy (p<0.05) and was found to pro- with itching erythema on his forehead, and anoth-
vide more rapid relief than a single dose (1000 mg) er one regarding a 36-year-old woman experienc-
of paracetamol (Schattner and Randerson, 1996). In ing severe dermatitis on her back (Schliemann et
a physiological study about the effects of two topi- al., 2011). Both cases reported a history of TB® use
cal products on leg circulation, TB® (unspecified on skin regions involved by contact dermatitis and
formula) was reported to increase the skin and calf were positive when patch tested with TB®
blood flow in combination with massage (p<0.05) (Schliemann et al., 2011). In another article a 52-
(Ljungfelt et al., 1994). In another study, TB® year-old woman with a history of cheilitis reported
(White formula ointment) was used as a control the use of TB® and showed a positive reaction
intervention to comparatively test the effects of a when patch tested with TB® (Leow et al., 1995).
lidocaine-based cream on sensory referral in Quality of these case reports ranged from 4 to 6
healthy participants performing an experimental out of 8, with 8 representing the highest quality
task (Case et al., 2013). Reported outcomes were (Leow et al., 1995; Schliemann et al., 2011).
touch-confusions (participants saying both sides
Seven articles reported cases of people who ex-
when the touching stimulus was applied only on
hibited a positive response after being patch tested
one side), subjective tingling (rated by the partici-
with TB® ointments to check whether they
pants using a 0-5 scale), and sensory acuity (rated
showed any contact allergy (Table 4) to these
by the participants using a 0-100 scale) (Case et al.,
herbal remedies (Lee and Lam, 1990; Leow et al.,
2013). Results of this double-blind RCT showed
1995; Leow, 1997; Lim et al., 2007; Schliemann et
that TB®, when applied over face skin, seems ca-
al., 2011; Shih et al., 2015; Anggraini et al., 2017).
pable of inducing a tingling sensation which ap-
Results of these studies were highly heterogene-
pears significantly more pronounced than that one
ous, with a number of included participants rang-
caused by the application of the anesthetic cream
ing from 1 to 1076 (median: 22), and a percentage
(p<0.01), without impairing the subjects’ estimated
ratio between the number of positive subjects and
sensory acuity more than a placebo moisturizing
the number of tested ones ranging from 0.0% to
cream (p=0.261) (Case et al., 2013). Moreover, TB®
100.0% (median: 5.5%) (Lee and Lam, 1990; Leow
and moisturizer did not differ significantly in the
et al., 1995; Leow, 1997; Lim et al., 2007; Schlie-
number of touch-confusions observed (p=0.27)
mann et al., 2011; Shih et al., 2015; Anggraini et al.,
(Case et al., 2013). In two pre-post uncontrolled
2017). In all but one study (Leow, 1997), tested
studies, topical applications of TB® ointments (un-
participants were patients with history of derma-
specified formula), another balm or warm water
tologic or allergic diseases, mostly allergic contact
were used as a remedy for cold-related headache,
dermatitis. If studies with less than 20 subjects are
reporting a significant improvement in perceived
excluded and only those ones involving patients
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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

with history of (or with a suspected) allergic con- tically significant, effect (Göbel et al., 1996). In an-
tact dermatitis to any substance other than TB® other RCT with a crossover design involving 32
are taken into account, pooled prevalence of pa- subjects with headache, pain was significantly re-
tients who were positive when patch tested with duced by applying on the forehead and temples a
TB® was 4% [95% CI, 3%-5%] (Fig. 2). This preva- combination of peppermint oil and ethanol, thus
lence remained the same when Red and White underscoring the potentially beneficial effects of
TB® ointments were considered separately (Fig. 2). peppermint-based topical products in relieving
cefalalgic symptoms (Göbel et al., 1994). Addition-
DISCUSSION ally, a study involving 60 patients with mechanical
neck pain showed that a topically applied menthol
Efficacy gel can significantly reduce reported pain (p<0.05),
In one RCT on TB®, its efficacy in relieving although a non-significant effect was found in
pain due to acute tension headache was tested in terms of changes in neck range of motion (Topp et
comparison with paracetamol (administered at a al., 2017). In a randomized trial with 40 patients
single dose of 1000 mg), and a placebo topical affected by either chronic neck pain or chronic low
ointment (Schattner and Randerson, 1996). When back pain, significant improvements in health sta-
critically appraising evidence from this RCT, it has tus and pain (p<0.05) were reported in the group
to be acknowledged that baseline characteristics of treated with “Gua Sha” therapy, compared to the
patients assigned to placebo and intervention waiting list group (Lauche et al., 2012). “Gua Sha”
groups had some heterogeneity in terms of report- therapy was defined as an instrument-assisted
ed headache frequency and duration, with a ten- massage of an area of the body surface lubricated
dency towards higher average frequency and with a balm containing camphor, menthol, and
longer average disease duration in subjects as- eucalypt (Lauche et al., 2012). Evidence from all
signed to the placebo group (Schattner and Rand- these studies seems to suggest that topical prod-
erson, 1996). Moreover, the authors recognized ucts containing camphor, menthol or peppermint
that the sample size was limited, since a power oil might be useful for the management of pain
calculation based on the hypothesis that the differ- due to muscular tension.
ence in severity between groups was at worst one In a physiological study about the effects of two
unit, demonstrated that 44 patients were required topical products on leg circulation, TB® was re-
in each group (around half of those ones actually ported to increase the skin and calf blood flow in
recruited) (Schattner and Randerson, 1996). How- combination with massage (p<0.05) (Ljungfelt et
ever, considering the overall high quality of this al., 1994). Similar findings have been reported in a
trial and the significance of its findings, it can be study with nine participants in which it was
concluded that TB® ointment massaged on the demonstrated that the application of a topical
temple may be a useful remedy for pain relief in preparation containing camphor or menthol on the
this condition on a short term. Moreover, in a forearm can increase skin and muscle blood circu-
double-blind RCT investigating the effects on ten- lation (Kotaka et al. 2014).
sion-type headache of a locally applied prepara-
Two other studies on TB® ointments therapeu-
tion with peppermint oil (one of the chemical
tic effects were performed in China and aimed to
markers of TB®), the remedy was discovered to
investigate the efficacy of Chinese massage tech-
significantly reduce the headache intensity if com-
niques in relieving symptoms of headache caused
pared to placebo (p<0.01) (Göbel et al., 1996). The
by cold or relapses of chronic asthma (Fan, 2009; Li
effect continued over the one-hour observation
et al., 2009). In both studies, intervention was ad-
period and was found to be comparable to the oral
ministered by domestic caregivers and family
intake of 1000 mg of paracetamol (Göbel et al.,
members, who had the opportunity to choose
1996). Coupling paracetamol and peppermint oil
among a range of three topical therapeutic options,
application led to an additive, although not statis-
including TB® (Fan, 2009; Li et al., 2009). There-
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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

fore, since no detailed information is provided, it pend on terpenes contained in camphor essential
cannot be argued how many patients were actual- oil (Chen et al., 2013a). A study with murine mod-
ly given a TB® ointment as a remedy. Moreover, els has also reported that a combination of men-
these studies simply assessed pre-post outcome thol and camphor, both present in TB®, can en-
variations in a relatively small population, thus hance skin penetration of methyl salicylate and
lacking any type of comparison or control group inhibit its hydrolysis to salicylic acid (Yano et al.,
(Fan, 2009; Li et al., 2009). Finally, due to the lim- 1991).
ited information provided about the nature of in-
Menthol, a cyclic terpene alcohol found in mint
tervention, confounding factors might have biased
(Mentha spp.), can stimulate TRP (transient recep-
study results.
tor potential) ion channels and, although irritating
and noxious at high doses, this compound can
Mechanisms of action
cause a pleasing sensation of cold when used in
Among all compounds included in TB® oint- moderate concentrations (Liedtke, 2006; Bautista et
ments, the most active ones from a pharmacologi- al., 2007). Studies in vitro and in vivo have high-
cal point of view are considered camphor, men- lighted the anti-nociceptive and muscle-release
thol, cajuput, mint oil, clove oil, and cinnamon oil effects of menthol, probably mediated by its action
(Faubert et al., 2010). However, the characteristic on receptors like the TRPM8, as well as on neu-
chemical markers of this herbal remedy are mainly ronal and skeletal muscle sodium channels (Hae-
considered camphor and menthol (A. Aldulaimi seler et al., 2002; Nomoto et al., 2008). Menthol has
and Li, 2016). Some formulations other than Red also a bimodal action on the TRPA1, characterized
or White TB® ointments (like the liquid TB® lini- by the activation of this receptor at sub-
ment) have been reported to contain methyl salicy- micromolar doses and inhibition at higher concen-
late, an aspirin-like compound which is a compo- trations (Karashima et al., 2007), and may be capa-
nent of many over-the-counter topical remedies ble of desensitizing the TRPV3 (Sherkheli et al.,
used for musculoskeletal aches and pain (Davis, 2009). Menthol inhalation can also reduce cough
2007). sensitivity to inhaled capsaicin and positively in-
Camphor (usually extracted from Cinnamomum fluence inspiratory flows (Millqvist et al., 2013).
camphora) has been hypothesized to have several Clove oil is traditionally obtained from Eugenia
biological properties, including antimicrobial, anti- caryophyllata and its major component is consid-
tussive and anti-nociceptive activities (Chen et al., ered to be eugenol (Chaieb et al., 2007). In a review
2013b). It is supposed that the analgesic effects of of the scientific literature, clove oil has been re-
camphor may be due to a de-sensitization of ported to potentially have several properties, in-
TRPV1 (vanilloid receptor 1) and a blocking of cluding antimicrobial, antioxidant, and analgesic
TRPA1 (transient receptor potential ankyrin 1) effects (Chaieb et al., 2007). In a study with mice,
(Chen et al., 2013b). Moreover, camphor can acti- the anti-nociceptive activity of eugenol was
vate and sensitize TRPM8 (transient receptor po- demonstrated with various experimentally in-
tential melastatin 8) with a dual and complex ac- duced pain models (Bodhankar et al., 2006). Euge-
tion (stimulating the receptor while inhibiting its nol can activate TRP channels, in particular A1,
response to menthol), and this mechanism is likely V1, V3, and M8 receptors, thus modulating senso-
to be responsible for the enhancement of cold sen- ry neuronal responses to warmth and noxious
sations by camphor (Selescu et al., 2013). Camphor stimuli (Klein et al., 2013;2014; Chung et al., 2014).
can also induce an agonist-specific desensitization
Cajuput oil is produced with Melaleuca cajuputi
of TRPV3 (transient receptor potential vanilloid-3
and it is considered a popular household medica-
ion channels), which has a specific role in ther-
tion in countries such as India, Indonesia, Malay-
mosensation and nociception (Moqrich et al., 2005;
sia and Vietnam, as well as among Australian Ab-
Sherkheli et al., 2009). Skin penetration enhance-
origines, mostly for the treatment of aches and
ment properties have been hypothesized to de-
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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

pains, and to reduce nasal and bronchial conges- esis is that it could work by counter-irritation, thus
tion (Doran, 2003). Cajuput oil can contain 40-70% giving a soothing feeling of warmth and a pain
of 1,8-cineole, active on M8, A1, and V3 TRP recep- relief effect in the underlying muscle (Derry et al.,
tors, with possible anti-inflammatory and anti- 2014). It is possible to hypothesize that the coun-
nociceptive effects (Sherkheli et al., 2009; Caceres ter-irritation effect of methyl salicylate may be due
et al., 2017). to its activity on TRPA1 and V1, thus inducing a
local cutaneous neurogenic inflammation (Gouin
Cinnamon oil is extracted from Cinnamomum
et al., 2017). The real efficacy of topical methyl sa-
zeylanicum and, in a cellular model of chronic in-
licylate-based products in the management of
flammation and fibrosis, has showed an anti-
acute and chronic musculoskeletal pain still re-
inflammatory activity mediated by the inhibition
mains unclear, with limited and contrasting evi-
of the production of several inflammatory bi-
dence in support of their use (Mason et al., 2004;
omarkers (such as vascular cell adhesion mole-
Derry et al., 2014).
cule‐1, intercellular cell adhesion molecule‐1,
monocyte chemoattractant protein‐1, interferon
Safety and toxicity
gamma‐induced protein 10, interferon‐inducible
T‐cell alpha chemoattractant, and monokine in- Camphor, if accidentally ingested, is a well-
duced by gamma interferon), and of some tissue recognized toxic compound, and its consumption
remodeling molecules (like epidermal growth fac- can result in neurologic symptoms like severe nau-
tor receptor, matrix metalloproteinase‐1, and sea, vomiting, convulsions, lethargy, ataxia, and
plasminogen activator inhibitor‐1) (Han and Par- even death (Manoguerra et al., 2006). A single,
ker, 2017). Moreover, cinnamaldehyde from cin- even nonlethal, ingested dose of camphor can
namon bark oil can activate the TRPA1, which has cause abortion, while a chronic intake has demon-
a role in modulating nociception and inflamma- strated hepatotoxic effects (Martin et al., 2004).
tion (Mendes et al., 2016), and it might also modu- Camphor is highly toxic if accidentally ingested by
late other thermos-TRPs like TRPV3 (Macpherson infants and small children, being deadly even at a
et al., 2006). small single dose (Euwema and Swanson, 2019). In
a study conducted in Cambodia, where TB® is
Another compound present in TB® ointments is rubbed on infants for several conditions (varying
paraffin (TIGER BALM RED; TIGER BALM
from rash to the common cold to muscle pains),
WHITE), which can have a role as a skin penetra-
the use of this product was found to be associated
tion enhancer (Chen et al., 2013a) and as a
with low levels of thiamine among pediatric pa-
skin‐protective material against contact irritants
tients, although it wasn’t clear whether TB®, once
and allergens (Zhai et al., 1998), thus promoting
absorbed, could directly influence this vitamin
the absorption of active substances contained in
metabolism or it was simply a marker of some yet
the balm and potentially limiting possible irrita-
unidentified exposure which can impair thiamine
tion caused by other constituents of the ointment.
levels (Keating et al., 2015). In another observa-
Methyl salicylate (not contained in Red or tional study with Cambodian children it was test-
White TB® ointments, but in other formulations ed the hypothesis that camphor-based topical
like the liquid TB® liniment) is an important com- products like TB® could trigger beriberi-
ponent of many rubefacients, namely topical rem- simulating tachypnea, regardless of any influence
edies used for muscular pain, which can cause on thiamine deficiency (Johnson et al., 2017). Nine-
skin reddening and irritation by dilating blood teen children (9 with tachypnea and 10 healthy
vessels and stimulating peripheral nerves (Derry subjects) using TB® were analyzed and no cam-
et al., 2014). Although chemically related to aspirin phor was found in their blood, thus possibly indi-
and other non-steroidal analgesic drugs, the cating that this compound, when applied topically
mechanism of action of methyl salicylate is not at small doses, is not related with tachypnea in
completely clear, even if the most relevant hypoth- Cambodian infants (Johnson et al., 2017). Howev-

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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

er, case reports of dermal exposure to topical cam- and muscle necrosis as well as persistent intersti-
phor-containing remedies among small children tial nephritis (Heng, 1987).
have described possible side effects like severe
In a study involving 24 healthy subjects, the
status epilepticus and impairment of liver func-
dermal absorption of camphor, menthol, and me-
tion, thus underscoring the potential toxicity of
thyl salicylate contained in medicated patches has
camphor among children even if only applied top-
been investigated (Martin et al., 2004). Each patch
ically and not ingested (Uc et al., 2000; Guilbert et
had 46.80 mg of camphor, 37.44 mg of menthol,
al., 2007). Moreover, chronic dermal exposure to
and 74.88 mg of methyl salicylate (Martin et al.,
camphor-based products has been associated with
2004). When two patches were applied, low plas-
the occurrence of systemic effects, contact dermati-
ma concentrations of these compounds were
tis, and significant allergic responses (Ford, 2001).
measured, near the limits of quantitation for each
Menthol can cause skin allergy and even sys- substance (Martin et al., 2004). Average Cmax val-
temic allergic reactions (Martin et al., 2004). Clove ues and standard deviation for camphor, menthol,
and cinnamon oil can cause allergic contact derma- and methyl salicylate were, respectively, 13.5 ± 4.8
titis too (Sánchez-Pérez and García-Díez, 1999). An ng/mL, 7.6 ± 2.6 ng/mL, and 8.6 ± 3.8 ng/mL, and
in-vitro study has suggested that clove oil and these compounds were not detectable beyond 8 to
eugenol may have cytotoxic properties towards 12 hours after application (Martin et al., 2004). The
human fibroblasts and endothelial cells, thus un- authors concluded that, for the number of tested
derscoring the need for further investigation on patches (up to 8 at a single time), there should be a
the topic (Prashar et al., 2006). relatively low systemic exposure to these poten-
tially toxic compounds (Martin et al., 2004).
Methyl salicylate (contained in formulations
like the liquid TB® liniment, but not in Red or The U.S. department of Health & Human Ser-
White TB® ointments) can be toxic if accidentally vices reports that TB® ointments are only for ex-
ingested and it is documented that, in children less ternal use (due to its toxicity if accidentally ingest-
than six years of age, a teaspoon or less of winter- ed), and any contact with eyes, genital area or
green oil (containing 98% of methyl salicylate) has damaged skin should be avoided (Household
been implicated in several deaths (Davis, 2007). Products Database, 2019). It is also recommended
Studies have demonstrated that, when topically not to use them for more than 7 days, especially if
applied, local tissue levels of salicylate from me- symptoms persist or worsen, and not to apply any
thyl salicylate formulations should be approxi- tight bandage over treated area (Household Prod-
mately 30-fold higher than plasma concentrations ucts Database, 2019). Possible side effects may be
(Cross et al., 1998). However, in a review of the allergic reactions or severe irritation (Lee and Lam,
scientific literature, seventeen cases of salicylism 1990; Leow et al., 1995; Leow, 1997; Lim et al.,
following the topical application of salicylate 2007; Schliemann et al., 2011; Shih et al., 2015;
preparations both in pediatric and in adult pa- Anggraini et al., 2017). Moreover, considering
tients with dermatologic diseases (mostly psoriasis available evidence on topical products with cam-
or ichthyosis) have been reported (Brubacher and phor, TB® ointments shouldn’t be used in chil-
Hoffman, 1996). Topical analgesic preparations dren, as well as in pregnant or lactating women.
with methyl salicylate may cause irritant or aller- Formulations with methyl salicylate shouldn’t be
gic contact dermatitis, as well as anaphylactic reac- recommended for patients taking anticoagulants
tions (Chan, 1996), and their excessive usage in or antiplatelet agents. The use of TB® ointments
patients under treatment with warfarin may result should never be followed by the application of
in adverse interactions and bleedings (Chan, 1996; heating pads. Patients with history of contact al-
Joss and LeBlond, 2000). A study reported the case lergy should be patch tested with the product be-
of a patient applying over skin a topical remedy fore applying it over a large body surface, since, as
containing menthol and methyl salicylate followed reported by our meta-analysis of prevalence, it
by the use of a heating pad, who experienced skin might be estimated that around 4% of such pa-
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Antonelli et al. Tiger Balm® ointments: a systematic review and meta-analysis

tients could be allergic to TB® ointments too (Fig. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T (2013)
2). Meta-analysis of prevalence. J Epidemiol Community
Health 67: 974–978.
Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI,
CONCLUSIONS Stucky CL, Jordt SE, Julius D (2007) The menthol receptor
TRPM8 is the principal detector of environmental cold.
Based on available evidence, TB® ointments
Nature 448: 204–208.
might be useful for the management of pain due to
Bodhankar SL, Kurian R, Arulmozhi DK, Veeranjaneyulu A
muscular tension and seem capable of increasing (2006) Effect of eugenol on animal models of nociception.
skin and muscle blood flow, especially if coupled Indian J Pharmacol 38: 341–346.
with massage. However, the most relevant find- Brubacher JR, Hoffman RS (1996) Salicylism from topical
ings of this review regard safety and tolerability of salicylates: review of the literature. J Toxicol Clin Toxicol
TB® ointments. Among possible adverse events 34: 431–436.
following application of TB® ointments, the most Bruze M, Conde-Salazar L, Goossens A, Kanerva L, White IR
reported ones seem contact skin irritation and al- (1999) Thoughts on sensitizers in a standard patch test
series. Contact Dermatitis 41: 241–250.
lergic reactions. Moreover, considering available
Caceres AI, Liu B, Jabba SV, Achanta S, Morris JB, Jordt SE
evidence on topical products with camphor, TB® (2017) Transient receptor potential cation channel
ointments shouldn’t be used in children, as well as subfamily M member 8 channels mediate the anti-
in pregnant or lactating women. Formulations inflammatory effects of eucalyptol. Br J Pharmacol 174:
with methyl salicylate shouldn’t be recommended 867–879.
for patients taking anticoagulants or antiplatelet Case LK, Gosavi R, Ramachandran VS (2013) Heightened
motor and sensory (mirror-touch) referral induced by
agents. Chronic use, large amounts of balm, and
nerve block or topical anesthetic. Neuropsychologia 51:
the application on damaged skin must be avoided 1823–1828.
too. Caution is recommended in the use of TB® Chaieb K, Hajlaoui H, Zmantar T, Kahla-Nakbi AB, Rouabhia
ointments among patients with any history of con- M, Mahdouani K, Bakhrouf A (2007) The chemical
tact skin allergy. Further studies are recommended composition and biological activity of clove essential oil,
to thoroughly outline the safety and tolerability Eugenia caryophyllata (Syzigium aromaticum L.
Myrtaceae): a short review. Phytother Res 21: 501–506.
profile of TB® ointments, as well as to better un-
Chan TY (1996) Potential dangers from topical preparations
derstand their efficacy in the symptomatic man-
containing methyl salicylate. Hum Exp Toxicol 15: 747–
agement of painful muscle problems. 750.
Chen K, Liang Y, Zhang Y (2013a) Study on reflection of
CONFLICT OF INTEREST human skin with liquid paraffin as the penetration
enhancer by spectroscopy. J Biomed Opt 18: 105001.
The authors declare no conflict of interest.
Chen W, Vermaak I, Viljoen A (2013b) Camphor--a fumigant
during the Black Death and a coveted fragrant wood in
ACKNOWLEDGMENTS ancient Egypt and Babylon--a review. Molecules 18:
This research was not funded and did not receive any spe- 5434–5454.
cific grant from funding agencies in the public, commercial, or Chung G, Im ST, Kim YH, Jung SJ, Rhyu MR, Oh SB (2014)
not-for-profit sectors. Activation of transient receptor potential ankyrin 1 by
eugenol. Neuroscience 261: 153–160.
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AUTHOR CONTRIBUTION:

Contribution Antonelli M Donelli D Valussi M

Concepts or ideas x x x

Design x x

Definition of intellectual content x x x

Literature search x x

Experimental studies

Data acquisition x x x

Data analysis x x x

Statistical analysis x x

Manuscript preparation x x x

Manuscript editing x x x

Manuscript review x x x

Citation Format: Antonelli M, Donelli D , Valussi M (2020) Efficacy, safety and tolerability of Tiger Balm® ointments: a systematic review and a
meta-analysis of prevalence. J Pharm Pharmacogn Res 8(1): 1–17.

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