Nixon Aug 06

Case Report
The use of totarol to treat

acne in an adolescent:
A case study
David Nixon MBChB, Daniel Hobbs MBChB

Correspondence to: David@mn.thedoctors.co.nz
David Nixon is Clinical Director of The

Doctors Masterton and Director of Primary Care IT Solutions. He is currently
involved with the roll out of the Chronic
Disease Management Programme The
Foundation Programme and the software CD Evolution throughout the medical practices in the Wairarapa.
Daniel Hobbs has recently entered general practice. His interests include trying to gain a better understanding of
patients perception of the therapeutic
experience but his main focus at present
is passing Primex in October.
Introduction
This case reports the use of totarol in
the form of an alcohol-based topical
medication followed by a totarol-containing moisturiser, for the treatment
of acne vulgaris in an adolescent. The
practice was made aware of the existence of these products and was offered the opportunity to try them. It
is anticipated that these products will
be commercially available nationwide
by the time of publication.
Case history
The patient was a 14-year-old Caucasian male with a 14-month history
of acne vulgaris. He had previously
tried Clearasil Medicated Wipes, with
little success. These contain 2% salicylic acid a keratolytic agent and
ethanol. The patient initially presented for an unrelated medical problem and was offered the opportunity
to try the totarol products to treat

his acne. He consented to trying the
products and to having his photograph taken from time to time to
monitor the products effects.
The treatment regime consisted of
applying the alcohol-based topical
medication, followed by the totarolcontaining moisturiser, twice daily. He
applied the products to the areas of
his face that had particularly prominent acne. He continued this twice
daily for four weeks, then once daily
for two weeks (patients discretion to
change the frequency of application).
His photograph was taken at intervals
throughout the treatment period.
Background to totarol
Totarol is a natural extract from
heartwood of the Totara tree
(Podocarpus totara). 2 It is also
extractible from other podocarps including rimu, some trees in the cypress family (cypress, juniper, thuja);
and rosemary.2 It is most abundant
in Totara trees.2 The extraction process2 is called supercritical extraction.
This is a process that uses high pressure carbon dioxide under defined
conditions of temperature, pressure
and gas flow to extract totarol from
powdered Totara deadwood (in the
form of old fence posts, telegraph
poles, house piles, and so on). The
process ensures that the extract and
residual wood has no harmful solvent residues, and that the highest
possible quality of extract is obtained. The water in the extracted
product is then removed by freezedrying. This extraction process results in a product containing approximately 60% totarol by mass.
Totarol is a broad-spectrum antibacterial, being active against Staphylococcus aureus;3 methicillin-resistant Staphylococcus aureus4 (epidemic, community, and multi-drugresistant strains2); Streptococcus
mutans;3,5 penicillin-resistant Streptococcus pneumoniae;6 Erythromycin-resistant Streptococcus pyogenes;2
high-level-gentamicin-resistant Enterococcus faecalis;6 vancomycin-resistant Enterococcus faecalis;2 Salmonella menston,5 Eschericia coli;5
Enterobacter aerogenes; 5 PseuFigure 1. Chemical structure:
Totara-8,11,13-trien-13-ol; C20H30O1
OH
i[Totara-8, 11, 13-trien-13-ol]
Figure 2. 3D totarol molecule
Volume 33 Number 4, August 2006
253
Case Report
domonas aeruginosa; 5 Bacillus
subtilis;5 Brevibacterium ammoniagenes; 5 and Propionibacterium
acnes.3 Beta-amino alcohol derivatives of totarol have demonstrated
antiplasmodial properties that have
no cross-resistance with chloroquine.7 Totarol from the Alaska Cypress tree (Yellow Cypress, Nootka
Cypress, Callitropsis nootkatensis,
Chamaecyparis nootkatensis8) has
demonstrated activity against Mycobacterium tuberculosis.9
Totarols mechanism of antibacterial activity is not known, however
some authors have suggested that it
compromises the functional integrity
of cell membranes.10 Haraguchi et al.
studied totarols actions on Pseudomonas and discovered that it inhibited oxygen consumption and respiratory-driven proton translocation
in whole cells, and oxidation of
NADH in membrane preparation (by
inhibiting a number of NADH-related
enzymes).11 Evans et al. alternatively
suggested that it disrupts bacterial
energy metabolism, although they
admitted that this action occurs at
much higher concentrations than are
significant for antibacterial activity.6
Although the exact mechanism of
action is not known, all proposed
mechanisms are dissimilar to those
of macrolides and tetracyclines. Thus
cross-resistance of macrolide- and
tetracycline-resistant bacteria to
totarol seems unlikely. Unfortunately
researchers have yet to produce a
totarol-derived systemic antibiotic,
since the potential benefits would
seem to be considerable.
Totarol has been tested for safety
in human applications. A skin irritation/sensitisation test of 0.05% totarol
solution on 50 human subjects resulted in no evidence of any toxic
effects on the skin.12 Furthermore,
totarol is not cytotoxic at concentrations required for antibacterial and
antioxidant activity in cosmetic applications.2 However, above these
concentrations it can be.
Totarol therefore has potential for
use in current practice as a topical
agent for treatment of acne vulgaris.
254
Figure 3. Totara tree
Figure 4a. Totarol extraction
Figure 4b. Totarol extraction
Since totarol has antibacterial activity against a bacterium that is related

to the development of acne,
Priopionibacterium acnes, its potential use for aiding patients with acne
is obvious. However a Pubmed search
revealed no papers on totarols application to clinical practice of any sort.
Totarol has already been marketed in an alcohol-based preparation for the treatment of acne, and in
a moisturiser. However these products are not available on the market
at the time of writing.
Figure 5. Totarol powder
Results
Noticeable improvement in the patients acne was seen over the period
that he used the products.
There is an apparent reduction in
inflammation and size and extent of
lesions over the six week period. The
patient was very pleased with the
results achieved to date.
Discussion
Webster13 summarises the pathophysiology of acne well:
Acne vulgaris is caused by abnormal desquamation of the keratinocytes
that line the sebaceous follicle, which
creates a microplug or microcomedo.
An increase in circulating androgens
at the onset of puberty stimulates the
production of sebum into the pilosebaceous unit. These events combine to

create an environment within the pilosebaceous unit that is favorable for
the colonization of the commensal bacteria, Propionibacterium acnes. With
proliferation, P. acnes secretes various
inflammatory molecules and chemotactic factors that initiate and perpetu-
Case Report
Figure 6a. Before treatment
Figure 6b. Day 42 of treatment
ate the local inflammatory response

and possibly induce keratinocyte
hyperproliferation as well.
Eradication of P. acnes, whether
through systemic or topical antibacterial agents, improves the acne. Totarol
falls into the class of topical antibacterial agents, with good activity against
P. acnes, S. aureus of many types, and
many other non-commensal bacteria.
This patient tried topical totarol in an
alcohol solvent and a moisturiser,
without the concomitant use of
keratolytics like salicylic acid or
adapalene. The improvement as indicated in the photographs is obvious; a
number of questions remain however.
Is the change really due to totarol?
Would the patients acne have improved more or less if he had used a
keratolytic as well? Would the patients
acne have improved more or less if he
had used a systemic antibiotic as well?
This case provides anecdotal evidence of improvement in acne with
the use of topical totarol; however to

establish a causal relationship, large
controlled trials are required. With
use of a keratolytic concomitantly,
there is the theoretical advantage of
improved pilosebaceous drainage, and
perhaps better antibiotic penetration
into the colony. However some experiments have demonstrated inhibition of antibacterial activity when certain antibacterials (not totarol) have
been used in combination with other
agents. Others have given evidence of
reduction in bacterial resistance and
acne with in vitro and in vivo use of
ancillary agents such as zinc salts.14
Therefore trials of totarol in combination with other agents are required.
With the possibility of future longterm and widespread use of totarol
for acne, one might also wonder
whether bacteria would become resistant to totarol. Furthermore, would
bacteria that are already resistant to
erythromycin and/or tetracyclines be
resistant to totarol already, or would

they be sensitive? Current theory suggests that antibiotic-resistant organisms should be sensitive to totarol,
but one cannot know for sure until
more studies have been done. Studies on the long-term use of totarol
alone for acne, against already antibacterial resistant organisms, and in
conjunction with other antibacterials,
would also be valuable.
Conclusion
This case report documents improvement in acne following regular application of an alcohol-based totarol
product and a totarol-containing moisturiser. Totarol has good theoretical
reasons for it to be a useful agent in
the treatment of acne, and has tested
as safe for topical (non-pregnant/nonlactating) human use. This is the first
case report that we could find of medicinal use of totarol, so at this early
stage rigorous data is absent. More research is therefore required in the form
of larger clinical trials.
Acknowledgements
Paul Williams, Mende Biotech Ltd
Competing Interests
Dr Nixon is medical advisor to
Mende Biotech Ltd. At the time of
writing this is an unpaid position.
References
1.
2.
3.
4.
5.
6.
7.
RCC Ltd. Totarol material safety datasheet.

Mende Biotech Ltd. Totarol information pack. Sourced from:
http://www.docs.totarol.com
Kubo I, Muroi H, Himejima M. Antibacterial activity of totarol and its
potentiation. Journal of natural products 1992; 55(10): 143640.
Muroi H, Kubo I. Antibacterial activity of anacardic acid and
totarol, alone and in combination with methicillin, against methicillin-resistant Staphylococcus aureus. J Appl Bacteriol. 1996
Apr; 80(4):38794.
Moorhead SM, Bigwood T, AgResearch. Report on the efficacy
of totarol and totarol in combination with tea tree oil as an
antimicrobial against gram-negative bacteria. Client report for
Mende-DEK Ltd Nov 2003.
Evans GB, Furneaux RH, Gainsford GJ, Murphy MP. The synthesis and antibacterial activity of totarol derivatives, part 3: modification of ring-B. Bioorganic and medicinal chemistry 2000;
8(7): 166375.
Clarkson C, Musonda CC, Chibale K, Campbell WE, Smith P.
Synthesis of totarol amino alcohol derivatives and their
antiplasmodial activity and cytotoxicity. Bioorg Med Chem. 2003
Oct 1; 11(20):4417-22.
8.
9.
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12.
13.
14.
Wikipedia the free encyclopedia. Available at: http://

en.wikipedia.org/wiki
Constantine GH, Karchesy JJ, Franzblau SG, LaFleur LE. Totarol
from Chamaecyparis nootkatensis and activity against Mycobacterium tuberculosis. Fitoterapia. 2001 Jun; 72(5):5724.
Micol V, Mateo CR, Shapiro S, Aranda FJ, Villalain J. Effects of
totarol, a diterpenoid antibacterial agent, on phospholipid
model membranes. Biochim Biophys Acta. 2001 Apr 2;
1511(2):28190.
Haraguchi H, Oike S, Muroi H, Kubo I. Mode of antibacterial
action of totarol, a diterpene from Podocarpus nagi. Plata Medica
1996; 62(2): 122-5.
AMA Laboratories Inc. 50 human subject repeat insult patch
test skin irritation/sensitisation evaluation (occlusive patch)
Jan 2000.
Webster GF. The pathophysiology of acne. Cutis 2005; 76 (2
suppl): 4-7.
Dreno B, Foulc P, Reynaud A, Mose D, Habert H, Richet H. Effect
of zinc gluconate on propionibacterium acnes resistance to erythromycin in patients with inflammatory acne: in vitro and in vivo
study. Eur J Dermatol. 2005 May-Jun;15(3):1525.
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Case Report

The use of totarol to treat

David Nixon MBChB, Daniel Hobbs MBChB

David Nixon is Clinical Director of The

to try the totarol products to treat

i[Totara-8, 11, 13-trien-13-ol]

Figure 2. 3D totarol molecule

Volume 33 Number 4, August 2006

Figure 3. Totara tree

Figure 4a. Totarol extraction

Figure 4b. Totarol extraction

Since totarol has antibacterial activity against a bacterium that is related

Figure 5. Totarol powder

Volume 33 Number 4, August 2006

production of sebum into the pilosebaceous unit. These events combine to

Figure 6b. Day 42 of treatment

ate the local inflammatory response

the use of topical totarol; however to

resistant to totarol already, or would

RCC Ltd. Totarol material safety datasheet.

Wikipedia the free encyclopedia. Available at: http://

Volume 33 Number 4, August 2006

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