TITLE: ALPHA LIPOIC ACID (ALA) AND SCAR FORMATION IN REPAIRED
CLEFT LIPS
AUTHORS: David G. Genecov, M.D.; Kenneth E. Salyer, M.D.; Sarah Goldberg; Joshua
Cho
International Craniofacial Institute, 7777 Forest Lane, Suite C-717, Dallas, TX 75230
Introduction
Controlled scar formation in cleft lip repair is surgically determined by atraumatic technique and a
tension-free closure. This is achieved by complete dissection of all misaligned lip and nasal softtissues. Even though we can accomplish this reliability with our technique, we still see patients
presenting with aesthetically unpleasing wound healing by the presence of hypertrophic scarring
or even keloid formation. This is particularly frustrating, as these pathological scar formations are
very difficult to reduce by further surgical scar revisions and potentially stigmatize these patients
throughout their life. Even though the primary closure had been executed correctly, scars do not
always correspond. The application of external measures like e.g. silicone sheets and local
pressure has proven not to be very practical in some infants that refuse to comply with this
conservative treatment. Clearly, there is a wide demand for better means to control postoperative
scar formation, especially in this central part of the face in children with cleft lip deformities. Even
though research is currently being carried out to further elucidate the complex wound healing
processes leading to inadvertent scar formation, there is no medication available to date, which is
capable of reliably controlling hypertrophic scar or keloid formation. Postoperative irradiation,
which has proven to have a significant beneficial; effect on pathological wound healing in other
anatomical areas, however, has no place in the treatment of children with cleft lip deformities due
to hereby inflicted detrimental craniofacial and dental growth disturbances.
It is known that oxidative processes with consecutive free radical formation play an
important role throughout wound healing and inflammatory processes. As local application of
antioxidative vitamins such as vitamin E have clinically shown, though statistically not proven, a
beneficial effect on scar formation, we wondered if local application of other, even more potent
and act more centrally within the inflammatory process interacting scavengers of reactive oxygen
species could be of any benefit to clinical scar formation outcome in our patients with cleft lip
repair.
-Lipoic Acid is found naturally occurring as a prosthetic group in -keto acid
dehydrogenase complexes of the mitochondria, and as such plays a fundamental role in
metabolism. It has the ability to alter the redox status of cells and interact with thiols and other
antioxidants. Therefore, it appears that this compound has important therapeutic potential in
conditions where oxidative stress is involved. Initial research on ALA noted its oxidative
protection of the dermis from the harmful effects of uv-irradiation. The product is currently used in
the cosmoseutical business as an antiaging cream, noted to improve the thickness of dermal
collagen.
-Lipoic Acid has successfully been used in the treatment of a number of conditions
relating to liver disease, including alcohol-induced damage, mushroom poisoning, metal
intoxification and CC14 poisoning, as well as in the treatment of insulin resistance, diabetic
polyneuropathy and peripheral nerve damage from ischemia reperfusion injury. -Lipoic Acid
moreover has shown to be able to recycle natural antioxidants such as Vitamin C and E,
important cofactors in collagen synthesis and cell wall stabilization, as well as to improve nerve
blood flow.
Those beneficial features exhibited by -Lipoic Acid lead us to empirically apply it to
healing cheiloplasty wounds in infants within a double-blind controlled clinical study.
Methods
Sixty-two patients underwent primary cheiloplasty with cleft nasal correction at the International
Craniofacial Institute/Cleft Lip and Palate Treatment Center from July 1, 1998 to June 30, 1999.
Twenty consecutive patients were randomly assigned to the study protocol. Each patient
underwent primary cleft lip and nasal correction using a modified rotation advancement
procedure. Each patient was treated postoperatively with suture removal at postoperative day 6
followed by taping of the lip until postoperative day 14. At that time, massage of the lip scar was
carried out 3 times a day for five minutes at a time with taping between each session. This
continued for 3 months.
Twenty vials of Alpha Lipoic Acid NTP (made by N.V. Periicone, MD Cosmoceuticals)
were mixed and numbered at the factory. Ten vials contained the active ALA complex and ten
were exactly the same except did not contain the active complex. This lotion was used by the
parents as massage lotion three times a day during the massage sessions.
Patients were followed bimonthly for 12 months. At one year follow up the patients
underwent scar evaluation using the quantitative scale developed by Beusang et.al.
Examinations were performed by three independent reviewers, one of which was a board certified
plastic surgeon and the other two were college interns at the Institute. Once patient exams were
completed, the data was analyzed using a paired T-Test.
Results
Of the twenty patients enrolled into the study, 6 patients were disqualified due to failure to follow
the study protocol or refusal to return for follow-up photographs and analysis. The remaining
fourteen were evaluated and their lips were scored according to the above noted scale. There
were no adverse reactions or complications associated with the lotions used. After scoring, the
numbered bottles were identified as either placebo or active complex. Seven patients ended up
in each group once the factory key was obtained. Mean score in the placebo group was 13.18
and in the active complex group, 8.12. Standard deviations were 3.13 and 2.52 respectively.
Using paired t-test analysis the scores and thus the scars in the active complex group were
significantly better than the control/placebo group by a p value equal to 0.05.
Discussion
Scarring after surgical procedures or injuries have long been difficult problems, from a functional
as well as an aesthetic standpoint. As a science and medicine interrogate the healing process
we can develop interventions to change the end result. Antioxidants have recently been under
the research microscope to assess their influence on aging skin, inflammation and wound
healing. As free radicals are developed in the inflammatory and healing stages of wounds, it is
only reasonable to think that true antioxidants like alpha lipoic acid could modify the resultant scar
if delivered in a consistent fashion.
Delivery of antioxidants to specific areas of treatment is a central issue in studying their
effects. Podda et. Al. have demonstrated the efficacy of delivering ALA in a kinetic study of
cutaneous and subcutaneous administration of ALA. N.V. Periicone, MD Cosmoceutical
company has developed the only clinically available topical treatment with ALA that is easily
administered to the patient. This study demonstrates the product’s ease of use and statistically
demonstrates improvement in scar formation inpatients undergoing primary cleft lip repair.
We are now moving towards the development of a multi center trial to better elucidate the
clinical effects of alpha lipoic acid.
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