Otolaryngol Clin N Am

38 (2005) 1119–1129

Cosmetic Uses of InjectablePhosphatidylcholine on the Face

Doris Maria Hexsel, MDa,*, Marcio Serra, MDb,Taciana de Oliveira Dal’Forno, MDc,

Debora Zechmeister do Prado, PHARMd

aCosmetic Dermatology Department, Brazilian Society of Dermatology, BrazilbSexually Transmitted Diseases Department, Brazilian Health Ministry,

Rio de Janeiro, RJ, BrazilcFederal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

dDoris Hexsel Dermatologic Clinic, Porto Alegre, RS, Brazil

Intravenous phosphatidylcholine was initially used in cardiology for thetreatment of lipid atheromas, hypercholesterolemia, fat embolism, and fattydeposits or plaque adhering to arterial walls [1–5]. It was also used forthe treatment of mental disturbances and hepatic and cardiac conditionsinduced by medication, alcohol, pollution, virus, and toxins [6–9].

The first report of the cosmetic use of phosphatidylcholine was in Italy,where Maggiori [10] presented his work with phosphatidylcholine in thetreatment of xanthelasmas.

In Brazil, the cosmetic use of phosphatidylcholine began on an off-labelbasis at the end of the 1990s. This article is a retrospective study usinga sample of patients who were treated before phosphatidylcholine was pro-hibited in Brazil in January 2003.

The objective of this article is to report the authors’ clinical experiencein the use of phosphatidylcholine for the treatment of localized fatty areasof the face, which is a frequent complaint from some patients and is usuallytreated by liposuction, a more invasive procedure.

Anatomic aspects of facial fat

The facial outline is determined by the subcutaneous cellular tissuetogether with the facial musculature and the prominence of the parotid

* Corresponding author. Plinio Brasil Milano 476, Porte Alegre, RS 90520-000, Brazil.

E-mail address: dohexsel@zaz.com.br (D.M. Hexsel).

0030-6665/05/$ - see front matter � 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.otc.2005.05.002 oto.theclinics.com

1120 HEXSEL et al

glands [11]. A layer of fat covers the muscles and is distributed over the facein compartments of different shapes and volumes, such as Bichat’s fattypads in the malar region, which are responsible for the shape of the cheeks.

Adipose tissue has metabolic, thermal protective, and mechanicalfunctions in addition to the esthetic effect of molding the body [12]. Withaging, a redistribution of fat occurs and the deposits of fat become reducedin size; at the same time, there is a reduction in the function, size, andnumber of adipocytes as well as a reduction of preadipocyte differentiation,probably caused by alterations in important transcription factors, suchas CCAAT/enhancer binding protein (C/EBP) and peroxisome proliferatoractivated receptor (PPAR) [13,14]. This also implies a change in the shape ofthe face, which acquires a more rounded form, similar to that of infancy,and the appearance of wrinkles and facial furrows. The redistribution ofadipose tissue may also occur as an adverse effect of some chronic diseases,such as HIV/AIDS infection and Crohn’s disease, for example.

In HIV infection, partial lipodystrophy occurs with the loss of peripheralfat in the face and limbs. One mechanism that causes this is the accelerationof apoptosis of adipose cells attributable to the mitochondrial toxicitycaused by some antiretroviral drugs, mainly the nucleoside reverse trans-criptase inhibitors (NRTIs). This process completely modifies the facialoutline, with the loss of Bichat’s fat pads as well as perioral, periocular, andother fat deposits and the resultant formation of large cavities in the face.These give the appearance of advanced age or terminal illness. At the sametime, an accumulation of fat around the center of the body, such as thetrunk and neck, may occur. In the face, the fat accumulation is seen withgreater frequency in the parotid, lateral maxillary, and submandibularregions (Fig. 1), mainly in patients using protease inhibitors, although themechanisms are as yet not well understood [15,16].

Available treatments of localized facial fat

Almost 20 years after its first application, liposuction is currently aprocedure commonly used in the cervicofacial region [17]. Neck and facialliposuction requires smaller cannulas [18]. Smaller and shorter cannulasconnected to a syringe or special machines creating negative pressure shouldbe used for the jowl area to avoid oversuctioning [18].

The ideal conditions for the use of liposuction are the existence ofsufficient elasticity of the skin, little excess skin, and sufficient subcutaneousadipose tissue to be suctioned. [17] Liposuction not only allows theflattening of contours but correction of sagging teguments, resulting in someskin retraction [17,19]. Submental liposuction is an adjunctive surgicalprocedure that allows relatively predictable soft tissue recontouring of thecervicofacial region [20].

A number of variations on the surgical techniques for face and neckliposuction have been described, including soft tissue shaver [21],

1121INJECTABLE PHOSPHATIDYLCHOLINE

ultrasound-assisted lipectomy [22–24], intraoral transmental suction lipec-tomy [25], five-incision method combining machine-assisted and syringeaspiration [26], and submental suction-assisted lipectomy [27]. This lattertechnique has traditionally been reserved for younger patients or for olderpatients who are not face lift candidates. Thus, in general, for older patients,suction-assisted lipectomy is typically used as an adjunct for face and necklifts [27].

The combination of well-tried and newly described liposuction techni-ques with techniques of facial or neck [28] lifting and augmentation [29] mayoffer enhancement of achievable results [30]. Liposuction may also be usedin combination with laser resurfacing to improve the results, often with noincrease in recovery time [31,32].

Injectable phosphatidylcholine

Phosphatidylcholine, for commercial ends, is mainly extracted fromlecithins from vegetable species, such as soy, sunflower, and mustard.Lecithin from eggs is also a source of phosphatidylcholine [33].

In the composition of phosphatidylcholine extracted from soy, fatty acidslike palmitic and stearic acids make up 19% to 24% of the total content.Monounsaturated fatty acids represent 9% to 11%, linoleic acid represents56% to 60%, and alpha-linoleic acid represents 6% to 9%. Choline re-presents approximately 15% of the composition of phosphatidylcholine[33–35].

Chemically, phosphatidylcholine is also known as 1,2-diacyl-:ussn:ue-glycero-3-phosphocholine, PtdCho, and lecithin [34]. The phosphatidylcholine

Fig. 1. Patient with fat accumulation in the parotid, lateral maxillary, and submandibular

regions.

1122 HEXSEL et al

molecule consists of a head group (phosphorylcholine), a middle piece(glycerol), and two tails (the fatty acids, which vary). The phosphatidyl-choline molecules present in the tissues of organisms may vary depending onthe radical of the fatty acid linked to the molecule [34].

Action mechanism

The most widely recognized action mechanisms for phosphatidylcholineare those of an emulsifier and tensoactivator [36]. Rotunda and colleagues [36]affirm that phosphatidylcholine behaves as a detergent in the subcutaneouslevel, causing nonspecific lysis of fat cell membranes. These authors injectedphosphatidylcholine and other detergents used in laboratories into pieces ofpig skin. The viability and lysis of the cell membranes from the pig skin wereevaluated after injection with these substances, and it was found that therewas a significant loss of viability, membrane lysis, and breakdown of thearchitecture of the muscles and fats in the areas injected [36].

Components of the injectable solution

Injectable phosphatidylcholine is composed of the following chemicalcomponents:

- Phosphatidylcholine, USP 96%: as individually prepared and commer-cial injectable products, 5% phosphatidylcholine (5 g in each 100 mLof solution or 50 mg/mL) is used according to the monograph of themedicine registered with the United States Pharmacopoeia (USP) [34].

- Sodium deoxycholate or monoethanolamine deoxycholate: an activecomponent that favors solubility of phosphatidylcholine and reduces itsviscosity

- Benzyl alcohol: used as a preservative in injectable products- Distilled water for reverse osmosis: the traditional vehicle for injectablepreparations

Conservation and storage

Conservation and storage of the injectable 5% phosphatidylcholinepreparation should be according to the manufacturer’s recommendationsand the specific legislation for injectable products. Phosphatidylcholineshould be contained in brown glass vials because it suffers degradation whenexposed to light. The manufacturer recommends that it should be keptunder refrigeration (4 �C–9 �C), although there is no reference to this medi-cine being sensitive to temperature.

Materials and methods

From January 2001 to December 2002, 20 patients were givenapplications of phosphatidylcholine for the treatment of localized fat on

1123INJECTABLE PHOSPHATIDYLCHOLINE

the face. Of these 20 patients, 17 were female and 3 were male. Their agevaried from 37 to 72 years for the women and from 32 to 47 years for themen. The mean age of the patients in the sample was 53.4 years. Threepatients were HIV-positive.

The technique used for facial and neck treatment was subcutaneousinfiltration with undiluted phosphatidylcholine (250 mg/5 mL), using a0,5 � 13 G needle directly into the area of localized fat. Those areaswith small fat deposits were infiltrated at only one central point, whereas inlarger areas, the injections were at equidistant points of approximately 1 cm.At each application site, 0.2 mL was injected, totaling 0.2 to 5.0 mL (10–250mg) per session. There were one to five sessions, with intervals of 3 to 4weeks, according to the necessities of each patient, based on the initialmedical evaluation and according to the results obtained from subsequentapplications. The treated areas were the jaw line in 14 patients, thesubmental/chin region in 8 patients, the malar area in 3 patients, and thepreauricular area in 2 patients.

The patients were asked to report any side effects that occurred duringtreatment. Digital photographs were taken before initiating treatment andat the end of the treatment course.

A follow-up questionnaire was administered by telephone up to 3 yearsafter the last treatment. The satisfaction level of the patients with thetreatment was evaluated as satisfied or unsatisfied. In those patients whoresponded that they were satisfied, the degree of reduction of localized fatwas evaluated as discreet, moderate, or marked. Patients were also askedwhether the reduction of localized fat was persistent up to 3 years afterapplication.

Results

All the treated patients had pain, itching, and erythema on the first andsecond days after the injections. The edema remained visible for a maximumof 10 days after the treatment. Bruising was also observed at the treated sitesand regressed spontaneously in the days immediately after treatment. Nosystemic side effect was reported by these patients. Although these sideeffects disappeared in a short time, they may cause more discomfort in facialareas than in body areas, where they can be hidden by clothing.

Of the sample of 20 patients, 18 (90% of the sample) reported a reductionin the deposits of localized fat on the face after phosphatidylcholinetreatment. Of these 18 patients, 9 (50%) reported a marked reduction, 6(33.3%) reported a moderate reduction, and 3 (16.6%) reported a discreetreduction. The 2 patients who did not report any improvement only had oneapplication session.

In the group that reported improvement, 16 patients (80% of the sample)reported that the improvement persisted up to 3 years after the treatment

1124 HEXSEL et al

sessions. The three HIV-positive patients reported marked and persistentimprovements.

Discussion

The youthful face is characterized by its rounded aspect and the presenceof adequate volumes of bone, teeth, fat, and collagen. The reabsorption ofthese volumes and the redistribution of the fat in some deposit areas of thelower face lead to an aged appearance. Treatment of the aging process hasled to a demand for specific treatments, such as fillers, lasers, botulinumtoxin, and other methods (eg, those that can remove localized accumu-lations of excess fat). With liposuction, there is a potential risk when dealingwith small volumes of fat in the face.

The demand for ever less-invasive techniques for the treatment of theaging face has given impulse to the search for alternative treatments. Fourhuman studies have been published on the treatment of localized fat with thesubcutaneous application of phosphatidylcholine [37–40]. The first studypublished included 30 patients with varying degrees of lower eyelid fat pads.The patients received one to four injections of phosphatidylcholine into the

Fig. 2. Patient with fat accumulation before treatment with injections of phosphatidylcholine.

Fig. 3. Patient with fat accumulation after treatment with injections of phosphatidylcholine.

1125INJECTABLE PHOSPHATIDYLCHOLINE

fat pads at intervals of 15 days. There was cosmetic improvement in allpatients [37]. In another study published by the present authors, 213patients, of whom 8 were HIV-positive, were treated with phosphatidyl-choline with the aim of reducing localized fat deposits. The patients weresubjected to one to five subcutaneous applications at an average interval of15 days. Thirteen patients from this study underwent laboratory evaluation,including blood tests, glycemia, lipid profile, and liver and renal functionbefore treatment and 48 hours and 14 days after application, and there wasno significant difference in the test results. Most patients reporteda reduction of localized fat deposits in the areas treated, and this wasconfirmed with medical examination [38]. Yet another study reported theresults of 50 patients who received applications of phosphatidylcholine forthe treatment of localized fat, with reduction of deposits in all treatedpatients and without recurrence of treatment for a period of 2 years [39].The most recently published clinical trial studied the efficacy and safety ofinjectable phosphatidylcholine for the treatment of eyelid fat pads. Ten

Fig. 4. Same patient before subcutaneous injections of phosphatidylcholine in the submento-

nian region.

Fig. 5. Same patient after subcutaneous injections of phosphatidylcholine in the submentonian

region.

1126 HEXSEL et al

patients were treated in three to five sessions. Improvement in fat herniationwas reported in 80% and 70% of patients as graded by the physician andpatients, respectively [40].

An animal model study was presented by Paschoal and colleagues [41].They injected phosphatidylcholine in 6 healthy pigs and another groupreceived placebo. Once a week, each pig received 10 subcutaneous injectionsof 0.5 mL phosphatidylcholine, 2 cm apart, into the flanks for 10consecutive weeks. The total dose administered per pig, per week were500 mg and the animals were submitted to physical and biochemicalexamination, over 6 months. Two days after the last injection, all the pigsbecame icteric (3þ/4þ), had prostration, and showed petechias, hematomas,bleeding from the mucous membranes and superficial ulcers at theextremities. Biochemical liver function alterations were observed in allpigs. The symptoms regressed in 5 of the 6 animals, following suspension ofthe treatment, but one of the pigs (from phosphatidylcholine group) died 2days after the last injection due to cholestatic hepatitis. Probably these dosesand frequency of injections can lead to hepatic overload, which may explainthe results in the studied pigs. The pigs in the control group did not presentcomplications. This is the first study reporting the effects of subcutaneousinjection in animals, as used for cosmetic purposes. This study confirmedthat further studies of phosphatidylcholine are needed to establish the safetyof this drug prior to approval in humans, such as dose levels and frequency,and total doses as well as other possible side effects.

The side effects described in the previously cited studies included localizedpain, infiltrative edema, erythema, localized heat, itching, and bruises atthe treatment sites. These lasted for only a few days after the applications[37–39].

The present study shows similar results to those of previously publishedhuman studies on the use of phosphatidylcholine in the treatment of

Fig. 6. Female patient before subcutaneous injections of phosphatidylcholine in the sub-

mentonian region.

1127INJECTABLE PHOSPHATIDYLCHOLINE

localized fat and shows high levels of satisfaction in the treatment of areas oflocalized fat on the face in the studied sample in healthy and HIV-positivepatients (Figs. 2–7). The local side effects reported by the patients in thisstudy are also the same as those reported in previous publications, and noother variation or systemic side effect was found.

Summary

Despite the temporary side effects that cause a degree of discomfort,phosphatidylcholine injections can be used successfully in the treatment oflocalized and small fatty areas of the face, as it requires a few injections andless than one vial. Injection of phosphatidylcholine seems to be a better,safer, and more cost-effective treatment than liposuction in these specificcases. We point out that more studies should be performed to trace thesafety profile and appropriate doses of phosphatidylcholine for thetreatment of localized fat.

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