Phosphatidylcholine and Sodium Deoxycholate in the Treatment of Localized Fat: A Double-Blind, Randomized Study
GIOVANNI SALTI, MD, ILARIA GHERSETICH, MD,y FRANCA TANTUSSI, MD,z BRUNO BOVANI, MD,z
AND TORELLO LOTTI, MDy

BACKGROUND

Recent articles have introduced the novel concept of chemical lipolysis through local injections. Phosphatidylcholine is the active drug in the commercial preparation used for this purpose,but some studies have suggested that sodium deoxycholate, an excipient of the preparation, could be the real active substance.

AIM We decided to investigate whether phosphatidylcholine and sodium deoxycholate have any clinical efficacy in chemical lipolysis and their respective roles. We also studied the safety and side effects of the treatments.

MATERIALS AND METHODS Thirty-seven consecutive female patients were studied for the treatment oflocalized fat in gynoid lipodystrophy. Each patient received injections of a phosphatidylcholine/sodium deoxycholate preparation on one side and sodium deoxycholate on the contralateral side, each single patient being herself the control. Four treatments were carried out every 8 weeks in a double-blind, randomized fashion. Metric circumferential evaluations and photographic and ultrasonographic measurements throughout the study allowed for final judgment. A statistical evaluation concluded our
study.
RESULTS An overall reduction of local fat was obtained in 91.9% of the patients without statistically significant differences between the treated sides. Reduction values on the phosphatidylcholine/sodium
deoxycholate–treated sides are in the order of 6.46% metrically and 36.87% ultrasonographically, whereas on the deoxycholate-treated sides they are in the order of 6.77% metrically and 36.06% ultrasonographically.
Both treatments, at the dose used in the study, proved safe in the short term. The most common side effects were local and few, but were more pronounced on the deoxycholate-treated sides.
No laboratory test was carried out.
CONCLUSION Both treatments have shown moderate and equivalent efficacy in treating localized fat, with sodium deoxycholate having a slower postoperative resolution, suggesting that sodium deoxycholate
could be sufficient by itself to determine fat cell destruction and that phosphatidylcholine could be useful for obtaining a later emulsification of the fat.
The authors have indicated no significant interest with commercial supporters.

 

The use of lipolytic drugs to induce a nonsurgical fat reduction is a common method in cosmetic medicine, either through topical treatments (creams, fluids) or through local injections,1–3 but very little scientific evidence sustains its widespread use.3
Recent articles have brought attention to a possible role of phosphatidylcholine in determining a chemical fat cell lysis through unknown mechanisms.4–6
Phosphatidylcholine (PPC), a phospholipid widely distributed in human cell membranes, is the main active substance of a commercially available injection lipolysis agent (Lipostabil N i.v. 5 mL, Artesan Pharma, Lu¨chow, Germany), a drug present in the European market for a long time and whose main clinical indication is the treatment of fat embolism. Its subcutaneous injection is an off-label use that seems to be efficacious in reducing local
adiposities.5–8

An interesting study by Rotunda and colleagues9 investigated the effect of the drug on fat cell lysis and suggested a possible major adipocytolytic role ofsodium deoxycholate (DEOX), an excipient contained
in the PPC formulation that would act as a detergent on fat cell membranes. This was indeed an in vitro study and its conclusions are not completely transferable to in vivo human patients. Further studies have also shown the efficacy of DEOX10 and PPC/DEOX11 in reducing the size of subcutaneous lipomas with intralesional injections of the drugs. We decided therefore to investigate whether DEOX could be considered an active drug able to induce a chemical lipolysis and to study the possible activities of DEOX and PPC on fat cell lysis. The safety profile of both substances was also studied.
Materials and Methods
We selected 40 consecutive female patients presenting  with bilateral gynoid lipodystrophy. Criteria of inclusion were localized fat as evaluated by the treating physicians, subcutaneous tissue thickness not less than 15mm on ultrasound, no previous treatment for at least 6 months, no cutaneous diseases in the treatment area, no systemic diseases, no known allergies, age 20 to 55 years, and no pregnancy or lactation. Once included, criteria of
exclusion were failure to follow the study protocol, concomitant diseases during the study, important adverse events, and weight gain or weight loss of more than 2 kg during the study. Each patient signed an informed consent to undergo a clinical trial with drugs used in off-label indication, according to the Declaration of Helsinki. The study protocol was approved by our institutional review board. The treatment sides and their respective drugs were  randomized by computer. Each patient underwent a 7.5-MHz ultrasonographic evaluation (CGR Scanel 300, Villenoy-Meaux, France) before treatment to rule out subcutaneous fatty tissue thickness.PPC/DEOX (Lipostabil, Natterman) and DEOX (Laboratorio Pineda, Sao Paulo, Brazil) were the active pharmacologic substances investigated. The PPC/DEOX preparation has a composition of 250/125 mg per vial (50–25 mg/mL in 5-mL vials).  The DEOX preparation has a composition of 237.5 mg per vial (47.5 mg/mL in 5-mL vials). To have comparable deoxycholate values, the dosing of the treatment was set to 1,000/500mg for the PPC/DEOX compound (four 5-mL vials) and 475mg  (two 5-mL vials) for the DEOX formulation, according to the known safety limits (15 mg/kg) of the PPC/DEOX formulation.12,13 Both formulations were diluted in saline to have 40mL of solution per infiltration side.
Each patient received bilateral subcutaneous injections n the gluteotrocanteric region with PPC/ DEOX on one side and DEOX on the contralateral side, each single patient being herself the control. The level of subcutaneous injections was approximately10 mm. Twenty-seven-gauge needles(0.413 mm; BD Microlance-3, Becton Dickinson, Franklin Lakes, NH) were used. Each point of injection received about 0.5mL of the pharmacological solution with an angle of injection to the plane of the skin of about 751 to 901 (almost perpendicular). According to previous literature, the area of treatment was strictly limited to 80 cm2 per side, with a mean number of 80 infiltrations per side, spaced approximately 1 cm apart.5,7 Because previous research had shown a resolution time of approximately 8 weeks for the postinfiltrative nodular reaction,14,15 four sessions of treatment were programmed, once every 8 weeks in a double-blind, randomized fashion, with a final evaluation 8 weeks after the last treatment. Our clinical evaluations included a circumferential metric measurement of the thighs at the level of the subgluteal fold, an ultrasonographic measurement at the level of the trocanteric fat pad, from skin to muscle fascia, and a photographic evaluation on a metric panel whose vertical lines were spaced 5 cm apart. Owing to the impossibility of getting exact  measures with a photographic evaluation, this was intended for 5% (approx. 2.5 cm) figure variations.

All subjective and objective signs and symptoms following each treatment session were recorded. A specific issue was devoted to the evaluation of pain in the area of treatment, with the help of a 0 (no pain at all) to 10 (intolerable pain) grading scale, that each single patient was asked to judge. No blood testing was carried out. All these evaluations were performed at every step of the study and 8 weeks after the last treatment for a final judgment. A statistical evaluation concluded our study.
Results
Thirty-seven of 40 patients completed the study, 2 patients were excluded for excess weight loss during the study, and 1 patient was lost to follow up. Three patients of 37 (8.1%) had no improvement at all and can be considered nonresponders. Thirty-four patients of 37 (91.9%) had some improvement. At the end of the study the majority (30) of patients had become slimmer. For the whole study group, the mean weight reduction was of 1.44% (58.53– 57.69 kg), with a mean body mass index value reduction of 1.3% (21.49–21.21 kg). The efficacy of treatments was evaluated in terms of overall reduction of thigh circumferences (metric measure) and subcutaneous thickness (ultrasound measure).
An overall reduction of local fat was clinically obtained in 34 patients without statistically significant differences between the treated sides. The mean circumferential metric value changed from 58.48 to 54.70 cm, with a 6.46% reduction on the PPC/DEOX-treated side, and from 58.67 to 54.70 cm, with a 6.77% reduction on the DEOX-treated side (Figure 1).
The ultrasound measures of the fat layer revealed much higher reduction values, again with no statistical difference. The mean ultrasonographic value changed from 36.13 to 22.81mm on the PPC/ DEOX-treated side, with a 36.87% reduction, and from 36.11 to 23mm on the DEOX-treated side, with a 36.06% reduction (Figure 2). The photographic evaluation resulted in an average 5% reduction as measured on a metric panel (Figure 3).
In those seven patients whose weight was not changed, the mean reduction was of 4.73% circumferentially (57.1–54.4 cm), 28.71% ultrasonographically (32.4–23.1 mm), and 5% photographically
on the PPC/DEOX-treated side and 4.92% circumferentially (57–54.2 cm), 32.77% ultrasonographically  (35.1–23.6 mm), and 5% photographically on the DEOX-treated side. Side effects of treatments are detailed in Table 1.
The treatment was quite painful for all patients: the pain at the injection site, usually short-lived, was more common (100% vs. 78.4%) and intense on the DEOX-treated side, with a mean grading of 6.2 for the DEOX side and 4.6  for the PPC/DEOX side on a 0 to 10 pain grading scale. Bruising was due to the Figure 1. Circumferential metric values. Figure 2. Ultrasonographic values. 6 2

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