In 2005, Rose and Morgan took skin biopsies, 1 and 2 weeks after mesotherapy, from a patient who had undergone the procedure with phosphatidylcholine and deoxycholate. Both biopsies revealed normal epithelium and dermis, with a mixed septal and lobular panniculitis. The investigators noted that the fat lobules were infiltrated by an elevated number of lymphocytes and macrophages, the latter of which consisted of conventional forms, foam cells, and multinucleated fat-containing giant cells. Serous atrophy and microcyst development was linked to inflammation. In this first histologic study to illustrate the mechanism of action of phosphatidylcholine and deoxycholate, the authors concluded that mesotherapy with these compounds clearly impacted subcutaneous fat. They speculated that inflammatory-mediated necrosis and resorption likely accounted for the decrease in subcutaneous fat (J. Cosmet. Laser Ther. 2005;7:17-9).
In 2007, Sasaki et al. conducted a study in nine healthy female volunteers with grade II-III thigh cellulite to determine the safety and efficacy of a phosphatidylcholine-based cosmeceutical anticellulite gel combined with light-emitting diode (LED) treatment at 660 nm (red) and 950 nm (near-infrared). In this double-blind, controlled study, volunteers were randomly treated twice daily for 3 months with an active gel on one thigh and a placebo gel on the control thigh. Each thigh underwent a 15-minute treatment with LED light twice weekly (totaling 24 treatments).
At the end of the 3-month study period, investigators found alterations in cellulite warranting a downgrade in cellulite grade, based on clinical examinations, digital photography, and pinch test assessments, in eight of nine thighs treated with the phosphatidylcholine-based anticellulite gel and LED. A statistically significant decrease in immediate hypodermal depth and echolike intrusions into the dermal layer in the treated thighs was determined using digital ultrasound at the dermal-adiposal interface. Few clinical alterations were noted in the nine thighs treated with placebo and LED. Edema, erythema, and pruritus were among the rare and transient adverse effects from treatment. Follow-up at month 18 for eight response thighs revealed that five thighs regressed to their initial cellulite grade, and three thighs maintained the improvement from therapy, suggesting the need for repeated treatments (J. Cosmet. Laser Ther. 2007;9:87-96).
Given the dearth of published studies on mesotherapy with phosphatidylcholine and other ingredients, in 2007, Co et al. sought to ascertain the efficacy of phosphatidylcholine alone vs. phosphatidylcholine and organic silicium in reducing submental fat. Twelve healthy patients (of whom 1 was lost to follow-up) with submental fat received one to five treatments, with 2 weeks as the average between-treatment interval. Baseline fat measurements were taken at each session. Both treatment options were found to be equally effective, with no findings of ultrasound or histopathologic changes. Significant decreases in fat were observed after three treatment sessions in both groups, and only rare side effects (mild and fleeting) were noted. The authors identified the small sample size and the lack of a double-blind, placebo-controlled design as important limitations of the study. The researchers concluded that while the supportive evidence for using phosphatidylcholine or phosphatidylcholine with organic silicium is sparse and the mechanisms of action still poorly understood, both regimens appeared in this small study to be safe, efficacious, and inexpensive alternatives to invasive fat removal surgery (J. Cosmet. Dermatol. 2007;6:250-7).
In 2008, Salti et al. sought to assess the clinical efficacy and safety of phosphatidylcholine and sodium deoxycholate in chemical lipolysis and to characterize the roles of the agents in this nonsurgical procedure, based on reports that sodium deoxycholate, the intended excipient, was actually the active ingredient, rather than phosphatidylcholine. In the double-blind, randomized study, 37 consecutive female patients seeking treatment for cellulite received injections of a phosphatidylcholine/sodium deoxycholate preparation on one side and sodium deoxycholate on the contralateral side, for a total of four treatments every 8 weeks. The investigators recorded an overall local fat reduction of 91.9%, with no significant differences between the treatments. Side effects were local and rare, though manifested more on the sides treated with sodium deoxycholate. Both treatments were deemed safe in the short term. The authors concluded that the slower postoperative resolution associated with sodium deoxycholate suggests that this compound alone may be adequate for achieving the destruction of fat cells, while phosphatidylcholine could be used subsequently to emulsify the adipose tissue (Dermatol. Surg. 2008;34:60-6).
Concerns About Tissue Fibrosis/Necrosis
A few months later, Schuller-Petrovic et al. reported on their investigation of the subcutaneous tissue effects of phosphatidylcholine solubilized with deoxycholate in rats and one human volunteer. In a 30-day study, the rats were treated subcutaneously on the abdomen three times with 50, 300, or 600 mcL of the combination formula. The human volunteer, scheduled for elective liposuction, was treated in the same fashion. The investigators noted dose-dependent decreases in membrane integrity and cell viability in the rats, as well as histologic changes such as fibroplasia, bandlike fibrosis near the cutaneous muscle, and partial muscle loss. Fat necrosis, fat cyst development, and necrotic alterations in the walls of small blood vessels were associated with the highest dose. In the human volunteer, dose-dependent panniculitis, fat cysts, and vessel necrosis were noted in histologic sections of subcutaneous tissue. The researchers concluded that tissue fibrosis and necrosis of adipose and vascular tissues result from injection lipolysis with phosphatidylcholine/deoxycholate, and that the long-term safety profile for this nonsurgical subcutaneous fat treatment is consequently murky (Dermatol. Surg. 2008;34:529-42).