Because of the seemingly endless array of topics to cover in this column, I have never directly revisited a subject here (although some botanical ingredients have received individual attention as well as some focus as members of a class of compounds). But much has changed since I last covered phosphatidylcholine in 2003. In this month’s column, I will review recent research and discuss new safety concerns regarding the use of phosphatidylcholine in mesotherapy.
Emerging about 50 years ago and popular in Europe and South America (J. Cosmet. Laser Ther. 2005;7:17-9), mesotherapy entails the subcutaneous injection of pharmaceutical, homeopathic, botanical, vitamin, or other agents with the intention of initiating localized lipolysis in cellulite or other areas with undesired fat deposits. While this is considered a noninvasive alternative to liposuction or lipectomy, the use of phosphatidylcholine for this purpose has not been approved by the U.S. Food and Drug Administration.
Off-Label Use of Phosphatidylcholine Products
The practice of using a formulation containing soybean-derived phosphatidylcholine in mesotherapy (also called lipo-dissolve, lipotherapy, or injection lipolysis) became popular in the mid-1990s in Brazil. The substance, known as Lipostabil, is a drug that was first used to reduce triglyceride and cholesterol levels in patients with coronary artery disease. However, lipo-dissolve products are marketed in the United States as natural compounds, even though the FDA considers such substances drugs and has not approved of their use for fat removal (http://www.npr.org/templates/story/story.php?storyId=11487499). Off-label use has become increasingly common in Europe and the United States. Given a spate of complications seen after the use of Lipostabil in Brazil, ANVISA, the Brazilian equivalent of the FDA, banned the phosphatidylcholine-containing product. This should give us all pause, since it is very rare for Brazil to ban medical drugs or devices.
Phosphatidylcholine, a component of lipoproteins, is a purified extract from lecithin. It was originally used in the medical setting for emergencies and treating atheroma plaques in cardiac disease (J. Drugs Dermatol. 2003;2:511-8). This phospholipid is a major component of all cell membranes and is the primary phospholipid in plasma. Composed of choline, phosphoric acid, and fatty acids, the phosphatidylcholine molecule occurs naturally in humans (especially in nerve tissue, the liver, and semen), and is obtained through consumption of soybeans, egg yolks, meat, and, rarely, vegetables. The consumption or injection of phosphatidylcholine is believed to augment phosphatidylcholine in lipoproteins, thereby enhancing their ability to mobilize fat and cholesterol. Further, phosphatidylcholine has been demonstrated to lower systemic levels of cholesterol and triglycerides and is believed to induce lipolysis (Dermatol. Surg. 2001;27:391-2).
Promising Findings for Use in Lipolysis
In the first paper that sparked the craze around this procedure, Rittes reported on the technique that she had begun using in 1995, with fellow Brazilian doctors. The procedure was introduced at the Dermatologic Brazilian Congress in 1999, and published in 2001 as a treatment of lower eyelid bulging caused by prominent fat pads (Dermatol. Surg. 2001;27:391-2). In the 2001 study, which featured subjective assessments of improvement and was not placebo controlled, Rittes concluded that phosphatidylcholine injections (250 mg/5 mL) into periorbital fat pads could postpone the need for or possibly substitute for lower eyelid blepharoplasty. (These findings on the use of phosphatidylcholine for correction of infraorbital fat pads were recently duplicated in an open-label study of 21 subjects conducted by Treacy and Goldberg [J. Cosmet. Laser Ther. 2006;8:129-32]).
In a 2003 study, Rittes continued to suggest that this in-office procedure was a suitable alternative to surgery, in this case lipectomy or liposuction. Specifically, 50 patients received injections of phosphatidylcholine (250 mg/5 mL) into fat deposits in the abdomen, neck, arms, or thighs in an 80-cm2 area using a 30G 1/2-inch insulin needle. Rittes observed clear improvement in all patients, with a significant decline in fat deposits and no recurrence or weight gain over a 2-year follow-up (Aesthetic Plast. Surg. 2003;27:315-8).
The next year, Hexsel et al. reported on their clinical experience using 250-mg/mL phosphatidylcholine injections to treat subcutaneous fat deposits in volunteers whose injections, in various localized fat deposits, were separated by a minimum interval of 1 week and mean interval of 15 days. They found that phosphatidylcholine was efficacious in diminishing the treated fatty areas, and was accompanied by minimal side effects. The investigators concluded that this noninvasive, off-label use of phosphatidylcholine was safe, effective, and inexpensive (J. Drugs Dermatol. 2003;2:511-8).
In 2004, Rotunda et al. assessed the mechanism of action and characteristics of the active components of a clinically used, injectable fat-dissolution formulation containing phosphatidylcholine and sodium deoxycholate, a bile salt incorporated to solubilize in water the natural phospholipid. In this experiment, the investigators performed cell viability and cell membrane lysis assays on cell cultures and porcine skin after treatment with the phosphatidylcholine product, isolated sodium deoxycholate, or common laboratory detergents. In comparing the results with phosphatidylcholine and isolated sodium deoxycholate, they found a significant and comparable loss of cell viability, cell membrane lysis, and disruption of fat and musculature in cell cultures and tissue specimens. The effects generated from the laboratory detergents were similar. The investigators concluded that the popular fat-dissolution formula based on phosphatidylcholine works mainly as a detergent, inducing nonspecific cell membrane lysis. Notably, they also suggested that sodium deoxycholate was the major active constituent causing the cell lysis, and urged caution for physicians regarding this procedure pending the availability of sufficient safety data (Dermatol. Surg. 2004;30:1001-8).