Phosphatidylcholine solubilized with deoxycholate for subcutaneous fat reduction

Injections of Phosphatidylcholine Solubilized With Deoxycholate Have Been Shown to Reduce Localized Accumulations of Subcutaneous Fat

Cutaneous injections of phosphatidylcholine solubilized with deoxycholate are one of the more popular treatments in Europe for the reduction of unwanted subcutaneous fat deposits. The popularity of these treatments has sparked the interest of U.S. pharmaceutical companies. However, at the present time, this compound is yet to pass the strict criterion of the FDA for acceptance as a treatment for subcutaneous fat. A literature review found that there are many studies that promote the effectiveness of phosphatidylcholine Solubilized with deoxycholate as a treatment option. However, not all studies agree that this substance as to which of these two compounds is responsible for the observe effects. Although a majority of research studies promote the use of phosphatidylcholine Solubilized with deoxycholate as an effective and safe treatment for subcutaneous fat, there are others that question its use due to the inability to determine the active ingredient.

Introduction

The search for a shapely body has led medical science to search for treatments that will provide the fastest results, with the least effort. Mesotherapy was developed in Europe and has become a popular method for containing unwanted fat deposits in the body. The treatment is beginning to spark interest in the United States as well. Mesotherapy to remove fat is cost effective as compared to liposuction and does not require the healing time. Mesotherapy costs between $1,000 to $6,000, as compared to liposuction that costs between $3,00 -$12,000 (Strauss, no date).

The treatment uses vasodialators, nonsteroidal anti-inflammatory drugs, and a combination of enzymes and hormones to reduce fat. One of the most common chemicals used in the treatment lecithin (phosphatidylcholine isoproterenol) (Kopera, Binder, and Topiac, 2006). However, recently it has been discovered that when lecithin is sulubilized with deoxycholate, the active ingredient was the deoxycholate, rather than the lecithin (Bechara, Sand, and Altmeyer, 2006).

In order to gain popularity in the U.S., the treatment protocol will have to undergo extensive testing by the FDA to determine its safety and efficacy for the intended condition. At this point, it appears that small amounts of deoxycholate are a safe and effective treatment for limomas (fat deposits). The use of phosphatidylcholine solubilized with deoxycholate cannot be confused with the practice of mesotherapy itself. Mesotherapy uses a combination of drugs, rather than a single compound. However, phosphatidylcholine solubilized with deoxycholate is one of the compounds used and is the one of greatest interest to the U.S. medical community, but more studies are needed before it will be released as a preferred treatment for fat deposit reduction in the U.S. (Moraru, 2006; Rotunda and Kolodney, 2006).

Literature Review

Mesotherapy using phosphatidylcholine solubolized with deoxycholate for the removal of subcutaneous fat deposits is an accepted practice. Yet, in the United States this form of treatment is only beginning to become recognized as an alternative to traditional methods. The acceptance of new treatments is treated with scrutiny in the U.S. Although treatment with phosphatidylcholine solubolized with deoxycholate is an accepted alternative in Europe, it might still be many years until it gains acceptance in the United States. Concerns over safety top the list of items of concern over this new therapy.

The use of phosphatidylcholine solubolized with deoxycholate for the removal of fat deposits was a side effect of the use of this compound for other conditions. The compound was first used to treat musculoskeletal pain and vascular disease (Moraru, 2006). However, it was soon discovered that the compound could remove small collections of adipose tissue, largely as a result of the detergent action of the compound. Deoxycholate acts as a detergent to dissolve the fat tissue (Moraru, 2006). It is believed that this is the major action responsible for the clinical affects. This study will concentrate on the use of phosphatidylcholine solubolized with deoxycholate on the dissolution of fat in the eyelids, as this represents the most popular use of this treatment to date, as well as the safety and efficacy issues to date.

Lipomas are benign deposits of mature fat cells that cause unsightly bulges in areas of the body such as the eyes, buttocks, and other areas of the body. Phosphatidylcholine solubilized with deoxycholate, a bile salt, have been shown to reduce unwanted accumulations of fat with considerable reliable results (Rotunda, Ablon, and Kolodney, 2006). There is sufficient clinical evidence to support the use of phosphatidylcholine solubolized with deoxycholate for the removal of unwanted fat cells (Hexsel, 2003). However, there is concern over the mechanism that phosphatidylcholine uses to accomplish this.

Thus far, in vitro studies have found that phospholipids increase actions that may help prevent fibrosis and cirrhosis of the liver. Phosphatidylcholine also demonstrates other protective effect in non-alcoholic liver disorders. This includes protection from other toxic substances (Atoba, Ayoola, and Ogunseyinde, 1985). Phosphatidylchoine has also demonstrated promise in These benefits are in addition to the affects observed on dissolving fat.

In the liver, phosphatidylcholine partitions into Sphingomyelin (SM) and Phosphatidylcholine (PC) layers (Ollila and Slotte, 2001). Phosphatidylcholine that contains a high percentage of polyunsaturated fatty acids has a tendency to dissolve cellular membranes. (Hanin and Ansell, 1987). This causes breakdown of cellular membranes and inhibits the repair mechanisms. This mechanism is associated with a number of disorders, including liver disease, neurological diseases, and various cancers (Hanin and Ansell, 1987). This is the primary concern over the use of phosphatidylcholine solubolized with deoxycholate for use in cosmetic procedures.

The use of phosphatidylcholine solubolized with deoxycholate has two sides,. On one side, it has the ability to treat many disease conditions, in addition to the fat reducing characteristics. However, it also demonstrates the potential to cause serious conditions by reducing cell membrane signal transduction (Hanin and Ansell, 1987). The jury is still out as to whether the benefits outweigh the risks of usage of this compound. This research concentrates on the use of phosphatidylcholine solubolized with deoxycholate for cosmetic use. This research will support the thesis that not enough is known about the negative effects of phosphatidylcholine solubolized with deoxycholate to warrant continued usage in cosmetic fat deposit removal.

Methods

This research employed a variety of research techniques. It employed a traditional library search of relevant technical journals. It also involved a search of the PUBMED database online in order to gain the most relevant clinical studies regarding phosphatidylcholine solubolized with deoxycholate. Several newspapers were consulted to gain a perspective on public opinion and acceptance of the procedure. This research technique yielded a wealth of information that presents an overall picture of the public and clinical aspects of the procedure.

This research method yielded a plethora of research studies from highly credible and specialized sources. A majority of the studies focused on the effects of phosphatidylcholine solubolized with deoxycholate on fat reduction. The newspaper articles utilized cited information similar to that found in the research articles. This adds a considerable amount of credibility to the newspaper articles. As this topic is associated with clinical research, many of the journal articles found were conduced in accordance with strict standards. The number and quality of research articles found Is considered to be sufficient to draw conclusion in this literature review. Only recent journal articles will be used in the combined data analysis of the research.

The analytical methods used for the combined analysis of the study will rely on the ability to identify studies that have similar research parameters. For instance, they studies selected have a similar sample population and will be determined to have eliminated or accounted for confounding variables. It is important that only studies with similar parameters will be used in the final analysis of the data. The study will use Excel formulas for computation of basic statistical parameters.

Combined data will be subject to any biases that are identified in the individual studies contained in this research. The researcher in this case, has no control over sample selection methods used in the individual research studies. However, a critical analysis will be necessary in order to identify biases and other factors that will affect the overall combined results of the study.

Hexsel

Hexsel did not provide sufficient statistical data to perform any further analysis on the combined data. The problem with the synthesis of this data is that the two studies do not have enough similarities to combine in a meaningful manner. Both concluded that treatment was 100% effective. However, without a control group and stricter experimental protocol, it is difficult to validate the results of either study.

Both Heinrich and Hexsel used before the after photos as their primary presentation method reports. It does appear from the photos that the injections were effective in reducing the fat deposits. However, as we discussed previously, photos of before and after photos do not meet the criteria of a valid research study.

Figure 1. Before and After Photos from Heinrich 1.

Figure 2. Before and After Photos from Hexsel 2.

These before and after photos were used as the primary evidence of improvement. As one can see from Heinrich's photos, it is difficult to see the results in some cases. However, in the lower photos, the improvement is much more obvious. Both authors substituted this photo evidence for graphic displays of their analysis.

Discussion

Numerous studies were located that supported the use of phosphatidylcholine solubolized with deoxycholate as a means to reduce unwanted body fat. The fat reducing characteristic of the compound was later used for the reduction of fat in other parts of the body as well. Phosphatidylcholine is a natural byproduct of certain bacteria (Sohlenkamp, Lopez-Lara, and Geiger, 2003). Several pathways of biosynthesis have been found in bacteria. Brucella melitensis, P. aeruginosa and Borrelia burgdorferi (Martinex-Morales, et al., 2003). Many of the studies conducted in the United States are animal studies using different species..

However, several studies were found that used antidotal evidence from South America, where the treatment is used as a low cost alternative to surgery (Takahashi, Y, Miaunuma, T., and Kishino, Y., 1982).One might note that drug testing in the U.S. is considered to be more rigorous than in other parts of the world. One must be careful when making assumptions based on evidence from another country as there testing methods might not meet the standards of those in the United States.

Research reports few side effects from treatments using phosphatidylcholine on humans for the reduction of fat. However, there is strong theoretical suggestion that there may be some more serious side effects present, such as kidney or liver damage (Hanin and Ansell, 1987). Yet, the popular media promotes the treatment as relatively safe. At this time there are insufficient studies to indicate that the compound is either safe or non-safe for human usage.

Claims in the mass media differ in tone from those in academic journals. Mass media reports tend to favor the use of phosphatidylcholine solubolized with deoxycholate as an alternative to liposuction or other surgery (Reiman, 2005). The primary use of phosphatidylcholine solubolized with deoxycholate is the cosmetic removal of fat tissue from specific areas of the body. Doctors in the United States are promoting the use of phosphatidylcholine solubolized with deoxycholate as an alternative to liposuction. They claim that it is less risky traditional surgical methods. However, the media might have jumped ahead of themselves by promoting as procedure that has been accepted in other countries, but that has not been approved for use in the United States for this purpose (Reiman, 2005).

Although research has indicated that the injections may have other medical uses, such as triglyceride metabolism, the primary use of this treatment remains cosmetic treatment of fat deposits. According to and interview with Dr. Hexsel (Reiman, 2005), the fat deposits cause "discomfort and anguish." Often the patients will choose to undergo surgery in order to alleviate these symptoms. The primary promoter of the technique in the United States is Dr. Hexsel, a former Brazilian dermatologist, now living in the United States. Dr. Hexsel is the primary source of much of the information regarding this treatment in the United States and backs up her claims with clinical research (Hexsel, 2003).

Phosphatidylcholine alters the structure of fat tissue (Reiman, 2005). According to Dr. Hexsel, the mechanism of this action has not been determined by histological or pharmacological methods. There are a number of hypotheses regarding how the mechanism works, but it cannot be definitively determined. This is one of the key criticism regarding the use of this agent in clinical use. There is evidence that phosphatidylcholine might not be the active ingredient responsible for the fat reducing action, but rather that it may be the solution into which it is desolved, deoxycholate, that is responsible for the actions (Rotunda, et al., 2006).

Typically, mass media articles have little value in an empirical study. However, in this case claims being made have filtered into mainstream society and might sway public opinion on the safety or efficacy of the treatment before the safety and efficacy can be established, according to FDA standards. Dr. Hexsel minimizes the risks discovered in other articles regarding the potential side effects and risks associated with the treatment, relying instead, on long-term use in Brazil. The same concerns cited in this research article were addressed by the Brazilian National Agency of Health Inspection (ANVISA), which regulates the use of medication in Brazil. They determined that there was insufficient evidence regarding the uncontrolled and overuse of phosphatidylcholine injections.

One of the key criticisms of Dr. Hexsel's experiment that is most cited in media articles promoting use of phosphatidylcholine injections is that the experiment was not conducted according to strict clinical guidelines. The clinical research available on the injections is still in the animal study and in vitro stage (Rittes, Rittes, and Amay, 2006). The research is in no way ready for introduction into human systems for testing. Many of the human studies found, were conducted outside of the United States.

During the human trials conducted to "prove" the safety and efficacy of the treatments, 18 patients were injected with phosphatidylcholine injections. They had five treatments over a 10 day period. Measures were taken to reduce the possibility of systemic effects from excessive or short intervals (Reiman, 2005). This measure introduces a variable that might not be present in the clinical setting. One cannot determine that the drug is safe if "precautions" were taken to avoid adverse effects.

Clinical studies performed by other researchers indicated the potential for serious side effects and reactions (Hanin and Ansell, 1987). Yet, these were ignored by Hexsel's reports to the media. Hexsel reported moderate swelling, minor skin irritation, and slight bruising as potential side effects. No mention was made of the potential toxic effects on the liver indicated in earlier studies. The use of phosphatidylcholine in the treatment of fat deposits is "off label" use, as there is no evidence from the FDA, as of yet, to support it. Dr. Hexsel's use of "precautions" to prevent adverse reactions goes against clinical empirical protocols and cannot be used as evidence that the treatment is "safe."

Another problem with off-label use of phosphatidylcholine is that each doctor uses their own dosage and formula. Safety and efficacy levels are an important part of the FDA licensing and approval process. This lack of dosage control affected the quality of the clinical results and the ability to draw conclusions regarding efficacy of the procedure. The original thesis of this research was that despite a growing body of evidence, and the presence of contradictory results phosphatidylcholine should not be used as a treatment for unwanted fat in the United States.

Conclusion

Despite a lack of clinical evidence to support the efficacy or safety of phosphatidylcholine solubilized with deoxycholate, this form of mesotherapy continues to grow in popularity. The FDA takes a stance of discouraging off label use of drugs, particularly those that are being used for cosmetic uses only. The literature review did not yield even one human study that met the criteria necessary to be considered evidence of phosphatidylcholine solubilized with deoxycholate's safety of efficacy. The research is still in the early stages in the United States. Although this mesotherapy is considered a standard treatment in other parts of the world, there is little reliable evidence to support it.

Hexsel, et al. (2003) compared the off label use of phosphatidylcholine to the off label use of Botox. From a clinical standpoint, this claim could be dangerous. One cannot compare one drug to another, without any proof that they are similar in composition and action. At this time, the mechanism by which phosphatidylcholine works is not understood. There is controversy that phosphatidylcholine might not even be the active ingredient, yet Hexsel and other doctors continue to use it on patients. The results of this literature review were disturbing, as they indicate rather reckless behavior by doctors that continue to use this therapy without evidence to support it.

The practice of prescribing off label usage of phosphatidylcholine solubilized with deoxycholate could have dire consequences for patients and doctors alike. The use of off label drugs can have an effect on the liability of the doctor and increase their chances of malpractice. On a global level, this case highlights the significance of the differences in approval protocol between the United States and other countries around the world. One might recall that the drug was taken off the market until more reliable testing could be conducted. The purpose of the FDA rules is to protect the public. When doctors break or bend these rules, the integrity of the system is jeopardized. This can place patients in undo danger.

It is difficult to read the articles written by Hexsel and Heinrich and not see some form of researcher bias present. This is particularly true when one considers the conflicting statements made by Heinrich regarding the number of patients that experienced reductions in the intended fat. When examining research, one has to consider who sponsored the research in question. In this case, both doctors have an interest in the outcome, as they both perform these procedures. Research sponsored by academic researchers that do not have an interest in the outcome are much more reliable than those in which the researcher has an interest in the study. This research supports that need to conduct further research and continue along the long road to FDA approval.