Phosphatidylcholine and deoxycholate injections 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.

Research Synthesis

One of the key difficulties in synthesizing research from different studies in this area is that no human studies have been performed to date in the United States. Several animal studies involving rats and rabbits were found, but research into the safety and efficacy of the procedure has not been performed to date. The primary researcher in this area of research is Dr. Hexsel and her many research associates. However, this research only involved a sample group of 18 patients and was not conducted according to FDA protocol (Hexsel, 2003 and Hexsel, et a., 2003).

The introduction of a variable involving the administration of a "preventative" treatment for potential adverse effects significantly impacted the ability of the study in such as way that it must be considered inconclusive. The conclusions drawn by this study do not even meet the minimal requirements for isolation of a dependent variable and the sample size is significantly small as well. Therefore, Hexsel's study will not be included in this analysis for failure to meet the study protocol.

Another human study involved a case study of a single patient. This Brazilian study represented a case study and does not meet the protocol for inclusion in this analysis either (Rittes, 2001). As there have been no human studies in the United States to date, we must rely on studies published in other countries for our meta-analysis. A study conducted in Vienna by Karl Heinrich will be used as one of the studies to be analyzed. This was the only study that could be located involving an actual population of human subjects, as this type of research is prohibited in the U.S. At this time.

The sample population used by Heinrich consisted of 86 individuals who received a standardized series of treatments. This study suffered from significant flaws that make the results questionable. For instance, the patients received between 1-3 injections, but no analysis between these groups was reported. Heinrich reports a reduction in 100% of the test subjects. However, there was no control group. To be considered valid according to FDA protocols, the study must be double-blind with one group receiving a placebo and the other receiving the treatment. This was not done in any study found during this research.

Heinrich reported different injection sites were used in the study, but did not group these sites by location on the body. No standardized amount of phosphatidylcholine was used. Amount to be injected were determined to be "according to the needs of the patient" (Heinrich, p. 120). It is impossible to determine effective dosages with this method. Some patients received one injection and others received three injections. However, these groups were not statistically separated, but rather were combined into one group. Patients were instructed to hold their body weight steady during the course of the study, but there was no verification that they were able to do so. Due to a lack of documentation, it is not known if intentional weight reduction affected the results of the study.

Heinrich noted that average reductions in fat area were "2.41 cm" per application. However, it is not known which concentrations were the most effective. Heinrich concluded that this reduction was statistically significant to warrant a broad conclusion that phosphatidylcholine is an effective treatment for fat deposits. The study makes conflicting statements such as, "Cosmetic improvement was seen in every patient" (Heinrich, p. 122). However, there were 13 cases where no reduction in the size of the fat area, corresponding to a non-response rate of 5.06%.

Heinrich noted that patients responded to the treatment to different degrees. This might have been due to the differing dosages and number of treatment sessions. However, Heinrich did not provide sufficient information make this determination. These differences could be due to confounding variables, but without a control group for comparison, there is no way to know this. Hexsel's study in the U.S. suffers from this same flaw, but goes even further away from empirical protocol by introducing "unknown" substances into the study to cover for fact that is was not conducted according to FDA protocol.

One could combine the study results of the only two human studies conducted thus far and obtain a sample population of 104 human patients. Both researchers reported a reduction in fat in all of the respondents. If one combines these statistics, this means that approximately 13% of all respondents did not respond to the treatment.

Table 1. Combined Results 1.

Total patients

Non-Respondents

Heinrich

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.