Consumers are forced to sift through conflicting information regarding new cosmetic surgery procedures that are constantly being presented in the media. Remarkably, and likely to the surprise of consumers, these procedures are often presented to the public at face value with almost no scrutiny. This means that a new procedure presented by a talk show hostess or morning news show is not scrutinized for its scientific validity before being passed on to consumers as the “next new thing.” These stories are handled without any investigation, essentially for entertainment value. The public is often fed the undiluted public relations message of the manufacturer of the new device that makes the service possible. This is bewildering because consumers rightly or wrongly have an expectation that media news programs have investigated these devices before promoting the service on their shows. Unfortunately this is simply not how the process works.
It seems that television programming be it a local news shows or programs like The Doctors have no capacity to independently assess the validity of the science upon which these devices are often promoted. This is unfortunate because it seems Television and Cable shows are just as uncritically attracted to big, expensive, shiny aesthetic procedure devices as the surgeons are. It is not well understood that the Federal Drug Administration does not apply the same level of scrutiny to the clearance of medical devices as they do to the approval of a new drug. There are different levels of device clearance and they are often subject to subsequent review based on clinical experience once the device is released.
This means that for medical devices released to the market, it can be a bit of buyer-beware (Caveat Emptor). The Zerona laser (Erchonia Corporation, McKinney, TX) is an excellent example of this marketing phenomenon. A promotional mailer sent by the company, which is intended for physicians to encourage them to buy the device, makes a number of scientific-sounding claims. Let’s look through the claims that are made in this advertising brochure. On the cover of this 4 page piece is the claim: “The first FDA-approved non-invasive body contouring procedure to effectively remove excess fat.” Inside the brochure in large bold print is the claim: “Zerona, the most researched medical procedure on the market.” What follows is a series of claims regarding the validity of the science behind the procedure. For ease in keeping track of these claims, I will number these:
- Studies prove that Zerona’s low level laser energy promotes the release of stored lipids and fatty material through the creation of a transitory pore within adipocyte membranes.
- After low level laser treatment, stored lipids and fatty material enter the interstitial space where the lymphatic system is readily capable of removing the fatty debris.
- Histological evidence shows that the clinical outcome of the Zerona laser is achieved without inducing adipocyte death.
- The adipocyte is an important endocrine organ that is responsible for the synthesis of bioactive peptides which participate in autocrine, paracrine, and endocrine pathways.
- The FDA granted market clearance following the completion of a Level 1 clinical investigation evaluating sixty-seven participants. The results obtained from this double blind, randomized, multi-site and placebo-controlled study was absent of diet restrictions, exercise component, or any other adjunctive components in order to properly illustrate the clinical efficacy of the Zerona laser and set the precedent on other aesthetic devices should be evaluated.
- The results proved Zerona is a safe and effective way to remove fat from the hips waist and thighs. Test patients lost an average of 3.64 inches of fat combined from their waist, hips and thighs, whereas placebo patients only lost an average of half of an inch. Statistical Significance of p<0.0001.
To assess the validity of these claims, we will look to the medical literature and assess the underlying papers that support or refute these claims.
The first claim is that the Zerona laser is the “The first FDA approved non-invasive body contouring procedure to effectively remove excess fat.” Keep this claim in mind and after you have read this review, asks yourself if you think this claim is valid. The issue is whether the company that manufactures the Zerona laser has in fact shown that its device effectively removes excess fat.
The next claim is that “Zerona, the most researched medical procedure on the market.” Really, the most researched medical procedure on the market? As they say, this one does not pass the sniff test. The National Library of Medicine maintains the most extensive online library of peer reviewed medical papers. A search on the medical procedure coronary artery bypass graft performed to restore the blood circulation to the heart reveals 51,213 published papers. A search on laparoscopic cholecystectomy or laproscopic gallbladder surgery finds 11,173. A search on the procedure tonsillectomy finds 8,459 published research papers. Looking at elective surgery, a search on the procedure facial laser resurfacing reveals 4,695 paper, facelift 2,340 papers, liposuction 3,146, Lasik 4,191, BOTOX 1,136 papers, Restylane 183 papers. However, this database contains zero papers on the Zerona laser. The statement: “Zerona, the most researched medical procedure on the market” is not remotely factual.
The company in its promotional literature cites 4 published studies on the Zerona laser. We will consider each of these studies:
1. Jackson RF, Dedo DD, Roche GC, Turok DI , Maloney RJ. Low-Level Laser Therapy as a Non-Invasive Approach for Body Contouring: A Randomized, Controlled Study
Lasers in Surgery and Medicine 41:799–809 (2009)
These authors investigated the use of low-level laser irradiation directed at the skin as a means of performing non-invasive body contouring of the waist, hips, and thighs. The authors state that their study was structured as a double-blind, randomized, placebo-controlled trial. The study included 67 volunteers. Subjects were randomized to low-level laser treatments three times per week for two weeks or a matching sham treatment. Measurements of the waist, hip and thighs was used as the treatment end point by comparing these measurements prior to treatment with those made at the end of the two week treatment period. The authors claimed that compared to controls, treatment patients showed a combined reduction of 3.51 inches, which was statistically significant compared to the control patients. The authors conclude that low-level laser was effective as a method of non-invasively contouring the body. The big problem with this study is it is not a double blind study. Double blind studies are studies where neither the subject nor the investigator know who is actually receiving treatment. This prevents the introduction of bias. However, this is not how this study was designed. The investigators who performed the treatments knew which device was actually a low-level laser and which device was the sham device. This means that investigators in some subtle way could have communicated their knowledge of which treatment the subject received. It is not hard to imagine that this could easily introduce study bias. Patients who have received encouragement of the likely success of their treatment might be more compliant with their usual diet and exercise during the course of treatment. In contrast, patients who consistently receive negative reinforcement from the investigator during the course of their treatment might not be as consistent with their usual diet and exercise program. This study flaw most likely accounts for any actual difference between the two groups.
Another issue with the study is the possibility of post-hoc data analysis. This generally means looking at the data after the study and finding the best way to present the data. The authors indicate that the overall success criterion determined by the FDA was a treatment difference of 35%. This equated to a combined circumference measurement reduction of 3.0 inches. It is interesting that this study exactly met this criterion. It is worth noting that the investigators knew which subjects were treated with the actual or the sham devices and these were the same investigators who also took the measurements. It is of concern that of 67 subjects, 8 subjects did not have circumference measurements recorded at the 2-week post-procedure measurements. Precisely half of these individuals had sham treatment and half had actual treatment. To handle this, the authors made up (fabricated) the data using the Last Observation Carried Forward method. This method is used to handle statistical analysis when patients drop out of a study. However, the absence of the data on these 8 patients is not the result of patient drop out, but, rather, investigator omission. Why might the investigator omit recoding this data even though this is the primary study endpoint? This is the effect of bias. There might be other explanations, however, it is likely that these investigators, knowing who was and was not treated by the actual device, recognized that the circumference measured on the final visit was inconsistent with the conclusions they anticipated. Failure to record this data may have been intentional or unintentional. In either case, this omission is highly damaging to the integrity of the study.
Under these circumstances, Last Observer Carried Forward method is not appropriate. At a minimum, the authors should have presented the analysis omitting these subjects. It would be essential to know that the statistical conclusions of these authors are supported by the data when these subjects are excluded. Even then the study is questionable because of the possibility of data manipulation. Because these authors failed to inform the readers of the effects of such an analysis, it can be concluded that excluding the subjects with omitted data substantially weakens the conclusions of the study. At the very least, the authors have subjected their data to post-hoc analysis, which is considered data manipulation that undermines study integrity. Given this weakness, and the fact that the study was not properly designed with double blind controls, the conclusions of this study should be considered unsubstantiated and unreliable. This study should not have been used as a basis for granting FDA clearance for the device.
2. Neira R, Jackson R, Dedo D, Ortiz CL, Arroyave JA. Low-level laser-assisted lipoplasty appearance of fat demonstrated by MRI on abdominal tissue. American J Cosmetic Surgery. 2001:18:133-140.
This is a study of 3 patients who had serial MRI before any treatment, after infiltration with tumescent anesthetic solution, and then after exposure to 4 and 6 minutes of Low-Level Laser (Electric diode 635nm laser). Following this the patients underwent liposuction. The study implies that each patient was subject to liposuction. The authors then analyzed the T1 weighted and T2 weight MRI images to conclude that low level laser energy applied to the outside of the body “liquefies fat by causing it to escape from inside the cell to outside (interstitial space).” Unfortunately authors make no effort to substantiate the changes in the MRI they claim exists. Looking at the images in the study, exposure of the abdomen to low-level laser treatment does not appear to make any differences the MRI images presented despite the author’s statements to the contrary. The authors fail to present any quantitative data to support their conclusions. The paper contains three scanning electron micrographs that the authors claim represent the tissue effects of the low level laser on adipose tissue. However, the authors do not explain how these images relate to their study. In fact no mention is made of subjecting the harvested fat to scanning electron microscopy and the material and methods section do not explain how these specimens were obtained. For this reason there is no logical connection between the presented scanning electron micrographs that illustrate this study and the study itself. These images appear to be very similar to images from the Neira, et. al. 2002 study.
3. Reduction in cholesterol and triglyceride serum levels following low-level laser irradiation: A noncontrolled, nonrandomized pilot study. American J Cosmetic Surgery. 2010; 27: 177-184.
The authors hypothesize that low-level laser irradiation (shining the laser on the skin) may suppress serum cholesterol and triglycerides by altering gene expression and inducing cellular adipocyte modifications. The authors claim that laser-induced alteration of cholesterol biosynthesis may play a vital role in the suppression of cholesterologenesis, the name for synthesis of cholesterol in the body. The authors make the claim this treatment could be used to lower serum cholesterol. The study included 19 patients between the age of 18 and 65 who were seen by the authors for liposuction. Prior to laser treatment, blood work was obtained to assess serum lipids. The subjects were treated with the Zerona laser for a total of 6 treatments over a 2 consecutive weeks (3 procedures per week each 2 days apart). The serum lipid levels were then rechecked after the course of treatment. The authors concluded that 84% of the study participants had a reduction of their serum cholesterol and this reduction was statistically significant. Unfortunately, as the authors indicate in the title of this paper, this is a uncontrolled and nonrandomized study. The series is not even a consecutive series. This means that we have no idea how these individuals came to be included in the study. For all we know, the individuals could have been included because their cholesterol was lower after the study. The authors attribute the decline in cholesterol to the low-level laser treatment.
Assuming that the authors did not cherry pick their data and this decline in cholesterol is real, is there any more likely explanation other than low-level laser? The answer is placebo effect. The placebo effect is the result the belief in a sham treatment. The patient’s in this study presented to the authors for liposuction. While the authors do not tell us what they told these individuals, presumable they were advised that the low level laser was an alternative to the liposuction procedure there were seeking. Believing in the effectiveness of the treatments might very well prompt these individuals to eat less and exercise more during the course of the treatment. The effect of this could more likely account for the noted change in cholesterol. It is interesting that these authors included very little information about the study participants such as their weights before and after the course of treatment. It is well known that even short-term weight reduction is associated with decreases in total cholesterol and serum light density lipid. These weaknesses make it difficult to place much stock in the conclusions drawn by these authors.
4. Neira R, Arroyave J, Ramirez H, Ortiz CL, Solarte E, Sequeda F, and Gutierrex MI. Fat Liquefaction: Effect of Low-Level Laser Energy on Adipose Tissue. Plast. Reconstr. Surg. 110:912-922, 2002
These investigators examined the effect of low-level laser energy in 12 patients who were exposed to 635-nm, 10-mW diode laser radiation for 0, 2, 4, and 6 minutes with and without tumescent liposuction. The authors claim that the adipose tissue was externally irradiated through the skin. Following this, superficial and deep fat samples were taken from the infraumbilical area. The authors then report in their methods section that fat samples extracted with out tumescent technique were also taken and irradiated after being harvested. The fat was then examined by scanning and transmission electron microscopy. The authors then describe the appearance of the adipose tissue according the the time of exposure. They observe that the specimens subject to tumescent solution and zero minutes of low level laser appear intact. After 4 minutes of exposure, the authors report partial adipocyte break down. After 6 minutes of exposure, “fat was completely removed from the cells and remained in the interstitial space. Comparing the fat that received tumescent anesthesia with fat that did not have this treatment, the authors conclude that the tumescent solution enhances the effect of low-level laser treatment. Analyzing the transmission electron micrographs, the authors conclude that laser exposure for 6 minutes: “ the (adipocyte) membrane is temporarily disrupted, creating a transitory pore that allows the liquefied fat to come out of the cell and be released into the interstitial space.” The authors did not report the difference between the superficial and deep fat specimens. Also the authors state that the low-level laser creates a transitory pore through which fat leaks out of the cell. However they do not in fact present evidence of this mechanism, which must be considered an unsubstantiated conjecture.
One of the measures of the validity of a scientific work is reproducibility. Not all scientific work has been taken up by other laboratories to validate a given set of experiments. This is not the case here. Investigators Brown, Rohrich, Kenkel, and Young, et. al. (Brown SA, Rohrich RJ, Kenkel J, Young L, Hoopman J, and Coimbra M. Effect of Low-Level Laser Therapy on Abdominal Adipocytes before Lipoplasty Procedures. Plast. Reconstr Surg. 2004; 113:1796-1804.) examined the validity of the study performed by Neira and colleagues, described above. Brown and co-workers took several approaches to investigate these claims. They used a low-level 635-nm laser to directly treatment cultured human preadipocytes for 60 minutes, a far longer and more intense exposure than that used by Neira and co-workers. Yet scanning electron microscopy did not detect a change in appearance between these irradiated cells and the non-treated control cell. The authors also studied a porcine model to compare lipoaspriates after exposure to low-level laser for 30 minutes with traditional liposuction, and ultrasound-assisted liposuction. Again, the tissue specimens were examined with light microscopy and scanning electron microscopy. Porcine skin exposure times to low-level laser prior to liposuction were 0, 15, 30, and 60 minutes with and without liposuction wetting solution. There were no differences in the appearance of the fat cells seen between the low-level laser specimens and standard liposuction with no exposure to low-level laser. Finally the authors studies three humans undergoing liposuction. Two patients had areas that were being aspirated as part of a planned liposuction exposed to low level laser prior to aspiration. No structural differences were detected in the human fat when comparing the areas irradiated with low-level laser and those areas that were not irradiated. These authors concluded exposure to low-level laser had no effect on the adipocytes. These authors found no support for the study of Neira and could not reproduce their work.
In Part 2, we will look at how this faulty data undermines the claims by the manufacture regarding the Zerona laser.