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Injectable Treatments for Adipose Tissue: Terminology, Mechanism, and Tissue Interaction
Abstract
Just as injectable fillers have addressed the need for non-surgical methods to restore desired volume, a number of injectable therapies purpor to play a comparable role to reduce undesired volume.
To review published literature on the history, mechanism of action, and tissue interaction of injectable methods that aim to reduce localized collections of fat.
Mesotherapy is an injection technique that has medical and cosmetic applications and is often confused with injectable fat loss therapies; injection lipolysis describes non-ablative fat reduction with agents (such as beta-agonists) that activate adipocyte lipolytic pathways; and adipolytic therapy using biologic detergents (such as deoxycholate) leads to permanent adipocyte ablation. None of these therapies have been cleared for use in fat reduction by any regulatory authority worldwide.
The mechanism of action and tissue effects of injectable fat reducing compounds are diverse but are becoming increasingly understood.
... Na lipoclasia se busca redução da gordura localizada com a morte ou destruição do adipócito. Na lipólise, o adipócito é estimulado a liberar a gordura, mas sem sofrer danos celulares estruturais 18 . O processo de lipoclasia quimicamente induzida por FC e DC revelou que o componente ativo para a redução de gordura era o DC, que causa necrose dos tecidos adiposos, diferentemente do que se supunha a princípio, pois a remoção da gordura era atribuída a FC, a qual na verdade atua apenas como emulsificante do DC 14 . ...
... Complicações relatadas incluíram nódulos e alopecia 16,17,19 . Os estudos iniciais sobre o tema aplicavam o uso de DC e FC, seus resultados foram positivos, indicando que apenas o DC possuiu ação na necrose dos adipócitos 18 . Estudos mais recentes passaram a utilizar apenas o DC para redução de gordura localizada obtendo resultados satisfatórios e reações adversas pequenas e localizadas. ...
... Rotunda et al., (2009) realizaram uma revisão de literatura sobre métodos injetáveis para redução de gordura localizada. De acordo com os autores, o DC solubiliza as membranas celulares, induz necrose tecidual, inflamação e redução permanente do volume. ...
Objetivo: avaliar as particularidades do uso de injetáveis na redução de gordura localizada facial, com foco no ácido desoxicólico e desoxicolato de sódio, com intuito de analisar sua eficácia e apresentar informações relevantes para a prática clínica. Revisão Bibliográfica: Os compostos que promovem lipoclasia, ácido desoxicólico e desoxicolato de sódio têm sido usados em tratamentos injetáveis para diminuição de depósitos de gordura localizados na face. O ácido desoxicólico é um ácido biliar sintético recentemente introduzido no âmbito das terapias em rejuvenescimento para a redução da gordura submentoniana. O desoxicolato de sódio é o sal do ácido desoxicólico, possui ação detergente e solubiliza as membranas celulares, induz necrose tecidual e redução do volume. A maioria dos estudos avaliados tratou a adiposidade da região submental, no entanto também foram relatados tratamentos nas regiões infrapalpebrais, mandibulares e nas regiões de terço médio e inferior de face. Observou-se que ambos as substâncias são eficazes e seguras, produzem resultados satisfatórios e causam reações adversas leves e locais. Conclusão: A redução de gordura localizada na face através da injeção de desoxicolato de sódio ou ácido desoxicólico possui uma ação singular no tratamento da gordura localizada por induzir a necrose dos adipócitos e neocolagênese.
... 12,13,[15][16][17][18][19][20] Generally, diversified nonsurgical techniques suitable for the reduction of localized fat and applied in clinical practice have lipolytic action aimed at reducing the local adiposity. 21 Lipolysis is the term given to the hydrolysis of lipids into their respective metabolites: fatty acids and glycerol. This process occurs in the adipocyte and is physiologically controlled by the enzymatic action of the hormone-sensitive lipase (HSL) and lipoprotein lipase. ...
... The lipoprotein lipase is synthesized in the adipocytes and transferred to the endothelial cells of blood capillaries (extracellular), and is responsible for the chylomicron breaks arising from food and very-low density lipoproteins. 6,21,22 The hypertrophy caused by increased lipid inclusion in the adipose tissue results in several metabolic consequences for the adipocytes. The physiologic lipolytic process induces other processes such as innate immune response activation and the activation of resident macrophages in the adipose tissue. ...
... Such methods are associated with physiologic lipolytic signaling pathways. 21 ...
Background:
The adipocytolytic non-surgical esthetic procedures are indicated for the reduction of localized fat and are effective in reducing local adiposity through the ablation of adipocytes with fast and lasting results, besides causing local inflammation.
Objective:
This study aimed to characterize the adipocytolytic procedures and correlate the phases of the inflammatory process with the results obtained from such procedures, in order to clarify the role of inflammation triggered by the adipocytolytic procedures and its relation with the lipolytic process, with a focus on body shaping.
Methods:
This work is an integrative literature review that presents a total of 72 articles published between 1998 and 2015, derived from the PubMed database, in order to establish a relationship between clinical and basic science research, assuming an important role in medical practice based on evidence.
Results:
The results show that the adipocytolytic procedures are characterized by triggering inflammation arising from the disruption of adipocytes by interfering with the lipolytic signaling pathways in both acute and chronic phases of inflammation through the direct action of proinflammatory cytokines or catecholamines. Therefore, inflammation plays an important role in modulating the lipolytic process, influencing body shaping.
Conclusion:
The inflammatory process assists the adipolytic process in all stages of inflammation, contributing to the reduction of body contouring.
... 19,20 Robust evidence for the efficacy and safety of non-specific, unapproved, lipolytic injectables is also limited. 10,21 ATX-101 is a proprietary formulation of synthetically derived deoxycholic acid (DCA) that has shown efficacy and acceptable tolerability in phase I and II studies for the reduction of unwanted SMF. [22][23][24][25] DCA disrupts the membranes of adipocytes through solubilization of the membrane lipids, 26 leading to cell breakdown, and induces a local inflammatory response that clears the adipocyte debris. ...
... [22][23][24][25] DCA disrupts the membranes of adipocytes through solubilization of the membrane lipids, 26 leading to cell breakdown, and induces a local inflammatory response that clears the adipocyte debris. 21,26,27 In relatively protein-rich tissues, such as muscle and skin, the action of DCA is attenuated by increased protein binding. 26 The results of a large, European, randomized, double-blind, placebo-controlled, parallel-group phase III clinical study for evaluation of the efficacy and safety of ATX-101 treatment for the reduction of SMF, based on physician-and patient-reported outcomes, are presented here. ...
... Appropriate, practiced technique is fundamental to adequate ATX-101 delivery into the SMF and to achieve efficient reduction with limited side-effects. The local inflammatory response that is induced by adipocytolysis, and is responsible for the clearance of cellular debris and removal of breakdown products, 21,26,27 may also contribute to the observed TEAEs. The transient nature of these TEAEs was predictable based on phase I studies, which showed that ATX-101 does not accumulate at the injection site and is absorbed rapidly and removed through protein binding. ...
Background
Unwanted submental fat (SMF) may result in an unattractive chin profile and dissatisfaction with appearance. An approved and rigorously tested non-surgical method for SMF reduction is lacking. Objective
To evaluate the efficacy and safety of ATX-101 for the pharmacological reduction of unwanted SMF in a phase III randomized, double-blind, placebo-controlled study. Methods
Patients (n = 360) with moderate or severe SMF were randomized to receive ATX-101 1 or 2 mg/cm2 or placebo injected into their SMF for up to four treatments ~28 days apart, with a 12-week follow-up. Coprimary efficacy endpoints were the proportions of treatment responders, defined as a ≥1-point reduction in SMF on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS), and those satisfied with their appearance in association with their face and chin after treatment on the Subject Self-Rating Scale (SSRS score ≥4). Secondary efficacy endpoints included a ≥1-point improvement in SMF on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) and changes in the Patient-Reported Submental Fat Impact Scale (PR-SMFIS). Additional patient-reported outcomes and changes in the Skin Laxity Rating Scale were recorded. Adverse events (AEs) and laboratory test results were monitored. ResultsCompared with placebo, a greater proportion of patients treated with ATX-101 1 and 2 mg/cm2 showed a ≥1-point improvement in CR-SMFRS (58.3% and 62.3%, respectively, vs. 34.5% with placebo; P < 0.001) and patient satisfaction (SSRS score ≥4) with the appearance of their face and chin (68.3% and 64.8%, respectively, vs. 29.3%; P < 0.001). Patient-reported secondary efficacy endpoints showed significant improvements in SMF severity (PR-SMFRS; P = 0.009 for ATX-101 1 mg/cm2, P < 0.001 for ATX-101 2 mg/cm2 vs. placebo) and emotions and perceived self-image (PR-SMFIS; P < 0.001). No overall worsening of skin laxity was observed. AEs were mostly transient, mild to moderate in intensity and localized to the treatment area. ConclusionATX-101 was effective and well tolerated, and may be an alternative to surgery for patients desiring improvement of their submental profile.
... 14 When injected subcutaneously, it physically disrupts adipocyte cell membranes, leading to local adipocytolysis and subsequent cell death. 16,17 Its selectivity for fat cells may result from the neutralizing effects of albumin and tissue-associated proteins, which attenuate the cytolytic activity of deoxycholic acid, thereby protecting nonadipose cells. 18,19 Adipocytolysis predictably elicits a mild, local, and transient inflammatory response, with macrophage infiltration diminishing over time as fibroblasts and fibrosis predominate. ...
... 5,21,22,26,28,[30][31][32] As described earlier, injection of ATX-101 results in adipocytolysis, with destroyed adipocytes no longer able to store or accumulate fat. 16,17,31 Adipocytolysis and the release of cell contents and membrane fragments elicit a mild, local inflammatory response, resulting in neutrophilic inflammation and attracting macrophages. 18,20,21 Local swelling and irritation likely result from adipocytolysis, inflammation, and temporary vascular injury (also observed at day 1); leakage from damaged vessels may also contribute to bruising. ...
Background:. ATX-101 is an injectable, synthetically derived formulation of deoxycholic acid used for submental fat reduction.
Methods:. A narrative review of references relevant to the mechanism of action of ATX-101 and its relationship to efficacy and inflammatory adverse events was conducted.
Results:. When injected into subcutaneous fat, deoxycholic acid physically disrupts adipocyte cell membranes, leading to local adipocytolysis, cell death, and a mild, local inflammatory reaction consisting of macrophage infiltration and fibroblast recruitment. At Day 28 postinjection, inflammation largely resolves, and key histologic features include fibrotic septal thickening, neovascularization, and atrophy of fat lobules. Based on the mechanism of action of ATX-101 and the demonstrated inflammatory response, localized inflammation and swelling are expected following treatment. Indeed, postinjection swelling and other local injection-site events, including pain, erythema, and bruising, are common during and after treatment. Because of inflammatory sequelae following injection, reduction in submental fat is gradual and may require months before the full response is apparent. Patients may also require multiple treatment sessions to achieve their treatment goals. Repeated treatments may result in less pain and swelling over time owing to a combination of factors, including less target tissue allowing for lower doses/injection volumes, persistent numbness, and greater tissue integrity from thickened fibrous septa.
Conclusions:. Physicians can manage expectations by counseling patients that, based on the mechanism of action of ATX-101 and data from pivotal clinical trials, ATX-101 treatment results in localized inflammation/swelling and gradual submental fat reduction. Patient education about common local adverse events is critical.
... [35][36][37] SD acts like a detergent, causing adipolysis (or adipocytolysis) when injected directly into the area with extra fat tissue. [36,38] SD lyses the adipocyte's membrane, which is deficient in cell associated proteins, resulting in necrosis. [37,38] The usage of SD has been limited to the removal of local fat tissue because the required active dose is high, 2 mg/ml (~5 mM) and 0.2 ml/cm 2 . ...
... [36,38] SD lyses the adipocyte's membrane, which is deficient in cell associated proteins, resulting in necrosis. [37,38] The usage of SD has been limited to the removal of local fat tissue because the required active dose is high, 2 mg/ml (~5 mM) and 0.2 ml/cm 2 . [37] Planar tricyclic oxygen containing xanthene molecules are known to have various bioactivities. ...
Overcrowded adipocytes secrete excess adipokines and cytokines under stress, which results in a deregulated metabolism. This negative response to stress increases the possibility of obesity and several of its associated diseases, such as cancer and atherosclerosis. Therefore, a reduction in the number of adipocytes may be a rational strategy to relieve the undesired expansion of adipose tissue. A newly synthesized xanthene analog, MI-401, was found to have two distinct effects on the regulation of the adipocyte’s life cycle. MI-401 efficiently down regulated the expression of transcription factors, PPARγ and C/EBPα, and lipogenesis proteins, FAS and FABP4. This down regulation resulted in the inhibition of adipogenesis. Without newly differentiated adipocytes, the total number of adipocytes will not increase. In addition to this inhibitory effect, MI-401 was able to actively kill mature adipocytes. It specifically triggered apoptosis in adipocytes at low micro molar concentration and spared preadipocytes and fibroblasts. These dual functionalities make MI-401 an effective agent in the regulation of the birth and death of adipocytes.
... 1 Despite lack of approval by any regulatory body, PC/DC combinations have been used off-label by healthcare practitioners to reduce subcutaneous fat in selected patients. 2,3 In Europe, the only drug with CE marking (approval) for the reduction of localized fat is Aqualyx (Marllor International; San Giovanni in Marignano, Italy). 4 Currently, it is approved in approximately 50 countries. ...
... This case corroborates the notion that not all DC-based solutions are fat-tissue selective, as evidenced elsewhere. 2,3,12 Therefore, injecting such products (eg, Aqualyx) to reduce localized adiposity can result in adverse events such as skin necrosis, which was demonstrated recently by a multiplex assay performed by Duncan. 4 As emphasized previously by Rauso et al, 8 because the safety of DC itself is still under investigation, it is surprising that this DC-based solution could have gained approval as a medical device. ...
Injectable fat-reduction techniques emerged in the world literature in 2001, when Patricia Rittes, a dermatologist in Sao Paulo, Brazil, reported reduction of infraorbital fat after direct, transcutaneous injection of phosphatidylcholine (PC) combined with sodium deoxycholate (DC) solution.1 Despite lack of approval by any regulatory body, PC/DC combinations have been used off-label by healthcare practitioners to reduce subcutaneous fat in selected patients.2,3
In Europe, the only drug with CE marking (approval) for the reduction of localized fat is Aqualyx (Marllor International; San Giovanni in Marignano, Italy).4 Currently, it is approved in approximately 50 countries. Aqualyx is a DC-based solution with a lactose-based delivery system, formulated to control and enhance the action of external ultrasound waves for the microcavitation of adipose tissue.5 It does not contain PC. Aqualyx was designed for the medical treatment (reduction) of localized adipose tissue5 and is sold exclusively to physicians trained in intralipotherapy, the injection technique for its insertion.6 The product has been in clinical use since 2009 for the nonsurgical reduction of localized adiposity, lipohypertrophy, subcutaneous lipohyperplasia, and “buffalo hump”.6-8
Aqualyx is an aqueous microgelatinous solution comprised of the following: polymer of 3:6-anhydro-L-galactose and D-galactose; buffer systems; 3-alpha-12alpha-dihydroxy-5-beta-24-oico cholanic acid sodium salt; and saline solution.7,8 The solution appears similar in composition to DC, but it is considered a medical device—not a drug. A claim regarding this matter has been submitted to the Italian Ministry of the Health.8
Aqualyx is marketed as a 2-step product: immediately following injection (step 1), it is recommended that external ultrasonography be performed (step 2).5 However, …
... Adipocyte lipolysis refers to the intracellular degradation of triglycerides into free fatty acid and glycerol components, which occurs in response to cell surface beta1/beta2 adrenoceptor stimulation by oral medications and injectable agents (e.g., salmeterol and catechol-containing compounds like isoproterenol). 1 Lipolysis thus mobilizes intraadipocyte fat stores while preserving the integrity and viability of cell membranes. 2 Adipolysis or adipocytolysis, however, describes the outright solubilization or perforation of adipocyte membranes leading to complete ablation of fat. 2,3 Although established body contouring therapies like "cryolipolysis" and "laser lipolysis" purport a lipolytic mechanism of action, nothing could be further from the truth. ...
... 2 Adipolysis or adipocytolysis, however, describes the outright solubilization or perforation of adipocyte membranes leading to complete ablation of fat. 2,3 Although established body contouring therapies like "cryolipolysis" and "laser lipolysis" purport a lipolytic mechanism of action, nothing could be further from the truth. Current "cryolipolysis" technology uses controlled thermal diffusion to preferentially target subcutaneous fat while sparing more superficial or deeper tissue layers. ...
... Injectable agents such as sodium deoxycholate (DC) produce adipolysis, degrading adipocyte cell membranes, and completely ablating fat. 106 Deoxycholate is an animal-derived bile salt and biologic detergent that helps solubilize phosphatidylcholine (PC), a soyderived phospholipid once believed to be the primary component of this adipolytic formula. Given recent research confirming that DC is just as potent as PC/ DC at causing adipocyte lysis and cell death, DC is now considered the major active component. ...
... Injection lipolysis describes the use of injectable agents to mobilize adipocyte fat stores while, unlike adipolytic agents, preserving the integrity and viability of adipocyte cell membranes. 106 Catecholcontaining drugs-isoproterenol, 125,126 isoprenaline, 127,128 and terbutaline 127 -are one such class of medication. These nonspecific b-AR agonists have all been shown to activate the lipolytic pathway by stimulating b 1 -AR and b 2 -AR on the surface of adipocytes. ...
The demand for aesthetic body sculpting procedures has expanded precipitously in recent years. Subcutaneous adipose tissue (SAT) deposits of the central abdomen are especially common areas of concern for both males and females.
To review the available literature regarding the underlying pathophysiology of subcutaneous fat accumulation in the abdominal area and available treatment options.
A MEDLINE and Google Scholar search was performed accordingly.
The preferential accumulation of SAT in the central abdomen is attributable to the reduced lipolytic sensitivity of its adipocytes. A number of therapeutic options are available for the treatment of central abdominal adiposity. Cryolipolysis, high-intensity focused ultrasound, nonthermal ultrasound, radiofrequency, and injection adipolysis lead to adipocyte destruction through multiple different mechanisms. Nonablative modalities such as injection lipolysis mobilize fat stores from viable adipocytes, although its effects may be curtailed in obese patients. Liposuction through tumescent technique, however, mechanically extricates SAT.
Although tumescent liposuction remains the gold standard for SAT removal, less invasive ablative and nonablative options for targeting localized deposits of adipose tissue now permeate the aesthetic marketplace. Limited results associated with these modalities mandate multiple sessions or combination treatment paradigms.
... 11 ATX-101, the subject of this study, is an injectable proprietary formulation of synthetically derived deoxycholic acid (DCA), which disrupts adipocyte membranes leading to irreversible cell breakdown (adipocytolysis). 12 After adipocytolysis, a mild inflammatory response is induced, with macrophage recruitment and phagocytosis, [12][13][14] through which cellular debris is cleared over time. Plasma lipid levels show no meaningful increase over time after ATX-101 treatment. ...
... Adipocytolysis leads to a mild inflammatory response and clearance of the lysed cellular material from the injection site. [12][13][14] Therefore, these AEs may result from a combination of both the mechanism of delivery and action of the agent. It is possible that higher doses of DCA might be associated with more severe AEs affecting nonadipose cell types. ...
Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation.
To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF.
In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm(-2) ) or placebo injections into their SMF at ≤4 treatment sessions ~28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders (patients with ≥1 point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale [CR-SMFRS]) and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored.
Significantly more ATX-101 recipients met the primary endpoint criteria versus placebo: on the clinician scale, 59.2% and 65.3% of patients treated with ATX-101 1 and 2 mg cm(-2) , respectively, were treatment responders versus 23.0% for placebo (CR-SMFRS; P<0.001); on the patient scale, 53.3% and 66.1%, respectively, versus 28.7%, were satisfied with their face/chin appearance (SSRS; P<0.001). Calliper measurements showed a significant reduction in SMF (P<0.001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 versus placebo. Most adverse events were transient and associated with the treatment area.
ATX-101 was effective and well tolerated for non-surgical SMF reduction. This article is protected by copyright. All rights reserved.
... Pure pigmentation and vascular problems account for only 19% of dark eye circles, and structural problems such as higher preseptal thickness and retro-septal orbital fat bulging contribute to the remaining causes [26,27]. Clinically, many transconjunctival or minimally invasive lower blepharoplasty techniques (such as injection lipolysis or laser resurfacing/lipolysis) have been reported for selective control of retro-septal fat and preseptal tissue tightening [4][5][6][7]28]. ...
Laser lipolysis may be considered for selective removal of excess orbital fat via minimally invasive lower blepharoplasty. To control the energy delivery to a precise anatomic location while avoiding complications, ultrasound guidance can be utilized. Under local anesthesia, a diode laser probe (Belody, Minslab, Korea) was introduced percutaneously to the lower eyelid. The tip of the laser device and changes in orbital fat volume were carefully controlled with ultrasound imaging. A 1470-nm wavelength was used for orbital fat reduction (maximal energy 300 J), and a 1064-nm wavelength was used to tighten the lower eyelid skin (maximal energy 200 J). From March 2015 to December 2019, a total of 261 patients underwent ultrasound-guided diode laser lower blepharoplasty. The procedure took 17 min on average. Total energy of 49 J–510 J (average = 228.31 J) was delivered in 1470-nm wavelengths or 45–297 J (average = 127.68 J) was delivered in 1064-nm wavelengths. Most patients were very satisfied with their results. Fourteen patients experienced complications, including nine cases of transient hypesthesia (3.45%), and three skin thermal burns (1.15%). However, these complications were not observed after strict control of the energy delivery below 500 J for each lower lid. Improvement in lower eyelid bags can be achieved using a minimally invasive approach in selected patients with ultrasound-guided laser lipolysis. It is a fast and safe procedure that can be performed in the outpatient setting.
... Over the years reduction of submental fat has been achieved with invasive surgical procedures such as liposuction, direct fat excision, and/or face/neck lift. However, due to the complications associated with invasive surgeries and their long recovery times, they are not a viable option for some patient populations [5][6][7]. ...
Background: Submental fullness has been a concern for patients in dermatology for years. Liposuction and cosmetic surgery were considered the mainstay for elimination of unwanted submental fat. However, these procedures are invasive and associated with major complications like prolonged recovery times, and the risk of contour irregularities. In 2015, Kybella (deoxycholic acid) was approved as a first-in-class injectable agent for the treatment of submental fullness. Although, it is non-invasive and has less complications than plastic surgery, it is still associated with adverse effects such as pain, swelling/edema, and bruising. The most concerning adverse effect for patients is the prolonged inflammation that may occur for up to 2 weeks post-injection. Objective: This is a comparison trial of deoxycholic acid injections with or without triamcinolone acetate for the reduction of submental fat in one patient. The study will also assess the effect of triamcinolone acetate on post-injection inflammation associated with deoxycholic acid injection in the treatment of submental fullness. Method: A 35-year-old female presented for evaluation of submental fullness and opted for treatment with Kybella. Her right submental treatment area was injected with 2ml of deoxycholic acid 10mg/ml plus 0.2ml triamcinolone acetate. The left submental treatment area was treated with 2ml of deoxycholic acid 10mg/ ml alone. The patient was observed over a duration of 3 months to evaluate inflammation and treatment response between the two treatment zones. Results: This split-neck study resulted in decreased postinjection swelling. However, at 3-month follow-up, there was no clinical improvement to the submental fullness bilaterally. Limitations: Small sample size, lack of objective measures, possible diffusion between treatment zones, and prior deoxycholic acid treatment. Conclusion: Triamcinolone can decrease post-injection swelling if given as an adjunct to Kybella treatment. Kybella; Submental; Triamcinolone; Deoxycholic Acid; Inflammation
... When injected into subcutaneous fat, the active ingredient of ATX-101 (deoxycholic acid) disrupts adipocyte cell membranes, and a subsequent inflammatory response clears the injection site of cellular debris and liberated lipids. [16][17][18][19][20][21] Treatment of jowl fat has been safely accomplished with ATX-101. 22,23 The current study was conducted to evaluate the efficacy and safety of ATX-101 for reduction of jowl fat. ...
Background:
Jowl fat overhang can reduce jawline definition. The most common treatment to reduce jowl fat is liposuction. ATX-101 (deoxycholic acid injection), a minimally invasive treatment approved for submental fat reduction, may also be an effective treatment for jowl fat. The current study evaluated the efficacy and safety of ATX-101 treatment for reducing jowl fat.
Methods:
In this prospective single-site study, 66 adults were treated for excess jowl fat with ATX-101 (area-adjusted dose: 2 mg/cm). Eligible patients had pinchable fat on the jawline and relatively minimal skin laxity in the jowl. Depending on the size of the treatment area, ATX-101 injections of 0.2 ml spaced 1.0 cm apart or 0.1 ml spaced 0.50 to 0.75 cm apart were administered. Improvement in jowl appearance was assessed ≥6 months after last treatment in person by the clinician. Improvement was also assessed by the patient and two independent plastic surgeons using blinded before/after treatment photographs. Safety was evaluated via adverse events (AEs).
Results:
The mean number of ATX-101 treatments received was 1.8, with a mean injection volume of 0.8 ml/treatment/jowl. The majority of patients (98%) experienced an improvement in jowl appearance. Common AEs were injection-site edema, numbness, tenderness, and bruising. Injection-site marginal mandibular nerve paresis and alopecia were experienced by three patients each; all events resolved without sequelae.
Conclusions:
ATX-101 effectively reduced jowl fat and was well tolerated in this small cohort. Care should be taken when injecting ATX-101 into jowl fat to avoid underlying anatomic structures such as the marginal mandibular nerve.
... The active ingredient of ATX-101, deoxycholic acid, disrupts adipocyte cell membranes when injected subcutaneously into fat, inducing an inflammatory response to clear cellular debris and liberated lipids from the injection site. [18][19][20][21][22][23] Since its initial approval in the United States in 2015, practitioners have reported using ATX-101 to reduce areas of localized body fat such as along the bra line. 24,25 In addition, it has been suggested that ATX-101 may be a suitable treatment for reduction of upper arm, axillary, and knee fat. ...
Facial appearance is critical to physical attractiveness, and maintaining a youthful face and neck is a major motivation for individuals seeking facial cosmetic procedures. A strong mandibular border without prominent jowls is one sign of a youthful face as jowling occurs with age, contributing to squaring of the face and loss of jawline definition. Excess jowl fat has traditionally been reduced with surgical liposuction when jowling is caused by fat flow across the mandible. The approval of ATX-101 (deoxycholic acid injection) for submental fat reduction provides a minimally invasive technique that may also be suitable for jowl fat reduction. The author has developed novel facial markings that consistently isolate the jowl fat area of concern at the mandible for treatment with ATX-101. The current work refreshes physicians on important jowl anatomical structures, defines the facial markings that consistently isolate the jowl, and describes an injection technique to safely treat excess jowl fat with ATX-101.
... Cryolipolysis was recently cleared in the United States for use in the submental area (using the CoolMini™ applicator; Zeltiq Aesthetics, Inc., Pleasanton, CA, USA) and may offer a less invasive alternative to surgery or liposuction for reduction of SMF [27]. Injectable therapy with phosphatidylcholine/deoxycholate also offers a less invasive option for reduction of SMF [28,29]; however, these products are produced by chemical compounding and are not regulated by the US FDA [30], Health Canada, or the CE commission. In contrast, ATX-101 (deoxycholic acid [DCA] injection; KYBELLA ® in the United States and BELKYRA™ in Canada; Kythera Biopharmaceuticals, Inc., Westlake Village, CA, USA [an affiliate of Allergan plc, Dublin, Ireland]) is the first injectable drug approved by the FDA and Health Canada for improvement in the appearance of moderate-to-severe convexity or fullness associated with SMF [31]. ...
Introduction:
The shape and contour of the chin and neck play an important role in facial aesthetics. As such, excess fat within the submental area (double chin) can negatively affect facial aesthetics and body image. Common treatments for submental contouring include invasive procedures such as surgical rejuvenation and targeted liposuction. Energy devices (lasers, radiofrequency, and ultrasound) may be used to improve submental skin laxity while cryolipolysis was recently cleared in the United States for use in the submental area. However, ATX-101 (deoxycholic acid injection) is the only injectable drug approved in the United States and Canada for reduction of submental fat.
Areas covered:
The efficacy and safety of ATX-101 have been extensively evaluated in a global clinical development program including multiple Phase I/II studies and four large Phase III trials. Available data from ATX-101 trials are reviewed. Expert Review: Injectables have been well established for facial rejuvenation. Extending injectable treatment into the chin and neck is a major advance for nonsurgical cosmetic correction. Overall, the evidence supports ATX-101 as a safe and effective, minimally invasive treatment alternative for reduction of submental fat that will provide a major tool for the aesthetic physician.
... As an exogenous subcutaneous injection, DCA disrupts the cell membranes of fat cells leading to focal adipocytolysis. 4,6 The ensuing local inflammation with neutrophils and T-cells attracts macrophages to remove the cellular debris and increases total collagen. 4,7 The activity of DCA is attenuated by albumin and tissue-associated protein; thus, surrounding skin and muscle tissue (which are protein rich) are mostly unaffected. ...
Objective:
To review trials evaluating purified synthetic deoxycholic acid (DCA; ATX-101) for the reduction of submental fat (SMF).
Data sources:
A literature search was conducted using MEDLINE (1946 to week 4 of April 2016) and Evidence Based Medicine Database (1974 to 6 May, 2016). Keywords searched included deoxycholic acid, ATX-101, and submental fat.
Study selection and data extraction:
All human studies published in English that addressed the effects of DCA for the reduction of SMF were selected for analysis.
Data synthesis:
Five phase III, multicenter, randomized, double-blinded clinical trials enrolling more than 1700 patients have demonstrated the efficacy of ATX-101 in the reduction of SMF via a variety of validated scales as well as objective measurements. Purified synthetic DCA 2 mg/cm(2) injected monthly for 4 to 6 treatment sessions demonstrated improvement in scales evaluated by both clinicians and patients. Improvement in skin caliper measurements of SMF and Magnetic Resonance Imaging (MRI) provide objective evidence of the efficacy of ATX-101. Adverse events (AEs) are very common but are transient and localized to the treatment area. Pain at the injection site is the most common AE, occurring in more than 80% of patients treated. Other common AEs include swelling, bruising, numbness, and induration. Appropriate injection technique is patient specific and requires detailed knowledge of the submental anatomy to minimize AEs.
Conclusions:
ATX-101 is the first pharmacological intervention approved for the reduction of SMF and offers an alternative to invasive measures to improve the submental profile and positively affect patient self-image.
... However, they may be appropriate for patients who are unwilling or unable to undergo surgical reduction of small collections of fat, and for patients who desire touchups for liposuction-induced irregularities. 1 Injectable fat-reducing techniques emerged in the world literature in 2001, when Patricia Rittes, a dermatologist in São Paolo, Brazil, reported reduction of infraorbital fat using direct, transcutaneous injection with a phosphatidylcholine (PC)-based product (Lipostabil; Sanofi-Aventis, Paris, France). 2 Lipostabil is marketed for intravenous use in Europe, South America, and South Africa as a treatment for numerous fat-related disorders, including hyperlipidemia, angina pectoris, and diabetic angiopathy. Lipostabil consists of soy-derived PC (5%), its solvent (sodium deoxycholate [DC]; 2.5%), dl-a-tocopherol (vitamin E), sodium hydroxide, ethanol, and benzyl alcohol, in sterile water. ...
Injectable fat-reducing therapies are not an alternative to liposuction. Rather, they may be best suited for patients who are unwilling or unable to undergo surgical reduction of small collections of fat, and for patients who desire touchups for liposuction-induced irregularities.
The authors report their 4-year experience with a novel injectable CE-marked drug, used in an off-label manner.
Between October 2009 and November 2013, 186 patients were treated by injection of an adipocitolytic solution in 1 of 4 private Italian aesthetic facilities, by 1 of 4 independent physicians. Treated areas included the neck, hips/saddlebags, abdomen/love handles, inner thighs, and buffalo hump. Complications and side effects were documented.
All patients experienced mild to moderate swelling and reddening of the skin, which resolved 3 to 5 days after injection. No major complications or side effects occurred, such as necrosis. Rates of transient events were as follows: hematoma, 1.61%; paresthesia, 1.07%; and ecchymosis, 6.45%. Pruritus was reported by 21.5% of patients, which began 3 to 7 days following injection. Subcutaneous nodules were noted in 1.61% and resolved within 4 months of injection. A transitory "unusual sensation" was reported by 12.9% of patients, which lasted up to 2 months after final injection.
Results demonstrate that this CE-marked agent appears to be effective and safe for medical treatment of fat reduction.
4 Therapeutic.
© 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.
... Lipolysis denotes the mobilization of intraadipocyte fat stores without disturbing cellular integrity and viability, which is typically a direct result of cell surface beta1/beta2 adrenoceptor stimulation. 8 Adipolysis (or adipocytolysis), on the other hand, describes the outright destruction of adipocytes and their cell membranes by various mechanisms, such as what is seen following "cryolipolysis." 8 Cryoadipolysis or lipocryolysis are thereby vastly more appropriate terms for this modality. ...
... 7,8 When injected subcutaneously, DCA physically disrupts the cell membranes of adipocytes causing focal adipocytolysis, the targeted destruction of fat cells, as shown by in vivo and in vitro studies. [9][10][11] The cytolytic activity of DCA is attenuated by albumin and tissue-associated protein; therefore, when injected into subcutaneous fat tissue, nearby relatively protein-rich tissues, such as skin, muscle, and blood vessels, remain largely unaffected, a feature that may contribute to an enhanced safety margin. 11 As shown in previous studies, injection of DCA and the resultant adipocytolysis elicits a mild and local inflammatory response in which macrophages are attracted to the area; natural processes then eliminate cellular debris and liberated lipids. ...
BackgroundATX-101 (deoxycholic acid injection, Kythera Biopharmaceuticals, Inc.) is a proprietary formulation of pure synthetic deoxycholic acid (DCA). It is undergoing clinical investigation as an injectable drug for contouring the submental area by reducing submental fat (SMF). When injected into subcutaneous fat, ATX-101 causes focal adipocytolysis, the targeted destruction of fat cells.Objectives
This phase 1 study evaluated the safety, pharmacokinetics (PK), and pharmacodynamic effects of ATX-101 (100-mg total dose).Methods
Following PK evaluation of baseline endogenous DCA, lipids, and adipokines in the initial stage of the study (samples collected at hours 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, 15.5, and 24.5), 10 subjects received subcutaneous injections of ATX-101 into abdominal fat. PK evaluation of DCA, lipids, and adipokines was repeated in the second phase of the study.ResultsAfter ATX-101 injections, plasma concentration of DCA increased transiently, reached a maximum plasma concentration rapidly, and returned to endogenous concentrations within 12 h postdose. ATX-101 injection was not associated with any clinically meaningful changes in systemic concentrations of total cholesterol, total triglycerides, free fatty acids, C-reactive protein, or interleukin-6. Adverse events were mild in severity, transient, and showed a temporal relationship to dosing.Conclusions
This study demonstrated favorable safety and PK profiles, and no clinically meaningful changes in DCA, lipids, and proinflammatory cytokines following subcutaneous injection of ATX-101. Our results support continued clinical investigation of ATX-101 as an injectable drug to reduce SMF.
... Mesotherapy for lipolysis, for example, has not gained unanimous consent for a variety of reasons. In fact, the different compounds tested have produced preliminary results on small numbers of patients, none of which have been approved for this indication [101][102][103][104][105] . We are aware that in some countries many physicians (as well as non-medical personnel) use these substances (aminophylline, isoproterenol, forskolin, yohimbine phosphatidylcholine, deoxycholate and others, either alone or in combination) on the basis of a pathophysiological rationale, but we cannot fully judge how much we must inoculate, how deep, how often, for how long, and more importantly, the real benefit (medium-or long-term) and safety cannot be guaranteed for the patient. ...
The Italian society of mesotherapy, after a national consensus, carried out an international web-based con-sensus by the Delphi method. Our objective was to clarify the role of mesotherapy, its advantages, limita-tions, and correct use in clinical practice with multidisciplinary experts. All the experts approved the final recommendations and mesotherapy has been redefined as a minimally invasive technique that consists of the introduction of small amounts of pharmaceutical substances with micro deposits in the surface layer of the skin. The slowly injected compounds diffuse into the underlying tissues and produce a drug-sparing effect compared to the parenteral route. Used properly, this technique can be useful in some clinical indications. Mammucari M, Vellucci R, Mediati DR, et al. What is mesotherapy? Recommendations from an international consensus? Trends Med 2014; 14:1-10. In 1975 the Italian Society of Mesotherapy be-gan to validate mesotherapy with preclinical stu-dies to establish the pharmacokinetics of active compounds injected intradermally 1-3 . Numerous clinical trials were conducted to verify the effi-cacy and tolerability in several clinical conditions with localized pain 4-35 . In the field of analgesia it was assumed that mesotherapy could act through two action mechanisms, the first generated by the local pharmacological activity of the drugs used, the second, supported by mechanical stimulation produced by the needles, with activation of local receptors and segmental reflex effects 36 . On the basis of these results, patient-selection criteria have been developed with algorithms for mana-ging localized pain 37 . The possibility of admini-stering drugs that act locally with mesotherapy has also stimulated studies to assess the effects on the signs and symptoms of chronic venous and lymphatic insufficiency 38-42 . Now defined as a minimally invasive technique, mesotherapy is based on microinjections of active ingredients into the surface layer of the skin corresponding to the area to be treated. This "micro deposit" gives rise to a slower release of the drug into the surroun-ding tissues compared to parenteral administra-tion, 43 therefore with the possibility of obtaining two advantages. On one hand, a lower dose of active compound can be used, on the other, a ra-pid onset and prolonged action duration can be achieved. 43 These benefits are now also well Original article
... However, during the past few years, Lipostabil also has been applied beyond this indication, namely, off label via an injection into the subcutis to reduce localized deposits of adipose tissue[1,14,15,24,27]. This method of treatment, called ''adipocytolysis,'' is said to result in an ablation of adipose tissue and a solubilization of adipocyte cell membranes[26]. Regarding the lipolytic effect of Lipostabil, it is reported that the active component is not phosphatidylcholine but rather deoxycholate, which as a detergent causes nonspecific cell lysis[29]. ...
Background
This preliminary ex vivo study aimed to clarify the pathophysiologic mechanisms of fat tissue depletion by subcutaneous drug application. Therefore, the lipolytic effects of phosphatidylcholine plus deoxycholate (Lipostabil) (L) and of deoxycholate (DC) alone were compared with those of sodium chloride (NaCl) and hydrogen peroxide (H2O2) as control agents. The study enrolled 10 patients receiving abdominoplasty. The treatment periods for each sample and solution were 1, 3, 5, and 7 h. The samples were analyzed morphologically using hematoxylin-eosin (H&E) staining and also immunohistochemically using Caspase 3 and tumor necrosis factor (TNF)-alpha. Morphologic changes were seen best after 5 h of application time. Except for NaCl, all the samples in the H&E staining showed marked damage of adipocyte cell membranes, with the greatest disruption of normal cell architecture after hydrogen peroxide (H2O2) application. Immunohistochemistry using TNF-alpha showed positive results for the deoxycholate and Lipostabil samples and highly positive results for the H2O2 sample. Data from this study indicate that Lipostabil and deoxycholate induce pathways of cell necrosis involving TNF-alpha. These short-term experiments indicate that Lipostabil affects fat tissue in the way of a chemical-toxic destruction rather than via a physiologically induced, programmed cell death.
No Level Assigned
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... As a proprietary, synthetically derived, purified formulation of deoxycholic acid, ATX-101 causes localized adipocytolysis when injected into subcutaneous fat. Histologic evidence indicates that disruption of adipocyte membranes by deoxycholate/deoxycholic acid prompts a mild inflammatory tissue response, which is responsible for clearing the cellular debris through macrophage recruitment and subsequent phagocytosis [20][21][22][23]. ...
Background
The injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies.
Methods
Patients with unwanted SMF were randomized to receive 1 or 2 mg/cm2 of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded.
Results
Significantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, and 28.6 % of the placebo recipients; p
... Current therapeutic approaches to treat abdominal bulging localized to the periumbilical area rely either on the ablation or physical removal of the adipocytes in the area, or alternatively utilize a nonablative approach, where exogenous drugs stimulate adipocytes in a targeted treatment area to undergo lipolysis and/ or enhance their cellular sensitivity to endogenous lipolytic stimuli. 12,13 While ablative therapies have the potential to be used relatively indiscriminately regardless of patient habitus, the use of nonablative therapies is necessarily strongly influenced by the underlying lipolytic threshold of the adipocytes in the area being treated. 14 Endogenous catecholamine neurotransmitters like epinephrine and catechol-containing drugs such as isoproterenol, albuterol, and salmeterol bind to betaadrenergic receptors on the surface of adipocytes to stimulate lipolysis. ...
A large and growing population of patients currently seeks minimally invasive therapeutic options for the aesthetic treatment of localized, central abdominal subcutaneous adipose tissue (SAT). We sought to evaluate the ideal population for aesthetic treatment of central abdominal SAT, highlight the existing disparities between SAT in obese (body mass index [BMI] ≥ 30; BMI) and nonobese (BMI < 30) patients, and review the available FDA-cleared, minimally invasive treatment options for central abdominal adiposity. The cosmetic issue of localized, central (periumbilical) abdominal adiposity in nonobese individuals is quite distinct from abdominal bulging secondary to obesity. Given the recognized clinical and physiologic differences between obese and nonobese counterparts, the exclusion of obese patients from clinical study by currently available FDA-cleared devices targeting abdominal fat, and the status of obesity as a chronic, systemic disease requiring medical, surgical, and/or lifestyle-altering therapies, minimally invasive therapeutic options for aesthetic reductions in central abdominal SAT must be limited to the nonobese population.
... This technique, termed ablative mesotherapy, is usually performed using a phosphatidylcholine and deoxycholate formulation, or more recently deoxycholate alone. Other terms for ablative mesotherapy include lipodissolve, adipolysis, adipocytolysis, adipocyte lysis, adipolytic therapy and fat necrosis (18,19). ...
Mesotherapy, which is the injection of substances locally into mesodermally derived subcutaneous tissue, developed from empirical observations of a French physician in the 1950s. Although popular in Europe for many medical purposes, it is used for local cosmetic fat reduction in the United States. This paper reviews manuscripts indexed in PubMed/MEDLINE under 'mesotherapy', which pertains to local fat reduction. The history of lipolytic mesotherapy, the physiology of body fat distribution, the mechanism of action of different lipolytic stimulators and their increased efficacy in combination are reviewed. Mesotherapy falls into two categories. Lipolytic mesotherapy using lipolytic stimulators requires more frequent treatments as the fat cells are not destroyed and can refill over time. Ablative mesotherapy destroys fat cells with a detergent, causes inflammation and scarring from the fat necrosis, but requires fewer treatments. The historic and empiric mixing of sodium channel blocking local anaesthetics in mesotherapy solutions inhibits the intended lipolysis. Major mesotherapy safety concerns include injection site infections from poor sterile technique. Cosmetic mesotherapy directs the area from which fat is lost to improve self-image. Studies were of relatively small number, many with limited sample sizes. Future research should be directed towards achieving a Food and Drug Administration indication rather than continuing expansion of off-label use.
... Following injection, the drug slowly reaches the underlying tissues achieving concentrations higher than those obtained with intramuscular administration [5]. Interestingly, some authors consider mesotherapy as an intra-or subcutaneous technique; however , subcutaneously administered drugs may have different pharmacokinetics (diffusion and distribution) and as a result different onset and duration of activity depending on the site of injection [20, 21]. For example, plasma glucose levels vary depending on the subcutaneous site of injection— abdomen, arm, or leg—due to the level of absorption at the various injection sites [22]. ...
Mesotherapy is the injection of active substances into the surface layer of the skin. This method allows a slower spread, higher levels, and longer lasting effects of drugs in the tissues underlying the site of injection (skin, muscle, and joint) compared with those following intramuscular injection. This technique is useful when a local pharmacological effect is required and relatively high doses of drug in the systemic circulation are not. Mesotherapy should only be undertaken following a complete clinical workup and subsequent diagnosis. Encouraging results have been reported in randomized, controlled clinical trials and in observational studies involving patients with various forms of musculoskeletal pain. Recommendations by experts from the Italian Society of Mesotherapy for appropriate use of mesotherapy in musculoskeletal pain and an algorithm for treating localized painful conditions are provided.
... A number of fat-reduction procedures have emerged over recent years to address a demand for less invasive approaches, with an ultimate goal of imparting less risk while producing favorable results. These include the use of tumescent solutions [1], smaller gauge cannulas [2], external ultrasound [3], low-level external laser [4], injection lipolysis [5,6], cryolipolysis [7], external radiofrequency energy [8], and percutaneous laser lipolysis [9]. Laser lipolysis has been described with and without concurrent suction lipectomy [9,10]. ...
Background and Objective. There has been a heightened interest in laser-assisted fat reduction procedures. We aimed to determine if lipolysis with the 1,320 nm Nd-YAG short-pulsed laser without subsequent suction results in satisfactory contouring of the upper extremity.
Materials and Methods. Unilateral laser lipolysis of the upper arm was performed on 5 patients. Subcutaneous, subdermal, and skin surface temperatures were monitored with flexible thermocouples throughout the procedure to aid in the establishment of a treatment endpoint. Photographs and arm circumference measurements were evaluated before and 3 months after laser lipolysis. Patients were given the choice of undergoing the procedure on the contralateral arm at 3 months.
Results. All patients achieved no improvement to minimal improvement in upper arm contour. One of five patients was elected to have lipolysis performed on the contralateral arm.
Conclusion. Laser lipolysis may be safely performed with the parameters utilized in this pilot study, although minimal improvement was seen in upper extremity contour.
The article describes a clinical case of a five-fold administration of a direct lipolytic–phosphatidylcholine / deoxycholic acid for cosmetic purposes, which resulted in widespread septal panniculitis, systemic inflammatory reaction, secondary myositis, thrombotic microangiopathic syndrome, fatty necrosis of the pancreatic head, necrotic nephrosis and multiple organ failure, which led to death of the patient.
Materials and methods . Analysis of medical records, histological examination of autopsy material.
Conclusions. Injection lipolysis using phosphatidylcholine / deoxycholate causes uncontrolled necrosis of adipose and vascular tissue, fibrosis, which makes the indefinitely long-term consequences of the administration of drugs for the non-surgical treatment of subcutaneous fat deposits. Phosphatidylcholine / sodium deoxycholate is not recommended for use in the presence of general obesity, somatic pathology, or in elderly patients.
INTRODUCTION: Mesotherapy is widely used to reduce localized body fat through the subcutaneous injection of lipolytic substances, such as sodium deoxycholate (DEOXI). DEOXI is a biliary salt that dissolves and emulsifies fat, although there is a lack of evidence regarding its safety in the literature. OBJECTIVE: To investigate short-term cardiometabolic effects of a single subcutaneous DEOXI injection on female Swiss mice. METHODS: CEUA approval nº 1011/2017. Four months-old female Swiss mice received one subcutaneous injection of 100 uL of saline (control), 13 ug (D13) or 130 ug (D130) of DEOXI into the right inguinal region. Mice were euthanized 6h, 24h or 7 days after the procedure. Body mass, food intake, serum analytes (glucose, triacylglycerol [TG], glycerol, total cholesterol (TC), HDL cholesterol and liver enzymes) were analyzed. Tissue TG and glycerol were measured int the left ventricle (LV), liver, and brown adipose tissue (BAT). Histopathology and morphometry were performed in the inguinal white adipose tissue (iWAT), BAT and liver. RESULTS: DEOXI did not change body mass and the weight of the collected tissues. Serum TG was higher in D13-6h compared to C-6h (+33,0%, P<0,05). Serum glycerol of D130 were 62,0% lower (P<0,01) in 6h, and 48,7% lower (P<0,05) in 24h vs. C-6h e C-24h, respectively. At 7 days, glycerol of D13 was lower than D13-6h (49,7%, P<0,01). HDL-c was elevated at all times in the D130 group vs. C e D13. TGO was elevated at 24h compared to D13 and C group (+45,7%, P<0,05), and D130 group vs. D13 (-28,4%, P<0,05). TGP was elevated in D13 group at all times. In the iWAT, there was acute inflammation and tissue remodeling. In the BAT, TG was +130,2% higher (P<0,05) in D130-6h, and +80,2% higher (P<0,01) in the D130-24h compared to control. BAT morphometry did not show significant changes between groups. In the liver, tissue TG in the D13-6h was higher than C-6h (+131,6%, P<0,001) and D13-6h (+108,1%, P<0,01). At 24h, hepatic TG of D13 was higher than C-24 (+195,0%, P<0,001) and D13-6h (+126,6%, P<0,001). At 7 days, liver TG of D13-7days group was higher than C-7days (+188,5%, P<0,0001) and D13-6h (+70,0%, P<0,05). Hepatic glycerol of D130-24h was lower than C-24 (-48,6%, P<0,05) and D130-6h (-55,0%, P<0,05), at 7 days was lower in D13-7days (-76,8%, P<0,001) compared to C-7dias and D130-6h (-77,9%, P<0,01). Liver morphometry showed a reduction of hepatocyte density per area in D13-24h, D130-24 and D130 groups compared to control. LV glycerol in D130-6h group was higher than C-6h (+204,8%, P=0,001) and D13-6 (+56,2%, P<0,05). DISCUSSION AND CONCLUSIONS: A single subcutaneous injection of DEOXI leads to both local and systemic changes, in the blood and in metabolically active tissue.
The desire to reduce and remodel undesirable fatty deposits has increased the popularity and use of aesthetic procedures, among them, cryolipolysis. However, repercussions on the autonomic nervous system must be considered, since the decrease in cutaneous body temperature can have repercussions on sympathetic and parasympathetic components. The aim was to evaluate the behavior of cardiac autonomic modulation during and after a single application of cryolipolysis. A single-arm, prospective interventional study evaluated data from 13 women with a mean age of 22.38 ± 2.95 years, who had an accumulation of abdominal fat of at least 1.5 mm, were using oral contraceptives, and were sedentary. A professional applied cryolipolysis in a single 40-min session. RR intervals were collected by means of a cardiofrequency meter, at rest prior to the technique for 10 min, during the performance of the technique, and immediately after the end of the technique for a period of 50 min. Heart rate variability (HRV) analysis was performed using time, frequency, and Poincaré plot indices. For the mean RR, SDNN, rMSSD, SD1, SD2, and LF [ms2] indices, the values increased during the execution of cryolipolysis when compared to rest. In the recovery period, increases in the mean values of the RR, SDNN, rMSSD, SD1, SD2, HF [ms2], LF [nu], and HF [nu] indices were also observed when compared to the baseline moment. Both during the technique and in the recovery period, there were changes in the behavior of HRV characterized by an increase in global and vagal indices. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Background
Optimizing post procedural recovery and outcomes for patients is the aim for all physicians. TransFORM Body Treatment with TriHex Technology (TFB) is a topical product that aids in the elimination of fat particles created during procedures and the reduction of associated inflammation, thus, speeding up post procedure recovery time.
Objectives
Evaluation of post procedural symptoms, signs and healing following submental deoxycholic acid (DCA) injections in combination with TFB post treatment.
Methods
Participants received two treatments of submental DCA injections. Post treatment 1 every participant received TFB to apply twice daily to the submental area. Follow-up visits included weeks 1, 2 and 4. After week 4, participants discontinued TFB for 30 days prior to the second treatment. At the second treatment visit, participants were randomized to receive either TFB or a bland moisturizer to apply twice daily with the same follow-up visits as post treatment one. Skinfibrometer measurements (objective induration measurements), submental fullness grading and standardized photography were captured at every visit. At all follow-up visits and prior to treatment 2, investigator assessments and participant assessments were completed.
Results
Post treatment two, investigator assessments of edema and induration decreased in participants using TFB at weeks 1 and 2 compared to the bland moisturizer. Skinfibrometer measurements objectively showed a statistically significant reduction in induration at week 2 (post treatment two) in participants using TFB compared to the bland moisturizer. Furthermore, participants reported less tenderness and soreness in the TFB group over the bland moisturizer.
Conclusions
Investigator assessments, participant query and objective skinfibrometer analyses have demonstrated that the use of TFB post DCA injections may reduce induration, edema and discomfort associated with this procedure.
Background:
ATX-101 is indicated for submental fat treatment.
Objective:
Evaluate ATX-101 versus placebo for reducing submental fat.
Materials and methods:
Adults with unwanted submental fat across 6 global sites were randomized to ATX-101 (0.5%, 1.0%, or 2.0%) or placebo for ≤4 treatments every 28 days. Outcomes included safety (adverse events and pain visual analog scale) throughout the study and efficacy (submental fat rating, patient satisfaction, and submental fat improvements) at Week 16.
Results:
Eighty-four of 85 enrolled patients received ≥1 ATX-101 treatment (0.5% [n = 20], 1.0% [n = 20], 2.0% [n = 22] or placebo [n = 22]). Most patients (n = 82) experienced adverse events, which were mostly mild/moderate, seemed to be dose-related, and led to no study discontinuations. The mean pain scores were highest in the ATX-101 1.0% and 2.0% groups. Week-16 change from baseline in the submental fat rating scale was significantly greater for ATX-101 0.5% and 1.0% versus placebo (p ≤ .05). At Week 16, 71%, 74%, 53%, and 40% of patients in the ATX-101 0.5%, 1.0%, 2.0%, and placebo groups, respectively, achieved a ≥1-grade reduction in submental fat from baseline. Satisfaction with appearance and patient-assessed global improvement ratings increased in all ATX-101 treatment groups versus placebo.
Conclusion:
All ATX-101 concentrations were safe and efficacious for moderate/severe submental fat reduction.
Background:
Excess submental fat (SMF), also called as a double chin, is an area of concern for men that can be addressed clinically. ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada, Australia, and various European countries) is the first injectable approved for reduction of SMF.
Objective:
To share the authors' clinical experience using ATX-101 in men with submental fullness and offer insights regarding how this treatment may be presented to men as an option to improve their submental profile.
Methods:
Retrospective review of the authors' medical records for male patients treated with ATX-101.
Results:
To allow for fewer ATX-101 treatments, it is recommended that a large surface area be treated at the first session. The positive changes and outcomes achieved with ATX-101 build confidence between the physician and patient, which often leads to male patients seeking other aesthetic treatments to improve their overall appearance.
Conclusion:
ATX-101 treatment is often an effective introduction to aesthetic medicine for men.
Background:
Men are increasingly seeking out cosmetic procedures, especially minimally and noninvasive body-contouring procedures.
Objective:
With the relative lack of scientific evidence related specifically to the use of body-contouring procedures in men, there is a need for more education and scientific discussion in this growing group.
Materials and methods:
Understanding the male anatomy and esthetics, and how body-contouring techniques and new modalities can be used in men, can lead to better outcomes.
Conclusions:
This review of body contouring in men emphasizes currently available literature and author experiences.
ATX-101 (deoxycholic acid) is the first pharmaceutical therapy approved by the FDA for the reduction in submental fat. Deoxycholic acid is an endogenous secondary bile acid that normally solubilizes dietary fat, contributing to its breakdown and absorption within the gut. This article reviews the identification of deoxycholic acid as a lipolytic agent, and the mechanism of action, pharmacokinetics, and pharmacodynamics of ATX-101. In addition to phase I/II trials, four Phase III clinical trials have evaluated safety and efficacy of ATX-101. These studies helped establish the appropriate dosage, administration techniques, warnings, and side effects of ATX-101. ATX-101 is effective in treating submental fat. Adverse events, although common, are mild and transient.
Die Injektions-Lipolyse ist mittlerweile ein anerkanntes Injektionsverfahren zur Reduzierung kleinerer Fettpolster. Über 80 Publikationen in hochwertigen Zeitschriften, mehrere Studien anerkannter Universitäten und Mediziner haben gezeigt, dass eine Zusammensetzung von Phosphatidylcholin (PPC) und Desoxycholsäure (DOC) in der Lage ist, bei einem moderaten Nebenwirkungsprofil kleinere, resistente Fettpolster abzuschmelzen. Durch mikrofeine Injektionen wird ein Entzündungsprozess initiiert, der die Zellmembran der Adipozyten zerstört und das freigesetzte Fett metabolisiert. Insofern ist die gängige Bezeichnung Lipolyse nicht ganz korrekt, besser kann man von Lipodestruktion sprechen.
Noninvasive procedures targeting the elimination of unwanted adipose tissues have recently been developed. injection adipolysis is the term for the injection of cytotoxic substances into these tissues, with the intent of cosmetic improvement by volume reduction. initial attempts in the field utilized intravenous preparations of sodium deoxycholate and soy-derived phosphatidylcholine, approved for the intravenous treatment of fat emboli and dyslipidemias in countries outside the United States. it was initially purported that the active ingredient in these injections was phosphatidylcholine. Subsequent research discovered that injections of sodium deoxycholate alone were capable of inducing cellular lysis in vitro. These compounds also demonstrated an affinity for adipose tissue, sparing the overlying dermis and epidermis. The United States Food and Drug administration (FDa) recently approved a formulation of sodium deoxycholate 10mg/mL for subcutaneous injection with the indication of aesthetic improvement of excess submental fat. it has shown moderate eFcacy with appropriate patient selection and good patient satisfaction. However, previous research leading to the development of this drug proposed that including phosphatidylcholine to a more appealing cosmetic result, with decreased severity of injection-site reactions. Future drugs in the field of injection adipolysis may attempt to combine these ingredients for improved cosmesis and tolerability.
Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well.
Introduction: Over the years, liposuction has been the standard treatment for localized fatty deposit. Lipolysis is a controversial procedure based generally on phosphatidylcholine and deoxycholate injection. The purpose of this study was to compare the efficacy of cholanic acid Aqualyx with the efficacy of liposuction in women with moderate submental fatty collection.
Materials and Methods: A prospective randomized study of 30 women with moderate submental fatty collection. Half of the subjects were treated with cholanic acid Aqualyx and the other half with liposuction. Responses were assessed clinically and statistically.
Results: Although the lipolysis group showed a better response, it is difficult to conclude that adipocytolisis leads to greater fat reduction compared with liposuction.
Neither photodynamic therapy (PDT) nor sterile water has not been well studied for the treatment of adipose tissue.
This investigation studied 2 different modalities, verteporfin PDT and sterile water, on adipose tissue compared with control.
Four light-skinned pigs were used. Test sites received verteporfin PDT or sterile water injection. Control sites received injection of verteporfin without PDT, normal saline injection, no intervention, exposure to laser only, or insertion of a needle or cannula only. Sites were evaluated clinically, by ultrasound, and with histology 4 to 6 weeks after treatment.
There was a decrease in adipose tissue by ultrasound after verteporfin PDT (15%, p < .001) and sterile water (2%, p = .23). Verteporfin without PDT showed a decrease in adipose tissue (17%, p = .21). All other control sites showed an increase in adipose tissue. Histologically, verteporfin PDT and sterile water showed moderate damage (median Grade 2, p < .001) 4 to 6 weeks after intervention.
Verteporfin decreased adipose tissue after treatment. Sterile water injection had a statistically significant effect on adipose tissue histologically but did not substantially decrease the adipose tissue by ultrasound 4 to 6 weeks after intervention. Longer follow-up may be needed.
This chapter gives an overview of the histology of normal subcutaneous tissue, and discusses the tumors and inflammatory processes affecting subcutaneous fat. The histology and physiology for white adipose tissue and brown adipose tissue is discussed here. White adipose tissue is widely present throughout the body and organized into collections called “depots.” Adipose tissue can affect other tissues via endocrine, paracrine, and autocrine signals. The number of fat cells in adults may remain stable or can increase or decrease according to diet and other factors. Brown adipose tissue can be identified at the 20th week of pregnancy, later than its white counterpart. Lipoma is the most common soft tissue tumor in adults. The hallmark of panniculitis is inflammation of subcutaneous fat. It can be divided into septal and lobular pannicultis.
Hintergrund Die Fettgewebsreduktion zur Körperformung ist ein sehr häufiger Wunsch von Patienten. Die Liposuktion hat sich dabei als die effektivste Methode herausgestellt. Durch Verfeinerung der Techniken hat sie heutzutage in der Hand des geübten Operateurs ein sehr niedriges Risikoprofil. Zusatzverfahren zur Absaugung versprechen eine additive Verbesserung vor allem bei der Gewebestraffung. Dennoch wurden in den letzten Jahren viele Alternativverfahren im nicht-invasiven Bereich auf den Markt gebracht. Ohne Ausfallzeit für den Patienten soll mit diesen eine optimierte Körperkonturierung erreicht werden. Fragestellung Welche operativen und nicht-operativen Methoden zur primären Verschlankung gibt es, welche Risiken sind damit verbunden und wie effektiv sind sie? Methode Der vorliegende Artikel stellt diese Methoden vor, ordnet sie und bespricht die Vor- und Nachteile sowie ihre Effektivität anhand der Literatur und persönlicher Erfahrungen. Schlussfolgerungen Die Liposuktion, besonders die vibrationsassistierte in Tumeszenzlokalanästhesie, ist die effektivste Methode der Fettreduktion. Sie sollte immer durch einen erfahrenen Arzt erfolgen. Nichtoperative Techniken kommen bisher noch nicht an die Effektivität der Absaugung heran. Vielversprechend sind jedoch die synergistischen Effekte bei der Kombination verschiedener Verfahren.
ATX-101 (deoxycholic acid [DCA] injection) is a proprietary formulation of pure synthetic DCA. When injected into subcutaneous fat, ATX-101 results in focal adipocytolysis, the targeted destruction of fat cells. ATX-101 is undergoing investigation as an injectable drug for contouring the submental area by reducing submental fat (SMF). The purpose of this study was to evaluate the safety and pharmacokinetics (PK) of the maximal therapeutic dose of ATX-101 (100 mg total dose). Following PK evaluation of endogenous DCA, subjects (N = 24) received subcutaneous injections of ATX-101 (2 mg/cm(2), with or without 0.9% benzyl alcohol) into SMF; PK evaluation was repeated periodically over 24 hours. Endogenous DCA plasma concentrations measured prior to injection were highly variable within and between subjects: Similarly, following ATX-101 injection, DCA plasma concentrations were highly variable, peaked rapidly, and returned to the range observed for endogenous values by 24 hours postdose. All subjects experienced at least 1 adverse event (AE). No death, serious AE, or AE-related discontinuations occurred. The majority of AEs were transient, associated with the area treated, and of mild or moderate severity. No clinically significant changes were reported for laboratory test results, vital signs, or Holter electrocardiograms postdosing. These data support the favorable safety and efficacy observations of ATX-101 as an injectable drug to reduce SW.
There are many points of contact between aesthetic medicine
and psychiatry are brought up, including the relationship
between the concept of body image and psychosocial,
cultural and familial factors. Statistical data on major psychiatric
and medical conditions related with aesthetics are
provided, highlighting the Body Dysmorphic Disorder
as a psychopathology to be considered in both medical
and cosmetic surgery consultations. Recommendations
are given on how to detect these disorders and on how to
promote a healthy global concept of beauty.
Aim of the studyThe goal of this study was to evaluate the efficacy of mesotherapy treatment with Ephedra and green tea extract in combination on localized fat of overweight women subjects.Materials and methodsTwenty-five overweight women, 20–35-years-of-age, body mass index ≥ 23 kg/m2 were randomly assigned into active (Ephedra + green tea, n = 13) and placebo (saline, n = 12) groups. A total eight herbal or saline mesotherapy administrations were performed into the thighs alternatively in two phases, each one comprising of four consecutive treatments on one thigh on weekly basis. Body composition parameters, circumference and subcutaneous fat area of thighs were measured before and after each phase, in addition to evaluating fasting free fatty acid (FFA) level of blood as well as adverse events of the therapy in volunteers.ResultsThere were no significant changes in the body weight, BMI, body fat, and subcutaneous fat area of thigh within or between the groups, but the change in thigh circumference within the active group was significantly lower compared to that within the placebo group. The blood FFA level at 1 h after the first herbal therapy was significantly higher than that recorded at other time points of pre- and post-treatment measurements.Conclusions
The herbal mesotherapy treatment produced a significant effect on thigh circumference and fasting-FFA level within the active group. Future studies that compensate for the limitations of this trial are required to fully ascertain the efficacy and safety of the proposed mesotherapy, and a very careful consideration is needed until then.
Injection of phosphatidylcholine (PC) and deoxycholic acid (DA) preparation is widely used as an alternative to liposuction for the reduction of subcutaneous fat. Nevertheless, its physiological effects and mechanism of action are not yet fully understood. In this report, PC and deoxycholic acid (DA) were respectively injected into adipose tissue. PC decreased tissue mass on day 7, but DA did not. On the other hand, a decrement of DNA mass was observed only in DA-injected tissue on day 7. Both PC and DA reduced the mRNA expression of adipose tissue hormones, such as adiponectin, leptin, and resistin. In lipolysisrelated gene expression profiles, PC increased hormone-sensitive lipase (HSL) transcription and decreased the expression other lipases, perilipin, and the lipogenic marker peroxisome proliferator-activated receptor-γ (PPARγ); DA treatment diminished them all, including HSL. Meanwhile, the gene expression of pro-inflammatory cytokines and a chemokine was greatly elevated in both PC-injected and DA-injected adipose tissue. Microscopic observation showed that PC induced lipolysis with mild PMN infiltration on day 7. However, DA treatment did not induce lipolysis but induced much amount of PMN infiltration. In conclusion, PC alone might induce lipolysis in adipose tissue, whereas DC alone might induce tissue damage.
The history of beauty is as old as mankind itself - throughout history people have tried to improve their attractiveness and to enhance their beauty. The technical basis for many of nowadays procedures like lipoplasty, breast augmentation or rhinoplasty was thereby initiated more than a hundred years ago and evolved to the modern standards of today. The aim of this article is to recall the early days of aesthetic medicine and show the swift progress up to the highly specialized medical discipline of our modern time. Combining the past, present and future of aesthetic medicine, allows to incorporate this perspective and ultimately to delivery better patient care.
J Drugs Dermatol. 2013;12(7):737-742.
Seit 2004 wird weltweit zu einer neuen Therapievariante des medizinisch-ästhetischen Spektrums geforscht: der sog. Injektionslipolyse (IL). Fortschritte im Wissen zu Wirksamkeit und den Wirkmechanismus betreffend gab es v. a. in Deutschland, weil hier im internationalen Vergleich die meisten Anwender zu finden sind. Hintergrund ist, dass in Deutschland für die Wirkstoffkombination Phosphatidylcholin und Desoxycholsäure (PPC-DOC) die Zulassung eines Medikamentes für die i.v.-Anwendung zur Behandlung von Fettembolien besteht. Es ist somit leicht verfügbar, trotzdem ist die subkutane Injektion des Medikaments „Lipostabil N®“ als sog. „off-label use“ einzuordnen. Mittlerweile hat sich die Injektionslipolyse für viele zu einem festen Baustein im Arsenal der ästhetischen Medizin entwickelt. Insbesondere der internationale Zusammenschluss der anwendenden Ärzte in dem sog. Netzwerk Lipolyse (weltweit über 2000 Mitglieder) hat die Entwicklung international gültiger Therapiestandards und -protokolle gefördert. Die Injektion von Phosphatidylcholin/Desoxycholsäure in subkutanes Fettgewebe hat die minimal-invasive ästhetische Medizin, bei strenger Indikationsstellung und nach intensiver Schulung der die Methode einsetzenden Mediziner um einen sinnvollen Baustein erweitert.
Objective:
Since its introduction in the 1950s, the use of mesotherapy has generated much interest among clinicians and patients. The Italian Society of Mesotherapy (SIM) brought together a panel of experts to review available evidence and to draw up a series of recommendations on the use of intradermal therapy (LIT) in clinical practice.
Consensus report:
There was overwhelming agreement among Consensus Group members that, when used correctly, LIT is a valuable therapeutic option in the treatment of painful, loco-regional conditions. They also emphasised that the clinical efficacy of LIT has been demonstrated in the management of chronic venous lymphatic insufficiency, oedematous fibrosclerotic panniculopathy and facial skin aging. The experts were unanimous on the use of LIT in vaccination. Mesotherapy is not a substitute for other therapeutic options and should only be used when the patient has been fully informed of its advantages and limitations. Likewise the procedure should only be carried out by an experienced qualified physician.
Conclusions:
Although there was widespread agreement among the Consensus Group on the place of LIT in several indications, the Authors reiterated the need for more large-scale clinical trials to determine the specific benefits and limitations in some areas of the application of intradermal therapy.
We describe an outbreak of severe subcutaneous infections due to nontuberculous mycobacteria following mesotherapy. Epidemiological
studies and molecular comparisons of Mycobacterium chelonae strains from different patients and the environment suggested that contamination may be associated with inappropriate cleaning
of the multiple-injection device with tap water.
To evaluate the effectiveness of disodium EDTA administration in the treatment of calcific tendinitis of the shoulder.
Eighty patients with radiographically verified calcific tendinitis of the shoulder were enrolled between September 2001 and October 2003. Patients were randomly assigned to either a study group (n = 40) or a control group (n = 40). Pain and functional level were evaluated before and after treatment and at 1-year followup. Radiographic modifications in calcifications were evaluated before and after treatment. Disodium EDTA was administered through single needle mesotherapy and 15 minutes of pulsed-mode 1 MHz-ultrasound.
The study group displayed improvement in all of the parameters analyzed after treatment and at the 1-year followup. Calcifications disappeared completely in 62.5% of the patients in the study group and partially in 22.5%; calcifications partially disappeared in only 15% of the patients in the control group, and none displayed a complete disappearance.
Our results suggest that the use of disodium EDTA for the management of calcific tendinitis of the shoulder is safe and effective, leading to a significant reduction in pain, improvement in shoulder function, and disappearance of calcifications after 4 weeks, without adverse effects.
Phosphatidylcholine was initially used in emergencies and in the treatment of atheroma plaques in cardiac diseases. Recently, it has also been used in the treatment of localized fat deposits. We report on the authors' clinical experience of the use of 250 mg/ml phosphatidylcholine injections in the treatment of subcutaneous fat deposits, showing the clinical response and side-effects. Volunteers received phosphatidylcholine injections in several areas of localized fat deposits, with a minimum interval of one week and mean interval of 15 days between applications. Laboratory tests were performed during the period of the drug use. Clinical results reflect that phosphatidylcholine was efficacious in reducing the fatty pads in the treated areas, with few side effects. From the authors' point of view, the off-label use of phosphatidylcholine in the treatment of fatty pads and small areas of localized fat is safe, low cost, and effective.
Subcutaneous phosphatidylcholine to cause local lipolysis has been performed effectively and safely in the nonsurgical treatment of periorbital fat pads and also in the treatment of localized fat deposits in the abdomen, neck, arms and thighs. However, the studies do not explain the mechanism through which injectable phosphatidylcholine causes localized fat reduction. This study aimed to compare the local action of a phosphatidylcholine formulation with that of a physiologic saline solution in a histologic study investigating the fat tissue of rabbits.
Using a randomized, blind approach, 10 rabbits were injected with an experimental assay of phosphatidylcholine (the biologic model), and another 10 rabbits were injected with physiologic saline. A histologic study was conducted, and the Mann-Whitney test was applied.
A marked difference was observed between the two groups with respect to necrosis, inflammatory exudation, and fibrosis.
Necrosis of the fat cells in all the phosphatidylcholine-injected animals was observed. Further studies should be performed to clarify and determine the mechanisms of action.
Despite the increasing interest in mesotherapy as an alternative method for body contouring, there are few reports of its safety, efficacy, and mechanism of action. A clinical examination was performed to evaluate the efficacy of mesotherapy for body contouring.
Twenty women were enrolled in this prospective, case-controlled study over a 12-week period. The authors injected a mixed solution (i.e., aminophylline, buflomedil, and lidocaine) into the superficial dermis of the medial aspect of one thigh weekly using a mechanical delivery gun. There was no treatment to the other thigh. The change in the fat level was evaluated by measuring the girth of the thighs and by computed tomographic scanning. The lipid profiles were checked to determine the effect of mesotherapy on lipid metabolism, and questionnaires were used to determine the satisfaction rate of the patients.
The loss of thigh girth on the treated side was not significantly different from that of the untreated side. The computed tomographic scans showed no statistically significant difference in the cross-sectional area or thickness of the fat layer between each group. There were no statistically significant changes in the lipid profiles except for the triglyceride level. A questionnaire asking about the effect of mesotherapy indicated poor patient satisfaction.
Mesotherapy is not an effective alternative treatment modality for body contouring.
There is little published research on the use of phosphatidylcholine injections for reduction of localized fat deposits, though the use of this modality in Europe has increased substantially in the past 3 years. This article reports on the treatment of 100 patients with localized fat deposits presenting to a cosmetic practice in the United Kingdom. The author's clinical experience using phosphatidylcholine injections (250 mg/mL) to treat subcutaneous fat deposits is described, as are the clinical effectiveness and side-effect profile. Patients received 1 to 3 subcutaneous phosphatidylcholine injections in various areas of localized fat deposits. Outcome measures included patient assessment of improvement, percentage reduction in skin thickness, and physicians' global improvement rating. Phosphatidylcholine was found to be effective in reducing subcutaneous fat in the treatment sites by a mean of 22.8% and produced few side effects. Regression analysis of the effectiveness of phosphatidylcholine against variables such as age, sex, treatment site, and body mass index showed little difference between the patient groups, indicating that this treatment approach may be used effectively for a wide patient demographic. Clinical experience with off-label use of phosphatidylcholine for small areas of localized fat deposits suggests that this treatment is relatively safe, inexpensive, and effective.
The present paper describes the preparation of mixed micelle solutions and liposome dispersions for parenteral use based on soya phosphatidylcholines. A minimum bile acid salt/phospholipid ratio of 0.72 (sodium glycocholate) or 0.82 (sodium desoxycholate) was required to produce optically clear, mixed micelle solutions. It was also necessary to add about 1% benzyl alcohol to obtain optically clear solutions at these concentration ratios. Mixed micelle solutions can be freeze-dried. The addition of small quantities of soya phosphatidylglycerol sodium salt or bile acid salts (0.05-0.1%) was found to be particularly suitable for the preparation of stable, highly transparent liposome dispersions with small particle sizes allowing sterile filtration. The use of a high pressure gap homogenizer allowed the preparation of such liposome dispersions on a production scale. After the addition of cyroprotectors liposome dispersions can be freeze-dried without the loss of their physical properties on rehydration. If an aqueous solution of doxorubicin or a similar substance is added to such lypophilisate, the hydration is simultaneously accompanied by an effective loading of the liposomes.
BACKGROUND: Recent articles have introduced the novel concept of chemical lipolysis through local injections. Phosphatidylcholine is the active drug in the commercial preparation used for this purpose, but some studies have suggested that sodium deoxycholate, an excipient of the preparation, could be the real active substance. AIM: We decided to investigate whether phosphatidylcholine and sodium deoxycholate have any clinical efficacy in chemical lipolysis and their respective roles. We also studied the safety and side effects of the treatments. MATERIALS AND METHODS: Thirty-seven consecutive female patients were studied for the treatment of localized fat in gynoid lipodystrophy. Each patient received injections of a phosphatidylcholine/sodium deoxycholate preparation on one side and sodium deoxycholate on the contralateral side, each single patient being herself the control. Four treatments were carried out every 8 weeks in a double-blind, randomized fashion. Metric circumferential evaluations and photographic and ultrasonographic measurements throughout the study allowed for final judgment. A statistical evaluation concluded our study. RESULTS: An overall reduction of local fat was obtained in 91.9% of the patients without statistically significant differences between the treated sides. Reduction values on the phosphatidylcholine/sodium deoxycholate–treated sides are in the order of 6.46% metrically and 36.87% ultrasonographically, whereas on the deoxycholate-treated sides they are in the order of 6.77% metrically and 36.06% ultrasonographically. Both treatments, at the dose used in the study, proved safe in the short term. The most common side effects were local and few, but were more pronounced on the deoxycholate-treated sides. No laboratory test was carried out. CONCLUSION: Both treatments have shown moderate and equivalent efficacy in treating localized fat, with sodium deoxycholate having a slower postoperative resolution, suggesting that sodium deoxycholate could be sufficient by itself to determine fat cell destruction and that phosphatidylcholine could be useful for obtaining a later emulsification of the fat.
Background. Patients with prominent periorbital fat pads often complain of having a persistent “tired” look and seek treatment from their dermatologist.Objective. A non-surgical treatment of fat pads.Methods. Thirty patients were treated for prominent lower eyelid fat pads with phosphatidylcholine injection. Pre- and posttreatment photographs were taken for long-term analysis.Results. A marked reduction of the lower eyelid fat pads was noted over the 2-year follow-up period. There were no recurrences.Conclusion. The injection of phosphatidylcholine (250 mg/5 ml) into the fat pads is a simple office procedure that may postpone or even substitute for lower eyelid blepharoplasty.
Dr. Rotunda is the co-inventor of a patent that describes the use of deoxycholate as a method to treat localized fat.
Subcutaneous injections consisting of the detergent, sodium deoxycholate, alone or in combination with the phospholipid, phosphatidylcholine, have been reported to reduce adipose tissue. The role of phosphatidylcholine remains unclear.
To evaluate the safety profile and efficacy of subcutaneously injected deoxycholate alone compared with a conventionally utilized mixture of phosphatidylcholine/deoxycholate in patients with undesirable accumulations of submental fat.
This was a single center, randomized, double-blind exploratory study. A total of 42 subjects were enrolled; 28 were injected into the submental fat with 1 mL of deoxycholate or phosphatidylcholine/deoxycholate, and 14 received 2 mL per treatment. Subjects received up to 5 treatments every four weeks, and completed a home diary and post-treatment self-assessment. Clinicians blinded to treatment performed injections, physical examination, and photographic evaluation.
Photographic assessment of 32 of the 42 enrolled patients revealed modest changes in submental profiles after a median of 5 deoxycholate or 4 phosphatidylcholine/deoxycholate treatments. Mean degree of improvement (0=none, 1=mild, 2=moderate, 3=significant) was 0.8 (+/-0.9) for deoxycholate and 0.6 (+/-0.5) for phosphatidylcholine/deoxycholate, with a median improvement of 0.5 (range, 0-3) for both groups. The incidence of correct before:after photographic sequence assignments was similar. There were no notable differences on physical examination, incidence, duration, and severity of adverse events (most commonly edema, erythema, pain, and burning) or subject self-assessment of fat loss, skin tightening, chin profile, and overall performance between the treatments.
Under the conditions employed, injections of deoxycholate or phosphatidylcholine/deoxycholate into the submental fat produced minimal aesthetic improvement overall. No apparent differences in efficacy or adverse events were observed with the inclusion of phosphatidylcholine. Enhanced neck profiles in several subjects demonstrate a proof of concept that warrants further study utilizing a validated, submental profile grading scale and methods to optimize dose and technique.
Mesotherapy is a popular procedure that poses risks that include scarring, contour changes and bacterial infections. The benefits of the procedure remain to be objectively delineated in a placebo-controlled, blinded study. Despite the lack of evidence to support its use, it is marketed as a "nonsurgical and safe" way to remove fat. The authors report a case of mycobacterial infection resulting from mesotherapy. This infection should be considered when a patient presents with a mesotherapy complication and should be discussed with the patient prior to the procedure. Options for treatment of the scarring are considered.
Subcutaneous injection of Lipostabil Endovena (Nattermann & Cie, Köln, Germany) has been used to treat periorbital fat pads, as well as localized fat deposits in the abdomen, neck, arms, and thighs. OBJECIVE: The goal of this article was to identify complications resulting from the use of Lipostabil Endovena for treating fat deposits.
A prospective study was conducted to identify complications associated with injection lipolysis with Lipostabil Endovena. Patients were surveyed at 48 hours, 2 weeks, and 2 months after the last injection session.
The 739 patients surveyed received a total of 2852 vials injected. No general symptoms, such as fever, dizziness, gastrointestinal disturbances, or visual disturbances occurred, although local symptoms, including edema, hematoma, pain, and nodules, were reported.
The lack of any reported general complications after injection lipolysis with Lipostabil Endovena is encouraging. However, larger studies are needed to confirm that the use of Lipostabil Endovena is safe.
According to the authors, Lipodissolve injections reduce the size of localized fat deposits and cause skin retraction in body regions containing small deposits of localized fat, cellulite, or postlipoplasty deformities. It will not replace traditional lipoplasty techniques, but is an excellent adjunct or alternative for those patients seeking minimally invasive treatment. Successful outcomes are highly dependent on the correct formula and injection technique, as well as proper patient selection.
This article describes the author's experience with lipodissolve, a nonsurgical treatment to reduce fat deposits via the injection of a single component, phosphatidylcholine, a natural product found in the body. Lipodissolve is a relatively new aesthetic procedure used to dissolve smallish, localized, and defined zones of fat in the face and body.
The unusual evolution of the practice of injection lipolysis has generated doubt regarding its safety and efficacy among many physicians. During the early years of this decade, mesotherapy was practiced by a few physicians, but the practice was not widespread. Paramedical practitioners and business developers saw the market potential for nonsurgical fat reduction, and the practice of injection lipolysis was packaged and sold before the mechanism of action was understood. Because of the early lack of scientific research and understanding of the limitations of injection lipolysis, many unsuitable patients were treated with this modality. To better understand the way injection lipolysis works, the inclusion and exclusion criteria for patients desiring treatment, and an accurate clinical evaluation format for potential treatment regions, a series of scientific studies was performed in 2007 and early 2008. These studies included a serial histopathology evaluation of treated patients over time, a stem cell study performed with the McGowan Research Institute in Pittsburgh, an animal study performed in conjunction with the Colorado State University veterinary school, and a prospective multicenter clinical trial using injection lipolysis in the back roll region. The purpose of these studies was to determine the way injection lipolysis works, how modifications of the formula and technique change the outcome, the role of each constituent component of various formulas, and the degree of fat reduction and skin retraction that is attainable with these treatments. The influence of depth of injection, distance between injection points, volume of injection, and ratios of constituent components was studied. The degree of topographic contour correction and the amount of volume reduction were evaluated. Following a review of these recent studies, an updated recommendation for the clinical practice of injection lipolysis was formulated.
The first part of this article familiarizes the reader with the evolution of mesotherapy, injection lipolysis, and the use of phosphatidylcholine and deoxycholate for subcutaneous fat reduction. There is an emphasis on the underlying basic science of fat metabolism and the biochemistry of phosphatidylcholine, so that practitioners will be able to understand future published research on these topics. The second half details some personal experience with injection lipolysis.
Phosphatidylcholine formulation has been used to dissolve local fat deposits. This study aimed to evaluate and compare the effects of phosphatidylcholine formulation and its vehicle sodium deoxycholate alone on different cell lines to understand better its mechanism of action.
Cells and media including 3T3-L1 preadipocytes, normal foreskin fibroblasts, neonatal human dermal microvascular endothelial cells (CADMEC), and fetal human skeletal muscle cells (HSkMC) were used. After 24 h, cells were exposed in 3-4, 5-dimethylthiazol-2-yl-2, 3-diphenyl tetrazolium bromide reagent (MTT assays) to increasing dosages of phosphatidylcholine formulation (0.0156-0.5 mg/ml) or an equivalent vehicle, sodium deoxycholate solution, pH 9.0 (0.0066-0.210 mg/ml). Viability was assessed after 1, 2, and 3 days of treatment. Fat tissue (4 x 4 cm) obtained ex vivo from the dorsal fat pads of five rabbits was injected with 2 ml of phosphatidylcholine formulation (50 mg/ml), sodium deoxycholate (21 mg/ml), or normal saline and incubated for 24 h. These were examined histologically to identify cell lysis and morphologic changes.
At 0.125- and 0.25-mg/ml doses of phosphatidylcholine solution, CADMEC and HSkMC were more sensitive (P < 0.001, one-way ANOVA) than adipocytes at all time points examined. Phosphatidylcholine formulation at a dose of 0.5 mg/ml and the equivalent vehicle, sodium deoxycholate, at a dose of 0.21-mg/ml both induced nearly 100% fat cell lysis after 24 h, and evidence of cell lysis as early as 6 h after exposure. After incubation of fat tissue for 24 h with phosphatidylcholine formulation, loss of intracellular lipid staining with an increase in extracellular lipids was seen.
Isolated sodium deoxycholate was almost as effective as the phosphatidylcholine formulation, at clinical concentrations, in reducing the viability of mature adipocytes over time. Similar cytotoxic effects of phosphatidylcholine formulation on normal foreskin fibroblasts, endothelial cells, and human skeletal muscle cells also were observed. The data prove that the formulation acts in a nonspecific manner and that its unintentional administration to other tissues causes cell death.
Subcutaneous phosphatidylcholine (PC) injection has become a popular technique for treating localized fat accumulation. Some clinical studies reported minor local soft tissue complications, such as ecchymosis, edema, and pain. However, there are no data on how PC affects the peripheral nervous tissue.
To investigate the local effect of PC on the peripheral nervous tissue of rats.
Twenty adult Lewis rats weighing between 200 and 300 g were divided into 2 experimental groups (n=10). In group 1, animals received an intrafascicular injection of 0.1 mL PC (Lipostabil 250 mg/5 mL) with a 30-gauge needle into the left posterior tibial nerve. In group 2, as a negative control group, 0.1 mL normal saline was injected intrafascicularly respectively. After the operation, rats were evaluated on days 7, 14, and 21 with walking track analysis. On day 21, all the animals were sacrificed and the left tibial nerves were taken for histologic study. Light and electron microscopic studies, along with morphometric analysis, were performed.
According to the tibial nerve indices, there were no signs of nerve damage observed in either of the groups, and there was no statistical difference between the groups (P> .05). The nerves that received PC and saline injections could not be distinguished grossly and appeared similar to segments of the nerve that did not come in contact with either solution. The number and diameter of fibers, the thickness of the myelin, and the percentage of neural tissue were comparable with normal controls. According to these analyses, there were no statistical differences between the 2 groups (P> .05).
This study demonstrates that in a rat model, even direct intraneural injection of PC causes no damage. This information should encourage people to consider broader applications of PC.
Skin-targeted ultrasound is a noninvasive technique that has been extensively used to evaluate age-related dermal changes, and the presence of a subepidermal low-echogenic band (SLEB) has been related to chronic UVR exposure in several studies. Since SLEB echogenicity is photoage-related, the aim of this study was to evaluate, through ultrasound imaging, the effects on skin photoaging of mesotherapy, a treatment approach currently used in cosmetic dermatology for skin rejuvenation. Twenty women (mean age: 46.7 range 40-60 years) with physical signs of moderate photoaging on the dorsum of the hands were enrolled and treated with multiple microinjections of hyaluronic acid (HA) salts of biotechnological origin (1.000 Kd) every week for 4 weeks. In all subjects, ultrasound evaluation was performed at each visit and 1 week after the last treatment to evaluate SLEB echogenicity changes during treatment. At the end of study, a statistically significant (p < 0.001) increase of SLEB echogenicity (with a mean increase of pixel numbers equal to 31.3%) was observed in 15 of 19 subjects who completed the study. Our preliminary study suggests that mesotherapy with HA may be an effective treatment for skin photoaging, as confirmed by ultrasound. Follow-up investigations on larger series of patients are necessary to further evaluate the safety, effectiveness, and duration of effect of this possible therapeutic approach to skin photoaging.
Mesotherapy, originally conceived in Europe, is a minimally invasive technique that consists of the intra- or subcutaneous injection of variable mixtures of natural plant extracts, homeopathic agents, pharmaceuticals, vitamins, and other bioactive substances in microscopic quantities through dermal multipunctures. Its application in cosmetic medicine and surgery is gaining in popularity and acceptance and is rapidly growing in profile at an alarming rate. Despite their attraction as purported rejuvenating and ''fat-dissolving'' injections, the safety and efficacy of these novel cosmetic treatments remain ambiguous, making mesotherapy vulnerable to criticism by the generally more skeptical medical community. The technique is shrouded in mystery and the controversy surrounding it pertains to its efficacy and potential adverse effects that are subject of much concern. As with any new technology, it is important to assess the benefits, safety, experience, and standardization of mesotherapy. More studies are necessary before it can be advocated as a safe and effective treatment for body contouring and facial rejuvenation. Although the claims made about mesotherapy may be hard to believe at face value, we must be cautious about rejecting new ideas. Just as absence of proof is not proof of absence, lack of scientific validation is not proof that it does not work.
Mixed dispersions of egg phosphatidylcholine (PC) and the bile salt sodium deoxycholate (DOC) were prepared by various methods, and their turbidities and proton magnetic resonance spectra were studied as a function of time. The spectra of dispersions prepared by dissolving both components in a common organic solvent and replacing the organic solvent by water did not change with time, indicating that the mixed aggregates formed represent "a state of equilibrium". In the 1H NMR spectra of these mixed aggregates, only signals from small mixed micellar structures were narrow enough to be observed. The dependence of the NMR line widths on the molar ratio of DOC to PC (R) is interpreted in terms of a model for the PC--DOC mixed micelles, according to which PC is arranged as a curved bilayer, the curvature of which increases with increasing R. Upon mixing PC with aqueous solutions of DOC, we found that the mixed aggregates formed are slowly reorganized and ultimately reach the same state of equilibrium. This reorganization was found to be a pseudo-first-order process, the rate constant of which depends linearly upon the detergent concentration. This process involves saturation of the outer bilayers of the multilamellar PC by detergent, followed by transformation of these bilayers into mixed micelles. It is concluded that the solubilization occurs through consecutive "peeling off" of lecithin bilayers.
Detergents are widely used for extracting and purifying membrane proteins. Four such detergents have been studied to find the extent to which they alone can alter black lipid film conductances. The slope of the plot of conductivity versus concentration for Triton X-100 is 4.54 in the range 0.025--0.15 mM; dodecyl sulphate 0.82 in the range 0.01--1 mM; sodium deoxycholate 1.03 in the range 0.01--1 mM and sodium cholate 1.37 in the range 0.1--10 mM. These ranges are below the respective critical micelle concentrations; above these concentrations the membranes break. Bilayer lipid membrane conductivity measured at constant detergent concentration increases with the conductivity of the bathing salt solution with a slope greater than 1, indicating an effect on the putative pore structures induced by detergents.
Beta-adrenergic stimulation and alpha 2-adrenergic inhibition increase lipolysis from fat cells. Twenty-eight obese women were placed on a calorie-restricted diet and one of five treatments was applied to one thigh three to five times per week for four weeks: (1) isoproterenol injections; (2) cream containing colforsin (forskolin), aminophylline, and yohimbine; (3) yohimbine cream; (4) colforsin cream; or (5) aminophylline cream. The opposite thigh was treated with a placebo (injection or cream). The treated thighs lost significantly more girth after treatment, both by injection and by cream. No adverse reactions were attributable to either the cream or the injections. It is concluded that local fat reduction from the thigh can be safely accomplished.
This communication addresses the state of aggregation of lipid-detergent mixed dispersions. Analysis of recently published data suggest that for any given detergent-lipid mixture the most important factor in determining the type of aggregates (mixed vesicles or mixed micelles) and the size of the aggregate is the detergent to lipid molar ratio in these aggregates, herein denoted the effective ratio, Re. For mixed bilayers this effective ratio has been previously shown to be a function of the lipid and detergent concentrations and of an equilibrium partition coefficient, K, which describes the distribution of the detergent between the bilayers and the aqueous phase. We show that, similar to mixed bilayers, the size of mixed micelles is also a function of the effective ratio, but for these dispersions the distribution of detergent between the mixed micelles and the aqueous medium obeys a much higher partition coefficient. In practical terms, the detergent concentration in the mixed micelles is equal to the difference between the total detergent concentration and the critical micelle concentration (cmc). Thus, the effective ratio is equal to this difference divided by the lipid concentration. Transformation of mixed bilayers to mixed micelles, commonly denoted solubilization, occurs when the surfactant to lipid effective ratio reaches a critical value. Experimental evaluation of this critical ratio can be based on the linear dependence of detergent concentration, required for solubilization, on the lipid concentration. According to the 'equilibrium partition model', the dependence of the 'solubilizing detergent concentration' on the lipid concentration intersects with the lipid axis at -1/K, while the slope of this dependence is the critical effective ratio. On the other hand, assuming that when solubilization occurs the detergent concentration in the aqueous phase is approximately equal to the critical micelle concentration, implies that the above dependence intersects with the detergent axis at the critical micelle concentration, while its slope, again, is equal to the critical effective ratio. Analysis of existing data suggests that within experimental error both these distinctively different approaches are valid, indicating that the critical effective ratio at which solubilization occurs is approximately equal to the product of the critical micelle concentration and the distribution coefficient K. Since the nature of detergent affects K and the critical micelle concentration in opposite directions, the critical ('solubilizing') effective ratio depends upon the nature of detergent less than any of these two factors.
An understanding of the action of many drugs requires a knowledge of how the drug reaches the site of action in a cell. A detailed knowledge of the structure and function of cell membranes is often required to understand the transport of drugs across the plasma membrane. To obtain this information proteins must be isolated. The isolation and characterisation of cell membrane proteins usually requires the solubilisation of the membrane and a method of separation of the various membrane proteins and glycoproteins. The starting point for such an investigation is the choice of a suitable surfactant (detergent) to solubilise the membrane. This review considers the range of surfactants that are available for membrane solubilisation, how surfactants interact with membranes, the part they play in the separation of integral membrane proteins and in the reconstitution of membrane proteins for functional studies. The solubilisation of specific membrane proteins and glycoproteins including the human erythrocyte anion transporter, mitochondrial porin, sarcoplasmic reticulum Ca(2+)-ATPase, the ATPase-active multidrug transporter P-glycoprotein, bacteriorhodopsin and rhodopsin are also discussed.
Patients with prominent periorbital fat pads often complain of having a persistent "tired" look and seek treatment from their dermatologist.
A non-surgical treatment of fat pads.
Thirty patients were treated for prominent lower eyelid fat pads with phosphatidylcholine injection. Pre- and posttreatment photographs were taken for long-term analysis.
A marked reduction of the lower eyelid fat pads was noted over the 2-year follow-up period. There were no recurrences.
The injection of phosphatidylcholine (250 mg/5 ml) into the fat pads is a simple office procedure that may postpone or even substitute for lower eyelid blepharoplasty.
Phosphatidylcholine injections are becoming an increasingly popular technique to treat localized fat accumulation. This formula is composed primarily of phosphatidylcholine and sodium deoxycholate, a bile salt used to solubilize the natural phospholipid in water. The mechanism through which this injectable phosphatidylcholine formulation causes localized fat reduction is unknown.
To investigate the active component and mechanism of action of an injectable phosphatidylcholine formulation in clinical use.
Cell viability and cell membrane lysis assays were performed on cell cultures and porcine skin after treatment with the phosphatidylcholine formula, isolated sodium deoxycholate, or common laboratory detergents Triton-X 100 and Empigen BB. In addition, we described the histologic changes after injection of these substances into porcine tissue.
A significant and comparable loss of cell viability, cell membrane lysis, and disruption of fat and muscle architecture was seen in cell cultures and tissue specimens treated with the phosphatidylcholine formula and isolated sodium deoxycholate. These findings were similar to the effects produced after treatment with laboratory detergents.
The phosphatidylcholine formula popularly used in subcutaneous injections for fat dissolution works primarily as a detergent causing nonspecific lysis of cell membranes. Our findings suggest that sodium deoxycholate is the major active component responsible for cell lysis. Detergent substances may have a role in eliminating unwanted adipose tissue. It is advised that physicians use caution until adequate safety data are available.
Despite the temporary side effects that cause a degree of discomfort, phosphatidylcholine injections can be used successfully in the treatment of localized and small fatty areas of the face, as it requires a few injections and less than one vial. Injection of phosphatidylcholine seems to be a better, safer, and more cost-effective treatment than liposuction in these specific cases. We point out that more studies should be performed to trace the safety profile and appropriate doses of phosphatidylcholine for the treatment of localized fat.
Lipomas are benign neoplasms of mature fat cells. Current treatments are invasive and carry the risk of scarring. Injections of phosphatidylcholine solubilized with deoxycholate, a bile salt, have been used to reduce unwanted accumulations of fat. Recent in vitro and ex vivo investigations indicate that deoxycholate alone causes adipocyte lysis.
We sought to report our experience treating lipomas using subcutaneous deoxycholate injections.
A total of 6 patients presenting with 12 lipomas were treated with intralesional injections of sodium deoxycholate (1.0%, 2.5%, and 5.0%) at intervals of 2 to 20 weeks. Tumor size, cutaneous reactions, and patients' subjective responses were recorded before and after treatment.
All lipomas decreased in size (mean area reduction, 75%; range, 37%-100%) as determined by clinical measurement (with ultrasound confirmation in one lipoma) after an average of 2.2 treatments. Several lipomas fragmented or became softer in addition to decreasing in volume. Adverse effects, including transient burning, erythema, and local swelling, were associated with higher deoxycholate concentrations but resolved without intervention. There was no clear association between deoxycholate concentration and efficacy.
Our clinical experience supports our laboratory investigations demonstrating that deoxycholate, rather than phosphatidylcholine, is the active ingredient in subcutaneously injected formulas used to treat adipose tissue. This small series suggests that low concentration deoxycholate may be a relatively safe and effective treatment for small collections of fat. However, controlled clinical trials will be necessary to substantiate these observations.
Cellulite describes the cutaneous dimpling of the thighs, buttocks, and hips that is seen predominately in women. Current evidence suggests that structural differences in fat architecture between the sexes account for its appearance. Mesotherapy, a method of delivering medication locally with the use of numerous cutaneous injections, has recently become a popular method to purportedly treat the condition.
An overview of cellulite and adipocyte physiology, with a literature review and appraisal of compounds commonly used in mesotherapy.
Experimental studies using individual mesotherapy ingredients for other conditions suggest a number of mechanisms, including lipolysis, disrupting connective tissue and augmenting circulation, which may theoretically improve cellulite. Peer-reviewed studies have not evaluated whether these effects translate clinically.
Until further studies are performed, patients considering mesotherapy for cellulite must be aware that the substances currently being injected to treat this cosmetically disturbing, but medically benign, condition have not been thoroughly evaluated for safety or efficacy.
Mesotherapy was originally conceived in Europe as a method of utilizing cutaneous injections containing a mixture of compounds for the treatment of local medical and cosmetic conditions. Although mesotherapy was traditionally employed for pain relief, its cosmetic applications, particularly fat and cellulite removal, have recently received attention in the United States. Another treatment for localized fat reduction, which was popularized in Brazil and uses injections of phosphatidylcholine, has been erroneously considered synonymous with mesotherapy. Despite their attraction as purported "fat-dissolving" injections, the safety and efficacy of these novel cosmetic treatments remain ambiguous to most patients and physicians.
To distinguish mesotherapy from phosphatidylcholine injections by reviewing their history and the relevant experimental or clinical findings.
A comprehensive search of Medline indexed literature and conference proceedings.
All the published studies evaluating the clinical efficacy of traditional mesotherapy currently originate from Europe. These reports focus primarily on musculoskeletal pain and vascular disease, rather than cosmetic applications. Although experimental data suggest that a number of traditional mesotherapy ingredients may theoretically reduce fat, these effects have not been supported in peer-reviewed studies. An increasing number of reports demonstrate that subcutaneous injections of a formula containing phosphatidylcholine combined with its emulsifier, deoxycholate, are effective in removing small collections of adipose tissue. Cell lysis, resulting from the detergent action of deoxycholate, may account for this clinical effect.
Mesotherapy is distinct from a method of treating adipose tissue with subcutaneous injections of deoxycholate alone or in combination with phosphatidylcholine. Additional clinical and experimental studies are necessary to more definitively establish the safety and efficacy of these treatments.
Orbital fat tissue, while important in protecting the eye, can protrude during aging, making a patient look 'tired'. Surgical correction, although traditionally the treatment of choice, can lead to scarring. Phosphatidylcholine (PPT) has been shown to reduce the size of these fat pads after direct injection. The compound, licensed in Europe for intravenous treatment of fat embolism, has recently gained interest for reducing localized fat by subcutaneous injection. However, there is a dearth of clinical data relating to efficacy and side effects.
An open-label study was conducted in 21 subjects with the goal of reducing the infraorbital fat pad size. The objective of this study was to evaluate the efficacy and safety of PPT after injection into infraorbital fat pads.
Twenty-one subjects were injected with 0.4 ml of PPT every 6 weeks to reduce prominent infraorbital fat pads. Pre- and post-treatment digital photographs were taken to document efficacy. In addition, side effects were recorded on a follow-up questionnaire.
In all, 74% of the subjects showed significant improvement after two to three treatments. Five of the enrolled subjects (23%) were non-responsive after two or more procedures and their treatment was discontinued. None of the patients had adverse side effects other than mild burning, erythema and swelling at the injection site. Nearly every patient maintained the results with no evidence of tissue damage after 6 months.
PPT injection into infraorbital fat pads resulted in a satisfactory cosmetic effect in most treated subjects. Most subjects required more than one treatment. This simple, office-based treatment provides a non-surgical alternative to patients with prominent infraorbital fat pads. More clinical data are required to fully assess the long-term safety and efficacy of this procedure.
Injection sclerotherapy is widely used for superficial varicose veins. The treatment aims to obliterate the lumen of varicose veins or thread veins. There is limited evidence regarding its efficacy.
To determine whether sclerotherapy is effective in improving symptoms and cosmetic appearance and has an acceptable complication rate; to define rates of symptomatic or cosmetic varicose vein recurrence following sclerotherapy.
We searched the Cochrane Peripheral Vascular Diseases Group trials register (April 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2006), MEDLINE and EMBASE (both inception to April 2006) and reference lists of articles. Manufacturers of sclerosants were contacted for additional trial information.
Randomised controlled trials (RCTs) of injection sclerotherapy versus graduated compression stockings (GCS) or 'observation', or comparing different sclerosants, doses, formulations and post-compression bandaging techniques on people with symptomatic and/or cosmetic varicose veins or thread veins were considered for inclusion in the review.
Data were extracted by authors and Review Group Co-ordinators independently.
Seventeen studies were included. One study comparing sclerotherapy to GCS in pregnancy found that sclerotherapy improved symptoms and cosmetic appearance. Three studies comparing sodium tetradecyl sulphate (STD) to alternative sclerosants found no significant differences in outcome or complication rates; another study found that sclerotherapy with STD led to improved cosmetic appearance compared with polidocanol, although there was no difference in symptoms. Sclerosant plus local anaesthetic reduced the pain from injection (one study) but had no other effects. Two studies compared foam- to conventional sclerotherapy; one found no difference in failure rate or recurrent varicose veins; a second showed short-term benefit from foam in terms of elimination of venous reflux. The recanalisation rate was no different between the two treatments. One study comparing Molefoam and Sorbo pad pressure dressings found no difference in erythema or successful sclerosis. The degree and duration of elastic compression had no significant effect on varicose vein recurrence rates, cosmetic appearance or symptomatic improvement.
Evidence from RCTs suggests that the choice of sclerosant, dose, formulation (foam versus liquid), local pressure dressing, degree and length of compression have no significant effect on the efficacy of sclerotherapy for varicose veins. The evidence supports the current place of sclerotherapy in modern clinical practice, which is usually limited to treatment of recurrent varicose veins following surgery and thread veins. Surgery versus sclerotherapy is the subject of a further Cochrane Review.
Phosphatidylcholine has been in safe use for over 30 years. Subcutaneous injections of phosphatidylcholine have now become used internationally for localized subcutaneous fat reduction on the face and body, but concerns about the safety of this treatment have arisen.
To assess retrospectively treatment outcomes and adverse effects associated with subcutaneous phosphatidylcholine use.
Thirty-nine UK doctors specifically trained and experienced in this treatment completed questionnaires, focusing on outcome and adverse effects experienced by patients.
Ten thousand five hundred and eighty-one treatments had been administered over a mean duration of 13.1 months. Localized adverse effects (swelling, erythema, burning/stinging, pain, tenderness and bruising) were described by most patients as "very mild' (18.4%) or "mild" (39.2%). The total incidence of systemic side-effects was 3%: diarrhoea, nausea, dizziness/light-headedness and intermenstrual bleeding were described by most patients as "very mild" (36%) or "mild" (55%). Only 15 (0.14%) "unexpected, unusually severe or prolonged" adverse reactions (commonly pain and/or swelling) were reported. These were all self-limiting and none were judged as serious. 73.8% of patients were either "very satisfied" or "satisfied" with treatment.
This treatment appears to be associated with minimal risks when used by specifically trained and experienced doctors. The possible risks associated with this treatment should be balanced against the risks of other treatment options.
Mesotherapy, as broadly defined, represents a variety of minimally invasive techniques in which medications are directly injected into the skin and underlying tissue in order to improve musculoskeletal, neurologic, and cosmetic conditions. There are few clinical studies evaluating the efficacy and safety of mesotherapy in any form. This study evaluates the histologic and clinical changes associated with one of the simplest formulations of mesotheraphy commonly used for skin rejuvenation.
Ten subjects underwent four sessions of mesotherapy involving multiple injections of a multivitamin and hyaluronic acid solution. Treatment was conducted at 4 monthly intervals. All subjects had pre- and post-treatment photographs and skin biopsies. Skin biopsies were evaluated with routine histology, mucin and elastin stains, and electron microscopy. Patient surveys were also evaluated.
Evaluation of photographs at 0, 3, and 6 months revealed no significant clinical differences. Light microscopic examination of pre- and posttreatment specimens showed no significant changes. Electron microscopic analysis of collagen fibers measurements did show smaller diameter fibres posttreatment.
No significant clinical or histologic changes were observed after multivitamin mesotherapy for skin rejuvenation. Multivitamin and hyaluronic acid solution facial mesotherapy does not appear to provide any significant benefit.
Injections with Lipostabil, a phosphatidylcholine (PDC) containing substance, have become a popular technique to treat localized fat accumulation and lipomas for aesthetic reasons. Despite its frequent use, the mechanism of action of PDC and histological changes of treated fat tissue still remain unclear. To investigate the histological changes of lipomas after treatment with PDC.
In all, fourteen lipomas (n = 14) in five patients presenting with multiple lipomas were treated with intralesional injections of PDC (Lipostabil, Nettermann, Germany). Histological changes with immunohistochemical analysis of the inflammatory process were evaluated 4, 10, 24, 48 h, 10 days, 30 days and 60 days after lipolysis.
Between 4 and 48 h after injection, histology shows a lobular neutrophilic infiltrate with partially destroyed fat cells. At day 10 the inflammatory process is accompanied by an infiltration of T-lymphocytes. After 60 days formation of macrophages with foam cells are visible, accompanied by thickened septa and capsula.
Lipolysis with PDC results in a distinct inflammatory reaction of affected fat tissue, similar to factitial panniculitis. Early destruction of fat cells may suggest the involvement of detergent or osmotic mechanisms in the process.
Recent articles have introduced the novel concept of chemical lipolysis through local injections. Phosphatidylcholine is the active drug in the commercial preparation used for this purpose, but some studies have suggested that sodium deoxycholate, an excipient of the preparation, could be the real active substance.
We decided to investigate whether phosphatidylcholine and sodium deoxycholate have any clinical efficacy in chemical lipolysis and their respective roles. We also studied the safety and side effects of the treatments.
Thirty-seven consecutive female patients were studied for the treatment of localized fat in gynoid lipodystrophy. Each patient received injections of a phosphatidylcholine/sodium deoxycholate preparation on one side and sodium deoxycholate on the contralateral side, each single patient being herself the control. Four treatments were carried out every 8 weeks in a double-blind, randomized fashion. Metric circumferential evaluations and photographic and ultrasonographic measurements throughout the study allowed for final judgment. A statistical evaluation concluded our study.
An overall reduction of local fat was obtained in 91.9% of the patients without statistically significant differences between the treated sides. Reduction values on the phosphatidylcholine/sodium deoxycholate-treated sides are in the order of 6.46% metrically and 36.87% ultrasonographically, whereas on the deoxycholate-treated sides they are in the order of 6.77% metrically and 36.06% ultrasonographically. Both treatments, at the dose used in the study, proved safe in the short term. The most common side effects were local and few, but were more pronounced on the deoxycholate-treated sides. No laboratory test was carried out.
Both treatments have shown moderate and equivalent efficacy in treating localized fat, with sodium deoxycholate having a slower postoperative resolution, suggesting that sodium deoxycholate could be sufficient by itself to determine fat cell destruction and that phosphatidylcholine could be useful for obtaining a later emulsification of the fat.
Injectable phosphatidylcholine, a lecithin-derived phospholipid, has been previously demonstrated to improve the appearance of infraorbital fat pad herniation. Current use internationally has led to a significant interest in this novel substance.
To evaluate the efficacy and safety of injectable phosphatidylcholine, we conducted an open-label study for the treatment of infraorbital fat pad herniation.
Patients received 0.4-mL phosphatidylcholine (50 mg/mL) injections within infraorbital fat pads every 2 weeks. Patient and physician grading of fat herniation, side effects, digital photographs, and a follow-up questionnaire was recorded.
Ten of the 13 enrolled patients had three to five treatments. Improvements in fat herniation were reported in 80% and 70% of patients as graded by the physician and patients, respectively. Sixty percent of patients assessed their improvement as equal or greater than 5 points (on a 10-point fat herniation scale); however, the physician judged 40% of patients improving to this degree. Little or no response was seen in three patients. Side effects included burning, erythema, and swelling at the injection site. At follow-up averaging 9 months, 50% of patients reported persistence of benefit, 20% experienced some fading, and 30% were the nonresponders.
Injectable phosphatidylcholine is a novel treatment for infraorbital fat herniation that may benefit some patients who are considering blepharoplasty. Larger studies evaluating long-term safety and efficacy of phosphatidylcholine for cosmetic purposes are warranted.
The safety of the lipodissolution procedure for the cosmetic treatment of fat is unknown.
The objective was to determine the subcutaneous tissue effects of phosphatidylcholine solubilized with deoxycholate (PC/DC) in rats and a human volunteer.
Rats were treated subcutaneously three times with 50, 300, or 600 microL of PC/DC formula on the abdomen in a chronic study (30 days). A human volunteer undergoing elective liposuction was similarly treated. Cell membrane lysis, cell viability, and histologic status were determined on fresh biopsies of subcutaneous fat from the injection sites.
PC/DC dose-dependently reduced membrane integrity and cell viability. Histologic alterations induced by PC/DC included fibroplasia, bandlike fibrosis in the region of the cutaneous muscle, and partial muscle loss. The highest dose caused widespread fat necrosis, fat cyst formation, and necrotic changes of the walls of small blood vessels. Histologic sections of subcutaneous tissue from the human volunteer showed dose-dependent panniculitis, fat cysts, and vessel necrosis. DC (2.5%), tested for comparison in the rat, exerted membrane and histologic effects similar to those of PC/DC. Solvent controls caused negligible alterations.
Injection lipolysis with PC/DC causes tissue fibrosis and necrosis of adipose and vascular tissues in rat and man, making the long-term safety of PC/DC for nonsurgical treatment of subcutaneous fat deposits uncertain.
Mesotherapy can be associated with noninfectious granulomatous panniculitis and consequent scarring.
AMRotundaMSKolodneyMesotherapy and phosphatidylcholine injections: historical clarification and review.Dermatol Surg200632446548016681654DPLeeSEChangSubcutaneous nodules showing fat necrosis owing to mesotherapy.Dermatol Surg200531225025115762227JESanchezSSanchezJLSanchezMVazquez-BotetPSanguezaSevere lobular panniculitis due to mesotherapy.Car J Dermatol2006334750