In August of last year, the Wall Street Journal Health Blog reported that there was "not much high-quality evidence" for the effectiveness of cellulite treatments;1 for example, massage treatments produce swelling that reduces dimpling, but the dimpling reduction is only temporary. In addition, lasers or energy sources that are claimed to affect the fat cells under the skin have not been proven to have any long-term effect, according to the report. "There's nothing that has been shown in any objective way to create improvement for cellulite," Robert A. Weiss, then president-elect of the American Society for Dermatologic Surgery, told the Wall Street Journal.
What was he thinking? Where was the discussion of the huge range2 of anticellulite products and professional methods available to treat cellulite--from topical products and oral regimens, to garments? How could he ignore the body of technical knowledge generated by the suppliers of anticellulite ingredients, and the manufacturers of anticellulite products?
Nevertheless, Weiss gets some support from Enzo Berardesca at the San Gallicano Dermatological Institute in Rome. In 2006, Berardesca admitted that the efficacy of cellulite treatments is often debated. He wrote, "The evaluation of cellulite is based principally on clinical observation, thigh circumference measurements, body mass index and thermography, but for testing anticellulite products, more objective and noninvasive methods of evaluation are requested."2
Both Weiss and Berardesca are asking for objective proof that anticellulite products work. This "Bench & Beyond" column examines selected patents, journal articles, product promotion pieces and one dissertation--all from the last six years--for signs indicating that objective proof is on the way.
"Cellulite is currently considered to be â€œan endocrine metabolic microcirculatory disorder that causes interstitial matrix alterations and structural changes in subcutaneous adipose tissue," according to Distante et al.,3 who then go on to describe four competing theories for how that disorder originates: a circulatory defect, hypertrophy of the fat lobule, a physiological event, and numerous biochemical and metabolic alterations. The cause of cellulite is still a matter of debate.
Normally, the vascular supply to the adipose tissue is characterized by a fine and regular mesh of blood and lymph vessels that provides oxygen and the necessary nutrition and allows the removal of toxic substances. The onset of cellulite formation brings numerous histological changes, as described in the following stages.3,4
1. Even before any cosmetic problems are seen, capillary networks are lost in the dermal region as a result of a breakdown in blood vessel integrity (lipoedema), which swells the adipose tissue. Fluid retention (lipolymphoedema) and clumping of engorged fat cells occur in the subcutaneous tissue.
2. Minimal visual signs (i.e., slight skin surface lumpiness) appear on the thighs. Heterogeneity of blood vessels affects microcirculation. The aggregation of adipose cells and the growth of collagen fibrils hamper blood circulation, leading to circulatory stasis.
3. Pinching of the skin exacerbates the visual appearance of cellulite. Dermal metabolism is reduced due to vascular deterioration. Dermal thinning occurs in response to minimized protein synthesis and deterioration. Adipose cells isolated from nutrition and waste removal swell into micronodules surrounded by a stiff collagen layer (fibrosis).
4. Thigh skin appearance is very heterogeneous. Hard fat nodules in the dermal region are located upon palpation. Micronodules agglomerate into macronodules.
These stages illustrate the variety of circulatory and structural changes that would need to be addressed by treatment approaches.
The Ingredients and Products
In her 2005 University of Cincinnati dissertation on quantitative models for the investigation of cellulite,4 Smalls described numerous treatment approaches: weight loss; surgical procedures; carbon dioxide therapy; mechanical massage; and pharmacological agents, both oral and topical. Her Internet search on the term cellulite treatment early that year revealed 223,000 reports. Her survey of the claims and contents of four affordably priced topical treatments then available, and recapped here, illustrates the range of ingredients and possible mechanisms already employed in marketed anticellulite products.
- Avon's Cellu-Sculpt Anticellulite Slimming Treatment contains caffeine and botanical extracts with anti-inflammatory effects (Ginkgo biloba leaf extract, Panax ginseng extract, Bupleurum falcatum extract (hareâ€™s ear), Lagerstremia indica extract, and Malva sylvestris (mallow) extract.
- Jergens Skin Firming Moisturizer contains a Fucus vesiculosis (seaweed) extract that has anticoagulant properties, may enhance skin fibroblast expression of integrins, and reportedly increases skin firmness and reduces skin thickness (in the cheek). The product also contains Centella asiatica extract that has been reported to induce lypolysis when taken orally.
- Neutrogena Anti-Cellulite Treatment contains retinol, an unspecified seaweed extract and caffeine.
- RoC Retinol ActifPur Anti-Cellulite Treatment uses retinol, ruscus and caffeine to make the skin "appear" smoother and firmer.
New active ingredients and mechanisms are introduced every year. One recent example is a sulfo-carrabioses solutiona from BASF Beauty Care Solutions. This red seaweed hydrolyzate contains a new molecule--called k-carrageenan or, more precisely, sulfo-carrabiose--that is capable of capturing two polyamines--spermine and spermidine--that trigger fat accumulation. The ingredient is a simple and natural sugar trap with the claimed ability to hinder the bioavailability of these two pro-cellulite polyamines, reportedly resulting in a significant reduction of the appearance of cellulite when used with caffeine and compared to caffeine used alone (See Supporting Claims for Sulfo-carrabioses Solution).5
Supplier companies acquire an expertise in preferred anticellulite approaches and develop refinements over the years, as seen in the chronology of patents and patent applications. Examples include L'Oreal's interest in xanthine, Pierre Fabre's nurturing of garlic bulb extracts, and Lipo's series of patents on optically activated particles. Table 1 follows six years of US patent activity at 12 ingredient suppliers.
Finished product manufacturers have devised formulations containing ingredients selected to address cellulite's multiple causes. One example is Life Extension's Cellulite Suppress Formula, which contains seven active ingredients claimed to help correct the underlying causes of cellulite and target existing cellulite (see Figure 1).6 According to Life Extension, the formula contains several proprietary "fat-fighting" ingredients:
- A blend of sorbitan laurate and lauroyl prolineb shrinks adipocytes by turning on fat-burning receptors while simultaneously switching off receptors that inhibit fat burning; it also boosts fat oxidation and inhibits an enzyme called lipoprotein lipase to prevent fat storage (See Supporting Claims for a Blend of Sorbitan Laurate and Lauroyl Proline).
- Chenopodium quinoa seed extractc blocks the formation of blood vessels needed to transform pre-adipocytes into fully formed fat cells, thereby inhibiting the formation of new fat.
- Laminaria hyperborea extractd and Gelidium cartilagineum extracte work in synergy to stimulate key lipolytic enzymes and prevent the formation of new fat cells. They also have a detoxification effect by increasing waste elimination and drainage, thus helping to improve circulation.
Another "fat-fighting" ingredient is glycyrrhetinic acid, which reduces the availability of cortisol, a hormone involved in fat deposition. For skin firming, the formula contains escin (horse chestnut seed extract) to help strengthen the integrity of veins and capillaries, and Centella asiatica to improve the synthesis of collagen around the venous wall, thereby improving skin firmness and elasticity against burgeoning fat cells.6
Evaluating the Efficacy of Anticellulite Products
Even as new ingredients are developed, new methods are evolving for evaluating their efficacy. And as ingredients and approaches are sometimes selectively combined to provide a multimodal approach for treatment, something similar can be said for test instrumentation and methodologies involved in evaluating treatment efficacy.
MRI: In a 2006 article,2 Rona, Carrera and Berardesca described the main noninvasive techniques used in monitoring some of the physical parameters related to the cellulite condition. Thigh circumference is used to monitor edema. Ultrasound monitors
the thickness and the quality of the connective tissue and the edematous component of cellulite. Laser Doppler flowmetry provides information on blood flow and eythema by reporting on skin microcirculation. Thermography is a method for imaging the local skin temperature as a function of blood flow. Skin distensibility, elasticity and hysteresis are among the mechanical properties measured. Plicometery yields data for calculating the percentage of fat in the human body.
Magnetic resonance imaging (MRI) can distinguish structures at a submillimeter scale. It can also describe the physiology of the different skin layers. High spatial resolution MRI can differentiate the different skin departments (epidermis, dermis and hypodermis), â€œgiving new and interesting opportunities for the evaluation of anticellulite treatments,â€ according to these authors.
Measuring dimples: Only last year in presenting an improvement in measuring the dimpling aspect of cellulite, Bielfeldt et al. gave their own "up to now: assessment of anticellulite treatment evaluation methods.7 Those methods included digital photography, visual scoring, circumferential thigh measurements and subjective assessments. Ultrasound imaging and confocal microscopy were used to evaluate structural aspects. Skin elasticity and blood circulation provided some biomechanical data. "The use of such a variety of methods illustrates that science still searches for the one method to classify cellulite by using only one parameter," these authors wrote.
Two areas of innovation by Bielfeldt et al. provided a standardized method for characterizing dimpling of skin. First, improvements made in the set-up (i.e., positioning, illumination, background and camera position) for macrophotography of skin at the thighs enabled standardized photography of the area and reduced the non-treatment-related variations in the images made at different treatment times; a computerized custom-made rating program standardized the rating procedure by using a randomized and blinded presentation of the images. Second, a computerized custom-made analysis program improved the analysis of the ultrasound imaging of the dermis-subcutis border line and allowed the calculation of a modified roughness parameter Ram that characterizes the severity of the adipose protrusions from the subcutis into the dermis; these protrusions correlate positively with dimpling severity. Skin elasticity, blood circulation and thigh circumference were also measured.
"The true improvement in our work is in the visual assessment of cellulite," Stephan Bielfeldt, director of cosmetic research at proDERM Institute for Applied Dermatological Research in Hamburg, Germany, told C&T magazine. "To our knowledge, the degree of standardization of our cellulite photographs was not achieved and published before. All published technical methods like profilometry, elasticity measurement and ultrasound lack in credibility as long as a reliable visual assessment is not available to prove their relevance for the customer. In our work, we added a visual grading tool and with it, we showed the relevance of the technical methods," Bielfeldt said.
Microcirculation: "The first step in cellulite treatment is stimulation of microcirculation and the removal of accumulated fluids and toxic elements," Distante has written.3 "This can improve the interstitial matrix basal regulation, fibroblast activity and decrease interstitial edema, with subsequent increase in lipolysis and a better oxygen and nutrition of the adipose tissue."
In 2006 Distante et al. reported two studies aimed at determining the efficacy of a multifunctional plant complex in the oral treatment of cellulite.3 Of interest here is the variety of instrumental noninvasive evaluations performed.
In the first study, both clinical and instrumental methods were used before starting the treatment, and again after 20 and 60 days of treatment. Color Doppler ultrasound measured the following: morphological characteristics of subcutaneous cellular tissue; distance between skin and muscular fascia; permeability and valve function of deep and superficial venous system; changes in the microvessel caliber at the subcutaneous cellular tissue level. Digital photoplethysmography measured hemodynamic changes in leg sites following tiptoe exercises to determine changes in venous filling time due to bed emptying after exercise. Videocapillaroscopy analyzed the density, area, diameter and perimeter of capillaries.
The second study obtained measurements after 3, 10, 15, 30 and 47 days of treatment on 145 patients. The following data was collected on all patients: height; weight; arterial pressure; oxidative stress; Fat Mass Index; abdominal, thigh and ankle circumference; clinical cellulite evaluation; and self-assessment. The following additional data was collected on half of the patients: blood chemistry (16 factors); videocapillaroscopy (baseline flow and capillary density); Doppler laser flowmetry (resting flow, transcapillar power); ultrasound; pain ultrasonic test; echo color Doppler; light reflection rheography; and thermography.
In the words of these researchers, "The data obtained prove that the mixture of plant extracts contained in the products under investigation are effective in contrasting several physiopathological steps involved in the pathogenesis of cellulite, thus improving all clinical signs and symptoms associated to this condition." Here, at last, is one clear example of objective data proving the efficacy of an anticellulite treatment.
As demonstrated in this survey, the variety of anticellulite ingredients runs the gamut from herbal to engineered. The variety of instruments and methods to test their efficacy is broad and broadening. Nevertheless, this survey has found suspicion--even among well-meaning people--about the claims made for anticellulite treatments. In addition, this survey has found a need--expressed even by experts within this industry--to standardize and objectify the testing procedures and to find a more perfect single parameter that can be used to measure anticellulite efficacy.
Beyond the scope of this discussion is Lola Smalls' description of a novel, non-contact method using three-dimensional laser scanning technologyf to objectively characterize cellulite. She also described systems to: examine skin biomechanical propertiesg; examine skin thickness and dermal-subcutaneous border morphology using ultrasound; analyze body composition by dual energy x-ray absorptiometry. She also reported that quantitative model development by linear regression analysis has revealed that the surface roughness parameters Svm (mean depth of the five deepest valleys) and Sdr (surface roughness ratio) quantitatively describe the cellulite condition. She has been able to relate those roughness parameters to measurable skin biophysical parameters and tissue composition of the thigh. "However, determining the remaining variables that contribute to the cellulite condition would require assessment of the ultrastructure of the skin to determine the features that change with cellulite improvement/worsening," Smalls wrote.4 "The ability to pinpoint the factors that change with changes in cellulite severity will allow scientists to move the needle closer to targeted treatment modalities to ameliorate the condition."
Only a year after those words were written, Enzo Berardesca was able to report that with MRI "the diffuse pattern of extrusion of underlying adipose tissue into dermis is clearly imaged, and was found to correlate with cellulite grading."2 He recently told C&T magazine, "I really trust cellulite can be measured and monitored noninvasively."
It seems clear that objective data can be obtained to support or reject claims of anticellulite efficacy for topical products. What may be less clear is whether that data will be objectively presented to the public.
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1. J Goldstein, Slim evidence for effectiveness of cellulite treatments (posted Aug 19, 2008) http://blogs.wsj.com/health/2008/08/19/slim-evidence-for-effectiveness-of-cellulite-treatments/ (accessed Nov 29, 2008)
2. C Rona, M Carrera and E Berardesca, Testing anticellulite products, Int J Cosmet Sci 28 169â€“173 (2006)
3. F Distante, PA Bacci and M Carrera, Efficacy of a multifunctional plant complex in the treatment of the so-called "cellulite": Clinical and instrumental evaluation, Int J Cosmet Sci 28 191â€“206 (2006)
4. LRK Smalls, Development of quantitative models for the investigation of gynoid lipodystrophy (cellulite) [dissertation], Cincinnati, Ohio: University of Cincinnati (Apr 21, 2005), p 210, available at: www.ohiolink.edu/etd/view.cgi?acc_num=ucin1115923913 (accessed Nov 29, 2008)
5. Slim-Excess, a technical brochure from BASF Beauty Care Solutions, available at:
www.deverauxspecialties.com/sitebuildercontent/sitebuilderfiles/slimexcess.pdf (accessed Nov 29, 2008)
6. L Barclay, A scientific solution to unsightly cellulite, Life Extension 14(8) 29-37 (2008)
7. S Bielfeldt, P Buttgereit, M Brandt, G Springmann and K-P Wilhelm, Noninvasive evaluation techniques to quantify the efficacy of cosmetic anti-cellulite products, Skin Res Technol 14(3) 336-346 (2008)
8. C Stoltz, New biological strategy to correct cellulite, Cosmetic Science Technology (2007), available at: www.cosmeticsciencetechnology.com/companies/articles/1371.pdf (accessed Nov 29, 2008)