Cellulite: An Evidence-Based Review

Abstract

Cellulite is a multifactorial condition that is present in 80-90 % of post-pubertal women. Despite its high prevalence, it remains a major cosmetic concern for women. A wide range of products and treatments for cellulite reduction is available; however, no systematic review has been performed so far to evaluate the efficacy of the available treatment options for cellulite.
The objective of this review is to provide a systematic evaluation of the scientific evidence of the efficacy of treatments for cellulite reduction.
This systematic review followed the PRISMA guidelines for reporting systematic reviews and meta-analyses. Only original articles in English or German reporting data on the efficacy of cellulite treatments from in vivo human studies were considered. In total, 67 articles were analyzed for the following information: therapy, presence of a control group, randomization, blinding, sample size, description of statistical methods, results, and level of evidence.
Most of the evaluated studies, including laser- and light-based modalities, radiofrequency, and others had important methodological flaws; some did not use cellulite severity as an endpoint or did not provide sufficient statistical analyses. Of the 67 studies analyzed in this review, only 19 were placebo-controlled studies with randomization. Some evidence for potential benefit was only seen for acoustic wave therapy (AWT) and the 1440 nm Nd:YAG minimally invasive laser.
This article provides a systematic evaluation of the scientific evidence of the efficacy of treatment for cellulite reduction. No clear evidence of good efficacy could be identified in any of the evaluated cellulite treatments.

Full text

1 23
American Journal of Clinical
Dermatology
ISSN 1175-0561
Am J Clin Dermatol
DOI 10.1007/s40257-015-0129-5
Cellulite: An Evidence-Based Review
Stefanie Luebberding, Nils Krueger &
Neil S.Sadick

1 23
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EVIDENCE-BASED REVIEW
Cellulite: An Evidence-Based Review
Stefanie Luebberding
1
•Nils Krueger
1
•Neil S. Sadick
2
ÓSpringer International Publishing Switzerland 2015
Abstract
Background Cellulite is a multifactorial condition that is
present in 80–90 % of post-pubertal women. Despite its
high prevalence, it remains a major cosmetic concern for
women. A wide range of products and treatments for cel-
lulite reduction is available; however, no systematic review
has been performed so far to evaluate the efficacy of the
available treatment options for cellulite.
Objective The objective of this review is to provide a
systematic evaluation of the scientific evidence of the ef-
ficacy of treatments for cellulite reduction.
Methods This systematic review followed the PRISMA
guidelines for reporting systematic reviews and meta-ana-
lyses. Only original articles in English or German reporting
data on the efficacy of cellulite treatments from in vivo
human studies were considered. In total, 67 articles were
analyzed for the following information: therapy, presence
of a control group, randomization, blinding, sample size,
description of statistical methods, results, and level of
evidence.
Results Most of the evaluated studies, including laser-
and light-based modalities, radiofrequency, and others had
important methodological flaws; some did not use cellulite
severity as an endpoint or did not provide sufficient sta-
tistical analyses. Of the 67 studies analyzed in this review,
only 19 were placebo-controlled studies with randomiza-
tion. Some evidence for potential benefit was only seen for
acoustic wave therapy (AWT) and the 1440 nm Nd:YAG
minimally invasive laser.
Conclusion This article provides a systematic evaluation
of the scientific evidence of the efficacy of treatment for
cellulite reduction. No clear evidence of good efficacy
could be identified in any of the evaluated cellulite
treatments.
Key Points
No biophysical measurement exists with which to
evaluate cellulite.
Most of the studies reviewed had important
methodological flaws.
No clear evidence of good efficacy could be
identified in any of the evaluated cellulite treatments.
Some evidence indicates acoustic wave therapy
(AWT) and the 1440 nm minimally invasive laser
treatment could have a potential benefit on cellulite.
1 Introduction
Cellulite is a topographic and localized skin condition that
is most commonly found on the posterolateral thighs, but-
tocks, and abdomen. It is often identified by a dimpled or
orange-peel appearance of the skin’s surface. In 1978,
Nu
¨rnberger and Muller [1] first described cellulite as a re-
sult of sex-related differences in the structure of skin and
subcutaneous tissue. It is widely accepted that the perpen-
dicular orientation of the fibrous septa in women allows the
underlying fat to protrude, creating a rippled appearance.
&Stefanie Luebberding
stefanie.luebberding@rosenparkresearch.de
1
Rosenpark Research, Wilhelminenstraße 13,
64283 Darmstadt, Germany
2
Sadick Dermatology, 911 Park Avenue, New York, NY, USA
Am J Clin Dermatol
DOI 10.1007/s40257-015-0129-5
Author's personal copy

The oblique nature of these fibers in men appears to prevent
this phenomenon. More recent studies confirm these sex-
related structural differences [2] and further explain the
appearance of cellulite as a result of several overlapping
physiological alterations, such as focally enlarged fi-
brosclerotic septa that tether the skin in areas of cellulite
and/or an uneven dermal–hypodermal interface [3,4].
Although exact epidemiological data are still lacking,
most studies claim that cellulite is present in 80–90 % of
post-pubertal women [3]. Given the ubiquitous nature of
cellulite, it is more appropriately thought of as a secondary
sex characteristic rather than a disease. However, digitally
altered photos in the media continue to not only alter the
perception of beauty, but also to deceive the public about
the true frequency of this condition that remains a major
cosmetic concern for women.
One of the main problems in the evaluation of anti-
cellulite products and procedures is the lack of a precise
and reproducible method for quantifying cellulite. Avail-
able methods that objectify skin topography are either not
precise enough (e.g., stereoscopic systems) or use a mea-
surement field that is too small to capture the whole cel-
lulite pattern (e.g., fringe projection systems). Therefore, a
myriad of techniques measure cellulite indirectly with a
surrogate marker instead of measuring the cellulite itself.
The most common approach taken to assess the im-
provement of cellulite is to compare thigh circumference
measurements before and after treatment [5,6]. However,
this technique has low reliability, and it is not yet proven that
a reduction in circumference and/or subcutaneous fat corre-
sponds with a decrease in cellulite severity. The same applies
to the use of calipers [7], magnetic resonance imaging (MRI)
[8], or X-ray imaging [9], although MRI assessments can be
used to identify the presence of underlying septa associated
with the presence of depressed cellulite lesions [4]. Another
approach taken to assess the efficacy of cellulite treatment is
the measurement of skin elasticity [10] or through dermal
parameters like dermal thickness or density measurements
[11]. While it is accepted that these are important in skin
aging, whether they have a significant influence on cellulite is
unclear. This also applies to other methods that assess blood
flow or vascularization, like laser Doppler [12] or thermog-
raphy [13]. As long as there is no clear proof for a correlation
between these parameters and cellulite, the suitability of
these methods remains speculative.
The clinical assessment of cellulite remains a subjective
one despite clear qualitative and quantitative measures
taken to make evaluation more effective and reliable. While
the 4-point Nu
¨rnberger–Muller (NM) scale has been used
for decades [1], the Cellulite Severity Scale (CSS) by
Hexsel et al. [14] has become the new standard classifica-
tion system for clinical evaluation and treatment response.
This scale adds four additional clinical morphologic
features to the NM scale: the number of evident depres-
sions, the depth of the depressions, the morphological ap-
pearance of skin surface alterations, and the grade of laxity
and flaccidity (sagging skin). The severity of each item is
graded from 0 to 3, allowing for a final sum between 1 and
15. The sum could also be 0, in case of complete cellulite
absence. Even though the scale is validated and comes with
a set of pictures illustrating each morphological feature, the
clinical rating of cellulite is still not entirely objective and is
subject to variation. This is complicated by the fact that the
process of taking standardized photos of cellulite is difficult
and might require special equipment with specific room
conditions for optimal performance [15].
The objective of this review is to provide a systematic
evaluation of the scientific evidence of the efficacy of treat-
ments for cellulite reduction. Providing physicians and
practitioners with an overview of available treatment options,
including their capabilities and limits, will increase under-
standing in the treatment of this challenging skin condition.
2 Materials and Methods
This systematic review followed the PRISMA (Preferred
Reporting Items for Systematic Reviews and Meta-
Analyses) guidelines [16]. In September 2014, we per-
formed a literature search in the PubMed and ScienceDir-
ect databases using the string: cellulite OR ‘edematous
fibrosclerotic panniculopathy’ OR ‘gynoid lipodystrophy’
OR ‘adiposis edematosa’, resulting in 1000 references.
Only original articles in English or German reporting data
on the efficacy of cellulite treatments from in vivo human
studies were considered. Two review team members (SL
and NK) retrieved and independently assessed the poten-
tially relevant articles as well as their references [3,17–28].
One relevant study that has not yet been published was also
added because study information is publicly available [29].
Conference papers and abstracts were excluded, as sug-
gested by PRISMA guidelines. In total, 67 articles were
analyzed for the following information: therapy, presence
of a control group (placebo, untreated, or active), ran-
domization, blinding, sample size, description of statistical
methods, results, and level of evidence (Fig. 1).
3 Results
Although cellulite is not a disease in the proper sense and
there is no current cure for it, a multitude of treatments
have been developed to improve its appearance. Along
with the application of laser, light, sound or radiofrequency
(RF) energy, more conventional treatment modalities have
been evaluated, including cosmeceuticals, supplements,
S. Luebberding et al.
Author's personal copy

and mechanical stimulation. Minimally invasive tech-
niques, like subcision and collagenase injections, are in-
tended to break the septa that cause dimpling. Although the
treatments widely differ, they are all designed to minimize
the cellulite appearance and to achieve a smoother skin
surface.
3.1 Mechanical Stimulation
One of the oldest methods of cellulite treatment is me-
chanical tissue stimulation. This involves lymphatic drai-
nage of the skin, which is either performed manually or
with an assisted device. A device-based modality delivers
positive pressure to the skin and subcutaneous tissue via
rhythmic folding and unfolding as well as negative pres-
sure through aspiration [30]. It is assumed that this me-
chanical stimulation causes damage to the subcutaneous fat
cells. As these damaged fat cells heal, they are purported to
rebuild with an improved distribution that evens skin
contour [31]. Manual mechanical stimulation of the skin is
further supposed to stimulate microcirculation as well as
lymphatic drainage to improve lymphedema, which may
further improve the appearance of cellulite [32,33].
Six studies evaluated the effect of mechanical stimula-
tion on the appearance of cellulite (Table 1). Among the
studies, only one was a randomized controlled study (RCT)
[7], whereas five were observational studies [30,32,34–
36]. The efficacy of the treatments was mainly assessed by
clinical assessment and circumference measuring. One
study used a digital caliper to determine fat thickness [7].
The device-based deep tissue massage was evaluated in
two uncontrolled studies [30,34]. In total, 151 subjects
were treated with 15 treatments each. Both studies found a
significant improvement in cellulite severity and circum-
ference reduction when compared with baseline. Three
studies [32,35,36], with a total of 39 subjects, evaluated
manual tissue stimulation and found a significant reduction
of thigh circumference after 10–14 treatments. However,
clinical improvement in cellulite appearance was not seen.
The only RCT, conducted by Bayrakci Tunay et al. [7],
compared the effectiveness of several massage techniques:
manual massage, manual lymphatic drainage, and con-
nective tissue manipulation. The results of 60 treated pa-
tients reported a significant decrease in thigh circumference
and fat thickness assessed by skin fold caliper in each of
the treatment methods.
Records idenfied through
database searching
(n = 1000 )
Screenin
g
Included Eligibility Idenficaon
Addional records idenfied
through other sources
(n = 1)
Records aer duplicates removed
(n = 743)
Records screened
(n = 272)
Records excluded
(not relevant)
(n = 471)
Full-text arcles assessed
for eligibility
(n = 101)
Full-text arcles excluded
(n = 171)
Studies included in
qualitave synthesis
(n = 67)
Excluded at data appraisal
(n = 34)
Fig. 1 Flow chart showing
identification and selection of
studies
Cellulite: An Evidence-Based Review
Author's personal copy

The efficacy of mechanical tissue stimulation in the
treatment of cellulite is not clear. Though an improvement in
cellulite grading and a reduction in thigh circumference was
observed after device-based deep tissue massage in most of
the studies, none of these studies compared mechanical tis-
sue stimulation with a placebo or an untreated control.
3.2 Topicals
Cosmetics and cosmeceuticals are among the most com-
monly used methods to reduce the unwanted appearance of
cellulite. Most anti-cellulite products contain caffeine, and/
or retinol formulations, and/or botanical derivatives as the
main active ingredients. The presumed therapeutic effect of
these ingredients is through the lipolysis of the adipose
tissue, the stimulation of the peripheral microcirculation to
facilitate lymphatic drainage, and the reduction of edema
[37]. Alkaloids, like caffeine, are used because of their
suggested effect on adipocyte lipolysis where phosphodi-
esterase activity is inhibited and cyclic adenosine
monophosphate (cAMP) levels are increased [23,38].
Caffeine should further activate the triglyceride lipase en-
zyme that converts triglycerides into free fatty acids and
glycerol [37]. Retinol serves as an anti-adipogenic by in-
hibiting the differentiation of human adipocyte precursor
cells [39,40] to improve skin thickness and tensile prop-
erties of cellulite skin in vivo [41]. The potential aim of
potent botanicals, such as Gingko biloba,Centella asiatica,
and horse chestnut are not only to slow lipogenesis and to
activate lipolysis, but also to act as antioxidants with anti-
inflammatory effects [37].
A total of 14 RCTs [12,13,41–52] plus one meta-
analysis with a systematic review [53] and two observa-
tional studies [54,55] that are missing inductive statistics
have been published on the treatment of cellulite with
topical formulations (Table 2). In total, over 600 patients
participated in these clinical trials. Five of these studies
enrolled fewer than 20 subjects [42,44,45,52,55], six
studies enrolled 21–50 subjects [12,41,43,46,49,54], and
four studies enrolled 51–100 subjects [47,48,50,51].
About half of the published studies evaluated complex
topical formulations combining caffeine and/or retinol with
other, mainly plant-derived, ingredients. Only two studies
[46,48] evaluated the effects of caffeine alone on cellulite
treatment, and two studies [45,55] evaluated retinol ex-
clusively. Of the four studies that tested a single active
ingredient, only one study [45] found the results of the
treatment group to be more promising than the results from
placebo treatment, whereas two studies [46,55] found only
a non-significant improvement of cellulite appearance after
the treatment. The efficacy of the treatments was mainly
determined by clinical assessment, comparison of circum-
ference measurements or additional biophysical measure-
ments, and/or by subject’s self-evaluation.
Of the 14 RCTs evaluating topical formulations, 11
were placebo-controlled RCTs [12,13,41–47,51,52]. Of
those 11, one [51] used oral placebo pills instead of a
topical placebo cream as a control. Nine studies [12,41,43,
45–47,49,52,54] were double-blind, three [13,42,50]
were single-blind, and four [44,48,51,55] were open-
label. Of the 14 controlled RCTs, only five [13,41,45,49,
51] found a significant improvement in cellulite grade and
circumference when compared with the control. Three
studies [12,43,47] found no difference between the
treatment and the control groups, and about three studies
[44,50,52] found no significant improvement post-treat-
ment in either the treated group or the non-active control
group.
Table 1 Overview of studies evaluating the efficacy of mechanical stimulation therapies in the treatment of cellulite
Therapy References Year Design Control Number Statistical
analysis
Results
a
Evidence
b
Device based Gu
¨lec¸[30] 2009 OS UC 33 Yes ?? 4
Combination Bayrakci Tunay et al. [7] 2010 RCT A 60 Yes NA 2b
Manual De Godoy and De Godoy [32] 2011 OS UC 14 Yes ?4
Manual De Godoy et al. [35] 2012 OS UC 10 Yes NA 4
Device based Kutlubay et al. [34] 2013 OS UC 118 Yes ?? 4
Manual Schonvvetter et al. [36] 2014 OS UC 15 Yes -4
Aactive, MA meta-analysis, NA not evaluated, OS observational study, Pplacebo, RCT randomized controlled study, SR systematic review,
Uuntreated, UC uncontrolled, ?indicates non-significant improvement, ?? indicates significant improvement, ??? indicates significant
improvement and superiority over control, -indicates no improvement to baseline, -- indicates worsening to baseline
a
With regard to the endpoint improvement of cellulite appearance
b
Levels of evidence: 1a =MA or SR (with homogeneity
a
) of RCTs; 1b =Individual RCT (with narrow confidence interval); 2a =SR (with
homogeneity) of cohort studies; 2b =Individual cohort study (including low-quality RCT); 3 =SR (with homogeneity) of case-control studies
or individual case–control Study; 4 =case-series (and poor-quality cohort and case–control studies); 5 =Expert opinion without explicit critical
appraisal, or based on physiology or bench research
S. Luebberding et al.
Author's personal copy

Despite the fact that primarily RCTs have been pub-
lished on this topic, there is little evidence that topical
treatments have a potential positive effect on the appear-
ance of cellulite. Most of the studies suggest that the
treatment has either no [44,50,52] or non-significant ef-
ficacy compared with baseline [46,54,55] or compared
with a non-active topical treatment [12,43,47]. The meta-
analysis by Turati et al. [53] corroborates this assumption.
3.3 Acoustic Wave Therapy
Shock waves are high-amplitude acoustic longitudinal
waves that transmit energy from the point of origin to the
therapy regions. Due to the high compressibility of gases,
even small pressure variations induce large changes in the
density and temperature of the treated medium [56,57]. In
the 1980s, high-energy focused extracorporeal generated
shock waves were first used for the lithotripsy fragmenta-
tion of kidney stones [58]. Today, less powerful acoustic
shock wave therapies (AWT) use focused or radial waves
to treat various diseases of the musculoskeletal system,
muscle aches, and pain syndromes. AWT has since been
introduced as a treatment option for cellulite [59]. It is
supposed that AWT may improve local blood circulation
via neovascularization [58]. Shock waves should further
increase cell proliferation of collagen and elastin fibers to
improve skin elasticity and to revitalize the dermis [56,58,
60]. AWT may also have a positive effect on lymphedema
by promoting lymph transport, which is a pathway often
associated with cellulite [61]. In vitro tests have further
shown that AWT may increase cell permeability, which
may stimulate the exchange of fat cells and activate
phospholipases through the beta-receptors on the fat cells’
membrane [60].
Seven publications [56,58,60,62–65] that evaluate the
effects of AWT on the appearance of cellulite are currently
available (Table 3). In total, 189 treated subjects received
approximately seven treatments in a period of 3–7 weeks
(averaging approximately 4.5 weeks). Only two of these
studies [63,64] are double-blind and placebo-controlled
RCTs. The other articles are open-label, of which four are
observational studies [56,58,60,65] and one is an RCT
using an untreated control [62]. Five studies [56,58,62,63,
65] treated one to 25 patients each, and two studies [60,64]
treated up to 59 patients. Biophysical measurements and
photographs were mainly used in the clinical assessment of
cellulite improvement. Overall, the study results are in-
consistent. Three [62–64] of the seven studies published
found AWT to be effective in the treatment of cellulite
when compared with the untreated control or compared
Table 2 Overview of studies evaluating the efficacy of topical therapies in the treatment of cellulite
Therapy References Year Design Control Number Statistical
analysis
Results
a
Evidence
b
Combination Epstein et al. [44] 1997 RCT P 11 Yes -2b
Retinol Kligman et al. [45] 1999 RCT P 19 Yes ??? 2b
Caffeine Lesser et al. [46] 1999 RCT P 41 Yes ?2b
Combination Collis et al. [50] 1999 RCT P/U/A 52 Yes -2b
Combination Pie
´rard-Franchimont et al. [42] 2000 RCT P 15 Yes NA 2b
Combination Bertin et al. [12] 2001 RCT P 46 Yes ?? 2b
Combination Rao et al. [54] 2005 OS P 34 No ?4
Retinol Fink et al. [55] 2006 OS U 15 No ?2b
Combination Sasaki et al. [52] 2007 RCT P 9 Yes -2b
Caffeine Lupi et al. [48] 2007 RCT U 99 Yes NA 2b
Combination Vogelgesang et al. [49] 2011 RCT P/A 50 Yes ??? 2b
Combination Mlosek et al. [51] 2011 RCT P 61 Yes ??? 2b
Combination Sparavigna et al. [13] 2011 RCT P 23 Yes ??? 2b
Combination Roure et al. [47] 2011 RCT P 78 Yes ?? 2b
Combination Al-Bader et al. [43] 2012 RCT P 35 Yes ?? 2b
Various Turati et al. [53] 2014 MA/SR UC NA NA -1a
Combination Dupont et al. [41] 2014 RCT P 40 Yes ??? 2b
Aactive, MA meta-analysis, NA not evaluated, OS observational study, Pplacebo, RCT randomized controlled study, SR systematic review,
Uuntreated, UC uncontrolled, ?indicates non-significant improvement, ?? indicates significant improvement, ??? indicates significant
improvement and superiority over control, -indicates no improvement to baseline, -- indicates worsening to baseline
a
With regard to the endpoint improvement of cellulite appearance
b
For categories of levels of evidence, see Table 1
Cellulite: An Evidence-Based Review
Author's personal copy

with those treated with the sham device. However, the
results of two studies [58,65] were not able to determine a
significant effect of AWT on cellulite improvement com-
pared with baseline.
Numerous meta-analyses and systematic reviews of
AWT in other medical applications have reported good
efficacy regarding the treatment of chronic plantar fasciitis
and tendinopathies [66–69]. Although more studies are
needed to further evaluate the ability of AWT to treat
cellulite, there might be some evidence that suggests AWT
has good efficacy.
3.4 Laser- and Light-Based Devices
Although the proposed mechanism of action is not yet fully
understood, non-invasive long-pulsed 1064 nm Nd:YAG
lasers have been used in the treatment of cellulite. This
wavelength has been used successfully for non-ablative
facial rejuvenation [70,71]. It is known to deliver thermal
energy into the deep dermis and the hypodermis to generate
a wound-healing response that promotes the formation of
new collagen [72,73]. Previous studies postulated that a
thicker layer of collagen may compress fat herniation,
thereby improving the appearance of cellulite [2,74].
So far, only two open-labeled randomized studies [74,
75] have been published evaluating the effect of non-in-
vasive 1064 nm Nd:YAG laser light on cellulite (Table 4).
In both studies, an untreated area served as a control. A
total of 31 subjects received three treatments at 3- to
4-week intervals. Bousquet-Rouaud et al. [75] found a
significant improvement of dermis density and a reduction
of dermis thickness assessed by ultrasound; however, a
significant improvement of cellulite severity was not ob-
served. This outcome is consistent with the results of Truitt
et al. [74], who reported a non-significant improvement in
cellulite grading only in 5 of 16 subjects. Heretofore, there
is little evidence that the non-invasive use of a 1064 nm
Nd:YAG laser is effective for the treatment of cellulite.
A different approach to treating cellulite is with the
minimally invasive pulsed 1440 nm Nd:YAG laser,
formerly 1064 nm. The apparatus has a side-firing fiber and
temperature-sensing cannula that is placed subdermally.
This technology is supposed to have three different effects on
the structural features that cause the clinical appearance of
cellulite. First, this technique should smooth the uneven
dermal-hypodermal interface by selectively melting the
hypodermal adipocytes that protrude into the dermis. Se-
cond, it should sever the hypodermal septa that connect the
dermal and muscle layers by thermal subcision. Lastly, the
1440 nm Nd:YAG laser should heat the dermis from the
inside out to increase dermal thickness and skin elasticity by
stimulating neocollagenesis and collagen remodeling [76].
Five observational studies [10,76–79] evaluated the
minimally invasive Nd:YAG laser for the treatment of
cellulite (Table 4). In total, 154 subjects participated in the
clinical trials, but only two studies included more than 50
patients [77,79]. All subjects received one treatment along
the upper thigh and buttock and were followed-up for be-
tween 6 and 30 months. The efficacy of the treatments was
mainly assessed through biophysical measurements, pho-
tographic documentation, and subject’s self-evaluation.
Three of these studies [10,77,78] utilized a blinded in-
vestigator to evaluate the results. Overall, the study results
confirmed positive efficacy of minimally invasive 1440 nm
Nd:YAG laser treatment on cellulite. In fact, two studies
showed a significant improvement of the clinical appear-
ance of cellulite, especially a reduction in dimple depth and
count, as well as a smoother contour [77,78]. In addition,
two studies [10,76] found a significant increase in skin
elasticity and dermal thickness post-treatment. However,
Goldman et al. [79] did not perform statistical analyses of
the collected data to corroborate previous trends.
Table 3 Overview of studies evaluating the efficacy of acoustic wave therapy in the treatment of cellulite
References Year Design Control Number Statistical analysis Results
a
Evidence
b
Angehrn et al. [58] 2007 OS UC 21 No ?4
Christ et al. [60] 2008 OS UC 59 No NA 4
Kuhn et al. [56] 2008 OS UC 1 No NA 4
Adatto et al. [62] 2010 RCT U 25 Yes ??? 2b
Russe-Wilflingseder et al. [63] 2013 RCT P 16 Yes ??? 2b
Knobloch et al. [64] 2013 RCT P 53 Yes ??? 2b
Schlaudraff et al. [65] 2014 OS UC 14 Yes ?4
NA not evaluated, OS observational study, Pplacebo, RCT randomized controlled study, Uuntreated, UC uncontrolled, ?indicates non-
significant improvement, ?? indicates significant improvement, ??? indicates significant improvement and superiority over control,
-indicates no improvement to baseline, -indicates worsening to baseline
a
With regard to the endpoint improvement of cellulite appearance
b
For categories of levels of evidence, see Table 1
S. Luebberding et al.
Author's personal copy

In addition to high-energy lasers, low-level lasers that
operate in the milliwatt power range are also used in the
treatment of cellulite. Unlike common high-energy lasers,
low-level laser therapy (LLLT) does not cause significant
heating in the tissue structure. The proposed increase of
cAMP production via cytochrome C oxidase should result
in the breakdown of the cell’s lipids in adipocytes, the
formation of transitory pores in their cell membrane, and
subsequent cell collapse [80]. Therefore, LLLT should
stimulate collagen synthesis by inducing a biological cas-
cade at the cellular level [81,82].
Three studies [83–85], which enrolled between 20 and
68 subjects each, have been published evaluating the effi-
cacy of LLLT on cellulite (Table 4). One study [84] used a
low-level laser light device employing a 532 nm wave-
length. This study is randomized, single-blind, and sham
controlled. Results indicate significant cellulite improve-
ment and circumference reduction within the treated group.
Nootheti et al. [83] published a second RCT on this topic
comparing the ability of a low-energy diode laser in the
808 nm infrared (IR) light spectrum to treat cellulite with
an RF device. The study does not show any significant
changes in cellulite severity after the treatment. An ob-
servational study [85] was recently published evaluating
the efficacy of 635 nm low-level laser light on localized
adiposity and cellulite. Though the results from the
ultrasound assessment showed a significant reduction of fat
thickness, there was no visible improvement in the clinical
appearance of cellulite verifiable.
In summary, whether LLLT is able to effectively treat
cellulite is unclear because of inconsistent results. There-
fore, more studies with larger sample sizes are necessary to
evaluate the true efficacy of these devices.
IR light, produced from light-emitting diode (LED) light
sources, is also used in the treatment of cellulite. The
heating of the skin is supposed to promote microcircula-
tion, lymphatic drainage, and collagen synthesis [86].
Paolillo et al. [87] conducted an RCT with 20 subjects who
were treated with 850 nm IR radiation (Table 4). The re-
sults indicate that tissue heating may significantly reduce
thigh circumference. In a double-blind RCT conducted by
Bagatin et al. [11], IR radiation has a significant positive
impact on the subjects’ quality of life, but not on the im-
provement of cellulite appearance.
Devices that combine laser- and light-based radiation
with mechanical stimulation are frequently used to treat
cellulite in practice today. A common approach combines a
lower-level 915 nm continuous wave diode laser and
650 nm LED energy with mechanical manipulation. The
IR 915 nm laser light is supposed to be absorbed by adi-
pocytes to elicit thermal effects [88], while the low-level
650 nm light should create temporary pores on the cellular
Table 4 Overview of studies evaluating the efficacy of laser- and light-based therapies in the treatment of cellulite
Therapy References Year Design Control Number Statistical
analysis
Results
a
Evidence
b
LLLT Nootheti et al. [83] 2006 RCT A 20 Yes ?2b
Combination Lach [8] 2008 RCT A 74 Yes NA 2b
1440 nm Nd:YAG minimally invasive Goldman et al. [79] 2008 OS UC 52 No ?4
1064 nm Nd:YAG Bousquet-Rouaud et al. [75] 2009 RCT U 12 Yes -2b
Combination Kulick [91] 2010 OS UC 17 No ?4
Combination Gold et al. [90] 2011 RCT U 83 Yes NA 2b
1440 nm Nd:YAG minimally invasive DiBernado [76] 2011 OS UC 10 Yes ?4
IR Paolillo et al. [87] 2011 RCT U 20 Yes NA 2b
1064 nm Nd:YAG Truitt et al. [74] 2012 RCT U 19 Yes ?2b
1440 nm ND:YAG minimally invasive DiBernado et al. [77] 2013 OS UC 57 Yes ?? 4
1440 nm ND:YAG minimally invasive Katz [78] 2013 OS UC 15 Yes ?? 4
1440 nm ND:YAG minimally invasive Sasaki [10] 2013 OS UC 20 Yes ?4
LLLT Jackson et al. [84] 2013 RCT P 68 Yes ?? 2b
LLLT Savoia et al. [85] 2013 OS UC 33 Yes NA 4
IR Bagatin et al. [11] 2013 RCT U 25 Yes -2b
Combination Hexsel et al. [92] 2013 OS UC 15 Yes ?4
Aactive, IR infrared, LLLT low-level laser therapy, NA not evaluated, Nd:YAG neodymium-doped yttrium aluminium garnet laser, OS obser-
vational study, Pplacebo, RCT randomized controlled study, Uuntreated, UC uncontrolled, ?indicates non-significant improvement,
?? indicates significant improvement, ??? indicates significant improvement and superiority over control, -indicates no improvement to
baseline, -- indicates worsening to baseline
a
With regard to the endpoint improvement of cellulite appearance
b
For categories of levels of evidence, see Table 1
Cellulite: An Evidence-Based Review
Author's personal copy

membrane to increase permeability. These actions allow
the fat to escape into the extracellular space [89]. Me-
chanical massage is not only supposed to facilitate the
transport of the fat into the lymphatic system, but also to
promote lymphatic drainage, subcutaneous blood flow, new
collagen deposition, and to firm and tone the skin [50,89].
Four studies have been published evaluating the efficacy
of treatment: two larger RCTs (n
total
=157) [8,90] and
two small, open-label observational studies (n
total
=32)
[91,92] (Table 4). The RCTs used either massage alone or
an untreated area as a control. Overall, the subjects re-
ceived 3–14 (average: 8.25) treatment sessions on the
thighs, ranging from 3 days to 6 weeks. All available
studies used circumference measurements and photo-
graphic documentation for clinical assessment. Only Gold
et al. [90] assessed the efficacy with a blinded evaluation of
the photographs, while Lach [8] used an MRI to evaluate
fat thickness. The reduction of thigh circumference in the
studies conducted by Gold et al. [90] and Hexsel et al. [92]
was significant, suggesting that combination therapy may
have relatively good efficacy. In a comparable study, Lach
[8] reported a reduction in fat thickness. However, none of
the published studies indicated a significant improvement
in cellulite appearance. Moreover, the observational study
by Kulick [91] only provides descriptive results.
In summary, it cannot be stated that all laser- and light-
based approaches are efficient. While there is very little
evidence that the non-invasive use of 1064 nm Nd:YAG
lasers is effective, the minimally invasive 1440 nm lasers
seem to significantly improve the clinical appearance of
cellulite, decrease dimple depth, the number of dimples,
and smoothen the contour of the skin. However, consistent
reproducibility of these results is still pending. The efficacy
of LLLT for the treatment of cellulite is also unclear, as
study results are conflicting. Because a significant im-
provement in cellulite appearance has not yet been found in
any of the clinical studies, devices that combine light en-
ergy and mechanical stimulation are not recommended
treatments at this point.
3.5 Radiofrequency
RF techniques are frequently used to treat cellulite. It is
commonly proposed that heating skin with RF energy leads
to a thermally mediated reaction in the dermis associated
with collagen denaturation and followed by tissue tight-
ening. The extent of the thermal effect in the skin is de-
pendent on the level of the tissue’s resistance to the
electricity flowing through it [93]. The heat that is deliv-
ered to the subcutaneous layer is presumed to be absorbed
by adipocytes to supposedly induce the breaking down of
fat cells through the membrane’s lysis [94,95]. Subse-
quently, a wound-healing process such as collagen
neosynthesis would therefore improve various tissue
characteristics [95,96].
An array of RF devices is used to treat cellulite that vary
on the basis of power (high- and low-RF devices) and whe-
ther they combine IR radiation and/or massage. So far, three
studies have been published investigating low-level RF en-
ergy up to 50 W: one observational study [97] and two RCTs
[95,98] (Table 5). The RCTs used either a sham device or an
untreated area as a control. In total, 106 patients were treated,
receiving 8–36 treatments each. The subject-blinded RCT
conducted by Mlosek et al. [98] found the low-level RF de-
vice to be superior to the sham device in improving cellulite.
A significant improvement was observed in epidermis/der-
mis thickness, cellulite appearance, and reduction of cir-
cumference. Though the findings of Boisnic et al. [95] and
Manuskiatti et al. [97] are consistent, there was no significant
clinical improvement in the appearance of the cellulite.
Four studies have been published evaluating uni- [93,
99,100] or bipolar [94] high-energy RF (150–200 W)
devices (Table 5). Subjects of these studies (n
total
=116)
received 2–12 treatments each. One RCT [99] and three
observational open-label studies [93,94,100] used the
untreated thigh as the control area. Though the studies
report an improvement in cellulite after high-energy RF
treatment, the results were either not significant or do not
provide proper statistical analysis.
A combination therapy of RF (1 MHz, 20 W), IR light
(700–1500 nm, 12.5 W), and suction (750 mmHg negative
pressure) is also used to treat cellulite. Among the RF
devices, combination therapy is the most investigated
technique, with nine published scientific papers. Two RCTs
[83,101] and seven observational studies [5,6,102–106]
are currently available. The studies enrolled between 2 and
35 subjects each (n
total
=142). Of the observational stud-
ies, five [5,6,103–105] only provided a descriptive
statistic, including a simple summary of observations
without supporting statistical evidence (Table 5). However,
no significant improvements were found in the RCTs that
used an untreated area or those that used another treatment
device as a control [83,101]. Only the observational study
conducted by Hexsel et al. [102] reported a significant
reduction in hip circumference and a significant improve-
ment of buttock cellulite severity; however, there was no
significant reduction of thigh circumference.
In summary, the evidence provided for the efficacy of
high-energy RF and RF combination therapy for treating
cellulite is low; either no valid statistical analyses were
provided or the results did not show significant treatment
success. One exception could be the use of low-level RF
because one RCT showed significant improvement in cel-
lulite appearance after the treatment. However, more
double-blind RCTs with larger sample sizes are necessary
to confirm these results.
S. Luebberding et al.
Author's personal copy

3.6 Other Modalities
Additional cellulite treatments have been evaluated and
published in scientific journals on the topics of weight loss,
nutritional supplements, minimally invasive subcision,
carbon dioxide (CO
2
) therapy, occlusive compression
stockings, phonophoresis with hyaluronidase, as well as
collagenase injections.
The correlation of weight loss and appearance of cel-
lulite was evaluated by Smalls et al. [9] (Table 6). Ultra-
sound, X-ray, skin biomechanical properties,
anthropomorphic measurements, as well as 3D laser sur-
face scanning were used to assess cellulite improvement in
a cohort of 51 women with visible cellulite. Female sub-
jects who participated in a medically supervised weight
loss program were compared with those in a stable weight
control group. On average, cellulite severity decreased
following weight loss. However, for some subjects, the
severity increased with weight reduction. As a study shows
that there is no irregular deposition of fat [33], this effect
may be caused by septa acting as a tethering system, thus
producing the typical dimpling pattern [4,107]. Another
possible explanation is that skin laxity might worsen with
major weight loss, which makes the appearance of cellulite
more prominent [9].
Several nutritional supplements are marketed with the
claim of improving the signs of cellulite. In two [108,109]of
the three published studies, the tested formulation contained
a plant complex based on Vitis vinifera,Ginkgo biloba,
Centella asiatica,Mellilotus officinalis,Fucus vesiculosus,
fish oil, and borage oil (Table 6). Savikin et al. [110]
evaluated the ability of organic chokeberry juice (OCJ) to
treat cellulite. The proposed mechanism of all these plant
extracts is an enhancement of cell metabolism by increasing
collagen and elastin synthesis, the reduction of edema and
intestinal inflammation, and the improvement of microcir-
culation. The plant extracts should further act as potent an-
tioxidants that inhibit the oxidation of tissue molecules [108,
110]. A total of 239 subjects received dietary supplements in
two RCTs [108,109] and in one observational study [110].
Distante et al. [108] found the active treatment to be superior
to the control treatment and reported a significant reduction
in weight and circumference. There is also a significant
improvement in edema and cellulite appearance. However,
Lis-Balchin [109] did not find any significant improvement
in cellulite appearance when investigating the effect of the
same plant-derived supplements, but a statistically sig-
nificant increase in body weight. The observational study of
Savikin et al. [110] found a significant improvement in
thickness of all skin layers after the consumption of 100 mL
OCJ for 90 days. However, changes in cellulite severity
were not statistically analyzed.
Lee [111] evaluated the efficacy of transcutaneous ad-
ministration of CO
2
for the treatment of cellulite (Table 6).
Table 5 Overview of studies evaluating the efficacy of radiofrequency in the treatment of cellulite
Therapy References Year Design Control Number Statistical analysis Results
a
Evidence
b
Combination Sadick and Mulholland [104] 2004 OS UC 35 No ?4
Combination Alster and Tanzi [5] 2005 OS U 20 No ?4
Combination Kulik [103] 2006 OS UC 16 No ?4
Combination Alster and Tehrani [106] 2006 OS UC 2 No ?4
Combination Nootheti et al. [83] 2006 RCT A 20 Yes ?2b
Combination Wanitphakdeedecha and Manuskiatti [105] 2006 OS UC 12 No ?4
Unipolar RF Emilia del Pino et al. [93] 2006 OS UC 26 No NA 4
Unipolar RF Goldberg et al. [100] 2008 OS UC 30 No ?4
Combination Sadick and Magro [6] 2007 OS U 16 No ?4
Combination Romero et al. [101] 2008 RCT U 10 Yes ?2b
Unipolar RF Alexiades-Armenakas et al. [99] 2008 RCT U 10 Yes ?2b
Bipolar RF van der Lugt et al. [94] 2009 OS UC 50 No ?4
Low-level RF Manuskiatti et al. [97] 2009 OS UC 37 Yes ?4
Low-level RF Boisnic et al. [95] 2010 RCT U 24 Yes ?2b
Low-level RF Mlosek et al. [98] 2012 RCT P 45 Yes ??? 2b
Combination Hexsel et al. [102] 2011 OS UC 11 Yes ?? 4
Aactive, NA not evaluated, OS observational study, Pplacebo, RCT randomized controlled study, RF radiofrequency, Uuntreated, UC
uncontrolled, ?indicates non-significant improvement, ?? indicates significant improvement, ??? indicates significant improvement and
superiority over control, -indicates no improvement to baseline, -- indicates worsening to baseline
a
With regard to the endpoint improvement of cellulite appearance
b
For categories of levels of evidence, see Table 1
Cellulite: An Evidence-Based Review
Author's personal copy

CO
2
therapy is supposed to disrupt adipocyte tissue and
alter microcirculation [112]. In this observational study,
101 female subjects underwent treatment of the abdomen
and the thigh. Though cellulite severity was not evaluated
over time, a significant weight loss and circumference re-
duction in the treated group was reported.
The influence of occlusive compression stockings on
cellulite was assessed in a randomized observational study
conducted by Rao et al. [113] (Table 6). The female subjects
used an anti-cellulite cream on both legs and were assigned
an occlusive neoprene garment to wear on either the left or
right leg. Of the 17 subjects who completed the study, 13
noticed an overall improvement of cellulite on both legs, but
only six noted a greater improvement on the leg that was
occluded. Independent evaluators found a slightly better
improvement on the leg treated with occlusion.
Da Silva et al. [114] evaluated the effect of ultrasound in
combination with topical hyaluronidase on patients with
cellulite (Table 6). The RCT included 42 subjects who
received ten ultrasound treatments of the gluteal region
over the course of 3 weeks. Either standard ultrasound
alone or ultrasound therapy with additional hyaluronidase
gel was applied. The drug was added with the intention of
promoting the depolymerization of fibrous edema in the
interstitial tissue to facilitate local metabolic changes. The
results show that combination therapy may significantly
decrease skin thickness better than exclusive ultrasound.
Changes in cellulite severity were neither specified nor
statistically analyzed.
The treatment efficacy of subcision, a technique in
which connective tissue septa is cut through to elevate
depressed and dimpled skin [115], was also reviewed as a
cellulite treatment option. In a retrospective observational
study, Hexsel and Mazzuco [116] evaluated the cases of
232 female patients. They found the surgical procedure to
be effective in the improvement of cellulite and to yield a
high patient satisfaction rating (Table 6). However, a reli-
able and inductive statistical analysis was not performed.
A new approach to treating cellulite is the injection of
collagenase (Clostridium histolyticum) into the septa that
supposedly cause cellulite dimpling. The results of a first
randomized controlled phase IIa study of 150 females indi-
cated that this approach seems to be safe and efficient for the
treatment of cellulite [29]. In this study, those who received
mid or high doses had a significant improvement in the cel-
lulite appearance, according to investigators and patients.
Scientific evidence for other cellulite therapies is
presently weak. While weight loss seems to improve cel-
lulite in most patients, it worsened in some. Additionally,
the use of nutritional supplements produced inconsistent
results. Only single studies have been published on CO
2
therapy, compression stockings, surgical subcision, or
combination of ultrasound and topically applied hyalur-
onidase treatment. None of the studies met the criteria to be
considered a viable efficacious option to treat cellulite. The
efficacy, safety, and result sustainability of collagenase
injections in the treatment of cellulite needs to be proven in
larger phase III studies.
4 Conclusion
This review provides for the first time a systematic
evaluation of previous scientific evidence (67 studies) re-
garding the efficacy of various cellulite treatments. Most of
these studies have important methodological flaws; some
do not use cellulite severity as an endpoint or do not pro-
vide sufficient statistical analyses. We strongly recommend
that more authors use the CONSORT (Consolidated Stan-
dards of Reporting Trials) statement to improve the quality
Table 6 Overview of studies evaluating the efficacy of different modalities in the treatment of cellulite
Therapy References Year Design Control Number Statistical
analysis
Results
a
Evidence
b
Nutrition Lis-Balchin [109] 1999 RCT P 20 Yes -- 2b
Subcision Hexsel, Mazzuco [116] 2000 OS UC 232 No ?4
Stockings Rao J et al [113] 2004 OS U 17 No ?4
Nutrition Distante [108] 2006 RCT A 190 Yes ??? 2b
Weight loss Smalls et al. [9] 2006 RCT U 51 Yes ??? 2b
CO
2
therapy Lee [111] 2010 OS UC 101 Yes NA 4
Hyaluronidase da Silva et al. [114] 2013 RCT A 42 Yes ?4
Nutrition Savikin et al. [110] 2014 OS UC 29 Yes -4
Aactive, NA not evaluated, OS observational study, Pplacebo, RCT randomized controlled study, Uuntreated, UC uncontrolled,, ?indicates
non-significant improvement, ?? indicates significant improvement, ??? indicates significant improvement and superiority over control, -
indicates no improvement to baseline, -- indicates worsening to baseline
a
With regard to the endpoint improvement of cellulite appearance
b
For categories of levels of evidence, see Table 1
S. Luebberding et al.
Author's personal copy

of study reporting in aesthetic medicine. The use of
blinding, randomization, and comparison with a placebo is
the most effective strategy to avoid potential bias in the
efficacy assessment. In many cases, the use of an intra-
patient design is an efficient strategy to reduce the number
of study subjects while increasing the quality of the trial.
The use of high-quality trial design is strongly encouraged
for testing the efficacy of cellulite treatments. A validated
cellulite scale should be used until an objective biophysical
method for the assessment of cellulite becomes available.
Of the 67 studies analyzed in this review, only 19 were
placebo-controlled studies with randomization.
Following a rigorous methodological approach proposed
by the PRISMA Statement, we were not able to identify
clear evidence of good efficacy in any of the evaluated
cellulite treatments, even with the most researched topics.
The only device with at least three RCTs that show clear
superiority over control is AWT. Another device that
showed congruent improvements in five studies was the
1440 nm minimally invasive laser. However, none of these
studies were controlled.
While there are precise techniques that assess many
dermatological conditions, there is still no biophysical
measurement technique to evaluate cellulite. Therefore,
most of the studies analyzed in this review used surrogate
markers to measure efficacy, including circumference
measurements, ultrasound, laser Doppler flowmetry, ther-
mography, plicometry, computerized tomography, and
MRI. Although a validated and widely accepted clinical
rating scale is available [14], a surprisingly high number of
studies did not use a clinical assessor’s rating. In conclu-
sion, the treatment of cellulite remains challenging. More
RCTs with high-quality trial design, a sufficient number of
subjects, and profound statistical analysis are needed for an
evidence-based recommendation.
Disclosures No funding was received for the conduct of the study or
the preparation of the manuscript. Stefanie Luebberding and Nils
Krueger have no conflicts of interest to disclose. Neil S. Sadick re-
ceived support for travel from Storz Medical AG and owns stock
options from Venus Concept.
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