Received: 21 September 2023 | Accepted: 10 October 2023
DOI: 10.1111/jocd.16039
REVIEW ARTICLE
Cryolipolysis: A promising nonsurgical technique for localized
fat reduction
Barbara Kania1 | David J. Goldberg MD, JD1,2
1
Skin Laser and Surgery Specialists,
A Division of Schweiger Dermatology
Group, Hackensack, New Jersey, USA
2
Icahn School of Medicine at Mt. Sinai,
New York, New York, USA
Correspondence
David J. Goldberg, Skin Laser and Surgery
Specialists, A Division of Schweiger
Dermatology Group, 20 Prospect Ave.
#702, Hackensack, NJ 07601, USA.
Email: drdavidgoldberg@skinandlasers.
com
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.
J Cosmet Dermatol. 2023;22(Suppl. 3):1–7. 
Abstract
Background: Cryolipolysis, also known as fat freezing, is a nonsurgical technique spe-
cialized for localized fat reduction. Utilizing targeted cold exposure to adipose tissue,
cryolipolysis devices induce cellular apoptosis in adipocytes while sparing surround-
ing tissues, resulting in the selective disruption of fat cells and subsequent removal of
damaged cells by macrophages. A reduction of the fat layer produces a noninvasive
cosmetic benefit that provides an accessible alternative to liposuction. Objective and
subjective measurements have demonstrated significant reduction in fat volume and
high patient satisfaction rates. Cryolipolysis has been proven to be safe with minimal
adverse effects. However, further research is needed to fully understand the mecha-
nism of cryolipolysis and its efficacy in different treatment areas. This paper aims to
provide a comprehensive overview of cryolipolysis, including its mechanism of action,
indications, contraindications, adverse effects, results and outcomes, safety profile,
and areas requiring further research.
Methods: Our primary phase of literature review consisted of a PubMed search look-
ing for all published literature around cryolipolysis. We employed a review approach
that examined over 30 papers with the key search terms of “cryolipolysis,” “fat-freez-
ing,” “cosmetic dermatology,” “body contouring,” “adverse effects,” “adipocyte apop-
tosis,” “Coolsculpting®,” “cold panniculitis,” and “localized fat reduction.” We then
analyzed each paper, extracting relevant information to gain a multidimensional un-
derstanding of cryolipolysis to provide a comprehensive review.
Conclusion: Cryolipolysis, with its ability to target and reduce localized adipose tissue,
has emerged as a promising nonsurgical technique in the field of body contouring. It
offers patients a valuable option for achieving their desired fat reduction without
the need for a lengthy recovery period or major surgery. Cryolipolysis has shown
to reduce the number of adipocytes in the treated area, a phenomenon that can be
objectively quantified through various means, including fat caliper measurements,
ultrasound assessments, and 3D imaging, or subjectively observed through patient
satisfaction rates, clinical observations, and investigator assessments. In addition to
its effectiveness in reducing localized adipose tissue, cryolipolysis also holds potential
in the area of skin tightening. Preliminary studies suggest that cryolipolysis may have
wileyonlinelibrary.com/journal/jocd | 1
 |

14732165, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.16039 by Univ of Sao Paulo - Brazil, Wiley Online Library on [26/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2 KANIA and GOLDBERG

a positive impact on skin elasticity and tightening. Further investigation of this mecha-
nism is needed to provide a better understanding of its potential in achieving optimal
cosmetic outcomes for patients. By combining the benefits of fat reduction and skin
tightening, cryolipolysis has the potential to offer a comprehensive nonsurgical solu-
tion for body contouring.

KEYWORDS
adverse effect, cool sculpting, cosmetic dermatology, cryolipolysis

1 | I NTRO D U C TI O N effectiveness in achieving body contouring noninvasively, while also

Body contouring has become increasingly popular in the field of der-
matologic surgery, as it offers a noninvasive alternative to major sur-
geries such as liposuction. The American Society for Dermatologic
Surgery reports that in the year 2019, 25% of all 1 000 000 body
1
contouring procedures were cryolipolysis procedures. Cryolipolysis,
also known as fat freezing, is a nonsurgical technique for localized
fat reduction. 2 The first report of cold sensitivity in adipose tissue
was in 1902 by Hovhsinger, who observed and described nodules
under the chin of children that he believed to be an “acute freez-
ing reaction.”3 Following this observation, Haxuthausen published
a case series of four children with a similar phenomenon of nodules
that were worsened by cold weather and named it “adiponecrosis
e frigore.”3 In 1970, Epstein and Oren founded the term “popsicle
panniculitis” based on the presence of a red indurated nodule fol-
lowed by fat necrosis in an infant's cheek who had been sucking on
3
a popsicle.
Cryolipolysis was thus developed in 2007 using this idea of
cold-induced panniculitis, in which lipid-rich tissues are more sus-
4
ceptible to cold injury than surrounding water-rich tissue. For this
reason, cryolipolysis primarily targets the physical properties of
fat that differentiate from the overlying epidermis and dermis, re-
sulting in the selective disruption of fat cells that spares its sur-
rounding tissues.4 Since 2007, there have been several devices
utilizing cryolipolysis for body contouring purposes in cosmetic
dermatology, including CoolSculpting®, CoolContour, Zeltiq, and
CoolTech.
2 | M E TH O D S
Our primary phase of literature review consisted of a PubMed
search seeking all published literature around cryolipolysis. We em-
ployed a review approach that examined over 20 papers with the
key search terms of “cryolipolysis,” “fat-freezing,” “cosmetic derma-
tology,” “body contouring,” “adverse effects,” “adipocyte apoptosis,”
“Coolsculpting®,” and “localized fat reduction.” The next phase of
our literature review involved compiling the papers that defined our
key terms and extracting information from each to present a con-
solidated review of different aspects of cryolipolysis. We wanted to
understand the proposed mechanisms behind cryolipolysis and its
exploring its safety profile. We also explored papers that discussed
the effect of cryolipolysis on skin tightening and collagen remod-
eling. We finally reviewed the indications, contraindications, and ad-
verse effects of cryolipolysis to provide a comprehensive literature
review.
2.1 | Mechanism of action
One of the earliest cases of cold panniculitis was discussed by
Duncan et al. in a case study regarding a very young boy who devel-
oped indurated nodules in his cheeks after sucking on a popsicle for
an extended amount of time.4,5 Intrigued, researchers took a 4 mm
punch biopsy after applying ice to the patient's buttock and thigh,
and identified a infiltration of histocytes most intensely present at
the dermal–subdermal junction.5 This reaction intensified at 48 and
72 h after removal of the ice.5 At this point, researchers noticed that
some of the adipose tissues had burst, lipid aggregated, and a more
intense histocyte reaction presented.5 To the researcher's surprise,
this reaction subsided completely 2 weeks following the boy's ex-
posure. Duncan hypothesized that the boy had a sensitivity to cold,
that he later grew out of once he surpassed 18 months of age.5
This understanding of cold panniculitis laid the foundation
for the development of cryolipolysis and localized fat reduction.6
Cryolipolysis utilizes external thermal devices to lower the tempera-
ture of the skin and underlying adipose tissue to achieve selective
tissue apoptosis.7 The temperature of the device typically ranges
from −3 to 6°C, which is cold enough to induce cellular changes,
but not cold enough to cause permanent damage to the skin.7
Depending on the device used, an applicator is applied to a localized
area of adipose tissue and set at a specific cooling temperature for a
preset period of time. The skin transitions from its body temperature
to a supercooled, unfrozen state across the dermal layer for the du-
ration of the treatment. The exposure to cold temperatures induces
crystallization of lipids in the adipose layer, triggering an apoptotic
cascade that ultimately results in the gradual resorption of these
damaged cells.7,8
There have been several proposed mechanisms attempting to
explain the cellular processes leading up to adipocyte apoptosis.9
One hypothesis suggests that the cold-ischemic injury inflicted
upon the adipose tissue during cryolipolysis triggers a cascade

KANIA and GOLDBERG
of cellular damage, characterized by cellular edema, diminished
Na-K-ATPase activity, reduced adenosine triphosphate levels,
heightened lactic acid concentrations, and the release of mito-
chondrial free radicals.10 Another proposed mechanism suggests
that the cold-ischemic injury induced by cryolipolysis is further
compounded by ischemia reperfusion injury, leading to the gener-
ation of reactive oxygen species, an elevation in cytosolic calcium
levels, and an increased activation of apoptosis.10 Ultimately, the
adipose layer experiences an inflammatory response as a result
of the cold injury, causing the adipocytes in the treated area to
undergo apoptosis.10 This allows for targeted destruction of the
adipocytes while sparing surrounding tissues including the skin,
nerves, vessels, and muscles.11 Over the course of the follow-
ing months, these damaged cells are engulfed and eliminated by
macrophages, contributing to the gradual reduction of fat in the
treated area.10
2.2 | Indications
Cryolipolysis devices have been specifically designed for the tar-
geted reduction of adipose tissue in localized areas.12 While several
devices exist, one of the most renowned and widely used cry-
olipolysis devices is the CoolSculpting® system. CoolSculpting®
is FDA cleared to treat the submental area, under the jawline,
the upper arms, lumbar rolls, brassiere rolls, flank area, abdo-
men, thighs and under the buttocks.12 Ferraro et al. explains that
cryolipolysis procedures cater to a diverse patient demographic,
13
encompassing both men and women. This treatment option is
particularly suitable for individuals who only require small to mod-
erate amounts of adipose tissue and cellulite removal.13 Moreover,
cryolipolysis appeals to those individuals who are seeking body
contouring but wish to avoid a lengthy recovery period associated
with invasive procedures.
Furthermore, cryolipolysis is an attractive solution for individu-
als who have concerns about potential adverse reactions to anesthe-
sia. It provides a safe and effective method for targeting stubborn
13
pockets of unwanted fat without the need for general anesthesia.
This aspect makes it an ideal choice for those who are new to the
realm of aesthetic surgery and are seeking a less intimidating ap-
proach to body contouring.
2.3 | Contraindications
While cryolipolysis has become increasingly accessible to a wide
range of patients, it is important to acknowledge that cryolipolysis
is not a suitable option for all patients. There are certain medical
conditions and circumstances that may contraindicate the use of fat-
freezing procedures. Patients with a history of cold-induced condi-
tions, such as cryoglobulinemia, cold urticaria, and paroxysmal cold
hemoglobinuria, may not be suitable candidates for cryolipolysis.14
These conditions involve abnormal reactions to cold temperatures,
|
14732165, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.16039 by Univ of Sao Paulo - Brazil, Wiley Online Library on [26/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
3
and subjecting the body to cryolipolysis may exacerbate their
symptoms.
In addition, cryolipolysis should not be performed on treatment
areas affected by severe varicose veins, dermatitis, or other cuta-
neous lesions.12 These conditions can compromise the integrity of
the skin and increase the risk of complications during cryolipolysis.
Furthermore, patients who exhibit poor blood circulation in the spe-
cific area to be treated may also be contraindicated for cryolipoly-
sis.12 Conditions such as Raynaud's disease, pernio, or chilblains can
impair blood flow and compromise the body's ability to respond to
the cold temperatures involved in cryolipolysis.12 In such cases, al-
ternative treatment options should be explored to ensure the safety
and effectiveness of the procedure.
While cryolipolysis has gained popularity as a noninvasive fat
reduction procedure, it is important to recognize that it may not be
suitable for everyone. Health care professionals play a crucial role in
assessing each patient's individual circumstances and medical his-
tory to ensure the appropriateness and safety of cryolipolysis as a
treatment option.
2.4 | Adverse effects
Since being FDA cleared in 2010, cryolipolysis has gained signifi-
cant traction as a noninvasive procedure, lauded for its favorable
safety profile and promising outcomes. While cryolipolysis is gener-
ally considered safe, it is crucial to acknowledge that complications
can arise, although infrequently.15 These complications encompass a
range of adverse effects, including rather mild symptoms including
bruising, swelling, redness, pain or discomfort, and skin discoloration
which often resolve spontaneously without intervention, to much
more serious ones.15
Cold burns, previously considered an unlikely risk of cryolipoly-
sis, have been reported.12,14,16
A case series presented by Barry et al. discussed eight fe-
male patients and two male patients between the years 2012 and
2020 who experienced cold burns on various body parts, includ-
ing the abdomen, limbs, neck, flank, and buttocks.16 These burns
ranged from superficial partial thickness to full thickness, neces-
sitating inpatient management and even skin grafts for two pa-
tients.16 Although rare, severe frostbite has also been reported
as an adverse effect of cryolipolysis.14 One case study presented
a 61-year-old woman who developed full-thickness frostbite
on her abdomen after undergoing cryolipolysis at a nonmedical
facility.13,14 The patient experienced significant pain following
treatment, and was required to be hospitalized for 2 days.13,14 It is
crucial to emphasize that the device used in this case was not FDA-
approved, underscoring the importance of seeking treatment from
reputable and regulated establishments.
Another potential adverse effect of cryolipolysis is the de-
velopment of a hernia.17 A hernia occurs when an organ or tissue
bulges through a weak area in the abdomen or abdominal wall lin-
ing. Cryolipolysis treatments in or around preexisting hernias or
 |
4 KANIA and GOLDBERG
structurally weak regions, such as surgical scars or the separation
between stomach muscles (commonly observed after pregnancy),
can exacerbate hernia formation.17 Patients with a history of hernias
are contraindicated for cryolipolysis to mitigate this risk altogether.
One of the most concerning and common adverse effects of
11
cryolipolysis is paradoxical adipose hyperplasia (PAH). PAH is
characterized by the counterintuitive growth of fatty tissues in the
treated area, rather than their reduction.11 This condition typically
develops two to five months after cryolipolysis and may necessitate
surgical intervention for removal.11 Jalian et. al presented a 41 years
old male who underwent a single cycle of cryolipolysis and devel-
oped a large mass on his abdomen 1–2 months following his treat-
ment.11,18 This patient had more pronounced adipose tissue at the
lateral edges of the handpiece, and reported the lesion being firm
but not hard, and non tender.11,18 Another patient who presented
as a 56 years old female with no significant medical history under-
went one cycle of cryolipolysis and developed a similar mass on her
11,18
abdomen. Upon surgically removing the mass with an abdomi-
noplasty and sending the specimen to pathology, Jalian et al. reports
11,18
areas with disorganized adipocytes in various shapes and sizes.
Jalian et al. also notes that there was an increase in vascularity within
the adipose layer of the treated area, but spared the epidermis and
dermis, indicating a localized fat reduction mechanism that is spe-
11,18
cific to adipose tissue.
The underlying mechanism behind PAH remains elusive; how-
ever, some have hypothesized that this phenomenon could happen
due to hypertrophy of preexisting adipocytes, recruitment of res-
ident circulation, and/or stem cell populations, changes in the ex-
pression of receptors or soluble factors associated with adipocyte
mechanism, reduction in sympathetic innervation, and hypoxic in-
11,18
jury. Researchers have also identified certain trends in patient
populations prone to experiencing PAH, including a higher incidence
among men, Hispanic demographics, treatment of the abdominal re-
11
gion, and the use of larger handpieces. Additionally, there may be
a genetic component, as evidenced by a study involving twins who
underwent cryolipolysis at different facilities and both developed
PAH.11,18
Reports of serious long-term adverse effects stemming from
cryolipolysis treatments continue to emerge. Other adverse effects
19
include cold panniculitis, transient loss of sensation, fat necrosis,
clots, systemic inflammation, fat embolism, and lipoma.6,12 While
cryolipolysis has been deemed to have a low-risk safety profile, it
is essential to be aware of the potential adverse effects associated
with this procedure. Health care professionals and patients must
weigh the potential risks and benefits before undergoing cryolipoly-
sis treatment, and it is imperative to continue reporting complica-
tions to enhance our understanding and make informed decisions.
3 | R E S U LT S A N D O U TCO M E S
Following cryolipolysis, patients may not immediately notice vis-
ible changes in their treated area. While some patients may notice a
14732165, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.16039 by Univ of Sao Paulo - Brazil, Wiley Online Library on [26/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
visible change as early as three weeks after treatment, the most sig-
nificant benefits are usually observed between three to six months
post-treatment. 20 This gradual process allows the body to naturally
eliminate the damaged fat cells and reshape the treated area. The
extent of adipose reduction achieved through cryolipolysis can vary
from patient to patient. Factors such as individual goals, treatment
area, and amount of unwanted fat to be treated all play a role in
determining the overall outcome. On average, patients can expect a
reduction of fat ranging from 10% to 25% per treatment. 21
Measuring the outcomes of cryolipolysis treatments is another
variable factor among published studies. Researchers employ both
objective and subjective measurements to quantify the effective-
ness of cryolipolysis treatments. 21,22 Objective measurements
include fat caliper measurements, ultrasound imaging, 2D and 3D
imaging, and histology,4,21 while subjective measurements include
subject satisfaction surveys and investigator assessments. 2
Early preclinical trials first demonstrated the efficacy of cryo-
lipolysis in reducing localized adiposity through subjective and
objective measurements. 2 One of the earliest studies showed im-
provement of the flank, or “love handle,” region following cryolip-
olysis in 32 subjects. 2 Of those 32 subjects, 10 subjects underwent
ultrasonography which demonstrated an average reduction of fat-
layer thickness of 22.4% at 4 months posttreatment. 2 A more sub-
jective measure confirmed these findings by demonstrating an 82%
accuracy rate among three blinded physician investigators who were
tasked with differentiating between pretreatment and posttreat-
ment sites treated with cryolipolysis. 2,23 These evidence-based im-
provements displayed the efficacy of cryolipolysis in fat reduction,
which lead to its FDA clearance for the treatment of flanks in 2010,
followed by clearance for the abdomen in 2012.3
Subsequent to FDA clearance, several clinical studies were
conducted and published that further substantiate the efficacy of
cryolipolysis. In one study, subjects treated with two sessions of
cryolipolysis in the petrochanteric area displayed an average reduc-
tion in caliper measurement ranging from 14.67% to 28.5%. 22 This
was further supported by ultrasound measurements that showed fat
reduction ranging from 10.3% to 25.5%. 22 Another study focused
on the submental region and involved 14 participants (12 women,
2 men). 21 Three-dimensional imaging demonstrated a mean fat re-
duction of 2.3 mm after two cryolipolysis treatments lasting 45 min
each. 21
A more recent study evaluated 30 female participants after
one treatment of Coolsculpting, using ultrasound assessment to
measure fat layer thickness and contour. 24 They demonstrated
that 6 months after their treatment, the mean abdominal fat layer
thickness reduction was 46.6%, and measured mean contour was
significantly reduced from 84.3, 99.2, 90.6, and 97.1 cm to 81.0,
93.6, 85.8, and 92.2 cm in the infracostal, supraumbilical, umbil-
ical, and ischiopubic regions, respectively. 24 The researchers also
looked at their ultrasound data more qualitatively and highlighted
the fact that there was an appearance of numerous bands of or-
dered and structured collagen fibers, indicating a potential skin
remodeling and/or tightening result of cryolipolysis. 24 Overall,

KANIA and GOLDBERG
these clinical studies provide compelling evidence that cryolipoly-
sis leads to reductions in subcutaneous fat while preserving the
surrounding tissues.
3.1 | Skin tightening
Although cryolipolysis treatments have proven to be effective in
reducing overall fat, there have also been numerous reports high-
20,21,25
lighting the enhanced skin appearance in the treated area.
In a study of bilateral submental cryolipolysis, 14 participants were
treated with the CoolSculpting CoolMini® applicator for two treat-
ments at 6 weeks apart, each lasting 60 min each. 21 Researchers uti-
lized several different measurements to quantify fat reduction in the
treated area including participant satisfaction surveys, caliper meas-
urement, 2D photographic evaluation, and 3D image evaluation.21
While 3D image analysis showed a statistically significant average
3
fat layer reduction of 4.8 cm , the 3D image analysis also allowed
researchers to assess the skin surface area reduction of the treated
area as well. 21 The image analysis demonstrated a mean surface area
reduction of 1.29 cm2 of 47.09 cm2, or an overall 2.7% reduction,
which they hypothesized to be a result of skin tightening as an out-
21
come of cryolipolysis.
Initially, Stevens hypothesized that the clinical observation of im-
proved skin laxity and quality was due to dermal thickening following
20
treatment, rather than due to skin tightening itself. Researchers
reasoned that thickening of the dermis potentially caused by stimu-
lated collagen production, new elastin formation, fibrosis and tissue
compaction would result in an improvement in thin, crepey skin. 20
Stevens investigated this mechanism further by measuring key bio-
markers located in the skin after one treatment of Coolsculpting®
to the abdomen for 35 min at about −11°C, followed by a 2 min
massage of the treated area. 20 Using a sample size of 7 subjects, a
sample was collected from both the treated side of the abdomen
and the untreated side of each subject, which were then analyzed
using RNA-sequencing, RNA in-situ hybridization (RNA-ISH), immu-
nohistochemistry (IHC), and heat map imaging. 20 Researchers found
that gene expression in the treated area displayed an upregulation
of specific collagen mRNAs COL1A1, COL1A2, and COL3A1 after
3, 10, and 24 days in comparison to the untreated area. 20 These
collagen mRNAs are primarily responsible for skin stiffness and
20
strength. This finding is further supported by their RNA-ISH anal-
ysis of COL1A1, which demonstrated increased COL1A1 expression
throughout the dermal layer following cryolipolysis treatment. 20
IHC analysis was also used to quantify transforming growth factor
beta (TGF-β), heat shock protein 47 (HSP47), Procollagen Type I, and
Tropoelastin. TGF-β, a key player in stimulating fibroblast prolifera-
tion, wound healing and remodeling, and collagen production, dis-
played a 2.91-fold increase in cryolipolysis treated tissue compared
20
to the untreated tissue. HSP47, specifically responsible for colla-
gen folding, assembly and transport, showed a 1.54-fold increase
in treated tissue. 20 Procollagen Type I, which interacts transiently
with HSP47 to properly fold and form collagen, displayed a 3.62-fold
|
14732165, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.16039 by Univ of Sao Paulo - Brazil, Wiley Online Library on [26/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
5
increase, and lastly, tropoelastin, the soluble precursor to the elastin
molecule, displayed a 1.57-fold increase in treated tissue compared
to the control. 20
This molecular and immunohistochemical analysis following
cryolipolysis treatment represents a pioneering study that provides
evidence supporting the occurrence of at least some degree of der-
mal remodeling following cryolipolysis. Stevens suggests that due
to the significant induction of molecular markers for Type I collagen
found in the dermis after cryolipolysis, TGF-β-fibroblast mediated
neocollagenesis could play a role in the improvement of skin quality
following cryolipolysis. 20 This proposed mechanism sheds light on
future treatment alternatives for conditions such as cellulite, which
require a more comprehensive aesthetic approach to simultaneously
enhance skin quality and reduce fat deposition.
3.2 | Sequential treatments
Multiple cryolipolysis treatments may lead to further improvement in
fat reduction than a single treatment would alone. In one case study,
a 32-year-old male underwent two treatments of CoolSculpting®
on the flank, with 2 months in between treatments. 26 The subject's
initial circumferential measurement was 97 cm at baseline. 26 Two
months following his first treatment, this measurement was meas-
ured at 96.4 cm, and then 94.6 cm 5 months after the second treat-
ment. Overall, this subject had a 2.4 cm reduction following two
treatments of cryolipolysis. 26 Following this observation, a larger
study conducted on the pertrochanteric area showed that patients
who received two treatments of cryolipolysis experienced a 28.5%
fat reduction, compared to 19.7% in those who received only one
treatment. 27 However, it is important to note that some studies have
shown that the reduction of fat in the second treatment is not as
dramatic as the first one. 27
These findings suggest that multiple cryolipolysis treatments can
indeed lead to further improvement in fat reduction compared to a
single treatment. The case study of the 32-year-old male who under-
went two treatments on the flank demonstrated a gradual reduction
in circumferential measurement over time. This indicates a potential
continued reduction in fat volume following each treatment. While
the mechanism remains unclear, the discrepancy has been proposed
to be due to either higher cold tolerance in surviving adipocytes
from the first treatment or the failure of remaining fat to reach the
optimal temperature of 4°C due to its proximity to the vasculature of
the muscle layer. 27 Further studies are needed to better understand
the mechanisms behind the enhanced fat reduction observed with
multiple cryolipolysis treatments.
4 | CO N C LU S I O N
As minimally invasive body contouring procedures become more ac-
cessible to the public, the demand for safe and effective devices will
continue to rise. Experts predict a 14.02% compound annual growth
 |
6 KANIA and GOLDBERG
rate by the year 2030 to meet the needs of millions of people seek-
ing treatment. 28
This growth reflects the increasing popularity of
nonsurgical options for fat reduction and body sculpting, as patients
seek alternatives to traditional invasive surgeries. Cryolipolysis, with
its ability to target and reduce localized adipose tissue, has emerged
as a promising nonsurgical technique in the field of body contour-
ing. It offers patients a valuable option for achieving their desired
body shape without the need for a lengthy recovery period or major
surgery. This is particularly appealing to individuals who may have
concerns about the risks and complications associated with invasive
procedures.
While cryolipolysis has shown promising results for thou-
sands of patients seeking noninvasive fat reduction, it is crucial
to continue advancing our understanding of its potential compli-
cations and adverse effects. It is also important to note that re-
ported cases of complications associated with cryolipolysis may
have various confounding variables that hinder our ability to fully
comprehend the risks involved. Factors such as patient charac-
teristics, treatment protocols, and device variations can all con-
tribute to the complexity of assessing and quantifying these risks.
Therefore, future research should focus on controlling for these
differences and standardizing the definition and measurement of
complications. This will enable us to better understand the poten-
tial risks associated with cryolipolysis and provide a safer treat-
ment experience for patients.
As our knowledge grows about cryolipolysis as a promising non-
surgical technique, further research becomes critical in areas that
are less known like the role that cryolipolysis plays in skin tighten-
ing. While newer studies are scratching the surface of this area of
research, future studies are needed to explore this mechanism to
ultimately provide a better cosmetic outcome for patients, improv-
ing their satisfaction and confidence in nonsurgical body contouring
procedures.
C O N FL I C T O F I N T E R E S T S TAT E M E N T
The authors have no conflicts to disclose.
DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from
the corresponding author upon reasonable request.
E T H I C S S TAT E M E N T
None.
ORCID
David J. Goldberg https://orcid.org/0000-0002-8950-439X
REFERENCES
1. Website. 2023. www.​fda.​gov/​medic​al-​devic​es/​aesth​etic-​cosme​tic-​
devic​es/​non-​invas​ive-​body-​conto​uring​-​techn​ologies.
2. Dover J, Burns J, Coleman S, et al. A prospective clinical study of non-
invasive cryolipolysis for subcutaneous fat layer reduction. Presented at
the national harbor, MD.
14732165, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.16039 by Univ of Sao Paulo - Brazil, Wiley Online Library on [26/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
3. Jalian HR, Avram MM. Cryolipolysis: a historical perspective and
current clinical practice. Semin Cutan Med Surg. 2013;32:31-34.
4. Stevens WG, Gould DJ, Pham LD, Jimenez Lozano JN. Molecular
and histological evidence detailing clinically observed skin im-
provement following cryolipolysis. Aesthet Surg J. 2022;42:56-67.
5. Duncan WC, Freeman RG, Heaton CL. Cold panniculitis. Arch
Dermatol. 1966;94:722-724.
6. Rotman H. Cold panniculitis in children. Arch Dermatol. 1966;94:720.
7. Dobke MK, Hitchcock T, Misell L, Sasaki GH. Tissue restructuring
by energy-based surgical tools. Clin Plast Surg. 2012;39:399-408.
8. Pinto H, Arredondo E, Ricart-Jane D. Evaluation of adipo-
cytic changes after a simil-lipocryolysis stimulus. Cryo Letters.
2013;34:100-105.
9. Pinto HR, Garcia-Cruz E, Melamed GE. A study to evaluate the ac-
tion of lipocryolysis. Cryo Letters. 2012;33:177-181.
10. Puntel GO, Carvalho NR, Dobrachinski F, et al. Cryotherapy re-
duces skeletal muscle damage after ischemia/reperfusion in rats. J
Anat. 2013;222:223-230.
11. Sclafani AP. Paradoxical adipose hyperplasia after cryoli-
polysis CoolSculpting. Facial Plast Surg. 2023;39:586-587.
doi:10.1055/s-0043-1769595
12. Hedayati B, Juhász M, Chu S, Mesinkovska NA. Adverse events as-
sociated with cryolipolysis: a systematic review of the literature.
Dermatol Surg. 2020;46(Suppl 1):S8-S13.
13. Ferraro GA, De Francesco F, Cataldo C, Rossano F, Nicoletti
G, D'Andrea F. Synergistic effects of cryolipolysis and shock
waves for noninvasive body contouring. Aesthetic Plast Surg.
2012;36:666-679.
14. Benoit C, Modarressi A. Severe frostbite complication after cryoli-
polysis: a case report. JPRAS Open. 2020;25:46-51.
15. Fischer JP, Wes AM, Serletti JM, Kovach SJ. Complications in
body contouring procedures: an analysis of 1797 patients from
the 2005 to 2010 American College of Surgeons National Surgical
Quality Improvement Program databases. Plast Reconstr Surg.
2013;132:1411-1420.
16. Barry NP, Jackson SR, D'Jamirze A, Gates RJ, Maitz PKM, Issler-
Fisher A. Cold burns as a result of cosmetic cryolipolysis: an emerg-
ing concern from the NSW statewide burn injury service. J Plast
Reconstr Aesthet Surg. 2023;76:289-291.
17. Yanes D, Sawaya J, Wanner M, Avram M. Predicting negative out-
comes of cryolipolysis in patients with and without Raynaud dis-
ease. Dermatol Surg. 2021;47:675-677.
18. Jalian HR, Avram MM, Garibyan L, Mihm MC, Anderson RR.
Paradoxical adipose hyperplasia after cryolipolysis. JAMA Dermatol.
2014;150:317-319.
19. Coleman SR, Sachdeva K, Egbert BM, Preciado J, Allison J. Clinical
efficacy of noninvasive cryolipolysis and its effects on peripheral
nerves. Aesthetic Plast Surg. 2009;33:482-488.
20. Carruthers J, Stevens WG, Carruthers A, Humphrey S. Cryolipolysis
and skin tightening. Dermatol Surg. 2014;40(Suppl 12):S184-S189.
21. Bernstein EF, Bloom JD. Safety and efficacy of bilateral submental
cryolipolysis with quantified 3-dimensional imaging of fat reduc-
tion and skin tightening. JAMA Facial Plast Surg. 2017;19:350-357.
22. Ingargiola MJ, Motakef S, Chung MT, Vasconez HC, Sasaki GH.
Cryolipolysis for fat reduction and body contouring: safety and
efficacy of current treatment paradigms. Plast Reconstr Surg.
2015;135:1581-1590.
23. Kaminer M, Weiss RA, Newman J, et al. Visible cosmetic improve-
ment with cryolipolysis: photographic evidence. Presented at the
annual meeting of the American Society for Dermatologic Surgery,
Phoenix, AZ.
24. Ponga-Manso M. Ultrasound assessment of abdominal adipose
panniculus in patients treated with a single session of cryolipolysis
in a clinical setting. J Cosmet Dermatol. 2022;21:307-315.
 |

14732165, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.16039 by Univ of Sao Paulo - Brazil, Wiley Online Library on [26/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
KANIA and GOLDBERG 7

25. Stevens WG. Does cryolipolysis lead to skin tightening? A first re-
port of cryodermadstringo. Aesthet Surg J. 2014;34(6):NP32-NP34. How to cite this article: Kania B, Goldberg DJ. Cryolipolysis: A
doi:10.1177/1090820X14539699
promising nonsurgical technique for localized fat reduction. J
26. Brightman L, Geronemus R. Can second treatment enhance clinical
results in cryolipolysis? Cosmet Dermatol. 2019;24:103-107. Cosmet Dermatol. 2023;22(Suppl. 3):1-7. doi:10.1111/
27. Putra IB, Jusuf NK, Dewi NK. Utilisation of cryolipolysis among jocd.16039
Asians: a review on efficacy and safety. Open Access Maced J Med
Sci. 2019;7:1548-1554.
28. Technology market consulting and research reports—grand view re-
search. n.d. Accessed September 6, 2023. https://​w ww.​grand​viewr​
esear​ch.​com/​indus​try/​techn​ology​