COSMETIC

Cryolipolysis for Fat Reduction and Body

Contouring: Safety and Efficacy of Current
Treatment Paradigms
Michael J. Ingargiola, M.D.
Background: Cryolipolysis is a nonsurgical technique for localized fat reduction.
Saba Motakef, M.D.
With the increased risk of complications from more invasive methods such as
Michael T. Chung, M.D.
liposuction, cryolipolysis presents a promising method for nonsurgical body con-
Henry C. Vasconez, M.D. touring. This study presents a systematic review of the available clinical data, with
Gordon H. Sasaki, M.D. an emphasis on the efficacy, methods, safety, and complications of cryolipolysis.
New York, N.Y.; Loma Linda, Calif.; Methods: To identify clinical studies that assessed outcomes of cryolipolysis,
Durham, N.C.; and Louisville, Ky. a systematic review of the MEDLINE and Cochrane databases was performed
with the search algorithm cryolipolysis OR cool sculpting OR fat freezing OR
lipocryolysis.
Results: The primary literature search returned 319 articles. After inclusion cri-
teria were applied and additional articles were idenfied via manual review of ar-
ticle references, 19 studies were selected for review. Average reduction in caliper
measurement ranged from 14.67 percent to 28.5 percent. Average reduction by
ultrasound ranged from 10.3 percent to 25.5 percent. No significant impact on
lipid levels or liver function tests after cryolipolysis treatments was noted in any
study. Only mild, short-term side effects, such as erythema, swelling, and pain,
were noted. Paradoxical adipose hyperplasia was described in one patient.
Conclusions: Cryolipolysis is a promising procedure for nonsurgical fat reduc-
tion and body contouring and presents a compelling alternative to liposuc-
tion and other, more invasive methods. This procedure appears to be safe in
the short term, with a limited side effect profile, and results in significant fat
reduction when used for localized adiposities. It remains unclear whether post-
treatment manual massage and multiple treatments in the same anatomic area
enhance the efficacy of cryolipolysis.  (Plast. Reconstr. Surg. 135: 1581, 2015.)

B
ody contouring remains among the most such as aesthetic improvements as well as numer-
common cosmetic surgical procedures per- ous metabolic benefits.1,2 Despite its popularity,
formed in the United States. Data from the there remain rare but significant risks regarding
American Society for Aesthetic Plastic Surgery indi- liposuction, including complications from anes-
cate that liposuction replaced breast augmentation thesia, infections, and even death.3 Clinical studies
as the most popular surgical procedure in 2013, have reported a 21.7 percent incidence of minor
with 363,912 procedures performed. Its popular- complications as well as a 0.38 percent incidence
ity has grown considerably because of advantages of major complications.4,5 Similarly, Fischer et al.
showed that the incidence of minor wound com-
From the Division of Plastic and Reconstructive Surgery, plications was 6.3 percent, and the incidence of
Mount Sinai Hospital; Department of Plastic Surgery, Loma a major morbidity was 6.8 percent within 30 days
Linda University; Division of Plastic, Maxillofacial, and Oral after a surgical body contouring procedure.6
Surgery, Duke University; and the Division of Plastic Surgery, Although liposuction is an effective thera-
University of Kentucky. peutic option for the removal of excess adipose
Received for publication July 3, 2014; accepted December
12, 2014.
Copyright © 2015 by the American Society of Plastic Surgeons. Disclosure: Gordon H. Sasaki, M.D., is a consul-
This is an open-access article distributed under the terms of the tant for ZELTIQ Aesthetics, Inc. (Pleasanton, Ca-
Creative Commons Attribution-NonCommercial-NoDerivatives lif.). The other authors have no financial interest to
3.0 License, where it is permissible to download and share the declare in relation to any of the products or devices
work provided it is properly cited. The work cannot be changed mentioned in this article. No funding was used for
in any way or used commercially. the preparation of this article.
DOI: 10.1097/PRS.0000000000001236

www.PRSJournal.com 1581
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 Plastic and Reconstructive Surgery • June 2015

tissue, it remains an invasive procedure and car- PATIENTS AND METHODS

ries the inherent risks associated with surgery. In
recent years, new modalities have been developed Search Strategy, Article Selection, and Data
to address body contouring from a less-invasive Extraction
perspective. These modalities primarily target the A systematic review of the MEDLINE and
physical properties of fat that differentiate it from Cochrane databases was performed with the
the overlying epidermis and dermis, thus resulting search algorithm cryolipolysis OR cool sculpt-
in selective destruction of fat. Devices using high- ing OR fat freezing OR lipocryolysis. Two inves-
frequency ultrasound, radiofrequency energy, tigators independently reviewed article titles
and laser light have the potential to improve and abstracts to identify studies that assessed
efficiency, minimize adverse consequences, and outcomes of cryolipolysis. Selected articles that
shorten postoperative recovery time. Through met these inclusion criteria then underwent full
thermal destruction, cavitational destruction, or article review by the two investigators. Additional
creation of a temporary adipocyte cell membrane articles were then identified by manual review
pore, the final result is that the number of adi- of the references of the articles that were ini-
pocytes is reduced, which, when translated over tially identified via the primary search. Review
millions of fat cells, results in a measurable reduc- papers and animal studies were eliminated. A
tion of fat.7 third investigator reconciled disagreements.
Cryolipolysis is one of the most recent forms The Cohen Kappa coefficient was calculated to
of noninvasive fat reduction to emerge. The devel- demonstrate the level of agreement between the
opment behind cryolipolysis stems from the clini- two initial investigators. The same two investiga-
cal observation of cold-induced panniculitis.8–10 In tors performed data extraction independently,
1970, Epstein and Oren coined the term popsicle and any discrepancies were again reconciled by
panniculitis after reporting the presence of a red the third. Table 1 lists the information extracted
indurated nodule followed by transient fat necro- from each article.
sis in the cheek of an infant who had been sucking
on a popsicle.9 Initially described in infants, cold- RESULTS
induced panniculitis has also been observed in
adult patients. These observations led to the con- Search Strategy and Article Selection
cept that lipid-rich tissues are more susceptible to The primary literature search returned
cold injury than the surrounding water-rich tissue. 319 articles (Fig. 1). The references of articles
With these historical observations in mind, Man-
stein et al. introduced a novel noninvasive method
Table 1.  Data Extracted from Reviewed Articles
for fat reduction with freezing in 2007, termed
cryolipolysis.11 This technique is performed by Study design
applying an applicator to the targeted area set at   Number of patients
  Treatment and control groups
a specific cooling temperature for a preset period Patient demographics
of time. This targets adipocytes while sparing the   Average age
skin, nerves, vessels, and muscles.   Age range
  Average BMI
Initial preclinical and clinical studies have   BMI range
demonstrated the efficacy of cryolipolysis for  Gender
subcutaneous fat layer reduction. However, the  Ethnicity
Method of delivery
exact mechanism of action for cryolipolysis is Location of delivery
not yet completely understood. In addition, the Outcomes
techniques of cryolipolysis treatment are not uni- Outcome measures
Follow-up length
formly applied. Studies have suggested that the Fat decrease and corresponding metric
addition of posttreatment manual massage may Laboratory findings
enhance the effectiveness of a single cryolipolysis Histological findings
Patient satisfaction
treatment, and that multiple treatments may lead Investigator assessment
to further improvement.12,13 Finally, we are cur- Adverse effects
rently still unaware of the long-term side effects Erythema
Bruising
and outcomes of this treatment. The aim of the Swelling
present review was to give an overview of cryolipol- Sensitivity changes
ysis with emphasis on the efficacy (volume reduc- Pain
tion), methods, safety, and complications. BMI, body mass index.

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 Volume 135, Number 6 • Systematic Review of Cryolipolysis

Fig. 1. Article search process and results, totaling 19 articles.

identified in the primary search were reviewed, measurement ranged from 14.67 percent to 28.5
yielding a total of 37 articles. Review papers and percent. Average reduction by ultrasound ranged
animal studies were eliminated, yielding a final from 10.3 percent to 25.5 percent (Table 3).
number of 19 articles, including 12 prospective Three studies evaluated lipid levels and liver func-
studies, three retrospective studies, one study with tion tests (Table 3).15–17 No significant impact was
both prospective and retrospective groups, and noted on lipid levels or liver function tests after
three case reports. The Kappa coefficient was cal- cryolipolysis treatments in any study.
culated at 0.885, indicating very good agreement Subjective assessments included both patient
between the investigators. satisfaction rates and investigator assessments.
In all cases, high satisfaction rates were noted, as
Efficacy demonstrated by posttreatment patient satisfac-
Common treatment areas included the abdo- tion surveys.13,15,16,18–20 Only one of the reviewed
men, brassiere rolls, lumbar rolls, hip rolls/flanks, studies used a validated survey to assess patient
inner thighs, medial knee, peritrochanteric areas, satisfaction.20 A clinically apparent difference
arms, and ankles (Table 2). Follow-up length gen- was noted by posttreatment investigator assess-
erally ranged from 2 to 6 months, although one ments.13,15,16,18,20,21 Investigator assessments were
study presented case reports on two patients at based on whether or not there was an appreciable
2 and 5 years after treatment,14 noting persistent fat reduction. Blinded investigators were able to
reduction at these time points when comparing correctly differentiate between pretreatment and
pretreatment and posttreatment photographs. posttreatment images in 89 percent of cases in
Objective outcome measures included fat caliper one study22 and 79 percent of cases in another.19
measurements, ultrasound measurements, and None of the studies reviewed included investiga-
three-dimensional imaging (VECTRA M3; Can- tor assessments that specifically evaluated other
field Scientific, Inc., Fairfield, N.J.). Every study factors, such as contour or texture.
that evaluated clinical outcomes using these out- The effect of posttreatment massage was eval-
come measures noted a significant reduction in uated in two studies. Sasaki et al. evaluated 5 min-
fat volume in treatment areas (Table 3). Although utes of posttreatment massage, noting an average
outcomes varied greatly based on treatment site fat reduction of 21.5 percent in treated areas by
and study design, average reduction in caliper caliper measurement at 6 months.20 Another study

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 Plastic and Reconstructive Surgery • June 2015

Table 2.  Reported Reduction in Caliper and Imaging Measurements after Cryolipolysis, Organized by Location
First Author, Year (ref.) Patient (n) Caliper (cm) Imaging
Abdominal
 Sasaki, 201420 55 1 (27%) n/a
 Boey, 201412 17 n/a 1.9 mm (10.3%);
2.7 mm (14.9%) (massaged)
 Shek, 201213 1 treatment: 21; 1 treatment: 4.5 (14.67%); n/a
2 treatments: 10 2 treatments: 4.9 (21.2%)
 Ferraro, 2012 15
14 4.5 n/a
Brassiere rolls
 Sasaki, 201420 4 0.5 (20%) n/a
Lumbar rolls
 Sasaki, 201420 2 0.8 (22%) n/a
Hip rolls/flanks
 Sasaki, 201420 20 1.0 (25 %) n/a
 Garibyan, 201419 11 0.6 (14.9%) 56.2 cc (three-dimensional
imaging)
 Shek, 201213 6 2 treatments: 4.3 (17.7%) n/a
 Brightman, 201133 1 1 treatment: 0.6; 2 treatments: 1.8 n/a
 Dover, 200934 32 n/a 22.40%
 Coleman, 200921 9 n/a 25.5%
Inner thighs
 Sasaki, 201420 3 0.5 (17%) n/a
 Lee, 201316 12 26.5 cm2 (19.55%) n/a
 Ferraro, 201215 18 3.6 n/a
Medial knee
 Sasaki, 201420 1 0.5 (18%) n/a
Pertrochanteric
 Pinto, 201223 1 treatment: 8; 1 treatment: 0.78 (19.7%); n/a
2 treatments: 8 2 treatments: 1.05 (28.5%)
Arms
 Ferraro, 201215 8 2.1 n/a
Buttocks
 Ferraro, 201215 6 4 n/a
Ankles
 Ferraro, 201215 4 1 n/a
Unspecified
 Dierickx, 201318 49 23% n/a

by Boey and Wasilenchuk compared patients statistically significant difference was not produced
receiving 2 minutes of posttreatment manual mas- with a second treatment on the love handles (p =
sage to a control group receiving only the stan- 0.084) (Table 3).13
dard cryolipolysis treatment.12 At 2 months after Histologic outcomes were evaluated in a
treatment, average fat layer reduction was 68 handful of studies. No evidence of fibrosis was
percent greater on the massaged side (12.6 per- noted in one study.12 Most studies demonstrate
cent on the nonmassaged side versus 21.0 percent an inflammatory response at different stages
on the massaged side, p = 0.0007). However, at 4 after cryolipolysis, with inflammatory cell infil-
months, average fat layer reduction was only 44 trates peaking at 30 days,12 which led to adipocyte
percent greater on the massaged side (10.3 per- apoptosis.15 Biopsy specimens of peripheral nerve
cent on the nonmassaged side versus 14.9 percent cells showed no long-term changes in peripheral
on the massaged side, p = 0.1).12 nerves, with equal and normal numbers of epi-
The effect of multiple treatments has also been dermal nerves.21
evaluated. In one study, patients receiving two
treatments in the peritrochanteric area yielded an Complications
average fat layer reduction of 28.5 percent, com- Common complications noted after cryoli-
pared with 19.7 percent in patients receiving only polysis included erythema, bruising, swelling,
one treatment (p = 0.046).23 The effect of multi- sensitivity, and pain (Table 4). These side effects
ple treatments was evaluated on love handles and are generally resolved within a few weeks after
abdomens of patients in another study demon- treatment. No persistent ulcerations, scarring,
strating different outcomes. Although a second paresthesias, hematomas, blistering, bleeding,
treatment yielded a significant decrease in cali- hyperpigmentation or hypopigmentation, or
per measurements on the abdomen (p = 0.020), a infections have been described. One isolated case

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 Table 3.  Study Design, Demographics, Methods, Follow-Up, and Final Outcomes from Reviewed Articles
First Author, Average Average
Year (ref) Study Type n Age (yr) BMI Methods Follow-Up Outcomes
Garibyan, 201419 Prospective 11 37.6 27.1 CIF 41.6, 60 min 2 mos Average fat volume loss by 3D imaging 56.2 cc in treated site (p < 0.0001),
average reduction in caliper measurement 14.9% (p < 0.001)
Pinto, 201223 Prospective 16 n/a n/a 3.1°C, 25–35 min, 40 days Average reduction by caliper measurement 19.7% in patients receiving 1
1 or 2 treatments treatment, 28.5% in patients receiving 2 treatments (p = 0.046)
Ferraro, 201215 Prospective 50 41.46 25.35 0 to −5°C + acoustic 8 wks Median reduction in fat circumference 6.86 cm for abdomen, 5.78 cm
probe, variable time of for thighs, 2.75 cm for arms, 5 cm for buttocks, 2.25 cm for ankles
treatment, average of (p < 0.0001); average reduction by caliper measurement 4.50 cm for
3.73 treatments abdomen, 3.60 cm for thighs, 2.10 cm for arms, 4 cm for buttocks, 1 cm
for ankles; cholesterol, triglycerides, LDL, HDL, AST/ALT, T-bili, and
albumin remained within normal limits
Boey, 201412 Prospective 17 n/a n/a CIF 42, 60 min + 2-min 4 mos Average fat layer reduction by US 68% greater on massaged side at 2 mos
massage (p = 0.0007), 44% greater at 4 mos ( p= 0.1)
Dover, 200934 Prospective 32 n/a n/a Manufacturer preset CIF 4 mos Average reduction by US 22.4% at 4 mos; fat layer reduction in 100% of subjects
Sasaki, 201420 Prospective 112 55.8 24.7 CIF 42, 60 min + 5 6 mos Average reduction by caliper measurement 21.5%; average reduction by US
-min massage 19.6% in abdomen
Klein, 200935 Prospective 40 40.9 26.1 CIF 42, 30 min 12 wks No meaningful changes in mean values were observed for any blood lipid
level or liver test at any point during 12-wk follow-up period
Lee, 201316 Prospective 14 28.57 23.12 CIF 42, 60 min versus 12 wks At 12 wks, fat-reducing efficacy in cryolipolysis-treated thigh −19.55% versus
radiofrequeny −28.20% in radiofrequency-treated thigh (not statistically significant); no
statistically significant difference in any measured blood lipid level or fast-
ing blood glucose at weeks 1, 4, or 12
Riopelle, 200917 Prospective 10 n/a n/a n/a 12 wks No change in lipids or liver function tests at 1, 4, 8, and 12 wks after treat-
ment in patients with a loss of fat evident via ultrasound
21
Coleman, 2009 Prospective 9 n/a n/a CIF 33, 60 min versus 6 mos Average reduction by US 20.4% at 2 mos, 25.5 % by 6 mos; nerve biopsy
CIF 37, 45 min showed no long-term change in nerve structure
Rosales-Berber, Prospective 42 n/a n/a CIF/duration n/a, 1 and 6 mos 79% of subjects observed efficacy within 2–4 mos of procedure
200936 2 treatments
Dover, 201137 Prospective 21 18 n/a n/a 6 mos 15 of 21 patients completed follow-up survey at 6 mos; 80% of patients
reported they were happy with results of treatment at 6 mos, rating
results 6.6 on a 1 to 10 scale
Volume 135, Number 6 • Systematic Review of Cryolipolysis

Shek, 201213 Prospective 21 46 23.96 CIF 41.6, 60 min, 1 treat- 2 mos Average reduction by caliper measurement 14.7% (p < 0.0001)
ment
Shek, 201213 Retrospective 12 47 22.5 CIF 41.6, 60 min, 2 mos Average reduction by caliper measurement after first treatment: 14.0% (p <
2 treatments 0.001) in abdomen, 13.4% (p = 0.003) in love handle; after second treat-
ment: 7.2% (p = 0.020) in abdomen, 4.3% (p = 0.084) in love handle
Dierickx, 201318 Retrospective 518 42.7 65.9 n/a 1 and 94% of patients showed reduction, with a 23% reduction compared with
2 mos control site at 3 mos by caliper measurements
Stevens, 201332 Retrospective 528 46.6 n/a 60 min 2 or 3 mos Consistent growth in procedure volume, with treatment cycles increasing by
823% from 2010 to 2012
Kaminer, 200922 Retrospective 50 n/a n/a n/a 6 mos Reviewers correctly differentiated between baseline/postprocedure photo-
graphs in 89% of cases evaluated
Brightman, Case report 1 32 n/a CIF 42, 60 min, 5 mos 2.4-cm reduction in circumferential abdomen/flank measurement by 3D
201133 2 treatments imaging
Jalian, 201424 Case report 1 40s n/a Manufacturer 5 mos Gradual, nontender growth of tissue at site of treatment area, stabilizing at
preset CIF 5 mos, corresponding to paradoxical adipose hyperplasia
Bernstein, 201314 Case report 1 44 27 CIF 42, 60 min 2 yrs Treated flank showed persistent reduction at 2 yrs after treatment when
images were compared with pretreatment photographs
Bernstein, 201314 Case report 1 45 23.7 CIF 34, 60 min 5 yrs Treated flank showed persistent reduction at 5 yrs after treatment when
images were compared with pretreatment photographs

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BMI, body mass index; CIF, cooling intensity factor; 3D, three-dimensional; LDL, low-density lipoprotein; HDL, high-density lipoprotein; AST/ALT, aspartate transaminase/alanine transaminase;

Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
US, ultrasound.
 1586
Table 4.  Complications and Complication Rates for Cryolipolysis from Reviewed Articles
Author Patient (n) Erythema Bruising Swelling (infiltrate) Sensitivity Pain Miscellaneous
20
Sasaki, 2014 112 100% for several n/a n/a 3% reported dysesthesia n/a n/a
days and hypersensitivity for
2–3 wks
Garibyan, 11 100% for up to n/a 100% at 10 min after 73% reported decreased 55% at 10 min after n/a
201419 1 wk treatment, 18% at sensation at 3 wks and treatment (36%
1 wk, 9% at 2 wks, 18% reported at 2 mos mild pain, 18%
and 0% at 3 wks moderate pain),
0% at 1 wk, 2 wks,
3 wks, or 2 mos
Jalian, 201424 1 n/a n/a n/a n/a n/a 3 mos after treatment, patient
noted gradual, nontender
growth of tissue at the site and
in the shape of treatment area
(stabilized in size by 5 mos
after treatment)
Boey, 201412 17 n/a n/a n/a One subject reported n/a n/a
slight numbness in the
massaged side for 8 wks
Stevens, 201332 528 n/a n/a n/a 0.6% reported mild to n/a n/a
moderate pain or neu-
ralgia for up to 4 days
Dierickx, 518 100% 9.8% at 1 mo 2.5% for up to 1 mo 0.4% reduced recovered 96% reported 52% reported clay-like feel
201318 ­immediately at 1 mo, 2.5% increased minimal to toler- at site (immediate), 48%
recovered at 1 mo able, 4% reported reported stiff at site immedi-
severe pain (dur- ate), one patient had vasovagal
ing treatment) reaction
Shek, 201213 1 treatment: 1 treatment: 1 treatment: n/a 1 treatment: 28.6% n/a n/a
21; 2 treat- 23.8% 9.5% for up reported numbness for
ments: 12 to 1 wk up to 3 mos
15
Ferraro, 2012 50 n/a n/a n/a n/a n/a n/a
Klein, 200935 40 n/a n/a n/a n/a 2.5% reported pain n/a
at treatment site
at 1 wk
Dover, 200934 32 n/a n/a n/a n/a n/a n/a
Riopelle, 10 n/a n/a n/a n/a n/a n/a
200917
Lee, 201316 14 n/a 21.40% n/a n/a 28.6% reported 7.1% (n = 1) noticed blood-
mild (7.1%), tinged stool
moderate
(14.3%), and
severe (7.1%)
pain at time of
procedure
Plastic and Reconstructive Surgery • June 2015

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 Volume 135, Number 6 • Systematic Review of Cryolipolysis

report described paradoxical adipose hyperplasia alanine transaminase, total bilirubin, albumin,
after cryolipolysis treatment.24 and glucose remained within normal limits dur-
ing and after cryolipolysis.15–17
With the relatively recent emergence of cryo-
DISCUSSION lipolysis, many factors still need to be considered
Recently, a surge of novel technologies involv- and investigated, including what type of patient
ing noninvasive, energy-based techniques have would benefit most from this procedure. Ferraro
been introduced to the market, signaling a poten- et al. suggested that patients who require only
tial paradigm shift in fat reduction and body con- small or moderate amounts of adipose tissue and
touring practices. The major goal of these novel cellulite removal would benefit most from cryo-
therapies includes volume reduction of tissue, lipolysis treatment.15 Contraindications to cryoli-
with a possible end point of noninvasive body polysis include cold-induced conditions such as
contouring.25 With more than 450,000 procedures cryoglobulinemia, cold urticaria, and paroxys-
performed thus far, cryolipolysis is becoming one mal cold hemoglobinuria.29 Cryolipolysis should
of the most popular alternatives to liposuction for not be performed in treatment areas with severe
spot reduction of adipose tissue.26 Because of its varicose veins, dermatitis, or other cutaneous
ease of use and limited adverse effects, this proce- lesions.23,27
dure is becoming the leading technology in non- Although all studies reviewed showed a
invasive techniques as well. This review sought to fat reduction in every area examined, it is still
explore the efficacy, methods, safety, and compli- unknown what areas are most responsive to
cations of cryolipolysis in the current literature. cryolipolysis. Various factors may play a role in
Although its mechanism is not fully under- the degree of fat reduction observed after cryo-
stood, it is believed that vacuum suction with lipolysis. The vascularity, local cytoarchitecture,
regulated heat extraction impedes blood flow and metabolic activity of the specific fat depots
and induces crystallization of the targeted adi- in question may play a role. Because of the lim-
pose tissue when cryolipolysis is performed.11,27 ited size and number of studies evaluating cryoli-
The temperatures induced in cryolipolysis have polysis in clinical populations, it is unclear which
no permanent effect on the overlying dermis and treatment sites are most amenable to cryolipoly-
epidermis. However, this cold ischemic injury may sis. Future comparative outcome studies should
promote cellular injury in adipose tissue via cellu- be adequately powered to determine which treat-
lar edema, reduced Na-K-ATPase activity, reduced ment sites are most suitable for fat reduction with
adenosine triphosphate, elevated lactic acid levels, this modality.
and mitochondrial free radical release.20 Another Because cryolipolysis is still a relatively new
mechanism proposes that the initial insult of crys- procedure, treatment protocols have yet to be
tallization and cold ischemic injury induced by optimized to maximize results. Recent studies
cryolipolysis is further compounded by ischemia have focused on maximizing the reduction of
reperfusion injury, causing generation of reactive adipose tissue by adjusting treatment protocols.
oxygen species, elevation of cytosolic calcium lev- Three studies assessed the theoretical enhanced
els, and activation of apoptotic pathways.20 Ulti- efficacy with multiple treatments in the same ana-
mately, crystallization and cold ischemic injury of tomic area and demonstrated that a second suc-
the targeted adipocytes induce apoptosis of these cessive course of cryolipolysis treatment led to
cells and a pronounced inflammatory response, further fat reduction.13,23 It is important to note
resulting in their eventual removal from the treat- that although a subsequent treatment leads to fur-
ment site within the following several weeks.7,11,25 ther fat reduction, the extent of improvement was
Histological studies show that within 3 months, not as dramatic as the first treatment. Interestingly,
macrophages are mostly responsible for clearing one study demonstrated that a second treatment
the damaged cells and debris.26,28 enhanced fat layer reduction in the abdomen
With the removal of the adipocytes internally, area but not the love handles.13 One hypothesis
there has been concern that cryolipolysis may for the diminished effect of the second treatment
cause rising blood lipid levels and elevations in may be that the fat exposed to the second heat
liver enzymes that may put the patient at additional extraction is closer to the muscle layer. The vas-
risk, particularly for cardiovascular parameters. cular supply to the muscle layer may impede the
However, multiple studies have demonstrated that efficiency of heat extraction so that the fat closer
cholesterol, triglycerides, low-density lipoprotein, to the muscle layer may not reach the intended
high-density lipoprotein, aspartate transaminase/ optimal temperature of 4°C. Another hypothesis

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 Plastic and Reconstructive Surgery • June 2015

is that adipocytes that survived the first treatment Rare side effects that have been described
have a higher tolerance to cold. include vasovagal reaction18 and paradoxical adi-
Boey and Wasilenchuk evaluated whether pose hyperplasia.24 Jalian et al. estimated an inci-
the addition of a posttreatment manual massage dence of 0.0051 percent, or approximately one
enhanced the efficacy of a single cryolipolysis in 20,000, for paradoxical adipose hyperplasia.24
treatment.12 Immediately after treatment, patients Affected patients exhibit fat loss after therapy
received a 2-minute manual massage. This con- and then develop a large, demarcated, tender fat
sisted of 1 minute of vigorous kneading of the mass at the site 2 to 3 months later. The hypoth-
treated tissue between the thumb and fingers esized pathogenesis includes recruitment of stem
followed by 1 minute of circular massage of the cells and hypertrophy of existing fat cells in the
treated tissue against the patient’s body. To exam- area.24 However, compared with traditional lipo-
ine the effects of massage on subcutaneous tis- suction side effects, cryolipolysis poses a minor
sue over time, histological analysis was completed threat to patients, with a very low incidence of
through 4 months after treatment. Although the complications.
difference at 2 months after treatment was statisti- Of note, the reviewed studies used a variety of
cally significant, the difference at 4 months after different modalities to determine the degree of
treatment was not. One hypothesis for potentially fat reduction after cryolipolysis treatments. Vari-
improved efficacy with manual massage is that ous studies have compared caliper, ultrasound,
manual massage caused an additional mechanism three-dimensional imaging, and manual tape
of damage to the targeted adipose tissue immedi- measurements. Although no single study has com-
ately after treatment, perhaps from tissue-reper- pared all of these modalities, the available data
fusion injury. Histological analysis revealed no suggest that these techniques correlate well with
evidence of necrosis or fibrosis resulting from the one another.30,31 Studies that used more than one
massage, thus showing posttreatment manual mas- of these modalities to assess outcomes after cryo-
sage to be a safe and effective method to further lipolysis also demonstrated that these measure-
reduce the fat layer after cryolipolysis. Sasaki et al. ments corresponded well.19,20
described cryolipolysis with 5 minutes of posttreat- A drawback of this work is the limited number of
ment integrated preset mechanical massage using high-quality, prospective, randomized clinical stud-
the device applicator with excellent outcomes.20 ies. Cryolipolysis was first described in 2007, and
A low profile of adverse effects is one of the although its popularity has increased dramatically,
main advantages with cryolipolysis, especially when the available literature remains limited. Tremen-
compared with more invasive measures. Only mild, dous variability exists in study design, machin-
short-term side effects, such as erythema, bruising, ery used, and outcome measures. Because of this
changes in sensation, and pain, were reported in lack of uniformity, comparing effect size becomes
the studies reviewed. Erythema was noted in multi- challenging, and the value of a meta-analysis of
ple studies immediately after the treatment and sub- the available data is limited. The variations in the
sided within a week.18–20 This is most likely because of available studies make it difficult to control for any
the strength of the vacuum and the temperature at bias present in the discussed studies. Despite these
which the tissue is kept for extended durations and limitations, clinical data demonstrate consistent fat
poses no threat to the patients. Swelling and bruis- reduction in treated subjects, which supports the
ing of the area were shown to a slightly lesser extent clinical utility of this technique.
than erythema, but are believed to be because of
the same processes. These complications also sub-
sided shortly after.13,16,18,19 Hypersensitivity and hypo- CONCLUSIONS
sensitivity were shown in studies but were never This study presents the first systematic review
debilitating nor persisted beyond 1 month. Cole- of the available data on cryolipolysis. Although
man et al. demonstrated that patients exhibiting the body of evidence is limited because of the
reduction in sensation recovered normal sensation nascence of this procedure, cryolipolysis is a
in 3.6 weeks.21 This study also showed that a nerve promising procedure for nonsurgical fat reduc-
biopsy taken at 3 months after treatment showed no tion and body contouring. While the outcomes
long-term changes to nerve fibers, concluding that of cryolipolysis are rather modest, this technol-
temperature and duration of cryolipolysis have no ogy is well suited for patients who desire nonsur-
permanent effect on nervous tissue.21 In one study, gical spot reduction at modestly sized adiposities.
pain during the procedure was generally nonexis- Cryolipolysis appeals to both men and women
tent to tolerable 96 percent of the time.18 and is an effective means by which new patients

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 Volume 135, Number 6 • Systematic Review of Cryolipolysis

can be drawn to the aesthetic surgery practice.32 11. Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski
Although the specific mechanism of cryolipoly- D, Anderson RR. Selective cryolysis: A novel method of non-
invasive fat removal. Lasers Surg Med. 2008;40:595–604.
sis has not been completely elucidated, this pro- 12. Boey GE, Wasilenchuk JL. Enhanced clinical outcome with
cedure appears to be effective and safe in the manual massage following cryolipolysis treatment: A 4-month
short term, with a limited side effect profile. study of safety and efficacy. Lasers Surg Med. 2014;46:20–26.
Posttreatment manual massage has the potential 13. Shek SY, Chan NP, Chan HH. Non-invasive cryolipolysis for
to improve the efficacy of cryolipolysis. Multiple body contouring in Chinese: A first commercial experience.
Lasers Surg Med. 2012;44:125–130.
treatments in the same anatomic area may lead 14. Bernstein EF. Longitudinal evaluation of cryolipolysis effi-
to further fat reduction, although the efficacy cacy: Two case studies. J Cosmet Dermatol. 2013;12:149–152.
of cryolipolysis appears to be attenuated with 15. Ferraro GA, De Francesco F, Cataldo C, Rossano F, Nicoletti
successive treatments. The efficacy of this tech- G, D’Andrea F. Synergistic effects of cryolipolysis and shock
nique in areas that have been treated previously waves for noninvasive body contouring. Aesthetic Plast Surg.
2012;36:666–679.
with liposuction remains to be studied. Future 16. Lee KR. Clinical efficacy of fat reduction on the thigh of Korean
studies should address which treatment sites are women through cryolipolysis. J Obes Weight Loss. 2013;3:1–5.
most amenable to cryolipolysis to enhance treat- 17. Riopelle JT, Kovach B. Lipid and liver function effects of the
ment stratification for body contouring patients cryolipolysis procedure in a study of male love handle reduc-
and should evaluate a potential role for cryoli- tion. Lasers Surg Med. 2009:82.
18. Dierickx CC, Mazer JM, Sand M, Koenig S, Arigon V. Safety,
polysis in skin tightening and the treatment of tolerance, and patient satisfaction with noninvasive cryoli-
cellulite. polysis. Dermatol Surg. 2013;39:1209–1216.
19. Garibyan L, Sipprell WH III, Jalian HR, Sakamoto FH,

Gordon H. Sasaki, M.D.
Avram M, Anderson RR. Three-dimensional volumetric
Department of Plastic Surgery
quantification of fat loss following cryolipolysis. Lasers Surg
Loma Linda University
Med. 2014;46:75–80.
11175 Campus Street, CP 21126
20. Sasaki GH, Abelev N, Tevez-Ortiz A. Noninvasive selec-

Loma Linda, Calif. 92354
tive cryolipolysis and reperfusion recovery for local-
[email protected]
ized natural fat reduction and contouring. Aesthet Surg J.
2014;34:420–431.
21. Coleman SR, Sachdeva K, Egbert BM, Preciado J, Allison J.
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 Plastic and Reconstructive Surgery • June 2015

33. Brightman L, Geronemus R. Can second treatment enhance

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Online CME Collections

This partial list of titles in the developing archive of CME article collections is available online at www.
PRSJournal.com. These articles are suitable to use as study guides for board certification, to help readers refamiliarize
themselves on a particular topic, or to serve as useful reference articles. Articles less than 3 years old can be taken for CME
credit.
Cosmetic
The Silicone Gel-Filled Breast Implant Controversy: An Update—Arshad R. Muzaffar and Rod J. Rohrich
Understanding the Nasal Airway: Principles and Practice—Brian K. Howard and Rod J. Rohrich
Lateral Canthal Anchoring—Clinton McCord et al.
Male Rhinoplasty—Rod J. Rohrich et al.
The Cosmetic Use of Botulinum Toxin (October 2003 Supplement)—Rod J. Rohrich et al.
Thrombolytic Therapy following Rhytidectomy and Blepharoplasty—Stephanie L. Mick et al.
Current Concepts in Aesthetic Upper Blepharoplasty—Rod J. Rohrich et al.
Breast Augmentation: Cancer Concerns and Mammography—A Literature Review—Michael G. Jakubietz et al.
Prevention of Venous Thromboembolism in the Plastic Surgery Patient—Steven Paul Davison et al.
Breast Augmentation—Scott L. Spear et al.
Otoplasty: Sequencing the Operation for Improved Results—James Hoehn and Salman Ashruf
Thromboembolism in Plastic Surgery—Daniel Most et al.
Otoplasty—Jeffrey E. Janis et al.
Fire in the Operating Room: Principles and Prevention—Stephen P. Daane and Bryant A. Toth
Patient Safety in the Office-Based Setting—J. Bauer Horton et al.
Frequently Used Grafts in Rhinoplasty: Nomenclature and Analysis—Jack P. Gunter et al.
Injectable Soft-Tissue Fillers: Clinical Overview—Barry L. Eppley and Babak Dadvand
Body Dysmorphic Disorder and Cosmetic Surgery—Canice E. Crerand et al.
Use of Herbal Supplements and Vitamins in Plastic Surgery: A Practical Review—George Broughton, II,
et al.
Psychological Considerations of the Bariatric Patient—David Sarwer

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