Received: 7 September 2023 | Accepted: 4 October 2023

DOI: 10.1111/jocd.16035

REVIEW ARTICLE

A review of research for a cryolipolysis technology

Michael H. Gold MD1,2 | Reyna E. Vargas Lamas MD, MSc3

1
Gold Skin Care Center, Nashville, USA
2
Tennessee Clinical Research Center,
Nashville, USA
3
Scientific and Clinical Department,
Sinclair, Barcelona, Spain
Correspondence
Reyna E. Vargas Lamas, Scientific and
Clinical Department, Sinclair 08950
Esplugues de Llobregat, Barcelona, Spain.
Email: rvargas@sinclair.com
Abstract
Background: Obesity and excess body fat are known health issues and a major aes-
thetic concern. Numerous modalities have been developed to address unwanted
deposits of adiposity, including the development of various noninvasive methods
overcoming the limitations and risks of invasive alternatives. Cryoadipolysis, also
known commonly as cryolipolysis, involves the harnessing of selective cryolysis, the
selective cold-based damaging of subcutaneous fat cells which die via apoptosis, and
are removed naturally by the body over time.
Aims: To provide a brief but comprehensive summary of the literature supporting
two related cryoadipolysis devices that are only available outside of North America,
Cooltech and Cooltech Define (Sinclair).
Results/Discussion: Review of 10 available clinical studies evaluating the two devices,
specifically, showed both devices to be safe, with side effects profiles comparable to
those of similar platforms in the armamentarium. Both operate by non-invasively low-
ering the temperature of localized subcutaneous fat and maintaining it at or below a
threshold that causes disruption of adipocytes via crystallization, inducing apoptosis
(programmed cell death). Over time, clinically significant reductions in fat thickness
and circumference of the treated area were noted. Patient satisfaction is high. The lit-
erature also highlights the necessity of adherence to patient selection and device use
guidelines to minimize potential for rare paradoxical adipose hyperplasia and maxi-
mize patient satisfaction.

KEYWORDS
cryoadipolysis, cryolipolysis, lipolysis, noninvasive body contouring, noninvasive fat removal

1 | I NTRO D U C TI O N
Obesity due to excess body fat is a major health issue with links
to increased risk of cancer, diabetes, and cardiovascular disease,
among others as well as being a top aesthetic concern. A variety of
invasive and noninvasive technologies have been developed to re-
duce unwanted adiposity, and new techniques continue to be sought
and developed. Liposuction was the most effective technique for
decades but is invasive and comes with inherent risks and limita-
tions.1 Among the noninvasive procedures developed as an alter-
native to liposuction, cryolipolysis induces death of subcutaneous
fat cells via induction of cold panniculitis. 2 The technique is depen-
dent on the principle of selective cryolysis proposed by Manstein
and colleagues in 2007, 3 whereby the noninvasive application of
cold was shown to cause damage to fat cells in pigs without injuring
overlying skin, resulting in localized fat reduction over time. It was

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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):25–30.  wileyonlinelibrary.com/journal/jocd | 25

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26
theorized that the lack of inflammatory response indicated that fat
cell death via apoptosis, followed by the natural removal of dead fat
cells by the body after treatment, was responsible for fat reduction.
In 2012 Ferraro, et al.4 demonstrated that while a small percentage
of cells die by necrosis, the majority of affected cells die via apopto-
sis. Scientific review of the literature has strengthened the support
for the overall technology1 and shown consistently high patient sat-
isfaction. A variety of devices harnessing this concept have been
marketed since.
This cryolipolysis device technology discussed here (Cooltech®
and Cooltech® Define, Sinclair) is a safe, noninvasive modality for
reducing unwanted fat. The CoolTech and CoolTech Define plat-
forms are shown in Figures 1 and 2, respectively. As with all de-
5
vices relying on the principle of selective cryolysis, these devices
use specially designed applicators to bring the temperature of an
area down to a predetermined therapeutic level and maintain it
for a given length of time, to induce cold panniculitis and apop-
tosis of fat cells in the target area without damage to overlying
skin and tissue. Treatment is well tolerated with mostly transient
side effects. The body naturally eliminates the cellular contents
and debris over time, reshaping the treated region. As with most
aesthetic body contouring devices, these are indicated for pa-
tients of normal weight or slight overweight. These devices are
currently not marketed or available in North America. The purpose
of this study is to provide a brief but comprehensive overview of
the literature and respective findings examining these devices for
cryolipolysis.
F I G U R E 1 The CoolTech platform.
14732165, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jocd.16035 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
GOLD and VARGAS LAMAS
2 | A PPLI C ATO R S A N D TR E ATM E NT
Applicators for the Cooltech and Cooltech Define devices use vac-
uum suction to isolate and compress the fat fold to be treated, to
ensure maximum exposure of adipose tissue in the treatment zone,
and simultaneously promote local ischemia to mitigate potential heat-
ing from circulating blood. Before treatment, skin in the treatment
area is coated in a cryoprotectant gel to prevent formation of ice and
subsequent untoward freezing damage. A patented Cool Gel Pad (a
cellulose membrane embedded in glycerin and other cryoprotectant
ingredients6) is mandatory for the treatment further protects the skin
and is placed in the treatment area before application of handpieces.
With the Cooltech device, tissue is drawn between parallel anod-
ized aluminum cooling plates in each of six available applicators, two
of which can be used simultaneously in a single session. Applicators
are designed for specific areas of the body and differ in cavity vol-
ume, cooling surface, and cavity depth.7 During treatment, Cooltech
applicators operate at −8°C; evaluation of the Cooltech handpieces7
showed that even over the course of a 70-min treatment session, the
temperature remained less than 0°C which is below various estab-
lished possible targets to ensure adipocyte crystallization. Skin tis-
sue remains undamaged. Figures 3 and 4 provide examples of results
using the Cooltech device.
In the case of Cooltech Define,8,9 each of nine available appli-
cators rely on larger volume concave applicators (termed “360°
cooling technology”), enhancing results by delivering more com-
prehensive coverage to the targeted treatment area. Up to four
areas can be treated in a single session. During treatment Cooltech
Define operates at a range of −8°C to −10°C, causing crystalliza-
tion of adipocytes. Evaluation of the Cooltech Define handpieces8,9
showed superior homogeneous cooling overall when comparted
to Cooltech handpieces, as well as faster time to target tempera-
ture, reducing treatment times over those of the Cooltech device.
Cooltech Define includes the creation of the “Smart Contact” Cool
Gel Pad, which features enhanced cryoprotection as well as an RFID
system that triggers the treatment when the authorized membrane
is applied. This enables the provision of safer treatments to patients.
Each Cool Gel Pad must be used individually and for each treat-
ment area to ensure proper protection during the treatment. Skin
tissue remains undamaged. Treatment comfort partially depends
on natural hypoesthesia of the skin due to cold. This occurs more
8,9
rapidly with the Cooltech Define applicators, thus treatment is
more comfortable for the patient. Vacuum suction with Cooltech
Define handpieces is also gentler,9 further improving patient com-
fort. Figures 5 and 6 provide examples of outcomes obtained using
Cooltech Define platform.
An adjusted physics model was used in numerous studies of
these technologies to validate the operation and effect of the
Cooltech and Cooltech Define devices.7–11 In each study, COMSOL
Multiphysics simulation software (COMSOL) was employed to model
the physics of heat exchange between treated tissue and different
handpiece configurations to determine cooling characteristics. This
method was validated through specific investigation10 involving

GOLD and VARGAS LAMAS
use of the Cooltech handpieces for known substances (olive oil and
water) which favorably compared with the simulation model.
3 | SA FE T Y A N D E FFI C AC Y
Overall, research evaluating the safety and efficacy of the Cooltech
and Cooltech Define devices has shown significant reduction in fat
thickness and circumference in treated areas.
F I G U R E 2 The CoolTech Define platform.
F I G U R E 3 Side view of a male patient
before (left) and after (right) a course of
treatment to the lower abdomen with
CoolTech using the Straight HP handpiece.
|
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27
Vélez González, et al.12 evaluated cryoadipolysis in patients
(n = 15, 11 women, average age 42 ± 15 years) with localized fatty
deposits in the abdomen and/or flanks. None were significantly
overweight, according to study doctors. Subjects were treated with
a single session using the Cooltech Straight HP applicator, cooled
to −8°C with suction at 235 mbar for 70 min; a coupler was fitted to
reduce the treatment area in some cases to accommodate smaller
treatment areas. A pulsed magnetic field device and topical corti-
costeroids were also used immediately after treatment to mitigate
inflammation and edema.
Assessment of results consisted of photography, circumfer-
ence measurements, skin fold caliper measurements of cutaneous
folds. Reduction in abdominal skin fold measurement averaged
19.6% (±8.50), and circumference measurements averaged 2.33 cm
(±3.13). Some pain at the beginning and in the end of treatment was
noted in the majority of cases, and all patients experienced tempo-
rary reduction in sensation of the treatment area which resolved
within 21 days after treatment.
A single center study by Fajardo Urdiales, et al.6 included
patients (n = 8, six women, mean age of 44 ± 9.17 years, mean
BMI 26.88 ± 2.38) with localized fat in the abdomen and flanks.
Cryolipolysis with the Cooltech device was administered to four
areas in total (two for the abdomen and one on each flank) all appli-
cations in same day session using the Straight HP applicator, cooled
to −8°C with suction at 220 mbar for 70 min.
Outcomes were based on before-and-after evaluation using
bioimpedance measurements, ultrasound, photography, and body
circumference measurement. Follow up occurred at weeks 4 and 8
after treatment. All patients experienced circumference reduction.
Ultrasound results showed a mean thickness decrease of 15.34%
(±13.32) in the abdomen and 11.03% (±25.21) and 4.57% (±25.68)
in the right and left flanks, respectively. Biopsy revealed adipocyte
death without sign of necrosis or residual inflammation. High patient
satisfaction was recorded as well. No major adverse events were re-
corded; all patients experienced some erythema and edema, with
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28 GOLD and VARGAS LAMAS

F I G U R E 4 Side view of a female

patient before (left) and after (right) a
course of treatment to submentum with
CoolTech using the Tiny HP handpiece.

F I G U R E 5 Rear view of a female patient before (left) and at 4 months after (right) a course of treatment with CoolTech Define. Treatment
includes two sessions using the Oval HP applicator to the inner thighs and one session to the flanks, one session each using the Straight HP
applicator to the arms and infrascapular region, one session under the buttocks (“banana rolls”) using the Curved HP handpiece, and one
session using the Tuny Curved HP applicator to the inner knees.

three patients experiencing mild to moderate pain sensation that
subsided within 24 h, and five patients experienced paresthesia last-
ing approximately 1 week.
A 2019 evaluation of Cooltech Define by Viera Mármol and col-
leagues9 included 23 patients (17 women, mean age 38 ± 10.41 years)
given a single session of up to four applicators (−10°C for 70 min for
large applicators, −5°C for 45 min for small applicators), resulting in
69 total areas treated. After treatment, each area was immediately
given gentle massage for 2–5 min.
Average skin fold reduction over all 69 areas was 7.80 mm
(±3.46) which, notedly, included both large and small treatment
areas. Average circumference reduction for all subjects was 32.2 mm
(±1.86) with the largest reduction measured as 80 mm. All side ef-
fects were reportedly mild, resolving quickly and without sequelae.
Satisfaction was reportedly high for all subjects.
4 | P OTE NTI A L S I D E E FFEC T S
Common side effects after cryolipolysis include bruising, erythema,
pain, sensitivity, and swelling, all of which resolve within a few
weeks at most.1
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GOLD and VARGAS LAMAS 29

F I G U R E 6 Front (top) and side (bottom) views of a female patient before (left) and at 2 months after (right) a course of treatment with
CoolTech Define. Treatment includes two sessions with the Tight HP applicator to infrapectoral region and one session to the arms, two
sessions each using the Straight HP handpiece to the abdominal station and infrascapular region, one session each using the Curved HP
applicator to the flanks and underneath the buttocks (“banana rolls”), two sessions with the Oval HP applicator to the inner thighs, and one
session using the Tiny Curved HP applicator to the inner knee area.

Paradoxical adipose hyperplasia (PAH) is a rare side effect in
which an increase in fatty tissue develops over the 2–5 months after
selective cryolipolysis treatment. The mechanism is not yet well
understood. A 2020 multicenter review of 2114 patients13 found
the incidence of PAH to be extremely rare, lower than 0.5% overall
(given as between 0.05% and 0.39%).
A single-center chart review of 7588 cryolipolysis procedures14
conducted between 2019 and 2020 examined the incidence of PAH
after Cooltech treatment, specifically, finding 31 cases (represent-
ing a 0.41% incidence of PAH) within the range reported throughout
the literature according to the study. Of these, 16 were interviewed
further for the study; 56.25% of cases were classified as related to
risk factors, 25% classified as procedure related, with the remain-
ing 18.75% remaining undetermined. Of the determined cases the
incidence of PAH was given as related to suboptimal practices and
presence of contraindications, suggesting that thorough patient
screening and correct device use could substantially reduce the like-
lihood of PAH. MRI was listed as an essential tool for proper PAH
diagnosis. Of the 16 cases, liposuction was used as a corrective mea-
sure in 12 cases and all 12 were successfully resolved.
Study conclusions highlight the important role of patient se-
lection, that patients be limited to those who are not significantly
overweight and those who do not show signs of serious issues of
self-image. Strict adherence to device use protocols, including choice
of applicator, are also essential. Posttreatment care to maximize out-
comes includes gentle massage of the treatment area, adherence to
a diet somewhat restrictive in fat and calories, and gentle exercise.
AU T H O R C O N T R I B U T I O N S
All authors were involved in the drafting and revision of the manu-
script and gave final approval for the version to be published. Each
author has agreed to be responsible for all aspects of the study to
ensure that issues relating to the accuracy or integrity of any part of
the job are properly investigated and resolved.
AC K N OW L E D G M E N T S
We thank Gregorio Viera Marmol, PhD; Reyna Vargas, MD;
and Cecilia Brambilla, PhD for expert data analysis and writing
contributions.
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 declare that the research was conducted in the absence
of any commercial or financial relationships that could be construed
as a potential conflict of interest.
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 Reyna Vargas upon reasonable request.
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30
E T H I C S S TAT E M E N T
Cooltech® and Cooltech® Define are CE-marked devices.
ORCID
Michael H. Gold https://orcid.org/0000-0002-5183-5433
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How to cite this article: Gold MH, Vargas Lamas RE. A
review of research for a cryolipolysis technology. J Cosmet
Dermatol. 2023;22(Suppl. 3):25-30. doi:10.1111/jocd.16035