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Available via license: CC BY-NC-ND 3.0
Content may be subject to copyright.
Lasers in Surgery and Medicine 46:20–26 (2014)
Enhanced Clinical Outcome with Manual Massage
Following Cryolipolysis Treatment: A 4-Month
Study of Safety and Efficacy
Gerald E. Boey, MD
and Jennifer L. Wasilenchuk
Arbutus Laser Centre, Vancouver, British Columbia, Canada
Background and Objectives: Cryolipolysis procedures
have been shown to safely and effectively reduce the
thickness of fat in a treated region. This study was
conducted to determine whether the addition of post-
treatment manual massage would improve efficacy while
maintaining the safety profile of the original cryolipolysis
treatment protocol.
Materials and Methods: The study population consisted
of an efficacy group (n¼10) and a safety group (n¼7).
Study subjects were treated on each side of the lower
abdomen with a Cooling Intensity Factor of 42 (72.9 mW/
cm
2
) for 60 minutes. One side of the abdomen was
massaged post-treatment and the other side served as
the control. Immediately post-treatment, the massage side
was treated for 1 minute using a vigorous kneading motion
followed by 1 minute of circular massage using the pads of
the fingers. For the efficacy group, photos and ultrasound
measurements were taken at baseline, 2 months, and
4 months post-treatment. For the safety group, histological
analysis was completed at 0, 3, 8, 14, 30, 60, and 120 days
post-treatment to examine the effects of massage on
subcutaneous tissue over time.
Results: Post-treatment manual massage resulted in a
consistent and discernible increase in efficacy over the non-
massaged side. At 2 months post-treatment, mean fat layer
reduction was 68% greater in the massage side than in the
non-massage side as measured by ultrasound. By 4 months,
mean fat layer reduction was 44% greater in the massage
side. Histological results showed no evidence of necrosis or
fibrosis resulting from the massage.
Conclusion: Post-treatment manual massage is a safe
and effective technique to enhance the clinical outcome
from a cryolipolysis procedure. Lasers Surg. Med. 46:20–
26, 2014. ß2013 The Authors. Lasers in Surgery and
Medicine Published by Wiley Periodicals, Inc.
Key words: body contouring; cryolipolysis; non-surgical
fat reduction; post-treatment massage
INTRODUCTION
Cryolipolysis is a novel non-invasive fat reduction
technique that applies controlled localized cooling to the
skin surface to reduce subcutaneous fat. Cryolipolysis
procedures can safely and effectively reduce fat without
damaging overlying skin or surrounding structures [1–3].
While the mechanisms of fat reduction are not entirely
understood, studies have shown that cold exposure induces
apoptotic cell death of subcutaneous fat cells [4–5].
Cryolipolysis is approved by the FDA, Health Canada
and the European Union as a non-invasive treatment for
the reduction of localized subcutaneous fat [6]. Recent
studies have focused on improving and optimizing cry-
olipolysis treatment protocols to enhance the reduction of
fat. Two studies suggest that a second successive course of
treatment may improve the efficacy of this procedure [6].
One study demonstrated, however, that a second treat-
ment improved efficacy in the abdomen area but not the
love handles [7]. Because cryolipolysis is still a relatively
new procedure, treatment protocols have yet to be refined
and optimized to maximize results.
The purpose of this study is to evaluate whether the
addition of a post-treatment manual massage enhances
the effectiveness of a single cryolipolysis treatment.
Additionally, this study evaluates the safety of incorpo-
rating post-treatment manual massage into cryolipolysis
treatment.
METHODS
All studies were conducted using a commercially
available non-invasive medical device for cryolipolysis
(CoolSculpting, ZELTIQ Aesthetics, Pleasanton, CA).
Subjects were selected from new patient consultations or
referrals from friends and family. Study subjects received
treatments free of charge but were not otherwise
This is an open access article under the terms of the Creative
Commons Attribution-NonCommercial-NoDerivs License, which
permits use and distribution in any medium, provided the
original work is properly cited, the use is non-commercial and
no modifications or adaptations are made.
Conflict of Interest Disclosures: All authors have completed
and submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest and have disclosed the following: [Dr. Boey is
a consultant to ZELTIQ. Ms. Wasilenchuk has no relevant
conflicts of interest to disclose].
Contract grant sponsor: ZELTIQ Aesthetics, Pleasanton, CA.
Correspondence to: Gerald Boey, MD, Arbutus Laser Centre,
2025 W. Broadway Suite 106, Vancouver, BC, Canada V6J 1Z6.
E-mail: geraldboey@hotmail.com
Accepted 18 November 2013
Published online 11 December 2013 in Wiley Online Library
(wileyonlinelibrary.com).
DOI 10.1002/lsm.22209
ß2013 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
compensated. Prior to treatment, trained clinicians col-
lected patient data including gender, weight, age, height,
BMI, and medical history.
Subjects were screened based upon the following
inclusion/exclusion criteria. Subjects included in the study
had a visible bulge of adipose tissue on their abdomen
below the umbilicus and stated willingness to maintain
weight within 10 lbs for the duration of the study. No
adjunctive fat reduction therapies were used over the
course of the study. Subjects were excluded if they had
undergone liposuction, other surgical procedures, or
abdomen contouring treatments in the past 6 months.
They were excluded for history of cryoglobulinemia,
paroxysmal cold hemoglobinuria, cold urticaria, areas of
impaired peripheral circulation, Raynaud’s disease, preg-
nancy, scar tissue, or extensive skin conditions, such as
eczema or dermatitis at the treatment area, impaired skin
sensation, open or infected wounds, and area of recent
bleeding or hemorrhage. Also, subjects with skin laxity or
enrolled for other clinical studies were excluded.
Efficacy was determined using photographic and ultra-
sound analysis at 2 and 4 months post-treatment. Safety
was evaluated from a separate group of 7 subjects by
assessing side effects and analyzing histology. Subjects
received cryolipolysis treatments prior to abdominoplasty
surgery and the resected tissue underwent histology
processing, imaging, and analysis.
Treatment Method
As illustrated in Figure 1, the cryolipolysis vacuum
applicator was used to sequentially treat the left and right
sides of the abdomen below the umbilicus for 60 minutes
each. Immediately following cryolipolysis treatment, one
side of the abdomen was manually massaged using a 2-
minute protocol, while the remaining side served as a
control.
Cryolipolysis was administered to abdominal tissue
drawn between cooled plates in the applicator. To ensure
consistent thermal coupling between the skin and the
applicator, a pad saturated with a coupling gel (ZELTIQ
Aesthetics) was placed on the skin surface prior to placing
the applicator on the abdomen. A medium applicator
(CoolCore applicator) was applied with moderate vacuum
pressure to gently draw a bulge of fat into the applicator
cup. Treatment was delivered at a Cooling Intensity Factor
42, corresponding to an average energy extraction rate of
72.9 mW/cm
2
.
Immediately following treatment, one side of the
abdomen was manually massaged for 2 minutes (Fig. 2).
The side of the abdomen that received the massage was
randomly assigned. The first minute of massage consisted
of a vigorous kneading motion, during which the tissue was
pulled together between the thumb and fingers and then
pulled away from the body. The second minute of massage
consisted of circular massage, during which tissue was
pushed down into the body and then moved in a circular
motion.
Method of Evaluating Efficacy
The efficacy of adding a 2-minute manual massage
following cryolipolysis was evaluated using pre- and post-
treatment photographs and ultrasound measurement of
fat layer reduction in the massaged and non-massaged
sides. Both photographic and ultrasound images were
taken at baseline, 2 months, and 4 months post-treatment.
Fat layer reduction, as demonstrated by fat layer
thickness changes measured by ultrasound, was confirmed
by comparing pre-treatment and post-treatment images,
in which each ultrasound image pair corresponded to the
same anatomic area. An ultrasound system (SonoSite
TITAN, Bothell, WA) with a 7.5-MHz high-resolution
linear transducer was used to acquire images of the fat
layer. A series of evenly spaced pre-treatment images were
acquired, as shown in Figure 3, with five images captured
through the untreated control area in the upper abdomen
and 10 through the treatment area in the lower abdomen.
Fig. 1. Cryolipolysis treatments were delivered using a vacuum
applicator to the left and right sides of the lower abdomen. One
side was manually massaged immediately post-treatment, while
the other side was the non-massage control.
Fig. 2. Immediately following cryolipolysis treatment, the tissue
was vigorously kneaded and pulled away from the body for
1 minute then pushed into the body in a circular massage motion
for 1 minute.
ENHANCED CLINICAL OUTCOME WITH MANUAL MASSAGE 21
Overall fat layer thickness changes were normalized by
subtracting the control site difference from the treated site
difference. For each subject, multiple fat layer reduction
measurements were obtained and averaged to determine a
mean fat layer thickness change.
Method of Evaluating Safety
The safety of adding a 2-minute manual massage
immediately following cryolipolysis was assessed on a group
of seven patients by monitoring procedural side effects and
evaluation of tissue histology. Patients were assessed
immediately following treatment (0 day) and 3, 8, 14, 30,
60,and120dayspost-treatmenttoevaluatedamagetothe
dermis or epidermis in the areas treated. Histology has been
used to assess cold-induced panniculitis at the dermal-fat
interface following cryolipolysis treatment and to evaluate
thetimecourseofinflammatoryactivity [2,3]. In this study,
the histology was also evaluated for additional tissue injury
induced by the post-treatment manual massage.
RESULTS
A total of 10 subjects were assessed for efficacy by
baseline ultrasound and photography and seven subjects
were evaluated for safety by histology. The analyzed
patient population was entirely female with age range 30–
50 years, weight range 129–147 lbs, BMI range 21–25, and
height 50200 to 50800. All patients maintained body weight
within the specified 10 lbs over the course of the study,
ranging from a 6 lb loss to an 8 lb gain. Of the original 10
subjects treated for efficacy assessment, one was lost at
2 months follow-up and an additional subject was lost at
4 months follow-up; both subjects were lost due to
inconvenience of follow-up rather than procedure-related
adverse event or treatment failure.
Efficacy Results
For all subjects treated, the cryolipolysis procedure
visibly reduced the size of the lower abdomen, as
demonstrated by ultrasound measurements and
Fig. 3. Ultrasound images were acquired of the cryolipolysis
treated lower abdomen and the untreated control upper abdomen.
Ten images were taken of the lower abdomen (five from the
massaged side, five from the non-massaged side) and five images
were taken from the control area.
Fig. 4. Subject #8 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.
22 BOEY AND WASILENCHUK
Fig. 5. Subject #10 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.
Fig. 6. Subject #6 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.
ENHANCED CLINICAL OUTCOME WITH MANUAL MASSAGE 23
photography. Figures 4–7 show photos taken at baseline,
2 months, and 4 months post-treatment.
Ultrasound measurements of fat reduction between
massaged and non-massaged sites 2 months post-treat-
ment are shown in Figure 8. In all patients at 2 months,
there was a significant decrease in fat layer thickness on
the side that was massaged post-treatment. The normal-
ized mean fat layer reduction was 12.6% with standard
deviation 7.2% and range 2.4 to 20.0% (mean 2.6 mm,
standard deviation 1.9 mm, range 1.1 to 5.0 mm) for the
non-massaged side and 21.0% with standard deviation
8.5% and range 10.0 to 34.9% (mean 4.2 mm, standard
deviation 2.2 mm, range 0.8 to 7.2 mm) for the massaged
side. Thus, mean fat reduction was 68% greater on the
massaged side at 2 months. At 4 months post-treatment,
the normalized mean fat layer reduction was 10.3% with
standard deviation 8.6% and range 2.6 to 25.8% (mean
1.9 mm, standard deviation 1.1 mm, range 0.5 to 3.9 mm)
Fig. 7. Subject #2 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.
Fig. 8. Fat layer reduction for nine subjects at 2 months. Mean fat
layer reduction was 68% greater for the massaged compared to the
non-massaged side following cryolipolysis.
Fig. 9. Fat layer reduction for eight subjects at 4 months. Mean
fat layer reduction was 44% greater for the massaged compared to
the non-massaged side following cryolipolysis.
24 BOEY AND WASILENCHUK
for the non-massaged side and 14.9% with standard
deviation 6.1% and range 5.3 to 22.1% (mean 2.7 mm,
standard deviation 1.5 mm, range 0.4 to 4.9 mm) for the
massaged side. At 4 months, the mean fat layer reduction
was 44% greater in the massaged side, Figure 9.
Safety Results
Treatment sites were evaluated immediately following
post-treatment manual massage for any epidermal, der-
mal, or subcutaneous findings. Non-massage sites were
assessed immediately following cryolipolysis. In all cases,
typical side effects, such as erythema, bruising, minor pain,
and transient loss of sensation, were observed. Aside from
one subject that reported slight numbness in the massaged
side for 8 weeks, typical side effects resolved spontaneously
within 14–30 days and no adverse events were reported.
Safety was evaluated by histological analysis at 0, 3, 8,
14, 30, 60, and 120-day time points post-treatment. As
shown in Figure 10, the post-treatment massage tissue
showed no evidence of necrosis or fibrosis at any of the time
points. The non-massage tissue also did not show
abnormality following cryolipolysis treatment at 0, 3, 8,
14, 30, 60, and 120 days post-treatment. The histological
timeline shows increasing inflammatory response, peak-
ing at 30 days with dense inflammatory cell infiltrate and
reduction in adipocyte size, then decreasing to a similar
response at 60 and 120 days, with reduced adipocyte size
and decreased infiltrates.
DISCUSSION
Incorporating manual massage immediately following
cryolipolysis treatment appears to significantly increase
treatment efficacy. While the 2-month follow-up data showed
68% increase in fat layer reduction in the massaged
compared to the non-massaged treatment area, the 4-month
measurements showed a 44% increase in fat layer reduction.
Although it is still an improvement in fat layer reduction, it is
unknown why the effect was more pronounced at the 2-
month timepoint. A paired t-test found significant effect from
post-treatment massage with P¼0.0007 at 2 months, but
P¼0.1 at 4 months. It may be indicative that manual
massage caused an additional mechanism of damage
immediately following treatment, perhaps from tissue
reperfusion injury. With additional time, however, the
cold-induced apoptosis is likely to cause gradual, ongoing
fat cell destruction in both the massaged and non-massaged
treatment areas. The mechanism of action by which
cryolipolysis induces damage to adipocytes is not well
understood and remains an ongoing subject of research.
The ultrasound fat layer measurements in this study yielded
results that were lower than the typical published results of
approximately 20%. This is likely due to the small sample
size since there is a significant range in patient response to
non-surgical fat reduction procedures, such as cryolipolysis.
The manual massage sensation was reported to be
uncomfortable but not painful, and it is likely that the level
of discomfort is acceptable to the patient given the
resultant increased treatment efficacy. No long-term side
effects or adverse events were reported. Therefore,
cryolipolysis is shown to be a well-tolerated, efficacious
treatment method for decreasing fat layer thickness in the
lower abdomen. As cryolipolysis treatment protocols
continue to be refined and optimized, post-treatment
manual massage is one technique that can be incorporated
to safely improve treatment efficacy.
CONCLUSION
This study found that post-treatment manual massage
improved cryolipolysis treatment efficacy. At 2 months
follow-up, the massaged sites had mean fat layer reduction
68% greater than the non-massaged sites. By 4 months
post-treatment, the massaged sites had 44% greater fat
layer reduction compared to the non-massaged treatment
sites. Histological analysis of massage tissue at 0, 3, 8, 14,
30, 60, and 120 post-treatment found no evidence of fibrosis
or necrosis. The massaged and non-massaged tissues
looked similar. Thus, post-treatment manual massage is
Fig. 10. Histology images of abdominal tissue manually massaged post-treatment showed no
evidence of necrosis or fibrosis. The massaged and non-massaged tissue looked similar. H&E stain,
40magnification.
ENHANCED CLINICAL OUTCOME WITH MANUAL MASSAGE 25
shown to be a safe and effective method to further reduce
the fat layer following a cryolipolysis procedure.
ACKNOWLEDGMENTS
The authors acknowledge Kevin Springer and Bill
Blaker for assistance with ultrasound imaging and clinical
photography.
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26 BOEY AND WASILENCHUK
