Carboxytherapy... magical or medical?

Medical analysis and proofs

Keywords: carbon dioxide; carboxytherapy; collagen; skin aging; skin laxity

Background and History

Carbon dioxide is made up of one carbon atom (C) and two oxygen atoms (O),
O-C-O, hence CO2. It is produced by all humans and animals during respiration
and by plants and trees for photosynthesis, which aids their growth.

CO2 is an odourless, invisible gas first discovered in 1648 (by Van Helmont) and
its anti-infective properties were described by Boyle in the 17th century and by
Lavoisier in the 18th century. Lalouette, in 1777, proposed a serial application of
CO2 for treatment of chronic skin ulcers in the lower limbs.

Further beneficial health benefits of carbon dioxide were discovered in France in

the 1930s, when it was noted that bathing in the pools of carbon dioxide rich
water at the Royat Spas helped to speed up wound-healing.

In1953 a group of cardiologists ascribed to the hospital of Clermont Ferrand,

used this therapy in patients with illnesses related to poor blood circulation, fat
accumulation and peripheric organic and functional arteriopathies
(Atherosclerotic, Buerger’s disease, Raynaud’s disease) and Jean Baptiste
Romuef M.D. published a paper about his 20 years of experience in the
subcutaneous injection of CO2.

CO2 has vasodilatory properties, which make it useful to the medical community.
The dilation of blood vessels leads to a decrease in blood pressure and a better
flow of oxygen rich blood around the body.(1)

How Does Carboxytherapy Work?

All cells in the body, regardless of their job, release carbon dioxide as a waste
product. Carbon dioxide is the ‘cost of doing business’ of any cell.

Whenever we breathe in oxygen, it is picked up by red blood cells. With each red
blood cell carrying four oxygen molecules, which it takes from the lungs to the
heart via the blood vessels and then into the arteries and on a journey around the
body to where they’re needed.
Whenever they encounter an area with high levels of carbon dioxide (which has
been created by cellular metabolism) the red blood cells release oxygen
molecules and pick up the carbon dioxide that they have produced.

Carboxytherapy is said to work by tricking the body, as by injecting a small

amount of carbon dioxide gas into the area, it will increase the dispatch of
oxygen laden red blood cells to the area to pick up the new ‘waste’ carbon
dioxide which the body will then naturally eliminate via the lungs.

By increasing the amount of oxygen getting to the area, cells will become more
active and thus speed up any healing or new cell production required to
rejuvenate the area.

Physiology: The Bohr effect

Carbon dioxide helps the release of oxygen from haemoglobin and as a result the pH
decreases, allowing the tissue to obtain enough oxygen to meet its demands.

It is demonstrated when comparing the oxygen dissociation curves when there is

less carbon dioxide present and when there is more carbon dioxide in the blood.

When carbon dioxide, in the presence of the catalyst carbonic anhydrase,

diffuses into the blood plasma and erythrocytes most of it reacts with water and
the following dynamic equilibrium is established: H2O + CO2 H2CO3

Carbonic acid (H2CO3) dissociates to form hydrogen ions and hydrogen

carbonate ions. H2CO3 H+ + HCO3-

The negatively charged HCO3- ions, inside the erythrocytes, diffuse from the
cytoplasm to the plasma. This is balanced by diffusion of chloride ions, Cl-, in the
opposite direction, maintaining the balance of negative and positive ions either
side.
The dissociation of carbonic acid increases the acidity of the blood (decreases its
pH). Hydrogen ions, H+, then react with oxy-haemoglobin to release bound
oxygen and reduce the acidity of the blood. Hb.4O2 + H+ HHb+ + 4O2

It is this reversible reaction that accounts for the Bohr effect.

What Happens During Carboxytherapy Treatment?

Carboxytherapy is similar to mesotherapy (a series of small injections with a thin

needle) but it delivers medical grade carbon dioxide gas in a controlled flow/dose
below the skin’s surface, rather than tiny quantities of a liquid formulation. (2,3)

Side effects and contraindications

During treatment some patients may feel a slight discomfort, pressure or stinging
sensation as the gas is delivered to the tissues, (often described as a crackling
sensation) and ecchymoses. Other side effects can include minor swelling,
redness (caused by the vasodilation), lasting anywhere from 1 – 5 days
depending on the area treated. In the case of cellulite treatment, a warm
sensation can be felt in the region for up to 24 hours.

Major adverse events are uncommon. In gynaecologic laparoscopic surgery,

large amounts of CO2 are used to expand abdominal cavity (up to 4 litres of
CO2) without any toxic effect.

At rest, with normal ventilation, the human body consumes 250 mL/min of
oxygen (transported from lungs to tissues) and exhales 200 mL/min of CO2
(removed from tissues and excreted through pulmonary alveoli).

In condition of hyperventilation, oxygen consumption can increase up to 4000-

5000 ml /minute and CO2 can be formed up to 4000-4500 ml/minute.
During carboxytherapy an average of 30-50 ml/minute CO2 are administrated per
session: the mild increase in CO2 levels are easily and therefore promptly
resolvable by mild hyperventilation at the end of treatment, without risk of
hypercapnia and respiratory acidosis.

Hypercapnia occurs when the lungs are unable to excrete CO2 and therefore
pCO2 (partial pressure of carbon dioxide) significantly increases at the alveoli
level. When alveolar PCO2 reaches 60-75 mmHg the patient can experience
severe dyspnoea.
With further increase up to 80-100mmHg they may become drowsy and lethargic
(hypercapnic coma). With PCO2 alveolar levels of 120-150mmHg the excessive
CO2 dampens respiratory bulbar centre.

In normal condition (healthy patients) there is no possibility to cause severe

hypercapnia by carboxytherapy.

The main excretion of CO2 and protons (H+) is performed by the kidneys and
lungs. Severe damage of these organs (renal or respiratory failure) may cause
excessive accumulation of CO2. In congestive heart failure, vessel circulations
markedly slow down, and consequently the amount of CO2 removed from tissues
is significantly lowered. Chronic congestive heart failure is another
pathophysiologic condition causing CO2 accumulation in which using
carboxytherapy is questionable.

Carboxytherapy should be also avoided in patients under treatment with carbonic

anhydrase inhibitors (acetazolamide, diclofenamide etc). As the use of the
inhibitor obstacles the main process by which CO2 can be carried to be excreted
through the lungs and kidneys.

Severe anaemia implies a significant decrease in red blood cell numbers,

therefore a significant decline in the availability of the main carrier by which CO2
can be usually transferred to the lungs and kidneys to be eliminated. Severe
anaemia implies a decrease in the haemoglobin levels and this also reduces the
possibility of CO2 binding to form carbamyl haemoglobin plasmatic, the second
most relevant CO2 carrier from tissues to lungs and kidneys.

A decrease in plasmatic protein levels (and consequently in carbo-haemoglobin

and plasmatic proteins) may be caused by chronic liver insufficiency that
constitutes another contraindication for carboxytherapy. Another contraindication
is the presence of gaseous gangrene. This severe infectious disease is caused
by anaerobic bacteria entered in the body through skin wounds and is
characterized by extensive tissue damage, necrosis, oedema and severe
generalised deteriorated conditions.

Indications and clinical datas

The most common aesthetic uses of carboxytherapy are for treating cellulite, fat
reduction, striae (stretch marks), acne scaring, skin laxity, dark circles under the
eyes and wrinkle reduction. Therefore treatments are generally focussed on the
face, neck, arms, abdomen and thighs. (4)

In 2001, University of Siena (Italy) investigated CO2 treatment of localised fat

deposits on the thighs, knees and/or abdomen in 48 women. The CO 2 was
administered via subcutaneous injections twice weekly for 3 weeks (equalling a
total of 6 treatment sessions).

The results showed that on average the women lost 2cms of circumference from
their thighs, 1cm from the knees and almost 3cms from the abdomen. The skin in
the treated areas also appeared thicker than before treatment, with cellulite
appearing smoother. Few minor side effects were observed all resolved very
quickly.

In 2004 the same university published another study looking at the effects of
carbon dioxide on skin irregularity and its use as a complement to liposuction. 42
patients treated for fatty tissue accumulations on the thighs and knees. They
were divided into three groups, with group 1 only liposuction was performed, in
the second group carboxytherapy was administered 3 weeks after liposuction in
twice weekly applications for 10 consecutive weeks, and in the third group
carboxytherapy alone was administered, again twice weekly, for 10 consecutive
weeks.

The results were then analysed by reporting on variations in circumference

measurements and skin elasticity after 2 months. The authors noted that
liposuction alone did not generally have a positive enough effect on skin
irregularity and could in fact cause uneven areas, however the addition of
carboxytherapy provided an improvement in skin smoothness and elasticity. CO2
therapy also showed positive results in reducing fat accumulation as the
circumferential measurement results of those treated with liposuction and carbon
dioxide were better than for those treated with liposuction alone.
In 2008, Ferreira et al. published in the Journal of Drugs in Dermatology. 2008
Mar;7(3):201-6. (5) Percutaneous infiltration of carbon dioxide improves the
appearance of the skin via visible compacting of collagen fibres following CO2
infiltration especially when administered intradermally.

In March 2008 a Brazilian study looked at whether the intradermal and

subcutaneous injection of carbon dioxide into the skin of rats would increase the
turnover of collagen. Following biopsies, it was noted that collagen turnover had
increased as compared to the control animals (which were injected with only
saline) and that the collagen formations were more pronounced in the areas
where the gas was injected intradermally, as compared to where it was injected
subcutaneously.

The most recent study February, 24th 2020 confirmed the beneficial effects
of Carboxytherapy on Skin Laxity

Suellen Matos Domingos Oliveira , Lenaldo Branco Rocha , Marco Túlio Rodrigues da
Cunha , Mariana Molinar Mauad Cintra , Nanci Mendes Pinheiro , Adriana Clemente
Mendonça

Abstract

Background: Carboxytherapy is capable of inducing tissue repair which results in

an increase in elastic and collagen fibers.

Objectives: To evaluate the effects of carboxytherapy upon human skin collagen

and elastic fiber synthesis.

Methods: Case study of nine volunteers who received a single application of

carboxytherapy in the left infraumbilical region, with infusion rate of 100 mL/min
and 0.6 mL/kg weight over an area of 25 cm2 . After 60 days on average, the skin
was collected for histological analysis and stained with picrosirius red for collagen
and Verhoeff for elastic fibers. The percentage of fibers found was marked by the
Image J® program and recorded in a Microsoft Excel spreadsheet. Statistical
analysis was performed using SPSS (version 20), with a significance level of 95%.

Results: An increase in the collagen and elastic fibers sample was observed in the
treated group. Morphometrically, a significant increase in the percentage of
collagen in the Carboxytherapy group (41.44 ± 4.50%) was observed compared
with the control group (37.44 ± 3.87%) with P = .04; for elastic fibers, the
percentage showed no significant difference between the control group (10.55 ±
4.33%) and the carboxytherapy group (10.44 ± 3.71%).

Conclusions: Carboxytherapy with the parameters used in this study was able to
stimulate collagen and elastic fiber synthesis, with significant differences in the
morphometry for collagen fibers.

Case Studies

Nasolabial folds and marionette lines on the face (before on the left, after on the
right) treated with 12 sessions of carboxytherapy, twice a week for the first 3
weeks and then once weekly for 6 more weeks.
Courtesy of Dr Cyrille Blum, Lausanne, Switzerland.
Photos © Copyright
 Arm (before on the left, close up on the skin in the middle an after on the right)
treated with 5 sessions of carboxytherapy, once per week.
Photos © Copyright Dr Daniel Sister, London, UK

Improved Adiposity through Lipolysis

CO2 Therapy Lipolysis effects:

– Fracturing of the adipose tissue
– Release of triglycerides in the intercellular spaces
– Adipocytes presenting thin fracture lines in the plasma membrane. These lines
did not involve the connective spaces where the major vascular structures are
located. (6,7)

“The data regarding measurements of the maximum circumference of the thigh,

knee and abdomen taken before and at the end of the study showed a significant
reduction in all patients”

At the injection site the CO2 gas penetrates and is spreads easily to other tissues
nearby, and keeps on doing its work liberating bradykinin, serotonin, histamine and
catecholamine, which stimulate the beta-adrenergic receptors, producing lipolysis
(destruction of fat cells). (8,9)

When the CO2 comes in contact with fat, it diffuses, with part of it going to red blood
cells, where when it comes in contact with the hemoglobin, it sends oxygen to the
tissue. This oxygen permits metabolic reactions and produces a stimulation of the
burning of fat.

Carboxytherapy works in three complimentary ways.

Firstly, carbon dioxide mechanically kills fat cells, by breaking off their
membranes.
Secondly, it has a strong vasodilatory effect (causes dilation of blood vessels) on
the capillaries in the area. It also increases the percentage of oxygen in the
tissue. Wider vessels mean bigger and stronger blood flow to the area. The
increase in oxygen is important because it eliminates the built up fluid from
between the cells.
And thirdly, it improves the cutaneous elasticity, and induces a rejuvenation of
the dermis.

Stomach (before on the left, after on the right) treated with 10 sessions of
carboxytherapy, twice per week for the first 2 weeks then once weekly for 6
weeks.
Photos courtesy of Dr Cyrille Blum, Lausanne, Switzerland © Copyright
Photos Dr Sster London © Copyright.
Photos courtesy of Carbomed/Taum © Copyright.

Carboxytherapy is generally cheaper for patients than a course Endermologie®,

Smartlipo®, Ultrashape®, Velasmooth®, Thermage®, Accent® or Coolsculpt®,
plus it’s a much cheaper investment for your clinic in terms of equipment, clinical
environment, insurance and per patient accessories. It is also much easier to
transport from clinic to clinic and there is almost no risk for the patient.

Dark circles under the eyes

One of the major causes of dark circles under the eyes is vascular pooling. The
capillary network under the lower eyelids can become congested for a number of
reasons. Normally tears drain from the eyelids into the nose, but if there is an
obstruction due to chronic nasal congestion from seasonal allergies, previous
nasal fracture, or a deviated septum, the drainage doesn’t function well, and the
blood flow to the lower eyelids becomes sluggish, giving rise to the boggy blue
tinge known casually as ‘allergic shiners.’

The lack of oxygenation to lower eyelid skin allows the bluish cast to show
through the thin skin. Carboxytherapy works to improve the capillary network of
the lower eyelids, as well as to increase the dermal collagen layer in the lower
eyelid skin. By injecting a small amount of carbon dioxide gas into the affected
areas, blood flow is increased and improved capillary networks are formed. The
bluish cast is replaced with a healthy pink tone. Once a series of treatments is
completed, the skin has a more luminous appearance that lasts approximately 6
months. (10,11)

Photos courtesy of dr L Zdiniak New York

k ©

Copyright.
Stretch marks

When treating stretch marks, note that studies show a better response to
treatment when the marks are recent, and still red in colour, rather than when
older and a more faded, silvery appearance. Newer stretch marks will most likely
require to be treated once a week for 2 – 4 weeks, although in some cases
(depending on severity) a single session is enough. Older stretch marks will need
3 or 4 treatment sessions at 3 - 4 weekly intervals. (13,14,15,16)
Stretch marks on the abdomen (before on the left, after on the right) treated with
4 sessions of carboxytherapy over 4 months.
Photos courtesy of Dr Cyrille Blum, Lausanne, Switzerland © Copyright.

Cellulite
Cellulite is partly a circulatory disorder at a local level. When drainage of fat cells does
not occur, waste and impurities build up. In the beginning as a liquid form, which then
acquires a thick consistency. (17,18,19,20,21,22,23)

Cellulite is the result of a number of Biochemical and Metabolic alterations which

all start on in the Interstitial Matrix and on connective structure levels.

 Ph alterations (acidity levels)

  Free radicals increase
 Temperature alterations
 Oxydo-reduction alterations
 Lymphatic stasis

Cellulite starts with:

Alterations in metabolic reactions at the interstitial matrix level:

• Alterations of fibroblasts
• Deposit of mono saccharides
• Decrease in the function of the fibroblast
• Decrease in the production of collagen.
• Decrease in the production of elastin
• Decrease in the Gluco Amino Glycans (GAG)
Leading to alterations in the extra cellular matrix.

The Glucosaminoglycans (GAG) are responsible of the movement of the blood in

the micro circulation. When GAG decrease, there is also a decrease in the
movement of the microcirculation, with less blood circulating and an alteration in
the form of the fat cells,
edema and fibrosis.

The accumulation of this thick liquid produces an irritation in the fibroblasts. They start
to produce collagen in larger volume; as a result, there is traction in the dermis, which
causes the ‘orange peel’ look.

When CO2 is injected in the affected area the situation is reverted. Vessel dilatation
occurs and with it the speed of the microcirculation improves. The tissue receives more
oxygen, toxins are eliminated, and the oedema reduces.

Through the therapeutically effects mentioned before, it re-establishes the morphology

and functionality of the microcirculation, the core of the problem, by raising the quantity
and speed of the blood flow, diminishing the accumulation of liquids between the cells,
disintegrating the fat of the hypodermis, and diminishing the fibrosis. In a few weeks,
natural local metabolism is stimulated, with the increase in the microcirculation, the
elimination of toxins and the activation of the lipolysis process (destruction of the
adipose tissue).

Scars
Dr. Sister London © Copyright

CONCLUSION:

New equipment makes Carboxytherapy a very easy to perform, cheap and

versatile option to treat multiple and various skin conditions. From vascular
disease to dark circles under the eyes. From cellulite to fat deposit. From
psoriasis to stretch marks and scars. (25,26,27,28,29)

I would like to take the opportunity to thanks Dr. C Blumm (Switzerland) and L.
Zdiniak(USA) as well as Carbomed (italia/UK) for sharing their photos.

Conflict of interest: none

REFERENCES

1- Hartmann BR, Bassenge E, Pittler M: Effect of carbon dioxide-enriched water and

fresh water on the cutaneous microcirculation and oxygen tension in the skin of
the foot. Angiology 48:337, 1997
2- Belcaro G: Flussimetria laser-doppler e microcircolazione. Minerva Medica:
Torino, p. 45, 1989
3- Ito T, Moore JI, Koss MC: Topical application of CO2 increases skin blood flow. J
Invest Dermatol 93:259, 1989
4- Pinheiro NM1, Crema VO, Millan BM, Carvalho FA, Mendonça AC. J Cosmet Laser
Ther. 2015 Jun;17(3):156-61. doi: 10.3109/14764172.2014.1003238. Epub 2015
Jan 30. Comparison of the effects of carboxytherapy and radiofrequency on skin
rejuvenation.
5- Ferreira et al. Journal of Drugs in Dermatology. 2008 Mar;7(3):201-6.
Percutaneous infiltration of carbon dioxide improves the appearance of the skin
via visible compacting of collagen fibres following CO2 infiltration especially
when administered intradermally.
6- Brandi C et al. Carbon dioxide therapy in the treatment of localized adiposities:
clinical study and histopathological correlations. Aesthetic Plast Surg.
2001;25:170-174
7- Lee GS. J Cosmet Dermatol. 2016 Dec;15(4):484-492. doi: 10.1111/jocd.12242.
Epub 2016 Jun 21. Quality survey on efficacy of carboxytherapy for localized
lipolysis.
8- Park JH, Wee SY, Chang J, Hong S, Lee JH, Cho KW, Choi CY. Aesthetic Plast Surg.
2018 Sep 7. doi: 10.1007/s00266-018-1222-y. [Carboxytherapy-Induced Fat loss
is Associated with VEGF-Mediated Vascularization.
9- Alam M, Sadhwani D, Geisler A, Aslam I, Makin IRS, Schlessinger DI, Disphanurat
W, Pongprutthipan M, Voravutinon N, Weil A, Chen BR, West DP, Veledar E, Poon
E.
10- J Am Acad Dermatol. 2018 Aug;79(2):320-326. doi: 10.1016/j.jaad.2018.04.038.
Epub 2018 Apr 24. Subcutaneous infiltration of carbon dioxide (carboxytherapy)
for abdominal fat reduction: A randomized clinical trial.
11- Nofal E, Elkot R, Nofal A, Eldesoky F, Shehata S, Sami M. J Cosmet Dermatol. 2018
Jan 3. doi: 10.1111/jocd.12478. Evaluation of carboxytherapy and platelet-rich
plasma in treatment of periorbital hyperpigmentation: A comparative clinical
trial.
12- Paolo F, Nefer F, Paola P, Nicolò S. J Cosmet Dermatol. 2012 Sep;11(3):223-8. doi:
10.1111/j.1473-2165.2012.00633.x. Periorbital area rejuvenation using carbon
dioxide therapy.
13- Podgórna K, Kołodziejczak A, Rotsztejn H J Cosmet Dermatol. 2017 Dec 6. doi:
10.1111/jocd.12465. [Epub ahead of print]. Cutometric assessment of elasticity
of skin with striae distensae following carboxytherapy
14- Ahmed NA, Mostafa OM. J Cosmet Dermatol. 2018 Jun 19.
doi:10.1111/jocd.12685 Comparative study between: Carboxytherapy, platelet-
rich plasma, and tripolar radiofrequency, their efficacy and tolerability in striae
distensae
15- Hodeib AA, Hassan GFR, Ragab MNM, Hasby EA. J Cosmet Dermatol. 2018 Jan 7.
doi: 10.1111/jocd.12481. Clinical and immunohistochemical comparative study
of the efficacy of carboxytherapy vs platelet-rich plasma in treatment of stretch
marks.
16- Podgórna K, Kołodziejczak A, Rotsztejn H. J Cosmet Dermatol. 2017 Dec 6. doi:
10.1111/jocd.12465. Cutometric assessment of elasticity of skin with striae
distensae following carboxytherapy.
17- Eldsouky F, Ebrahim HM. J Cosmet Laser Ther. 2018 Jan 17:1-6. doi:
10.1080/14764172.2017.1400175. Evaluation and efficacy of carbon dioxide
therapy (carboxytherapy) versus mesolipolysis in the treatment of cellulite.
 18- Pianez LR, Custódio FS, Guidi RM, de Freitas JN, Sant'Ana E. Clin Cosmet Investig
Dermatol. 2016 Aug 22;9:183-90. doi: 10.2147/CCID.S102503. eCollection 2016.
Effectiveness of carboxytherapy in the treatment of cellulite in healthy women: a
pilot study.
19- Rosenbaum M, Priedo V, Hellmer J, Boschmann M, Krueger J, Leibel RL, Ship AG:
An exploratory investigation of the morphology and biochemistry of cellulite.
Plast Reconstr Surg 101:1934, 1998
20- Draelos ZD, Marenus KD: Cellulite. Etiology and purported treatment. Dermatol
Surg 23:1177, 1997
21- Lee GS Aesthetic Plast Surg. 2010 Apr;34(2):239-43. doi: 10.1007/s00266-009-
9459-0. Epub 2010 Jan 29. Carbon dioxide therapy in the treatment of cellulite:
an audit of clinical practice.
22- J Cosmet Laser Ther. 2018 Jan 17:1-6. doi: 10.1080/14764172.2017.1400175.
23- Eldsouky F, Ebrahim HM Evaluation and efficacy of carbon dioxide therapy
(carboxytherapy) versus mesolipolysis in the treatment of cellulite.
24- Draelos ZD, Marenus KD: Cellulite. Etiology and purported treatment. Dermatol
Surg 23:1177, 1997
25- Kołodziejczak A, Podgórna K, Rotsztejn H. Dermatol Ther. 2018 Aug 28:e12699.
doi: 10.1111/dth.12699. Review. Is carboxytherapy a good alternative method in
the removal of various skin defects?
26- Moftah NH, El Khayyat MAM, Ragai MH, Alaa H. Dermatol Surg. 2018
Oct;44(10):1332-1341Carboxytherapy Versus Skin Microneedling in Treatment of
Atrophic Postacne Scars: A Comparative Clinical, Histopathological, and
Histometrical Study.
27- Al Taweel AI, Al Refae AA, Hamed AM, Kamal AM. J Cosmet Dermatol. 2018 Apr
22. doi: 10.1111/jocd.12561. Comparative study of the efficacy of Platelet-rich
plasma combined with carboxytherapy vs its use with fractional carbon dioxide
laser in atrophic acne scars.
28- Kamel AM, Abdelghani R Carboxytherapy for treatment of localized chronic
plaque psoriasis: Clinical and histopathologic evaluation.
29- Khiat L, Leibaschoff GH.. Surg Technol Int. 2018 Jun 1;32:81-90. Clinical
Prospective Study on the Use of Subcutaneous Carboxytherapy in the Treatment
of Diabetic Foot Ulcer.

J Cosmet Dermatol
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