Carboxytherapy in the Management of Selected Skin Conditions–Applications in Monotherapy and Combined Treatments

Abstract

Carboxytherapy is a non-invasive therapeutic method involving the transcutaneous or subcutaneous administration of carbon dioxide (CO₂), which stimulates microcirculation, neoangiogenesis, and collagen production. This narrative review summarizes the latest scientific findings (2020–2025) on the effectiveness of carboxytherapy in treating selected dermatological and aesthetic skin conditions, including periorbital dark circles, stretch marks, scars, and signs of skin aging. The article discusses both monotherapies and combination protocols, particularly with laser therapies and chemical peels. Numerous clinical studies confirm that carboxytherapy significantly improves skin elasticity, tone, hydration, and structure through mechanisms such as improved oxygenation, stimulation of fibroblasts, and controlled inflammation. Moreover, combination therapies frequently offer superior outcomes, especially in scar and stretch mark reduction. Carboxytherapy demonstrates high safety, minimal side effects, and broad applicability, making it a valuable tool in both medical and cosmetic dermatology.

1. Introduction

Carboxytherapy is a minimally invasive procedure involving the transcutaneous or subcutaneous administration of medical-grade carbon dioxide (CO₂). About 70% of the total carbon dioxide present in the body reacts with the water in the plasma to produce carbonic acid. Bicarbonate is produced and dissolved in plasma according to the following formula: CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻. The result of these reactions is a decrease in tissue pH, which induces an increase in microvascular blood flow. Ultimately, the Bohr effect is inducted, which is represented by an increase in the partial pressure of CO₂ or a decrease in pH, which is visible as a shift to the right in the O₂ hemoglobin dissociation curve. A local increase in the concentration of CO₂ and H⁺ ions in the extracellular fluid causes an immediate relaxation of the smooth muscles of the blood vessels, resulting in their temporary dilation—an increase in regional blood flow, which, in turn, increases oxygen availability in tissues, including the skin [1,2].

The treatment improves tissue oxygenation and stimulates microcirculation, fibroblast activity, and collagen and elastin production, leading to enhanced skin elasticity and appearance [1,2,3]. These effects are mediated through mechanisms such as vasodilation, controlled inflammation, and angiogenesis, triggered by growth factors, including vascular endothelial growth factor-A (VEGF-A) and fibroblast growth factor (FGF) [4,5,6,7].

Initially introduced in medicine for the treatment of hard-to-heal wounds and ulcers, carboxytherapy has since been widely adopted in dermatology and aesthetic medicine. It is applied in the management of psoriasis, alopecia, cellulite, localized adiposity, periorbital hyperpigmentation, stretch marks, scars, and signs of skin aging [8,9,10]. The procedure is considered safe and minimally invasive, with the most common adverse effects being transient erythema, swelling, or mild discomfort. However, contraindications such as pregnancy, breastfeeding, active skin infections, or inflammation at the treatment site and uncontrolled diabetes, hypertension, or other chronic medical conditions should be considered (Figure 1) [3,4,6,8,9,10].

In recent years, there has been growing interest in combining carboxytherapy with other treatment modalities—such as fractional CO₂ laser therapy, chemical peels, microneedling, or platelet-rich plasma—to achieve synergistic effects [3,8]. Despite increasing clinical use, there is limited synthesis of the latest evidence from 2020–2025 regarding its efficacy and safety across different dermatological and aesthetic indications.

The purpose of this review is to summarize and critically assess the latest scientific evidence on the application of carboxytherapy in the treatment of periorbital dark circles, stretch marks, scars, and signs of skin aging, with a focus on both monotherapy and combination protocols.

The purpose of this publication is to review literature and provide current knowledge supported by research on the use of carboxytherapy in treatments that include the reduction of dark circles under the eyes, stretch marks, scars, and anti-aging procedures.

2. Materials and Methods

The study is a narrative review summarizing scientific reports on the effectiveness of carboxytherapy in selected skin defects that are most commonly encountered in cosmetology practice. A search of the PubMed and Scopus databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [11]. Databases from 2020 to 2025 (up to and including May 2025) were reviewed. Search terms included: ‘carboxytherapy’, ‘carbon dioxide therapy’ and ‘carboxytherapy periorbital dark circles’, ‘carboxytherapy in skin aging’, ‘carboxytherapy scars’, ‘carboxytherapy striae distensae’, ‘carboxytherapy stretch marks’, and ‘carboxytherapy combined protocols’. Duplicate articles, articles without full text available, letters to the editor, case reports, and review articles were excluded.

2.1. Description of the Procedure and Equipment Used in Carboxytherapy

Carboxytherapy involves the transcutaneous or subcutaneous administration of sterile, medical-grade carbon dioxide (CO₂) using a dedicated device equipped with precise flow control and filtration systems. Based on the Carboxytherapy Medika^® device (Warsaw, Poland), the standard carboxytherapy set consists of a CO₂ cylinder connected to an electronic control unit that regulates gas flow rate, volume, and temperature. A heating system is often incorporated to warm the gas prior to tissue delivery, which improves patient comfort and reduces vasoconstriction. The gas is administered via a disposable sterile needle attached to a flexible tube connected to the main device. Local anesthesia is usually not required due to the minimally invasive nature of the procedure, although topical anesthetics may be applied in sensitive areas. The treatment is generally well-tolerated, with transient erythema, swelling, mild pain, excessive tenderness, or a mild burning sensation reported in some patients [2,3,4,6,9]. In cosmetology, this method is employed to support the treatment of conditions such as periorbital hyperpigmentation, stretch marks, and scars. Moreover, it plays a significant role in anti-aging procedures by contributing to the overall improvement of skin condition and appearance. When used as a standalone procedure, carboxytherapy is particularly valued for its minimally invasive nature and the absence of systemic side effects. The localized injection of CO₂ induces vasodilation and a mild inflammatory response, which activates fibroblasts and promotes dermal remodeling. Additionally, CO₂ enhances lymphatic drainage and cellular metabolism, contributing to visible skin rejuvenation. The findings of this review indicate that in combination therapies, carboxytherapy is frequently integrated with agents such as chemical peels, microneedling, or laser treatments. These multimodal approaches enhance clinical outcomes by synergistically targeting different aspects of skin defects [3,8].

Key parameters influencing the effectiveness and safety of treatment were taken into account. Gas flow rate usually ranges from 5 cc/min to 100 cc/min, depending on the indication and anatomical area. Total gas volume per session varies between 1 and 150 cc, depending on the treatment site (e.g., periorbital vs. abdomen). Injection depth may be intradermal or subcutaneous, tailored to the target tissue. Needle size and length are selected based on the area treated and skin thickness, most often 30 G–32 G and 4 or 13 mm. Frequency and number of sessions are typically performed in weekly or biweekly intervals, with 3 to 10 sessions per treatment cycle.

While the assessment methods of each study are concisely outlined in the main text, detailed methodological descriptions are presented separately in the accompanying tables.

2.2. The Use of Carboxytherapy to Reduce Dark Circles Under the Eyes

Defects of the eye area are one of the most frequently reported aesthetic problems in both men and women [12]. This is also a very difficult area due to the thin epidermis and dermis, the smooth cutaneous–epidermal boundary, the small number of sebaceous glands (which often causes dryness), and poor subcutaneous tissue. The skin around the eyes is prone to irritation, allergies, bruising, and swelling. It is also characterized by reduced elasticity compared to other areas, which may be related to its thickness: the thickness of the eyelid skin is approximately 0.5–1.0 mm [13]. Dark circles under the eyes are one of the most common aesthetic problems with complex pathogenesis. They can be temporary (resulting, for example, from fatigue, dehydration, vitamin deficiencies, smoking) or permanent, e.g., genetic [14]. Dark circles under the eyes are divided into vascular, pigmentary (post-inflammatory), structural (shadow effect), constitutional, and other types [15,16]. Vascular shadows are most often caused by genetic factors; hormonal disorders; heart, liver, or kidney disease; deficiencies, e.g., iron or vitamin K; or the use of certain medications. They are characterized by the shallow location of blood vessels in this area and the slow circulation of poorly oxygenated blood (deoxygenated hemoglobin is purple in color, giving the skin a bluish tint) [13,17]. Pigment shadows (hyperpigmentation) are most often the result of inflammation and are caused by the accumulation of melanin and hemoglobin and its enzymatic breakdown products (biliverdin, bilirubin, methemoglobin, and hemosiderin) in the epidermis and dermis [13,18]. Structural/true shadows in the color of unchanged skin are a symptom of aging—they are caused by the loss and downward displacement of fatty tissue (along with the progression of skin laxity and the effects of gravity). They may also be related to the natural anatomical structure of the eye area or result from age-related recession and a reduction in the volume of the orbital bone (especially its edges). The shadow forms in sunken areas and depends on the angle of light [13,19].

There are many methods for reducing dark circles under the eyes of various origins, including laser therapy, carboxytherapy, chemical peels, platelet-rich plasma, and a combination of the above techniques [20,21].

The effectiveness of four carboxytherapy sessions in reducing periorbital dark circles was assessed using a 10-point visual analogue scale (with 10 indicating the intensity of the dark circles before treatment was the darkest), showing progressive improvement with each session [22]. The scale was measured in all subjects before and after each carboxytherapy session. The final evaluation of the results was performed two weeks after the last session. All subjects reported the highest satisfaction at the end of the third session, compared to the first and second carboxytherapy sessions.

The reduction of under-eye shadows was also observed in a study involving four treatment sessions administered at weekly intervals [23]. To collect quantitative data on the color difference between the pigmented areas of the eye socket (lateral, central, and medial regions) and the adjacent normal skin in the extra-orbital area, measurements of skin pigmentation variation were performed using the VisioFace^® device (Courage-Khazaka Electronic, Cologne, Germany). The degree of color difference was assessed based on changes in pigmentation intensity between the treated and surrounding skin. Follow-up assessments were performed before, 1 week, and 5 weeks after the last session. Based on the measured differences in skin color between the pigmented and adjacent normal areas, a significant reduction in pigmentation was observed in all regions treated with carboxytherapy. No statistically significant differences were observed between the lateral, central, and medial regions of the periorbital area, indicating that carboxytherapy demonstrated comparable efficacy across all examined sites. Regarding patient satisfaction with the treatment, 60% of patients rated their experience as ranging from slight to moderate, while 40% reported satisfaction levels from good to excellent. The adverse events documented in the study comprised erythema, extended swelling, and, in two instances, eyelid blinking. These events resolved either spontaneously within roughly one week or following the application of warm compresses and massage. Participants who presented with increased eyelid blinking were promptly referred for ophthalmological assessment and managed with conservative therapy. No enduring adverse effects were detected during the follow-up period.

A group of 39 Caucasians participated in a study which examined and compared the effects of carboxytherapy as monotherapy and in combination with selected chemical peels on periorbital dark circles [24]. Changes in melanin and hemoglobin levels in the skin around the eyes after a series of carboxytherapy treatments were assessed using a Mexameter^® MX 18 probe connected to a Multi Probe Adapter Courage + Khazaka electronic GmbH. A single carboxytherapy treatment performed in the area around the right eye significantly reduced the severity parameter of erythema (vascular shadows). A reduction of −3.3 units on average (improvement in 69.2% of study participants) was observed in the tear trough and −7.8 units (improvement in 82.1% of participants) in the central part of the eye. The chemical peel procedure was performed on the left side. The researchers used 20% lactobionic acid with a pH of 2.1 or 14% ferulic acid with a pH of 4.0–5.0 in combination with 12% L-ascorbic acid. Ferulic acid with L-ascorbic acid was used on pigmented shadows, and lactobionic acid was used on individuals with vascular shadows. An improvement was also observed on the left side, where combination therapy was used. A 7.2 reduction in the erythema index (EI) was reported (improvement in 82.1% of subjects) in the tear trough area. However, the effect of treatment on the melanin index (MI) was not statistically significant. During carboxytherapy, participants experienced brief subcutaneous gas sensation with mild pain, pressure, stinging, burning, itching, or tingling, typically lasting about three minutes. Local circulation stimulation increased skin temperature by 1 °C–1.5 °C for roughly ten minutes, measured intermittently with a non-contact infrared thermometer. Minor ecchymosis occurred in two participants and resolved within 2–3 days; mild morning swelling occurred in four participants and subsided within two hours. These transient periprocedural effects are considered normal and do not require medical intervention.

A split-face study was conducted to compare the effects of carboxytherapy and microneedling combined with topical glutathione (600 mg/5 mL per vial, approximately 0.25 mL per session) in the treatment of periorbital dark circles [25]. Approximately 0.25 mL of glutathione was used per session to reduce dark circles under the eyes. Carboxytherapy was performed on the right side of the face and microneedling with topical glutathione on the left eye area. After 3 months, a visual analogue scale (VAS), dermoscopic evaluation, photographic documentation, patient satisfaction, a quality of life questionnaire, and a safety assessment were used for evaluation. Carboxytherapy showed a greater significant improvement in VAS assessment compared to microneedling with glutathione. Dermoscopy and the questionnaire also showed a statistically significant improvement in the carboxytherapy group. In terms of patient safety, there was no significant difference between the right and left sides. Among the reported adverse effects, only 12.9% (4/31) of patients with microneedling using topical glutathione developed ecchymosis, whereas no adverse events were recorded with carboxytherapy.

In a subsequent study investigating the effects of carboxytherapy on infraorbital dark circles, both the overall efficacy of the treatment and the comparative effectiveness of two different carbon dioxide flow rates were evaluated [26]. A group of 80 people with dark circles under the eyes was divided into two equal groups: in group A, carbon dioxide was applied at a flow rate of 30 mL/min, and in group B, it was applied at a flow rate of 60 mL/min. The same amount of gas was administered in both groups. The results were evaluated 6 weeks after the last session. The study reported a significant lightening of the shadows in both groups. However, no significant differences were found in the effects between the carbon dioxide flow rates used, but significantly more adverse effects (e.g., heaviness and puffiness followed by headaches) were observed in the group using the higher flow rate (60 mL/min). Less frequent adverse events included pain, erythema, and ecchymosis. No significant differences in overall satisfaction of subjects after treatment were found between the two groups.

The efficacy of carboxytherapy in reducing infraorbital dark circles was confirmed in a prospective clinical study involving 35 patients [27]. Each treatment session consisted of bilateral injections into the tear trough area. Standardized pre- and post-treatment photographs were captured using a 16-megapixel camera under consistent lighting conditions, prior to the initial session and six months following the final treatment. The primary outcome measures were assessed using an objective facial evaluation tool, the “New Face Objective Photo-Numerical Assessment Scale,” developed by the authors’ research team. For the purposes of this study, only the subsection pertaining to infraorbital dark circles was utilized. This scale employs a scoring system ranging from 0 (absence of discoloration) to 3 (pronounced and clearly visible discoloration). Photographs were obtained prior to the initiation of treatment and six months following the final procedure. The images were subsequently randomized and assigned to individual evaluation forms. Each form was independently assessed by three blinded evaluators to ensure objectivity in scoring. Carbon dioxide treatment for infraorbital dark circles yielded satisfactory outcomes, demonstrating a noticeable improvement in the appearance of the treated areas. Both the pre- and post-treatment scores, as evaluated by the three blinded assessors and self-reported by the patients, indicated a statistically significant enhancement. Furthermore, by the conclusion of the study, patients also exhibited a reduction in both deep and superficial periorbital wrinkles. No other secondary effects were noted.

Several studies have compared the effectiveness of carboxytherapy with other treatment modalities—such as laser therapy or platelet-rich plasma (PRP)—in reducing periorbital dark circles. One such study was a split-face trial involving 23 patients, in which PRP was administered to the right side and carboxytherapy to the left [28]. The final assessment, conducted three months after the last session using both clinical and histopathological evaluations, revealed a significant improvement on both sides. However, the PRP-treated side showed a greater reduction in melanin content, a more pronounced clinical response, shorter recovery time, and similarly acceptable side effects, compared to carboxytherapy.

The effectiveness of two commonly used methods to reduce dark circles under the eyes in the orbital area was evaluated in a group of 28 people [29]. Subjects were randomly divided into two groups of equal size: the first group received carboxytherapy, and the second group received fractional Q-switched Nd:YAG laser treatment with a wavelength of 1064 nm. In the carboxytherapy group, the treatment was performed six times, with 1-week intervals between sessions. In the Nd:YAG laser group, the treatment was performed in four sessions, with 1-month intervals between sessions. The results were evaluated using biometric evaluation and visual analogue scale (VAS) scoring by both researchers and patients, as well as patient satisfaction. Side effects of the treatments were also evaluated. The results showed that both carboxytherapy and Nd:YAG laser are effective in treating dark circles under the eyes in the orbital area, but carboxytherapy is significantly more effective. In the carboxytherapy group, an increase in skin brightness and a decrease in melanin content was observed in the periorbital skin, and these changes were more pronounced in this group, compared to the Nd:YAG laser group. In addition, adverse effects such as erythema and post-inflammatory hyperpigmentation were less severe with carboxytherapy than with the Nd:YAG laser.

Other researchers have also compared the effectiveness of carboxytherapy and laser therapy in reducing dark circles under the eyes [30]. A split-face study involved 30 subjects who underwent carboxytherapy on one side of the face and fractional CO₂ laser therapy on the other. The evaluation was based on both subjective methods (patient satisfaction and the opinion of the person who performed the treatment) and objective methods (based on standard digital photographs). The degree of improvement from the perspective of the subject and the practitioner was assessed during various treatment sessions in comparison with the improvement after the first session. After the second treatment session, patient satisfaction was significantly better in the fractional CO₂ laser therapy group than in the carboxytherapy group as time progressed. According to the researchers’ satisfaction, the improvement rate was higher after the second and sixth weeks in the fractional CO₂ laser therapy group than in the carboxytherapy group, while in other sessions, there were no statistically significant differences. No significant side effects were observed in either group after each treatment.

The characteristics of the treatment protocols discussed in this study, which involve the use of carboxytherapy for the reduction of periorbital dark circles, are summarized in

Table 1. Characteristics of studies involving carboxytherapy treatments to reduce dark circles under the eyes (W = women, M = men; * the gas was administered at an angle of 30–45 degrees, consistent with a subcutaneous route of injection [31]).

Group	Age	Administration of CO2	Gas Flow Rate	Gas Volume	Needle Size	Local Anesthesia	Treatment Series	Ref
27 (24W, 3M)	24–45	intradermal	20 cc/min	2 cc per eye	32 G	yes	4 treatments every 2 weeks	[22]
20 (1W, 8M)	20–50	intradermal	20 cc/min	10–20 cc	not stated	not stated	4 treatments every week	[23]
39 (35W, 4M)	25–55	intradermal	10 cc/min	3 cc per eye	32 G, 4 mm	no	5 treatments every week	[24]
31W	18–45	intradermal/ subcutaneous	5 cc/min	20–30 cc	insulin	no	6 treatments every 2 weeks	[25]
Gr A: 40 (36W, 4M) Gr B: (35W, 5M)	mean 30.83 ± 9.31	subcutaneous	Gr A: 30 cc/min Gr B: 60 cc/min	Not stated	32 G	not stated	6 treatments every week	[26]
35	not stated	subcutaneous	not stated	2 cc per eye	32 G	no	3 treatments every week	[27]
23 (22W, 1M)	not stated	not stated *	1 cc/s	1–2 cc per eye	32 G	yes (2.5% lidocaine with 2.5% prilocaine)	4 treatments every week	[28]
28 (24W, 4M)	18–65	subcutaneous	1 cc/s	2 cc per eye	30 G	yes (2.5% lidocaine with 2.5% prilocaine)	6 treatments every week	[29]
30	23–52	intradermal/ subcutaneous	not stated	5 cc	not stated	not stated	4 treatments every 2 weeks	[30]

.

2.3. The Effect of Carboxytherapy on the Symptoms of Skin Aging

Aging is a natural and inevitable process, described as a set of changes that progress over time. The visible symptoms of skin aging include wrinkles, discoloration, sagging of the face, and laxity—changes that can have a negative impact on mental health and quality of life. Skin aging is a complex process in which various regulatory and metabolic changes occur at the same place and time. Depending on whether we are dealing with chronological aging or a predominance of exogenous factors, different symptoms are observed in the skin. In chronological aging, the following can be observed, among others: a reduction in the activity of basal cells, a tendency for melanocytes to accumulate in clusters, flattening of the skin–epidermis boundary, fibroblast dysfunction and, as a result, a reduction in type I collagen, a decrease in glycosaminoglycans in the extracellular matrix, a loss of vascularization, and atrophy of the subcutaneous adipose tissue [32,33]. Carboxytherapy increases skin elasticity, breaks down ‘old’ collagen, and induces the production of new collagen, which has a structure characteristic of young skin. Furthermore, after carboxytherapy, new capillaries appear [13,34].

The effect of carboxytherapy on skin aging was evaluated in a split-body study, in which one side of the abdomen showing signs of aging was treated, while the other side served as an untreated control [35]. The study included 28 participants, with 15 randomly selected for molecular analysis. Two weeks following the final treatment session, 5 mm sterile disposable punch biopsies were collected from both the right and left sides of the abdominal area at the site of the cesarean section for further analysis. Subsequently, a total of 30 human skin samples—comprising 15 from the treatment group and 15 from the control group—were examined for the expression of genes: Collagen I, Collagen III, Collagen IV, elastin, FGF, TGF-β1, and VEGF, using β-actin as the housekeeping gene. Quantitative real-time PCR (qRT-PCR) was employed for this analysis. Analysis of gene expression levels for all Coll I, Coll III, and Coll IV genes, elastin, TGF-β1, FGF, and VEGF showed a statistically significant difference between the intervention and control groups (p < 0.05). All seven genes exhibited increased expression in the intervention group, with Coll IV, VEGF, FGF, and elastin demonstrating the most pronounced average changes.

The thickness of the epidermis and dermis in aging abdominal skin was also assessed in a related study, which demonstrated significant increases in both layers following carboxytherapy [36]. Two weeks after the final carboxytherapy session, 5 mm sterile disposable punch biopsies were obtained from both the right and left sides of the abdominal region for subsequent histopathological and immunohistochemical (IHC) analyses. For the IHC analysis, the expression levels of TGF-β1 and VEGF were evaluated. A total of 30 samples were obtained from 15 female participants. The thicknesses of the epidermis, dermis, collagen, and elastin were assessed using hematoxylin, Masson-trichrome, and Orcein Giemsa staining. Histological analysis revealed that the mean epidermal thickness was 0.25 mm (±0.06) in the interventional group and 0.14 mm (±0.02) in the control group. Similarly, the mean dermal thickness measured 3.2 mm (±1.02) in the interventional group, compared to 1.5 mm (±0.8) in the control group. Paired t-test analysis demonstrated that the increases in both epidermal and dermal thicknesses in the interventional group were statistically significant (p < 0.001). The researchers also demonstrated reorganization of collagen and elastic fibers as a result of carboxytherapy. IHC studies revealed significantly increased expressions of TGF-1 and VEGF during carboxytherapy.

The effect of carboxytherapy on skin elasticity in the periorbital area was assessed in a cohort of 39 individuals using a Cutometer^® probe [37]. Two key parameters were evaluated: R2 (a measure of overall skin elasticity, including changes in skin viscosity during both deformation and retraction; it measures the ratio of “final skin retraction” to “final deformation.” An increase in this parameter indicates an increase in skin elasticity) and R7 (a measure of immediate return of elasticity after complete deformation, which is related to elasticity; the higher the values (approaching 100%), the more elastic the skin is). The authors observed a significant improvement in skin elasticity. In addition, photographic documentation was performed using the Fotomedicus photographic system and a Canon EOS camera with zoom control. The study found a statistically significant increase in the R2 parameter as a result of the treatment series. In 29 of the 39 subjects, carboxytherapy significantly improved skin tone and elasticity. In 28 participants, a beneficial change in the R7 parameter was observed.

The effects of carboxytherapy, IPL (Intense Pulsed Light), and radiofrequency in facial skin rejuvenation were compared [38]. The study involved 60 patients with facial wrinkles. Patients were divided into three groups (Group 1–IPL, Group 2–RF, and Group 3–carboxytherapy). All subjects received four sessions at 3–to 4-week intervals and were monitored 3 months after the end of treatment. Standardized facial digital photographs were captured for each participant at baseline, before each treatment session, upon completion of the treatment course, and at a 3-month follow-up. Clinical evaluation was conducted using Glogau’s photoaging classification. In addition, at the end of each session and at the 3-month follow-up, three independent dermatologists assessed the percentage of clinical improvement for each participant. Patients were also asked to self-evaluate and report their level of satisfaction with the treatment as a percentage. In addition, histopathological evaluation was conducted to further assess the tissue-level changes following treatment. A 2 mm punch skin biopsy was obtained from each patient prior to treatment and following the final session. Specimens were processed and stained with routine hematoxylin and eosin (H&E) to evaluate general histological features, including dermal thickness and the thickness of the dermoepidermal junction, using image analysis techniques. Moreover, immunohistochemical analysis was performed using an anti-MMP-1 antibody to assess its expression in the studied samples and to evaluate treatment-induced alterations. The results showed that all treatments were effective. Hematoxylin and eosin (H&E)-stained sections from both the IPL and carboxytherapy groups demonstrated a moderate increase in the density and number of collagen fibers, as well as a moderate thickening of the dermis and the dermoepidermal junction. In contrast, sections from the RF group exhibited only a mild increase in collagen fiber density and number, along with a mild thickening of both the dermis and the dermoepidermal junction. With respect to MMP-1 expression, a statistically significant increase was observed in Groups 1 and 3 following treatment, compared to baseline. In contrast, Group 2 exhibited no significant change in MMP-1 expression after treatment. In group (1), 8 participants (40%) reported a burning sensation, and 12 (60%) experienced transient erythema lasting one day post-session. In group (2), pain was reported by 10 participants (50%), while 4 (20%) developed transient erythema. In group (3), all participants (100%) experienced mild pain during CO₂ injection; 12 (60%) presented with edema that resolved within 48 h; and 6 (30%) developed ecchymosis that resolved within one week. All participants were monitored for three months following treatment cessation, during which the therapeutic effect was maintained.

Skin aging affects the skin of the entire body. Oliveira et al. investigated the effect of carboxytherapy on skin laxity [10]. Nine subjects underwent a carboxytherapy treatment at a single point in an area of 25 cm² on the left side of the subumbilical region. A skin sample from the treated area and a control sample were taken during surgery, approximately 60 days after application, and then sent for histological analysis. Histological sections of 5 μm thickness were prepared using a microtome and mounted on poly-L-lysine-coated slides. The sections were stained with Picrosirius Red for the evaluation of collagen fibers and with Verhoeff’s stain to assess elastic fibers. Histological findings demonstrated an increase in collagen synthesis and elastic fibers in the treated groups, compared with the control group. Morphometric analysis demonstrated a significant increase in the percentage of collagen fibers in the carboxytherapy-treated group, compared to the control group (p = 0.04). However, no significant difference was observed between the carboxytherapy and control groups regarding the proportion of elastic fibers. Although the study provides valuable preliminary insights and appears methodologically sound, the sample size is small, and the treatment regimen was limited to a single session. In clinical practice, carboxytherapy protocols usually involve a series of 4–8 treatments to achieve more pronounced and sustained effects. Although the study appears interesting and well designed, the sample size is small, and the treatment series is too limited. Typically, a series of 4–8 treatments is performed.

The characteristics of the discussed treatment protocols using carboxytherapy for skin aging symptoms are presented in

Table 2. Characteristics of studies involving carboxytherapy for signs of aging (W = women, M = men).

Study Group	Age	Treatment Area	Administration of CO2	Gas Flow Rate	Gas Volume	Needle Size	Local Anesthesia	Treatment Series	Ref
15	40–56	abdomen	intradermal	not stated	150 cc	30 G, 4 mm	not stated	10 treatments every week	[35]
15W	40.0–56.5	abdomen	intradermal	not stated	150 cc	not stated	not stated	10 treatments every week	[36]
39 (35W, 4M)	25–55	eye area	intradermal	10 cc/min	3 cc per eye	32 G	no	5 treatments every week	[37]
60 20 participants received carboxytherapy	not stated	face	intradermal	not stated	5 cc	30 G	no	4 treatments every 3–4 weeks	[38]
9W	not stated	abdomen	not stated	100 cc/min	not stated	not stated	not stated	1 treatment	[10]

.

2.4. The Use of Carboxytherapy in the Reduction of Stretch Marks

Histopathologically, stretch marks have a structure similar to scars, with damage to elastin and collagen fibers and thinning of the dermis and epidermis. In the early stages, they are pink or red (striae rubra), but with time and with atrophic changes, they turn white (striae alba). Stretch marks occur in all races and are generally found on the buttocks, thighs, abdomen, knees, calves, and lumbosacral region. They are more common in women, for example, on the abdomen after pregnancy. They may also accompany diseases such as Cushing syndrome, Marfan syndrome, obesity, or appear physiologically during puberty [3,39]. In the treatment of mature white stretch marks is conditioned by an increase in the amount of oxygen in tissues, the initiation of neoangiogenesis, and the production of new collagen fibers and their more parallel distribution. The formation of a new network of blood vessels contributes to a change in skin color within stretch marks to pink/purple, as is the case with fresh stretch marks [13,39].

A study evaluating the efficacy of carboxytherapy in diminishing stretch marks involved thirty female participants presenting with stretch marks on their bodies [40]. Each participant underwent a series of carboxytherapy treatments. Patients were evaluated at baseline, prior to each treatment session, and four weeks after the final session. High-resolution digital photographs were taken at each time point using standardized camera settings. Treatment outcomes were assessed by two blinded dermatologists, who compared pre- and post-treatment images using the Global Aesthetic Improvement Scale (GAIS). The degree of patient satisfaction with treatment outcomes was evaluated using a 5-point Likert scale, where 1 indicated ‘very dissatisfied’, and 5 indicated ‘very satisfied’. According to GAIS assessments, the majority of patients demonstrated improvement, with some showing marked improvement, a few exhibiting no change, and none experiencing worsening. In terms of patient satisfaction, most participants reported being satisfied or very satisfied, while a smaller number were neutral or unsatisfied. No patients reported being very unsatisfied. Among the 30 patients treated with carboxytherapy, 20 (66.7%) reported mild, tolerable pain, 9 (30%) experienced transient erythema, and 1 (3.3%) developed itching immediately post-injection, which resolved within 10–60 min. No adverse effects were observed at the 4-week follow-up.

The efficacy of carboxytherapy in reducing abdominal striae alba—through improvements in skin texture and firmness—was demonstrated in a clinical study involving 30 female participants [41]. A total of 10 carboxytherapy treatments were performed. Evaluation was conducted using standard photographic documentation and patient-reported outcomes, as well as histological (to assess collagen and elastin fibers) and immunohistochemical analyses. Biopsy was taken before the treatment series and 2 months after the last treatment. Histopathological evaluation of the biopsies after the series revealed a significant improvement in the average thickness of the epidermis, and a significant increase in the number of collagen bundles and elastin fibers was also observed. Compared to pretreatment biopsies, sparse and loosely packed collagen became densely packed and more organized. The authors demonstrated the effectiveness of carboxytherapy in reducing stretch marks in all patients.

In another study presented in this review, twenty patients received eight sessions of intradermal carbon dioxide injections, performed at two-week intervals using a carboxy gun [42]. The patients were photographed, and skin samples were taken from the treated area before and after four months of treatment. Clinical improvement in striae distensae (SD)—including changes in width, length, number, texture, color mismatch, and skin atrophy—was evaluated by patients, two physicians, and two independent observers using a five-point scale, both at baseline and four months after treatment initiation. Skin topography at the treatment site was assessed in vivo with the Antera 3D imaging system, which provides two- and three-dimensional, as well as multispectral, analysis of skin features such as texture, pigmentation, and vascularity. Additionally, 4 mm punch biopsies were collected from SD lesions at baseline and four months post-treatment. Researchers demonstrated statistically significant clinical improvement in striae distensae (SD) following carboxytherapy (p < 0.05). Greater improvement was observed in striae rubra compared to striae alba. Antera 3D imaging revealed significant improvements in skin indentation and texture. Prior to treatment, histological analysis revealed disorganized collagen bundles and a marked reduction in dermal elastic fibers, which appeared fragmented and irregular. Post-treatment, newly formed collagen bundles appeared more compact and organized, accompanied by a significant increase in elastic fibers exhibiting a normal linear microfibrillar pattern.

A comparative study was performed to evaluate the efficacy of carboxytherapy versus CO₂ laser treatment in the reduction of stretch marks [43]. The study was conducted using the split-body method on 30 individuals. The left side was treated with a fractional CO₂ laser and the right side with carboxytherapy in the same session. Clinical evaluation was performed by measuring the width of the widest stretch marks on both sides, the global aesthetic improvement scale (GAIS), and the Likert satisfaction scale. Radiological evaluation was performed by measuring the skin thickness of the widest stretch marks on both sides using ultrasound. The study demonstrated a reduction in the width of the widest stretch marks on both sides. Both fractional CO₂ laser and carboxytherapy can be considered safe and effective methods for the treatment of stretch marks, but fractional CO₂ laser showed excellent clinical and radiological improvement, compared to carboxytherapy. Following fractional CO₂ laser sessions, patients experienced transient erythema that resolved completely within two days. One patient with skin phototype IV (3.3%) developed mild hyperpigmentation accompanied by inflammation after the first treatment session, attributed to non-adherence to post-procedure care; the pigmentation, associated with severe inflammation, partially subsided within 12 days of topical potent corticosteroid application. Immediately after carboxytherapy sessions, patients reported tolerable pain and transient erythema at the injection site, which resolved within one hour. No additional adverse effects were observed.

Table 3. Characteristics of studies involving carboxytherapy for stretch marks (W = women, M = men).

Study Group	Age	Area	Administration of CO2	Gas Flow Rate	Gas Volume	Needle Size	Local Anesthesia	Treatment Series	Ref
30W	18–50	stretch marks on abdomen, arms, thighs, breasts, buttocks	intradermal	not stated	0.1–0.3 cc	30 G	yes (5% lidocaine)	6 treatments every 4 weeks	[40]
30W	not stated	stretch marks on abdomen	intradermal/ subcutaneous	80/100 cc/min	not stated	30 G	no	10 treatments every week	[41]
20W	18–39	striae alba-12 striae rubra-8	intradermal	not stated	15–45 cc	32 G, 3 mm	no	8 treatments every 2 weeks	[42]
30	19–45	stretch marks	intradermal	not stated	0.1–0.3 cc	30 G	no	6 treatments every 4 weeks	[43]

provides a detailed overview of the treatment protocols utilizing carboxytherapy for the reduction of stretch marks, as discussed in the present article.

2.5. The Effect of Carboxytherapy on the Reduction of Various Types of Scars

Scars develop at the site of a previous injury and are defined as fibrous connective tissue. The structure of a developing scar is different from that of normal healthy skin. In a newly formed scar, capillaries grow between the collagen fibers and can persist for up to 6 months after the injury. The juvenile form of a scar has the appearance of a raised red structure, which flattens and lightens as it matures. A mature scar does not have appendages and has a different collagen composition (scar tissue consists of approximately 80% type III collagen and 20% type I collagen; normal skin has the opposite proportion of these fibers) and is also characterized by greater resistance to mechanical factors [44,45]. Mechanical stretching of tissues caused by intradermal and subcutaneous injection of carbon dioxide triggers a cascade of processes, starting with a decrease in pH, increased oxygen distribution, and initiation of subclinical inflammation through the activation of macrophages, fibroblasts, and endothelial cells, which stimulate neovascularization and remodeling of the extracellular matrix, as well as reconstruction and reorganization of collagen fibers, leading to a more physiological regeneration process and, consequently, better scars [5,46].

In a pediatric population with pathological scars (atrophic and hypertrophic) resulting primarily from burns or surgical trauma, a clinical study evaluated the efficacy of carboxytherapy in lesions persisting for more than six months [46]. A carboxytherapy device and a sterile disposable needle were used to inject CO₂ into the skin. No serious side effects were observed during the procedure or during subsequent follow-up. The quality of the scar before and after treatment was evaluated using the Vancouver scar scale, which consists of a total of 15 points, where the lower the score, the better quality of the scar. A statistically significant improvement in the median Vancouver scar scale score was observed 6 weeks after the second session. No serious adverse events were recorded during the procedure or throughout the follow-up period. All patients exhibited erythema and edema at the injection site, which resolved spontaneously within 10–15 min. Subcutaneous emphysema resulting from CO₂ injection occurred in all patients with atrophic scars and consistently subsided within one hour. In three patients, painless hematomas developed within the treated area during the first 24 h post-procedure, resolving spontaneously within one week. The study was conducted on a relatively small sample and included only two treatment sessions, whereas standard practice for such procedures usually involves multiple sessions. The study was conducted on a relatively small sample and involved only two treatment sessions, which is not standard practice for these procedures.

Carboxytherapy was applied to twelve mature scars in a study conducted by Stolecka-Warzecha A. et al., focusing on post-traumatic, post-surgical, and acne-related lesions [44]. A small amount of heated medical CO₂ was injected until the scar turned white. Skin parameters—including hydration, color, and elasticity—were assessed prior to the initial treatment and again 4 to 7 days following the completion of four carboxytherapy sessions. Skin parameters were assessed using Corneometer^® CM 825, Mexameter^® MX 18, and Cutometer^® MPA 580 probes (Courage + Khazaka Electronic GmbH, Köln, Germany). Additionally, alginate molds were created to evaluate the morphometric characteristics of the scars. A 3D scanner with structured light was used to determine the exact morphology of the scars. Post-treatment evaluation revealed a marked increase in the average hydration levels of scar surfaces following carboxytherapy. The most significant enhancements were observed in specific post-acne scars, whereas some scars exhibited minimal changes or slight reductions in hydration. Most scars initially presented with low concentrations of hemoglobin and melanin. Post-carboxytherapy, hemoglobin levels generally increased, particularly in scars exhibiting significant visible improvement. Melanin content also increased in several scars, while others showed localized pigment decreases. Scar morphology was quantitatively analyzed by superimposing pre- and post-treatment reconstructions along the scar’s long axis. This allowed measurement of height deviations reflecting treatment effects. Most scars exhibited a reduction in volume and flattening, with the greatest changes observed at scar edges. Maximum height differences varied by scar location, with some scars showing reductions approaching 1 mm. The analysis demonstrated that carboxytherapy effectively reduced scar convexity and volume, particularly in raised scars, while atrophic scars showed volume decreases primarily from the edges inward. Similar to the previous study, this investigation was conducted on a small sample size, which limits the statistical power of the findings and may reduce their generalizability to a broader population. A larger cohort would allow for more robust analysis, greater reliability of the results, and a better assessment of potential variability in treatment outcomes and adverse effects.

Carboxytherapy is a commonly employed technique for scar management, particularly in the treatment of acne scars [47]. A comparative study was conducted to evaluate its efficacy relative to botulinum toxin injections. The study was conducted on a group of forty patients aged 18 to 50 with mild to severe acne scars, who were randomly and evenly divided into two groups: Group A received three sessions of intradermal injections of BTX-A, and Group B underwent three sessions of carboxytherapy on acne scars. The clinical response to treatment was assessed every 3 weeks and 1 month after the last session using photographs and a global scar assessment system, and patient satisfaction was also evaluated. Using the Goodman and Baron qualitative scarring grading system, no significant differences were found between the two treatment groups at baseline or after treatment, indicating comparable efficacy. Group A (treated with BTX-A) included patients with grade II to IV scars prior to treatment, with most showing good responses afterward. Group B (treated with carboxytherapy) comprised patients with grades ranging from I to IV, also demonstrating predominantly good responses. The differences in outcomes between the groups were not statistically significant. Both BTX-A and carboxytherapy represent effective, well-tolerated, safe, and noninvasive treatment options for atrophic acne scars. After each carboxytherapy session, patients experienced transient erythema, warmth, and swelling at the injection site, which subsided within 10 min to 1 h. Both BTX-A and CXT (carboxytherapy) injections were associated with mild, tolerable pain that diminished shortly after treatment. At the two-month follow-up following the final BTX-A or CXT session, no adverse effects were observed.

The characteristics of carboxytherapy treatment protocols for the reduction of various types of scars are presented in

Table 4. Characteristics of studies involving carboxytherapy for scars (W = women, M = men).

Study Group	Age	Area	Administration of CO2	Gas Flow Rate	Gas Volume	Needle Size	Anesthesia	Treatment Series	Ref
16 (11W, 5M)	8.5–15.2	scars (14 atrophic scars, 11 hypertrophic scars)	intradermal/ subcutaneous	not stated	not stated	30 G	yes (sedation)	2 treatments during 6 weeks	[46]
10	23–45	post-traumatic, post-surgical, acne scars	not stated	100 cc/min	not stated	30 G, 13 mm	not stated	4 treatments every 2 weeks	[44]
40 (20 participants received carboxytherapy)	18–50	acne scars	intradermal	not stated	0.1–0.3 mL	30 G	yes (2.5% lidocaine with 2.5% prilocaine)	3 treatments every 3 weeks	[47]

.

2.6. The Use of Carboxytherapy in Combination Therapies

Carboxytherapy has been used as a monotherapy for many years, but more and more researchers are deciding to combine this treatment with other procedures, such as chemical peels, laser therapy, and radio waves. Combination therapies allow for even better results. In recent years, combining carboxytherapy with fractional CO₂ laser has become a commonly explored approach for treating atrophic scars, stretch marks, and facial skin aging. One such study involved 20 patients with atrophic acne scars who underwent three sessions of fractional CO₂ laser resurfacing on both sides of the face, with additional carboxytherapy applied to the right side [48]. The duration of acne scars was less than 4 years in 35% of patients and more than 4 years in 65% of patients. Standardized photographs were taken before and three months after the last session and evaluated by two independent, unaware dermatologists for the degree of improvement. A much greater improvement in scar reduction was demonstrated on the right side, that is, the side that underwent combination therapy.

Another study evaluated combination therapies for skin aging. In all cases, 8 carbon dioxide therapy (CDT) sessions were performed on the Rt side, and the technique was combined (6 carbon dioxide sessions and 2 fractional CO₂ sessions in between, one after the second CDT session and the other after the fourth CDT session) on the Lt side at 2-week intervals [49]. Both sides of the face were evaluated by volunteers and 2 independent dermatologists at the beginning and 4 months after the end of the treatments. High-resolution digital photographs of the face were taken using identical camera settings before the start of treatment, before each session, and two weeks after the last session. This allowed comparison and evaluation of wrinkles, as well as signs of improvement in aging after treatment. The skin topography in the periorbital area was measured using an Antera 3D^® skin imaging device (Miravex Limited, Dublin, Ireland) before the first treatment and after 4 months of treatment. In all cases, a biopsy was performed on both sides using a 3 mm punch biopsy before and 4 months after treatment (two weeks after the last session). All cases (100%) were satisfied with the treatment results. Both sides showed improvement in signs of aging. Skin analysis using the Antera 3D camera showed an improvement in facial wrinkles (large, medium, and small) and changes in facial texture, which was correlated with clinical improvement after 4 months of treatment on both sides. No differences were observed between the sides of the face. Histological examination showed a more significant increase in epidermal thickness after combined treatments. A significant reduction in wrinkles was observed on both sides of the face, but there was no significant difference in the percentage of improvement in wrinkles. Meanwhile, the texture changes showed a more promising improvement with combined treatment, compared to the other side treated with carboxytherapy alone. Furthermore, an objective assessment of epidermal thickness showed a very significant increase after treatment on both sides of the face, with a more significant increase on the left side treated with the combined technique. Incorporating carboxytherapy into fractional CO₂ laser resurfacing treatments can increase the rate of improvement without causing noticeable side effects.

The same authors also compared the effects of combined fractional CO₂ laser therapy and carboxytherapy with carboxytherapy alone on reducing stretch marks [50]. The effectiveness of the treatments was confirmed on both sides, but unlike previous studies, no statistically significant differences were observed between the sides. Carboxytherapy as a standalone treatment was found to be highly effective in reducing stretch marks. For each subject, a pair of stretch marks of similar shape and size and located almost symmetrically were selected. The treatment protocol was as follows: Right side: carboxytherapy was used exclusively. Left side: combined carboxytherapy and fractional CO₂ laser treatment was used. Clinical changes and improvement in stretch marks in terms of width, length, number, texture, color mismatch, and skin atrophy were assessed by patients, two physicians, and two independent observers before and four months after the start of treatment. The clinical evaluation showed significant clinical improvement in SD changes after both techniques in terms of length and width, texture, and pigmentation changes. Although the side that received the combined treatment showed slightly better improvement, the difference was not statistically significant. Skin analysis using the Antera 3D^® camera also showed an improvement in stretch marks reduction with both techniques (solo and combined), and a slight advantage of combined therapy was also demonstrated, although it was not statistically significant. Very similar results were obtained in the histological study. Researchers observed a slightly greater improvement in all study parameters in the group receiving combination therapy, although this improvement was not statistically significant. All of the above results confirm that the CDT alone is a good treatment for SD and that fractional CO₂ laser does not significantly enhance its effect.

Kołodziejczak et al. conducted a study comparing the effects of monotherapy with carboxytherapy and carboxytherapy combined with chemical peels with ferulic acid and vitamin C (for signs of photoaging, wrinkles, and/or dark circles under the eyes) or lactobionic acid (vascular dark circles, dry skin, and wrinkles) [51]. The effects of the treatments on parameters such as skin hydration and elasticity around the eyes (parameter R6) were assessed. An objective assessment of skin parameters was performed using a CM 825 probe of the Corneometer^® (to measure hydration) and the Cutometer^® MPA 580 probe (to measure elasticity). A statistically significant improvement in skin viscoelasticity (R6 parameter) was observed after treatment on both sides of the face. Although hydration changes measured with the Corneometer^® were not statistically significant, more than half of participants showed improved hydration, particularly on the side treated with combined therapy. Both treatment types were similarly effective, with no significant differences between them. The study confirmed that combination therapies are more effective in all parameters tested.

The characteristics of the treatment protocols using carboxytherapy in combination therapies for various skin problems are presented in

Table 5. Characteristics of combined protocols with carboxytherapy (W = women, M = men).

Study Group	Age	Combined Protocol	Area	Administration of CO2	Gas Flow Rate	Gas Volume	Needle Size	Local Anesthesia	Treatment Series	Ref
20	17–42	CO2 laser	acne scars	not stated	not stated	0.1–0.3 cc	not stated	yes	1 treatment, 2 weeks before laserotherapy	[48]
20W	17–36	CO2 laser	stretch marks	intradermal	not stated	15–45 cc	32 G, 3 mm	no	6 carboxytherapy treatments every 2 weeks, 2 laser CO2 treatments after 2 and 4 carboxytherapy treatment	[50]
25W	49.1 ± 5.4	CO2 laser	face	intradermal	not stated	3 cc na per side	32 G, 3 mm	no	6 carboxytherapy treatments every 2 weeks, 2 laser CO2 treatments after 2 and 4 carboxytherapy treatment	[49]
39 (35W, 4M)	25–55	ferulic acid with C vitamin or lactobionic acid	eye area	intradermal	10 cc/min	3 cc per eye	32 G	not stated	5 treatments every week	[51]
39 (35W, 4M)	25–55	ferulic acid with vitamin C or lactobionic acid	eye area	intradermal	10 cc/min	3 cc per eye	32 G, 4 mm	not stated	5 treatments every week	[24]

.

3. Conclusions

Current evidence indicates that carboxytherapy is a safe and well-tolerated minimally invasive technique with documented efficacy in the management of selected dermatological and aesthetic concerns, including periorbital hyperpigmentation, striae distensae, various types of scars, and clinical signs of skin aging. While its effects as a monotherapy are modest to moderate, depending on the indication, carboxytherapy demonstrates clear histological and clinical benefits, particularly in skin elasticity, hydration, and vascularization. Furthermore, emerging studies support its role as a valuable adjunctive modality in combination protocols—especially with fractional laser therapy and chemical peels—where it may contribute to enhanced therapeutic outcomes. Although it should not be regarded as the first-line treatment in all cases, carboxytherapy holds a relevant position within a multimodal, individualized approach to aesthetic skin management.