Expanding the Role for Topical Carboxytherapy: An Advisory Board Discussion

In recent years there has been growing interest in the beneficial effects of increasing tissue oxygen (O₂) availability and enhancing microcirculation to treat various conditions. This can be achieved with carboxytherapy, the transcutaneous administration of gaseous carbon dioxide (CO2). The mechanism of action by which the transcutaneous administration of CO2 leads to an increase in tissue O₂ is known as the Bohr effect.¹ As CO2 has a higher affinity for hemoglobin than O₂, increasing tissue CO2 decreases the affinity of hemoglobin for O₂ resulting in a right-ward shift in the oxygen-hemoglobin dissociation curve. This produces greater unloading of O₂ by hemoglobin in capillaries which allows more O₂ to be available to tissues.² Over time, the repeated administration of CO2 further increases the available O₂ supply by a compensatory increase in capillary size.^3,4 The interest in carboxytherapy has been especially appealing among dermatology and aesthetic medicine practitioners.^5,6

Carboxytherapy was originally performed by injecting CO2 gas directly into subcutaneous tissues for a wide range of skin-related conditions. Several studies have demonstrated that repeated subcutaneous and intradermal injections of pure CO2 gas into the periorbital areas can decrease hyperpigmentation^7,8 and improve skin elasticity.9 Histological studies have shown that carboxytherapy in this area can stimulate collagen remodeling and increase elastin fibers.¹⁰

The subcutaneous injection of CO2 gas has also been shown to improve the appearance of cellulite. In one study, weekly subcutaneous injection of CO2 gas over the course of 8 weeks significantly improved the appearance of cellulite.¹¹ The changes in appearance were confirmed by ultrasound examination which revealed positive changes in the dermis and subcutaneous tissue, as well as the subcutaneous associated with cellulite. Analysis of ultrasound revealed morphological improvement with respect to subcutaneous tissue and fibrotic septa. Other studies have demonstrated significant reductions in thigh circumference measurements and cellulite appearance following carboxytherapy.¹²

Additional work has provided evidence that carboxytherapy can improve alopecia,¹³ stretch marks^9,14,15 and can enhance the outcomes of skin rejuvenation.^9,14,16 Carboxytherapy has also been shown to reduce the amount of subcutaneous adipose tissue in the upper arms, thighs, knees, and abdomen^17-19 It is unclear if these reductions in adipose tissue are sustained longer than a 6-month period, particularly in the abdomen, and more research will be required to demonstrate long lasting results.¹⁹

Carboxytherapy can also be combined with many other aesthetic treatments such as mesotherapy, superficial peels, microdermabrasion, photorejuvenation, and topical and injectable platelet-rich plasma treatments, to enhance their efficacy.²⁰

Carboxytherapy has also been used to potentiate wound healing. Animal models have demonstrated that transcutaneous application of CO2 as a topical hydrogel increases angiogenesis, improves survival of skin flaps,²¹ and speeds the healing of excisional wounds.²² Clinically, the subcutaneous injection of CO2 improves microcirculation, reduces scar formation and promotes the healing of diabetic foot ulcers.^23,24

Topical Carboxytherapy

While carboxytherapy administered through transcutaneous injection of CO2 gas has many potential clinical benefits, disadvantages include pain, crepitus, and bruising at the injection site.^6,15 Injection also required administration by a competent and experienced medical provider.²⁰ A novel topical gel has been developed which offers all the benefits of CO2 injections without the disadvantages, such as discomfort (CO2Lift, Lumisque, Inc.; Weston FL).^25,26

The product is prepared by simply mixing two packages containing the gel and activator for 30 seconds. Following activation, this proprietary topical gel is topically applied where it becomes solidified. There, it releases CO2 for 45 minutes, increasing tissue oxygenation via the Bohr effect and improving microcirculation via vasodilation and sustain capillary expansion. Mean capillary diameter increased from 26.9 to 34.3 μM and capillary density increased from 11 to 14 per mm² (for each, P<0.05).³ The gel has been shown to improve skin quality and can be used to enhance clinical outcomes following various facial procedures.¹⁶ Other applications include facial skincare, vaginal health, and wound healing. Following application, carboxytherapy gel is peeled from the skin.

Although this topical carboxytherapy gel is relatively new, there is a growing body of evidence and clinical experience indicating that it may have a similar efficacy to subcutaneous injections of CO2. Microscopic assessments have revealed that topical carboxytherapy provides the same vascular effects as CO2 injections with both immediate vasodilation and long term improved microcirculation.³

One randomized trial found that topical application of the carboxytherapy gel improved clinical outcomes following nanofractional radiofrequency facial resurfacing. These outcomes included decreased dryness, erythema, edema, crusting and more rapid healing.¹⁶ In this trial, treated subject were highly satisfied with the cosmetic outcomes of the gel therapy and reported no adverse events.

A novel use for the product is for vulvovaginal rejuvenation in postmenopausal women. Women experiencing symptoms of menopausal genitourinary syndrome achieved significant improvements in Female Sexual Function Index²⁷ and Impact of Vaginal Aging²⁸ scales after ten applications administered once daily over the course of two weeks.²⁹ Tissue biopsies of the vulvovaginal tissues revealed regenerative effects including tissue maturation and neovascularization in treated individuals.²⁹

Topical carboxytherapy has also demonstrated efficacy in treating medical conditions such as diabetic ulcers.³⁰ Twice-weekly application of the topical carboxytherapy was found to significantly speed the healing of diabetic ulcers that were resistant to prior treatment.

This growing body of evidence demonstrates an efficacy of topical carboxytherapy gel that matches that of the well-established injectable subcutaneous carboxytherapy with CO2 gas. A significant advantage of the gel option for carboxytherapy over the injectable gas form is the ease of use and the ability for patients to do the treatments outside of the office, broadening the scope of use and range of applications.

Insight From The Advisory Board

An advisory board meeting was convened last March during the Dallas Cosmetic Medicine & Rhinoplasty Meeting in Dallas in March. The invited attendees, including the authors of this report, were plastic surgeons and the objective of the meeting was to increase awareness of topical carboxytherapy among attendees as well as to explore the possibility of including carboxytherapy in their surgical practices.

The following questions were submitted from attendees prior to the meeting and the discussion was moderated by a board-certified plastic surgeon with two years of experience using the carboxytherapy CO2 gel in her practice for a broad range of applications from skin care to surgical enhancement; other questions occurred during the live discussion.

How is CO2 gel different from CO2 being administered via transcutaneous or subcutaneous injection? Are the levels of CO2 and O2 in the tissues similar between the two different modalities of administration?

As established by the Bohr effect, CO2 always increases the partial pressure of O2 regardless of application method. The primary difference between a topical gel and an injected gas is that the injection of gaseous CO2 produces more patient discomfort than the topical CO2 gel. Some of the equipment used for CO2 injection has high flow rates that may cause pain when there is rapid subcutaneous injection resulting in tissue emphysema.²⁶ Studies evaluating the tissue levels of O2 and CO2 or the microcirculation have shown that injected CO2 generates a microcirculatory increase of 28% in vertical and horizontal capillaries for the transcutaneous CO2 gel.³ In contrast with CO2 injections, treatment with carboxytherapy gel achieves excellent skin hydration.

Does this topical carboxytherapy gel achieve the same CO2 levels as other methods?

When activated and applied to the skin, the gel combination produces CO2 for 45 minutes. Studies have demonstrated the clinical results are similar to injected CO2 with similar depth of CO2 penetration.3

What are the complications if the gel is left on the skin for more than 45 minutes?

After 45 minutes, the activated gel stops producing CO2. The inert gel can then be peeled off the skin. There are no complications from leaving the gel for longer than 45 minutes.

Is this CO2 gel administered by a doctor? Nurse? Patient? Can it be done at home?

The carboxytherapy gel is easy to apply and can be done in the clinic by any provider or at home by the patient following simple instructions from the provider.

How does your product compare to other commercially available topical carboxytherapy gels?

Other commercial topical carboxytherapy gels are formulated as a single solution without a CO2 activator and therefore, do not generate CO2. Comparative capillaroscopy studies showed no change in microcirculation observed following application of these products compared to the original CO2 gel which does increase microcirculation.

How often do you recommend administering this product?

There is no specific application protocol, and the timing of application can vary depending on the patient and prior treatment procedure. One useful schedule is to administer once weekly for 1 month, then monthly thereafter as a maintenance treatment.

For facial rejuvenation with energy-based devices, the CO2 gel can be applied on top of the anesthetic gel, reapplied after the procedure, and again at home the following day to soothe and enhance skin healing. Skin flap survival is enhanced when the carboxytherapy gel is used to enhance microcirculation pre- and post-surgical procedures such as face and neck lifts. Each product package provides sufficient material for treating the entire face. The product is also beneficial following breast and vaginal procedures. Dermatologists have already discovered the benefits of using carboxytherapy gel following energy-based treatments such as lasers and microneedling. Patients find it to be soothing.¹⁶

How painful is the use of this product? Is there any burning, itching, or swelling as side effects?

To date, no adverse events have been reported.¹⁶ The activated gel is nonirritating and can be applied over the eyes, lips and open wounds without discomfort. It can be applied vaginally for treating vaginal atrophy.²⁹

How do the results of CO2 gel compare to those from a hyperbaric oxygen chamber?

Topical application of CO2 gel increases tissue oxygenation similar to hyperbaric oxygen but without the disadvantages and adverse effects of HBO, such as claustrophobia and potential barotrauma.³¹

What effect would carboxytherapy with CO2 gel have on soluble sutures such as are used in facial (facelift) and vaginal (labiaplasty) surgical procedures?

Carboxytherapy enhances skin regeneration. It can be used pre- and postoperatively to speed recovery improve tissue quality. It has not been found to speed the breakdown of soluble sutures.

What benefit does carboxytherapy have after a platelet-rich plasma injection to the vagina (O-Shot®)?³²

The O-Shot has a delayed effect, increasing clitoral and G-Spot blood flow in about 2-3 months. Carboxytherapy can increase genital skin blood flow in days to weeks. Vaginal atrophy studies revealed significant histological improvement following CO2 gel therapy.²⁹

Has topical carboxytherapy gel been used after facelift on thin skin flaps (areas of skin threatened with skin shedding or de-epithelialization) or delays in wound healing?

It has shown itself to be useful following numerous procedures, such as facial resurfacing, neck lifts, and fat grafting. Its use is becoming the standard of care for facelift flaps, not just for treating problem situations although more studies are needed to quantify these effects.

Is treatment with carboxytherapy gel expensive?

The cost of treatment is comparable to many other skin care products. It is packaged for patient convenience in packs of three.

Conclusion

Carboxytherapy using a novel topical CO2 gel provides the same beneficial effects as CO2 injections, has fewer side effects than historical injection for CO2 gas, is easy to activate and apply, has a wide array of applications and is suitable for home application. Growing evidence suggests topical CO2 administration and may replace conventional carboxytherapy for many aesthetic applications.

The authors report no financial interests.

1. Bohr C, Hasselbalch K, Krogh A. Concerning a biologically important relationship - the influence of the carbon dioxide content of blood on its oxygen binding. Skand Arch Physiol. 1904;16:401-412.

2. Kaufman DP, Kandle PF, Murray I, Dhamoon AS. Physiology, oxyhemoglobin dissociation curve. In: StatPearls [Internet]. Treasure Island FL: StatPearls Publishing; 2022.

3. Leibaschoff GH, Coll L, Roberts WE. A prospective clinical and instrumental study on the effects of a transcutaneous cosmeceutical gel that is claimed to produce CO₂. Surg Technol Int. 2018;32:33-45.

4. Finzgar M, Melik Z, Cankar K. Effect of transcutaneous application of gaseous carbon dioxide on cutaneous microcirculation. Clin Hemorheol Microcirc. 2015;60:423-435.

5. Kolodziejczak A, Podgórna K, H. R. Is carboxytherapy a good alternative method in the removal of various skin defects? Dermatol Ther. 2018;31:e12699.

6. Ahramiyanpour N, Shafie’ei M, Sarvipour N, Amiri R, Akbari Z. Carboxytherapy in dermatology: A systematic review. J Cosmet Dermatol. 2022;21:1874-1894.

7. Assaf HA, Ahmed D, Abdelhamed A. Efficacy and safety of carboxytherapy versus combined microneedling with topical glutathione in the treatment of patients with periorbital hyperpigmentation: An evaluator-blind, split-face, controlled pilot clinical trial. Indian J Dermatol. 2022;67:504-511.

8. Zaheri H, Beyzaee AM, Rokni GR, Patil A, Golpour M, Goldust M. Comparison of the efficacy of carboxytherapy versus fractional CO2 laser therapy for the treatment of periorbital dark circles: A randomized clinical trial. J Cosmet Dermatol. 2023;22:512-516.

9. Kolodziejczak A, Rotsztejn H. Objective, measurable assessment of the elasticity of the skin around the eyes following the carboxytherapy treatment. J Cosmet Dermatol. 2023;Jan 31, Epub ahead of print.

10. Pinheiro NM, Crema VO, Millan BM, Carvalho FA, Mendonça AC. Comparison of the effects of carboxytherapy and radiofrequency on skin rejuvenation. J Cosmet Laser Ther. 2015;17:156-161.

11. Pianez LR, Custódio FS, Guidi RM, de Freitas JN, Sant’Ana E. Effectiveness of carboxytherapy in the treatment of cellulite in healthy women: a pilot study. Clin Cosmet Investig Dermatol. 2016;9:183-190.

12. Eldsouky F, Ebrahim HM. Evaluation and efficacy of carbon dioxide therapy (carboxytherapy) versus mesolipolysis in the treatment of cellulite. J Cosmet Laser Ther. 2018;20:307-312.

13. Doghaim NN, El-Tatawy RA, Neinaa YME, Abd El-Samd MM. Study of the efficacy of carboxytherapy in alopecia. J Cosmet Dermatol. 2018;17:1275-1285.

14. Kroumpouzos G, Arora G, Kassir M, et al. Carboxytherapy in dermatology. Clin Dermatol. 2022;40:305-309.

15. Elmorsy EH, Elgarem YF, Sallam ES, Taha AAA. Fractional carbon dioxide laser versus carboxytherapy in treatment of striae distensae. Lasers Surg Med. 2021;53:1173-1179.

16. Medrano K, Arruda S, Oza N, Sadick N. Carboxytherapy mask as post nanofractional radiofrequency treatment for improvement of facial skin quality and photoaging. J Drugs Dermatol. 2021;20:461-465.

17. Brandi C, D’Aniello C, Grimaldi L, et al. Carbon dioxide therapy in the treatment of localized adiposities: clinical study and histopathological correlations. Aesthetic Plast Surg. 2001;25:170-174.

18. Lee GS. Quality survey on efficacy of carboxytherapy for localized lipolysis. J Cosmet Dermatol. 2016;15:484-492.

19. Alam M, Sadhwani D, Geisler A, et al. Subcutaneous infiltration of carbon dioxide (carboxytherapy) for abdominal fat reduction: A randomized clinical trial. J Am Acad Dermatol. 2018;79:320-326.

20. Zelenkova H, Stracenská J. Carboxytherapy: A non-invasive method in aesthetic medicine and dermatology. Glob Dermatol. 2017;4:1-5.

21. Saito I, Hasegawa T, Ueha T, et al. Effect of local application of transcutaneous carbon dioxide on survival of random-pattern skin flaps. J Plast Reconstr Aesthet Surg. 2018;71:1644-1651.

22. Brochado TMM, de Carvalho Schweich L, Di Pietro Simões N, Oliveira RJ, Antoniolli-Silva ACMB. Carboxytherapy: Controls the inflammation and enhances the production of fibronectin on wound healing under venous insufficiency. Int Wound J. 2019;16:316-324.

23. Khiat L, Leibaschoff GH. Clinical prospective study on the use of subcutaneous carboxytherapy in the treatment of diabetic foot ulcer. Surg Technol Int. 2018;32:81-90.

24. Stolecka-Warzecha A, Chmielewski Ł, Deda A, Śmich A, Lebiedowska A, Wilczyński S. The influence of carboxytherapy on scar reduction. Clin Cosmet Investig Dermatol. 2022;15:2855-2872.

25. CO2Lift Carboxy Gel. Available: https://co2lift.com/. Accessed: March 15, 2023.

26. Jamshidian-Tehrani M, Sheikhghomi S, Kasaee A. Post periorbital carboxytherapy orbital emphysema: a case report. Orbit. 2022;41:123-126.

27. Rosen R, Brown C, Heiman J, et al. The Female Sexual Function Index (FSFI): A multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000;26:191-208.

28. Huang AJ, Gregorich SE, Kuppermann M, et al. Day-to-Day Impact of Vaginal Aging questionnaire: a multidimensional measure of the impact of vaginal symptoms on functioning and well-being in postmenopausal women. Menopause. 2015;22:144-154.

29. Leibaschoff GH, Arrieta CTN, Reyes CLG, Melamed JL. A pilot randomized, double-blind, placebo-controlled clinical trial on the efficacy and safety of a transdermal gel that delivers CO2 in the treatment of vulvovaginal atrophy. Surg Technol Int. 2021;38:234-239.

30. Clark CM. Interventional Case Study Using CO2Lift Pro for Management of Wound Care. Available: https://lumisque.com/studies/. Accessed: May 01, 2023.

31. Roberts WE. Topical Carboxytherapy for Skin Rejuvenation. Presented: Generational Dermatology Palm Springs Symposium, February 15-18, 2023; Rancho Mirage, CA.

32. O-Shot® Official Home Page. Available: https://oshot.info/. Accessed: March 15, 2023.