Concurrent infusion of glutathione, tranexamic acid, and Vitamin C as oral mesotherapeutic agents for management of gingival hyperpigmentation: A case series

Abstract

Gingival melanin pigmentation, although physiologically benign, often poses a significant esthetic concern, particularly in individuals with high smile lines. This case series aimed to assess the clinical outcomes of mesotherapy using a combination of Vitamin C, tranexamic acid, and glutathione as a minimally invasive approach to gingival depigmentation. Two systemically healthy patients exhibiting diffuse melanin pigmentation in the anterior maxillary gingiva were managed with intramucosal injections administered at weekly intervals over three sessions. Clinical evaluation was performed using the Dummett and Gupta Oral Pigmentation Index at baseline and at a 3-month follow-up. Both cases demonstrated a marked reduction in gingival pigmentation with satisfactory esthetic improvement and no reported adverse effects or recurrence. These preliminary findings suggest that mesotherapy with a synergistic combination of antioxidant and depigmenting agents may offer a viable, conservative alternative to conventional depigmentation techniques.

INTRODUCTION

The smile constitutes a key element of facial esthetics and significantly influences an individual’s social acceptance and interpersonal perception.[1] The gingiva provides a supportive framework for the teeth, and its health plays a crucial role in determining the overall esthetic outcome of an individual. The color of healthy gingiva is usually pink, resembling shades such as salmon or coral pink.[2] Melanocytes in the basal or suprabasal layers within the epithelium produce the melanin pigment, which mostly determines the gingiva’s natural color. The prevalence of gingival pigmentation in India is estimated to be between 20% and 50%. The condition is more common in adults than in children, and it is also more common in women than in men.[3] Although not a medical problem, physiological gingival melanin hyperpigmentation is a prevalent esthetic concern, particularly in people who have large gingival exposure and noticeable smile lines. Patients seek therapy due to the perception that the presence of dark gums hurts their facial esthetics and overall image.

Conventional surgical methods, including the use of scalpels, bur abrasion, cryosurgery, radiosurgery, gingival grafting, electrocautery, and lasers, have been found to be effective in treating hyperpigmentation in a single session.[4] Gul et al., in a systematic review and meta-analysis, compared conventional and advanced gingival depigmentation techniques. Diode lasers were the most commonly used, providing better esthetic results, faster healing, and greater patient satisfaction. However, they showed a higher tendency for repigmentation at 6 months compared to other methods.[5] Thus, it was necessary to use more sophisticated therapeutic strategies that interfere with melanogenesis. The goal of mesotherapy is to reverse the patient’s condition by injecting small doses of vitamins, minerals, amino acids, prescription medications, and preparations directly into the mesoderm area. In 1952, Pistor, the pioneer of mesotherapy, introduced this technique.[4] Traditional mesotherapy is being used for body contouring and cosmetic procedures, including fat and cellulite removal, marking the beginning of a new age in esthetic medicine. Yussif et al. adapted the original dermatological mesotherapy technique to develop oral mesotherapy, a procedure that involves the use of fine needles to inject depigmenting agents into the superficial layers of the oral mucosa. This technique delivers treatment directly into the region between the basement membrane and the superficial connective tissue, offering a localized approach to gingival depigmentation with minimal invasiveness.[6]

In a comparative study conducted by Iraji et al. to evaluate the effectiveness of combination mesotherapy in melasma patients, the authors found that mesotherapy yielded satisfactory outcomes regardless of the type of agents used. However, treatment with a glutathione-containing cocktail (Cocktail A) demonstrated superior results compared to the combination containing tranexamic acid (TA) and Vitamin C without glutathione.[7] To date, to the best of our knowledge as per review of the literature, there is no study that has evaluated mesotherapy (glutathione, TA, and ascorbic acid) for the management of gingival melanin hyperpigmentation. Hence, the objective of this case series was to assess the effectiveness of mesotherapy using glutathione and TA along with ascorbic acid in managing gingival melanin hyperpigmentation.

CASE REPORTS

This case series has been written according to CARE 2013 guidelines for case reports.

Case 1

A young, healthy female patient aged 20 years reported to the department of conservative dentistry and endodontics with the chief complaint of dark spots on the gums, which looked esthetically unpleasant while smiling. On intraoral examination, it was found that the patient had diffuse medium-brown pigmentation in the upper arch. It was decided to use mesotherapy for the depigmentation. The patient was explained about the depigmentation procedures using mesotherapy agents of Vitamin C, glutathione (Gluta C, Vesco Pharma), and TA (Texakind, Mankind Pharma Ltd.). Written informed consent was taken before the treatment.

Full-mouth oral prophylaxis was done before the therapy. Preoperative photographic documentation was done using a DSLR (aperture – f/22, ISO 100, shutter speed 1/125 and 1/32-0.7, flash exposure) under standard light operating conditions.[8] Anesthesia was administered locally via infiltration (Lox 2%, Neon Lab., New Delhi). The clinical procedures were performed under ×3 magnification and illumination. Glutathione (1000 mg), TA (4 mg/ml), and Vitamin C (1000 mg) were administered to patients in a 1:1:1 ratio using an insulin syringe. A 30-gauge needle was used to locally administer a 1-1.5 cc intramucosal injection. The injection was given with precision, ensuring that the needle was positioned no more than 1 mm below the epithelial surface [Figure 1a-d]. After the procedure, the patient was cautioned to avoid traumatic foods, alcohol, and acidic beverages during the 1^st week. The patient was told to refrain from mechanical oral hygiene for 1 day. Rescue analgesia (ibuprofen 400 mg) was given if needed. Clinical evaluations were conducted at baseline as well as 3 months for the presence/absence of gingival hyperpigmentation. This assessment was carried out using the Dummett and Gupta Oral Pigmentation Index’s predetermined score criteria[9] [Table 1].

Figure 1.

(a) Preoperative clinical picture of Case 1, (b) intraepithelial injection of mesotherapy agents, (c) clinical picture immediately after injection, (d) 3-month follow-up

Table 1.

Dummett and Gupta oral pigmentation index

Score	Scale of pigmentation
0	No clinical pigmentation (pink tissue)
1	Mild clinical pigmentation (mild light brown color)
2	Moderate clinical pigmentation (medium brown or mixed pink and brown coloration)
3	Heavy clinical pigmentation (deep brown or blue-black tissue)

Case 2

A 24-year-old healthy male patient reported with chief complaints of visible dark spots on upper gums. On intraoral examination and the patient’s history, it was diagnosed as physiologic gingival melanin hyperpigmentation. After oral prophylaxis, intraepithelial administration of the mesotherapy agent was done as described for case 1 [Figure 2a-e]. This was repeated once every 3 weeks. Re-evaluation was done at 3 months.

Figure 2.

(a) Preoperative image of Case 2, (b) 1^st week after mesotherapy, (c) 2^nd week after mesotherapy, (d) 3^rd week after mesotherapy, (e) 3-month follow-up

DISCUSSION

Oral mesotherapy, a minimally invasive technique delivering agents like Vitamin C directly to gingival tissues, offers an alternative to traditional surgical depigmentation methods.[4] Esmat et al. found that the efficacy of Vitamin C mesotherapy is comparable to diode laser therapy in the treatment of gingival hyperpigmentation.[10] It has been found that mesotherapy with Vitamin C injections outperforms topical application as well as traditional surgical procedures.[11] However, Dawar et al. emphasized that Vitamin C alone is insufficient for severe pigmentation, highlighting the need for adjunctive therapies.[4] In addition, the antioxidant efficacy of Vitamin C may also be used to increase the bond strength of composite to the tooth post nonvital bleaching.[12] TA, traditionally used in the treatment of melasma, has demonstrated promising outcomes when administered orally, topically, or through localized microinjections. However, a study by Hadidi et al. found no significant difference between the oral and microinjected forms.[13] Nevertheless, despite these encouraging results in dermatology, currently, the evidence supporting the use of TA as a mesotherapy agent for gingival depigmentation is lacking. Glutathione, a potent antioxidant with anti-melanogenic properties, has gained popularity for its skin-lightening effects.[14] In addition, it has been proven to increase the shear bond strength when used for extracoronal bleaching.[15] However, the depigmenting effect of glutathione has not been studied in detail. Both oral and topical forms of glutathione have demonstrated efficacy in skin lightening while maintaining favorable safety profiles.[16] The rationale for employing a combination of Vitamin C, glutathione, and TA was to achieve faster, more sustained results with the potential for long-lasting effects, while also minimizing the risk of recurrence commonly associated with laser-based treatments. The choice of localized microinjection was based on its ability to deliver a continuous and controlled release of the agents directly into the basement membrane, the site where melanocytes reside.

The present case series demonstrated that mesotherapy using a combination of Vitamin C, glutathione, and TA is a novel, safe, effective, and minimally invasive approach for gingival melanin depigmentation. In both the cases, there was a gradual change from the brownish-black discoloration to pinkish hue within 1 week of mesotherapy. At subsequent visits, the gingival color exhibited good results with no signs of re-pigmentation [Figures 1 and 2]. Patients reported only minor gingival irritation lasting one to 2 days posttreatment. Both the patients were highly satisfied with the overall results and improvement in gingival color at the 3-month follow-up. The minimally invasive, bloodless procedure and short chair time contributed to strong compliance and a positive overall experience. This is the first case series that has utilized a combination of Vitamin C, glutathione, and TA for gingival depigmentation. However, the limitation of the current case series is the relatively short follow-up period of only 3 months. Hence, extended follow-up durations and a study with a larger sample size are essential to accurately assess the recurrence rate associated with this treatment approach.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.