Table 1.

Characteristics of the studies included in the Systematic Review

Authors & Year of Publication	Country	Aim	Tissue assessed Gingiva/Skin	Type of study	Sample size, Comparison group & control group	Methodology	Conclusion
Shimada Y, Tai H, Tanak A, Suzuki I, Takagi K (2009) 16	Japan	To investigate the inhibitory effects of a gel containing ascorbic acid 2-glucoside (AS-G gel) on gingival melanin pigmentation.	Gingiva	Double-masked placebo- controlled clinical trial, split-mouth design (randomised controlled trial)	73 subjects with symmetric gingival melanin pigmentation. (22 males and 51 females). The mean age was 37.2±1.0 years (range, 25 to 57 years).	AS-G test gel was applied to left the side and placebo gel was applied to the right side of the gingiva. Using a spectrophotometer the color of the keratinized gingiva was measured at four points (canine and lateral incisor; and between lateral incisor and incisor) in each subject. Three consecutive measurements were taken at one site, and the mean of individual measurements was calculated at 0 weeks, 4 weeks, 8 weeks and 12 weeks.	Ascorbic acid (AS-G) seems to have potential for the treatment of gingival melanin pigmentation at home.
Yussif NM, Zayed SO, Hasan SA, Sadek SS (2016) 5	Cairo University, Egypt	To evaluate the efficiency of injectable Vitamin C as a depigmenting agent in physiologic gingival hyperpigmentation	Gingiva	Experimental Study	40 patients in age range of 20-44 years with physiologic gingival melanin hyperpigmentation	A 200-300mg (1-1.5 ml) ascorbic acid (ampoule) was injected in the gingival tissues once per week until no visible pigmentation. The patients were recalled after 1, 3& 6 months for follow up. Decrease in pigmentation indices scores & reduction in area of pigmentation was assessed.	Vitamin C injection is a safe, minimally invasive non-surgical depigmenting technique for gingival tissue.
Yussif NM, Abdel Rahman AR, Elbarbary E (2019)17	Cairo University, Egypt	To evaluate the efficacy of intra-epidermal vitamin C injection in comparison to the conventional surgical technique in gingival hyperpigmentation	Gingiva	Experimental Study	30 patients with mild to severe hyperpigmented gingival tissues were divided into Group 1(Control group-conventional scalpel depigmentation performed) & Group 2(Test group- Vitamin C was injected intra-epidermal)	Maximum 0.1 ml of ascorbic acid was recommended for each point with 2-3 mm apart. The same dose was repeated once per week for maximum 4 visits till no further color improvement gained. The same operator performed all the surgical procedures. For gingival ablation, epithelial layer and part of the connective tissue layer were removed using 15c blades till the pigment disappeared. Caution was taken at the canine region to avoid bone exposure. Two different color assessment indices (Takashi and Kumar indices) were assessed. The pain and itching grades were reported using VAS Scale.	Usage of vitamin C injection for depigmentation showed comparative results to the conventional surgical technique.
Ratnam AV, Sastry PB, Satyanarayana BV (1977)18	India	To estimate tde content of ascorbic acid in normal pigmented skin in comparison to the depigmented skin of vitiligo.	Skin	Experimental study	Control group-10 subjects with normal pigmented skin. Study group-12 vitiligo cases with variable loss of pigmentation and 1 was albino.	The estimations of ascorbic acid levels were repeated after saturation with daily doses of 70 mg ascorbic acid per stone body weight. The skin samples were obtained from the lateral aspect of the leg in all the subjects and extracts were prepared from full thickness skin. The ascorbic acid contents of skin, plasma and urine were assessed	Ascorbic acid has an important role to play in the metabolic functions of the epidermis, the most important of these being keratinization and melanogenesis.
Kameyama K, Sakai C, Kondoh S, Yonemoto K, Nishiyama S, Tagawa M (1996)19	California	To examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of Ascorbic acid.	Skin	Experimental study	34 patients with phelides. chloasma, senile freckles, nevus of Ota, or healthy skin	VC-PMG cream 10% was applied twice a day to the skin. The effectiveness of the lightening of the pigmentation was judged by a color-difference meter	VC-PMG was effective in lightening the skin of some patients with hyperpigmentation disorders and some subjects with normally pigmented healthy skin.
Kim HM, An HS, Bae JS, Kim JY, Choi CH, Kim JY (2017)20	Korea	To investigate the effects of palmitoyl-KVK-L-ascorbic acid on skin aging, the anti-wrinkle and depigmentation.	Skin	Experimental study	21 healthy Korean women aged between 41 and 55 years	The cream with 0.075% (0.75 mg/mL) of Palm-KVK-AA or without Palm-KVK-AA was applied to each half of the participant’s face, twice daily for 12 weeks. The allocation of the cream was based on a double-blind randomized method. Skin replica images were evaluated using a visiometer. Visual assessment was performed using the global photodamage score at baseline, 4, 8 and 12 weeks after the application of the cream	Palmitoyl-KVK-L-ascorbic acid is an effective anti-aging agent that reduces wrinkles and abnormal skin pigmentation.
Jaros A, Zasada M, Budzisz E, Debowska R, Rzepka MG, Rotsztejn H (2019)21	Poland	To evaluate selected capillary skin parameters after applying 5% vitamin C concentrate.	Skin	Experimental study	(50.1 ± 3.9 years) 30 women of 30-60 years of age with capillary skin indicating visible signs of erythematous plaques. Control group of 11 patients	The participants were instructed to use 5% Vitamin C concentrate once a day during the evening and apply it on their facial skin. The participants were asked to fill out a questionnaire where they evaluated the properties of the applied concentrate throughout the period of 6 weeks	5% Vitamin C concentrate is very effective in treating Erythema as well as decreasing the visibility of telangiectasia