Efficacy and safety of a topical cream containing terpinen-4-ol and niacinamide following 1064-nm picosecond Nd:YAG laser treatment for facial hyperpigmentation reduction

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Arch Aesthetic Plast Surg. 2026;32(3):55-61

Publication date (electronic) : 2026 July 30

doi : https://doi.org/10.14730/aaps.2026.01641

Sung Woon Kim, Seung Min Nam, Hyung Hwa Jeong, Han Gyu Cha, Chang Yong Choi, Eun Soo Park

Department of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea

Correspondence: Seung Min Nam Department of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon 14584, Korea E-mail: zodiac1003@schmc.ac.kr

Received 2026 May 24; Revised 2026 June 11; Accepted 2026 June 16.

Abstract

INTRODUCTION

Hyperpigmentation disorders, including melasma, postinflammatory hyperpigmentation, and lentigo senilis, are characterized by abnormal melanin overproduction [1]. Abnormal melanocyte activation may result from ultraviolet (UV) exposure, hormonal changes, and genetic predisposition [2-4]. Skin pigmentation is determined by the quantity and type of melanin synthesized by melanocytes and by its subsequent transfer to keratinocytes [4,5].

Niacinamide, also known as nicotinamide or 3-pyridinecarboxamide, is the physiologically active amide form of niacin (vitamin B₃) [6]. Several studies have shown that niacinamide has antioxidant and anti-inflammatory effects and can prevent photoimmunosuppression [7,8]. In addition, niacinamide is an established depigmenting agent that reduces skin pigmentation by suppressing melanin synthesis and inhibiting melanosome transfer from melanocytes to keratinocytes [6,9].

Tea tree oil (TTO) is a colorless oily liquid with a camphoraceous, mint-like aroma that is obtained by steam distillation of fresh Melaleuca alternifolia leaves [10,11]. This essential oil has antibacterial, anti-inflammatory, antiviral, antioxidant, and insecticidal properties. Terpenes are the major components of TTO and account for approximately 80% to 90% of its composition [10]. Terpinen-4-ol, the primary terpene, is regarded as the principal active component responsible for the anti-inflammatory and antibacterial effects of TTO [12-14].

We hypothesized that topical application of a cream containing terpinen-4-ol and niacinamide could improve facial hyperpigmentation after 1064-nm picosecond Nd:YAG laser treatment. Therefore, we evaluated the efficacy and safety of this topical cream as adjunctive therapy after 1064-nm picosecond Nd:YAG laser treatment for facial hyperpigmentation.

METHODS

A split-face study was conducted to evaluate the efficacy of a topical cream containing terpinen-4-ol and niacinamide after 1064-nm picosecond Nd:YAG laser treatment. Among patients who underwent 1064-nm picosecond Nd:YAG laser treatment for facial hyperpigmentation between December 2025 and March 2026, 27 patients with Fitzpatrick skin types III–IV who understood and agreed to the study rationale and methods were enrolled. Patients were excluded if they had a history of keloid scarring, recent oral retinoid use, pregnancy, immunosuppressive agent use, active systemic or local infection, or psychiatric illness. The study followed the Declaration of Helsinki, and written informed consent was obtained from all patients for both the procedure and publication of clinical photographs. The Institutional Review Board of Soonchunhyang University Bucheon Hospital approved the study protocol (IRB No. 2026-02-007).

RESULTS

Of the 27 patients treated with a 1064-nm picosecond Nd:YAG laser for facial hyperpigmentation, 26 were female and one was male. The mean age was 36.1 years (range, 27–44 years), and the mean follow-up period was 4 weeks (Table 1). The most common transient adverse events were erythema, edema, and pain; no infections were observed during follow-up.

Table 1.

Demographic characteristics of patients

Using a split-face design, we evaluated the efficacy of a topical cream containing terpinen-4-ol and niacinamide as adjunctive therapy to laser treatment (Figs. 1, 2). Skin pigmentation was assessed with an automated skin analysis system (Mark-Vu). In each patient, the right hemiface received the topical cream immediately after picosecond laser treatment, whereas the left hemiface served as the control and received laser treatment alone.

Fig. 1.

A 32-year-old woman with facial hyperpigmentation. (A, B) Clinical and ultraviolet (UV) photographs of the right hemiface, which was treated with picosecond laser therapy and a topical cream containing terpinen-4-ol and niacinamide, at baseline. (C, D) Clinical and UV photographs of the left hemiface, which was treated with picosecond laser therapy alone. (E, F) Clinical and UV photographs of the right hemiface at 4 weeks after treatment. (G, H) Clinical and UV photographs of the left hemiface at 4 weeks after treatment.

Fig. 2.

Clinical and ultraviolet (UV) photographs of a 38-year-old woman with facial hyperpigmentation. (A, B) The right hemiface received picosecond laser therapy followed by a topical cream containing terpinen-4-ol and niacinamide, at baseline. (C, D) The left hemiface received picosecond laser therapy alone. (E, F) Clinical and UV photographs of the right hemiface at 4 weeks after treatment. (G, H) Clinical and UV photographs of the left hemiface at 4 weeks after treatment.

On the right hemiface, the median skin pigmentation score (SPS) decreased from 30 (interquartile range [IQR], 28–31) at baseline to 27 (IQR, 25–28) at 4 weeks after treatment; this reduction was statistically significant (P<0.001). On the left hemiface, which served as the control, SPS decreased significantly from 29 (IQR, 28–30) at baseline to 28 (IQR, 27–29) at 4 weeks after treatment (P<0.001) (Fig. 3). The between-hemiface comparison showed no statistically significant difference in SPS at baseline (P=0.106). However, at 4 weeks after treatment, SPS was significantly lower on the right hemiface than on the left hemiface (P=0.004) (Fig. 4).

Fig. 3.

On the right hemiface, which received picosecond laser therapy followed by a topical cream containing terpinen-4-ol and niacinamide, the SPS was 30 (IQR, 28–31) at baseline and 27 (IQR, 25–28) at 4 weeks after treatment. The difference between baseline and 4 weeks after treatment was statistically significant (P<0.001). On the left hemiface, which received picosecond laser therapy alone, SPS was 29 (IQR, 28–30) at baseline and 28 (IQR, 27–29) at 4 weeks after treatment. This difference was also statistically significant (P<0.001). SPS, skin pigmentation score; IQR, interquartile range.

Fig. 4.

SPS was compared between the right and left hemifaces at baseline and 4 weeks after treatment. No statistically significant difference in SPS was observed between the hemifaces at baseline (P=0.106). In contrast, a statistically significant interhemifacial difference was observed at 4 weeks after treatment (P=0.004). SPS, skin pigmentation score.

Changes in MSS were also assessed between the right and left hemifaces. On the right hemiface, MSS decreased significantly from 2 (IQR, 2–3) at baseline to 1 (IQR, 1–2) at 4 weeks after treatment (P<0.001). On the left hemiface, MSS changed from 2 (IQR, 2–3) at baseline to 2 (IQR, 2–2) at 4 weeks after treatment (P=0.014) (Fig. 5). Interhemifacial comparisons showed no statistically significant difference in MSS at baseline (P=0.317). However, at 4 weeks, the right hemiface showed significantly greater improvement in MSS than the left hemiface (P<0.001) (Fig. 6).

Fig. 5.

Improvement in the MSS was compared between the right and left hemifaces. On the right hemiface, MSS was 2 (IQR, 2–3) at baseline and 1 (IQR, 1–2) at 4 weeks after treatment, with a statistically significant difference (P<0.001). On the left hemiface, MSS was 2 (IQR, 2–3) at baseline and 2 (IQR, 2–2) at 4 weeks after laser treatment, with a statistically significant difference (P=0.014). MSS, melanin severity score; IQR, interquartile range.

Fig. 6.

MSS was compared between the right and left hemifaces at baseline and 4 weeks after treatment. No statistically significant difference in MSS was observed between the hemifaces at baseline (P=0.317). In contrast, a statistically significant interhemifacial difference was observed at 4 weeks after treatment (P<0.001). MSS, melanin severity score.

DISCUSSION

With advances in laser-based treatment for dermal pigmentation disorders, the 1064-nm picosecond Nd:YAG laser has become widely used to manage facial hyperpigmentation [16,17]. This laser disrupts melanin while minimizing collateral thermal injury to surrounding tissues because its pulse duration is substantially shorter than the thermal relaxation time of melanosomes [4,17].

Hyperpigmentation is a common aesthetic concern, characterized by symmetrical or asymmetrical melanin accumulation in sun-exposed areas and is associated with increased melanogenesis [18-20]. Although melanin has photoprotective effects and contributes to tanning that protects the skin from UV radiation, focal melanin overproduction can cause unwanted cosmetic changes [21-23]. Melanin synthesis is mediated by melanocyte-specific enzymes, including tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2, all of which are regulated by microphthalmia-associated transcription factor (MITF) [24,25]. Therefore, tyrosinase inhibitors are considered useful agents for reducing melanogenesis. Several tyrosinase inhibitors, including hydroquinone, kojic acid, and arbutin, have been used for skin lightening; however, their use is often limited by adverse effects [26]. Consequently, the development of whitening cosmetics has shifted toward natural products with more favorable safety profiles.

We evaluated the efficacy of a topical cream containing terpinen-4-ol and niacinamide applied after 1064-nm picosecond Nd:YAG laser treatment. SPS improved significantly from baseline to 4 weeks after treatment on both hemifaces. The right hemiface, which received the adjunctive topical cream after laser treatment, showed significantly greater improvement in SPS than the left hemiface. Although the 1064-nm picosecond Nd:YAG laser remains central to the treatment of facial hyperpigmentation, adding a topical cream containing terpinen-4-ol and niacinamide may provide an adjunctive benefit. Terpinen-4-ol, a major active constituent of TTO, has documented antioxidant and anti-inflammatory effects in lipopolysaccharide-stimulated human monocytes [27,28]. Niacinamide, the biologically active form of vitamin B3, has anti-inflammatory properties and prevents photoimmunosuppression in the skin [7,29]. Furthermore, niacinamide induces skin-lightening effects by inhibiting melanosome transfer from melanocytes to keratinocytes [6]. On the basis of these mechanisms, adjunctive use of a topical cream containing terpinen-4-ol and niacinamide may accelerate improvement in facial hyperpigmentation through combined anti-inflammatory activity and inhibition of melanosome transfer.

This study has several limitations. First, the follow-up period was relatively short, which limited assessment of long-term changes in skin pigmentation. Second, the sample size was small, and the study population consisted exclusively of Asian patients with Fitzpatrick skin types III–IV. Third, the treatment side was not randomized; the topical cream was applied consistently to the right hemiface in all patients, which may have introduced side-assignment bias. Therefore, further studies with larger sample sizes, longer follow-up periods, randomized side allocation, and more diverse populations are needed to validate these findings.

In conclusion, despite these limitations, adjunctive application of a topical cream containing terpinen-4-ol and niacinamide after 1064-nm picosecond Nd:YAG laser treatment was associated with greater improvement in facial hyperpigmentation than laser treatment alone.

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