Clinical Research: PIH Prevention

By Dr Anna Funikova, Dr Tiina Orasmae-Meder and Dr Yehor Kolodtchenko / 04 Sep 2019

Practitioners conduct a clinical study to determine the possibilities of minimising the risk of secondary hyperpigmentation after laser resurfacing and phenol peels


We have conducted a study to determine the possibility of reducing the risk of secondary hyperpigmentation after phenol peels and laser resurfacing of the face. It has been previously established that pigmentation disturbances during recovery after moderately and severely traumatic treatments are one of the key problems concerning the patients’ wellbeing and satisfaction.1,2

During the course of this study, the patients applied a water-soluble product (serum) with 0.5% niacinamide and a complex of plant ingredients (the extracts of cane sugar, maple sugar, aloe vera, blueberry leaves and berries, sweet orange and citron) for seven to 10 days before their phenol peel treatment (35% phenol's solution) or ablative laser resurfacing.

Following the treatments, the patients continued applying the serum for 30 days. In the phenol peel group (Group 1), there were 20 patients that applied the serum, plus nine patients in the control group. In Group 2, which underwent fractional ablative erbium laser resurfacing, there were 15 patients that applied the serum and 10 patients in the control group.

All patients noted the serum’s high tolerability, skin brightening effect and the absence of skin irritation. No side effects, including post-inflammatory and transitory pigmentation, were registered in either group of patients (20 phenol peel patients and 15 laser resurfacing patients).

In the control groups, one case of post-inflammatory pigmentation was recorded after phenol peel, and one case of post-inflammatory pigmentation after laser resurfacing. The data stayed consistent after three months. Both groups using the serum noted a shorter recovery period: the shedding of post-treatment scabs took three to four days, whereas in the control group it was five to seven days. 

Based on the results obtained thus far, we believe that high tolerability, possible reduction of the side effects and the patients’ faster return to social life led to increased wellbeing and satisfaction, providing sufficient grounds for including such topical solutions in the protocols of pre and post-treatment skincare. Further studies should be conducted to obtain more substantial data on the efficacy of topical solutions for the prevention of post-inflammatory hyperpigmentation.


Laser treatments in aesthetic medicine have been growing increasingly popular in the last decade, and this trend is likely to persist.3,4 Laser can be used for a variety of purposes, from acne therapy to scar and skin tag removal; and controlled epidermal injury plays a significant part in the practice of aesthetic practitioners.

According to research, the risk of side effects and complications resulting from aesthetic laser treatments can be considered low.5-7 However, certain side effects, usually classified as insignificant, cause noticeable discomfort and can lead to patients’ dissatisfaction with the treatment effect, even when the results are satisfactory from an objective point of view.

Among such side effects is pigmentation disturbance caused by epidermal injury and the development of inflammatory changes in the tissue in the process of post-laser recovery.8,9 Post-inflammatory hyperpigmentation (PIH) is one of the most commonly described side effects of laser treatments. Various research data shows that the rate of PIH after non-ablative fractional laser treatment reaches 31% for melasma therapy,10 25% for antiageing,11 and 41% for post-acne scarring removal.12

Ablative laser treatment bears even higher degree of risk; up to 80% of PIH with CO2 laser and 60% with Erbium YAG.13 The power of laser impact correlates with the risk of post-treatment pigmentation.14

Generally, patients with already present melasma need to be informed that laser therapy, including non-ablative laser, may increase pigmentation after a single treatment.15

Thus, PIH prevention must be one of the priorities in the patients’ preparation for laser treatment. In the presence of risk factors, such as melasma, PIH manifestation in the past, the use of photosensitising skincare in the previous few weeks and the taking of photosensitising drugs, prophylactic measures are recommended for at least 14-28 days prior to the treatment.16,17

Today the standard for PIH prevention is applying topical solutions with confirmed anti-tyrosinase activity.18 Most commonly used are solutions based on kojic acid, azelaic acid, arbutin and hydroquinone, the latter often used in combination with tretinoin and topical steroids19 (the use of hydroquinone-containing solutions is banned in EU20). Apart from these, the daily use of sunscreens with SPF UVA UVB 30-50 is routinely recommended to laser patients.21,22

However, most of the above, with the exception of sunscreens, actually increase the skin’s sensitivity to ultraviolet, exposing patients to the risk of PIH in the recovery period after laser or other treatment involving epidermal injury.23

The aim of this research is to explore the possibilities and prospects of PIH prevention with the use of a topical solution with a brightening and anti-inflammatory effect, which does not increase the skin’s sensitivity to UV radiation.


This research was conducted in several clinics in Ukraine. It involved 54 women, aged 25-52. Participants were selected to the following criteria:

  • Good general health at the time of research
  • Lack of pigmentation
  • Fitzpatrick skin type II and III
  • Regular menstruation
  • No previous ablative CO2 or erbium laser treatments, no medium depth and deep chemical peels in the past
  • No photosensitising topical solutions used in the previous four weeks
  • No potentially photosensitising medicine taken in the previous four weeks
  • No skin inflammation at the time of treatment

A complete medical history was taken and all patients signed informed consent forms and the research aims and methods were explained to them in full.

Patients were divided into two groups of 25 and 29 people. The first group of 29 people had a 35% phenol peel. There were 20 patients who were given a topical solution to use in the 14 days prior to their chemical peel, and then resume application on the fifth day after the treatment and continue for 30 days. The control group of 10 patients did not use topical solutions in the pre and post-peel periods.

In the second group, all patients had fractional ablative erbium laser resurfacing. There were 15 patients who were given a topical solution to use in the 14 days prior to their laser treatment, and then they were instructed to resume application on the fifth day after the treatment and continue for 30 days. The control group of 10 patients did not use topical solutions in the pre and post-treatment periods.

Neither group had any information about the composition, manufacturer or price of their topical solution.

The topical solution recommended to research participants was a water solution of:

  • Blueberry leaf and berry extract (3.42%)
  • Cane sugar (1.5%)
  • Sweet orange extract (0.48%)
  • Citrus medica extract (0.48%)
  • Aloe barbadensis leaf juice (0.2%)
  • Canadian maple juice (0.18%)
  • Niacinamide (0.5%)

The expected effects of the solution were: a stronger antioxidant protection of the skin, the smoothing of epidermal keratinous layer, reduced activity of melanocyte-keratinocyte melanin transfer, the decrease of melanin synthesis due to the deactivation of tyrosinase, and restoration of capillary tone in the microcirculatory bed.

It was suspected that the affect would be achieved with synergetic impact of niacinamide and a complex of natural antioxidants in the citruses and blueberry extracts, combined with the effect of maple and sugar cane syrups’ polysaccharides and aloe. 

The aim of the solution is to create a protective film on the skin surface, creating favourable conditions for comfortable recovery. At the same time, the solution aims to subdue inflammatory reactions, activate epidermal regeneration and stimulate the syntheses of dermal structural elements.

The effect of ingredients applied


Topical application of niacinamide has a range of confirmed effects on the skin. In particular, applying niacinamide-containing solutions for several weeks aims to reduce trans-epidermal water loss by up to 24% in four weeks through increasing the contents of free fatty acids (67%) and ceramides (34%) in the keratinous layer of the skin.24

The syntheses of epidermal proteins: keratin, filaggrin and involucrin is also known to increase.25 
Together, these proteins optimise the aggregation of keratinocytes in the keratinous layer, preserve the integrity of corneous envelopes of corneocytes and the smooth structure of the keratinous layer.26 Research of niacinamide’s effect on the human fibroblast culture has revealed the increased syntheses of new fibroblasts (20%) and collagen type I (54%).27,28 

Niacinamide is widely used as a brightening agent, which is especially active during the therapy of post-traumatic, post-inflammatory and chronic recurring hyperpigmentation. The mechanics of niacinamide action is as follows: niacinamide inhibits the melanocyte-to-keratinocyte transfer of pigment granules (melanosomes) up to 68% in vitro in the co-culture of melanocytes and keratinocytes.29 Niacinamide acts in synergy with certain antioxidants,30 increasing the effect of an antioxidant’s impact and advancing all the results described above.

Blueberry extract

Blueberry extract contains specific anthocyanins and polyphenols with antioxidant effect. They are also able to reduce the damaging effect of oxidative stress, prevent the skin’s photodamage, especially when connected with UVB damage.31 Anthocyanins are capable of absorbing a wide spectrum of UV rays, helping to reduce the skin’s sensitivity to ultraviolet radiation with daily use. Blueberry anthocyanins, in particular cyanidin-3-glucoside, petunidin-3-glucoside, malvidin-3-glucoside, and delphinidin-3-glucoside, can also prevent the overexpression of genes responsible for the synthesis of metal proteinase and the suppression of collagen synthesis by dermal fibroblasts.32 

Aloe barbadensis

Aloe barbadensis (aloe vera) juice extract contains more than 75 active agents with pronounced biological effect.33 Polysaccharide glucomannan and gibberellin interact with the fibroblasts’ growth factor receptors and stimulate the proliferative activity of the cells leading to the activation of collagen synthesis.34 The topical application of aloe juice extract is known to increase the synthesis of hyaluronic acid and dermatan sulphate in the granulation tissue after an injury,35 as well as the increase of proliferation-promoting activity of dermal cells in general accelerating healing and oxygenation.36 Aloe juice extract has anti-inflammatory effect as well, due to its ability to inhibit the cyclooxygenase pathway of inflammation and to reduce the activity of prostaglandin E2. It appears that this particular effect of aloe extract is due to its contents of C-glucosyl chromone.37 Finally, aloe has a proven antioxidant effect thanks to glutathione peroxide superoxide dismutase and some phenol derivatives.38 

Cane sugar

Cane sugar extract contains natural flavonoids and phenolic acids with pronounced antioxidant effect.39 The daily application of solutions with cane sugar extract helps reduce the negative effects of oxidative stress and UV-related damage in various skin structures.40

Maple sugar

The maple (Acer rubrum) is a rich source of phenolic compounds which possess galloyl groups. These glucitol-core containing gallotannins (GCGs) have reported antioxidant and anti-glycative effects and also the anti-tyrosinase and anti-melanogenic effects of a proprietary phenolic-enriched red maple leaves extract.41 The extract is able to:

  1. Reduce the levels of reactive oxygen specie
  2. Down-regulate the expression of MITF, TYR, TRP-1, and TRP-2 gene levels in a time-dependent manner
  3. Significantly reduce protein expression of the TRP-2 gene

Therefore, the anti-melanogenic effects of red maple GCGs can help reduce a risk of PIH.41

Citrus medica extract

Citrus medica extract is a source of natural ascorbic acid and different flavonoids, including nobiletin,42 hesperidin et al.43 The extract helps smooth and brighten the skin because of tyrosinase inhibition effect, prevents inflammatory reaction and accelerates healing process after an injury.44

Sweet orange extract

Sweet orange extract (citrus aurantium extract) contains a range of low-molecular substances with anti-inflammatory and capillary-strengthening effect, also with a capacity for tyrosinase inhibition (TI) and pigment inhibition.45


All patients in both groups noted good tolerability of the solution, ease of application and lack of pronounced subjective sensations during the application, both in pre- and post-treatment (phenol peel and fractional ablative erbium laser resurfacing) periods. Neither group displayed any side effects potentially connected to the use of the solution. 

In Group 1, among the patients who used the solution, there were no cases of PIH, whereas in the control group, one case of PIH was diagnosed and the patient received additional therapy to correct hyperpigmentation. The rate of shedding of the crusts among the patients who used the solution was three to four days, whereas, in the control group it was five to seven days. 

Group 2 displayed similar results. Among the patients who used the solution there were no cases of PIH, while in the control group, one case of PIH was diagnosed and additional therapy prescribed. The rate of crust shedding was three to four days for the patients who used the solution, and five to seven days for the patients in the control group. The data is summarised in Table 1.

Group Number MethodNumber of PatientsRate of PIHRate of crust shedding (days)
135% phenol peeling, with the solution
135% phenol peeling, control group 
2Ablative Erbium laser resurfacing, with the solution  
2Ablative Erbium laser resurfacing, control group

Table 1: The results of the study 


Given the results of this research, we can suppose that the application of a topical solution based on plant extracts and niacinamide in the periods of preparation for and rehabilitation after laser treatment or deep chemical peel is highly likely to shorten the recovery period and reduce the risk of post-inflammatory hyperpigmentation (PIH). 

A shorter recovery period and a reduced possibility of the most common side effect increases the patients’ satisfaction, improves their socialisation and makes the early rehabilitation period more comfortable, which is beneficial for the remote results of the treatment, and the performance of clinic and its practitioners. Good tolerability and lack of contraindications make the solution suitable for preparation and recovery after laser treatments and chemical peels combined with sun protection. 

Disclosure: For the purposes of this research, 100 bottles of Meder Beauty Science Nrj-Soin Serum were provided. The packaging was 50ml airless bottles, unmarked. The serum was provided by Meder Beauty International Ltd (UK). The research participants were not rewarded. The clinical professionals, who participated in the research, did not receive any grants, rewards, payments or any other compensation, material or otherwise. This article was written without any sponsor support from the manufacturing company. 

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