Evaluation of changes in skin biophysical parameters and appearance after pneumatic injections of non-cross-linked hyaluronic acid in the face

Background: Pneumatic injections of non-cross-linked hyaluronic acid are effective in skin rejuvenation, however, the associated biophysical parameters and appearance have not been evaluated. Objectives: To determine the changes in skin biophysical parameters after facial pneumatic injections of non-cross-linked hyaluronic acid. Patients and methods: Twenty-eight healthy female volunteers received pneumatic injections of non-cross-linked hyaluronic acid into the face for consecutive 5 weeks. Skin biophysical parameter assessment and clinical evaluation were performed using the CK Multi-Probe Adapter and Visia system. Five of the volunteers also underwent retroauricular skin biopsy before and after the last treatment. The skin tissues were all stained with Masson-trichrome, Verhoeff-van Gieson stain, and hematoxylin-eosin to evaluate the changes in collagen, elastic fibers, and the epidermis, before and after the last treatment. Results: Transepidermal water loss was significantly lower in week 4 (18.46 ± 4.70 g/h/m²) than at the baseline (22.03 ± 7.15 g/h/m², p < 0.05). Skin texture was better in week 4 (599.29 ± 354.32) than at the baseline (668.43 ± 342.55, p < 0.05). Skin pores also improved significantly at week 4 (934.07 ± 458.78) compared to the baseline (1024.57 ± 415.31, p < 0.05). Skin wrinkles were improved at the 3-month follow-up (29.29 ± 11.11) compared to the baseline (35.83 ± 16.05, p < 0.05). Conclusion: Pneumatic injections of non-cross-linked hyaluronic acid improved skin TEWL, texture, pores, and wrinkles.     

A 12-week clinical and instrumental study evaluating the efficacy of a multisource radiofrequency home-use device for wrinkle reduction and improvement in skin tone,skin elasticity,and dermal collagen content

This study was performed in order to evaluate the safety and efficacy of a new handheld home-use multisource radiofrequency device on facial rejuvenation. Forty-seven male and female subjects were enrolled. All subjects received a NEWA^® 3DEEP^? home-use device (EndyMed Medical, Caesarea, Israel) to be used on facial skin three times per week for the first four weeks and then reduced to two times per week for the following eight weeks. Assessments included expert clinical grading for efficacy, instrumental evaluation, image analysis, and photography. Forty-five subjects completed the study; all subjects reported the treatment to be painless with only mild erythema lasting up to 15 minutes post-treatment. No other adverse events were reported. Statistically significant improvements were noted in the appearance of marionette lines, skin brightness, elasticity, firmness, lift (facial), lift (jawline), texture/smoothness, tone, and radiance/luminosity by expert visual assessment. Statistically significant improvements in skin firmness and elasticity were found using a Cutometer MPA 580, as well as in collagen and hemoglobin content of the skin using a SIAscope. The results of this study indicate that the NEWA^® multisource radiofrequency home-use device is effective in self-administered skin rejuvenation.     

Clinical evaluation and in-vivo analysis of the performance of a fractional infrared 1550 nm laser system for skin rejuvenation

Background: This study was done to demonstrate the safety and efficacy of a novel fractional 1550 nm laser device with a rolling mechanism (FRAX1550 Ellipse Medical, Horsholm, Denmark).

Objectives: To evaluated the effectiveness of the 1550 nm device for improvement in wrinkles, pigmentation, and texture on a six point (?1 to 4) global improvement scale.

Methods: Five female subjects between the ages of 44 and 71 years, with visible wrinkles and/or dyspigmentation were enrolled in the study. Two full face treatments were performed four weeks apart Follow-up visits at 1 and 3 months posttreatment were scheduled for photographic assessments. Assessment of improvement were performed by the investigators and two blinded evaluators through use of a six-point scale.

Results: All subjects demonstrated improvement in all monitored parameters. The mean improvement scores were: wrinkles 1.6, skin texture 1.8, and pigmentation 1.7. All score improvements were statistically significant. Biopsy was performed on one patient immediately post-treatment and showed 800 μ penetration depth at a treatment level of 88 mJ and 400 μ at 44 mJ.

Conclusions: The new rolling fractional 1550 nm laser device from this study offers improvement of aging facial skin with short downtime and minimal side effects.     

A randomized,single-blind,study evaluating a 755-nm picosecond pulsed Alexandrite laser vs. a non-ablative 1927-nm fractionated thulium laser for the treatment of facial photopigmentation and aging

Background: Laser toning is one of the most popular strategies to treat facial photopigmentation and aging. Several laser modalities, including fractional non-ablative, Q-switched (QS) lasers and new generation picosecond lasers have been used for this indication. However, there is paucity of head to head comparisons of older generation of lasers with new ones.

Objective: To compare a 755 nm picosecond pulsed alexandrite laser with a non-ablative 1927 nm fractionated thulium laser for the treatment of facial photopigmentation and aging through a randomized, single-blind study.

Materials and methods: 20 subjects (skin types I–IV) were randomized to receive either four 755-nm picosecond alexandrite laser treatments, spaced 3 weeks apart, or two dual wavelength thulium fiber fractionated 1550/1927 nm laser treatments, spaced 6 weeks apart. Follow-up assessment visits occurred 4 and 12 weeks after the last study treatment.

Results: At the 4- and 12-week follow-up, both groups showed significant improvement of photoaging, pigmentation, skin quality according to the investigator and subjects assessments. When comparing the two groups, subjects in 755 nm group had statistically significant greater improvement in investigator assessments of photoaging/skin quality and subject satisfaction than those in the 1927 nm group.

Conclusion: Both the non-ablative 1927 and 755 nm picosecond laser can improve facial photopigmentation, but the latter can yield superior results with less pain and side effects according to patient and investigator assessments.     

Two years’ outcome of thread lifting with absorbable barbed PDO threads: Innovative score for objective and subjective assessment

Background: Thread-lifting rejuvenation procedures have evolved again, with the development of absorbable threads. Although they have gained popularity among plastic surgeons and dermatologists, very few articles have been written in literature about absorbable threads. This study aims to evaluate two years’ outcome of thread lifting using absorbable barbed threads for facial rejuvenation. Methods: Prospective comparative stud both objectively and subjectively and follow-up assessment for 24 months. Results: Thread lifting for face rejuvenation has significant long-lasting effects that include skin lifting from 3–10 mm and high degree of patients’ satisfaction with less incidence rate of complications, about 4.8%. Augmented results are obtained when thread lifting is combined with other lifting and rejuvenation modalities. Conclusion: Significant facial rejuvenation is achieved by thread lifting and highly augmented results are observed when they are combined with Botox, fillers, and/or platelet rich plasma (PRP) rejuvenations.     

Combined treatment for skin laxity of the aging face with monopolar radiofrequency and intense focused ultrasound in Korean subjects

Background: Although various minimal invasive approaches are available for aging skin laxity, they alone may not lead to notably satisfactory results. Objective: To evaluate the effectiveness and safety of combination regimen with monopolar radiofrequency (MRF) and intense-focused ultrasound (IFUS) in facial lifting and tightening. Methods: Twenty-two Korean participants with aging face received a sequential single session of MRF and IFUS treatment. Objective and subjective assessments for improvement were performed at the 20-week post-treatment. Safety profiles were also recorded, and skin biopsies were taken at baseline and follow-up visit. Results: Based on the objective assessment for the overall facial skin tightening and laxity, 19 patients (90%) demonstrated “moderate” or better improvements (more than 25%) compared with baseline. Specifically, improvements of skin laxity and sagging, and droopy jaw line were more noticeable compared with that of superficial skin texture (P < 0.05). Subjective satisfactions were generally consistent with objective findings, and no serious adverse effect was observed. Histologic evaluation showed increased dermal collagen fibers throughout the dermis after treatments (P < 0.05). Conclusion: Combination treatment of MRF and IFUS has cumulative benefits for skin lifting and tightening with satisfactory safety profiles in Asian subjects.     

Fractional carbon dioxide laser for facial rejuvenation: A prospective study to evaluate the efficacy and the safety

Background: The aim of this study was to evaluate the efficacy and safety of the fractional ablative carbon dioxide laser for facial rejuvenation. Materials and Methods: Twenty-nine female who have the complaint of facial aging were recruited for the study. Participants received a maximum of three laser treatment sessions with one-month intervals and were scored using a 5-point scale on seven categories for facial aging before and after the treatment by the physicians. Self-assessments by participants were done at the last month of follow-up period and 3 years after the last session. Results: Mean facial aging score before the treatment was 11,24 ± 4,30 and after the treatment was 10,51 ± 3,86 (p = 0.003). The decrease in the score was mild in 18 (62,1%) participants, whereas it was moderate in only 1 (3,4%) participant. None of the participants had significant or perfect improvement. When the seven categories were analyzed seperately, the only statistically significant alteration in the score was found in the skin tone category (p = 0.0001). Conclusion: Results show that rejuvenation with the fractional ablative carbon dioxide laser decreases mildly the symptoms of facial aging in more than half of the patients.     

Application of a new fractional radiofrequency device in the treatment of photoaging skin in Chinese patients

Background and objectives: Fractional radiofrequency (FRF) has been used in the treatment of photoaged skin for a long time. This study was intended to examine the efficacy and safety of electrode pin FRF in the treatment of photoaged skin in Chinese patients.

Materials and methods: Twenty healthy Chinese subjects with facial photoaged skin were enrolled in this study. Each subject received three FRF treatments at 4-week intervals. Changes of photoaging were analyzed by a global evaluation, subjective Assessment, a Mexameter, and VISIA.

Results: In total, 12 of 18 patients (66.7%) and 11 of 18 patients (61.1%) had good or excellent improvement respectively according to investigator A and investigator B. Also, 13 of 18 patients (72.2%) rated their satisfaction of the overall improvement as satisfied or very satisfied. Mean melanin index and erythema index values significantly decreased between baseline and 12-week follow up (P < 0.05). The average wrinkle percentile was increased at 12-week follow-up (79.0 ± 8.4) compared to baseline (58.8 ± 10.2). Adverse effects were limited to erythema, tiny scabs and mild pain.

Conclusions: FRF is a safe and effective method for photoaging skin in Chinese patients.     

Correction of nasolabial folds wrinkle using intraoral non-ablative Er:YAG laser

Background: The accentuated nasolabial folds (NLFs) is the most pronounced sign of aging. Non-ablative erbium:yttrium aluminum garnet laser (ER:YAG), Smooth mode was used for the treatment of mucosal tissue. It was reported that it is effective in facial rejuvenation.

Aim: To assess the safety and the effectiveness of intraoral ER:YAG Smooth mode laser in the treatment of NLFs wrinkle. Materials and methods: A total of 20 patients with different grades of NLFs wrinkle treated with 2940 nm Er:YAG laser intraorally. Six sessions were done every 2 weeks. The efficacy was assessed by two blinded dermatologists. Photographs were taken at the baseline, end of treatment and 6 months after the final session to document visible changes in NLFs wrinkle. The assessment was based on Modified Fitzpatrick Wrinkle Scale (MFWS) and by comparing the photographs. Patient’s self-assessment and patient’s satisfaction were used for assessment of final results and any side effects associated to treatment were observed. Results: There was significant reduction of the NLFs wrinkle. The MFWS was significantly improved 6 months after treatment compared to before treatment (p < 0.001). At the end of the follow-up period, there was improvement in overall appearance of the wrinkles. Patient’s self -assessment and satisfaction demonstrated better cosmetic outcomes. Conclusion: Intraoral Er:YAG laser is safe, painless, and effective treatment option for NLFs wrinkle.     

The efficacy of conditioned media of adipose-derived stem cells combined with ablative carbon dioxide fractional resurfacing for atrophic acne scars and skin rejuvenation

Objective: To evaluate the effects of conditioned medium of adipose-derived stem cells (ADSC-CM) on efficacy and side effects after fractional carbon dioxide laser resurfacing (FxCR) when treating subjects with facial atrophic acne scars or with skin rejuvenation needs. Materials and methods: Twenty-two subjects were enrolled in the study and divided into two groups. Nine subjects were included in skin rejuvenation group and thirteen subjects were included in acne scar group, and all subjects underwent three sessions of FxCR. ADSC-CM was applied on FxCR site of one randomly selected face side. Evaluations were done at baseline, 1 week after first treatment, and 1 month after each treatment. The outcome assessments included subjective satisfaction scale; blinded clinical assessment; and the biophysical parameters of roughness, elasticity, skin hydration, transepidermal water loss (TEWL), and the erythema and melanin index. Biopsies taken from one subject in skin rejuvenation group were analyzed using hematoxylin and eosin, Masson's Trichrome, and Gomori's aldehyde fuchsin staining. Results: ADSC-CM combined with FxCR increased subject satisfaction, elasticity, skin hydration, and skin elasticity and decreased TEWL, roughness, and the melanin index in both acne scars and skin rejuvenation groups. Histologic analysis showed that ADSC-CM increased dermal collagen density, elastin density, and arranged them in order. Conclusion: ADSC-CM with FxCR is a good combination therapy for treating atrophic acne scars and skin rejuvenation.

Trial registration: JSPH2012-082 – Registered 14 Feb 2012     

Facial skin rejuvenation by combination treatment of IPL followed by continuous and fractional radiofrequency

Objective: The objective of this study was to evaluate the safety and efficacy of combination facial treatment by 3 technologies. Materials and methods: Eleven patients completed the clinical trial that consisted of alternate treatments of intense pulsed light (IPL) in 3 sessions and continuous + fractional bipolar radiofrequency (RF) in 3 alternating sessions, 3 weeks apart. Follow-up visits were made at 6 and 12 weeks following the last treatment. Lesions were evaluated by photographs taken at baseline and at follow-up time points according to predetermined scales. Results: Results showed statistically significant improvement in wrinkling (24% after 6 weeks and 33% after 12 weeks), pigmentation (38% after 6 weeks and 62% after 12 weeks), vascular lesions (29% after 6 weeks and 67% after 12 weeks), and laxity (37% after 6 weeks and 40% after 12 weeks). Conclusions: Combination facial treatment by IPL, and continuous and fractional RF is safe and enables the treatment of a variety of facial lesions, taking advantage of accessible applicators for different clinical indications on the same device. Thus, comprehensive facial skin rejuvenation has become feasible.     

The lamellar peel: A sequential nonablative and ablative laser treatment for facial skin rejuvenation

Objectives. Ablative and nonablative laser treatments have established themselves independently in the rejuvenation of aging skin. This study was designed to determine the effects of sequential nonablative and ablative laser treatments on facial skin.

Materials and methods. Twelve patients, ages 32–56 years, with skin phototypes I‐IV, received three treatments spaced six weeks apart. Each treatment consisted of one pass with 1319‐nm Nd:YAG laser at 16 J/cm², 50 ms pulse duration. This was immediately followed by one pass of 2940‐nm Er:YAG laser at 5 J/cm². Photographs and biopsies were taken prior to the first treatment and following the third treatment.

Results. Clinical improvements in facial skin tone and texture, acne scarring and dyschromia were noted in all patients. Histologic changes included a more compact epidermal granular layer and lamellar collagen formation with decreased solar elastosis in the dermis. Compared to controls, treated skin had a thicker, more homogeneous papillary dermis.

Conclusion. The sequential use of nonablative and superficial ablative laser treatments clinically and histologically improved photodamaged and chronologically aged skin. This occurred with minimal recovery and little morbidity, demonstrating this laser application to be a safe and effective method for facial rejuvenation.     

A study to determine the efficacy of combination LED light therapy (633 nm and 830 nm) in facial skin rejuvenation

Background. The use of visible or near infrared spectral light alone for the purpose of skin rejuvenation has been previously reported. A method of light emitting diode (LED) photo rejuvenation incorporating a combination of these wavelengths and thus compounding their distinct stimulation of cellular components is proposed.

Objective. To assess the efficacy and local tolerability of combination light therapy in photo rejuvenation of facial skin.

Methods. Thirty‐one subjects with facial rhytids received nine light therapy treatments using the Omnilux^TM LED system. The treatments combined wavelengths of 633 nm and 830 nm with fluences of 126 J/cm² and 66 J/cm² respectively. Improvements to the skin surface were evaluated at weeks 9 and 12 by profilometry performed on periorbital casts. Additional outcome measures included assessments of clinical photography and patient satisfaction scores.

Results. Key profilometry results Sq, Sa, Sp and St showed significant differences at week 12 follow‐up; 52% of subjects showed a 25%–50% improvement in photoaging scores by week 12; 81% of subjects reported a significant improvement in periorbital wrinkles on completion of follow‐up.

Conclusion. Omnilux^TM combination red and near infrared LED therapy represents an effective and acceptable method of photo rejuvenation. Further study to optimize the parameters of treatment is required.     

Evaluation of effects of platelet-rich plasma on human facial skin

Abstract

Introduction: Platelet-rich plasma (PRP) has been used for rapid healing and tissue regeneration in many fields of medicine. This study was conducted to evaluate the effects of PRP application procedure on human facial skin. Methods: PRP was applied thrice at 2-week intervals on the face of ten healthy volunteers. It was applied to individual's forehead, malar area, and jaw by a dermaroller, and injected using a 27-gauge injector into the wrinkles of crow's feet. Participants were asked to grade on a scale from 0 to 5 for general appearance, skin firmness–sagging, wrinkle state and pigmentation disorder of their own face before each PRP procedure and 3 months after the last PRP procedure. While volunteers were evaluating their own face, they were also assessed by three different dermatologists at the same time by the same five-point scale. Results: There was statistically significant difference regarding the general appearance, skin firmness-sagging and wrinkle state according to the grading scale of the patients before and after three PRP applications. Whereas there was only statistically significant difference for the skin firmness–sagging according to the assessment of the dermatologists. Conclusion: PRP application could be considered as an effective procedure for facial skin rejuvenation.     

The assessment of the effects of the combination of microdermabrasion and cavitation peeling in the therapy of seborrhoeic skin with visible symptoms of acne punctata

Objective: The aim of this study was to assess objectively the effects of the combination of corundum microdermabrasion and cavitation peeling in the therapy of seborrheic skin with visible symptoms of acne punctata.

Material and methods: The study involved a group of nine women. A series of six treatments with the combination of microdermabrasion and cavitation peeling were performed within facial skin at 10–14 days intervals. Corneometric measurements examining skin hydration level and sebumetric measurements analyzing skin sebum level were made before the series of treatments and after second, fourth and sixth procedure in five facial areas. Clinical assessment of the efficacy of the therapy was performed on the basis of photographic documentation (Fotomedicus). Anonymous questionnaires were used in order to evaluate patients’ satisfaction rate.

Results: Statistically significant improvement in skin sebum level was observed in all examined areas (forehead p = 0.002; nose p = 0.001, chin p = 0.01, left cheek p = 0.009, right cheek p = 0.007). In case of skin hydration, significant improvement was found only in the area of chin (p = 0.03). 78% of participants estimated that the improvement was in the range of 55–70%, while 22% of participants of 75–100%. The reduction in the amount and visibility of comedones and pimples were demonstrated on the basis of questionnaire and photographic documentation.

Conclusions: Combined microdermabrasion and cavitation peeling treatments improve the condition of seborrheic skin.     

Long‐term clinical results of IPL photorejuvenation

BACKGROUND: Non‐ablative photorejuvenation is characterized by the reduction of intrinsic and extrinsic changes in photodamaged skin. Only short‐term improvement has been documented previously.

OBJECTIVE: To evaluate quantitatively the short‐term and long‐term clinical effectiveness of multiple full‐face IPL treatments for non‐ablative facial photorejuvenation.

METHODS: A total of 47 patients with varying degrees of photodamaged skin and rosaceal dermatitis underwent a series of four to five IPL treatments with a Vasculight (Lumenis Corp). Treatments were conducted every 3–4 weeks. Photographs were taken at baseline and after the treatment series was completed at both 6 weeks and 6 months. Adverse effects and clinical improvement were documented. A patient satisfaction questionnaire was completed and reviewed at the 6‐month evaluation period.

RESULTS: Standardized evaluation of rhytids showed a statistically significant improvement in wrinkles at both evaluation endpoints. Some degradation occurred over time. Facial vascularity, dyschromia, and large pore size progressively improved from the 6‐week measurement to the 6‐month measurement.

CONCLUSION: This clinical study demonstrates that non‐ablative facial rejuvenation is associated with long‐term clinical improvement of facial rhytids, abnormal vascularity and pigmentary disorders with minimal risks and side effects to the patient.     

Application of plasma-combined regeneration technology in managing facial acne scars

Background and Objectives: Plasma skin regeneration (PSR) and platelet-rich plasma（PRP） have gained popularity in the treatment of acne scars due to their efficacy and improved tolerability. The objective of this investigation was to evaluate the synergistic effect of PRP plus PSR (plasma-combined regeneration technology, PCRT) in managing facial acne scars.

Methods: From March 2015 to June 2017，a total of 25 cases with facial atrophic acne scars were treated with PCRT treatment for three to five times. Treatments were repeated at an interval of 8 weeks．Treatment parameters were titrated to an immediate end point of moderate erythema. The clinical end point for cessation of treatment was the attainment of satisfactory clinical results. Results were monitored photographically up to 6 months after treatment. The efficacy and adverse effects were evaluated by using the following outcome parameters： the duration of edema,erythema and crusting; the degree of hyperpigmentation, hypopigmentation and scarformation; subjective effective rate was evaluated by patients and physicians.

Results: 22 of 25 participants completed the study, and were followed up for 6–12 months. After three to five treatments, evaluation by patients showed that the total effective rate was 90.91%. Evaluation by two physicians showed that the total effective rate was 86.36%. Treatment was well tolerated by all participants. The total duration of side effects was 6.7 ± 1.7 days of edema, 8.1 ± 2.3 days of erythema,6.5 ± 1.8 days of crusting, respectively. No hyperpigmentation, depigmentation, and worsening of scarring were observed by the conclusion of the follow-up period．

Conclusion: These results provide initial evidence for the safety and effectiveness of PCRT as a well-tolerated modality for the treatment of acne scars. PCRT is an ideal treatment for facial acne scars with minimal side effect．     

Efficacy of protein extracts from medium of Adipose-derived stem cells via microneedles on Asian skin

Objectives: To explore efficacy of protein extracts from medium of Adipose-derived stem cells (ADSCs) via microneedles on Asian skin in a double-blind, split-face, randomized, control study. Methods: Thirty volunteers received the treatment, left-side and right-side of their face were randomly assigned to test side and control side. The protein extracts from medium of ADSCs were applied via microneedles into the test side and ultrapure water was applied into the control side. The only person who knew what was being used by each subject on each side of the face was the therapist. Clinical evaluation including instrument test and self-questionnaire was performed by independent observers before and after the treatment, which lasted for 3 months. Results: All subjects completed the study. Compared to ultrapure water, the protein extracts from medium of ADSCs showed a statistically significant improvement for melanin index, skin brightness, gloss, skin roughness, elasticity, and wrinkles (p < 0.05). More than 70% of the participants described that all wrinkles, firmness, elasticity, hydration, whitening, and radiance were strongly improved in the test side. Conclusions: Protein extracts from medium of ADSCs presented anti-aging and whitening efficacy via microneedles on Asian skin without skin adverse side.     

810 nm diode laser for hair reduction with Chill-tip technology: prospective observational analysis of 55 patients of Fitzpatrick skin types III,IV,V

ABSTRACT

Background: Various light based technologies like Diode, long pulsed Nd:Yag and Intense Pulsed Light are used commonly for long-term hair reduction. The commonest indication is hirsutism.

Aim: 1. To evaluate efficacy and safety of 810 nm Diode laser in Fitzpatrick skin types III, IV and V.

2. To assess percentage of cases on the basis of indications, average number of sessions, fluence required, the long-term results and complications using diode laser in darker skin types.

Methods: A prospective observational study of 55 consecutive patients who came for laser hair reduction by 810 nm Light Sheer Diode laser with Chill tip technology was carried out. The sessions were conducted at an interval of 4–6 weeks and the patients were followed up over a period of 2 years. Data was analyzed using software SPSS (Statistical Package for Social Science. Ver.12, Inc. Chicago, USA).

Results: Fifty-five patients (51 females and 4 males) were studied. 67.3% (n = 37) had skin type IV. The most common area treated was chin (n = 23). The average growth reduction of terminal hair at the end of three sessions was 61.25%. Only 8% (n = 4) had short-term side effects.

Conclusion: Diode laser is highly effective for long-term hair reduction of terminal hair growth in Fitzpatrick skin type III, IV and V with no permanent side effects.

Abbreviations: LHR (Laser Hair Reduction)     

Protective effects of fermented honeybush (Cyclopia intermedia) extract (HU-018) against skin aging: a randomized,double-blinded,placebo-controlled study

Background: Oxidative stress and photodamage resulting from ultraviolet radiation exposure play key roles in skin aging. Fermented Cyclopia intermedia, which is used to brew honeybush tea, exerts antioxidant and anti-wrinkle effects by inhibiting reactive oxygen species production and downregulating matrix metalloproteinase activity. Objectives: This randomized, double-blinded, placebo-controlled study aimed to evaluate the efficacy and safety of fermented honeybush (Cyclopia intermedia) extract (HU-018) for skin rejuvenation. Methods: 120 Korean subjects with crow’s feet wrinkles were randomized to receive either low-dose extract (400 mg/day), high-dose extract (800 mg/day), or placebo (negative control, only dextran) for 12 weeks. Wrinkles were evaluated using JANUS^® and PRIMO pico^®. Skin elasticity, hydration and transepidermal water loss were measured. Results: Global skin wrinkle grade was significantly improved in both low-dose and high-dose groups compared to placebo group, as well as for skin hydration and elasticity. Both the low- and high-dose groups showed significantly decreased TEWL compared to the placebo group. There were no adverse effects during the entire study period. Conclusion: Our data indicate that HU-018 is effective for improving skin wrinkles, elasticity, and hydration. Therefore, daily supplementation with fermented honeybush could be helpful for protecting against skin aging.