Combination of Oral and Topical Whitening Agents for Reducing Skin Pigmentation

Combination of Oral and Topical Whitening Agents for Reducing Skin Pigmentation in Healthy Women: A Randomized Controlled Trial

The goal of this study is to evaluate the safety and efficacy of a combination use of oral supplement and topical serum in improving skin pigmentation in healthy women. The main questions it aims to answer are:

Does combination use able to reduce the dark spot? Is there any adverse effect associate with the product use?

Study Overview

• Status: Active, not recruiting
• Conditions: Dark Spots
• Intervention / Treatment: Dietary supplement: oral supplement; Other: Retinol serum

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Selangor
    • Petaling Jaya, Selangor, Malaysia, 47810
      • USMARI Research & Innovation Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Healthy Malaysian women.
• Aged 30 - 60 years old.
• Fitzpatrick skin type III-V
• Exhibiting signs of skin pigmentation such as post-inflammatory hyperpigmentation, freckles and solar lentigines.

Exclusion Criteria:

• Participants with melasma.
• Pregnant, breastfeeding women, or those planning pregnancy during the study period.
• Participants with documented chronic medical conditions such as kidney disease, diabetes, heart problems, liver disease, gastrointestinal disorders, and others.
• Participants with documented autoimmune diseases.
• Participants with inflammatory or allergic skin problems such as atopic dermatitis, rosacea, or psoriasis.
• Use of topical agents for skin brightening within the past three months.
• Consumption of food or supplement products containing L-glutathione, L-cysteine HCL monohydrate, polypodium leucotomos leaf extract, pine bark extract, or other similar supplements, as well as the use of topical products containing niacinamide, glycyrrhiza glabra (licorice) root extract, retinol, or other products for skin brightening or rejuvenation within three months prior to the study.
• Undergoing any cosmetic procedures such as botox, laser and light treatment, facial surgery, or any procedures aimed at improving skin conditions (e.g., skin brightening, elasticity, wrinkles, pores) prior to the study.
• Consumption of any medical or hormonal treatments that could interfere with the study results, such as isotretinoin, tranexamic acid, and others.
• Allergy to any ingredients that may be found in the product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral supplement; Oral supplement contain L-glutathione, L-cysteine HCL monohydrate, polypodium leucotomos leaf extract, and pine bark extract.	Dietary supplement: oral supplement; Oral supplement need to be consume for 12 weeks. Subject need to consume the capsule once daily, during the first week. After the first week, if there are no adverse effects, they need to consume the capsule twice daily (normal dosage).
Active Comparator: Oral supplement + Retinol serum; Oral supplement is the same as the other arm. Topical serum containing niacinamide, glycyrrhiza glabra (licorice) root extract, and retinol.	Dietary supplement: oral supplement; Oral supplement need to be consume for 12 weeks. Subject need to consume the capsule once daily, during the first week. After the first week, if there are no adverse effects, they need to consume the capsule twice daily (normal dosage).; Other: Retinol serum; Serum need to be apply daily at night only, in a thin layer. The application schedule is as follows: in week 1, once a week; in week 2, twice a week (if no adverse reactions occur in week 1, such as skin dryness); in weeks 3 and 4, twice a week; and from week 4 onwards until the study is completed, three times per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin spots assessment	Changes in skin spots (assessed under polarized and UV light) are evaluated using the JANUS III Facial Skin Analysis System.	Baseline, Week 6, Week 12
Skin brightening assessment	Changes in skin brightness (L value) are evaluated using the JANUS III Facial Skin Analysis System.	Baseline, Week 6, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The safety of the oral supplement and topical products will be evaluated throughout the study by monitoring adverse events (AEs) such as gastrointestinal discomfort, body skin tingling, itching, stinging sensation, erythema or obvious signs of dry skin, desquamation, flushing and other symptoms reported by the participants.	12 weeks
Participants satisfaction	Participants' satisfaction with regards to skin brightness, spots, wrinkles, and pores will be assessed through a survey. Participants will answer questions about their preferences using a 5-point scale: 5 - Strongly Agree, 4 - Agree, 3 - Neutral, 2 - Disagree, and 1 - Strongly Disagree.	Week6, Week12

Collaborators and Investigators

• Sponsor: USMARI Research & Innovation Centre

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Supplements
• Other Study ID Numbers: UMRAMREC005-24-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No