Potassium 4-Methoxysalicylate (4MSK) Exerts a Skin Lightening Effect by Acting on Melanocytes and Keratinocytes.

Summary

4MSK decreases melanin in melanocytes and 3D epidermal models and enhances keratinocyte differentiation marker expression. In a double-blind split-face clinical study, 4MSK increased cheek skin lightness in both pigmented and non-pigmented areas and reduced desquamation, supporting dual-cell action and clinical efficacy.

Key Findings

• 4MSK significantly reduced melanin content in human melanocytes and 3D epidermal equivalents.
• 4MSK increased expression of keratinocyte differentiation markers.
• In a double-blind, split-face, placebo-controlled study, 4MSK increased skin lightness in both pigmented and non-pigmented cheek areas and reduced desquamation area ratio.

Clinical Implications

Supports incorporating 4MSK into regimens for hyperpigmentation and overall brightening; its keratinocyte-differentiation effects suggest barrier-compatible use, pending larger trials and diverse phototypes.

Limitations

• Sample size and study duration were not reported in the abstract.
• Single formulation context; long-term safety and durability of effects not addressed.

Future Directions

Larger, multi-ethnic RCTs with quantitative colorimetry and histologic endpoints; head-to-head comparisons versus standard agents (e.g., hydroquinone) and combination regimens with photoprotection.