{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:10:02Z","timestamp":1783721402956,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004357","name":"Procter and Gamble","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004357","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intern J of Cosmetic Sci"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Niacinamide is a well\u2010established ingredient known for reducing hyperpigmentation by inhibiting melanosome transfer from melanocytes to keratinocytes. This study aimed to explore the potential synergistic effects of niacinamide and low pH in melanogenesis pathways and their impact on skin hyperpigmentation in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro experiments were conducted using human melanocyte and\/or keratinocyte cultures to investigate the effects of niacinamide at varying pH levels (neutral pH\u20097 and low pH\u20092.5\u20134). Melanin synthesis, melanocyte dendricity, melanosome transfer and melanosome degradation were assessed. Transcriptome analysis was performed to identify gene expression changes in human melanocytes. Additionally, vehicle\u2010controlled facial clinical trials were conducted among Caucasian and Chinese females to evaluate the effects of niacinamide formulations at neutral and low pH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Niacinamide in neutral pH solutions and simple low pH solutions (without niacinamide) did not inhibit melanin synthesis or melanocyte dendricity, as expected. However, niacinamide in low pH solutions significantly inhibited both, indicating a synergistic interaction. Enhanced suppression of melanosome transfer and degradation was also observed, although these effects appeared to be additive to the effects of neutral pH niacinamide. Transcriptome analysis revealed downregulation of genes and pathways associated with melanogenic cytokine signalling, melanin biosynthesis, melanocyte dendricity and melanosome transfer for niacinamide in low pH formulation, but not niacinamide in neutral pH or simple low pH formulations (without niacinamide), further supporting the synergistic effect. A 4\u2010week clinical trial among Caucasian females using 2% niacinamide formulation at pH\u20092.5 revealed a marked reduction in the appearance of facial spots compared to 2% niacinamide neutral pH or vehicle formulations. Similarly, an 8\u2010week clinical trial conducted with Chinese females using 5% niacinamide formulation at pH\u20094 demonstrated significantly greater efficacy in both facial spot reduction and skin brightening in appearance than neutral pH niacinamide and vehicle formulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our series of in\u00a0vitro and clinical studies revealed groundbreaking findings on the role of pH modulation in enhancing the efficacy of niacinamide for hyperpigmentation reduction. By elucidating the synergistic mechanisms involved, this research paves the way for developing more effective treatments aimed at achieving a brighter and more uniform complexion safely.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ics.70044","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T12:46:36Z","timestamp":1764506796000},"page":"445-455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic effects of niacinamide and low\n                    <scp>pH<\/scp>\n                    on melanin synthesis, melanocyte function and hyperpigmentation: In\u00a0vitro and clinical insights"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8882-1863","authenticated-orcid":false,"given":"Tomohiro","family":"Hakozaki","sequence":"first","affiliation":[{"name":"The Procter &amp; Gamble Company Mason Business Center  Mason Ohio 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