L. Law, L. Luo, N. Zhang
Background: Skin aging is multifactorial, and finished multi-ingredient oral beauty supplements require dedicated clinical evaluation because their effects cannot be inferred from individual ingredient data alone. Objective: To explore, in a 56-day single-arm open-label study, whether daily oral intake of NatureU(R) Mind Care BeautyU Caps is associated with within-participant changes in crow's-feet wrinkle count (primary endpoint), stratum corneum hydration (secondary endpoint), and additional exploratory skin-aging parameters in adult women. Methods: A single-center, open-label, single-arm exploratory study enrolled 33 healthy women aged 36-56 years, eligible only if baseline cheek hydration was below 60 corneometer units (C.U.); 31 completed the protocol. Participants took one capsule orally once daily for 56 consecutive days. Assessments at D0, D28 and D56 used PRIMOS CR, Corneometer CM 825, Cutometer MPA580, Glossymeter, Colorimeter CL400, Mexameter MX18, VISIA CR, DermaScan and a structured self-assessment. Results: PRIMOS CR crow's-feet wrinkle count fell from 965.3 {+/-} 333.7 at D0 to 514.2 {+/-} 171.0 at D56 (-46.73%; Wilcoxon P = 1.2e-06), and Corneometer hydration rose from 44.3 {+/-} 7.8 to 70.3 {+/-} 9.9 (+58.57%; P = 1.2e-06). Both changed in all 31 completers. Average wrinkle depth changed only non-significantly (-4.81%; P = 0.058), decreasing in 19 participants and increasing in 12. Individual-participant data obtained after version 1 show that the reduction in wrinkle count was almost exactly proportional across a 5.9-fold range of baseline values (D56/D0 ratio 0.535 {+/-} 0.041; coefficient of variation 7.7%, lower than any other endpoint), was uncorrelated with baseline severity (r = -0.15, P = 0.42), was complete by D28 (D56/D28 ratio 0.990 {+/-} 0.096), and was uncorrelated with the change in wrinkle depth (r = +0.30, P = 0.096) or hydration (r = +0.23, P = 0.21). No adverse reactions were reported. Conclusion: Daily intake over 56 days was associated with an increase in stratum corneum hydration that cannot be accounted for by the low-hydration entry criterion alone; regression to the mean is bounded at approximately 8-30% of the observed rise under a range of assumptions. A reduction in crow's-feet wrinkle count was also recorded, but its uniformity across participants, its independence of baseline severity, its completion at the first follow-up visit, and the absence of the PRIMOS segmentation threshold, region-of-interest definition and image-registration parameters needed to reproduce it mean that the authors do not interpret it as evidence of a biological anti-wrinkle effect. This conclusion supersedes that of version 1. Findings are hypothesis-generating; randomized, placebo-controlled trials are required.