Introduction: We aimed to investigate the effect of orally ingested collagen peptides (CPs) on skin condition and elucidate their mechanism of action. Methods: A randomized, placebo-controlled, double-blind trial was conducted in 99 healthy Japanese women, aged 35–50 years. The subjects were randomized into 3 groups (33 subjects/group) to receive 1 or 5 g of CP or placebo once daily for 12 weeks. Skin water content, transepidermal water loss (TEWL), skin elasticity, and skin thickness were evaluated before treatment and after 4, 8, and 12 weeks of treatment. The level of natural moisturizing factor (NMF) constituents in the stratum corneum (SC) was quantified before treatment and after 12 weeks of treatment. Results: Oral ingestion of CP increased the water content in the SC and epidermis and decreased TEWL. Furthermore, the NMF level in the SC was increased. However, skin elasticity and skin thickness remained unchanged. Conclusions: The improvement in skin water content following the oral ingestion of CP can be attributed to an increase in the level of NMF in the SC. Trial Registration: UMIN000030375 (retrospectively registered).

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