Oral keratin hydrolysate Kera-Diet® metabolites boost human fibroblast activity and protect against oxidative stress

Maintaining skin homeostasis and combating signs of aging often relies on supporting dermal fibroblast function, which can decline due to factors like oxidative stress. Current topical strategies have limitations in deep tissue penetration and sustained efficacy. Nutricosmetic approaches, utilizing orally ingested compounds, offer a systemic route to deliver beneficial molecules to the skin. This study explores whether a sustainable, keratin-derived hydrolysate (Kera-Diet®) can provide bioavailable metabolites that directly enhance fibroblast function and resilience against oxidative damage, addressing a gap in effective systemic skin support.

Ten healthy fasted men ingested a single dose of 5,000 mg Kera-Diet®. Plasma amino acid levels were monitored via UPLC-MS over 240 min to identify the peak absorption time (~20 min). Paired naïve human serum (NHS, pre-ingestion) and enriched human serum (EHS, peak time) were collected. Primary human dermal fibroblasts were then incubated with either NHS or EHS. Researchers assessed fibroblast viability, migration using a scratch assay, and hydration markers including glycosaminoglycans and hyaluronan release. Oxidative stress was induced with H₂O₂, and endpoints such as reactive oxygen species (ROS) via DCF-DA, apoptosis (caspase-3), ER stress (XBP1 mRNA), and senescence (β-galactosidase) were measured.

Circulating amino acid levels peaked at approximately 20 min post-ingestion of 5,000 mg Kera-Diet®. When primary human dermal fibroblasts were exposed to EHS (serum collected post-Kera-Diet® ingestion) compared to NHS (pre-ingestion serum), significant improvements in key skin health markers were observed. EHS increased glycosaminoglycan release by +11% and hyaluronan release by a notable +43%. Furthermore, EHS significantly enhanced early fibroblast migration in the scratch assay. Under induced oxidative stress, both Kera-Diet® (applied in vitro) and EHS (applied ex vivo) demonstrated protective effects. They mitigated cellular stress by reducing ROS levels, decreasing caspase-3 activity (a marker of apoptosis), blunting XBP1 mRNA induction (indicating reduced ER stress), and lowering senescence markers. Importantly, these protective effects were achieved while preserving overall fibroblast viability.

EHS increased hyaluronan release by +43% and glycosaminoglycans by +11%, demonstrating enhanced fibroblast hydration and extracellular matrix support.