Topical Menaquinone-7 (Vitamin K2, MK-7) as a Mitochondrial Bioenergetic Activator for Skin Anti-Aging: Mechanistic Evidence in Skin Cells and a Randomized Split-Face/Neck Study

Abstract

Mitochondrial dysfunction contributes to skin aging by limiting cellular energy supply, shifting redox balance, and amplifying oxidative injury, which together favor extracellular matrix breakdown and loss of tissue mechanics. Vitamin K2 (menaquinone-7; MK-7) has been proposed to support mitochondrial electron transport, yet its bioenergetic activity in the skin and its effects on aging-related outcomes remain insufficiently characterized. To evaluate whether MK-7 can improve mitochondrial bioenergetics in skin-relevant cells under oxidative stress and whether these effects translate into quantifiable anti-aging benefits in a controlled human study. In vitro, human skin cells were exposed to UVA or hydrogen peroxide to model oxidative stress and then treated with MK-7. ATP content, NAD+/NADH ratio, mitochondrial membrane potential (ΔΨm), mitochondrial DNA (mtDNA) copy number, respiratory chain complex activities (I–V), and senescence-associated secretory phenotype (SASP) expression were assessed using established assays. In vivo, a randomized, double-blind, split-face/neck, vehicle-controlled trial enrolled women aged 35–60 years (n = 30 completers). Participants applied a 0.05% MK-7 face-and-neck cream to one randomized side and placebo to the contralateral side twice daily for 8 weeks. Wrinkles/roughness, elasticity, and sagging were instrumentally quantified at baseline and weeks 2, 4, and 8. MK-7 increased ATP production, elevated the NAD+/NADH ratio, restored ΔΨm, preserved mtDNA copy number under oxidative challenge, enhanced activities of multiple respiratory complexes, and reduced UVA-induced SASP marker expression. In human efficacy evaluations, MK-7 produced significant improvements versus placebo in wrinkle roughness on face and neck, improved elasticity parameters, and attenuated sagging over 8 weeks. MK-7 was associated with improved mitochondrial bioenergetic readouts in vitro and measurable anti-aging effects in a split-face/neck study, supporting further development of mitochondrial targeting approaches for skin aging.