Vitamin C promotes cell proliferation to thicken skin

Photo by Laura Villela via Pexels

Researchers in Japan have discovered that vitamin C helps thicken the skin by directly activating genes that control skin cell growth and development. Their findings, published online in the Journal of Investigative Dermatology, suggest that vitamin C may restore skin function by reactivating genes essential for epidermal renewal.

This study was led by Dr. Akihito Ishigami, Vice President of the Division of Biology and Medical Sciences at Tokyo Metropolitan Institute for Geriatrics and Gerontology (TMIG), Japan, in collaboration with Hokuriku University, and ROHTO Pharmaceutical Co., Ltd.

“[Vitamin C] seems to influence the structure and function of the epidermis, especially by controlling the growth of epidermal cells. In this study, we investigated whether it promotes cell proliferation and differentiation via epigenetic changes,” said Dr. Ishigami in a press release.

To investigate the effect of vitamin C on skin regeneration, the team utilized laboratory-grown human epidermal skin models that closely mimic real human skin.

The researchers used this model and applied vitamin C at concentrations of 1.0 and 0.1 mM—levels comparable to those typically transported from the bloodstream into the epidermis. Upon assessing its effect, they found that vitamin C-treated skin exhibited a thicker epidermal cell layer without significantly affecting the stratum corneum by day seven. By day 14, the inner layer was even thicker, and the outer layer was found to be thinner, suggesting that vitamin C promotes the formation and division of keratinocytes. Samples treated with vitamin C showed increased cell proliferation, demonstrated by a higher number of Ki-67-positive cells—a protein marker present in the nucleus of actively dividing cells.

Notably, the study revealed that vitamin C helps skin cells grow by reactivating genes associated with cell proliferation. It achieves this by promoting the removal of methyl groups from DNA, a process known as DNA demethylation. When DNA is methylated, methyl groups attach to cytosine bases, which can prevent the DNA from being transcribed or read, thereby suppressing gene activity. Conversely, by promoting DNA demethylation, VC promotes gene expression and helps cells to grow, multiply, and differentiate.

The study suggests that vitamin C supports active DNA demethylation by sustaining the function of TET enzymes (ten-eleven translocation enzymes), which regulate gene activity. These enzymes convert 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC), a process in which Fe2+ is oxidized to Fe3+. VC helps maintain TET enzyme activity by donating electrons to regenerate Fe2+ from Fe3+, enabling continued DNA demethylation.

The researchers further identified more than 10,138 hypomethylated differentially methylated regions in vitamin C-treated skin and observed a 1.6- to 75.2-fold increase in the expression of 12 key genes related to proliferation. When a TET enzyme inhibitor was applied, these effects were reversed, confirming that vitamin C functions through TET-mediated DNA demethylation.

These findings reveal how vitamin C promotes skin renewal by triggering genetic pathways involved in growth and repair. This suggests that vitamin C may be particularly beneficial for older adults or those with damaged or thinning skin, enhancing the skin's natural ability to regenerate and strengthen itself.

“We found that [vitamin C] helps thicken the skin by encouraging keratinocyte proliferation through DNA demethylation, making it a promising treatment for thinning skin, especially in older adults,” said Dr. Ishigami.