Table 2.

Summary of key in vitro studies investigating potential effects of vitamin C on the skin.

Study Description	Measured Parameters	Outcome and Comment	Reference
Effects on collagen and elastin synthesis
Vit. C effects on collagen and elastin synthesis in human skin fibroblasts and vascular smooth muscle cells.	Monitored vit. C time of exposure and dose on collagen synthesis and gene expression, and elastin synthesis and gene regulation.	Vit. C exposure increased collagen, decreased elastin. Stabilization of collagen mRNA, lesser stability of elastin mRNA, and repression of elastin gene transcription.	[81]
Effect of vit. C on collagen synthesis and SVCT2 expression in human skin fibroblasts. Vit. C added to culture medium for 5 days.	Vit. C uptake measured into cells, collagen I and IV measured with RT-PCR and ELISA, and RT-PCR for SVCT2.	Vit. C increased collagen I and IV, and increased SVCT2 expression.	[73]
Effect of vit. C on elastin generation by fibroblasts from normal human skin, stretch-marked skin, keloids and dermal fat.	Immunohistochemistry and western blotting for detection of elastin and precursors.	50 and 200 µM vit. C increased elastin production, 800 µM inhibited. No measures of vit. C uptake into cells.	[69]
Effects on morphology, differentiation and gene expression
Vit. C addition to cultures of rat keratinocytes (REK).	Effect on differentiation and stratum corneum formation.	Morphology showed enhanced stratum corneum structure, increased keratohyalin granules and organization of intercellular lipid lamellae in the interstices of the stratum corneum. Increased profilaggrin and filaggrin.	[97]
Effect of vit. C on human keratinocyte (HaCaT) cell line differentiation in vitro.	Measured development of cornified envelope (CE), gene expression.	CE formation and keratinocyte differentiation induced by vit. C, suggesting a role in formation of stratum corneum and barrier formation in vivo.	[99]
Effect of vit. C supplementation on gene expression in human skin fibroblasts.	Total RNA nano assay, for genetic profiling, with and without vit. C in culture medium.	Increased gene expression for DNA replication and repair and cell cycle progression. Increased mitogenic stimulation and cell motility in the context of wound healing. Faster repair of damaged DNA bases.	[78]
Effect of vit. C on dermal epidermal junction in skin model (keratinocytes and fibroblasts).	Keratinocyte organisation, fibroblast number, basement membrane protein deposition and mRNA expression.	Vit. C improved keratinocyte and basement membrane organisation. Increased fibroblast number, saw deposition of basement membrane proteins.	[102]
Effect of vit. C on cultured skin models—combined human epidermal keratinocytes and dermal fibroblasts.	Monitored morphology, lipid composition.	Vit. C, but not vit. E, improved epidermal morphology, ceramide production and phospholipid layer formation.	[98]
Protective effects against UV irradiation
Effect of vit. C on UVA irradiation of primary cultures of human keratinocytes.	Vit. C added in low concentrations, monitored MDA, TBA, GSH, cell viability, IL-1, IL-6 generation.	Vit. C improved resistance to UVA, decreased MDA and TBA levels, increased GSH levels, decreased IL-1 and IL-6 levels.	[109]
Effect of vit. C uptake into human keratinocyte (HaCaT) cell line on outcome to UV irradiation.	Accumulation of vit. C in keratinocytes, antioxidant capacity by DHDCF and apoptosis induction by UV irradiation.	Keratinocytes accumulated mM levels of vit. C, increasing antioxidant status and protecting against apoptosis.	[108]
Effect of UVB on vit. C uptake into human keratinocyte cell line (HaCaT) and effects on inflammatory gene expression.	Cellular vit. C measured by HPLC, mRNA expression for chemokines, western blotting for SVCT localisation.	Vit. C uptake was increased with UVB irradiation, chemokine expression decreased with vit. C uptake.	[107]
Protective effects against ozone exposure
Effect of antioxidant mixtures of vit. C, vit. E and ferulic acid on exposure of cultured normal human keratinocytes to ozone.	Cell viability, proliferation, HNE, protein carbonyls, Nrf2, NFkappaB activation, IL-8 generation.	Vit. C-containing mixtures inhibited toxicity. The presence of vit. E provided additional protection against HNE and protein carbonyls.	[118]
Protection of cultured skin cells against ozone exposure with vit. C, vit. E, and resveratrol. 3-D culture of human dermis—fibroblasts with collagen I + III.	Cell death, HNE levels, expression of transcription factors Nrf-2 and NfkappaB	Extensive protection against cell damage with mixtures containing vit. C. Increased expression of antioxidant proteins. Additional effect of vit. E + C. No effect with Vit. E alone.	[119]