The effects of a novel amphiphilic vitamin C derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (disodium 2-(1,3,3-trimethyl-n-butyl)-5,7,7-trimethyl-n-octyl-L-ascorbyl phosphate, VCP-IS-2Na), possessing a C18 alkyl chain attached to a stable sodium L-ascorbic acid 2-phosphate (VCP-Na), on the proliferation of fibroblasts and collagen synthesis, and inhibition of matrix metalloproteinase-1 (MMP-1) in normal human fibroblasts, NHDFs and NB1RGBs, were evaluated. Compared with proliferation of non-treated fibroblasts, VCP-IS-2Na at 50 microM increased proliferation to 123 and 135% of that in NHDFs and NB1RGBs. On the other hand, L-ascorbic acid (vitamin C) and VCP-Na had little effect on proliferation. At a concentration of 5.0-50 microM, VCP-IS-2Na stimulated collagen synthesis with an effectiveness comparable to that of vitamin C and VCP-Na. The amount of type I collagen in the culture medium was increased by treatment with VCP-IS-2Na for 72 h, in a concentration-dependent manner. Maximum increases of 126 and 1067% were seen with VCP-IS-2Na at 50 microM in NHDFs and NB1RGBs, respectively, whereas vitamin C and VCP-Na only had a small effect. VCP-IS-2Na had a small inhibitory effect on MMP-1, but vitamin C did not inhibit MMP-1, and VCP-Na had very little effect. VCP-IS-2Na exerted its collagen synthesis-promoting activity after being converted to vitamin C by phosphatase. This vitamin C promoted proliferation, collagen synthesis and inhibition of MMP-1, which are prolonged through sustained conversion of VCP-IS-2Na.