Cardiovascular Effects of Cyclical Dietary Vitamin C Withdrawal in Mice Deficient in Internal Synthesis Vitamin C and producing human lipoprotein (a): Gulo(-/-); Lp(a)+

Abstract

Background: Scientific knowledge of the impact of periodic dietary vitamin C intake and withdrawal on the development of cardiovascular disease has been limited. Our earlier study using a transgenic Gulo(-/-); Lp(a)+ mouse model mimicking human metabolism in respect to a lack of internal synthesis of vitamin C and expression of human lipoprotein (a) [Lp(a)], a recognized risk factor for cardiovascular disease, showed that vitamin C deficiency triggers vascular deposition of Lp(a) and atherosclerosis. In this study we used this mouse model to investigate the effect of cyclical vitamin C withdrawal and its continuous supplementation on metabolic factors related to cardiovascular health, such as lipid profile and vascular plaque development. Methods: Gulo (-/-); Lp (a)+ mice were subjected to 4 weeks of dietary vitamin C withdrawals followed by 4 weeks of a resupplementation pattern for 20 weeks in total. Mice supplemented with vitamin C continuously for 20 weeks served as reference control. Mice were harvested after 4, 8, 12, 16, and 20 weeks and analyzed. Serum ascorbic acid, lipid profile, lipoproteins, vascular lesion, and Lp(a) deposition were evaluated. Results: We observed that periodic vitamin C withdrawals resulted in a less healthy blood lipid profile and showed indications of metabolic adaptation to vitamin C withdrawals. In addition, mice experiencing recurring dietary vitamin C withdrawals were prone to the development of early atherosclerotic lesions with Lp(a) deposition in the structurally compromised areas of the vascular wall, compared to mice continuously supplemented with vitamin C. Conclusion: This study further supports the importance of consistent and sufficient intake of vitamin C in assuring optimum profile of blood risk factors, and maintaining vascular wall integrity and optimal cardiovascular health.