“Impact of Vitamin C on Plasma Levels of Lipoprotein(a), Interleukin-6, and Fibrinolytic Activity” : A systematic review

Ischemic heart disease remains a leading cause of global mortality, primarily attributed to atherosclerosis-induced blockage in the coronary arteries. A key contributor to atherosclerosis is the accumulation of lipoprotein(a), which functions akin to vitamin C in vascular matrix healing. Elevated lipoprotein(a) levels correlate with increased Interleukin-6 (IL-6) and reduced fibrinolytic activities, further exacerbating atherosclerosis. This review aims to elucidate whether vitamin C supplementation mitigates lipoprotein(a) levels, and IL-6 expression, and enhances fibrinolytic activities in both humans (CAD patients, type 2 diabetic patients, and healthy adults) and animal models ( sepsis model of rats, transgenic mice, and wild type rats). A systematic search of Pubmed, Cochrane Library, and Google Scholar databases was conducted up to December 31, 2022, employing predefined selection criteria and a comprehensive search strategy. Of the 539 articles identified, 11 met the inclusion criteria, comprising 4 animal and 7 human studies. Animal trials demonstrated favorable outcomes with vitamin C supplementation, showing reductions in plasma lipoprotein(a) levels and decreased aortic accumulation of lp(a). Additionally, animals supplemented with vitamin C exhibited lower IL-6 production and enhanced fibrinolysis. Conversely, human studies reported no significant change in plasma lipoprotein(a) levels post-vitamin C supplementation (doses ranging from 500 mg to 4500 mg/day) in coronary artery disease (CAD) and healthy cohorts. However, supplementation did reduce serum IL-6 levels and increase fibrinolytic activities in both CAD and diabetic patients at doses between 1000 mg and 2000 mg of ascorbic acid. Vitamin C deficiency is prevalent among atherosclerosis patients, prompting lipoprotein(a) accumulation to counter intravascular scurvy in the absence of ascorbic acid. This review underscores the positive effects of vitamin C on atherosclerosis-associated factors, including lipoprotein(a), IL-6, and fibrinolytic activities. Optimal benefits are observed within the range of 1000 mg to 2000 mg/day, with higher doses conferring no additional advantages.