Chiara Pollicino

Recently, a growing interest has been focused to the role of vitamin C in chronic diseases. Type 2 Diabetes Mellitus and the Metabolic Syndrome are complex, chronic disorders intrinsically linked by a common underlying element, such as chronic low-grade inflammation and excessive oxidative stress. Vitamin C, or ascorbic acid, is an essential water-soluble micronutrient and a highly potent non-enzymatic antioxidant that is critical for scavenging reactive oxygen species and maintaining cellular redox balance. It represents a cofactor for many enzymes, being involved in many biological functions, such as normal immune system functioning, catecholamine metabolism, dietary iron absorption, and collagen biosynthesis. Individuals with type 2 diabetes mellitus and metabolic syndrome frequently exhibit lower circulating and dietary vitamin C levels compared to healthy controls, a deficiency that may be associated with disease-related inflammation and higher body weight. In this sense, it has been shown that vitamin C improves skeletal muscle insulin sensitivity in experimental settings and modulates critical functions like vascular endothelial health. However, this potential is challenged by the fact that chronic hyperglycemia can interfere with the active cellular uptake and transport of vitamin C, potentially leading to relative intracellular deficiency in diabetic patients regardless of intake. It is interesting to note that different studies have demonstrated an inverse relationship between vitamin C concentrations and the prevalence of metabolic syndrome and type 2 diabetes. Vitamin C supplementation in people with diabetes and metabolic syndrome has controversial effects. While several studies indicate a significant reduction in fasting blood glucose or HbA1c, others revealed no significant effect on insulin resistance. This review aims to explore the pathophysiological role and therapeutic potential of vitamin C in type 2 diabetes and metabolic syndrome.

In the last decades, it has become increasingly evident that the role of vitamin D extends beyond the regulation of calcium homeostasis and the maintenance of bone health. A significant extraskeletal function of vitamin D is its role in modulating the immune system, particularly highlighted in the context of immune-mediated inflammatory diseases, where correlations between vitamin D status and genetic variations in the vitamin D receptor have been observed about the incidence and severity of these conditions. Additionally, different studies have reported the existence of immunomodulatory effects of vitamin D, particularly the effects of vitamin D on dendritic cell function, maturation, cytokine production, and antigen presentation, and that its deficiency may be associated with a sub-inflammatory state. In this sense, different clinical trials have been conducted to assess the therapeutic efficacy of vitamin D in different immune-mediated inflammatory disorders, including asthma, atopic dermatitis (AD), rheumatoid arthritis (RA), psoriasis, thyroid diseases, infectious diseases, and systemic lupus erythematosus (SLE). This review will provide a comprehensive overview of the current understanding of the molecular mechanisms underlying vitamin D’s immunomodulatory properties, its role, and innovative therapeutic applications in patients with immune-mediated inflammatory diseases.