|The key antioxidant of the body||Reverses the oxidation of lipids by the neutrophil reactive oxygen species (ROS) [32,33].|
Reduces depletion of other antioxidants (e.g., vitamin E and glutathione) to prevent oxidation of lipids, proteins and DNA [34,35,36,37,38,39,40].
|Norepinephrine biosynthesis||Cofactor for Dopamine ß-Hydroxylase, catalyzing the formation of norepinephrine from dopamine.|
Enhances adrenergic receptor activity .
|Dopamine biosynthesis||Facilitates recycling of the enzyme cofactor tetrahydrobiopterin (BH4); a required and rate-limiting step in the hydroxylation of l-tyrosine to form l-DOPA [42,43].|
|Vasopressin biosynthesis||Cofactor for peptidylglycine α-amidating monooxygenase (PAM), involved in vasopressin biosynthesis .|
|Connective tissue maintenance||Vital in wound healing; cofactor for Propyl 3-hydroxylase, prolyl 4-hydroxylase, and lysyl hydroxylase which catalyze the formation of procollagen and elastin biosynthesis [45,46].|
Catalyzes the hydroxylation of procollagen to form the collagen triple-helix .
Induces fibroblast collagen gene expression, stimulating the production of new collagen .
|Regulation of cellular gene expression in response to hypoxia and stress||Needed for the hydroxylation (thus downregulation) of Hypoxia Induced Factor 1α (HIF-1α) by propyl and lysyl hydroxylases and FIF-1 (asparaginyl hydroxylase or factor inhibiting HIF-1) [49,50,51].|
HIF-1α is a protein-transcription factor that regulates hundreds of genes in response to hypoxia and cellular stress, and is a marker of cellular hypoxia with increased expression in states of shock .
|Carnitine biosynthesis||Cofactor for γ-butyrobetaine hydroxylase, a dioxygenase involved in carnitine synthesis, which transports fatty acids into the mitochondria [53,54].|
L-Carnitine can down-modulate tumor necrosis factor (TNF-α) by endotoxins, affect lipid metabolism, and reduce septic shock severity .
|Phagocytic cell function||Severe vitamin C deficiency (scorbutic) results in impaired neutrophilic phagocytosis and ROS generation [56,57,58,59,60].|
In situations of impaired neutrophilic ROS production, vitamin C enhances the hexose monophosphate shunt (HMPS) and antibody dependent cell cytotoxicity (ADCC) resulting in increased bacterial killing .
Improves chemotaxis .
Accumulation in neutrophils may protect them from neutrophil dependent oxidative bursts [62,63].
Reduces inflammation and ROS via attenuation of NF-κB activation [64,65,66].
|Inflammation: Immune cell clearance||Promotes neutrophil apoptosis, instead of necrosis via activation of caspase-3 proteins [67,68].|
High-dose intravenous vitamin C (HDIVC) treatment has been shown to decrease circulating plasma cell-free DNA (resulting from neutrophil extracellular trap (NET) formations, or NETosis), and have been implicated in sepsis-induced end-organ failure [69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84].
|Lymphocytic function||May promote lymphocytic proliferation, differentiation, and maturation [85,86].|
|Epigenetic modulation||Cofactor for ten-eleven translocation (TET) enzymes and Jumonji-C domain-containing histone demethylases (JHDMs); vitamin C increasing enzymatic activity of both, resulting in increased DNA demethylation and histone demethylation, respectively, which controls gene transcription and gene activation or repression [87,88,89].|
|Direct antimicrobial activity||High concentrations directly inhibit bacterial growth and exhibits bactericidal activity in vitro [90,91].|
|Inflammatory mediators||Modulates cytokine production and can decrease circulating histamine levels [61,92,93,94].|
|Endothelial function||HDIVC decreases circulating thrombomodulin, an endothelial membrane protein receptor for thrombin that converts thrombin to an anticoagulant capable of activating protein C .|
Decreases plasma Syndecan-1 levels, a by-product of endothelial glycocalyx shedding [96,97,98,99,100,101,102,103,104,105,106,107,108].
|Platelet function and Thrombosis||Alters platelet oxidative states by inhibiting CD40 ligand expression on platelet surfaces .|
Prolonged platelet exposure to HDIVC increases Thromboxane-B2 and Prostagladin-E2 levels [110,111].
HDIVC stabilizes ADAMTS13 levels and its von-Willebrand factor cleavage activity .