TABLE 3.

Role and potential benefits of vitamin C on various organ systems, adapted from; all described benefits were derived from clinical studies unless stated explicitly.

Patient group/Afflicted organ system	Special role of vitamin C in the organ system	Pathology/Condition studied	Pathophysiology related to potential usefulness of vitamin C	Benefits from vitamin C administration
				Described benefits of vitamin C in the organ system/Condition	Described or potential mechanisms through which vitamin C may be beneficial
					Mitigation of oxidative stress + restoration of other antioxidants	Improved endothelial function and microcirculation	Improved vasopressor response	Improved platelet function and decreased capillary plugging	Reduced extravasation and edema	Enhanced immune function and antibacterial properties
Central nervous system	● Elevated levels up to 80 times to protect neurons (92, 93) ● Essential for the differentiation and myelinization of neurons (94, 95)	Stroke/Cerebral ischemia	● I/R injury and subsequent oxidative stress ● Shift of vitamin C from the intra- to extracellular compartment and intraneuronal vitamin C deficiency (75)	● Reduces infarct volume in experimental models (83–85) ● Decreases ischemic stroke-related lipid peroxidation (96)	×	×		×	×
		ICB Head trauma	● Hemorrhage/tissue damage ● Increased ICP and subsequent reduction of cerebral perfusion	● Inversely correlated with major diameter of lesion and severity of neurological impairment (97)	×	×	×	×	×	×
Cardiovascular system	● Frequent vitamin C deficiency (98) ● Vasopressor synthesis	Cardiac surgery Post-reanimation	● I/R Injury and subsequent oxidative stress ● Hemodilution and extracorporeal circulation ● Compromised cardiac function and hemodynamics	● Decreases myocardial injury (99) and higher cardiac index (99) ● Decreases rate of post-op arrhythmia (76–82), ICU (76, 79, 80) and hospital stay (76, 79–81, 100) and ventilation time (76, 77, 81) ● Decreases bleeding (101)	×	×	×	×	×	×
		CAD and MI	● Chronic inflammatory disease leading to increased need of antioxidants	● Promotes endothelial and NO dependent vasodilation ● Reduces AKI after coronary angiography (89)	×	×	×	×
Respiratory system	● High levels in alveolar type II cells and macrophages (102) ● Collagen synthesis, endothelial restoration and alveolar proliferation (103)	ARDS Pneumonia COPD Asthma Cystic fibrosis	● Most common organ system to suffer from reactive oxygen species (103) ● Acute or chronic inflammation leading to increased need of antioxidants ● Plasma histamine levels correlate inversely with vitamin C levels (102)	● Reduces I/R injury and lung damage in experimental models (65) ● Reduces pulmonary inflammation (104) ● Reduces mortality in ARDS (105) ● Prevents/ameliorates pneumonia (106, 107)	×	×	×		×	×
Renal system	● Renal excretion	Contrast mediated nephropathy	● Drug toxicity	● Decreases risk for AKI (89)	×	×
		COVID-19 SIRS	● Systemic inflammation and oxidative stress ● Vitamin C can reduce the expression of ACE2, which hinders the entry of the virus into cells, and stabilizes blood pressure (108)	● In experimental models: protects kidneys from injuries caused by external factors, facilitates repair (108)	×	×
Oncology	● Induces pluripotent stem cell differentiation ● Drug metabolism	Chemo- and radiotherapy	● Reduced uptake due to anorexia and cachexia ● Drug toxicity ● Reduced organ function ● Clotting disorder	● Decreases drug toxicity (90) ● Attenuation of apoptosis and DNA damage (91) ● Decreased intestinal mucosa damage in experimental design (109) ● Increases chemosensitivity	×	×				x
Critical illness	● Frequent vitamin C deficiency (73–75) ● Drug metabolism	Sepsis/septic shock,	● Systemic inflammation ● Imbalance between vitamin C loss/requirements and vitamin C uptake	● Reduces vasopressor requirement (86, 87) ● Reduces mortality (86, 87, 105, 110, 111) and organ failure (87) ● Shortens ICU stay (111)	×	×	×	×	×	×
Burn injury	● Induces pluripotent stem cell differentiation ● Collagen and carnitine synthesis	Severe thermal injury with large% TBSA burned Inhalation trauma	● I/R Injury and subsequent oxidative stress ● Hemodilution ● Large wound surfaces and increased losses ● “After-burn” and disturbed microperfusion	● Reduction of resuscitation volume (112–114) ● Shorter time to wound healing (115) ● Reduces vasopressor requirement (113) ● Increases urine output (113, 116) ● Shorter mechanical ventilation (112) ● Improved hospital survival (117)	×	×	×	×	×	×

ACE II, angiotensin converting enzyme II; ARDS, acute respiratory distress syndrome; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; ICP, intracranial pressure; ICU, intensive care unit; ICB, intracranial bleeding; I/R, ischemia- and reperfusion; MI, myocardial infarction; NO, nitric oxide; SIRS, systemic inflammatory response syndrome; TBSA, total body surface area.