Critical illness decreases vitamin C concentration in the plasma due to the abrupt release of oxidants in response to sepsis. This article discusses various studies that were conducted to understand the effect of vitamin C administration in critical care.

Vitamin C in critical illness

Studies as early as 1990 have demonstrated the superiority of ascorbate as the most effective antioxidant in humans. Vitamin C deficiency mimics:

• Critical illness by causing hypotension
• Exaggerated inflammation
• Poor wound healing

Administration of vitamin C to patients with sepsis has been shown to lower CRP and other pro-inflammatory biomarkers and decrease organ failure.

Studies

A highly contentious and controversial article by Paul E Marik in 2017, concluded that the early use of intravenous vitamin C, together with corticosteroids and thiamine, is effective in preventing progressive organ dysfunction, and in reducing mortality of patients with severe sepsis and septic shock.

These findings spurred widespread interest in the use of vitamin C for treating sepsis since they claimed a more than 4-fold decrease in mortality rates in the treatment group.

Subsequently, Fowler et al, in 2020, through the CITRIS-ALI RCT, concluded that the infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Similarly, Sevransky et al, in 2021, published results from the VICTAS RCT which studied over 500 participants and reported that the cocktail failed to decrease the need for vasopressors and ventilator use.

While the earlier studies showed no benefit of vitamin C in sepsis, results from the latest phase 3, multicentric, RCT - Lessening Organ Dysfunction with Vitamin C (LOVIT) proved that use of Vitamin C was associated with poorer outcomes in patients.

Lamontagne et al conducted a randomised, placebo-controlled trial in which 872 patients were randomised to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. They concluded that those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received a placebo. 

Given the reports of harm related to intravenous vitamin C therapy, we recommend that high-dose vitamin C must not be used in regular clinical practice in the ICU with the goal to reduce sepsis-related mortality.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr Aju Mathew is a medical oncologist, haematologist, internist and epidemiologist practising in Kochi.

Dr Athul Raj and Dr Edwin Saji are research associates at Kerala Cancer Care, Kochi, India.