Does High-Dose Vitamin C Help Treat Covid-19 Patients in Intensive Care?

Covid-19 Pandemic has profoundly affected every area of medicine, but intensive care and infectious diseases have undoubtedly been the most affected and attracted the most attention. Around 5-6% of patients with confirmed Covid-19 receive advanced treatment in intensive care, and one of the main clinical conditions intensive care specialists manage is sepsis.

Sepsis is organ damage caused by an abnormal response to infection. It is a highly critical condition with a high mortality rate and requires intensive medical intervention. Standard treatment includes early recognition, rapid fluid administration, antibiotics, and respiratory and circulatory support. Nevertheless, a small number of doctors persistently claim that alternative approaches such as high-dose vitamin C are also effective in treating sepsis and Covid-19. We therefore examine the role of high-dose vitamin C in sepsis treatment in light of the latest scientific evidence.

The Surprising History of Vitamin C

In 1519, Portuguese explorer Ferdinando Magellano led a fleet of five ships setting sail from Andalusia. Seeking a connection between Europe and Asia, he undertook an expedition that would enter the annals of history—an exceptionally bold venture for its time. With no intermediate ports for resupplying, he embarked on a voyage across the open sea that would last months, not knowing what lay ahead or whether he would succeed. During this long, arduous journey, the crew began developing strange symptoms that grew increasingly severe: fatigue, weight loss and bleeding gums. Later, sailors lost their teeth, and even small wounds in their gums and empty tooth sockets enlarged and became easily infected. By the end of an expedition lasting almost 3 years, 80% of the crew had died. As far as we know, the history of vitamin C dates back to those days—to one of history’s great ocean voyages and sailors deprived of fresh fruit and vegetables for long periods. Some 200 years after this voyage, British surgeon James Lind identified vitamin C deficiency and the name of the disease: scurvy, also known as the sailors’ disease.

What Are the Properties of Vitamin C?

Known in chemistry as ascorbic acid, vitamin C is an odorless organic compound. It is a monosaccharide derivative, structurally similar to glucose and other six-carbon monosaccharides. Ascorbic acid is found in all living tissues. This vitamin is widespread in nature, with fresh fruits and vegetables providing the richest sources.

Many animals and plants can produce their own vitamin C from glucose. Humans, some fruit bats, guinea pigs and humanlike primates cannot make vitamin C and must obtain it from food. It is therefore essential for this group of organisms, including humans: the body cannot produce it and must obtain it externally. Water-soluble vitamin C plays a role in physiological processes such as immune function and collagen production. It also acts as an antioxidant in many chemical reactions in the body.

The Origins of the Idea of Vitamin C for Sepsis Treatment...

Today, vitamin C deficiency severe enough to cause scurvy is very rare and easily treated. However, considering its role in the immune system, researchers thought it might have a place in treating sepsis. Sepsis is a clinical condition in which an infection progresses and affects other organs. When sepsis cannot be controlled, multiple organ systems, including the heart and circulatory system, are affected, resulting in life-threatening low blood pressure. These patients need monitoring in intensive care. This advanced condition is called septic shock. Numerous studies have led to substantial advances in treating sepsis and septic shock. Nevertheless, the risk of death remains high. Many further studies therefore continue to examine how it develops and how to treat it.

The idea that vitamin C might have a role in sepsis treatment does not arise solely from its immune functions. It was considered worth investigating because it helps synthesize substances produced during severe infection: catecholamines, molecules particularly important for heart and vascular function, and cytokines, molecules produced when infection or other causes trigger inflammation. Some studies have also shown low vitamin C levels in patients who develop sepsis.

Results of Studies of Vitamin C for Sepsis

Case reports and case series suggested that vitamin C might produce some favorable outcomes in patients diagnosed with sepsis. However, these weak and conflicting findings were insufficient for vitamin C to become a recommended treatment in sepsis guidelines. Let us examine some of the most prominent studies.

In 2017, a clinical trial published in Chest generated excitement: Paul Marik and colleagues divided patients with sepsis into 2 groups. One received standard sepsis treatment; the other also received vitamin C, steroid medication and thiamine (vitamin B1). The rationale for this combination was that each molecule in the three-drug regimen theoretically had properties capable of correcting the pathophysiology of sepsis. The results provided some evidence that the combination reduced mortality and damage to organs affected by sepsis. However, the study had methodological limitations. Nevertheless, it generated great interest and surprise, leading to further research.

A more comprehensive meta-analysis published in 2019, evaluating whether vitamin C has a place in intensive care, also sheds light on the subject. Of the 16 studies included, 6 investigated vitamin C treatment in intensive care patients with sepsis. The meta-analysis showed that vitamin C had no effect on patients’ length of stay in hospital or intensive care, or on survival.

Then, in October 2019, JAMA published a clinical trial called "ALI-CITRUS." It enrolled 167 patients in intensive care receiving mechanical ventilation who had sepsis and ARDS (acute respiratory distress syndrome, lung dysfunction generally associated with sepsis). Patients were divided into two subgroups, one of which received high-dose intravenous vitamin C in addition to standard sepsis treatment. The results did not confirm expectations. The severity of sepsis-related organ damage was the same in the 2 groups. Blood markers indicating inflammation and vascular injury were also similar in the 2 groups. Although 28-day mortality was better in the vitamin C group, the analysis did not adjust for other variables influencing this outcome. It therefore did not allow a firm conclusion that mortality was lower in the vitamin C group.

Finally, a recent trial called "VITAMINS," which could be considered a summary of research in this field to date, was published in JAMA in January 2020. Based on the hypothesis that deficiencies of vitamin C and vitamin B1 might contribute to sepsis, it enrolled a substantial number of patients: 216 with septic shock. Half received high-dose vitamin C, vitamin B1 and cortisone in addition to standard treatment; the other half received only cortisone medication alongside standard treatment. The results showed that adding vitamin C or vitamin B1 provided no additional benefit.

Conclusion

Despite theory and reasoning, there is currently no evidence that vitamin C improves survival when treating serious conditions such as sepsis and septic shock. Research continues in this critically ill patient population, with nearly 20 studies still underway. Their results will undoubtedly clarify the issue further. In light of current scientific evidence, however, it is clear that high-dose vitamin C provides no treatment benefit. For this life-threatening condition, the undisputed mainstay of care is the approach recommended by treatment guidelines: rapid administration of antibiotics, treatment of circulatory collapse with intravenous fluids and catecholamines to support circulation, and mechanical ventilation when necessary.

Below, it can be seen that high-dose vitamin C is not included in national or international COVID-19 treatment guidelines:

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