Vitamin C and Sepsis Revisited: No Benefit

It wasn’t all that long ago when sepsis-related social media chatter focused on a new proposed treatment for septic shock: a combination of vitamin C, corticosteroids, and thiamin by intravenous (IV). In 2017, a critical care physician wrote that he had tried this treatment on his patients with success and that he would continue to do so. This news was exciting for many people who survived sepsis and those who lost loved ones to sepsis. Could it really be such an easy solution? [Please see editor’s note below]

The medical teams that treat patients with sepsis are always on the lookout for a better treatment. While this proposed treatment could be promising, physicians were cautious. There have been many potential sepsis treatments that turned out not to be helpful at all. That’s not to say the physicians weren’t hopeful. But before widely prescribing this treatment, they wanted more robust research. That meant running a randomized, blinded clinical trial, comparing vitamin c/thiamine/corticosteroids to a placebo, and objectively determine if the treatment works.

Another Look Vitamin C: The ACTS Study

In February 2018, researchers at 14 centers across the United States began enrolling patients into the ACTS clinical trial. The study ran until October 2019 and the results were published this past August.

A total of 101 patients received the drug combination, 99 a placebo. Otherwise, all patients received the usual sepsis care. The treatments lasted 72 hours.

The results were not promising. The researchers found the patients who received the study drug combination did not do any better than the other patients. The rate of kidney failure was similar, as well as the need for mechanical ventilation (needing a ventilator to help breathing). There also was little difference in how many patients died.

Both groups also experienced about the same number of serious adverse events  or complications. The most common ones were hyperglycemia (elevated blood sugar), hypernatremia (elevated blood sodium), and new hospital-acquired infections.

The study’s interpretation

Looking at the findings, the researchers determined that the combination of vitamin C, thiamine, and corticosteroids did not protect the patients’ organs. This was similar to what two earlier studies found.

The VITAMINS randomized clinical trial, which took place from May 2018 to July 2019 in Australia, New Zealand, and Brazil, compared patients who received the same drug combination to patients who received only hydrocortisone. The goal was to see if the combination would prevent or delay the need for medications to increase the patients’ blood pressure (vasopressors) and if they would live longer. The researchers did not find any differences between the two groups.

The CITRIS-ALI trial ran from September 2014 to November 2017, with a follow-up in January 2018. These patients received either high dose vitamin C or placebo. The researchers wanted to see if the vitamin would affect the amount of inflammation in the patients’ body and if it would prevent or minimize organ damage. For this study too, there was no significant differences between the two groups.

Continuing Vitamin C Research

There are over 2,000 studies from all over the world looking at sepsis, from early diagnosis to new proposed treatments. Seventy-five are or were looking at vitamin treatments, including vitamin C.

Researchers haven’t given up on the idea of using the vitamin at various points during the sepsis to septic shock timeline, as well as in combination with other drugs or vitamins. But at this point, giving vitamin C to patients with severe sepsis does not seem to provide any benefit. “These data do not support routine use of this combination therapy for patients with septic shock,” the ACTS study researchers concluded.

If you are interested in learning about on-going or upcoming studies on sepsis, you can visit ClinicalTrials.gov. There you can narrow down your search depending on what you are interested in, including location.

Editor’s Note: The study described in the article “Early use of high-dose vitamin C is beneficial in treatment of sepsis” was retracted by the journal on October 5, 2022.