Sepsis, a bodywide inflammation in response to infection, is a leading cause of death in U.S. hospitals, with up to 300,000 deaths reported each year, according to the National Institute of General Medical Sciences. New research led by Virginia Commonwealth University and published in the October issue of the Journal of the American Medical Association suggests that patients with sepsis and septic lung injury could have a better chance of survival and recover more quickly when treated with vitamin C infusions.

Alpha A. “Berry” Fowler III, M.D., a professor in the Division of Pulmonary Disease and Critical Care Medicine in the Department of Internal Medicine at the VCU School of Medicine, has studied sepsis and related lung injury for over 30 years, pioneering the use of vitamin C in hopes of creating a more effective therapy than the current standard of care. Acute lung injury is one of the leading causes of death in sepsis.

Fowler’s latest research discovered that intravenous vitamin C therapy reduced mortality in septic patients from 46% in the placebo group to almost 30% in the vitamin C group at day 28.

“This therapy could potentially transform the way we care for sepsis patients. We may have found a lifesaving therapy,” said Fowler, who is also executive director of the VCU Johnson Center for Critical Care and Pulmonary Research and associate director for team science at the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research. “While further research is needed, the results from our preliminary study are encouraging.”

Shortening hospital and intensive care unit stays

Designed to study the effect of vitamin C on organ failure, a common complication of sepsis that often leads to death, the CITRIS-ALI trial showed that patients receiving intravenous vitamin C spent significantly fewer days in the intensive care unit and in the hospital overall.

“We conducted this phase II, proof-of-concept trial to explore if vitamin C is a more effective therapy for organ failure than the current standard of care for sepsis,” Fowler said. “We did not find evidence that vitamin C improves sepsis-related organ failure in this particular trial, but it significantly reduced how long patients were hospitalized.”

On average, the vitamin C group spent three fewer days in the ICU (seven days compared to 10) at day 28 and a week less in the hospital overall (15 days versus 22) by day 60 than the placebo group.

A $3.2 million National Institutes of Health grant funded the clinical trial that involved 167 patients across seven enrollment sites, including the Cleveland Clinic, the Medical College of Wisconsin, the University of Kentucky and Emory University. It was the first randomized, double-blind, placebo-controlled multicenter trial related to vitamin C and its potential impact on sepsis and acute respiratory distress syndrome, a lung disease often associated with sepsis worldwide. The study was conducted from September 2014 to November 2017.

Fowler does not rule out that vitamin C could improve organ failure in subsequent trials, depending on the study design. “Higher doses of vitamin C and longer administration times could make a big difference,” Fowler said.

Other possible benefits for patients and hospitals

More studies are underway to understand how vitamin C could benefit other conditions that involve systemic or significant inflammation. Fowler consults on various trials across VCU Health, including a bone marrow transplant trial at VCU Massey Cancer Center.

“We hope to better understand the potential benefits of vitamin C in treating graft-versus-host disease, a condition where donor cells mistakenly attack a recipient patient’s tissue after transplant, leading to severe inflammation,” Fowler said.

Intravenous vitamin C may also provide hope to patients undergoing treatment for atrial fibrillation, a condition in which the heart beats irregularly, and in open-heart surgery patients. In both cases, vitamin C may be able to reduce inflammation, a common side effect of cardiac procedures.

“The list of potential applications for vitamin C therapy goes on and on,” Fowler said. “We are actively looking into the benefits of vitamin C therapy in cases of cystic fibrosis and head injuries.”

Besides improving the physical health of patients, vitamin C therapy could also improve the financial health of hospitals. Sepsis is a major contributor to health care costs in the U.S. and worldwide. Patients with sepsis accounted for $23.7 billion in U.S. hospital costs in 2013 alone, according to the Agency for Healthcare Research and Quality.

“Taking care of a septic patient in the ICU costs tens of thousands of dollars each day,” Fowler said, pointing out costs for nursing, equipment, antibiotics and imaging studies, just to name a few. “Improving clinical outcomes for sepsis means significant cost savings for the U.S. health care industry.”

Fowler will be one of more than 300 international speakers at the 32nd annual congress of the European Society of Intensive Care Medicine taking place in Berlin in October. There, he will share the results of the CITRIS-ALI trial with over 6,000 physicians from 97 countries.

“The use of vitamin C in sepsis was pioneered by Dr. Fowler at Virginia Commonwealth University,” said Peter F. Buckley, M.D., dean of the VCU School of Medicine and executive vice president for medical affairs at VCU Health System. “Our faculty address some of today’s toughest health care challenges with innovative research that paves the way for better patient care.”

A large-scale, phase III clinical trial with hundreds of participants is in the planning stages.

“Imagine two fully loaded 747s crashing every day — that’s how many people die of sepsis every year in this country,” Fowler said, stressing the need to develop a more effective standard of care. “The CITRIS-ALI trial could form the basis for a larger, more definitive trial.”