Vitamin C for sepsis? Researchers want to study treatment while others move ahead with trial – Virginian-Pilot
The buzz generated by a vitamin C concoction that a Norfolk doctor uses to treat sepsis set social media ablaze in March.
Dr. Paul Marik, a critical care doctor at Sentara Norfolk General Hospital, announced to mainstream media he was using infusions of vitamin C, hydrocortisone and thiamine and seeing remarkable turnarounds in septic patients.
Since then, Marik, chief of pulmonary and critical care at Eastern Virginia Medical School, has been inundated with requests for information and comment, and he heard from Greek researchers who want to provide what skeptics say is missing: a randomized, controlled trial.
But he has also received plenty of skeptical pushback, with some critics using terms like “tooth fairy science.” One blog, the Skeptics Guide to Emergency Medicine, which has the motto “Be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine,” interviewed 11 medical experts who raised a litany of concerns about using the treatment before more study is done, including potential harms.
“Things that are so remarkable that they are astonishing probably would have been noticed a long time ago if it was really true,” Jerome Hoffman, an emergency doctor in Los Angeles and a professor of emergency medicine at University of Los Angeles, said on the blog. “If something seems magnificent and you had no idea about it, I’d be extraordinarily cautious.”
VCU team is studying Vitamin C
Meanwhile, off the social media circuit, Dr. Alpha “Berry” Fowler, head of pulmonary disease at Virginia Commonwealth University’s school of medicine, and his team of researchers are methodically toiling over a study involving vitamin C and sepsis that they started years ago.
An earlier trial of theirs was one of several that inspired Marik to try vitamin C and two additional ingredients.
But here’s where the two doctors part ways:
Marik is trying to spread the word about his treatment through webinars to save lives in the here and now.
Fowler is finishing up a federally funded clinical trial. He’s concerned that doctors will begin using vitamin C in a “willy nilly” fashion to treat sepsis.
“We want this done in a scientific way,” he said.
It’s a halls of science debate that has been aired in the media, health blogs and medical skeptic columns since Marik turned to mainstream media. He had first used the treatment when a patient in septic shock showed up in Norfolk General’s intensive care unit in January 2016.
Marik decided to use vitamin C infusions and steroids in a sort of “Hail Mary” pass. By the next day, the patient had vastly improved. He tried the concoction on two other septic patients and got the same results.
That’s when he started tracking patients for a study that was published online in December in CHEST, an American College of Chest Physicians medical journal: In 47 patients with sepsis treated in Norfolk General’s ICU, four died in 2016, an 8 percent mortality rate. Of those four, none died of sepsis but rather the conditions that led to sepsis in the first place. The previous year, 19 of 47 septic patients died, a 40 percent mortality rate.
Medical experts, though, said that such retrospective studies are fraught with limitations, and that what’s needed is the gold standard: a randomized, double-blind, placebo-controlled study in which patients with the same condition are observed in the same period, and health care providers in multiple sites don’t know who is receiving the treatment or a placebo.
Marik, 58, agreed, but he doubted that funding – from, say, a pharmaceutical company – would be available for a treatment that uses relatively inexpensive products already on the market.
Vitamin C’s intriguing history
Fowler, 68, a doctor and researcher who has spent most of his career studying sepsis, is not surprised that the news coverage, which ranged from National Public Radio to local media to health blogs across the globe, generated so much interest.
First, there’s the disease: “Imagine two fully loaded 747s. That’s 822 people. Imagine two crashing every day. That’s how many people die of sepsis.”
So at any given time, there’s a family in a hospital waiting room looking for answers. Sepsis occurs in more than 1 million people a year in this country, with 28 to 50 percent dying. The condition can stem from a variety of different ailments that cause infection.
Natural chemicals released in the body trigger widespread inflammation, which leads to blood clots and leaky vessels. That slows blood flow, damaging the organs by depriving them of nutrients and oxygen. In the worst cases, blood pressure drops, the heart weakens and the patient goes into septic shock.
The second viral aspect of this story is vitamin C, a nutrient with a fascinating story line, in both alternative medicine and scientific circles.
For instance, most animals produce vitamin C, with the notable exception of humans, and guinea pigs. That means they must get it through nutrition, something a Scottish surgeon in the Royal Navy discovered in the 1700s when he found that scurvy could be cured by eating oranges or lemons.
While vitamin C has been shown to have protective qualities and to bolster the immune system, there have also been vitamin C treatments that sounded good at the beginning but failed to live up to scientific scrutiny.
For instance, Nobel Prize winner and chemist Linus Pauley touted mega daily doses of vitamin C in the 1970s to prevent colds and cancer. But subsequent studies disproved the theory and found that excess vitamin C ends up going down the toilet in urine.
Fowler’s interest in vitamin C goes back decades. A critical step for his team occurred in 2009 when they compared five mice with sepsis that received infusions of vitamin C with five that did not. Thirty minutes later, the five without the vitamin C infusions had died. Those who received the infusions were alive.
That led to what’s called a Phase I clinical trial, which was published in 2014. That randomized, blind placebo study of 24 patients showed that those who received the high doses of vitamin C infusions had lower rates of organ failure and death. The high doses did not show any safety issues.
Like Marik, Fowler faced an uphill battle to get funding because no pharmaceutical company would take on a study of something already on the market. So he turned to a difficult but highly respected source: The National Institutes of Health.
“We expected an ‘Oh, come on, vitamin C, are you serious?’ response,” Fowler said.
But the strength of the trial prompted the institute to provide $3.2 million in funding in 2013.
It’s a double-blind, placebo study that is enrolling patients at four sites: VCU, Cleveland Clinic, Medical College of Wisconsin and the University of Kentucky. They are measuring the extent of organ failure and biomarkers of inflammation in the blood.
The goal is to enroll 170 patients, and they currently have 124.
Fowler expects there will likely be some patients who also received steroids, which Marik believes is a vital added component. But he won’t know until the study is complete and the data can be revealed. He expects to finish enrolling subjects late this year, or in 2018.
Reaction ranged from interest to pushback
Marik, though, is operating by a somewhat different matrix: He believes if doctors are facing a dying patient on a gurney, they should be able to offer his treatment to patients, since there have been safety studies on high-dose vitamin C infusions.
Marik wrote a letter to federal health officials in April detailing his treatment, the worldwide interest in it, and even the critical pushback from doctors who believe he is overstepping the boundaries of federal health protocols. The letter was posted on an emergency medicine blog, EMCrit, including this summary statement: “As clinicians our primary responsibility is and will always be to do what is right for the patient.”
He said doctors from 50 different centers have told him they’ve tried the treatment. He has continued to use it on his patients and is still seeing good results.
Two critical care doctors at the University of Athens in Greece, Dr. Stylianos Orfanos and Dr. Anastasia Kotanidou, told Marik they want to test the treatment in a randomized, controlled trial.
An email from Kotanidou, one of the researchers, said they hope to enroll 200 patients who have been diagnosed with septic shock at a number of different centers.
Treat now or wait for answers?
The debate shows a divide: Do you wait until a large, controlled study verifies a particular treatment? Or if the products are already on the market and deemed relatively safe, do you move forward?
Arthur Caplan, a professor of medical ethics at New York University Langone Medical Center, said it’s true that the substances can be used without the U.S. Food and Drug Administration’s permission since there’s no new drug or experimental product, but he said it’s a good idea to contact the agency to report that he’s doing it. A controlled trial in real time would add another layer of legal protection.
Fowler said the FDA had intervened at one point in his study of vitamin C, saying he needed to submit an investigative new drug application because it was being used in an innovative way.
Dr. David Carlbom, an associate professor of pulmonary critical care at the University of Washington, said he tried Marik’s treatment on about six patients with good results, but then stopped when surgical colleagues raised concerns about the impact of the steroids on wound healing. And a pulmonary doctor friend of Marik’s, Dr. Mark Rumbak, is also using it in Tampa with good results.
Fowler understands the lure of wanting to save patients. And it’s been difficult work, going to patients’ families and asking permission to enroll their relative in a clinical trial for a treatment that they may or may not get.
But he’s committed to the scientific underpinning:
“Critical care doctors will grab anything they can to improve survival. We’re not blaming them, but we want this done in a scientific way to be sure.”