After 28 years teaching and practicing critical care medicine, Dr. Paul Marik knows when a patient is at death’s door. So in January 2016, when 53-year-old Valerie Hobbs came into his intensive care unit with a severe case of sepsis, he expected it would be for the last time.
Hobbs had been admitted to Virginia's Sentara Norfolk General Hospital for an infected gall-bladder that had led to septic shock. Now, the confounding infection was causing her blood pressure to bottom out and her organs to fail. Marik’s best guess was that she would be dead by morning.
"Faced with a young patient who is dying, you have to say to yourself, what else can I do?" he recalls. There was one thing he could do: order intravenous vitamin C.
Yes, vitamin C, the ubiquitous nutrient that children are encouraged to consume by eating dark leafy greens as well as citrus, peppers and other orange-hued produce. It’s well-known to prevent scurvy and help with heart function. But Marik, who is chief of the pulmonary and critical care medicine unit at Eastern Virginia Medical School, had been reading research papers that also showed some success treating sepsis patients with intravenous vitamin C—along with a steroid to reduce inflammation and thiamine to help with absorption.
More than a million Americans fall ill from severe sepsis annually, and between 28 and 50 percent of them die, according to the National Institute of General Medical Studies. Because it often requires a long hospital stay, sepsis costs U.S. hospitals about $23 billion annually. The Global Sepsis Alliance reports that sepsis kills between 6 and 8 million people each year. That's more deaths than those caused by prostate cancer, breast cancer and AIDS combined.
Given the stakes, the vitamin C treatment didn't seem so crazy. After all, Marik knew that sepsis patients often have undetectable levels of the nutrient, compared to healthy patients. Animals produce increased levels when they are stressed, but humans, thanks to a fatal mutation, are unable to make it on their own. The studies Marik read reported that replenishing vitamin C in sepsis patients could help them deal with shock and prevent organ damage. Why not give it a try?
"Most times you don't have intravenous vitamin C, but fortunately our pharmacy had a small amount," he says. "It was like the stars were aligning." He gave Hobbs a cocktail of intravenous vitamin C, hydrocortisone and thiamine, and waited.
The next morning, Marik came in to discover Hobbs alive and already off the medication supporting her blood pressure. Her kidney function had improved. Two hours later, she was taken off a ventilator. Three days later, she went home. "You say, wow, what just happened?" Marik recalls. If the vitamin C protocol really did cure her, the consequences would be profound. Still, he thought, it might have been a fluke.
Not long after, Marik he had another patient come in seriously ill with sepsis. He tried the same protocol and had the same success. The X-rays of a third patient who came in with pneumonia and severe sepsis revealed that, one day after the protocol, his lungs were 50 percent clearer. The second day, they were 100 percent better, Marik says.
"At that point, I knew there was something here,” he says. “This was not just a fluke."
Marik is no loose cannon. Even skeptics of his results acknowledge his expertise. He has authored more than 400 medical journal articles and four books, including a critical care textbook—together “an extraordinary contribution to the literature in critical care,” says Dr. Craig Coopersmith, a leading sepsis researcher at the Emory University School of Medicine.
Still, his colleagues at the hospital told him he was talking nonsense until they saw the results.
After successfully treating about 25 patients, Marik shared the protocol with physician friends in other cities. He collected data on his first 47 patients and wrote a paper published in the journal Chest about a year after he first treated Hobbs. In it, he noted that vitamin C and hydrocortisone have multiple and overlapping beneficial effects when it comes to treating sepsis, including supporting the body’s defenses, mitigating leakage through blood vessel cells, and decreasing inflammation that leads to organ damage.
Four of the 47 patients Marik documented in his paper died in the hospital. But their deaths, Marik reported, were from underlying diseases, not from sepsis. By comparison, 19 of the 47 patients he'd treated before trying vitamin C and steroids had died. So far, he's treated more than 150 patients with the protocol and he says only one has died from sepsis.
Today, Marik gets about 100 emails a day on the subject, and says more than 50 medical centers are using his protocol. "My goal was never to find a cure for sepsis," he says. "It happened. It's certainly the coolest thing that's ever happened to me. People are doing this across the world and they're getting the same results."
For many doctors, Marik’s protocol represents a dilemma. There seem to be no ill effects. Yet, there are also no randomized clinical trials. Should they embrace an untested treatment?
Online, the debate is raging. After Marik published his results, a discussion on PulmCrit, a blog by an assistant professor of pulmonary and critical care medicine at the University of Vermont, generated 96 comments. Doctors at one extreme were arguing that the evidence showed it was about as effective as healing incantations; those on the other side called it promising and worth trying, given the mortality statistics. Another blog run by doctors, the Skeptics’ Guide to Emergency Medicine, published a post titled “Don’t Believe the Hype – Vitamin C Cocktail for Sepsis.”
Marik and others enthusiastic about the treatment agree with skeptics who say blind, randomized clinical trials need to be done to validate the treatment’s efficacy. However, they also say that the dramatic results so far mean doctors should embrace the treatment in the meantime—an unorthodox proposition, to say the least.
During an interview in his office, Marik called up Dr. Joseph Varon, a pulmonologist and researcher at the University of Texas Health Science Center in Houston. "It does sound too good to be true,” Varon said over the phone. "But my mortality rates have changed dramatically. It is unreal. Everything we have tried in the past didn't work. This works."
Last year, Marik reached out to Dr. John Catravas at nearby Old Dominion University to study how his treatment worked at the cellular level. The two met when Catravas was recruited to the university three years ago, and have stayed in touch. Catravas has spent decades studying endothelial cells, the thin layer that lines blood vessels; patients with sepsis leak blood through the cell walls, causing pulmonary edema and death.
To test Marik's protocol, Catravas and his team cultured endothelial cells from lung tissue and exposed them to the endotoxin found in septic patients. Vitamin C alone did nothing. Neither did steroids. When administered together, however, the cells were restored to normal levels. "We have a clinical answer," Catravas says. "We have part of the mechanistic answer. There is satisfaction in that as a scientist. There is also satisfaction knowing that a lot of people worldwide are going to get an amazing benefit."
Other sepsis researchers advise caution, including Dr. Jim O'Brien, an ICU doctor and member of the board of the Sepsis Alliance. “The probability that a heterogeneous disease like sepsis is able to be defeated this easily is pretty darn low," says O’Brien, who is also system vice president of Quality for OhioHealth, a network of 11 hospitals. "So that should cause us, when we see results that surprise us this much, to look at this with a little bit more of a cautious eye."
O'Brien notes that other studies have promised sepsis treatments in the lab, but ended up falling short. "We've cured sepsis in mice many times over," he says. "The problem is when we get into the clinical arena, we've seen things fall apart."
As of this week, Coopersmith of the Emory University School of Medicine is involved in planning a national, multi-center trial to test the efficacy of the vitamin C protocol, with funding from the Marcus Foundation. “If this is validated, this would be the single biggest breakthrough in sepsis care in my lifetime,” he says.
Although Coopersmith is not using the protocol himself, he says some of his colleagues are. “While some components of this are assuredly safe, there are with every medication risks involved,” he says. “I think people who are early adopters of this because the results are so tremendous, I fully support. I also fully support people who would want to wait for additional data.”
Kurt Hofelich, Norfolk General’s president, says he wants to see a double-blinded study. But the hospital, an academic medical center, has already made the protocol its standard of care and is in the process of deciding when to roll it out to other intensive care units in Sentara’s 12 hospitals.
"I think we have a very, very promising innovative approach that didn't require anybody to invent a new drug," he says. "It's a very rare thing when you can use things that are readily available and inexpensive and the combination has this kind of impact."
Hofelich says there are no skeptics among the nurses who treat patients. "Do I have the level of evidence and confidence this should be imposed on the entire industry? No,” he says. "Do I think we're going to get there? Absolutely."
Marik knows it will take time for his protocol to be tested and eventually adopted, even if his results are reproduced. The history of medicine contains many stories of doctors whose unlikely cures were spurned for decades. In 1983, for instance, two Australian doctors discovered a bacteria that caused ulcers, but it took about two decades before most doctors began prescribing antibiotics. In 2005, they received the Nobel Prize for their discovery.
When he speaks at conferences, Marik often tells the story of Ignaz Semmelweis, the Hungarian physician who went on a quest to discover why so many women were dying in a maternity clinic at a hospital in Vienna in 1847. There were two wards, one attended by doctors, and one attended by midwives. Over time, Semmelweis realized women in the doctors’ ward were dying because the doctors were doing autopsies then delivering babies without washing their hands.
He ordered the staff to clean their hands and instruments with a chlorine solution. Semmelweis didn't know anything about germs; Louis Pasteur and his famous fermentation experiments wouldn't come along for another decade. He thought the solution would remove the smell from autopsies. Just like that, illness and death in the ward dropped dramatically.
But doctors were upset because his action made it look like they were making the women ill. Eventually, they stopped washing their hands. Semmelweis lost his job. He continued pushing his theory with few takers, and only published his findings 13 years later. At the age of 47, he was committed to an insane asylum in 1865. He died two weeks later of an infection, likely sepsis.
Marik draws a parallel for his audience between his solution and the one championed by Semmelweis, now considered a pioneer in antiseptic treatment. "It's a simple intervention based on an observation that changed treatment of the disease,” he says. “And nobody wants to believe it. It's going to take time for people to accept it.”
In the meantime, Marik continues to use the protocol and continues to see good results. "It is the most amazing thing. When it happens, every time I have to pinch myself,” he says. “These people come in with septic shock and they leave within three days."