Vitamin C for sepsis study may be fraudulent — data was too perfect

As you all know, I am a skeptic of almost all supplements, and I never thought that using vitamin C for sepsis was supported by robust and repeated data. Well, an analysis by an Australian physician, statistician, and Ph.D. student may have found fraudulent data, and it’s becoming a topic of conversation among physicians who have used the protocol to treat sepsis.

Let’s take a peek at this story since it is so amazing because this shows how science really works.

close up of fruits in bowl vitamin c sepsis
Photo by Pixabay on

Vitamin C for sepsis — how this started

A paper, published on 6 December 2016, by Paul Marik, MD and colleagues, in CHEST, described a protocol that could prevent death from sepsis. It included a simple regimen of hydrocortisone, ascorbic acid (vitamin C), and thiamine (the procedure was dubbed the HAT protocol), that could save many lives. The paper has been the subject of significant debate in the intensive medicine community since it was first published.

Other studies contradicted Marik’s study adding to the debate about the validity of the HAT protocol. Several larger and more methodologically robust studies followed, and to date, none of at least nine randomized trials — including the VITAMINS and VICTAS clinical trials — has shown a similar reduction in mortality. Even if the original study was not fraudulent, it was becoming clear that other independent data did not support the effectiveness of the HAT protocol.

Dr. Kyle Sheldrick, MD, who is completing his Ph.D. at the University of New South Wales, alleges that the pre- and post- comparison groups involved in the small 94-patient study were too good to be realistic. Dr. Sheldrick wrote to the editors of CHEST outlining several factors that lead him to the conclusion of fraud. He concluded:

There is simply no apparent explanation for this other than fraud. The methods are described clearly and these are explicitly two cohorts of consecutive patients, so the only real innocent explanation here (undisclosed matching by baseline characteristics) did not occur (and it clearly didn’t anyway as matching patients this exactly would not be possible even with thousands of such patients).

OUCH! I’m so used to very careful language in science (well, I’m not one of those), it was remarkable to see such blunt commentary on Marik’s paper.

In an interview with MedPage Today, Dr. Sheldrick described how he figured out that the vitamin C protocol for treating sepsis was probably bogus:

…the key problem with the Marik paper is “probably the most common sign of fraud that we see, which is overly similar groups at baseline.”

Generally, when people are asked to fake a random distribution, they will consistently fake an even distribution, he explained: “You will fake data that’s far too close to the averages with not enough variation.”

Sheldrick said he first looked at the study methods, which noted a pre- and post- comparison design, rather than a randomized or matched case-control design. With such a design, one would expect a more random distribution of baseline characteristics, but that wasn’t the case for the Marik paper, he said.

He calculated P-values for the comparisons of the baseline characteristics using the Fisher Exact test, which he would expect to range fully from 0 to 1 given the study design. But he found the majority of P-values were 1 — meaning they were distributed perfectly evenly across two time periods — and only one fell below 0.5.

“We would expect to see these evenly spread between 0 and 1,” he told MedPage Today, with an overall average of around 0.5.

I can’t believe that Dr. Sheldrick was the first person to notice that the p-values were 1.0. I hate statistics, and if I saw perfect p-values I would have wondered what was going on. There should be a simple rule of science — if the data is too good to be true, be skeptical. Very skeptical.

Dr. Sheldrick said:

This is extreme. This is probably the most obviously fake data I have seen. … These groups are more similar than would be probable.

Dr. Sheldrick sent a letter to CHEST and Dr. Marik’s former employer, Sentara Norfolk General Hospital, but neither responded to him. However, MedPage Today was told by a spokesperson for CHEST that it couldn’t confirm whether they had begun an investigation of Marik’s paper based on Sheldrick’s letter to them. Apparently, the journal does have a procedure for investigating claims about published articles, but they won’t comment on the process.

Of course, Dr. Marik responded that these were false allegations with no merit. He cites two studies that support his claims while ignoring the seven other, much better, studies that show no difference in sepsis outcomes with vitamin C therapy. This is a perfect example of cherry-picking, but Marik is trying to defend his work by deflecting to other studies. He makes no mention of his perfect p-values, which was the basis of Dr. Sheldrick’s claims.

citrus fruits slice
Photo by Trang Doan on

More about Paul Marik

But the story gets better. Dr. Marik co-authored a paper, that was published in November 2021 in the Journal of Intensive Care Medicine that described the MATH+ protocol for COVID-19. The MATH+ protocol, which includes methylprednisolone, ascorbic acid, thiamine, and low molecular weight, supposedly improved COVID-19 outcomes. He even created one of those quack groups that push COVID-19 treatments like ivermectin.

In case you were wondering, Marik’s COVID-19 paper was retracted.

In other words, Marik has discovered two “miracle” cures, one for sepsis and another for COVID-19, within a few years of each other. It makes my skeptical radar blare all kinds of warnings.

Vitamin C is useful for treating scurvy and probably not for sepsis (and certainly not for COVID-19), that’s it. I wish people would quit giving it more magical powers than that, but that’s what people do to push vitamin C.


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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!