IV Vitamin C in Sepsis: Does it cause harm?

How I use IV Vitamin C in my practice

Since 2017, I have been providing the cocktail of intravenous (IV) vitamin c, thiamine, and stress dose steroids to my patients in septic shock. At my institution, we have complied many patients to whom we have given this regimen. We are looking to use this data for a propensity matched, case-control, retrospective study.

Anecdotally, meaning without any actual evidence, I feel that I have seen a positive response if provided early in the course. My objective outcomes data is regards to mortality, duration of vasopressor use, etc. Again, this is not substantiated by any data. This is my opinion at this time. When it comes to that regimen, I provide my patients with 1500mg IV q6h. That’s not medical advice. Do not do this without carefully examining the pro’s and con’s (see below) of this therapy.

The doubters (and I don’t blame them)

There are individuals who are quite vocal against this therapy. They typically have no idea of the multitude of benefits that these three components have in our critically ill patients. I am not going to break down in detail here but you can check out my posts here. This post is about harm. Many people do not know that we cannot synthesize our own vitamin C. Nor do they know that it is a necessary co-factor for endogenous catecholamine production (as I have covered on this post). Without vitamin C, you cannot make dopamine, norepinephrine, nor epinephrine. I have written a full 45 minute or so lecture on metabolic resuscitation and how it works. That I will be presenting at various conferences/seminars.

The contrarians yell at the top of their lungs about “calcium oxalate crystals”, “kidney stones”, and the unknown side effects of intravenous (IV) vitamin C. Well, now there’s data where they’ve looked directly at this. The study was published on 5/13/2020 in the Critical Care Medicine Journal. They looked at 74 studies which included 2801 patients who were on “high-dose” vitamin C.
As a point of reference, Marik’s paper in Chest in 2017 used 1.5gm IV q6h which ends up being 6gm per day. The median dose in this paper was 22.5gm/d. That’s far more than what I am using in my practice.

If you notice, Paul Young is one of the authors. He was also involved in the VITAMINS trial (that I covered extensively here) which showed, within the spectrum of how they administered the regimen, that the cocktail did not work for their endpoints. I cannot represent his official stance on the matter, but I wouldn’t say he’s someone glowing with enthusiasm for the regimen after watching him discuss the findings on the internet broadcast of said trial.

What are the reported adverse effects of IV vitamin C?

Heres what they found (out of 2801 patients):
– 5 cases of oxalate nephropathy
– 5 cases of hypernatremia
– 3 cases of hemolysis in patients with G6PD deficiency
– 2 cases of glucometer error
– 1 case of kidney stones

The authors went on to call the incidence of these events “rare”. I disclosed my bias above but I agree. They described that it is not more harmful than placebo. As an aside, it is postulated that thiamine protects the kidneys by avoiding the conversion of glyoxylate to oxalate via glyoxylate aminotransferase. Hypernatremia could be due to the vitamin c being sold as sodium ascorbate. I personally cannot recall taking care of one single patient with G6PD deficiency due to my geographic location and patient population, but it’s something to keep an eye out for and avoid it.

When it comes to the glucometer errors, they mean it reads the blood glucose to read a higher value than what it really is. This only applies to certain glucometers (not all), and does not affect the values provided by our central labs. Please check with the manufacturers of your device to see if it would be affected by the high-dose vitamin C infusion. I have covered the glucometer issue before (link to that post) That’s going over the cases where there was harm.

How often are adverse effects reported?

16 reported instances of adverse effects 2801 patients. I’ll let you be the judge as to whether, for the benefits, it is worthwhile to provide intravenous (IV) vitamin C for your patients of whom 88% have hypovitaminosis C and 38% have severe deficiency when critically ill.
– EJ

Unfortunately, the paper is not open access but the link to the article is down below.


Yanase F, Fujii T, Naorungroj T, et al. Harm of IV High-Dose Vitamin C Therapy in Adult Patients: A Scoping Review [published online ahead of print, 2020 May 13]. Crit Care Med. 2020;10.1097/CCM.0000000000004396. doi:10.1097/CCM.0000000000004396

Link to Abstract

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2 thoughts on “IV Vitamin C in Sepsis: Does it cause harm?

  1. Violetta

    Nice blog Dr.Eddy easy to read and share with co workers.
    Also, what does do you usually use for your patients ?

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