Here’s my bias before I even read the article. I want to see a positive response in providing IV Vitamin C/ascorbic acid in patients who have Acute Respiratory Distress Syndrome (ARDS). Why? Because I want me patients to do better with treatments that are inexpensive and easy to manufacture rather than the latest immunologic that ends in -mab and costs tens of thousands of dollars. If before you read this summary, you already think that Vitamin C is a bunch of bullpoop, you need some deep reflections in the mirror. You SHOULD want it to work. Now whether it does or doesn’t is different and that’s where the data comes in to play. This study has a catchy name, the CITRIS-ALI trial. I also created a post titled “Vitamin C: Everything you need to know”.

The IV Vitamin C Dose:

Before we even get started, we need to look at the study drugs, or lack thereof. The cocktail that was used in the Marik trial that was monumental in finding a mortality benefit in sepsis included ascorbic acid at 1.5gm q6, thiamine 200mg, and steroids. There is a rationale as to why these three go together that Dr. Marik explains far better than I could ever explain. The three are necessary today. Heck, even Gianfranco Meduri has been using steroids for ARDS for years and it’s not part of this study. Red flag number one. Not hating on the authors, I am just saying. Haven’t finished reading on it yet. Reserve the right to change my mind. In fact, a quick search shows there’s no mention of the word “thiamine” in the entire paper.

Outcomes of IV Vitamin C

The primary outcome was modified sofa scores at 96 hours and biomarkers.
I am not going to go over the secondary outcomes but there are 46 of them. They’re covering ALL the bases! Good job.

They enrolled 167 patients. This is remarkable that they were able to enroll this many patients in these 7 centers from 9/14 until 11/17.


Let’s talk results. That’s why you’re here. Are you going to start giving vitamin C to your patients with ARDS, yes or no?
Primary outcome: mSOFA and biomarkers: NO DIFFERENCE.
Secondary outcomes: 43 of 46 had NO DIFFERENCE.

But here is the kicker. The three secondary outcomes that had a difference are pretty important.
1. All-cause mortality (p=0.03). 46.3% in the placebo group vs. 29.8% in the Vitamin C group
2. ICU-free days (p=0.03). Patients were transferred out of the ICU faster in the Vitamin C group
3. Hospital-free days (p=0.04) 22.6 in the vitamin C group vs 15.5 in the placebo

Think of all the money that could be saved by this inexpensive vitamin in shortening time in the hospital. $6 a dose, if I’m not mistaken.

No difference in the biomarkers? Well, this may be my off-kilter idea but maybe we are looking or do not full understand our biomarkers.

There were NO adverse effects that occurred during the trial! I’ve had many people talk about kidney stones, renal dysfunction, terrible side effects of vitamin C. Well, there were none.

Wrapping it up

Now, there are many limitations in this study. The authors admit to that full and well. Physicians like myself who are on the pro-vitamin C side will interpret the data the way I just did. Those who are contrarians on the matter will be able to look at the numbers and interpret it differently. They will point out all the flaws in the study and throw the findings of the endpoints in the trash. I may be completely off base with my interpretation of these results, but I want to do EVERYTHING that’s reasonable to take care of my patients. And if that means spending $24 a day on Vitamin C, I will do it.

A shameless appeal to emotion

If you were the patients on the ventilator with ARDS, would you want the doctor treating you to give you vitamin C?
– EJ


Fowler AA 3rd, Truwit JD, Hite RD, et al. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial [published correction appears in JAMA. 2020 Jan 28;323(4):379]. JAMA. 2019;322(13):1261‐1270. doi:10.1001/jama.2019.11825
Link to Abstract and FULL FREE Article

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