MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

I very rarely discuss animal experiments on this blog. Their applicability to clinical situations in human patients is almost invariably doubtful. Of course, this does not mean that they cannot be important; on the contrary, they may point the way towards relevant research and help formulate hypotheses.

This study might be exceptionally relevant in this way. To investigate the safety and efficacy of megadose sodium ascorbate in sepsis, sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg).

Sepsis-induced fever (41.4 ± 0.2°C; mean ± SE), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial PO2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue PO2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01).

Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary PO2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg).

These physiologic findings were subsequently confirmed in a coronavirus patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours.

The authors concluded that IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.

As always with animal experiments, it is difficult to extrapolate to clinical situations in human patients. However, the fact that the authors did try their approach on one COVID-19 patient is encouraging. I agree with their conclusion that careful human studies are now required.

21 Responses to Vitamin C reversed the pathophysiological and behavioral responses to Gram-negative sepsis

    • a video is not acceptable evidence.

      • Edzard!
        this answer is small-minded and not worthy of yours. Are you open to new knowledge or not? For once, this is not about homeopathy, so you can react more loosely….

        https://www.evms.edu/covid-19/covid_care_for_clinicians/

        https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

        As you can see, I also look in different directions apart from homeopathy…..
        I try to find out, what helpes most!

        • it is not small minded to ask for evidence, I believe.
          it is dangerous to act on non-evidence such as a video of an interview.
          I do not rue out that VitC has an effect [hence my post] but I still want to see evidence in human patients.

          • Edzard on Friday 04 December 2020 at 20:58 said:
            “…it is dangerous to act on non-evidence such as a video of an interview…”

            If this were true, then there would be no need for interviews, courts, witnesses or cross examination. The whole thing could be decided by “science” and “experts” who *know* what truth is because they are “qualified” in this and that speciality (e.g. SID) by using machines such as lie detectors (e.g. Klaus Fuchs).

            The beauty of video (or preferably face-to-face) is that lying is virtually impossible without hesitating or prevaricating e.g. if Paul Marik is lying, the same thing that happened to Andrew Wakefield, would have happened to him, he gives his full name, his position and his hospital and low and behold, he is still allowed to practice.

            Your constant demand for evidence is never going to happen because vitamin C is vital hence there can be no control arm, the *only* test possible is the dose and all previous clinical studies have assumed that 100mg is the correct amount and 2,000mg is the upper limit – no, Irwin Stone showed that this is way too small to be effective under oxidative stress.

            As Stone said, we, the primates are “hypoascorbemic” as he coined it, “low-vitamin-C” hence permanently vulnerable to a whole bunch of (mainly degenerate) diseases that none of the other (self-producing, vitamin C-on-demand) animals and plants and insects suffer from.

            Anyone can easily prove this for themselves by taking a few grams per day and notice e.g. that they don’t suffer from bleeding gums anymore or any mouth damage fixes itself in 24 hours instead of a painful week later – I take *far* more than this – but you would have to watch a video of my taking it, at the very least because no one would believe it otherwise, including myself.

          • “The beauty of video (or preferably face-to-face) is that lying is virtually impossible without hesitating or prevaricating”
            you are joking, aren’t you!
            have you seen videos of Wakefield, for example?

          • Edzard on Saturday 05 December 2020 at 16:11
            “…you are joking, aren’t you!
            have you seen videos of Wakefield, for example?”
            Sure, e.g.
            https://www.bitchute.com/video/AP8346mphRUL/

          • “The beauty of video (or preferably face-to-face) is that lying is virtually impossible without hesitating or prevaricating”

            I dunno about that. I mean, you already do a perfectly seamless job of lying in text. Congrats.

            All video does is enable a liar to lie with extra emotion. Great for manipulating the marks, not for fact-checking the content. Hence the demand for primary sources: while still no guarantor of truth, at least it’s one less fecal firehose to shovel through. Or do you have something to hide?

          • Prof Ernst: “have you seen videos of Wakefield”

            A great example. Probably the wrong question to ask though, as what are the odds that Old Bob isn’t also a worshipper of that child-abusing psychopath.

  • This looks like an important study, though of course there are a lot of differences between humans and sheep. Also nobody with sepsis would be managed that way on ITU (e.g. denied antibiotics). Although only 10 animals were used in here, they would have been far more similar than any human patients, of course (matched for age, sex, variety and were probably closely related to one another), so the small numbers aren’t really the problem that they would be in a clinical study.

    I don’t think it is possible to draw any conclusions from the reponse of the single human that they mentioned, as so many factors were different, and I am sure that vitamin C would not have been the only treatment they received. I’m not even sure that “compassionate use” is an appropriate term here.

    What we need now is more human studies. They would have to be A vs. A+B, as the only ethical way to do it would be best existing care plus or minus high-dose infusional vitamin C, but although that isn’t ideal from a statistical perspective it would still give us an answer if the effect is large enough to be clinically useful.

    • I do agree but the studies can use a better design and even employ a placebo given in addition to standard treatment, I think.

      • I think most people with sepsis, if they are conscious at all, wouldn’t be particularly aware of which of the many tubes going into them contained a placebo, so it is really a question of blinding the Intensive Care staff. However, with patients this sick the situation can change very quickly, and I would imagine the doctors looking after them would want to know what they were giving at all times.

        Quite often it simply isn’t possible to use placebos or to blind patients to which treatment they are having. I have been involved in trials comparing different radiotherapy schedules, for instance, when it is fairly obvious to everybody concerned who gets what. This one, for instance, which has just been published in The Lancet, comparing early radiotherapy after prostatectomy for high-risk cancer against deferred radiotherapy for relapse (I am listed as the 33rd author):
        https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31553-1/fulltext

  • Linus Pauling would be proud of you.

  • That vitamin C has a role as an adjuvant in the complex treatment of sepsis has been known for a long time and this knowledge is still evolving. This is not something that is easily studied, as JMK points out. Good science is often a slow process. It does not work by itself and is neither a miracle nor panacea. Neither does this fact corroborate the commonly exploited zombie of a misconception that vit-C can prevent or cure the common cold, Covid-19 or what have you.

    That perfectly good mutton needs to be wasted in experiments to clarify the action physiology, dosages etc, is sad but necessary. Especially if they are poorly performed. I would rather brine it and slow roast 🙂

    I am not hopeful but our altmed enthusiastic friends might learn something from this, if they want to be educated: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996765/

  • I think that he who knows it all, none other than Björn Geir, is maybe on a slippery slope here. He seems to accept that vitamin C has a role as an adjuvant in the complex treatment of sepsis.
    If Björn ends up becoming a CAM fanatic though over the next twenty years as science gets round to it , he hopefully will also realise that CAM doesnt Cure everything.

    • Dendra! You would come in second!

      Not that you have contributed much of rational substance, but just out of curiosity. Is there any reason why we should take your outlandish views seriously? What is your education, training and experience?

  • I dont come on here for you to take any of my views seriously any time soon. We both have our ideas fixed.
    I come on here to gently challenge you as your tone reminds me of a few Drs i saw in the 80s who also knew it all. Whilst i would agree that you have high status in your medical speciality i personally think that you know very little about CAM and how it can help people like me.People who have education, experience and training in non medical science and who can justify the right to an an opinion. People who have suffered from EBM and for listening to so called experts.

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