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Sodium ascorbate treatment for sepsis moves to next phase of human trials
- thenerdhead 3y ago> Promising results from an initial clinical trial at the Austin Hospital in Melbourne, published today in Critical Care, show that sodium ascorbate – a pH-balanced formulation of vitamin C – is effective in treating sepsis > “In our trial at Austin Hospital, patients were given sodium ascorbate into their bloodstream, resulting in promising improvements to multiple organs.” Oh boy, vitamin C is having a very strange year. First cancer, now sepsis.
- irrational 3y agoWhat is the vitamin C and cancer thing? Vitamin C causes cancer?
- thenerdhead 3y agoTaking C and E makes some cancers grow faster. But also mega dosing C can help improve some cancers. Lots of back and forth.
- WithinReason 3y agoWhat do you mean by "improving" cancer?
- pazimzadeh 3y agoIt's the delivery method that is the difference, not just the dose. Vitamin C IV is pro-oxidant (promotes damage to mitochondria (cancers have famously messed up mitochondria already), etc) whereas Vitamin C that passes through the gut is anti-oxidant. https://www.cancer.gov/research/key-initiatives/ras/ras-central/blog/2020/yun-cantley-vitamin-c https://www.cancer.gov/research/key-initiatives/ras/ras-cent...
- thenerdhead 3y agoAh yes! That's one I was looking to link. Specifically Mark Levine's work. i.e. https://pubmed.ncbi.nlm.nih.gov/15068981/ https://pubmed.ncbi.nlm.nih.gov/15068981/
- nikolay 3y agoI've read that vitamin C over 500mg even oral causes mitochondrial damage.
- cyberax 3y agoThis kinda makes sense. Cancer cells are under severe oxidative pressure, and vitamin C in reasonable doses is an anti-oxidant. But in _very_ high doses another mechanism kicks in, and the vitamin C causes generation of reactive oxygen species: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285147/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285147/
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- cheaprentalyeti 3y agoI thought they just pretended to definitively disprove the whole vitamin C/sepsis thing?
- tea-coffee 3y agoThis is using sodium ascorbate, bit different from vitamin C (ascorbic acid).
- mcpackieh 3y agoSodium ascorbate is the sodium salt of ascorbic acid. It satisfies your dietary requirement for Vitamin C. https://ods.od.nih.gov/factsheets/VitaminC-Consumer/#h4 https://ods.od.nih.gov/factsheets/VitaminC-Consumer/#h4
- tea-coffee 3y agoI understand. I meant "bit different" in the nuanced context of this study. As the authors note in their introduction of the paper [1]: "Regrettably, these studies used ascorbic acid, a compound associated with the induction of metabolic acidosis and acidemia [15]. This makes it uncertain whether the unclear effects in human sepsis were due to the administration of a suboptimal preparation of the study medication. In contrast, sodium ascorbate (NaAscorbate) has a physiological pH, does not contribute to acidosis, can be given at a much greater dose, and may carry a different efficacy profile." 1 = https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04644-x https://ccforum.biomedcentral.com/articles/10.1186/s13054-02...
- djtango 3y agoYeah to try to maybe draw an analogy, NaAscorbate vs Ascorbic Acid is a bit like CSV vs JSON encoding - you might be sending the exact same data but if the serialisation format isn't what the API expects, then you could get errors but that doesn't necessarily mean that you sent the wrong data. The body can react differently to salt vs pure form for the same active ingredient - eg crack vs cocaine
- Khelavaster 3y agoAffirmation of "Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study" https://pubmed.ncbi.nlm.nih.gov/27940189/ https://pubmed.ncbi.nlm.nih.gov/27940189/
- codeTired 3y agoI used to be in the camp that supplements/vitamins are bs in general and unless you are deficient they won’t do a thing for you. However, I am now learning that serum levels don’t often tell the whole truth. For example, many suffers of neurological disorders benefit greatly from using B1 even if their levels are not below “good” threshold. There is a physician who has done a lot of work on this. You can technically megadose b1 without any negative side effects. I am now seeing neurologists even recommending things like ALA to patients along with meds to stop symptoms. I welcome the open mindedness because the online groups of suffers often discover pretty interesting things. Years ago I talked to a chemist who cured his neuropathy with pirenzepine(drug used for ulcers with good safety profile), there is a startup now with a cream that uses pirenzepine as main ingredient to treat neuropathy. They are in stage 3 trials and have seen success.
- polishdude20 3y agoDo you have more info on this? What sort of neurological disorders can this help?
- codeTired 3y agohttps://pubmed.ncbi.nlm.nih.gov/34685573/ https://pubmed.ncbi.nlm.nih.gov/34685573/ https://www.researchgate.net/profile/Derrick-Lonsdale https://www.researchgate.net/profile/Derrick-Lonsdale Some links to get you started. B1 deficiency can be caused by things like alcoholism. He also thinks we don’t get enough of b1 in our diet and the current scale is not sufficient. Symptoms can vary and can involve different nervous systems. Things like tingling, insomnia, fatigue. A lot of people talk about getting paradoxical reaction or refeeeding syndrome, meaning once they start taking b1 they get massive flare up of symptoms.
- polishdude20 3y agoCan we get enough B1 by just diet alone? It seems a lot of foods either have in naturally or are fortified with it. Why the need for extra supplements?
- d--b 3y agoDoes anyone here understand the actual study? It doesn’t sound like a revolution just yet…
- tea-coffee 3y agoOf course it is not a revolution. In modern medicine, there are hardly ever revolutions, more so incremental progress.
- Engineering-MD 3y agomRNA vaccines and CART seem pretty revolutionary tbh. Watch this space.
- billiam 3y agoReduce 50% of all hospital deaths even moderately and I'd say you should get a Nobel prize.
- d--b 3y agoIt doesn’t look like the original study came anywhere close to preventing 50% of deaths due to septis.
- RCitronsBroker 3y agothat’s not what the comment said tho, he just stated that death by septic shock made up about 50% of hospital fatalities, as in if you are able to even somewhat help that large of a pt group, that’s a pretty big step forward.
- d--b 3y agoWell the comment was edited… the author added “even moderately”, so…
- goda90 3y agoFrom the linked paper: > One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Just in case people see "vitamin c", and think it's safe to use IV or high dose medicine for day to day supplementation.
- op00to 3y agoThese are septic people whose organs are shutting down. Don’t draw conclusions between what affects someone with profound organ damage and a healthy person.
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- majkinetor 3y agoGreat, I just got myself 10g of C IV. I am happy to see that medicine is finally acknowledging that vitamin C in large doses is a thing with virtually 0 side effects. No wonder all living creatures make it in huge doses. Orthomolecular researches claimed this "discovery" decades ago. At least we didn't have to wait hundreds of years.
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- AlbertCory 3y agoI personally know someone who died of sepsis, quite recently. As they said in the article, it happens very fast, within a day or so.
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- dreamcompiler 3y agoI've had patients with sepsis standing up and talking to me, complaining about being tired and feeling woozy. And in the middle of a sentence they fall to the floor dead and we start CPR. Put the pads on them but never got a shockable rhythm after 45 minutes of high quality CPR. Sepsis can indeed take you fast.
- sunkenvicar 3y ago[dead]
- arinazari 3y agolinus pauling took a lot of heat in his post-nobel day for his vitamin c advocacy: https://www.vox.com/2015/1/15/7547741/vitamin-c-myth-pauling https://www.vox.com/2015/1/15/7547741/vitamin-c-myth-pauling i would love if years later it turned out he didn't just have "nobelitis" and was right in some respects. but this is one small pilot study and the larger body of literature around it shows mixed results. not saying it should be disregarded, but there are several reasons why it's not exciting and it shouldn't be mistaken for a anything more than a pilot trial to evaluate safety. i'm sure there's a lot more to criticize than i can see, but: 1) study's primary outcome of increased urine output is not necessarily clinically meaningful---urine output (UOP) is selected because in septic shock (sepsis + low blood pressure), organs slowly shut down with the kidneys typically being the first to go. thus, UOP can be informative as a measure of renal perfusion and ultimately end-organ damage. however, the control arm received D5 fluids [water? saline?] alone, whereas intervention group received D5 fluids + NaAscorbate, thus ultimately receiving more solute. you would expect when given a more osmolar solution, you would see increased diuresis (solute will draw in water in the kidney's tubules, thus more urine output). additionally, vitamin c itself is renally excreted, thus if the kidneys are working to excrete high doses of NaAscorbate, the tubular cells could alter their usual reabsorption and secretion patterns, potentially affecting overall fluid balance. 2) as above this is a small pilot study; however, the authors (laudably) include their power calculations in which they used an effect size of 900cc UOP. the difference in mean UOP between the groups was 891cc's, so it's dubiously powered (even if we ignore consideration (1)). accordingly, their 95% confidence interval itself crosses 0 meaning no difference in effect was detected in urine output (thus their p values was >0.05). you have to wonder what statistical games might have been played to p-hack when results come so close. ultimately why this isn't news is that the 'next phase of human trials' have already been conducted on vitamin c in sepsis. there's a few other things: mean baseline CRP was notably much higher in the intervention group, and it makes me wonder if this affects the effect size considering that anyone in sepsis might benefit from fluids (though they received so little overall).
- DoreenMichele 3y agoI've looked a little at the literature and I doubt Linus Pauling was right. His ideas remind me of a saying from a favoriteprofessor: "I am the primitive of my way." I am all for using nutrition to heal people but I think his ideas were half baked. He was maybe kind of "on to something" but in a general ballpark kind of way, I suspect.
- carbocation 3y agoTo me it seems like a poor study design to have the placebo be a glucose infusion rather than a matched quantity of sodium chloride. They cannot say that the beneficial effects were not just due to sodium. Figure 3[1] shows that sodium concentrations indeed rose compared to placebo. They acknowledge this in their limitations, but this is a flaw of study design that could have been foreseen from the beginning. 1 = https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04644-x#Fig3 https://ccforum.biomedcentral.com/articles/10.1186/s13054-02...
- tea-coffee 3y agoWould they need to have 2 placebo arms to make this an optimal study design then? One for glucose (as sodium ascorbate was diluted using a glucose solution), and another placebo group for sodium chloride?
- carbocation 3y agoHonestly if they had balanced the sodium via almost any mechanism, I wouldn't have had much to say about it. The difficulty with 2 placebo arms is that you have to expand your study population which I think poses an ethical issue, but otherwise yes.
- anigbrowl 3y agoConsidering that saline drips a the norm for IV hydration, it might be that a saline infusion added to a saline IV line would be superfluous. Interested to get a medically qualified person's take on this.
- carbocation 3y agoIt would not be superfluous because they are talking about nearly a gram of additional sodium in one arm vs none in the other. They describe the carrier solution, which is a 5% glucose solution (D5W). D5W is isotonic and does not include sodium.
- ijustlovemath 3y ago
- DoreenMichele 3y agoSugar (like from a glucose infusion) can raise your blood pressure and low blood pressure is one metric for concluding it is sepsis. A quick search brings up one source that says antibiotics and other drugs are used, another that indicates IV fluid is also routinely used. A couple of things I skimmed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506238/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506238/ https://my.clevelandclinic.org/health/diseases/12361-sepsis https://my.clevelandclinic.org/health/diseases/12361-sepsis I don't understand the study, why they concluded this might help, what they think is going on with sepsis nor do I see any indication of how one would make a differential diagnosis of this sepsis patient might benefit from this, this other one might not.
- et2o 3y agoThis has been beaten to death in high quality randomized controlled trials in sepsis. Don’t believe a university press release lol. HN is a pretty poor source of health information overall.
- olliej 3y agoLook, if you can't trust university press releases posted to a tech forum for health advice, who can you trust?
- deeviant 3y agoBeaten to death as in proven, or disproven?
- letmevoteplease 3y agoThe study says: "Randomized controlled trials, however, have shown variable results or even possible harm [10,11,12]. Moreover, current guidelines and a Bayesian re-analysis of a previous trial have led to recommendations not to use intravenous vitamin C in patients with sepsis because of possible harm [13, 14]. Regrettably, these studies used ascorbic acid, a compound associated with the induction of metabolic acidosis and acidemia [15]. This makes it uncertain whether the unclear effects in human sepsis were due to the administration of a suboptimal preparation of the study medication. In contrast, sodium ascorbate (NaAscorbate) has a physiological pH, does not contribute to acidosis, can be given at a much greater dose, and may carry a different efficacy profile [16]." https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04644-x https://ccforum.biomedcentral.com/articles/10.1186/s13054-02...
- deleted 3y ago[deleted]