To 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.
Glucose is a common carrier fluid, and in this particular case is given at a very low concentration (D5%). You need to infuse glucose as part of your parental nutrition regimen. This is standard practice across intensive care units, and they probably wouldn't have gotten approval for the protocol without it.
As an aside, my company [1] is working on solving this and other problems by focusing on glucose control. When you keep the blood sugar under control, sepsis develops at much lower rates and mortality decreases across the board by 20-30%.
Considering 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.
Would 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?
This 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.
The 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]."
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).
I'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.
I 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.
B vitamins are water soluble, so they are generally relatively safe to take in large amounts because they don't accumulate in the body, so you can't poison yourself like you can with some things. Some water soluble vitamins are associated with kidney stones if taken in high doses, so "unlikely to poison yourself" does not mean zero side effects.
I am seeing conflicting reports on B1 aka thiamine. If you don't have a compelling reason to try megadoses, I wouldn't do it. There's a lot we don't know.
But for many things, it's completely reasonable to increase your consumption of B vitamins. There's a lot of space between do nothing and megadoses that is safer to play in than skipping straight to megadoses.
> 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.
Megadosing vitamins despite normal serum levels is a favorite of alternative medicine practitioners. The story has played out for nearly every vitamin you can name that doesn't have immediate toxicity upon overdose: Vitamin C, Vitamin D, various B vitamins, etc.
It's never a good sign when there's "a physician who has done a lot of work on this" is the primary source, the claim is that all of medical knowledge to this point has missed it, the range of conditions/symptoms covered is so broad that nearly anyone could be considered impacted, and they preemptively try to claim that blood tests can't diagnose it or must be ignored. It's textbook alternative medicine pseudoscience and it's playing out for every vitamin, mineral, and supplement out there.
I'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.
> 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.
These are septic people whose organs are shutting down. Don’t draw conclusions between what affects someone with profound organ damage and a healthy person.
> 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.
Sugar (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.
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.
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.
[+] [-] carbocation|2 years ago|reply
1 = https://ccforum.biomedcentral.com/articles/10.1186/s13054-02...
[+] [-] ijustlovemath|2 years ago|reply
As an aside, my company [1] is working on solving this and other problems by focusing on glucose control. When you keep the blood sugar under control, sepsis develops at much lower rates and mortality decreases across the board by 20-30%.
[1] - https://idealmedtech.com
[+] [-] anigbrowl|2 years ago|reply
[+] [-] tea-coffee|2 years ago|reply
[+] [-] 4death4|2 years ago|reply
[+] [-] et2o|2 years ago|reply
[+] [-] letmevoteplease|2 years ago|reply
https://ccforum.biomedcentral.com/articles/10.1186/s13054-02...
[+] [-] olliej|2 years ago|reply
[+] [-] deeviant|2 years ago|reply
[+] [-] Khelavaster|2 years ago|reply
https://pubmed.ncbi.nlm.nih.gov/27940189/
[+] [-] arinazari|2 years ago|reply
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).
[+] [-] djtango|2 years ago|reply
[+] [-] DoreenMichele|2 years ago|reply
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.
[+] [-] d--b|2 years ago|reply
It doesn’t sound like a revolution just yet…
[+] [-] tea-coffee|2 years ago|reply
[+] [-] billiam|2 years ago|reply
[+] [-] cheaprentalyeti|2 years ago|reply
[+] [-] tea-coffee|2 years ago|reply
[+] [-] codeTired|2 years ago|reply
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.
[+] [-] DoreenMichele|2 years ago|reply
I am seeing conflicting reports on B1 aka thiamine. If you don't have a compelling reason to try megadoses, I wouldn't do it. There's a lot we don't know.
But for many things, it's completely reasonable to increase your consumption of B vitamins. There's a lot of space between do nothing and megadoses that is safer to play in than skipping straight to megadoses.
/not a physician and don't play one on TV.
[+] [-] Aurornis|2 years ago|reply
> 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.
Megadosing vitamins despite normal serum levels is a favorite of alternative medicine practitioners. The story has played out for nearly every vitamin you can name that doesn't have immediate toxicity upon overdose: Vitamin C, Vitamin D, various B vitamins, etc.
It's never a good sign when there's "a physician who has done a lot of work on this" is the primary source, the claim is that all of medical knowledge to this point has missed it, the range of conditions/symptoms covered is so broad that nearly anyone could be considered impacted, and they preemptively try to claim that blood tests can't diagnose it or must be ignored. It's textbook alternative medicine pseudoscience and it's playing out for every vitamin, mineral, and supplement out there.
[+] [-] polishdude20|2 years ago|reply
[+] [-] alecco|2 years ago|reply
[+] [-] yjftsjthsd-h|2 years ago|reply
"Technically"?
[+] [-] unknown|2 years ago|reply
[deleted]
[+] [-] AlbertCory|2 years ago|reply
[+] [-] dreamcompiler|2 years ago|reply
Sepsis can indeed take you fast.
[+] [-] unknown|2 years ago|reply
[deleted]
[+] [-] goda90|2 years ago|reply
> 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|2 years ago|reply
[+] [-] unknown|2 years ago|reply
[deleted]
[+] [-] sunkenvicar|2 years ago|reply
[deleted]
[+] [-] thenerdhead|2 years ago|reply
> “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|2 years ago|reply
[+] [-] unknown|2 years ago|reply
[deleted]
[+] [-] DoreenMichele|2 years ago|reply
A couple of things I skimmed:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506238/
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.
[+] [-] majkinetor|2 years ago|reply
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.
[+] [-] unknown|2 years ago|reply
[deleted]