4 ms·

Finally Confirmed Vitamin D Nearly Abolishes ICU Risk in Covid-19

89 points by ahiknsr 6y ago

kevingadd 6y ago
Only 76 patients and only 25 in the control group? Are sample sizes that small normal for this sort of experiment? I understand putting more people in the treatment group if you believe it'll help, but that seems like such a small test group...
- drno123 6y ago
  I understand this is small, but the study was fully random and double blind, done at a single hospital. And it is consistent with other studies related to vitamin D and Covid.
  - philipn 6y ago
    It was not blinded. It was open-label and the outcomes were subjective (ICU admission). The doctors involved with the trial knew who got what and may have biased their actions based on that. Given the subjective outcome and small number of participants, this is particularly important. The trial would be slightly underpowered even if it were blinded. Other studies on Vitamin D are retrospective cohort / observational studies which are heavily biased with possible confounders with respect to Vitamin D. My personal opinion is that Vitamin D may help in COVID-19 but this trial does not 'confirm' that. Someone should run a similar trial with more participants and/or a fully blinded trial / a trial with more outcomes (biomarkers, etc).
    - himinlomax 6y ago
      There may be some subjectivity at play alright when deciding if borderline patients go to ICU or not, and that certainly lowers confidence in the numbers, but the effect size is quite large. What would be interesting would be a follow up to see if patients have suffered lasting damages as has been reported; that could be done blind if the data is collected by imaging (for say heart damage) and analyzed by a different group. Though I have no idea how common those damages are.
    - lhl 6y ago
      While it's important to acknowledge the limitations of the pilot RCT, I think calling the outcomes as "subjective" goes too far - besides ICU admission, patients were tracked until discharge or death - a pretty hard outcome, to say the least. The ICU admission procedure is also discussed: "The patients were admitted to the ICU by applying the rigorous protocol of the Reina J Sofia University Hospital (see supplementary material). Several fundamental aspects were considered when evaluating admission to the ICU: Presence of comorbidities, either individually or quantified in the modified age Charlson Comorbidity Index; Barthel's Index for functional assessment. It establishes the level of dependence of a patient according to his or her needs and clinical criteria: CURB-65 and SOFA scale and ATS/IDSA criteria [27]. A multidisciplinary Selection Committee was created, made up of intensivists,pulmonologists, internists and members of the ethics committee who decided on admission to the ICU." WRT to bias, the description of the study is a bit confusing to me as it is described as "open label" (treatment known to the doctors and the patients) but also "double masked" which should hide the appearance of the treatment to the patient, investigator, or medical personnel. The study describes the masking as: "The list generated was accessible randomization only to nonmasked specialists in the study in an attempt to minimize observation bias. The patients' data were recorded in the hospital's electronic medical record, with blind access by the technical data collectors and the statistician who carried out the study." This description still leaves me confused, so hopefully that can get clarified (since treatment was oral, should be simple to mask w/ placebo), but in any case, the results are strong enough (and in concordance not only with the prior suggestive retrospective studies on Vitamin D and COVID, but also many mechanistic and RCT studies on Vitamin D's effects on respiratory illnesses and immune function) that hopefully a more rigorous, larger scale followup is being done somewhere. (Some other things about the study that I noticed is that patients didn't have Vitamin D status collected on intake, and as mentioned in the paper, obesity, BMI, and other metabolic markers weren't measured either.)
      - deleted 6y ago
        [deleted]
- himinlomax 6y ago
  The sample size would be ridiculous if this was an observational study and if the effect size was small; but this is a controlled study AND the effect size is enormous (basically ∞ as far as intensive care is concerned.)
- roenxi 6y ago
  The effect size is enormous. When things are that stark there isn't really much need to worry about sample sizes or statistical tests. Statistical analysis is basically useless when comparing 13/26 to 1/50. They are different, we don't need maths to verify that. There might be problems in the experimental design, but the sample size isn't an issue in this case.
  - deleted 6y ago
    [deleted]
weavie 6y ago
> 106,400 IU vitamin D This is quite a lot of vitamin D? > I think the best way to take action on these findings is to maintain 25(OH)D in 30-40 ng/mL. Also what does this mean in layman's terms?
- ht85 6y ago
  He gives possible dosages at the bottom of the article, but this should obviously be done with medical supervision, at least to measure initial levels.
  - weavie 6y ago
    Ah thanks I missed that. (It was too close to the 'share this' section for my eyes to wander down there!)
- cmrx64 6y ago
  there’s an app called dminder that will help you reach an estimated level, given dietary intake plus location and estimates of sun exposure.
- lambdaba 6y ago
  That's a normal one-time dose for correcting a deficiency, I've heard of much larger doses, even 50K IU daily for months. 30-40 ng/mL is the suitable level, on the mid-range, not even a high level (optimal levels might be even higher)
  - himinlomax 6y ago
    Note that one study showed that small, daily doses (or medium, weekly doses) had significant preventive effect against respiratory infections, whereas a large monthly dose had no such effect.
    - lambdaba 6y ago
      This might be both because vitamin D has low oral absorption, especially in high doses, and that staggering is necessary, and that some systemic effects take time to manifest.
viraptor 6y ago
Topic-adjacent: Some time ago there was an article posted, but I can't find it anywhere. It was about why does vitamin D seem to correlate with a lot of health issues / recoveries. Does anyone know what was the main idea, or what other keywords I could look for? (It was serious content, not one of the "vitamin D cures everything including cancer" people)
- lambdaba 6y ago
  Since obesity is correlated with nearly all chronic disease, one explanation is vitamin D being fat-soluble, it's plausible that some vitamin D gets trapped in fat and is therefore reduced in circulation.
- rriepe 6y ago
  Could be https://www.devaboone.com/post/vitamin-d-part-1-back-to-basics https://www.devaboone.com/post/vitamin-d-part-1-back-to-basi...
  - viraptor 6y ago
    Not the article I was thinking about, but it has the same ideas. Thank you very much.
- nfin 6y ago
  search for „devaboone“ (and other obvious keywords)
- mixmastamyk 6y ago
  It's a necessary component of the immune system. Deficiency means a weak response.
mindfulhack 6y ago
I wonder how much a connection there is between levels of vitamin D production from exposure to the sun depending on how much melanin your skin has (and also how much exposure you give your skin), and higher rates of ICU admission and death among people with black and brown skin? How much of the higher rates are caused by physical health issues due to genetics, rather than social policy issues as has been said in the media (at least the media that I watch)? Since March I've been taking 5000 IU of vitamin D every day regardless of my skin colour. This seems like major news and if I were in the health system or in a position of power I would personally not be waiting for larger trials before rolling out vitamin D right now. This is because I don't want people to die. (Do our politicians have the same goal?) Vitamin D is already known to be safe if not taken at too high a dose. Sometimes solutions to health problems are simple, and it's beautiful.
- Dahoon 6y ago
  >Vitamin D is already known to be safe if not taken at too high a dose. There were some posts on here by a doctor that have seen problems with people who were inside the norm of D.vit. so I wouldn't trust the above. I have to take D vitamins because there's something wrong with me and doctors want to monitor my blood levels because of it. Calcium levels are one thing that can become too high with normal range d.vit. if taking supplements. Vitamin D supplement is medicine which most people seem to forget. Using medicine means seeing a doctor to make sure it is safe, at least a blood test every 6 months. Edit: here's one of her threads: https://news.ycombinator.com/item?id=24138590 https://news.ycombinator.com/item?id=24138590
  - mantap 6y ago
    People see the word "vitamin" and think it's a food like vitamin C. But Vitamin D isn't like that, there's not many foods that are high in vitamin D and most that are are fortified. If we could get sufficient vitamin D from food then we wouldn't have evolved a mechanism to get it from the sun. Vitamin D also accumulates, which is a feature if you are getting it from sunlight but a potential problem if you are taking supplements.
andybak 6y ago
How far does this go in explaining the huge variance in seriousness? I'm thinking things like: 1. The age correlation might be partly down to indoor vs outdoor activities 2. The drop in ICU admissions over time might correlate to improved weather. 3. Geographical differences might correlate with climate and lifestyle? 4. Ethnic and gender differences could be partly behavioural/dietry?
- haxiomic 6y ago
  Age correlation is primarily linked to expression of coronavirus binding sites (ACE2), which are more prevalent in older people and people with lung damage. ACE2 expression is also affected by genetics and lifestyle factors Reference: Individual variation of the SARS‐CoV‐2 receptor ACE2 gene expression and regulation https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13168 https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13168
- narag 6y ago
  FWIW, Córdoba is very sunny, and the hottest place in Spain.
DangerousPie 6y ago
Can we please change this to the actual study rather than this somewhat suspect-looking personal blog of a guy who is trying to sell books about vitamins and supplements? https://www.sciencedirect.com/science/article/pii/S0960076020302764?via%3Dihub https://www.sciencedirect.com/science/article/pii/S096007602... The difference they report there between patients receiving calcifediol (Vitamin D) and those that do not is strikingly large, to the point where it makes me somewhat suspicious: > Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) If that is true and replicates in larger sample sizes this would be an incredible powerful drug, wouldn't it?
- neuronic 6y ago
  And it would tell us heaps about how serious vitamin D deficiency (and likely other deficiencies) can really be. If, for example, reports of large amounts of African Americans being vitamin D deficient are true and vitamin D plays a significant role in many pathologies, safely getting those people to the right level without inducing vitaminosis could possibly lead to improvements in health issues that occur with higher incidence in African Americans (asthma comes to mind). It would have huge benefits to individuals and by extension healthcare systems. For everyone reading this, please make sure to get blood work done before supplementing more than 1000 or 2000 IU per day. Taking vitamin D in its complete and ready form sidesteps the bodies regulation mechanism because that happens before the body produces vitamin D from components after sun exposure. Taking it orally basically skips that regulation and therefore you CAN overdose with potentially severe health consequences.
  - yehosef 6y ago
    >For everyone reading this, please make sure to get blood work done before supplementing more than 1000 or 2000 IU per day. rewritten for to be more actionable: For everyone reading this, make sure to take 1000 or 2000 IU per day since you may be deficient (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259547/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259547/). You should, if possible, get a blood test to see if you are severely deficient and if so to take higher doses according to your doctor's recommendation.
doliveira 6y ago
I'm very uncomfortable with the assertive tone of this post. It's probably the right move to push for vitamin supplements, but we really should be careful with asserting the benefits with basically 100% confidence like he does, to the point of guaranteeing causal connection and claiming that further studies will only illuminate few more details in the picture. It's almost irresponsible, specially in the context of an ongoing pandemic. And I've read that vitamin D has been touted and later dismissed as the solution so many times...
- yehosef 6y ago
  FUD - Fear, uncertainty and doubt - many/most people are vit-D deficient (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581139/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581139/) and mild doses (1000-2000 IU/day) are not typically dangerous (less so than being deficient)
wwweston 6y ago
Let’s say we take the benefits of D supplementation at face value. How do you get a hold of some that you can be confident is actually what it says it is and well-formulated for bioavailability, given reports that it’s common for what’s sold in stores to be dodgy? https://well.blogs.nytimes.com/2015/02/03/new-york-attorney-general-targets-supplements-at-major-retailers/ https://well.blogs.nytimes.com/2015/02/03/new-york-attorney-...
- yosito 6y ago
  Sit in the sun for 20 minutes a day. Of course that comes with it's own risks.

89 points by ahiknsr 6y ago

Only 76 patients and only 25 in the control group? Are sample sizes that small normal for this sort of experiment? I understand putting more people in the treatment group if you believe it'll help, but that seems like such a small test group...

drno123 6y ago
I understand this is small, but the study was fully random and double blind, done at a single hospital. And it is consistent with other studies related to vitamin D and Covid.
- philipn 6y ago
  It was not blinded. It was open-label and the outcomes were subjective (ICU admission). The doctors involved with the trial knew who got what and may have biased their actions based on that. Given the subjective outcome and small number of participants, this is particularly important. The trial would be slightly underpowered even if it were blinded. Other studies on Vitamin D are retrospective cohort / observational studies which are heavily biased with possible confounders with respect to Vitamin D. My personal opinion is that Vitamin D may help in COVID-19 but this trial does not 'confirm' that. Someone should run a similar trial with more participants and/or a fully blinded trial / a trial with more outcomes (biomarkers, etc).
  - himinlomax 6y ago
    There may be some subjectivity at play alright when deciding if borderline patients go to ICU or not, and that certainly lowers confidence in the numbers, but the effect size is quite large. What would be interesting would be a follow up to see if patients have suffered lasting damages as has been reported; that could be done blind if the data is collected by imaging (for say heart damage) and analyzed by a different group. Though I have no idea how common those damages are.
  - lhl 6y ago
    While it's important to acknowledge the limitations of the pilot RCT, I think calling the outcomes as "subjective" goes too far - besides ICU admission, patients were tracked until discharge or death - a pretty hard outcome, to say the least. The ICU admission procedure is also discussed: "The patients were admitted to the ICU by applying the rigorous protocol of the Reina J Sofia University Hospital (see supplementary material). Several fundamental aspects were considered when evaluating admission to the ICU: Presence of comorbidities, either individually or quantified in the modified age Charlson Comorbidity Index; Barthel's Index for functional assessment. It establishes the level of dependence of a patient according to his or her needs and clinical criteria: CURB-65 and SOFA scale and ATS/IDSA criteria [27]. A multidisciplinary Selection Committee was created, made up of intensivists,pulmonologists, internists and members of the ethics committee who decided on admission to the ICU." WRT to bias, the description of the study is a bit confusing to me as it is described as "open label" (treatment known to the doctors and the patients) but also "double masked" which should hide the appearance of the treatment to the patient, investigator, or medical personnel. The study describes the masking as: "The list generated was accessible randomization only to nonmasked specialists in the study in an attempt to minimize observation bias. The patients' data were recorded in the hospital's electronic medical record, with blind access by the technical data collectors and the statistician who carried out the study." This description still leaves me confused, so hopefully that can get clarified (since treatment was oral, should be simple to mask w/ placebo), but in any case, the results are strong enough (and in concordance not only with the prior suggestive retrospective studies on Vitamin D and COVID, but also many mechanistic and RCT studies on Vitamin D's effects on respiratory illnesses and immune function) that hopefully a more rigorous, larger scale followup is being done somewhere. (Some other things about the study that I noticed is that patients didn't have Vitamin D status collected on intake, and as mentioned in the paper, obesity, BMI, and other metabolic markers weren't measured either.)
    - deleted 6y ago
      [deleted]
himinlomax 6y ago
The sample size would be ridiculous if this was an observational study and if the effect size was small; but this is a controlled study AND the effect size is enormous (basically ∞ as far as intensive care is concerned.)
roenxi 6y ago
The effect size is enormous. When things are that stark there isn't really much need to worry about sample sizes or statistical tests. Statistical analysis is basically useless when comparing 13/26 to 1/50. They are different, we don't need maths to verify that. There might be problems in the experimental design, but the sample size isn't an issue in this case.
- deleted 6y ago
  [deleted]

weavie 6y ago

> 106,400 IU vitamin D This is quite a lot of vitamin D? > I think the best way to take action on these findings is to maintain 25(OH)D in 30-40 ng/mL. Also what does this mean in layman's terms?

ht85 6y ago
He gives possible dosages at the bottom of the article, but this should obviously be done with medical supervision, at least to measure initial levels.
- weavie 6y ago
  Ah thanks I missed that. (It was too close to the 'share this' section for my eyes to wander down there!)
cmrx64 6y ago
there’s an app called dminder that will help you reach an estimated level, given dietary intake plus location and estimates of sun exposure.
lambdaba 6y ago
That's a normal one-time dose for correcting a deficiency, I've heard of much larger doses, even 50K IU daily for months. 30-40 ng/mL is the suitable level, on the mid-range, not even a high level (optimal levels might be even higher)
- himinlomax 6y ago
  Note that one study showed that small, daily doses (or medium, weekly doses) had significant preventive effect against respiratory infections, whereas a large monthly dose had no such effect.
  - lambdaba 6y ago
    This might be both because vitamin D has low oral absorption, especially in high doses, and that staggering is necessary, and that some systemic effects take time to manifest.

viraptor 6y ago

Topic-adjacent: Some time ago there was an article posted, but I can't find it anywhere. It was about why does vitamin D seem to correlate with a lot of health issues / recoveries. Does anyone know what was the main idea, or what other keywords I could look for? (It was serious content, not one of the "vitamin D cures everything including cancer" people)

lambdaba 6y ago
Since obesity is correlated with nearly all chronic disease, one explanation is vitamin D being fat-soluble, it's plausible that some vitamin D gets trapped in fat and is therefore reduced in circulation.
rriepe 6y ago
Could be https://www.devaboone.com/post/vitamin-d-part-1-back-to-basics https://www.devaboone.com/post/vitamin-d-part-1-back-to-basi...
- viraptor 6y ago
  Not the article I was thinking about, but it has the same ideas. Thank you very much.
nfin 6y ago
search for „devaboone“ (and other obvious keywords)
mixmastamyk 6y ago
It's a necessary component of the immune system. Deficiency means a weak response.

mindfulhack 6y ago

I wonder how much a connection there is between levels of vitamin D production from exposure to the sun depending on how much melanin your skin has (and also how much exposure you give your skin), and higher rates of ICU admission and death among people with black and brown skin? How much of the higher rates are caused by physical health issues due to genetics, rather than social policy issues as has been said in the media (at least the media that I watch)? Since March I've been taking 5000 IU of vitamin D every day regardless of my skin colour. This seems like major news and if I were in the health system or in a position of power I would personally not be waiting for larger trials before rolling out vitamin D right now. This is because I don't want people to die. (Do our politicians have the same goal?) Vitamin D is already known to be safe if not taken at too high a dose. Sometimes solutions to health problems are simple, and it's beautiful.

Dahoon 6y ago
>Vitamin D is already known to be safe if not taken at too high a dose. There were some posts on here by a doctor that have seen problems with people who were inside the norm of D.vit. so I wouldn't trust the above. I have to take D vitamins because there's something wrong with me and doctors want to monitor my blood levels because of it. Calcium levels are one thing that can become too high with normal range d.vit. if taking supplements. Vitamin D supplement is medicine which most people seem to forget. Using medicine means seeing a doctor to make sure it is safe, at least a blood test every 6 months. Edit: here's one of her threads: https://news.ycombinator.com/item?id=24138590 https://news.ycombinator.com/item?id=24138590
- mantap 6y ago
  People see the word "vitamin" and think it's a food like vitamin C. But Vitamin D isn't like that, there's not many foods that are high in vitamin D and most that are are fortified. If we could get sufficient vitamin D from food then we wouldn't have evolved a mechanism to get it from the sun. Vitamin D also accumulates, which is a feature if you are getting it from sunlight but a potential problem if you are taking supplements.

andybak 6y ago

How far does this go in explaining the huge variance in seriousness? I'm thinking things like: 1. The age correlation might be partly down to indoor vs outdoor activities 2. The drop in ICU admissions over time might correlate to improved weather. 3. Geographical differences might correlate with climate and lifestyle? 4. Ethnic and gender differences could be partly behavioural/dietry?

haxiomic 6y ago
Age correlation is primarily linked to expression of coronavirus binding sites (ACE2), which are more prevalent in older people and people with lung damage. ACE2 expression is also affected by genetics and lifestyle factors Reference: Individual variation of the SARS‐CoV‐2 receptor ACE2 gene expression and regulation https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13168 https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13168
narag 6y ago
FWIW, Córdoba is very sunny, and the hottest place in Spain.

DangerousPie 6y ago

Can we please change this to the actual study rather than this somewhat suspect-looking personal blog of a guy who is trying to sell books about vitamins and supplements? https://www.sciencedirect.com/science/article/pii/S0960076020302764?via%3Dihub https://www.sciencedirect.com/science/article/pii/S096007602... The difference they report there between patients receiving calcifediol (Vitamin D) and those that do not is strikingly large, to the point where it makes me somewhat suspicious: > Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) If that is true and replicates in larger sample sizes this would be an incredible powerful drug, wouldn't it?

neuronic 6y ago
And it would tell us heaps about how serious vitamin D deficiency (and likely other deficiencies) can really be. If, for example, reports of large amounts of African Americans being vitamin D deficient are true and vitamin D plays a significant role in many pathologies, safely getting those people to the right level without inducing vitaminosis could possibly lead to improvements in health issues that occur with higher incidence in African Americans (asthma comes to mind). It would have huge benefits to individuals and by extension healthcare systems. For everyone reading this, please make sure to get blood work done before supplementing more than 1000 or 2000 IU per day. Taking vitamin D in its complete and ready form sidesteps the bodies regulation mechanism because that happens before the body produces vitamin D from components after sun exposure. Taking it orally basically skips that regulation and therefore you CAN overdose with potentially severe health consequences.
- yehosef 6y ago
  >For everyone reading this, please make sure to get blood work done before supplementing more than 1000 or 2000 IU per day. rewritten for to be more actionable: For everyone reading this, make sure to take 1000 or 2000 IU per day since you may be deficient (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259547/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259547/). You should, if possible, get a blood test to see if you are severely deficient and if so to take higher doses according to your doctor's recommendation.

doliveira 6y ago

I'm very uncomfortable with the assertive tone of this post. It's probably the right move to push for vitamin supplements, but we really should be careful with asserting the benefits with basically 100% confidence like he does, to the point of guaranteeing causal connection and claiming that further studies will only illuminate few more details in the picture. It's almost irresponsible, specially in the context of an ongoing pandemic. And I've read that vitamin D has been touted and later dismissed as the solution so many times...

yehosef 6y ago
FUD - Fear, uncertainty and doubt - many/most people are vit-D deficient (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581139/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581139/) and mild doses (1000-2000 IU/day) are not typically dangerous (less so than being deficient)

wwweston 6y ago

Let’s say we take the benefits of D supplementation at face value. How do you get a hold of some that you can be confident is actually what it says it is and well-formulated for bioavailability, given reports that it’s common for what’s sold in stores to be dodgy? https://well.blogs.nytimes.com/2015/02/03/new-york-attorney-general-targets-supplements-at-major-retailers/ https://well.blogs.nytimes.com/2015/02/03/new-york-attorney-...

yosito 6y ago
Sit in the sun for 20 minutes a day. Of course that comes with it's own risks.