64 ms·

The First Randomized Controlled Trial on Vitamin D and Covid-19

• bdamm 6y ago
  Noteworthy that this is in combination with anti-viral drugs at hospital admission: hydroxychloroquine (400 mg every 12 hours on the first day, and 200 mg every 12 hours for the following 5 days), azithromycin (500 mg orally for 5 days). Regardless, I'm going to assume this means being outside and getting sun is good for me.
  • nicholasjarnold 6y ago
    Azithromycin is a common antibiotic, not an anti-viral drug. This is an important distinction. Also hydroxychloroquine is an anti-malarial drug, which is also not an anti-viral.
    • LinuxBender 6y ago
      Hydroxychloroquine is a zinc ionophore which helps zinc get into the cells in your lungs and slows the viral replication. It was not designed to be used this way, it just happens to work. This is mostly useful before your viral load is high. Same goes for Quercetin, also a zinc ionophore. They are good proactive measures to slow down the viral transcription before you reach a critical stage. It won't help everyone, especially if given late in their infection and especially if their immune system is compromised or otherwise dysfunctional.
      • jogundas 6y ago
        Wiki says that "Hydroxychloroquine is being studied to prevent and treat coronavirus disease 2019 (COVID‑19), but all clinical trials conducted during 2020 found it is ineffective and may cause dangerous side effects." https://en.wikipedia.org/wiki/Hydroxychloroquine https://en.wikipedia.org/wiki/Hydroxychloroquine
        • LinuxBender 6y ago
          That is mostly correct based on the studies I have been following. In most cases, by the time people are admitted to the hospital, the viral load is too high and their immune system has not been able to keep up. There is a whole lot more going on, all the way from interactions with ACE to VWF to clotting, that administering zinc ionophores late in the game may be a bit too late.
        • viggity 6y ago
          millions of people take HCQ on a daily basis for their lupus. Ask any rheumatologist, the danger of Torsades de Points is only a concern for HCQ if the patient already has a serious heart condition, or if the patient has been taking HCQ for years. Millions more take HCQ as a malaria treatment. It is generally recognized as safe, if you do not have a heart condition (and even then a short course is unlikely to yield adverse outcomes).
          • outworlder 6y ago
            > It is generally recognized as safe There are no safe drugs for a patient admitted to intensive care. We should not start administering anything in large scale just because most healthy people can tolerate it well.
          • aden1ne 6y ago
            Covid has severe effects on the cardiovascular system, with myocardial injury being a frequent occurrence of those covid patients admitted to hospital.
          • deelowe 6y ago
            The dosages are different (much higher) for Covid-19.
          • Filligree 6y ago
            > Millions more take HCQ as a malaria treatment. It is generally recognized as safe, if you do not have a heart condition (and even then a short course is unlikely to yield adverse outcomes). COVID-19 can infect the heart and damage it. As safe as HCQ might be on its own, here it's adding extra load to a system that's already under stress.
      • ReflectedImage 6y ago
        The issue is it stops viral transcription at levels that also happen to be lethal to humans :p
        • amluto 6y ago
          My recollection is that it stops viral replication in vitro in monkey cells but does not stop viral replication in vitro in human cells.
          • acqq 6y ago
            Yes, it just stops replication "within the glass" (that's the meaning of "in vitro") with the cell culture, not in living human patients, and even "within the glass" only when using the "the Vero E6 cell line which is derived from kidney cells of green monkeys." https://www.infectioncontroltoday.com/view/new-study-hydroxychloroquine-works-in-monkeys-not-humans https://www.infectioncontroltoday.com/view/new-study-hydroxy... "The mechanism of action of hydroxychloroquine is to block entry of the virus into cells. Viral entry requires a helper enzyme. In the Vero E6 cell line, this enzyme is cathepsin L which hydroxychloroquine blocks. However, in the human lung cell line, the helping enzyme is TMPRSS2. Hydroxychloroquine does not effectively block this enzyme and cellular entry of the virus occurs." So, inspired by the reports of the experiments with wrong cells a French doctor made some false claims about his success when treating patients, which were then promoted by one person wanting to be reelected, and then the followers... the results can be seen in the comments here.
    • gojomo 6y ago
      While neither azithromycin nor hydroxychloroquine are primarily thought of as anti-virals, both are hypothesized by some to have some anti-viral effect, and it's still unclear whether any potential effects they have on Covid-19 are via such anti-viral effects, or other effects.
      • azinman2 6y ago
        Just because something helps with issues created by a virus doesn’t make it an anti-viral. For example it seems to be now that steroids are aiding those in the ICU with covid, but I don’t think anyone could plausibly call a steroid an anti-viral, as much as a bandaid can’t be called an antibiotic even if it helps heal a cut and prevent additional bacterial infection.
        • gojomo 6y ago
          True, but if you look in the literature, you will find both of these compounds referred to as having some anti-viral effects, and their hypothesized mechanism(s) against Covid-19 may involve those effects. For example, in <https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30293-7/fulltext> https://www.clinicalmicrobiologyandinfection.com/article/S11..., even though the study concludes other anti-virals are better, we see the footnoted, uncontroversial claim: "The antiviral properties of CQ were first explored against viral hepatitis as far back as 1963 [1]. Since then many observations from in vitro and animal experiments have suggested a beneficial role of HCQ and CQ in viral infections [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]." There are of course hundreds more such authoritative references to observed anti-viral activity. Or regarding Azithromycin (AZM) in <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290142/> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290142/>, we see: "It has been shown that AZM has significant antiviral properties. In contrast with CQ or HCQ, its antiviral activity has been shown in vitro and/or in vivo on a large panel of viruses: Ebola, Zika, respiratory syncytial virus, influenzae H1N1 virus, enterovirus, and rhinovirus [4–13]. Its activity against respiratory syncytial virus has been demonstrated in a randomized study in infants [10]. Azithromycin exhibited a synergistic antiviral effect against SARS-CoV-2 when combined with HCQ both in vitro [11] and in a clinical setting [13]." That HCQ is mainly known as an antimalarial doesn't refute that it has, and is often tried for, antiviral effects. That AZM is mainly known as an antibiotic doesn't refute that it has shown broad antiviral effects as well. (If you're stuck on 'antiviral' as some binary category, or mutually-exclusive with other categories, you're going to miss all the interesting incremental effects in real chemistry/biology. That sort of "sharply-bounded categories" thinking has killed a lot of people recently, as with those insistent on 'droplets vs aerosols' instead of a continuum including every size/variant of both.)
  • mortehu 6y ago
    All patients received hydroxychloroquine and azithromycin, i.e. the control group also, meaning the difference in outcome between the intervention and control groups is not due to these drugs.
    • schoolornot 6y ago
      The American media would have you believe that hydroxychloroquine and Z-packs are completely ineffective. Are we still in the "we don't know" stage? Is there any conclusive data to show that it helps/hurts/or does nothing in the beginning/middle/end stages of infection?
      • mortehu 6y ago
        This experiment compares vitamin D to no vitamin D, and doesn't say anything about those drugs statistically.
        • schoolornot 6y ago
          Then why introduce two unknown variables into the study?
          • mortehu 6y ago
            The point is they are not variables, but rather constants (everyone got them), and they were not introduced, but standard care at the time. I suspect you have the wrong idea about how the results of the trial are supposed to be interpreted. The point isn't to compare to results outside the study. You should only compare the intervention group to the control group in the same study.
          • not2b 6y ago
            Because it's unethical to leave people who are sick with Covid-19 untreated, so they all got what were considered possibly effective treatments at the time.
      • ReflectedImage 6y ago
  • zamfi 6y ago
    To be clear, all patients received these supplemental drugs, as at the time they were considered the best standard of care. (Also to be clear: they're not anti-virals.) Of the 75 patients in the trial, 50 people received additionally Vitamin D3 supplementation (in the form of calcifediol), and 25 did not. Notably, though, diabetes and high blood pressure were substantially more frequent in the control group, which are HUGE risk factors. Also they didn't track BMI or obesity. Still, check out table 2. Even with these limitations, seems powerful.
    • im3w1l 6y ago
      > Notably, though, diabetes and high blood pressure were substantially more frequent in the control group How did this happen? Just bad luck with randomization?
      • zamfi 6y ago
        That's the implication from the paper.
      • stjohnswarts 6y ago
        ack those could definitely affect this, isn't that why they normally try to select otherwise healthy patients as a baseline? Bring in the unhealthy people for the big studies and they'll most likely be spread much more evenly
    • hannob 6y ago
      Hydroxychloroquine was never the "best standard of care". It's a quack treatment that was pushed by some bad studies. Reading Hydroxychloroquine mentioned in this study should make one very suspicious.
      • zamfi 6y ago
        This is a substantial oversimplification. Hydroxychloroquine looked promising for a while, and was being studied in an RCT, but that RCT was ended before completion because of the release of an observational study that suggested strongly negative outcomes from Hydroxychloroquine. Later, that observational study was retracted because it was discovered to be based on falsified data. So, unfortunately, we don't know very much about Hydroxychloroquine's effectiveness and risks in use -- but we do know that it has become a massive political hot potato, as your comment indicates.
  • DenisM 6y ago
    Except for all the skin cancer, right? FWIW, I was told that when the Sun is above 45 degrees over the horizon you will accrue DNA damage, and it stacks up over your entire lifetime. There is no "reset" or "heal", it just adds up. For that reason I'm doing my darnest best to stay in the shade between 9am and 3pm. Or covering clothing.
    • eholk 6y ago
      I'd be really interested to see a comparison of the relative risks between skin cancer and vitamin D deficiency. A lot of what I've read lately suggests we're discovering a lot of benefits of vitamin D that were previously unknown, and some evidence that the recommended vitamin D levels should be higher than they are. For a generation or so we've told people the sun is dangerous because of skin cancer, and obviously skin cancer is really bad. But I wonder if we have a case of need to weight risks that are high cost, low probability (skin cancer) compared with low cost, high probability (low vitamins D complications). What is the overall effect of these two things?
      • agarden 6y ago
        This article gets into that: https://www.outsideonline.com/2380751/sunscreen-sun-exposure-skin-cancer-science https://www.outsideonline.com/2380751/sunscreen-sun-exposure... Short excerpt: People don’t realize this because several different diseases are lumped together under the term “skin cancer.” The most common by far are basal-cell carcinomas and squamous-cell carcinomas, which are almost never fatal. In fact, says Weller, “When I diagnose a basal-cell skin cancer in a patient, the first thing I say is congratulations, because you’re walking out of my office with a longer life expectancy than when you walked in.” That’s probably because people who get carcinomas, which are strongly linked to sun exposure, tend to be healthy types that are outside getting plenty of exercise and sunlight.
        • function_seven 6y ago
          > The most common by far are basal-cell carcinomas and squamous-cell carcinomas, which are almost never fatal. My grandpa died due to complications from a basal-cell skin cancer. He was almost 90 years old. The cancer itself was a few decades old. He served in the Navy during WWII, and likely got it from years of tropical sun exposure with no sunscreen.* So, yeah, as far as cancers go, that's one you'd rather get if given a choice. * (Well, and the additional years of fishing and other outdoor activities. Obviously the cause can't be pinpointed like that, but it must have contributed)
  • axaxs 6y ago
    I always assumed getting sun(in moderation) was good for oneself. As much as I dislike the heat in general, I always have way more energy after spending a few hours in the sun. I assume(perhaps incorrectly) this was due to a Vitamin D bump. Further, I've known two people in my life who get weird skin issues if they stay out of the sun too long. My wife is one of them! Really weird, considering how damaging the sun is considered.
    • anoraca 6y ago
      UV light kills things that might grow on your skin otherwise, might be related to that.
  • JabavuAdams 6y ago
    Yes. This study doesn't show that a non-hospitalized person who is not taking hydroxychloroquine and azithromycin should expect better outcomes from Vitamin D. At best, one could argue that if you get hospitalized, it would be good to have built up some Vitamin D. I'm still supplementing with Vitamin D, though, but may cut back having been reminded that it's a fat-soluble hormone (and not really a vitamin at all).
  • nradov 6y ago
    Besides vitamin D, sunlight exposure also stimulates production of nitric oxide and thus lowers blood pressure. We also know that high blood pressure is a risk factor for COVID-19 so it seems plausible that there could be a connection. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593895/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593895/
  • deleted 6y ago
    [deleted]
• maxander 6y ago
  From the results: “Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) p value X2 Fischer test p < 0.001.” Which sounds like as strong a signal as a study of this scale could hope to show.
  • zamfi 6y ago
    Yes, this is strong. Worth noting the limitations though: > Randomization generated groups with comparable percentage of unfavorable risk factors as there was no significant difference in subjects with at least one risk factor, except for high blood pressure and diabetes mellitus, known risk factors for unfavorable disease progression [2], which were more frequent in patients not treated with calcifediol. These are HUGE risk factors. Also: > This pilot study has several limitations as it is not double-blind placebo controlled. On the other hand, in the first studies evaluating risk factors for severe disease and/or death from COVID-19, the possible role of obesity was not considered. Therefore, given the isolation characteristics of the patients, we did not collect the BMI, which would have allowed us to add obesity as a risk factor for severe evolution of COVID-19 [37] It is striking to consider that obesity shares with aging and black or asian ethnicity a surprising overlap as risk factors for severe COVID-19 and vitamin D deficiency. Yeah, BMI would've been nice too. Still, check out table 2. Even with these limitations, seems powerful.
    • acqq 6y ago
      The group receiving Calcifediol had more "no bad risk" patients: "At least one prognostic bad risk factor(@) Group receiving Calcifediol: 48% Group without Calcifediol: 61.54%" "@) Patients with at least one of the following risk factors (age >60, previous lung disease, chronic kidney disease, diabetes mellitus, hypertension, cardiovascular disease or Immunosuppressed and transplanted patients)." That's what can be concluded from "at least one": (52% had no bad risk in D group, but only 38.46% had no bad risk in the other group). But it is also not clear where there were more patients with "multiple" factors! Or if they were those who had more problems at the end. The whole paper contains neither raw data nor any graphs and only means and standard deviations, as far as I see? I would personally really like to see the graphs of distributions or to use raw data to check myself. The critical question is how good the randomization was done.
• nautilus12 6y ago
  "Don't go outside, you'll get COVID", sounds more and more like horrible advice. Before knowing the virus died in sunlight, I still couldn't fathom why people were avoiding going out to parks and stuff. It was totally non sequitor.
  • AlanSE 6y ago
    Because the parks have people in them not wearing masks?
    • vorpalhex 6y ago
      You don't need masks if you are maintaining distance of 6 feet. Masks are for situations where distance can not be maintained such as trains and stores.
      • ad404b8a372f2b9 6y ago
        You need masks indoors even if you are able to maintain a distance of 6 feet.
      • PaulDavisThe1st 6y ago
        Evidence suggests that aerosols can remain in the air for minutes after being placed there by another non-masked individual. You could pass through the aerosol and inhale. Masks make sense outside too, at least in some circumstances.
        • JabavuAdams 6y ago
          Considering that the risk of transmission seems to depend on how long you are inhaling shared air from an infected person, and their viral load, I don't think it makes sense to worry about intermittently going through someone else's exhaust plume. I use a mask outside if I'm on a narrow sidewalk, but otherwise, I don't think there's much point. My favourite thing is the people who wear a mask over the mouth, but not the nose. Like worst of both worlds.
• ReflectedImage 6y ago
  And that's why I've been taking Vitamin D pills for the past 6 months. (It's been suspected for some time to have an effect) This doesn't mean go outside and get covid.
  • dgellow 6y ago
    You can always go outside to locations that aren't crowded.
  • arkitaip 6y ago
    I've been taking Vitamin D3 5000 IU and Vitamin K2 MK-7 100 mcg daily since February to boost my immune system, and I've noticed a radical difference in my colds. I used to get a major cold every 2-3 month and they were really bad lasting two weeks with fever, fatigue, coughs, colds, really stuffy nose, etc. Now? The two colds I've had were over in a week and the symptoms were so incredibly mild - mostly a light runny nose - that I'm legit grateful when I get a cold. Regardless of vitamin D's effect on covid-19, the supplement has already paid off big time as far as I'm concerned. I've started to take 1g of vitamin C for the same reason, i.e. to boost my immune system. I should add that I live in a Nordic country with long dark winters and that I can't/don't go outside as much as I should.
    • outworlder 6y ago
      Vitamin C is fine. Careful with Vitamin D. When you get a chance, go see your doctor and ask him to check your vitamin D levels. Don't forget to tell them you are taking suplements.
    • ouid 6y ago
      Don't really know why you haven't found the most obvious explanation for why you've gotten fewer colds.
      • arkitaip 6y ago
        Obviously thought about that but the intensity of the colds is way different.
• autokad 6y ago
  when i was doing the covid19 kaggle competitions in march and april, someone asked me what I learned. I was like I dont know, the data is messy but the sun seems to have something to do with reducing fatalities. (I used weather data as additional covariates)
  • dcolkitt 6y ago
    In general, the segment of the population that avoids sun exposure has twice as high an all-cause mortality rate as the segment that actively seeks sun exposure.[1] To put that in context that's on par with the health difference found between smokers and non-smokers. [1]https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12251 https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12251
    • amelius 6y ago
      Maybe also because staying inside makes it easier for the virus to spread.
      • briankelly 6y ago
        That study is from 2014.
      • deleted 6y ago
        [deleted]
• natcombs 6y ago
  > parallel pilot randomized open label, double-masked clinical trial. Dumb questions: What is a parallel pilot | what is open label? And Is double-masked the same as double-blind?
  • legerdemain 6y ago
    "Parallel" generally means that different groups of patients receive different treatments. The opposite is a within-patient study, where all patients get all treatments over time (possibly varying the order to prevent order effects). "Open-label" generally means "not blind at all." Basically, the patient knows what treatment is being administered. "Double-masked" is usually synonymous with "double-blind," because "masking" sounds less violent than "blinding." What did they actually do in the study? Well, §2.2.1 says the following: > 2.2.1. Randomization and Masking > > An electronically generated randomization 2:1 list was prepared by > independent statisticians. The list was accessible 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. My takeaway is that... the authors don't do a great job of describing who had access to what information. It sounds like those who analyzed the data didn't know which group was which, but in the case of unequal 2:1 group allocation it is typical for the larger group to be the treatment group. Why was unequal assignment used in the first place? The descriptor "open-label" suggests that someone knew which patients were in which groups: was it the people who administered the treatment, or the patients, or both? Unclear. The authors themselves write: "This pilot study has several limitations as it is not double-blind placebo controlled."
    • gruez 6y ago
      >"Double-masked" is usually synonymous with "double-blind," because "masking" sounds less violent than "blinding." This is literally the first time I've heard of "double-blind" being interpreted this way.
      • legerdemain 6y ago
• woeirua 6y ago
  Looks promising, but I would want to see a true double blinded RCT on a few thousand people before we say that Vitamin D is an effective treatment. Also, there's going to be a confounding question based on this study: is it just Vitamin D, or is it Vitamin D in combination with HCQ / Azithromyacin? That said, it probably wouldn't hurt you to supplement with Vitamin D this winter, even if it doesn't treat Covid.
  • gojomo 6y ago
    In combo with other observational studies correlating Vitamin-D-deficiencies with the worst Covid-19 outcomes, the case is growing. Vitamin-D in moderate amounts is pretty safe, so for those not already getting adequate sun exposure, it's a low-risk, high-potential-reward supplement.
  • cameldrv 6y ago
    It's difficult to imagine how the placebo effect could produce this result. Both arms of the trial were receiving HCQ and Azithromycin, so to the extent that there is a placebo effect, you'd think that adding a vitamin wouldn't change the result very much.
    • woeirua 6y ago
      I’m not saying it’s a placebo effect. Instead there could be unknown interactions between Vitamin D and HCQ/Az that could be the causal effect.
• asah 6y ago
  Non-white skinned people: sunlight may not be enough to increase your vitamin D. https://www.google.com/search?q=dark+skin+vitamin+d+minutes https://www.google.com/search?q=dark+skin+vitamin+d+minutes
  • AnonC 6y ago
    A non-tracking search link with DuckDuckGo: https://duckduckgo.com/?q=dark+skin+vitamin+d+minutes https://duckduckgo.com/?q=dark+skin+vitamin+d+minutes
  • gnur 6y ago
    Actually, even lighter skinned people can have lots of trouble generating sufficient vitamin D. My wife's family has the lightest skin possible but they all have vitamin D deficiency, if you have some kind of fatigue it is truly worth having your vitamin levels checked!
    • DoofusOfDeath 6y ago
      If they're that fair-skinned, is it possible that they're so careful about sunburn/cancer that they're getting less UV than most people?
      • serf 6y ago
        Pale complexion / skin can also be a symptom of anemia, and certain types of anemia are implicated/related to vitamin D deficiency. In such cases, both conditions may required supplementation to correct. So, fair to say that it can get complicated.
  • Brakenshire 6y ago
    Even white skinned people who spend long times outdoors may not get enough Vitamin D, especially if you live somewhere northern.
  • kyleee 6y ago
    Is there a scientific classification system for evaluating how light vs. dark a person's skin is? I'd like to know how much my relatively darker skin is preventing vit D uptake / creation in the body
• akimball 6y ago
  (db)RCTs are good. Fetishizing them is bad.
• gshotwell 6y ago
  This follows quite a lot of observational evidence. There are currently 11 studies that have found an association between serum vitamin D and Covid severity. These are listed here: https://github.com/GShotwell/vitamin_d_covid https://github.com/GShotwell/vitamin_d_covid
• Emphere 6y ago
  This is not a strong signal. The adjusted odds ratio is 0.03 (95% CI: 0.003 - 0.25). For randomised trials, it makes no sense to say that the difference in baseline is not significant because we have already observed the outcomes. It is better to use ASDs and in such small trials, small differences in baseline matter a lot. In this case it's pretty obvious the effect of vitamin D would easily be non significant if you shift around some variables. Reeks of p hacking imo
  • sauwan 6y ago
    Can you elaborate? As a statistical noob, this feels like a huge effect (1 of 50, or 2% - vs - 13 of 26, or 50%).
    • Emphere 6y ago
      You're absolutely right. Please disregard my entire comment.
  • mlyle 6y ago
    > This is not a strong signal. The adjusted odds ratio is 0.03 (95% CI: 0.003 - 0.25) Are you for real? Smallest effect in the 95% CI is a 4x reduction in ICU admission. Yes, it's probably closer to the bottom end of this range, but this is a fantastically different. > For randomised trials, it makes no sense to say that the difference in baseline is not significant For randomized trials, the baselines are not likely to be massively different. And, of course, the authors compared risk factors and ages to rule out some of the ways that the trial could be ridiculously tilted from the outset. > In this case it's pretty obvious the effect of vitamin D would easily be non significant if you shift around some variables. ...??? The endpoint was pre-declared, and we're just comparing two pre-randomized groups. Exactly what variables would you shift around? > Reeks of p hacking imo If you're going to cast aspersions, be a little more concrete.
    • Emphere 6y ago
      I...had such an epic brain fart, I don't even know what to say. Please disregard my entire comment.
• scott_paul 6y ago
  Anyone else notice that Calcifediol is the most expensive vitamin-D analogue on the market? What a huge surprise that the study chose that form of vitamin-D specifically.
  • hellofunk 6y ago
    Correlation is not causation.
  • JabavuAdams 6y ago
    That's quite a leap. Also, this study was done in Spain, so US intuitions probably don't apply without further study. D3 takes 7 days to be fully metabolised to calcifediol. When Drs measure your D levels, they're actually measuring calcifediol.
  • SamBam 6y ago
    oral Calcidefiol is significantly more potent than vitamin D3, and is a faster way to boost blood Calcidefiol, which is the purpose of ingesting vitamin D. I assume that the researchers picked it (1) to increase the chances of seeing a significant effect, if there is one, and (2) because if hours are at stake in saving a person's life, the fastest boost may be needed.
• notadoc 6y ago
  >All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 hours on the first day, and 200 mg every 12 hours for the following 5 days), azithromycin (500 mg orally for 5 days. Fascinating how hydroxychloroquine is routinely used and considered standard of care in most countries where the drug has not been politicized.
  • notatoad 6y ago
    >The best available treatment that at the beginning of the outbreak in our hospital, included the use of hydroxychloroquine/azithromycin therapy [23,24,26]. However, taking into consideration more recent data on the safety and efficacy of chloroquine and hydroxychloroquine in small randomized clinical trials, case series, and observational studies this treatment is no longer considered effective [32] in treating COVID-19. calling it the "standard of care" in the present tense is very disingenuous. it was briefly considered to be effective at the beginning of the outbreak. it was determined relatively quickly that it was not actually an effective treatment. this has nothing to do with politics.
  • jeffbee 6y ago
    Doesn't that have more to do with the timing of the study than anything else? Studies showing that HCQ isn't effective didn't begin to emerge until June.
• jonplackett 6y ago
  Surly now it's time to just start giving everyone some free vitamin D. Best case scenario: Less dead people. Worst case scenario: We all have healthier bones.
  • Giorgi 6y ago
    Free vitamin D? Like... Sun?
    • manmal 6y ago
      During the summer months, long sun exposure should suffice, yes. But the November sun (if any) will not do much for your vitamin D status.
  • jhawk28 6y ago
    Worst case is actually vitamin d toxicity. You can take too much.
    • D-Coder 6y ago
      I looked into that when I was told to take 2,000 IU daily, since I had no idea what an IU of vitamin D involved. A web search said that people who were taking megadoses of vitamin D, which was mislabeled and actually 10 times stronger than what they thought they were getting, started developing problems in a month or so. It's available right off the shelf. As long as people aren't taking an entire bottle all at once, it seems pretty safe to me. (Disclaimer: Dammit Jim, I'm a software engineer, not a doctor.)
    • jonplackett 6y ago
      Drinking too much water will kill you too. The point I’m making is there is basically no drawback to giving people a normal, healthy, vitamin D supplement. Plus possible upsides.
      • blithedale 6y ago
        Except the dosing in this study is a massive supra-physiological bolus that's something like 50x the daily RDV.
• tboyd47 6y ago
  Good on you, Spain. A study like this could never take place in the USA :( Too many powerful people are heavily invested in the belief that there is no treatment for it.
  • vore 6y ago
    Seems like a ridiculous claim when I'm sure almost absolutely everyone would like to get out of this mess.
    • jerf 6y ago
      It shouldn't be hard to sit for a moment and think of some people who would certainly like for there not to be a treatment consisting of ~$3-5 worth of off-the-shelf, completely unpatentable medicines and vitamins. There are absolutely some powerful vested interests in not seeing an easy treatment for this disease, or, by the same logic, pretty much any other disease either since there's nothing special about this one. (A not infrequent complaint on Hacker News.) I can't prove they're driving the discourse on treatment for COVID-19, but it sure isn't disproved by what I see happening out there.
      • deleted 6y ago
        [deleted]
      • vore 6y ago
        The original claim said "invested in the belief that there is no treatment for it", not "no inexpensive treatments". What you are rebutting is not against what OP is claiming.
    • tboyd47 6y ago
      You cannot fast-track a vaccine if there are other treatments available. Letting the word out that you can be cured from COVID-19 could make a lot of people lose much money. Both Vitamin D and the other one (it rhymes with byfroxymorophin) are cheap and out of patent. * https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track https://www.fda.gov/patients/fast-track-breakthrough-therapy...
• mikenew 6y ago
  There's a handful of blood-test-by-mail sites you can use to do a vitamin D test. Cost is around $50.
• koboll 6y ago
  Can anyone here help demystify how "oral calcifediol (0.532 mg)" maps to an equivalent amount of Vitamin D in the form you can buy in a drugstore?
  • gremlinsinc 6y ago
    I don't know, but I take 5000 ius a day and because of my gastric sleeve I'm still somehow deficient. So upped it to 7500 ius by adding a multivitamin. I'm also O positive (which means I won the damn blood lottery for covid hehe), but overweight, so gotta hedge my bets as best as I can. I also take zinc.
  • delecti 6y ago
    I take 5000 IU pills, and they're labeled as 125 mcg. The 0.532mg pills they were getting would thus be around 4.25x as much, or a bit over 21,000 IU based on how D3 is usually labeled for over-the-counter purchase. Though my pills are "cholecalciferol" not "calcifediol", so there's not a perfect 1:1 correspondance, but your body converts cholecalciferol into calcifediol, so based on nothing else my above calculation is probably not far off.
  • unibic 6y ago
    This is equivalent to 106400 IU of Vitamin D bought from a store.
  • cortesano 6y ago
    calcifediol (0.266 mg; 15,960 IU calcifediol) https://patents.google.com/patent/WO2016124724A1/en https://patents.google.com/patent/WO2016124724A1/en so may be 32.000 IU ???
• dilippkumar 6y ago
  Previously on HN, a physician shared some thoughts on treating Vitamin D as a medication and not as a dietary supplement: Part 1: https://news.ycombinator.com/item?id=24138590 https://news.ycombinator.com/item?id=24138590 Part 2: https://news.ycombinator.com/item?id=24261948 https://news.ycombinator.com/item?id=24261948 To summarize - popping in large doses of Vitamin D is not exactly safe.
  • blithedale 6y ago
    Thank you thank you thank you. There is a craze for popping Vitamin D related to the raft of observational studies, here... so many of which never find a causal link. Take my own particular condition: an inherited vascular dysplasia which causes frequent nose and GI bleeds. People with low Vitamin D seem to have a worse time of it in OBSERVATIONAL studies. But people with GI bleeds so bad they have daily diarrhea from hemorrhages and anemia that disables them to the point they can't work aren't going to be out in the sun, and aren't going to be able to absorb as many vitamins in their gut due to the havoc the hemorrhaging is yielding. Thinking really hard about the direction the arrow of causality runs here is massively important. Is it: LOW VITAMIN D ---> BAD BLEEDING? Or: BAD BLEEDING ---> LOW VITAMIN D And as the consequences of overdosing show, this isn't like popping an extra Metamucil cracker a day or something - dire stuff can happen.
    • ellyagg 6y ago
      People dose themsevles with OTC vitamin D all the time, including me. It doesn't appear to be a crisis. C19, otoh... You saw the apparent effect size in this study, right?
  • ellyagg 6y ago
    From the evidence I've seen, vitman D deficiency is a bigger problem than vitamin D toxicity. We already have dozens of RCTs showing that vitmain D supplements prevent respiratory infections. https://www.bmj.com/content/356/bmj.i6583 https://www.bmj.com/content/356/bmj.i6583
  • conorh 6y ago
    Deva is deep into writing part 3 at the moment (the physicians husband here) where she reviews these trials, what they mean and how they should be interpreted. I think she will be finished soon.
• tus88 6y ago
  Vaccine or bust.
• gumby 6y ago
  This seems pretty promising, though small n, result. Vitamin D is so ably we’ll well attested as a prophylaxis for pulmonary infections — in fact there was a large UK study published in January on this very facto. Starting in February I went on a prophylactic supplement of Vit D, Vit C and aspirin because of the then-unnamed Covid-19 virus. The aspirin (actually started that in april) is because of the pervasive excess clotting and sudden strokes in young people showing up in ERs (less attested in the US than some other countries for reasons I’m not sure about). I’d never taken supplements before. I’m immuno compromised so with my doctor we worked out the regime above plus some prescription drugs I won’t mention. So far, so good, but I’m isolating' so this could be a case where I’m also preventing tiger attacks.
  • ellyagg 6y ago
    N can be small when the effect size is huge.
    • gumby 6y ago
      It can be, depending on the protocol. This was a double blind yet open label (?) study. I’ve never done an open label study so don’t know how they have to be powered (and I’m not a biostatistician so won’t render a guess)
• mucinoab 6y ago
  Anyone knows what rol sunscreen plays in vitamin D intake/generation by sunlight?
  • graywh 6y ago
    the body makes vitamin D3 when UVB rays hit cholesterol in the skin sunscreen either blocks, scatters, or absorbs those rays seems to reason that sunscreen slows down sun burn and vitamin D3 production
  • graeme 6y ago
    This is not a direct answer, but: 1. Uva is the cause of most skin cancer 2. Uvb generates vitamin d and sunburns 3. When uvb is present, you can make sufficient vitamin d quite quickly This would suggest you would want sunscreen for longer exposures, or with much uva exposure. And could get vitamin d from a briefer exposure pre sunscreen. I can’t say how completely sunscreen blocks vitamin d however.
    • dralley 6y ago
      Given that sunburn is a response to cellular damage of your skin cells, why would it be the case that the two are de-coupled w/r/t UVA and UVB?
      • graeme 6y ago
        Actually, it seems I was wrong. I thought it was just UVA, but uvb also causes melanoma. I’d delete the above comment if I could. The main point that you can get vitamin d from short exposure without sunburn is correct, but I was incorrect on the risk. But he fact I was wrong about uvb and melanoma also makes me think I may be incorrect on the risk of uva during periods without uvb. https://en.wikipedia.org/wiki/Melanoma#UV_radiation https://en.wikipedia.org/wiki/Melanoma#UV_radiation
• IAmNotBatman_ 6y ago
  Yeah we wear too much sunscreen, a significant number of people are vitamin D deficient. From the UltraMind Solution book, you need the active form cholecalciferol in your supplements. You can safely take 5000-10000 IU a day for 3 months to get up to the optimal levels, then 2000 IU a day for maintenance. The Ideal range is 50 to 80 ng/ml in your blood tests. Also just minimal outdoor sun exposure is the best way to get it, no sunscreen. 15 minutes if you're light skinned, 35 if you're really dark.
  • beebmam 6y ago
    Please note that latitude, season, and cloud cover makes a big difference in the amount of time you need outdoors without sunscreen
  • kardos 6y ago
    > Also just minimal outdoor sun exposure is the best way to get it, no sunscreen. 15 minutes if you're light skinned, 35 if you're really dark. These prescriptions seem to always lack the amount of exposed skin. Is exposed hands enough or should one be naked?
    • pscsbs 6y ago
      The guidance is usually given for exposed arms and legs.
    • IAmNotBatman_ 6y ago
      Yeah the time is dependent, I just try to think of like our evolutionary history, pre clothes and where your ancestors are from. So I try to sunbathe by the pool during the summer. But if you work indoors, cholecalciferol is useful and you can get the blood tests for your levels.
  • liability 6y ago
    If you search "sunburn [location]" on wolfram alpha, you can get sun exposure guidance for that particular date and location, factoring in weather and your skin tone. Since I began using this a few months ago I have not been burnt.
• meiraleal 6y ago
  Meat (vitamin B) and sun (vitamin D) are the bane of COVID. We definitely have not been fighting this pandemic with the right tools.
• sradman 6y ago
  > Serum 25OHD concentrations at baseline or during treatment are not available. This is mind boggling. These 76 patients had extensive blood work done so why did the study design not include serum concentration testing before and after treatment?
  • blithedale 6y ago
    Welcome to every Vitamin D study done ever. I follow some PHD/RD combination researchers on Twitter and they all get together each time one of these studies is done and bang their heads against a wall.
• lrem 6y ago
  Can someone tell what is the equivalent dose of said calcifedol in regular D3? The article claims 0.532 mg have been used, which seems too large. From [1] I gather it's about 3x more potent, meaning we are talking about equivalent of 1.596mg of D3. Or, 10000% of RDA according to [2]. Is that right? [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460735/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460735/ [2]: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessiona...
  • graeme 6y ago
    That’s about 60,000 IU? Not necessarily out of line for such interventions. In cases of deficiency doctors will often prescribe weekly doses of 50,000 I believe. Have also seen RCT on vitamin d and the flu where groups where given 250,000-500,000 IU’s in one shot. ....obviously nobody reading this should take anything near those doses without consulting a doctor and without knowing your current blood level, to be clear.
    • lrem 6y ago
      Yup, 60kIU from my understanding. And here I am wondering if the 2kIU I'm doing would have any effect...
      • ac29 6y ago
        The amount used as an interventional or short term treatment can greatly exceed what is a prudent amount to take daily. Taking 50k/day long term is probably a bad idea.
        • graeme 6y ago
          No probably about it, it’s a disastrous idea.
      • graeme 6y ago
        Again: those are medical doses, given either very temporarily or in weekly/monthly doses. 2k definitely ha san effect on a daily basis. To really know, there are two things you can do: 1. Get a vitamin d test. Fairly cheap online 2. Use the dminder app to track estimated D over time from supplements and sun exposure I don’t think I was clear enough in my post: 60,000 is not a daily dose! Higher than 4000 IU daily over a long period can lead to excess, according to Deva Boone, a doctor who was posting here and wrote some articles on this topic. 60,000 is something I’ve read about where 1. A doctor wants to correct a large deficiency, and 2. Judges large, infrequent doses are best. (My guess would be for adherence) Do not, do not. Do not take anything anywhere in that range on your own. Stick to sub 4,000 for a daily doses, and ideally get a blood test.
• MivLives 6y ago
  Is there a trustable authority that measures the actual contents of supplements in the US? When I try to search it, it's pretty heavily SEO'd.
  • sk0g 6y ago
    LabDoor [0] maybe? Use them for their protein rankings mainly, but they have a Vitamin D section too. [0] https://labdoor.com/rankings/vitamin-d https://labdoor.com/rankings/vitamin-d
• ilaksh 6y ago
  In the future we may decide on windows that permit some UV B.
• epmaybe 6y ago
  You know, at this point, I'm basically over debating the merits of vitamin d. Take it, don't take it, I don't really care, just please tell your doctor you're taking it. To pharmaceutical companies or supplement companies, or the NIH: fund a well powered study, pretty please?
• afrojack123 6y ago
  Every year they issue a winter influenza vaccine instead of making vitamin D pills and artificial sunlight available. Young people never take the winter flu vaccine and are fine.
• longtimegoogler 6y ago
  As someone with low vitamin D this kinda sucks. Does anyone know how effective OTC vitamin D is at raising vitamin D levels and what kind of doses to take?
  • neckardt 6y ago
    OTC vitamin D is effective, recommended dose is 600IU per day: https://en.wikipedia.org/wiki/Vitamin_D#Recommended_levels https://en.wikipedia.org/wiki/Vitamin_D#Recommended_levels
  • jp42 6y ago
    In my experience, it is certainly effective. I take 2000IU fairly regularly since last few years and it certainly helped to keep vitamin D level slight above minimum required.
  • amai 6y ago
    Dai (2018): Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial https://pubmed.ncbi.nlm.nih.gov/30541089/ https://pubmed.ncbi.nlm.nih.gov/30541089/ "Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. "
• doublekill 6y ago
  Experts and health authorities were adament to tell us that vitamins have zero effect against COVID. Not: we don't know and taking a Vitamin C can't hurt, unless you count an upset stomach. But: stop sharing fake health information, this is an infodemic! Just wash your hands. So to add to the infodemic: selenium and iodine deficiency also increases severity. Take some iodized salt and Brazil nuts now, or wait 5 months for the authorities to understand that absence of evidence is not evidence of absence. And no matter what Youtube bans you for going against the WHO: tumeric is an efficient antiviral.
  • sbelskie 6y ago
    Any examples of the CDC, FDA, or NIH statements telling us that vitamins have zero effect on COVID? I’d also be interested in statements from the WHO, but that one I wouldn’t be at all surprised by.
    • doublekill 6y ago
      Vitamin C is listed as fake news on WHO. Fact checker sites listed vitamin D as false, then switched to correct after research. Doctors, journalists, and health experts in Brazil and the Netherlands chided social media for not removing "fake" info on vitamin supplements. I'll check some CDC sources later to contextualize these claims to the US.
      • BickNowstrom 6y ago
        Mayo Clinic: Debunking COVID-19 (coronavirus) myths. Extremely unlikely to work and might cause serious harm. [...] Supplements. Many people take vitamin C, vitamin D, zinc, green tea or echinacea to boost their immune systems. While these supplements might affect your immune function, research hasn't shown that they can prevent you from getting sick. Notice the weird mind crinkle: Got to debunk it, and use "prevent you from getting sick" as the reason for it not working (and the subtle differences between: "No research has shown", "research hasn't shown", and "research has shown that it can't prevent you"). Even though plenty of research shows it prevents you from getting severely sick, when you do get sick. Willing to bet that garlic (a famous folk knowledge cure for the flu, smashed boiled garlic with hot water) is actually effective in recovery and severity, but the fact checkers present it as a "COVID cure" and of course that can be debunked. But it is a debunking based on a weird strawman we saw with masks: Masks are not protective to COVID because the eyes can catch it too. As if protectiveness and immune health is binary and anything else than 0 or 1 has to be a lie. Could not find anything about the CDC, just https://www.cdc.gov/nutrition/infantandtoddlernutrition/vitamins-minerals/vitamin-d.html https://www.cdc.gov/nutrition/infantandtoddlernutrition/vita... where they recommend Vitamin D for children under 2 years old, to prevent deficiency, but no where mention a recommendation for using it during a pandemic to keep your immune system healthy. As for selenium deficiency and iodine deficiency, the research is slowly catching up: > Certain micronutrients are seen as supportive for the treatment of and protection against viral diseases with some vitamins (A, B6, B12, C, D, and E) and essential trace elements (zinc, iron, selenium (Se), magnesium, or copper) discussed as particularly promising . > However, the data base is very small and it is unknown whether certain vitamins or trace elements are deficient in patients with COVID-19, and whether the concentrations are related to disease severity or mortality risk. > The collaborative research team from Germany hypothesised that Se may be of relevance for infection with SARS-CoV-2 and disease course of COVID-19 and that severe Se deficiency is prevalent among the patients and associates with poor survival odds in COVID-19. As for turmeric, mentioned in relation to COVID a bannable offense on Youtube: It inhibits and suppresses Zika, Hepatitis, HIV, Noro, coxsackie, HBV, herpes, influenza, encephalitis, dengue, corona, and chikunya. It also suppresses cytokine signalling. But experts warn that it may interfere with the immune system when fighting COVID, and that it is neither a cure nor a treatment nor a helpful supplement. WHO lists it under hoaxes (except when discussing Chinese traditional medicine). And you are a bad person if you share this potential online, because you don't have a randomized trial to back up that it works against SARS-CoV-2. MedicalNewsToday: In a rapid review of the evidence published on May 1, 2020, researchers from the Centre for Evidence-Based Medicine at the University of Oxford in the United Kingdom unequivocally conclude: “We found no clinical evidence on vitamin D in [the prevention or treatment of] COVID-19.” They also write that “[t]here was no evidence related to vitamin D deficiency predisposing to COVID-19, nor were there studies of supplementation for preventing or treating COVID-19.” Potential Effect of Curcumin Treatment of COVID-19: Curcumin may have beneficial effects against COVID‐19 infection via its ability to modulate the various molecular targets that contribute to the attachment and internalization of SARS‐CoV‐2 in many organs, including the liver, cardiovascular system, and kidney. Curcumin could also modulate cellular signaling pathways such as inflammation, apoptosis, and RNA replication. Curcumin may also suppress pulmonary edema and fibrosis‐associated pathways in COVID‐19 infection. WHO Fact or Fiction: There is no scientific evidence that lemon/turmeric prevents COVID-19.
• ptest1 6y ago
  The problem I see with this trial is that it’s open-label, small n, and has subjective endpoints (ICU admission as the primary outcome). The study is underpowered to detect mortality. Given the open-label nature of the trial, the subjective outcome with the small n makes this result less strong. Why is this the case? Well, for this trial the physicians treating patients knew who got the Vitamin D and who didn’t, and thus they may have been more likely to admit those who didn’t to the ICU (subjective). Something like mortality is not as subjective, but there are too few study participants to detect a mortality signal in this trial. If I had been conducting this small open label trial I would have picked some less subjective outcomes, like maybe P/F Ratio.
• sagebird 6y ago
  It would be tragic if taking vitamin D supplements had a negative effect on Covid survivability. I think that it is extremely unlikely, though possible unless a specific study has ruled this out. EG: Perhaps vitamin D supplementation upon Covid-19 diagnoses is only effective if you have not been supplimenting. Like: Maybe drinking alcohol at a party is helpful to court a new partner, unless you are an alcoholic already. Not the best analogy but I hope you'll take my point in good faith.
• robertofmoria 6y ago
  This test really doesn't hold a lot of useful data. It doesn't calculate any of the statistics of those that died which is kinda of important when age and previous health conditions are important. It doesn't gather BMI, physical activity levels, ethnicity, secondary/multiple infections, cause of death, type 1 or 2 diabetes, etc. Medical trials are hard because of all the variables. I think it actually works against this trial having it randomized especially when there is no placebo group.
• fithisux 6y ago
  GPT-3 ?
• stjohnswarts 6y ago
  Very small scale but sounds promising. I've been taking 2000UI/day for few years now since my doc found my vitamin D was pretty low, it's now far up in the normal range now. I didn't let him give me the massive doses that they want to give you for low vitamin D, and opted for just starting to take the supplement, when I went back in 3 months later everything was in the normal range. I don't actually get much sunlight as a den dwelling programmer so it's the next best thing.
  • neuronic 6y ago
    Sounds great. What's important to understand with high vitamin D doses is that overdoses can occur unregulated by the body. The regulation of vitamin D usually occurs before its synthesis after sunlight exposure. Supplementing synthesized vitamin D circumvents the regulation and allows vitaminosis to happen. I have read wildly different recommendations for the dose. Typical package is 1000 IU, you take 2000 IU, others recommend upwards of 8000 IU due to possible issues with earlier studies leading to FDA/regulatory agencies recommendations. Again, rather stay below 5000 IU unless explicitly told otherwise by a doc. Always get blood work done to REALLY figure out your levels and how to fix them. Again, why we can overdose with supplements but too much sunlight won't cause an overdose: Sunlight + components ---> X (regulation) <---> Vitamin D ---> effect in body Supplements start behind the regulation step...
• amai 6y ago
  Dai (2018): Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial https://pubmed.ncbi.nlm.nih.gov/30541089/ https://pubmed.ncbi.nlm.nih.gov/30541089/ "Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. "
• BiteCode_dev 6y ago
  It this gets confirmed, we'll have a dilemna: confined people will become deficient in D vitamin by lack of sun exposure.
• jamesfisher 6y ago
  > open label, double-masked clinical trial Aren't "open label" and "double-masked" contradictory? "An open-label trial, or open trial, is a type of clinical trial in which information is not withheld from trial participants. In particular, both the researchers and participants know which treatment is being administered." (Wikipedia) "Double-Masked Study. A type of clinical trial in which neither the participants nor the research team know which treatment a specific participant is receiving." (NIH)