Talk:Vitamin D

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Covid-19

I have added the last three words to the following sentence (which is under the "Immunity" subheading):

"Deficiency has been linked to increased risk or severity of viral infections, including HIV[82][83] and possibly Covid-19."

I'm not an experienced Wiki editor, so don't know the correct process or standards for my change (e.g. is "Covid-19" the correct name, and how to make it linkable). Perhaps someone can do it properly for me.

My source for my edit is mainly Dr. John Campbell. I am watching his YouTube channel during the Covid-19 pandemic, and he often strongly suggests that Vitamin D deficiency is very important to how badly people suffer from this virus. (I also don't know how to insert sources in the main article).

Regards, 122.62.138.18 (talk) 06:24, 8 May 2020 (UTC)Martyn

Added link and two medical reviews. Jrfw51 (talk) 08:17, 8 May 2020 (UTC)

COVID-19

Text and two references removed from article: "...and possibly COVID-19."

References

These references and others in the literature speculate that low vitamin D exacerbates severity of COVID-19 infection, and that some of the known COVID-19 severity risk factors (obesity, African and Hispanic...) are linked to having low vitamin D status. The connection may be true, but in my opinion premature until several clinical trials are completed and reviews confirm the connection. Nutrition research has been fraught with correlation getting ahead of proof of efficacy. Examples, selenium and vitamin E for preventing prostate cancer. Extraordinary claims require extraordinary evidence. At clinicaltrials.gov there are multiple clinical trials looking at exactly this question. When those are completed and published it will be appropriate to add content to this article. David notMD (talk) 13:08, 8 May 2020 (UTC)

Yes indeed, no multivariate analyses and no randomised, prospective placebo-controlled clinical trials or systematic reviews. Hence the "possibly", based on two different articles in reliable source journals, one an editorial and one a review. Your opinion may be right -- but consider the quality of this evidence related to some of the other Covid-19 associations and the comparison with influenza. Jrfw51 (talk) 17:27, 8 May 2020 (UTC)

BTW, Covid-19 (lower case) in NEJM, BMJ, Times and Guardian. Jrfw51 (talk)

Indeed they use covid-19. Though WHO (who named it), PHE, CDC, Nature, The Lancet use COVID-19. I don't think that 'possibly' overstates the connection, but tend to agree with David that this probably isn't evidence enough for the article. Vitamin D is said to be involved with pretty much every disease at one time or other. |→ Spaully ^~talk~  19:08, 8 May 2020 (UTC)

Page visits to Vitamin D have increased 1/3 in recent days. Vitamin C visits saw a doubling and then decline in March, when some news was being reported about C and COVID-19. David notMD (talk) 23:47, 15 May 2020 (UTC)

FYI - I was taken to task (and reverted) for adding information about vitamin C and COVID-19 to the Vitamin C article, as being premature, given the unfortunate tendency for nutrient and non-nutrient dietary supplements being touted as cure-alls. As with vitamin D, for vitamin C there are ongoing clinical trials listed at clinicaltrials.gov. David notMD (talk) 01:32, 9 May 2020 (UTC)

FYI, here's the set of clinical trials testing Vitamin D and Covid-19 that I found:

• 200 mild Covid patients. Done 2020-06. https://clinicaltrials.gov/ct2/show/NCT04334005?term=Vitamin&cond=Covid-19
• 1080 new Covid patients. Done 2020-12. https://clinicaltrials.gov/ct2/show/NCT04363840?term=Vitamin&cond=Covid-19
• 600 high-risk normals. Done 2021-08. https://clinicaltrials.gov/ct2/show/NCT04335084?term=Vitamin&cond=Covid-19
• 260 elders with Covid. Done 2020-07. https://clinicaltrials.gov/ct2/show/NCT04344041?term=Vitamin&cond=Covid-19
• 1008 Covid patients. Done 2020-08. https://clinicaltrials.gov/ct2/show/NCT04366908?term=Vitamin&cond=Covid-19

Gnuish (talk) 03:45, 13 May 2020 (UTC)

Those are the dates the trials are expected to be done, if recruiting goes as planned. Actual status as of today is that one trial is recruiting subjects and the other four not yet recruiting. Once "Done" the results will need to be analyzed and published. David notMD (talk) 09:55, 13 May 2020 (UTC)

Evidence of the association of low plasma 25-OH-vitamin D and COVID-19 infection here PMID:32397511. Clearly still preliminary, primary data. Jrfw51 (talk) 17:46, 15 May 2020 (UTC)

Yes, preliminary. Compared n=27 COVID-positive to n=80 COVID-negative. The positives were vit D defic, as serum 11.1 ng/ml was well below the 20 ng/ml definition of defic. Other observational studies reporting more severe course of disease and higher risk of death if low D. Begs question is D protective? Treatment? Both? All interesting (I've starting taking a D supplement), but I really, really want to see clinical trial results. David notMD (talk) 20:25, 15 May 2020 (UTC)

Here is a multivariate analysis showing no association.PMID:32413819 Jrfw51 (talk) 10:47, 20 May 2020 (UTC)

It is still observation rather than an intervention clinical trial (several of which are ongoing or starting soon). It looked at a small number of subjects (less than 500) and did subset analysis to see if serum vitamin D still indicative after race controlled for as a variable. I am still against any content in the article until clinical trials are reported. I am asking here how other editors feel about this topic. David notMD (talk) 11:40, 20 May 2020 (UTC)

Data from nearly 400,000 Biobank subjects. 494 diagnosed positive with COVID-19. Multivariate analysis of all subjects (not subset) adjusted for ethnicity, sex, month of assessment, Townsend deprivation quintile, household income, self-reported health rating, smoking status, BMI category, age at assessment, diabetes, SBP, DBP, and long-standing illness, disability or infirmity. Strengths: big data, good stats, shows the association has been considered. Limitations: primary data, not interventional, a topic of immense current interest that editors want to add to WP. Jrfw51 (talk) 14:57, 20 May 2020 (UTC)

Then this should not be the only observational study described and cited. David notMD (talk) 17:29, 20 May 2020 (UTC)

Agree. Added some text. Hope this is reasonable now. Jrfw51 (talk) 07:32, 21 May 2020 (UTC)

Added a sentence and ref to the list of trials at clinicaltrials.gov. David notMD (talk) 12:47, 21 May 2020 (UTC)

Evidence Supports a Causal Role for Vitamin D Status in Global COVID-19 Outcomes. There is also some data showing Vitamin D supplementation is useful for the treatment of COVID-19. This Google Doc was created by Dr Gareth Davies (PhD), Dr Joanna Byers (MBChB), Dr Attila R Garami (MD, PhD), to track all of the relevant studies, and to outline the mechanisms by which Vitamin D helps combat COVID-19. https://docs.google.com/document/d/1jffdZOSuIA64L_Eur8qyCQ12T7NXrHSKPxtMe134C0Y/edit?fbclid=IwAR2nzFz2X393A7VZ-t4H9ZgmQcmvGyUVRAD1etDd4ly3yOhxBW9xTtusTqY#heading=h.hrvlw7sle0sz There is too much information contained in this Google Doc to paste here, but a number of these studies should be useful references. These doctors published a summary paper here... https://www.medrxiv.org/content/10.1101/2020.05.01.20087965v3.full.pdf Tvaughan1 (talk) 23:57, 19 July 2020 (UTC)

A new peer-reviewed randomized controlled trial shows that giving large doses of Calcifediol (the active form of Vitamin D) to COVID-19 patients massively reduces the percentage of patients that will need ICU care, as well as reducing the mortality. https://www.sciencedirect.com/science/article/pii/S0960076020302764 Tvaughan1 (talk) 06:24, 4 September 2020 (UTC)

This appears to be the first published clin trial (actually, pre-pub and not yet found via PubMed). It was small (total of 75 subjects), and all subjects were getting hydroxychloroquinone and azithromycin as part of standard treatment at that time, but the results looked strong. The study did not assess the vitamin D status of the enrolled subjects. Dosing was 21,280 IU at start, then 10,640 on days 3 & 7 and weekly thereafter. My search at PubMed on vitamin D and COVID-19 yielded 38 reviews and no RCTs. David notMD (talk) 12:17, 4 September 2020 (UTC)

Interesting. Would be better to get a secondary source to review this.Jrfw51 (talk) 19:47, 4 September 2020 (UTC)

This study is better evidence than anything in the article now. It's the only peer reviewed randomized controlled trial (pre-) published on the topic, and the results are overwhelmingly positive. We would be doing Wikipedia readers a disservice not to mention it. Tvaughan1 (talk) 20:10, 4 September 2020 (UTC)

By itself, it does not meet Wikipedia's standard for medical research (WP:MEDRS). The article's authors wrote "This pilot study has several limitations as it is not double-blind placebo controlled." and also acknowledged that baseline vitamin D status was not measured. In my opinion, Wikipedia can wait until the authors' follow-up (larger) trial is completed, along with the other vitamin D trials in progress. David notMD (talk) 21:40, 4 September 2020 (UTC)

It doesn't need to be double-blind. It was a randomized controlled trial. Baseline Vitamin D level would be nice to know, but this study used a fairly massive dose of the active form of Vitamin D. In terms of Vitamin D as a treatment, post COVID infection there is less scientific evidence. In terms of pre-existing Vitamin D levels before COVID infection, there are many studies and peer reviewed meta-analysis https://www.medrxiv.org/content/10.1101/2020.05.01.20087965v3.full.pdf. Here is yet-another published study demonstrating that Vitamin D deficiency leads to worse COVID-19 outcomes... https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770157 Tvaughan1 (talk) 23:09, 4 September 2020 (UTC)

The conclusion from the JAMA article: "In this single-center, retrospective cohort study, likely deficient vitamin D status was associated with increased COVID-19 risk, a finding that suggests that randomized trials may be needed to determine whether vitamin D affects COVID-19 risk." David notMD (talk) 07:53, 5 September 2020 (UTC)

The conclusion from "Evidence Supports a Causal Role for Vitamin D Status in Global COVID-19 Outcomes (a peer reviewed paper)... "Conclusions: Our novel causal inference analysis of global data verifies that vitamin D status plays a key role in COVID-19 outcomes. The data set size, supporting historical, biomolecular, and emerging clinical research evidence altogether suggest that a very high level of confidence is justified. Vitamin D prophylaxis potentially offers a widely available, low-risk, highly-scalable, and cost-effective pandemic management strategy including the mitigation of local outbreaks and a second wave. Timely implementation of vitamin D supplementation programmes worldwide is critical with initial priority given to those who are at the highest risk, including the elderly, immobile, home bound, BAME and healthcare professionals." Tvaughan1 (talk) 17:57, 5 September 2020 (UTC)

I have added the recent Castillo RCT as the results are clearly significant and important. I hope further studies and reviews will allow us to better fulfil WP:MEDRS. Jrfw51 (talk) 12:18, 5 September 2020 (UTC)

I consider this premature but will not revert it. Looking forward to more research being published. David notMD (talk) 14:18, 5 September 2020 (UTC)

At this point, with the most recent studies, the statement "there is only preliminary evidence of a direct association between vitamin D deficiency and COVID-19 infection" is clearly misleading. No one has claimed that adequate Vitamin D prevents COVID-19 infection... that's a red herring. The role of Vitamin D is to enable the immune system to successfully handle a COVID-19 infection, enabling a patient to avoid ICU care or death. It has been established in multiple peer reviewed papers that Vitamin D deficient patients have far worse outcomes than those with adequate Vitamin D. To include the above misleading statement, but bury all of the good evidence that Vitamin D levels minimize the rate of ICU care and death is irresponsible. The UK Biobank study mentioned in the next sentence only sought to determine if Vitamin D reduced the risk of infection - again... a red herring. As well, the UK "evidence summary" mentioned in the following sentence was weak compared to the much more thorough analysis of Gareth Davies (PhD), Attila R Garami (MD, PhD), Joanna Byers (MBChB), which established a causal relationship. The JAMA article established a causal relationship. People's lives are at stake. So let's not bury the best information we have. Vitamin D doesn't prevent infection, but it sure helps you survive it.Tvaughan1 (talk) 01:04, 6 September 2020 (UTC)

While I stated I would not revert, I support Zefr's revert. Wikipedia is intended to be a trailing indicator for health science, not breaking news. Physicians who are treating COVID-19 patients do not need a Wikipedia article to stay current. David notMD (talk) 03:06, 6 September 2020 (UTC)

No one suggested physicians use Wikipedia as a primary source for medical information. I really hope they don't. Wikipedia is an encyclopedia. The best available notable, relevant, authoritative information should be included. To clarify, there are 3 possible questions with regard to COVID-19 and Vitamin D. 1 - Does higher/adequate D level help to prevent infection? 2 - Does higher/adequate D level improve the outcome for those who become infected? 3 - Can D help as part of the treatment? The article currently focuses only on question 1. We leave readers totally in the dark as to question 2 and 3, despite solid information being available. I agree that there is no evidence that adequate Vitamin D levels can prevent infection. That's kind of a stupid hypothesis, in my opinion. It's not worth spending a lot of words on. I'm fine with the article mentioning briefly that there is no evidence that adequate Vitamin D helps to prevent a COVID-19 infection. For question 2, we have peer reviewed papers that show a strong causal relationship, and we have a wealth of studies that explain the biological mechanisms by which adequate Vitamin D helps the immune system respond better to respiratory viruses, and in particular COVID-19. For question 3 we now have a peer reviewed study that showed overwhelmingly positive results. Of course we also have tons of anecdotal evidence from many doctors who have been giving Vitamin D as part of their treatment regimen (including the CDC and a number of other organizations ok'ing it as an adjunctive therapy for COVID patients). Although the latter isn't good enough for Wikipedia, medical experts understand the many ways Vitamin D is crucial for the immune system, and when you look at the statistically certain, overwhelmingly positive result (there is no possible way to explain that result by random chance or ANY OTHER WAY), I believe it's worthy of a mention. Tvaughan1 (talk) 20:02, 6 September 2020 (UTC)

Here is another study (non peer reviewed preprint) The link between vitamin D deficiency and Covid-19 in a large population from Israel examining 52,405 infected individuals and comparing them with 524,050 control individuals. The study found "a highly significant correlation between prevalence of vitamin D deficiency and Covid-19 incidence", as well as "A significant protective effect was observed for members who acquired liquid vitamin D formulations (drops) in the last 4 months". Tvaughan1 (talk) 18:35, 8 September 2020 (UTC)

And now we have a peer-reviewed, published meta-analysis involving Vitamin D and COVID-19. https://www.frontiersin.org/articles/10.3389/fpubh.2020.00513/full . "Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes." This article criticizes and questions the studies that are referenced in Vitamin D. "Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions." So, basically Vitamin D presents only bad analysis, while ignoring / suppressing the many higher quality studies. Tvaughan1 (talk) 19:53, 11 September 2020 (UTC)

Yes it's an interesting and extensive review of associations. Not itself a meta-analysis. Single author. It could be added to the first sentence about concerns and associations. I would also suggest that section is moved back to where it was. Research could continue to keep trials that are questionable -- like for having "pilot" in the title! Jrfw51 (talk) 13:45, 12 September 2020 (UTC)

I'm going to remove the UK Biobank / NICE study citations and all references to them. They are outdated, and a number of better studies have contradicted their preliminary conclusions. The UK Biobank study tried to correlate Vitamin D data from 2006-2010 with COVID status in 2020. Obviously, that's a far cry from measuring the Vitamin D levels today. The Benskin study and the https://www.sciencedirect.com/science/article/pii/S0960076020302764 are clearly more authoritative. Neither of these (and many other studies that were examined by Benskin) were not available when NICE made its preliminary recommendation. Tvaughan1 (talk) 21:02, 13 September 2020 (UTC)

I have updated this with some dates and new sources. In terms of quality of evidence, the NICE commissioned review is higher quality than a single author review, however recent and detailed. I accept the reservations about the Biobank data but we cannot discard that as the analysis is thorough. We need Balance and I think must stick with published peer-reviewed articles. Until there are secondary sources we can quote, in this Research section, good quality primary research trials (prospective/cohort) should be acceptable. When there are the RCTs and reviews/guidelines from bodies we can quote, this can be updated and moved back to the main section of the article. Jrfw51 (talk) 14:43, 14 September 2020 (UTC)

The NICE study was not peer reviewed. It was highly criticized (debunked, even) by multiple authors. These criticisms were summarized by Dr. Linda Benskin in the "Debate Over Reports Using “Big Data” (the UK Biobank and EPIC, see Results and Retrospective Chart Reviews That Are Neutral or Strongly Oppose the Hypothesis)" section of her paper. Besides comparing ancient Vitamin D blood test readings with COVID outcomes today, it should be obvious that if you're studying the causal relationship between Vitamin D and COVID-19, you don't adjust for dark skin or obesity, both of which lower Vitamin D levels. These are not confounders, they're causal factors. Given the wealth of valid criticism of the NICE study, it can only be regarded as misinformation today. We have no "balance" in the COVID-19 research section of Vitamin D. We have only the misleading conclusion that Vitamin D does nothing to help prevent COVID-19. Meanwhile multiple peer-reviewed articles, including RCT studies demonstrate a statistically unassailable correlation between Vitamin D levels and COVID-19 outcomes, and a peer-reviewed study also shows a statistically overwhelming positive benefit from Vitamin D as part of a COVID-19 treatment plan. Other Wikipedia articles, such as Coronavirus disease 2019#Research present solid peer reviewed research on COVID-19 as preliminary research, while we await more meta-analysis, and eventually, policy changes.Tvaughan1 (talk) 17:23, 14 September 2020 (UTC)

Yes but remember we are writing an encyclopedia here rather making than our own arguments. The distinction between confounding and causal factors is difficult. I supported and did include the Castillo peer-reviewed and published RCT, first in the main text and then in this research section.PMID:32871238 I think it is the key initial RCT with impressive benefits for 25(OH)D (calcifediol) supplementation cautiously presented. It has been reverted twice. Are there any other editors who are prepared to see this important early finding included in this Research section? Jrfw51 (talk) 19:35, 14 September 2020 (UTC)

The UK Biobank studies (one of which NICE relied on) were shot down in flames by multiple papers. Benskin summarized all of the flaws in her section "Debate Over Reports Using “Big Data”. Did you read this section, and follow the citations? These papers make it clear that these studies were severely flawed in many ways. The Benskin paper is a much better, peer reviewed analysis of more recent studies, during a time frame when COVID testing was much more widespread and accurate, measuring CURRENT Vitamin D levels (not levels from 10 to 14 years ago). In addition to Benskin and Castillo, we also have Evidence Supports a Causal Role for Vitamin D Status in Global COVID-19 Outcomes (peer reviewed). And we have this recent study published in the Journal of the American Medical Association... Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. The weight and quality of the more recent evidence overwhelms the earlier, flawed evidence in the UK Biobank and NICE studies. In addition to sketchy data, there was very sketchy analysis of the data, and this was thoroughly criticized by multiple follow-up papers. Tvaughan1 (talk) 22:08, 14 September 2020 (UTC)

I reverted your deletion as currently the UK NICE evidence summary would be classed as high quality of evidence, being multi-authored by experts from a national body. Yes there have been further publications, and the Benskin single-author updated review has more data (but is not a meta-analysis) and has criticisms of some earlier conclusions. We cannot include the as-yet unpublished (and not peer-reviewed) medrxiv paper by Davies, Garami and Byers. When it is published it will add more weight. The Meltzer paper is in JAMA Netw Open (not JAMA); I have added that to the papers cited to show evidence of an association. Vitamin D levels are most recent, within a year, and not "current" levels. Regarding vitamin D levels and ethnicity, the effects of polymorphisms in the vitamin D-binding protein become important. See PMID:24256378. Sorting out whether this is causal or confounding is difficult! That's why we need the intervention studies such as that by Castillo. Jrfw51 (talk) 09:00, 16 September 2020 (UTC)

Yet another peer-reviewed, published study demonstrates the clear inverse relationship between vitamin D levels and COVID-19 infection rates. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels "The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983–0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges."Tvaughan1 (talk) 19:46, 18 September 2020 (UTC)

An Italian study announced in Medscape... Low Vitamin D in COVID-19 Predicts ICU Admission, Poor SurvivalTvaughan1 (talk) 19:49, 18 September 2020 (UTC)

I've added the peer-reviewed, published study by Kaufman which is large, has multivariable analysis, and balances the other reports with nonrecent 25(OH)D levels. When other papers are published, they can be added. We need to continue to be alert for new review articles and any randomized, controlled trials. Jrfw51 (talk) 16:53, 19 September 2020 (UTC)

• We really need to be very strict about WP:MEDRS and cite the WP:BESTSOURCES for any material relating to COVID-19. This topic area is subject to discretionary sanctions: I have added a page banner above as a reminder. I have cleaned out a vast number of primary and other questionable sources that had accumulated in the article. Alexbrn (talk) 12:44, 1 October 2020 (UTC)

Yes I am very aware of the WP:MEDRS requirements. This is in the Research section of the article, where novel primary sources often and up, and all of the sources are published, peer-reviewed papers or reputable main-stream press reviews. Also the quality of the Frontiers Public Health article is in fact very good and I nuanced how this was presented for balance. There is debate here (see today's Times) and of course there is considerable interest. I have worked hard to try to keep this balanced with due weight. Please consider reverting or discuss further. Jrfw51 (talk)

There is no exemption to WP:MEDRS for a research section (though POV pushers of many stripes have tried to claim that!). A single author narrative review in a Frontiers journal is not an approrpiate counter to a strong WP:MEDRS. If and when we have more good sources they may be included. What you have reverted is a mess. Continue this and you risk getting sanctioned. Alexbrn (talk) 14:03, 1 October 2020 (UTC)

@Alexbrn: this was the what you have reverted:

(The COVID-19 pandemic raised concerns that, as vitamin D deficiency is a risk factor in respiratory infection ...,) the incidence, severity and outcomes of COVID-19 infection could be associated with differences in vitamin D levels, with possible benefits resulting from supplementation.

As of October 2020, there are increasing numbers of published reports of case series showing direct associations between vitamin D deficiency, COVID-19 infection and severity. As many other other factors can influence 25(OH)D levels, multivariate analysis of these findings has been performed in some studies to adjust for confounding factors such as ethnicity. In studies using UK Biobank data of people with vitamin D levels measured at least 10 years previously, associations of low 25(OH)D with a higher incidence of COVID-19 infection, severity and mortality were no longer significant when adjusted for ethnicity, obesity and lower socioeconomic status. A large US study showed that the association between lower SARS-CoV-2 positivity rates and higher 25(OH)D levels remained significant in a multivariable logistic model which adjusted for demographic factors including latitude, race/ethnicity, sex and age. Some of the variations in the prevalence of COVID‐19 and mortality rates between countries and ethnicities may be explained by differences in vitamin D metabolism and blood levels due to different frequencies of polymorphisms in the vitamin D-binding protein.

References

The first reference (Rhodes) is an editorial. The others are narrative reviews, of which the Frontiers is the fullest even if it is single author. I am aware of current discussions re Frontier journals, but I recommend you read this article, even if it doesn't stay. Some of these other reviews need to be included. There are two mainstream press articles giving balance (6 and 8).

I have no point of view, except that there is widespread scientific and lay debate at the moment. You deleted the different takes on ethnicities, where there is a balance needed, and the DBP polymorphisms have been shown to be relevant. You are threatening me with sanctions ... ? Perhaps you will selectively restore what you have slashed. You may think 8-10 citations are a mess -- and yes we would prefer one high quality systematic review -- but they take time. We have disagreed before, but there is great interest in this area at present and I think the page visits reflect this. Please restore the first sentence so it makes sense and add back some more of the rest. Jrfw51 (talk)

It is simply incorrect that these sources are reviews, they are nearly all primary sources, i.e. unreliable for non-trivial biomedical claims. Yes, this is a subject of great interest which is precisely why is it the responsibility of editors to uphold the highest standards rather than create a big blob of unreliable content, and why discretionary sanctions are in place to remove editors who do not adhere to Wikipedia's relevant WP:PAGs for this subject. If in doubt, raise this at WT:MED. Alexbrn (talk) 18:14, 1 October 2020 (UTC)

I meant the others in the first section. We do not need to cite all of these. The first sentence still needs correction. I will amend how I write about the associations to include only the Lancet Diabetes and Endocrinology commentary.Jrfw51 (talk) 20:30, 1 October 2020 (UTC)

I appreciate the full and frank discussion elsewhere. What do others think of this newly published review in an OK impact factor (5.3) journal? PMID:32755992 It reviews relevant mechanisms and will add to the scientific side of this article. Jrfw51 (talk) 11:36, 4 October 2020 (UTC)

Looks useable. Could be used to support some statement like "as of November 2020, it was still unclear whether vitamin D had any role to play in relation to COVID-19". Alexbrn (talk) 12:26, 4 October 2020 (UTC)

Thanks Alexbrn. This review concludes with "The pervasive actions of vitamin D on many organ systems have raised many possible interactions between it and the mechanisms by which the SARS-CoV-2 virus infects human beings. While the data are far from conclusive in attributing a role for vitamin D in influencing the risk and outcome of this disease, it is nevertheless also clear that more research would be timely and revealing." I think this is the basis of the wording we should use but will leave it to you to insert this as you think is appropriate. Jrfw51 (talk) 13:33, 4 October 2020 (UTC)

As I said elsewhere, the article Mechanisms in Endocrinology:Vitamin D and COVID-19 is a decent source, but we have to be clear that it isn't reaching any conclusions about COVID-19 that differ from the NIH and NICE statements from a couple of months ago. Its review of the mechanisms of effect of vitamin D on older respiratory diseases is very much on-topic for the article, particularly the Mechanism of action section, but also to add extra information to the Use of supplements section which is rather sketchy in the Infectious diseases sub-section. It's already in use in the COVID-19 section, but I would be very cautious about trying to read more into it than the text presently says. --RexxS (talk) 18:26, 4 October 2020 (UTC)

Doses in COVID-19 clinical trials

This reverted edit was not a recommendation for the general public, but is in the section on Infectious diseases and COVID-19, and pertains to establshing semi-normal vitamin D blood levels in people deficient of the vitamin and who have severe COVID-19 disease. The Bergman review discussed high bolus (then weekly) doses of 10,000 IU per day or as much as 100,000 IU per month for some disease conditions where severe vitamin D deficiency is seen. The Ebadi review addresses using such high doses for vitamin D deficient people hospitalized with COVID-19 infections. This is new territory with ongoing clinical studies, so there are no reviews of completed trials to state firm conclusions, but there is evidence from the clinicaltrials.gov studies that large bolus amounts are being used to adjust vitamin D levels in the people with deficiency and severe COVID infection. As examples, this study is using a 25,000 IU bolus, this uses a bolus of 200,000 IU as "high" and 50,000 IU as "standard" (for correction), and this uses 5,000 IU per day for 2 weeks (70,000 IU total). Citing the Ebadi review is not Wikipedia's recommendation, but sources a reputable Nature review on a plan of action for adjusting toward normal the vitamin D deficiency that may be a risk factor for severity of COVID-19 infection, especially for hospitalized people in a clinical trial. Zefr (talk) 20:14, 21 May 2020 (UTC)

There are many protocols for treating vitamin D deficiency, but describing details in the context of COVID-19 (Ebadi) implies that this is the right amount, when it is not yet known if any amount prevents COVID-19 or reduces severity of symptoms of COVID-19. David notMD (talk) 21:25, 21 May 2020 (UTC)

The Ebadi article puts into words what the protocol details of the trials shown on clinicaltrials.gov state. As an ongoing event which editors are choosing to write into the encyclopedia, WP:NOW, if we're going to point to clinicaltrials.gov as evidence of how vitamin D is being used in COVID-19 studies, then there can be no legitimate objection to citing doses discussed by Ebadi and other clinical experts. The discussion requires context: bolus mega-doses are the choice of clinical trial designers and physicians, and they're only for hospitalized people with vitamin D deficiency and severe infection being studied in a clinical trial. Zefr (talk) 21:53, 21 May 2020 (UTC)

Vis-a-vis COVID-19: more reviews than trials

Still looking forward to results from the clinical trials. As of 19 September 2020, fifty (!!!) clinical trials of vitamin D for COVID19 are listed at clinicaltrials.gov. Until then, there is far more smoke than fire. I personally am not opposed to the evolving research section in the article, but consider it premature to mention treatment amounts until some of these trials reach publication. David notMD (talk) 16:53, 19 September 2020 (UTC)

We now have many reports of analyses of associations of 25(OH)D with incidence and severity, with multivariate analyses to address the confounding issues of ethnicity and other factors. Some are reviews. Regarding effects of treatment, I have tried to include the RCT from Castillo and have had it reverted on two occasions, once because it has "pilot" in the title. It has 76 patients, is prospective, double-masked, randomized 2:1 with calcifediol vs. best available therapy, and has clear highly significant differences in severity, measured as ICU admission. Yes there is a bigger study on the way. This study has been quoted in the mainstream media [1]. I would like to see this trial included in the Research section on RCT but will not add unless that is the consensus here. Jrfw51 (talk) 19:16, 19 September 2020 (UTC)

I am against including the Castillo trial in the article. In addition to being small (yes, I consider that small), vitamin D status was not determined, and furthermore, all patients were treated with hydroxychloroquine and azithromycin. For all we know, the vitamin D reduced the drug adverse effects. Unlikely, but still. David notMD (talk) 21:27, 19 September 2020 (UTC)

Hmm. Your theory is not discussed in this otherwise good paper. Very unlikely in my opinion based on what we now know. Included a multivariate analysis. ICU admission: Calcifediol 1 in 50 vs. 13 in 26 on standard care. Have you seen this is in WP here: COVID-19 drug repurposing research#Vitamins? Would you like to include that? Jrfw51 (talk) 18:38, 22 September 2020 (UTC)

It looks like there are some reviews available, but most are either primarily about something else (e.g., sleep apnea) or extend prior, non-COVID-19-specific work to COVID, e.g., "Level 1 and 2 evidence supports the use of thiamine, vitamin C, and vitamin D in COVID-like respiratory diseases, ARDS, and sepsis." WhatamIdoing (talk) 16:02, 2 October 2020 (UTC)

Without a good-quality review supporting the use of vitamin D in COVID-19 itself, attempting to extrapolate its effect on similar respiratory diseases is classic WP:SYNTH. --RexxS (talk) 16:37, 2 October 2020 (UTC)

Natural levels.

In the last 6 months the only credible research about desired blood concentrations I have seen with rational basis and detectable endpoints have ALL suggested a MINIMUM level of 75nmol/l (30ng/ml) with MOST of them favouring levels over 100nmol/l (40ng/ml) and extending to 150 to 250nmol/l (60 to 80ng/ml). Yet this page only references old recommendations that have been shown to be ill founded and based on strange historical fear limits before any actual trials were ever done on danger levels.

This article needs to bring to front and centre what the NATURAL level of this pro-hormone is that we need to function optimally. The fact that all but a few papers indicate benefits of increasing serum levels up to around 75 to 125nmol/l (30 to 50ng/ml) as required to achieve physiological saturation and substrate repletion is indicative of a real physiological use for the substance. This article is wrong and costing human society thousands of lost lives per day from a long list of ailments that can be reduced by changing a simple number. There are dozens of research papers that are more up-to-date and more credible that propose higher serum levels yet here we have an encyclopaedia that caves in and quotes the research with the lowest figures and then throws in a bit of unfounded fear as we approach the lower end of the healthy scale.

Fixing this ONE THING will do so much more than trying to guess about doses and waiting for CoViD-19 research to verify the action on yet another corona virus as has been seen previously. Right now I put on record here that Wikipedia is party to a massive crime against humanity if it only shows one side (the wrong side) of an argument about how much Vitamin-D metabolite we should have in our blood.

Here is a random sample paper that is just one of MANY that conclusively show that we were designed to operate with higher than advertised levels of 25(OH)D.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868557/

P.S. The smoking gun for me is that you need over 110nmol/l (44ng/ml) (or was it 114nmol/l) in a lactating mothers blood before her breast-milk will start to express Vitamin-D for the infant. It is simple, if we get rickets our hips do not form correctly for childbirth, until the mother has enough Vitamin-D (= sunshine) the society cannot survive. Therefore we KNOW that PRE-URBAN woman had natural levels from the fact that WE ARE HERE. This cannot be explained away with U or J shaped curves and heath risks from mega-doses or Vitamin-A poisoning when eating Bear livers on Arctic trips that were blamed on Vitamin-D or trials and treatments with fast acting metabolites and analogues or null effects from micro doses or ignoring of skin synthesis when calculating winter doses. This Wikipedia page is wrong on the optimal blood level and there is lots of research to prove it so.

Once this single point of failure error is corrected the rest of the speculation will collapse into determining how much we should take, winter and summer and latitude dependant or tested against out blood levels.

Idyllic press (talk) 12:17, 22 September 2020 (UTC)

Per the article section on recommended serum levels, the U.S. Institute of Medicine concluded in 2011 that a serum 25(OH)D level of 20 ng/mL (50 nmol/L) is needed for bone and overall health. The Institute found serum 25(OH)D concentrations above 30 ng/mL (75 nmol/L) are "not consistently associated with increased benefit", and that serum 25(OH)D levels above 50 ng/mL (125 nmol/L) may be cause for concern. The serum levels can be achieved when vitamin intake is at the RDAs (or equiv for other countries). Please keep in mind that Wikipedia is an encyclopedia rather than a worldwide medical authority that dictates medical practice. If enough evidence accrues that serum levels should be higher to achieve optimal health, then that will be summarized is reliable sources and changes to government recommendations - and Wikipedia will report that. David notMD (talk) 14:18, 1 October 2020 (UTC)

Exposure to sunlight

86.190.128.126 (talk · contribs) added the following text:

NICE pointed out that some people may have had less exposure to sunlight during the pandemic due to staying indoors, and that people with dark skin are more likely to have low vitamin D levels.<ref name="NICE2020"/>

but it was reverted by Spaully as Unnecessary detail for this article.

I understand the argument that it may be WP:UNDUE, but I'm not sure I agree. The statement is well-sourced, relevant, and doesn't seem to be covered elsewhere that I can find. Can I ask Spaully to reconsider, please? --RexxS (talk) 12:22, 5 October 2020 (UTC)

I would argue that 2 paragraphs on this pandemic is unduly long, particularly where there the synthesis is that there is "no evidence for or against taking vitamin D supplements specifically to prevent or treat COVID-19". I agree the above statement is well sourced, though is essentially speculation, but that the relevance of the current pandemic to this overarching article on the vitamin itself is probably worth 2 sentences total rather than expansion. The nuance probably ought to go in the COVID-19 treatment/research articles. |→ Spaully ^~talk~  12:44, 5 October 2020 (UTC)

@RexxS: when I made my original edit, I included the text as well as consider supplementation to correct for the lower vitamin D naturally produced from lack of sun exposure. to try and account for this part of it (i.e. potential increased need for supplementation due to pandemic) - if my wording is not clear I think we should fix that rather than have a whole separate sentence about it. I agree it merits mentioning, but I think my current sentence was sufficient - even if it (almost certainly) could be worded better. -bɜ:ʳkənhɪmez (User/say hi!) 13:04, 5 October 2020 (UTC)

@Spaully and Berchanhimez: thanks both, for your thoughts on this. There is a lot of pressure to include information on COVID-19 in articles that it may be relevant to, and I'm grateful for your measured contributions to keeping that in perspective. Cheers --RexxS (talk) 13:10, 5 October 2020 (UTC)

RexxS, no problem at all - I think many articles will, for at least a year or two, merit specific sub-sections regarding COVID-19 simply because it's due weight at this time because of the extreme amount of weight the news has been giving it for months. That doesn't mean that they merit more than a paragraph or so (5-6 sentences most) imo in any article unless there's something more to say. I agree that there's a lot of pressure to include irrelevant COVID-19 information in articles it shouldn't be in - but we need to balance fighting that pressure with actually including the encyclopedic and due information that "it is being studied for COVID" or "it's not recommended for COVID"... that doesn't mean we include the entire genome of the COVID spike protein in an article about some failed treatment to explain why they thought it would work in the first place, for example :P - TLDR: basic information yes good include, but we must fight the pressure to include tons of other info beyond the basics. I also agree that (sub)sectioning should be evaluated on a case by case basis. -bɜ:ʳkənhɪmez (User/say hi!) 13:16, 5 October 2020 (UTC)

• I've expressed my views on this at the MED talk page, here (see [2]) in the context of a broader discussion of what constitutes appropriate coverage/weight in cases like this. I absolutely understand that there are weight considerations within the page. But, fwiw, I believe that our responsibility to provide clear and appropriate information to readers who turn to Wikipedia as a go-to source of valid (and generally reliable :) information in the current crisis may outweigh that consideration, and also provide a real-world rationale for giving somewhat greater weight - for the time being - to COVID-19/pandemic-related content. But I acknowledge I don't have any specific WP guidance at hand to support (or contest) that view. 86.190.128.126 (talk) 13:50, 5 October 2020 (UTC)