For a comprehensive overview of vitamin D and the immune system and of the need for proper (e.g. 0.125 mg 5000 IU /day or more, for 70 kg bodyweight) vitamin D3 supplementation, please see: https://vitamindstopscovid.info/00-evi/ .

Please also see:

You are reading the best efforts of an electronic technician and computer programmer.   What I write will hopefully help you understand the research, but should not be mistaken for medical advice.  Medical advice is what you get after a doctor has examined you.  Even if I was a doctor, I haven't examined you!

The recommendation for a single oral dose of 0.014mg calcifediol per kg body weight (1mg for 55 to 85kg people) comes from Professor (retired) Sunil Wimalawansa MD, of New Jersey: LinkedIn (recommendation).  He is a long-time vitamin D researcher: Google Scholar.

Please read the research carefully and make your own decisions.  If you don't clearly understand it, please consult with someone who does. 

Doctors and nurses can understand all this and evaluate the research, but they are very busy.  Many of them cannot believe that something so simple and inexpensive as vitamin D could be so crucial to the proper operation of the immune system, or to ending the COVID-19 pandemic. They should read the research.

Page	Description	Last update
#guide	Guidance for those considering using calcifediol for early treatment of COVID-19.	2021-12-21
#00-sv	Short version.	2021-12-21
#01-rapid	Full version. #c19vax Sidebar on good 25-hydroxyvitamin D not being a guarantee of moderate COVID-19 symptoms.  To what extent should the current mRNA and adenovirus vector vaccines be used with good 25OHD levels and access to multiple early treatments.  The Novavax protein subunit vaccine would be safer, but is not yet available. #emergency I am only suggesting a single oral dose of calcifediol for emergency use.  This is not something where you get sick, order calcifediol and wait days or a week for it to be delivered. Bolus D3 is the best solution if you don't already have calcifediol in stock.  But since you know of the need for 25-hydroxyvitamin D levels, you and your loved ones will already have attained this before you get sick - so you won't need calcifediol or bolus vitamin D3.	2021-12-21
#02-presc	Calcifediol used to be prescription only, and difficult to obtain in most countries.	2021-12-21
#03-ray	Rayaldee is prescription only and is available in the USA for a very high price.	2021-12-21
#04-faes	Faes Farma in Spain make inexpensive prescription only 0.266m calcifediol capsules which are available in Spain and Italy and a few nearby countries.  It is possible they might be obtainable without prescription.	2021-11-21
#05-fortaro	Online, non-prescription small (0.01mg) tablets in Australia, with delivery of 3 bottles max to any other country.  This is a product of DSM.	2021-11-21
#06-dvelop	Similar non-prescription tablets available online with delivery to the USA - also from DSM.   A similar European product will probably be available soon. #liquid how to make 100 of these tablets into a drink or a thicker syrup for ingestion via a spoon or syringe.	2021-12-21
#07-ratio	A single oral dose of 0.014mg calcifediol / kg bodyweight will safely replete any person to 50ng/ml or more circulating 25-hydroxyvitamin D.	2021-12-21
#08-lab	Lab grade and agricultural grade calcifediol is also available.	2021-12-21
#99-barc	(Low key.) An observational study of D3 and calcifediol supplementation in Barcelona is less interesting than it might at first seem.	2021-11-21

• Most people who have not been properly supplementing vitamin D3 for months have circulating 25-hydroxyvitamin D (AKA 25OHD) levels of 5 to 25ng/ml (8 to38nmol/L).  This is 1/10th to 1/2 of the 50ng/ml 125nmol/L 25-hydroxyvitamin D the immune system needs to function properly.  See https://vitamindstopscovid.info/05-mds/ for the most pertinent research on the three vitamin D compounds and the immune system.
  
  
• Ordinary healthy D3 supplemental intakes such as 0.125mg 5000IU / day (70kg bodyweight) take two or so months to raise 25-hydroxyvitamin D levels from a typical unsupplemented level of 18ng/ml to the desired 50ng/ml or more level needed for proper immune system function.  (Graph below.) This is completely inadequate for any clinical emergency.  So you need either bolus (single, high dose) vitamin D3 (cholecalciferol) or a single oral dose of ~1mg calcifediol (55 to 85kg bodyweight).  
  
  
• A small, single oral dose of calcifediol (also known as 25-hydroxyvitamin D,  25OHD, 25(OH)D and "calcidiol")) raises blood vitamin D (25OHD) within 4 hours to at least this desired, healthy, 50ng/ml 125nmol/L level.  For 70kg 154lb bodyweight, 1 milligram is a good amount.  Daily vitamin D3 should be used to sustain this initially boosted level.
  
  
• This is faster than the few days it takes for a bolus dose of vitamin D3 cholecalciferol to raise 25OHD to these levels, due to the slow conversion of D3 to 25OHD by the liver.
  
  
• All people suffering from COVID-19, sepsis, ARDS, Kawasaki disease, Multisystem Inflammatory Syndrome etc. urgently need their levels raised to at least 50ng/ml 125nmol/L.
  
  
• Calcifediol is now available, in the USA and Australia, without prescription, at affordable prices, in quantities needed for emergency vitamin D repletion:  DSM's d.velop and Fortaro.
  
  
• If you already have calcifediol in stock, then for most people, who have not been supplementing D3 properly for months, a single oral dose of calcifediol is the most important early treatment for COVID-19 or the other acute medical emergencies listed above in red.
  
  
• If you don't already have calcifediol in stock, it is best to use bolus D3 ASAP rather than order calcifediol and wait several days or more for it to to be delivered.
  
  
• The best approach is to make such urgent treatments unnecessary by attaining long-term, lasting, good 25-hydroxyvitamin D levels by daily to weekly D3 supplementation in the appropriate amounts for your bodyweight.
  
  
• So:
  
• Use good D3 supplementation now and indefinitely to attain good 25-hydroxyvitamin D levels all year round.  (Start with a higher intake to get your levels up faster.)
  
  
• There's no need to buy calcifediol for those in your care who supplement D3 properly.
  
  
• If someone else becomes ill and you have no calcifediol in stock, then bolus vitamin D3 is the best option.
  
  
• Generally, for long-term vitamin D supplementation, vitamin D3 is perfectly good - there is no need to use calcifediol in the long term.  My only interest in calcifediol is for emergency boosting of 25-hydroxyvitamin D in clinical emergencies.
  
  Therefore, the only reason for purchasing calcifediol is for for emergency 25-hydroxyvitamin D boosting for other people - friends, family, neighbours (or if you are a doctor or a nurse, for your patients) - who have not been supplementing vitamin D properly for a few months, who are reasonably suspected of or confirmed by PCR test as having contracted COVID-19 (or have sepsis, etc. as mentioned above), and for whom you want to be ready to boost their 25-hydroxyvitamin D levels in 4 hours, rather than over a few days with bolus D3.
  
  
• For a bolus (high, single) dose of vitamin D3 cholecalciferol I suggest up to 12.5mg 500,000IU D3 all at once, or over two or three days, for a 70kg 154lb person.  Unless they have already got extremely high 25-hydroxyvitamin D levels there is no chance of toxicity.  (It would take months of unusually high vitamin D3 intakes to reach such levels - such as weeks of 50,000 IU a day or months or half this - and even then only some people would find this leads to toxicity - problems with calcium metabolism.)
  
  The person's life hangs in the balance, so you might as well do a proper job.
  
  Bolus D3 quantities as a ratio of bodyweigth.  These ratios work will work for all bodyweights, from newborns to sumo wrestlers: a single oral dose of 0.175mg 7000 IU per kg bodyweight for  most people, or up to 0.250mg 10,000 IU per kg bodyweight for those suffering from obesity.
  
  Best give it after a meal with some fats.  Oil-filled capsules may be more effective than tablets or dry powder capsules.  The 2019 ESPEN guideline on clinical nutrition in the intensive care unit recommends up to 12.5mg 500,000IU D3 in the first week, for an unspecified but presumably adult bodyweight.  See Han et al. 2016 https://aminotheory.com/cv19/#2016-Han who gave 100,000IU D3 / day for 5 days to mechanically ventilated ICU patients and so halved the average number of days they remained in hospital.
  
  
• The initially boosted 25-hydroxyvitamin D levels from a single dose of calcifediol or vitamin D3 need to be maintained in the days, months, years and decades which follow by regular vitamin D supplements, such as once every day to once a week.  Longer periods between intakes are best avoided.
  

• For yourself and those in your immediate care, there is no point in ordering calcifediol in case one or more of you get COVID-19 or any of the abovementioned diseases.  It would be much better for you all to properly supplement with D3, so you always have good 25-hydroxyvitamin D levels.   Since it takes two months or so of ordinary healthy daily D3 intakes to attain these levels, you might want to start with much higher intakes for a week.
  
  
• Afshar et al. 2020 https://vitamindstopscovid.info/01-supp/#2020-Afshar found that 70 to 100IU D3 per day per kilogram bodyweight was a good range of ratios.  This was in Dubai, which is sunny but in which many people - especially women - avoid sun exposure of their skin. In their use of these ratios with 500 patients over many years, these doctors found the resulting 25-hydroxyvitamin D levels were between 40ng/ml 100nmol/L and 79ng/ml 198nmol/L which is a perfectly good range to aim for.
  
  On this basis, with a 72IU/kg ratio, 70kg 154lb gives 0.125mg 5000IU D3 a day.
  
  
• If you took 5 times this (0.725mg 25,000IU) per day, for a week, that would be 4.4mg 175,000IU vitamin D3 in the first week - a modest bolus dose for an average weight adult to get your level well on its way to a healthy stable level, in a week rather than a month or so.

COVID-19 patients urgently need their blood vitamin D levels boosted to 50ng/ml (125nmol/L) or more, within hours - not days, weeks or months.  Only calcifediol - the pharmaceutical name for 25-hydroxyvitamin D can do this.  Calcifediol is 25-hydroxyvitamin D (25OHD), which is the form of circulating vitamin D directly needed by all immune system cells.  This 50ng/ml or more level is needed for their immune system cells to function properly - to directly combat the virus and to limit self-harming, cytokine storm, overly inflammatory responses which cause severe COVID-19.  This is only 1 part in 20,000,000 by mass.

For average weight adults (70kg, 154lb) a single oral dose 1.0 milligram calcifediol will do this within 4 hours.   Half this will usually do it too - 1mg is to allow for some people absorbing it poorly and to allow for some people suffering from obesity.  The excess fat cells in obesity absorb and do not return both D3 and circulating 25OHD.  Obesity is in part an inflammatory disorder and carries many risks for those who contract COVID-19: https://aminotheory.com/cv19/obesity/ .

Ordinary, healthy, vitamin D3 intakes such as 0.125mg (5000 IU) per day (for a 70kg = 154lb adult) will achieve these levels in the long term, but it takes months.

Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience
Patrick J McCullough, Douglas S Lehrer and Jeffrey Amend.
Journal of Steroid Biochemistry and Molecular Biology 2019-01-04
https://www.sciencedirect.com/science/article/abs/pii/S0960076018306228 (Paywalled.)
https://sci-hub.se/10.1016/j.jsbmb.2018.12.010

Bolus D3, such as 3.75mg 150,000IU over three days, as recommended by Dr Lindsey Berkson https://drlindseyberkson.com/coronavirus-update-integrative-natural-answers/ would probably (depending on absorption, bodyweight and potential obesity) raise levels towards or over 50ng/ml within several days to a week. 

This is good, but 1 milligram of oral calcifediol will raise levels towards over 50ng/ml in 4 hours and so enable the person, in general, to overcome the infection - and generally to reverse any over-inflammatory responses - much faster.



Most doctors cannot imagine that vitamin D is so important to the immune system.  Most have not heard of vitamin D based intracrine and paracrine signaling, which was first discovered in the mid-2000s and is not widely enough understood.  These needs of the immune system have nothing to do with the one hormonal function of the vitamin D compounds - a very low level of circulating 1,25OHD (calcitriol), produced from circulating 25OHD by the kidneys, which regulates calcium-bone metabolism.  https://vitamindstopscovid.info/02-intracrine/#02-nothorm .

Calcifediol has been very hard to obtain, but since May 2021, it is available, without prescription, as a packet of 60 x 0.01mg d.velop tablets = 0.6mg total, initially for USD$30 including shipping, to customers in the USA:  https://dvelopimmunity.com .  In mid-November 2021 the cost is USD$20 a bottle, plus taxes including shipping, within the USA only.  Similar Fortaro tablets are available from Australia, with shipping of up to 3 bottles (1.8mg total) to any country.  Full details below.

In order to understand the crucial importance of easily available calcifediol, in the current COVID-19 crisis, and for other deadly health conditions, there are a number of things you should read, if you have not already done so. 

Sidebar on using some other nutrients and Ivermectin as well:


There is very little vitamin D3 (cholecalciferol) in food.  There is no such thing as a vitamin D rich food.  Unless a person takes supplemental D3, the D3 they need must be supplied by UV-B (short-wavelength ultraviolet, ~295nm) light converting 7-dehydrocholesterol in the skin to D3.   This naturally occurs with high elevation (no more than 45% from the vertical) sunlight, but glass, sunscreen and clothing block UV-B.  There are good reasons to avoid UV-B skin exposure since it damages DNA and so raises the risk of skin cancer.  Melanin-rich skin greatly reduces the amount of incident UV-B which reaches deep enough into the skin. 

So people with black or brown skin have generally low circulating 25-hydroxyvitamin D levels unless they take proper quantities of supplemental D3, such as, for a 70kg person, 0.125mg (5000IU) D3 a day, on average: https://vitamindstopscovid.info/01-supp/ .  This is especially so if they are far from the equator and it is winter, or even in summer if they don't get a lot of direct sun exposure.  Muslim women are especially at risk if they cover head to toe, even when outside.

Please see the UK white and BAME vitamin D levels by month graph at:  https://aminotheory.com/cv19/#2020-UK-vit-D-BAME for how low the average levels are in the UK, even for people with low-melanin (white) skin, in summer.  For those with melanin-rich skin, in summer it is much worse, and marginally worse still - to the point of being disastrously low - in winter.  

The graph below is from Quraishi et al. research into hospital acquired infections and wound site infections from surgery patients in Massachusetts.  It shows clearly that 50g/ml, (50 parts per billion, by mass 125nmol/L) circulating 25-hydroxyvitamin D (25OHD, calcifediol)  is required for major parts of their immune system to function properly.  In these people, when 25OHD levels were too low, bacterial and perhaps yeast and fungal infections occurred at much higher levels than when they had sufficient 25OHD.  The affected parts of the immune system are those cell types which create direct, innate, responses to bacteria etc. infections and the adaptive responses - the generation and deployment of antibodies and the cell-destroying immune cells which get rid of any cell (our own, or bacteria) or virus which antibodies recognise and attach themselves to.

All these patients were morbidly obese. They were in hospital for a Roux-en-Y gastric bypass [WP]  operation, which is a major abdominal procedure.  I know of no reason to believe that their immune cells needed higher circulating levels of 25OHD than is needed by the immune cells of people who are not suffering from obesity.  So this important, and unusually direct, observation of healthy and unhealthy circulating vitamin D (25OHD = 25-hydroxyvitamin D = calcifediol) levels surely applies to all people.  

Here is the graph.  The article link and summary is at: https://vitamindstopscovid.info/02-intracrine/#04-quraishi .



This justifies the 40 to 60ng/ml recommendation of the Call to D*Action MDs and researchers in 2008: https://www.grassrootshealth.net/project/our-scientists/ and more recent review articles such as: https://doi.org/10.3390/nu12072097 .

Here is another graph, in case anyone needs convincing of how important good vitamin D levels are to immune function and so to reducing the chances of severe COVID19.  Links to the articles cited are at https://aminotheory.com/cv19/ .



#c19vax

Sidebar on to what extent good 25-hydroxyvitamin D levels and access to multiple early treatments mean it is not necessary to use the current mRNA or adenovirus vector vaccines

There is some vitamin D2 is in some mushrooms and fortified milk and other foods.  These are at low levels and D3 is better in every respect.

Newly ingested or UV-B produced D3 circulates in the bloodstream.  Over a period of days to a week or so,  it is converted by an enzyme in the liver to circulating 25-hydroxyvitamin D.  

This is also known as calcifediol - and occasionally as "calcidiol" which is a confusing term since it resembles "calcitriol" (1,25-dihyroxyvitamin D).   Hereafter I refer to it as 25OHD if it is in the body, and as calcifediol if it is a pharmaceutical.  These are different names for same molecule.  Every microgram of D3 which enters circulation (the bloodstream) is converted to, very approximately, about 1/3 microgram of 25OHD which goes into circulation.  There is no consensus on the ratio of how many micrograms of D3 are required for the liver to produce a microgram of circulating 25OHD.  3:1 is a reasonable estimate, but values of 2 to 6 might be true, depending on the circumstances.

Circulating 25OHD has a half-life of a month or so at healthy levels, such as 50ng/ml (125 nmol/L).  At higher levels another enzyme, found in many parts of the body, is more active and breaks the 25OHD down in a self-limiting system, so the half-life is shorter.  Very few people in the whole world are either getting sufficient UV-B skin exposure all year round or taking sufficient quantities of supplemental D3 to have such healthy vitamin D levels. 

For 70kg adults, on average, 0.125mg 5000IU D3 a day is sufficient to achieve these healthy 25OHD levels, in most people, after a few months (see top graph of two, below).  See also D3 supplemental intake quantities as ratios of body weight: https://vitamindstopscovid.info/01-supp/ .  
"5000 International Units" may sound like a lot, especially in countries where most doctors recommend much less, where the largest D3 capsules available are 1000IU, and where most doctors are alarmed at anyone taking 4000IU or more.  However, it is a gram every 22 years - and ex-factory, in 1kg lots, pharma-grade D3 costs USD$2.50 a gram

Most people don't supplement properly like this, and for all those who don't, and who also do not get sufficient UV-B skin exposure all year round (the elderly get little sun, and their skin is not so good at producing D3 even if it is exposed . . . and the elderly with brown or black skin . . . . . ) and so have levels in the 5 to 25ng/ml range most of the year. At these lower levels circulating 25OHD's half life is, very approximately, two months or so.

Circulating (meaning in the blood, specifically in the liquid = plasma part of the blood, rather than the cells) 25OHD is what is measured in vitamin D blood tests.

Circulating 25OHD diffuses into the tissues and into cells, through their cell membrane.  There is no active transporter system to get it into cells.

This 25OHD which diffuses from the blood into cells is required by many types of cells for their intracrine and paracrine signaling systems, where it is consumed, and turned into 1,25OHD AKA calcitriol inside the cell.  This is part of a signaling system - conveying information within each cell, from the mechanisms which detect a particular external circumstance to the mechanisms in the nucleus which control which genes are transcribed into messenger RNA molecules.  The mRNA molecules control how much of each type of protein the cells make.  So changing how genes are copied into mRNA molecules changes the behaviour of the cell.

Neither vitamin D3 nor 25OHD is a hormone.  A hormone is a substance which is produced in one  location in the body and travels through the bloodstream and by diffusion in the tissues to cells in distant parts of the body.  The level (the chemical concentration, such as in trillionths of a gram per gram of blood) affects those distant cells by controlling some aspects of the cell's behaviour in proportion to the concentration of the hormone molecules.   Hormones are long distance cell-to-cell signaling molecules of endocrine (hormonal) signaling system. 

Circulating 25OHD has two roles.  The first one is known by all doctors and nurses.  The second role is hardly known at all.  Most doctors have a vague idea of "vitamin D" affecting immune cells and cells of other types, which is true.  However, very few doctors understand the mechanisms - intracrine and paracrine signaling - since these have mainly been discovered since the mid-2000s.  https://vitamindstopscovid.info/02-intracrine/

The first role of circulating 25OHD is to provide the kidneys with a small amount of 25OHD which they convert (in a process controlled by the parathyroid hormone, the level of which is controlled by various aspects of the body's calcium handling system) into 1,25OHD (calcitriol) which goes into circulation.   This circulating 1,25OHD acts as a hormone.  The exact level of circulating, hormonal, 1,25OHD is precisely controlled by the kidneys.  This level is sensed by multiple types of cells in various parts of the body and controls both the absorption of calcium from the intestines into the bloodstream and the actions of osteoblasts, osteoclasts and other cells which are involved in the constant remodeling necessary for bone health.  The calcium level in the blood need to be very tightly regulated, since it affects numerous processes in all cells.

Unfortunately it is common for even the most experienced vitamin D researchers to state that "vitamin D" (here meaning the three compounds collectively - D3, 25OHD and 1,25OHD) "is a hormone", or "is a secosteroid hormone" which sounds even more impressive.   The vitamin D compounds are extraordinarily important, but the only one of them which acts as a hormone is 1,25OHD, and this is only when it is circulating in the bloodstream, which it does at a very low level, such as 0.045ng/ml .

Sidebar on 1,25OHD:

• Hormonal signaling: circulating 1,25OHD diffuses into the cell and binds to VDR molecules in the cytosol (the main volume of the cell, not the nucleus).
  
  
• Intracrine signaling: 1,25OHD molecules just produced in the cytosol binds to VDR molecules in this cytosol - all within the same cell.
  
  
• Paracrine signaling: 1,25OHD produced as part of intracrine signaling in nearby cells, diffuses from that cell into a nearby cell and binds binds to VDR molecules in that cell's cytosol.  (The nearby cell is probably of a different type to that which produced the 1,25OHD.)
  

This circulating, hormonal, 1,25OHD is at a very low level: such as 1000  times less concentrated than the (ideally) 50 parts per billion of 25OHD.  https://vitamindstopscovid.info/02-intracrine/#02-nothorm  Its half-life is a day or less.  The kidneys can maintain the required level pretty well with circulating 25OHD levels of 20ng/ml or so - though, unfortunately, many people don't even have this.  Some people have 25OHD levels below 10ng ml, and so have poor bone health.   Doctors generally think of deficiency being below 20ng/ml or perhaps 30ng/ml (75nmol/L) - but this is just for bone health.

The second role of circulating 25OHD is the one everyone needs to understand, since it concerns all aspects of the immune system, as well as a large number of other cell types which have not yet been so well researched.   Very few MDs understand this.

In this role, circulating 25OHD is used by numerous cell types, all over the body, to be converted inside the cell to 1,25OHD, for the purpose of activating vitamin D receptors inside the cell, to alter gene expression and so protein synthesis and the whole operation of that particular cell.  This is intracrine signaling - a form of signaling which occurs entirely within the cell.  

Other types of molecules are involved in other intracrine signaling arrangements and here we are only interested in 25OHD being converted to 1,25OHD.  This intracrine signaling is not to maintain a steady state, such as with calcium- bone or some other stable bodily system.  The intracrine signaling conversion to 1,25OHD is only turned on in particular circumstances.   Vitamin D based intracrine signaling is a crucial part of how most immune cell types, and many other cell types, respond to their changing circumstances.  This has nothing to do with hormonal signaling.  The levels of 1,25OHD produced inside the cell are much higher than the very low levels of hormonal circulating 1,25OHD.  The half-life of 1,25OHD inside the cell is short - probably hours or less - since enzymes there degrade it.

Paracrine signaling is a closely related signaling system in which 1,25OHD, produced in a cell from 25OHD - as for, or as part of, intracrine signaling - diffuses out of the cell and to nearby (millimetres) cells, which sense its level and alter their behavior accordingly.

Since I couldn't find a good, illustrated, tutorial on intracrine and paracrine signaling, I made this page:


adapting illustrations from a 2011 article by Martin Hewison and colleagues, in which they report their discoveries.   If you have time, please read this page and at least some parts of the research articles it cites.   If you have understood the current page so far, you know more about vitamin D intracrine and paracrine signaling than the great majority of doctors.  By  reading and understanding the 02-intracrine page, you will attain a still better understanding of these processes.   It includes references to research which:

• Indicates that 50ng/ml or more circulating 25OHD is needed for immune cell intracrine and paracrine signaling to work properly - at least for those cell types which directly defend against bacteria.  (Quraishi et al. 2014.  See the graph above.)  It is reasonable to assume from this, and from observations of vitamin D levels which reduce excessive inflammation, that Th1 regulatory lymphocytes need similar circulating 25OHD levels to function properly.
  
  
• Shows in full detail how Th1 lymphocytes rely on good levels of circulating 25OHD for their intracrine signaling. (Chauss et al. 2021.) When 25OHD levels are very low, Th1 lymphocytes remain stuck in their initial pro-inflammatory program and fail to respond to signals which should cause them to switch to their anti-inflammatory shutdown program.  This continued excessive inflammation (cell-destroying immune responses) is the cytokine storm which causes some people to develop severe COVID-19. 
  
  It is reasonable to assume that the exact same dysfunction - Th1 dysregulation of self-destructive inflammatory immune responses, due to inadequate vitamin D levels (circulating 25OHD), together with similar failures of intracrine/paracrine signaling by other regulatory cells - is the primary cause of sepsis [Wikipedia link: WP], Kawasaki disease [WP and https://aminotheory.com/cv19/#2015-Stagi], Multisystem Inflammatory Disorder [WP] and ARDS [WP] - however see the note below on helminths.  
  
  I regard this work: Chauss et al. 2021 (linked to, summarised and discussed at: https://aminotheory.com/cv19/icu/#2021-Chauss) as the most important research work ever done on the mechanisms of severe COVID-19.  Every doctor should understand this, but the research is relatively new and so it is not yet widely known.
  
  
• Report on the remarkable effectiveness of a small (0.532 milligram), single, oral dose of calcifediol, which goes into circulation within hours, where we call it 25OHD, raising initially low levels to healthy 60ng/ml or more, on average, within a few hours.  This is the work of Castillo at al. 2020 (linked to and summarised at: https://aminotheory.com/cv19/#2020-Castillo), in Cordoba, Spain and is well known among all vitamin D researchers and vitamin D aware doctors and nurses.  
  
  This single dose of 0.532mg calcifediol, given at the earliest opportunity to hospitalised COVID-19 patients is the main reason why ICU rates were reduced from 50% to 2% and deaths from 8% to zero.
  
  This is extraordinary result is partly due to the control group having a greater incidence of co-morbidities, but the impact of the calcifediol treatment is still responsible for most of the reduction in ICU admissions.  (The reduction in deaths is not so statistically significant due to the small number of subjects in the trial.)
  
  A single dose of calcifediol such as this would be still more effective if given withing a day or so of COVID-19 infection being known, such as from a positive PCR test.  The Castillo trial involved giving the dose at a much later stage - when the person's symptoms were serious enough that they were admitted to hospital.
  

Once you understand vitamin D intracrine / paracrine signaling, the need for 50ng/ml or more circulating 25OHD for it to work properly, that many types of immune cell need such levels to work properly (those cell types which directly attack pathogens, develop antibodies and correctly regulate potentially self-destructive inflammatory immune responses - Chauss et al. 2021), then it is clear why low 25-hydroxyvitamin D (25OHD = calcifediol) drives the development of severe COVID-19 and why a tiny quantity of oral calcifediol is so extraordinarily effective at preventing hospitalised COVID-19 patients from progressing to full-blown severe, cytokine storm, endothelial cell destruction, hypercoagulative blood, micro-embolisms and larger blood clots, severe COVID-19.

If you are keen, you will find links to and summaries of dozens of research article here at https://vitamindstopscovid.info and at its more extensive and less well organised companion https://aminotheory.com/cv19/ .  Please also see https://VitaminDWiki.com and the meta-analysis of the latest vitamin D intervention and observational studies concerning COVID-19: https://vdmeta.com . 

Those with the most inquiring minds will want to know why humans, domestic animals and agricultural animals suffer, generally and according to  considerable genetic variation, from such a large number of overly-inflammatory conditions.  The answer is that we have no longer are infested by helminths (intestinal worms): https://vitamindstopscovid.info/06-adv/#02-helminths .


There are a plethora of reasons why everyone should supplement vitamin D3 to aim for 25OHD levels of 50ng/ml or so.  For suggestions for how much D3 to take, on average (it is generally regarded as OK to have larger intakes up to a week apart), depending on body weight and morphology (people suffering from obesity need more D3 per kg bodyweight), please see:


Long-term supplementation along these lines raises circulating 25OHD over a week or two, and then over a few months, to a final healthy steady state, all year round.  

For most people, this is fine and there is no need for them to think about calcifediol == 25OHD.

#emergency
However, if a person is suffering from, or at significant risk of developing, any of these conditions:

• Severe COVID-19 - or probably any symptomatic form of COVID-19, since this carries high risks of lasting harm, even if the person does not die.
  
  
• Sepsis - infection triggers gross immune system dysregulation with inflammatory (cell destroying) processes wreaking havoc all over the body - especially the lungs.  Sepsis develops rapidly, has a variety of mixed up symptoms, is frequently not diagnosed anywhere near fast enough and can kill within hours. [WP]  See also Reyes et al. 2021 who state that Bacterial sepsis and severe COVID-19 share similar clinical manifestations.  According to Rudd et al. 2020 nearly 20% of all deaths, worldwide, are due to sepsis.
  
  
• Kawasaki disease - triggered in children, especially by COVID-19, including with very mild COVID-19 symptoms.  KD - like sepsis, MIS, ARDS and severe COVID-19 - is a condition of extreme, overly inflammatory, immune system dysregulation.   It is primarily a disease of the vasculature - blood vessels.  [WP]
  
  
• Multisystem Inflammatory Syndrome (MIS). [WP] AKA Paediatric Inflammatory Multisystem Syndrome Temporally associated with Severe acute respiratory syndrome coronavirus 2 (PIMS-TS) Darren et al. 2021: https://doi.org/10.1017/S0007114521001562 report on melanin rich skin UK children in ICU with this condition averaging 7.8ng/ml 25OHD.  MIS-C and Kawasaki disease are separate diagnostic categories which cover parts of a spectrum of disease with the same underlying causes, but with somewhat different symptoms.
  
  
• Acute Respiratory Distress Syndrome (ARDS). [WP]
  
  
• Pre-eclampsia [WP]  From Borzychowski et al. 2006 "Pre-eclampsia is a common and potentially dangerous disorder of human pregnancy. The maternal syndrome of hypertension, proteinuria and oedema is part of a severe systemic
  inflammatory response that includes leukocyte and endothelial cell activation." 
  
  There are plenty of research articles on pre-eclampsia and vitamin D, but this does not mean that most OB/GYNs recognise this and so ensure that pregnant women have good 25-hydroxyvitamin D levels.
  

then it is likely that their circulating 25OHD levels are dangerously low and have been for weeks or months.  (Also, these infections can marginally reduce these levels, presumably due to 25OHD being consumed by immune cells' intracrine and paracrine signaling systems.)

Without rapid repletion of their 25OHD, they will be at high risk of serious harm and death - depending on the success of any anti-inflammatory drugs, which MDs and nurses frequently use at present to tackle these emergencies.  MDs and nurses also tackle other problems such as high or low blood pressure.  These anti-inflammatory drugs - such as prednisone and dexamethasone can cause psychosis and deadly fungal diseases.  See: https://vitamindstopscovid.info/05-mds/#04-cortico .  They also reduce innate and adaptive responses to bacteria, viruses and fungi.


Bolus (AKA stoss or loading dose)  D3, as described above, usually helps.  But these people need their 25OHD levels raised now, not in days or a week or so.

Such brief, higher than normal, D3 intakes, or the ~1mg single dose oral calcifediol discussed below - are unlikely to cause any harm, even if someone has been supplementing higher than ideal D3 levels for months.  So there's no need for a 25OHD blood test, unless perhaps the results can be known in a few minutes.  Time is of the essence and the sooner their 25OHD level is raised the better chance the person has of overcoming any pathogens and what might otherwise be a progression to self-harming hyper-inflammatory immune system dysregulation.

Magic bullet AKA silver bullet is a strong term in medicine.   It broadly refers to a drug which knows exactly where to go in the body, and what to do there, to completely fix a particular problem.

However, calcifediol is not a drug.  It is simply the molecule the immune system needs to function.  It doesn't go any one place - it goes into solution in the blood stream and then diffuses into all tissues.  There it diffuses into most or all cell types. All immune cells - and many other types of cell - need it inside their cell bodies so it can be used when their vitamin D based intracrine signaling systems are activated.  So it does go exactly where it is needed - into circulation and from there into all the tissues and cells.

I am just an electronic technician, and you should make up your own minds about all this, after reading the research yourself, rather than rely on my opinions.  However, I think it is reasonable to regard a milligram or so of calcifediol (for 70k bodyweight), in a one-off oral dose (with continuing support with D3 in the days which follow), as a magic bullet when tackling the conditions listed above, all of which are made very much worse by low circulating 25OHD levels.  Most likely if the person had good vitamin D levels of 50ng/ml or so, they would not have become ill in the first place.

0.532mg of oral calcifediol (in oil-filled capsules, which improves absorption from the intestine into the bloodstream) provided dramatic benefits to the hospitalised COVID-19 patients in Cordoba (Castillo et al., above).

The purpose of the rest of this page is to discuss how such single dose calcifediol treatments can do much the same magic bullet work as in Cordoba, in the abovementioned #emergency emergency medical conditions, where the primary, correctable, problem is low circulating (blood) levels of 25OHD = 25-hydroxyvitamin D = calcifediol.   The earlier they can have their level boosted, the better.

Assuming the person is conscious and can ingest liquids, all we need to do, for 70kg bodyweight is give them about 1mg oral calcifediol and we will have their 25OHD levels high enough to meet the needs of all their immune cells, within a few hours.  (In principle injections or IV drips could be used as well, but this page concerns only oral calcifediol.)

The precise amount is not critical.  0.014mg calcifediol per kilogram bodyweight is recommended by Prof. Sunil Wimalawansa, which is about 1mg for 70kg.

In the middle of 2020, calcifediol was difficult to obtain.  As far as I know, the only option in the USA (and perhaps Canada) was the prescription capsules "Rayaldee".   As detailed at https://aminotheory.com/cv19/#calcifediol-availability  a packet of Rayaldee contains 30 capsules, each containing 30 micrograms = 0.03mg of calcifediol.  The whole packet contains 0.9mg of calcifediol.  Since each packet costs USD$1,206.88, this is USD$1,340.98 per milligram.

Rayaldee uses a patented sustained release arrangement.  This supposedly confers benefits for the patients for which it is FDA approved in the USA, such as those with kidney disease.  However, it makes no sense that this sustained release provides benefits in addition to those which arise from the calcifediol being quickly absorbed in the intestine, since the half-life of calcifediol in the blood is weeks at least, and more likely one or several months.

I believe that Rayaldee is a vastly overpriced preparation and that its promotion inherently disparages the value of plain oral calcifediol.  However, my opinion is of no consequence regarding anyone's treatment decisions.  Ask your doctor what he or she thinks - and point them to this page.

Until early 2021, to the best of my knowledge, the only other source of pharma-grade calcifediol ready for oral use in patients was the oil-filled capsules and glass ampoule forms of Hidroferol, the awkward trade name of long-established Spanish company Faes Farma.   More details at: https://aminotheory.com/cv19/#hidroferol .

However, in May 2021, I was told of Italian Neodidro, which are very similar or perhaps identical capsules, also prescription only, which are available for €10 for 10 capsules of 0.266mg each.  This is about USD$12.14 and so USD$4.56 per milligram.  More details at: https://aminotheory.com/cv19/#neodidro .   Someone on Twitter mentioned that his sister in Italy asked for some Neodidro at a pharmacy and had to wait for it to come back into stock - but that she would be able to obtain it without a prescription.  Can anyone tell me more about an such non-prescription sources of calcifediol?

These Hidroferol capsules, each containing 0.266mg calcifediol, were used in the Cordoba trial https://aminotheory.com/cv19/#2020-Castillo, so we know these are good.  The patients received two such capsules at the earliest opportunity, and then one capsule on days 3, 7, 14, 21 etc.  The first two capsules  made all the difference.  The subsequent smaller doses would have maintained the newly boosted circulating 25OHD levels perfectly well, but regular vitamin D3 capsules, averaging (for 70kg adults) 0.125mg 5000 IU per day (https://vitamindstopscovid.info/01-supp/), would have maintained these levels just as well.

As far as I know these are available within Spain.  They seem to be available from pharmacies in Georgia (the country, not the US state).  The  43.71 Gel price for ten capsules equates to about USD$14.

If we assume a price of USD$15, for 10 x 0.266 = 2.66mg, then this is USD$5.64 per milligram.  The challenges are having a prescription for it, finding a seller who will export it to the country of interest, and getting it through customs.

In February 2021, leading Dutch human and animal feed supplement manufacturer DSM (https://dsm.com , WP)  launched Fortaro with online sales, no prescription required, for customers in Australia.  I bought some and you can read all about it at:


Each bottle costs AUD$24.99 (about USD$19.22 and contains 60 small (150mg) tablets, each with 10ug 0.01mg calcifediol per tablet. 


By May 2021 they had updated their system to handle free shipping to any country, with a maximum of 3 bottles (1.8mg calcifediol) per international order.  (Shipping is free to Australian destinations, and there is no 3 bottle limit.)

The cost of 3 bottles (1.8mg calcifediol) was AUD$74.97, which (2021-06-12) after adding 6% for credit card fees and exchange rate spread, is about USD$61.20.   Assuming no entry fees to the USA, which seems reasonable, this is USD$34.00 per milligram calcifediol.  However, the quantities are limited to 3 bottles per order to overseas destinations.  Delivery to the USA or Canada would take a lot longer than ordering from the USA.

In April 2021 DSM launched a similar product d.velop for online sales, with no prescription required, for customers in the USA and Canada:


However, within a few months the shipping was only to addresses in the USA.  By November 2021, the price was reduced from USD$30 for 60 0.01mg tablets to USD$20.  (The default pricing of $18 is for a continuing "subscription" of 3 bottles every 3 months.)

Since:

1. There are numerous packet forwarding companies in the USA - such as the one I use: https://www.shipito.com - who can either purchase items from sellers or ship packages to you in other countries if you buy them directly with delivery to their warehouse.
   
   
2. The product is labeled as "Vitamin D", is made in Switzerland and is non-prescription in the USA, so I expect there would be few difficulties getting these into other countries.

people in countries other than the USA and Australia have choices such as these for obtaining either of these packets/bottles of 60 x 0.01mg calcifediol tablets:

1. Order up to 3 Fortaro tablets from Australia.  Maybe make repeat orders to the same or different addresses if more are required.
   
   
2. Find a packet forwarding company in Australia and order more than 3 bottles of Fortaro, to be sent to the company - or have the company order them - and then have the company ship them to any other country.
   
   
3. This is probably the best option: Find one of the numerous packet forwarding companies, such as https://www.shipito.com/en/ in the USA and get them to send d.velop tablets, again perhaps with them placing the order.
   

So I believe that these 60 x 0.01mg calcifediol tablets are available, in practical terms, to anyone who wants them, no matter which country they live in.

Here are the details of the d.velop tablets:

Each packet contains 60 tablets each with 10ug 0.01mg calcifediol.  This is 0.6mg calcifediol for USD$20 including shipping within the USA.  So this is USD$33.33 per milligram calcifediol.   However, when I tried ordering some in November 2021 for delivery to ShipiTo in California, each USD$20 bottle had an additional USD1.90 tax added.

In May 2021 I ordered 3 packets, which were sent to ShipiTo.com in California, who posted the package to me using USPS.  (Their cheapest shipping option uses AusPost, who apparently won't handle packages containing nutritional supplements.  Overall, with their handling costs, this adds a lot to the cost.)   The package arrived on 2021-05-21.

These tablets are almost identical to the Fortaro tablets.  They are 148mg, 6mm in diameter and 3.5mm high.  Like the Fortaro tablets they disintegrate rapidly in water and, for me at least, have no taste.  They contain the same 0.01mg quantity of calcifediol.  Instead of being in a plastic bottle, they are in a small box with 6 blister pack trays of 10 tablets each.  They are the "product of Switzerland" and the bar code is 810077300008.

The benefit of calcifediol over D3 is very fast repletion.  So calcifediol is only really needed for emergencies.   Therefore, it needs to be ordered and ready to use when the emergency occurs -  such as someone who has not been robustly supplementing D3 for few months is diagnosed with COVID-19, sepsis, Kawasaki disease etc.  

In July 2021, DSM received approval for similar products in Europe: https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2021.6660 .

#liquid
Making a drinkable suspension from these 0.01mg calcifediol tablets - or a spoonable syrup with water and glycerol

For many people, to ingest 1mg of calcifediol, it will be a little odd, but perfectly practical and not at all unpleasant to swallow 3 or maybe a few more of these tablets, take a sip of water, swallow and repeat 33 times or so.

However, there may be problems taking larger numbers of tablets like this - or even taking tablets at all for babies and toddlers.  Also, in a medical setting, some patients might think the doctor or nurse is giving them an  excessive quantity of something if it requires 100 tablets or so.

The alternative is to mix the tablets into some water and make a drinkable suspension / slurry. On 20 December 2021 I tried this out with 100 d.velop tablets = 1mg.  I think the Fortaro tablets would behave in exactly the same way.   I used a small (150ml) glass.   Please click the small image to see a larger version.  The USB plug is an everyday item so you can perceive the size of the small tablets and small glass.

The tablets occupy a volume of about 20ml.  The tablets start puffing up within seconds when water is added. This is not a fizzy reaction - they gently disintegrate as they absorb water.


I added 50ml of cold water.  After two minutes or so the tablets puffed up:


I stirred this and it formed a suspension, which settled to some extent after a minute or two.  The  top 8mm or so of water has fewer suspended particles.


After taking the third photo, I stirred it and drank it.  A little was left in the glass, so I added some more water.

Stirring seconds before drinking is important, since it does settle.  There's no taste.  I guess it would be similar to drinking a solution of chalk, though not as heavy as actual chalk.  There are 14.8 grams of tablet and 50 grams of water, so this is a 23% by mass suspension / slurry.

I don't know of any professional pharmaceutical preparations which directly resemble this, but a 5% suspension of cephlahexin is somewhat similar.


To explore making a thicker suspension, I tried a single Fortaro tablet with a little glycerol. It remained firm, except at the edges.  I added a little water and after a minute or two the tablet puffed up and then disintegrated when I pressed it with a spoon. This is probably a better approach than the water suspension technique above.  I suggest, but have not tried with multiple tablets:

 
I am 69kg and take 1.25mg 50,000 IU vitamin D3 a week (7143 IU / day).  I guess my 25-hydroxyvitamin D level is most likely to be in the 60 to 100ng/ml.  I could not be anywhere near potentially toxic levels (above 150ng/ml) and I have no concerns about this single 1mg calcifediol dose causing toxicity.  (I formed this opinion after consulting with Prof. Wimalawansa, who has decades of clinical and research experience with vitamin D compounds.)  In terms of long-term capacity to raise 25-hydroxyvitamin D levels, this 1mg calcifediol is probably equivalent to 3 or 4mg vitamin D3 = 120,000 or 160,000 IU, which is a small bolus dose.

In this emergency vitamin D repletion scenario, you would be using Fortaro and d.velop products quite differently to the daily (or twice daily for d.velop) use the manufacturer recommends.   So you would be taking full responsibility for our actions - not giving me or DSM a hard time if something bad happens.

The prescription-only 0.266mg Hidroferol and Neodidro were probably initially intended for long-term supplementation, and so for a capsule to be taken every week or few weeks.  However, I understand that Faes Farma provided the Hidroferol capsules for the Cordoba trials, so I doubt they would quarrel with anyone using them two at a time (or perhaps four at a time) to save people from suffering, harm and death due to severe COVID-19.


Assuming plenty of calcifediol is available, I tried to arrive at a micrograms per kg bodyweight ratio, which would be helpful for everyone, from babies to sumo wrestlers.  I consulted with Prof. Sunil Wimalawansa MD, of New Jersey (long-time vitamin D researcher CV, Google Scholar) he advised that 14 micograms per kg bodyweight would be a good ratio to use. 

This is confirmed in a post Oral Calcifediol Repletes Blood Vitamin D Concentration within 4 Hours on Dr Wimalawansa's LinkedIn feed, where he has (2021-11-20) 13,143 followers.

This is about double the micograms / kg bodyweight which was so successful in the Cordoba trial and is 1mg for a 70kg person. 

Doubling the amount per kg gives some allowance for poor absorption and people suffering from obesity, for whom it is more difficult to raise their circulating 25OHD levels due to excessive fat absorption.  https://aminotheory.com/cv19/obesity/  

1mg of calcifediol is very approximately as effective, in long-term use, for raising circulating 25OHD levels, as 3 times this amount of D3.  (On this basis, 1mg calcifediol is roughly equivalent to 3mg 120,000 IU vitamin D3 cholecalciferol.   This is would be a small bolus D3 dose, and on average the Cordoba https://aminotheory.com/cv19/#2020-Castillo patients did well with a little more than half half this.

Since this is a single dose, there is no risk of toxicity unless perhaps the person had been excessively supplementing D3 for months. 

Due to the urgency of the situation, with the person's long-term health and perhaps life hanging in the balance, it makes sense to do a good job of repleting circulating 25OHD levels in a way which will still be effective if obesity and/or marginally poor absorption are problems.

So a 70kg person would get 1.0 mg = 100 tablets of Fortaro (100 / 60) * 25 = AUD$41.67 or d.velop tablets at a cost of (100 / 60) * 30 USD$33.33.  This is a good deal considering how serious all the above conditions could be.  Even if it made only a barely perceptible difference of a few percent to the outcomes, it would be a good deal. 

In Cordoba https://aminotheory.com/cv19/#2020-Castillo, with presumably some or many of the patients suffering from obesity, and so with bodyweights well over 70kg, 0.532mg calcifediol (54 d.velop tablets costing USD$27) was the primary cause of the huge reduction in symptoms, suffering and need for intensive care.  If the Cordoba patients averaged 76kg bodyweight (this seems reasonable, though no such data is presented) then in this trial the crucial initial dose of calcifediol would have been  about 0.007mg per kg bodyweight.

If the calcifediol was available on only limited quantities, I suggest distributing it evenly over multiple people according to their bodyweight and risk of serious harm.  Any amount will help. 

0.014mg calcifediol per kg bodyweight is an approximate recommendation, not some critical ratio to be adhered to closely.  It would be fine to remember:


which covers most adults and older adolescents.  For babies and children, the frail, overweight and obese adults outside this range, 0.014mg / kg is good guidance.

Another way of thinking about it, with Fortaro or d.velop 0.01mg tablets is:


Please see this section, which I wrote  before these two DSM product releases.  I suggest a single calcifediol dose followed by robust D3 supplementation in the days, weeks and years which follow:


I suggest taking D3 and perhaps calcifediol with some oil, such as fish oil, or at least towards the end of a substantial meal which contains fat, to activate the fat absorption mechanisms in the upper intestines.   Don't wash it down with a lot of water or any other drink.   However, while D3 is more soluble in fat than water, calcifediol, with its extra hydroxyl group, is more soluble in water.

Please remember that you are reading the best efforts of an electronic technician - not a doctor!   However, this proposal is based on the recommendation of one of the foremost vitamin D researchers who is a retired (but still very active) professor of medicine.

My interest in these Fortaro and d.velop tablets is to use several dozen to two hundred or so of them at once, which is completely different to how these products are intended to be used.   If you do this, it your decision.  

There are a few things to remember about these excellent DSM products - and of Hidroferol and Neodidro:

1. Despite the claims of DSM that Fortaro and d.velop have advantages over vitamin D3 cholecalciferol for long-term supplementation, I see no reason to believe this - unless it could somehow be shown that particular individuals had significant absorption problems for D3 and/or liver conversion problems, with no such absorption problems for calcifediol.  This may be the case: 
   
   
   A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25-hydroxyvitamin D3 and vitamin D3 in healthy adults with differing BMI and in adults with intestinal malabsorption
   Nipith Charoenngam, Tyler A Kalajian, Arash Shirvani, Grace H Yoon, Suveer Desai, Ashley McCarthy, Caroline M Apovian and Michael F Holick, American Journal of Clinical Nutrition 2021-05-19
   https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqab123/6277980  (Paywalled.)
   https://sci-hub.se/https://doi.org/10.1093/ajcn/nqab123
   
   
2. While these calcifediol tablets and capsules would work for long-term supplementation, they are a lot more expensive than alternatives such as 100 1.25mg 50,000 IU capsules for USD$30.  (Link to US manufacturer deleted at their request due to concerns about US regulations regarding advertising COVID-19 treatments.)   My wife Tina and I take one a week - so 0.179mg 7143IU a day.)   USD$30 buys 125mg D3 = USD$0.24 per milligram D3.  For USD$20, 60 d.velop tablets provide a total of 0.6mg calcifediol.  Assuming we accept the 3:1 ratio suggested by DSM, this is equivalent to only 1.8mg D3.  This is USD$11.11 per 1mg D3 equivalent.  On this basis, for long-term nutrition, d.velop is 46 times as expensive than these 50,000IU D3 capsules.
   
   
3. The only reason I am interested in these products is for one-off emergency vitamin D repletion.  This means they must be purchased ahead of time in anticipation of someone becoming ill with one of the abovementioned conditions, with that person not having been supplementing vitamin D3 properly for several months beforehand, and so reasonably assumed to have 25-hydroxyvitamin D levels far below the desired 50ng/ml 125nmol/L.
   
   
4. Most doctors know little or nothing about all the research mentioned on this page, so they might be opposed to the suggestions here.  Please ask them to read this page and hopefully at least look a the research articles cited here.   Another account of what they need to know, with more references, is at https://vitamindstopscovid.info/05-mds/ .
   

Lab grade calcifediol is also available but MDs would probably have to break regulations and so threaten their career of they did not use pharma grade - though with these tiny quantities, the lab grade calcifediol would be just as effective and with no possibility of there being a significant quantity of impurities. 

Likewise, almost certainly, the much cheaper agricultural feed products I researched at: https://aminotheory.com/cv19/agri25OHD/ where a bucket of poultry water feed powder costs about USD$100 and contains 1.875 grams of calcifediol. This is USD$0.0533 per milligram. 

The base cost of agricultural grade calcifediol is even lower.  1.25% calcifediol (DSM Rovimix Hy-D in 25kg bags) was worth (according to public import price records) USD$350/kg in 2020, which is USD$0.028 per milligram.

This 2021-07-17 article:

Vitamin D supplementation and COVID-19 risk: a population-based, cohort study
J. Oristrell, J. C. Oliva, E. Casado, I. Subirana, D. Domínguez, A. Toloba, A. Balado & M. Grau
Journal of Endocrinololgical Investigation 2021-07-17
https://link.springer.com/article/10.1007/s40618-021-01639-9

is not particularly significant - but I mention it here since a naive interpretation of its results might be misleading.  This was an observational study.  Ideally a study of the effects of D3 or calcifediol supplementation would involve randomly chosen supplementing subjects with those not chosen forming the control group.

There was no real control group and the people considered who were supplementing D3 or calcifediol were all doing so as part of prescriptions from their doctors.   So this study places people who are supplementing D3 of their own accord in the control group.

In the case of those prescribed to take calcifediol, only those who had been tested for creatinine [WP] were included.  This may be a standard medical test.  To some extent it may indicate that these people with some or many of them were suffering from from CKD (Chronic Kidney Disease), which is a deadly condition which greatly increases the risks of bad outcomes with COVID-19.   The control group for those people was a statistical selection (propensity score matching [WP]) of people who were not prescribed either D3 or calcifediol (but who may nonetheless have been supplementing D3, or less likely calcifediol, without prescription) where those control subjects were matched as closely to the subjects in the calcifediol supplementation group.  This is a dodgy process, to say the least.

The calcifediol supplementation group (and the group of individuals selected for the control group) had an average age of 70, and 83% were women.  This age and sex skew compared to the general population - and the fact that most or all of the control group, and probably many (due to propensity score matching) suffered from kidney disease means the results tell us little or nothing about what would happen if the general population supplemented with calcifediol.  

Furthermore, for the general population, I am not aware of any advantage of supplementing with calcifediol instead of D3.  My sole interest in calcifediol is as described above - for rapid 25OHD repletion in emergencies.