A small 1mg single oral dose of calcifediol (25-hydroxyvitamin D = 25OHD) raises blood vitamin D (25OHD) within a few hours to the 50ng/ml 125nmol/L levels which all immune cells need to function properly.

It does this in 4 hours, instead of the days or week or so it takes even 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, MIS etc. urgently need their levels raised to at least 50ng/ml.

Only calcifediol can do this.

Calcifediol is now available, in the USA, Canada and Australia, without prescription, at affordable prices, in quantities needed for emergency vitamin D repletion:  DSM's d.velop and Fortaro

Quadruple headings - this is big news! 

../ To the main page of this site.

Robin Whittle rw@firstpr.com.au  19 July 2021    Twitter: https://twitter.com/RobinWhittle3
(First established 2021-05-02.)

Disclaimer:

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!

That said, 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 are perfectly capable of understanding all this, but they are very busy, and are generally discouraged from thinking of vitamin D as being important to the immune system.

Please see this page https://vitamindstopscovid.info/05-mds/ for links to and discussion of the key research articles all MDs (and nurses . . . really everyone who aspires to medical knowledge) need to know about - but generally don't - regarding vitamin D and the immune system.

Contents

Page
Description
Last update
#00-sv
Short version.
2021-07-19
#01-rapid
Full version,
2021-07-19
#02-presc
Calcifediol used to be prescription only, and difficult to obtain in most countries.
2021-07-19
#03-ray
Rayaldee is prescription only and is available in the USA for a very high price.
2021-07-19
#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.
2021-07-19
#05-fortaro
Online, non-prescription small (0.01mg) tablets in Australia, with delivery of 3 bottles max to any other country.  (DSM.)
2021-07-19
#06-develop
Similar non-prescription tablets available online with delivery to the USA and Canada.   A similar European product will probably be available soon.
2021-07-19
#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.
2021-07-19
#99-barc
(Low key.) An observational study of D3 and calcifediol supplementation in Barcelona is less interesting that it might at first seem.
Not finished yet.


#00-sv

Short version

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.

For average weight adults (70kg, 154lb) a single oral dose 1.0 milligram calcifediol will do this within 4 hours.   (Actually, half this will usually do it too - 1mg is to allow for some people absorbing it poorly and to allow for some people being obese.  The excess fat cells in obesity absorb and do not return both D3 and circulating 25OHD.)

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 raise levels over 50ng/ml within several days to a week. 

This is good, but 1 milligram of oral calcifediol will do it in 4 hours and so enable the person, in general, to overcome the infection - and generally to reverse any over-inflammatory responses - much faster.

A single oral 1mg dose of calcifediol boosts vitamin D levels fast - hours rather than days (bolus vitamin D3) or months (ordinary 0.125mg 5000 IU / day D3).

The original version of this graph is from the end of the PDF version of this patent by Faes Farma:

Calcifediol soft capsules
Josep María SUÑÉ NEGRE,
Ignacio Ortega Azpitarte, Pepa Del Arenal Barrios, Gonzalo HERNÁNDEZ HERRERO
WIPO WO 2016/124724 A
l   2016-08-11
https://patents.google.com/patent/WO2016124724A1/

Most doctors cannot imagine that vitamin D is so important to the immune system.  They have never heard of vitamin D based autocrine 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-autocrine/ .

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, for USD$30 including shipping, to customers in the USA and Canada:  https://dvelopimmunity.com .  Similar Fortaro tablets are available from Australia, with shipping of up to 3 bottles (1.8mg total) to any country.  Full details below.



25-hydroxyvitamin D calcifediol now non-prescription and available in Australia, Canada and the USA


#01-rapid

Why RAPID (within a few hours) repletion of circulating 25-hydroxyvitamin D is a crucial step in preventing or reversing the progression of severe COVID-19 etc. and why calcifediol tablets or capsules (or potentially injections or IV drips) are the only way of achieving this

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:

Here we concentrate on vitamin D, but in the emergency situations described below in which there is an active viral infection, and/or hyper-inflammatory immune responses, Ivermectin is likely to be highly effective too.  These two interventions - rapid repletion of circulating 25-hydroxyvitamin D with calcifediol and anti-viral anti-inflammatory Ivermectin - operate by completely separate mechanisms, and so should complement each other.  Please see: https://ivmmeta.com and https://covid19criticalcare.com/ivermectin-in-covid-19/

Other nutrients including zinc, magnesium, boron, vitamin C and B vitamins (PMC7428453) should be considered too.  Omega 3 fatty acids are important for immune system functioning, but would take months to build up in the body.

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) 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 cut out the 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, but there is 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-autocrine/#04-quraishi .

At least 50ng/ml 125nmol/L blood vitamin D levels are required for all immune system cells to function properly

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/ .




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 there to 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, after a few months (see top graph of two, below).   D3 supplemental intake quantities as ratios of body weight: https://vitamindstopscovid.info/01-supp/ .   This 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 8 to 22ng/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 plasma 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 autocrine and paracrine signaling systems, where it is consumed, and turned into 1,25OHD AKA calcitriol inside the cell. 

Neither 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 most people and all doctors.  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 - autocrine and paracrine signaling - since these have mainly been discovered since the mid-2000s.  https://vitamindstopscovid.info/02-autocrine/

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.

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 secosteriold 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.

Sidebar on 1,25OHD:

1,25OHD is the only one of the three compounds which strongly activates vitamin D receptor (VDR) molecules.  A 1,25OHD molecule binds to a VDR molecule and together, as a bound complex, they alter the patterns of gene expression (copying of gene data in the DNA to messenger RNA) and so the rates at which the cell produces various proteins.  (You may see 1,25OHD referred to as "activated vitamin D".  Vitamin D terminology is confused and confusing.)  The changes to gene expression depend entirely on the cell type.  

In any given cell type, VDR molecules can be "activated" (bind a 1,25OHD molecule, and so change their shape and behavior) when any of these three processes occur:
In all cases the bound complexes of 1,25OHD and VDR "migrate" to the nucleus. (I have not found a good description of this.  Perhaps they simply diffuse.  I haven't read of an active transporter system to push them into the nucleus, and as far as I know, the bound complexes don't have a GPS and propellers so they actually move themselves towards and into the nucleus.)

Once in the nucleus, the activated VDRs bind to some other molecules and the resulting complex alters various DNA management arrangements, including how parts of particular chromosomes are unwound from their normally tightly wound (not the spiral structure, see histones) state to expose particular genes to the enzymes which copy their data to new messenger RNA molecules, which go to the cytoplasm and direct ribosomes [WP] to make a particular protein.

So the presence of 1,25OHD-VDR complexes in the nucleus alters the cell's behavior by altering its protein production by altering its transcription of genes.  Exactly which genes are upregulated and downregulated differs from one cell type to the next.

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-autocrine/#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 autocrine signaling - a form of signaling which occurs entirely within the cell.  

Other types of molecules are involved in other autocrine signaling arrangements and here we are only interested in 25OHD being converted to 1,25OHD.  This autocrine signaling is not to maintain a steady state, such as with calcium- bone or some other stable bodily system.  The autocrine signaling conversion to 1,25OHD is only turned on in particular circumstances.   Vitamin D based autocrine 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, autocrine 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 autocrine and paracrine signaling, I made this page:

https://vitamindstopscovid.info/02-autocrine/

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 autocrine and paracrine signaling than the great majority of doctors.  By  reading and understanding the 02-autocrine page, you will attain a still better understanding of these processes.   It includes references to research which:
Once you understand vitamin D autocrine / 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), then it is clear why low vitamin D drives the development of severe COVID-19 and why a tiny quantity of 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://aminotheory.com/cv19/#helminthsgone .


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 (obese people need more D3 per kg bodyweight), please see:

https://vitamindstopscovid.info/01-supp/

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.

However, if a person is suffering from, or at significant risk of developing,any one of these conditions:
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' autocrine 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 all MDs and nurses 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 .


Bolus (stoss) D3 supplementation usually helps - such as a single 5mg 200,000IU dose or several such doses over a few days.  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.

#02-presc

Calcifediol is a magic bullet, but until early 2021, has been prescription-only and very hard to obtain except in Spain, Italy and some nearby countries.

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 diffused into all tissues.  There it diffuses into most or all cell types, and all immune cells - and many other types of cell - need it inside their cell bodies so it can be used when their autocrine signaling systems are activated.  So it does go exactly where it is needed - into circulation and from there into all the tissues.

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, 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 medical conditions, where the primary, correctable, problem is low circulating (blood) levels of 25OHD = 25-hydroxyvitamin D = calcifediol.

Assuming the person is conscious and can ingest liquids, all we need to do is give them 0.5 mg to perhaps 2mg (for obese adults) 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.)

#03-ray

Rayaldee from the USA

When I started advocating one-off, 1 milligram or so, calcifediol oral intervention in the middle of 2020, calcifediol was very hard 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.

(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 possibly 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 miligram.

#04-faes

Hidroferol from Spain and Neodidro from Italy

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 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 recieved 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.

https://profesionalessalud.faesfarma.com/productos/hidroferol/



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.


#05-fortaro

DSM's Fortaro, for customers in Australia - and now to any other country

In late 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:

https://aminotheory.com/cv19/#calcifediol-avail-au

Each bottle costs AUD$24.95 (about USD$19.22 and contains 60 small (150mg) tablets, each with 10ug 0.01mg calcifediol per tablet

https://shop.fortaro.com/products/fortaro

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, which is less expensive than ordering d.velop(below) from the USA.  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.

#06-dvelop

DSM's d.velop for customers in Canada and the USA

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

https://dvelopimmunity.com/products/vitamin-d-times-three

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, Canada 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. 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.

2021-05-21: I previously reported that these were 0.02mg tablets, but this is the serving size of 2 x 0.1mg tablets. 

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$30 including shipping within the USA.  So this is USD$50 per milligram calcifediol.

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, so generally I think it is better to order Fortaro from Australia for delivery to countries outside the USA or Canada.)   The package arrived on 2021-05-21.

These tablets are almost identical to the Fortaro tablets.  They are about 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 .

#07-ratio

How much calcifediol to use, as a ratio of bodyweight?

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 DSM a hard time if something bad happens, or me!

The prescription only 0.266mg Hidroferol and Neodidro are 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 at 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 11,948 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 proper 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$50.  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) lead to a 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 was about 0.07mg 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:

55 to 85kg: 1mg calcifediol
120 to 190lbs: 2mg calcifediol

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:

Multiply the bodyweight in kg by 1.4 to get the number of tablets.

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:

https://aminotheory.com/cv19/#25plusD3

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!   My interest in these Fortaro and d.velop tablets is to use several dozen of them at once, which is completely different to how these products are intended to be used.   If you do this, it your decision.   Don't complain to me or DSM if something bad seems to have occurred due to using this product in ways other than they intend.

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 D3 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 - see the latest research on this (only the abstract was available without cost on 2021-06-12, but you can request a copy from the first author https://www.researchgate.net/publication/351732512): 

    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

  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: https://www.biotechpharmacal.com/collections/bone-health/products/d3-50-50-000-iu-vegetable-caps .  (Tina and I take one a week - so 0.179mg 7143IU a day.)   USD$30 buys 125mg D3.  For the same price, 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, making d.velop 70 times more expensive than these BioTech Pharmacal 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.   At a pinch, one might use D3 to start with, order the calcifediol product and use it as soon as it arrives.  

  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.   A briefer account of what they need to know is at https://vitamindstopscovid.info/05-mds/ .

#99-barc

(Low-key) Oristrell et al. 2021: Barcelona vitamin D3 and calcifediol supplementation study of April 2019 to February 2020

This section is not finished.  I will return to it in a few days.

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.  I believe this  means that those included were all, or almost all, suffering 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.












© 2021 Robin Whittle   Daylesford, Victoria, Australia