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 email@example.com 19 July 2021 Twitter: https://twitter.com/RobinWhittle3
(First established 2021-05-02.)
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
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
). 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.
|Calcifediol used to be prescription only, and difficult to obtain in most countries.
|Rayaldee is prescription only and is available in the USA for a very high price.
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
|Online, non-prescription small (0.01mg) tablets in Australia, with delivery of 3 bottles max to any other country. (DSM.)
tablets available online with delivery to the USA and
Canada. A similar European product will probably be
|A single oral dose of 0.014mg
calcifediol / kg bodyweight will safely replete any person to 50ng/ml
or more circulating 25-hydroxyvitamin D.|
|(Low key.) An
observational study of D3 and calcifediol supplementation in Barcelona
is less interesting that it might at first seem.
|Not finished yet.
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
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.
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 Al 2016-08-11
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/
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
0.6mg total, for USD$30 including shipping, to customers in the USA and
. Similar Fortaro
tablets are available from Australia, with shipping of up to 3 bottles (1.8mg total) to any country. Full details below.
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
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
the graph. The article link and summary is at: https://vitamindstopscovid.info/02-autocrine/#04-quraishi
This justifies the 40 to 60ng/ml
recommendation of the Call to D*Action MDs and researchers in 2008
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
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
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)
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
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:
- 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).
- Autocrine signaling: 1,25OHD molecules just produced in the cytosol binds to VDR molecules there.
signaling: 1,25OHD produced as part of autocrine
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.)
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
] 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
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
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.
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:
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
By reading and understanding the 02-autocrine 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 autocrine 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 autocrine signaling. 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.
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
autocrine/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: McGregor et al. 2020 (linked to, summarised and discussed at: https://aminotheory.com/cv19/icu/#2020-McGregor) 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
This single dose of 0.532mg calcifediol, given at the earliest opportunity to hospitalised COVID-19 patients, reduced ICU rates from 50% to 2% and deaths from 8% to zero.
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)
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:
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:
- Severe COVID-19 - or probably any symptomatic form of COVID-19,
since these carry high risks of lasting harm, even if the person does
- 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.
- 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]
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
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
as high or low blood pressure. These anti-inflammatory drugs -
such as prednisone and dexamethasone can cause psychosis and deadly
fungal diseases. See:
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
, 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.
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.
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
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.)
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
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
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 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
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
) launched Fortaro
sales, no prescription required, for customers in Australia. I
bought some and you can read all about it at:
Each bottle costs AUD$24.95 (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
, which is less expensive than ordering d.velop
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.
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:
- 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
- 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:
- Order up to 3 Fortaro tablets from Australia. Maybe make repeat orders to the same or different addresses if more are required.
- 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.
- 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
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
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
In July 2021, DSM received approval for similar products in Europe: https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2021.6660
How much calcifediol to use, as a ratio of bodyweight?
In this emergency vitamin D repletion
scenario, you would be using Fortaro
products quite differently to the
daily (or twice daily for d.velop
) use the manufacturer
recommends. So you would be taking full responsibility for
- not giving DSM a hard time if something bad happens, or me!
The prescription only 0.266mg Hidroferol
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
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
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
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
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.
, with presumably some or many of the patients suffering from
obesity, and so with bodyweights well over 70kg, 0.532mg calcifediol (54 d.velop
USD$27) lead to a huge reduction in symptoms, suffering and need for
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
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
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
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
Please remember that you are reading the best efforts of an electronic technician - not a doctor!
My interest in these Fortaro
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:
- 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
- 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
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
order the calcifediol product and use it as soon as it
- 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/ .
(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:
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
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