The urgent need for at least 50 ng/mL 125 nmol/L 25-hydroxyvitamin D

(The final section was updated on 2022-02-26.)

Important update 2022-03-08: The Front Line COVID-19 Critical Care Consortium (Dr Paul Marik, Dr Pierre Kory, Dr Joseph Varon and colleagues) have updated the PDF version 16 of their MATH+ hospital protocol for COVID-19 to recommend a single oral dose of 0.014 mg / kg bodyweight calcifediol as the preferred treatment, with bolus vitamin D3 if this is not available. See Table 1 in the PDF at:

covid19criticalcare.com/covid-19-protocols/math-plus-protocol/

The background to this is given in their recent article in the Canadian peer-reviewed Journal of Clinical Medicine Research: “MATH+” Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale: www.jocmr.org/index.php/JOCMR/article/view/4658.

Below are the details of why this calcifediol recommendation is the best early treatment for COVID-19 and other diseases, including sepsis, Kawasaki disease, MIS-C etc. with further details on how to obtain calcifediol, and on long-term maintenance of good 25-hydroxyvitamin D with vitamin D3 supplementation. The final section concerns how to prepare the DSM d.velop and Fortaro non-prescription 0.01mg calcifediol tablets into a drinkable suspension.
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Our immune cells need a good, 50 ng/mL 125 nmol/L level of 25-hydroxyvitamin D (as measured in vitamin D blood tests) to function properly.

Without a lot of recent ultraviolet B skin exposure, or months of vitamin D3 supplements - such as 0.125 mg 5000 IU a day for 70 kg bodyweight (a gram every 22 years) - most people have only 5 to 25 ng/mL 25-hydroxyvitamin D.

25-hydroxyvitamin D levels well below 50 ng/mL result in weak innate and adaptive immune responses to bacterial and viral infections, as well as a higher risk of self-destructive inflammatory (indiscriminate cell destruction) responses.

This article concerns using a single oral dose of calcifediol to boost the 25-hydroxyvitamin D level safely over 50 ng/mL, in 4 hours or so, to enable the immune system to function properly, perhaps for the first time in the person’s life. The boosted level is sustained with ordinary daily vitamin D3 supplements. “Calcifediol” is the pharmaceutical name for 25-hydroxyvitamin D.

In Spain and Italy, the most likely way this calcifediol will be taken is as 0.266 mg prescription-only capsules. In most other countries, the most obtainable form of approximately 1 milligram calcifediol is a larger number - such as 100 - of small (6mm) non-prescription tablets, each containing 0.01 mg calcifediol. At the end of this article are links to where these can be ordered from, and a suggestion for making them into a drinkable suspension, similar to (but without the urky taste and colour of) the widely-used cephalexin antibiotic suspension.

This use of calcifediol is not for long-term supplementation, or for boosting levels over a few days or weeks. This rapid boosting of 25-hydroxyvitamin D levels in 4 hours is critically important to enable full strength, rapid, innate and adaptive immune responses, with greatly reduced risk of dysregulated, hyper-inflammatory indiscriminate cell-destroying responses (cytokine storm), for clinical emergencies including:

COVID-19, at any stage, but the earlier the better.
Sepsis [Wikipedia: WP] - the common, hyper-inflammatory, self-destructive, immune system over-reaction to a variety of conditions, such as bacterial, viral and fungal infections, and burns. Also known as septicemia, this can be difficult to diagnose since there can be a whole range of troubling symptoms. The person’s life can be in danger as the inflammatory attack on the lungs and other organs develops within hours. Perceptive nurses and doctors will usually identify it, but not everyone can get to see them in time. A variety of symptoms can progress rapidly to organ failure and the need for intensive care - often with mechanical ventilation - in a battle to save the person’s life. In 2020, the Global Burden of Disease Project wrote that about 19.7% of deaths worldwide are caused by sepsis.

As with the other conditions listed here, most doctors do not understand importance of treating sepsis urgently by boosting 25-hydroxyvitamin D levels - because they don’t realise that most people’s ordinary levels, often below 20 ng/mL, are far below what their immune systems need. Risk factors for sepsis, severe COVID-19 and the other conditions listed here include obesity, diabetes, high blood pressure and dark skin and/or sun-avoidant lifestyles, especially when living far from the equator. These all partly cause and/or are partly caused by low 25-hydroxyvitamin D levels.
Kawasaki disease [WP] is a diagnosis for children, mainly under 5 years of age, who suffer vasculitis [WP] - inflammation of the medium-sized blood vessels. This often damages their coronary arteries by the formation of enlarged segments, know as aneurysms [WP]. KD is relatively rare, but is the most common cause of acquired heart disease in children in the USA [Rowley & Shulman 1998]. It is triggered by a variety of infections, but in some cases no such infection is known. Rashes and “strawberry tongue” are obvious symptoms. KD’s incidence has increased greatly since 2020 due to COVID-19 - including mild or asymptomatic infections - triggering the immune response into its self-destructive, hyperinflammatory state.

It is reasonable to assume that genetic variations predispose some children to KD. Dark skin, obesity, and winter/spring seasonality are risk factors. Where have we heard this before? These all cause low 25-hydroxyvitamin D levels.

Despite this, and despite Stagi et al. 2014 [summary and link] reporting that KD children have very low 25-hydroxyvitamin D levels, most pediatricians today never consider that their KD patients’ typically low 25-hydroxyvitamin D levels play a crucial role in the development of this disease. Stagi et al. found the KD children’s average 25-hydroxyvitamin D levels were 9.2 ng/mL, while aged-matched healthy controls averaged 23.3 ng/mL. The KD children with coronary artery abnormalities averaged just 4.9 ng/mL - a tenth of what their immune system needs to function properly.
Multisystem Inflammatory Syndrome in Children / due to COVID-19 AKA MIS-C [WP] is a diagnosis much the same as Kawasaki disease, except that it generally is applied to children between the ages of 5 and 18 and that it is always triggered by COVID-19 (SARS-CoV-2 viral infection).

Other diagnoses with much the same criteria include: Paediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 infection (PIMS-TS) and Paediatric multisystem inflammatory syndrome (PMIS).

Almost every pediatrician who writes about these conditions in recent academic journal articles about KD, MIS-C and PIMS-TS is completely clueless about these children’s urgent need for 50 ng/mL 25-hydroxyvitamin D. Stagi et al. is only rarely cited. I retrieved the 50 most significant articles on these conditions since the start of 2021 via Google Scholar and only one of them recognised the causative role of low vitamin D. In a forthcoming article I will report on what happens when I send the corresponding authors of these articles an email with links to the most pertinent research on vitamin D and the immune system.
Acute respiratory distress syndrome (ARDS). From the Wikipedia article [WP] “ARDS is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased quality of life is common.”
Pneumonia is an inflammatory condition of the lungs in which the tiny alveoli (air sacs) become filled with fluid. This can be caused by a variety of infections. From the Wikipedia page [WP] “Each year, pneumonia affects about 450 million people globally (7% of the population) and results in about 4 million deaths.”
Pre-eclampsia [WP] is a potentially deadly condition which develops after the 20th week of pregnancy, involving abnormal vascular development in the placenta and hypertension. A quick search of Google Scholar for “pre-eclampsia” and “inflammation” [GS] or “organ damage” [GS] indicates we can think of this as akin to sepsis. Google Scholar also reveals that its association with low 25-hydroxyvitamin D levels [GS] is well established. Yet, as with all these conditions, it seems that most doctors do not think this easily correctable nutritional deficiency plays a significant role in the etiology of pre-eclampsia.

When 50 ng/mL 25-hydroxyvitamin D is regarded as the proper threshold of vitamin D repletion, rather than the more commonly used thresholds of 20 or 30 ng/mL, low 25-hydroxyvitamin D in pregnancy is almost ubiquitous unless Mom has been supplementing vitamin D3 properly for months.

Low 25-hydroxyvitamin D in pregnancy always needs to be corrected - not least to protect the mother and improve the baby’s neurodevelopment, such as by reducing the risk of autism. (See also Scientific American 2009.) Pre-eclampsia is a medical emergency for both Mom and Babe-to-be, and should be tackled in hours to save them both from harm.
Influenza. Low 25-hydroxyvitamin D drives influenza transmission and severity nutritionmatters.substack.com/p/covid-19-seasonality-is-primarily and there are multiple studies which indicate that influenza vaccines make little or no difference to hospitalisation and death rates: nutritionmatters.substack.com/p/influenza-vaccines-do-not-reduce and nutritionmatters.substack.com/p/influenza-vaccines-do-not-reduce-1da. Doctors and other medical professionals can best protect their patients from influenza by having them properly supplement vitamin D3, or failing that, having calcifediol (ideally, otherwise bolus vitamin D3) on hand to replete their 25-hydroxyvitamin D levels if they contract influenza.
Any other illness . . . I can’t think of any illness where a faster return to health would not be achieved by boosting common, lousy, 25-hydroxyvitamin D levels to at least 50 ng/mL ASAP.

Granulomatous diseases including sarcoidosis - in which dysregulated immune responses cause some cells to release excessive 1,25-hydroxyvitamin D into the circulation - are often thought to be best treated by reducing 25-hydroxyvitamin D. See vitamindstopscovid.info/01-supp/#sarc for an article which reports that sarcoidosis patients do better with higher 25-hydroxyvitamin D levels.

Calcifediol needs to in-stock, on hand - otherwise use bolus vitamin D3

If there is a need for urgently boosting 25-hydroxyvitamin D, there is no point in ordering calcifediol and waiting days for it to be delivered. The best alternative then is to use bolus (single, high dose) vitamin D3, which can usually be obtained locally within a day. This takes, very approximately, 4 days to raise 25-hydroxyvitamin D levels above 50 ng/mL, due to the need for hydroxylation in the liver.

The person’s life hangs in the balance, so unless it is known that the person has been supplementing vitamin D3 adequately for months, calcifediol (below) or (second best) bolus vitamin D3 is the most important step which can be taken to provide the conditions in which their immune system can function properly.

The ESPEN guideline on clinical nutrition in the intensive care unit. Clinical Nutrition, 2009. states that:

In critically ill patients with measured low plasma levels (25-hydroxyvitamin D < 12.5 ng/mL, or 50 nmol/L) a high dose of vitamin D3 (500,000 IU) as a single dose can be administered within a week after admission.

This assumes average adult bodyweight of ~70 kg. Measuring the patient’s blood 25-hydroxyvitamin D level make take days, or at least hours, when every hour really matters. (I have been reliably informed, US hospitals typically charge insurers USD$300 per vitamin D test.) So it would be better to supply a bolus dose ASAP, rather than wait for test results, unless there was reason to believe the person had been supplementing vitamin D3 at high levels for some time.

Han et al. 2016 www.sciencedirect.com/science/article/pii/S2214623716300084 ran a Randomized Controlled Trial (RCT [WP]) in Atlanta, Georgia, involving mechanically ventilated ICU patients whose average age was ~60 and whose average BMI was about 32. This means that most of them were suffering from obesity, so we can reasonably assume an average bodyweight well above 70 kg. Their 25-hydroxyvitamin D levels at admission averaged ~21 ng/mL, which remained stable in the placebo group. The first intervention group received 1.25mg 50,000 IU a day of vitamin D3 (cholecalciferol [WP] for 5 days, for a total of 250,000 IU. At 7 days, their 25-hydroxyvitamin D levels averaged 46 ng/mL. I imagine this level would have risen another 10 or so ng/mL in the next week or so as the D3 in circulation was hydroxylated in the liver. This is all very well, but what they need is good 25-hydroxyvitamin D levels immediately, not a week or two later. The second intervention group received twice this: 500,000 IU over 5 days, which raised their 7 day 25-hydroxyvitamin D levels to an average of 55 ng/mL.

The average length of time in hospital for the 250,000 IU group was reduced from 36 days (placebo group) to 25 days for the 250,000 IU group and 18 days for the 500,000 IU vitamin D3 group.

Toxicity may become a problem if 25-hydroxyvitamin D levels rise above 150 ng/mL 375 nmol/L: www.endocrine.org/clinical-practice-guidelines/vitamin-d-deficiency (2011). Self-limiting mechanisms mean that such levels can generally only occur after very high vitamin D3 intakes for weeks or months. I know of no reports of toxicity resulting from bolus vitamin D3 doses.

In Australia, retail shops are not permitted to sell vitamin D3 capsules containing more than 0.025mg 1000 IU. Consuming several hundred of these at once is probably inadvisable, so it is much better to use 1.25 mg 50,000 IU (typically powder filled) capsules, which are quite small. These are available from American manufacturers, for instance via Australian eBay sellers. In the USA, bottles of 100 to 120 50,000 IU D3 capsules retail for ~USD$25. 10,000 IU capsules are readily available at Walmart, CVS, Walgreens etc.

This is not medical advice

Medical advice is what you get from a doctor or other healthcare professional after he or she has examined you.

You are reading the best efforts of an electronic technician and computer programmer. My aim is to point you to the best research I know of concerning nutrition and health. This would not be necessary if most doctors were fully up to speed on vitamin D and the immune system. For a number of extremely perplexing and difficult to understand reasons, most are not.

I collaborate with MDs and other researchers, including professors of medicine, retired and not, who have been researching and trying to raise awareness of vitamin D among the medical profession for decades.

Your mission, should you choose to accept it, is to make your own decisions based on the best research you can find - including perhaps by working with healthcare professionals and others you trust who are able to understand biochemical processes better than you can on your own.

You need to ascertain the veracity of everything you read here, and ideally consider other sources of information as well.

If all you read on this page is true - and I attest that it is - then you must be wondering why almost every doctor does not already know it. The current situation regarding vitamin D and more broadly nutrition and simple, safe, inexpensive early treatments for COVID-19 is analogous to a world in which most electronic technicians are oblivious to the idea that batteries can be insufficiently charged, or in which motor mechanics are constantly adjusting and tweaking sputtering engines, unable to imagine that fuel can be contaminated, fuel pumps can be flaky, and filters blocked. In this nightmare scenario, some technicians and mechanics are busting their gut trying to make their colleagues aware of the importance of good supplies to subsystems: stable, precisely regulated, voltage to electronic systems and a full flow of uncontaminated fuel to motor car engines.

Figuring out how this situation arose in medicine, and what to do about it, is the real work. This nightmare of groupthink and corrupted regulatory agencies is much more difficult than understanding the immune system’s need for vitamin D, how to ensure this is met in the long term, and how to boost 25-hydroxyvitamin D in medical emergencies.

Vitamin D3 cholecalciferol, 25-hydroxyvitamin D calcifediol and 1,25-dihydroxyvitamin D calcitriol

In order to understand why 25-hydroxyvitamin D levels need to be 50 ng/mL or more, please see the Quraishi et al. 2014 graph at the start of my first Substack article: nutritionmatters.substack.com/p/vitamin-d-and-early-treatment-vs . This - and numerous observations of the strong relationship between low 25-hydroxyvitamin D levels and severe COVID-19 symptoms (see the second graph there) - vindicates the 48 MDs and researchers (many were both) who called for 40 to 60 ng/mL 25-hydroxyvitamin D to be the standard of vitamin D repletion, in the 2008 Call to D*Action: grassrootshealth.net/project/our-scientists/.

Further observations of low 25-hydroxyvitamin D levels driving COVID-19 severity come from Dror et al. 2022, Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness: journals.plos.org/plosone/article?id=10.1371/journal.pone.0263069 , which includes the following:

and:

To understand why just taking 5000 IU vitamin D3 a day (for 70 kg bodyweight) takes months to attain 50 ng/mL 25-hydroxyvitamin D, you need to understand how vitamin D3 is hydroxylated in the liver to 25-hydroxyvitamin D, which is stored in the bloodstream and used as an essential input to immune cells and cells of other types for their autocrine (inside each cell) and paracrine (to nearby cells) signaling systems. This is unrelated to the kidneys hydroxylating some of the circulating 25-hydroxyvitamin D to produce a very low, but precisely controlled, level of circulating 1,25-dihydroxyvitamin D, which acts as a hormone (long distance endocrine signaling via the bloodstream) to regulate calcium, phosphate and bone metabolism.

All medical professionals know about the 25-hydroxylation in the liver and the 1-hydroxylation in the kidneys, for the hormonal regulation of bone metaolism. However, very few understand autocrine signaling. Some doctors mistakenly assume that hormonal 1,25-dihydroxyvitamin D levels affect the immune system and that boosting circulating levels, such as by ingesting calcitriol (the pharma name for 1,25-dihydroxyvitamin D) will improve immune system function.

To understand all the above, please see my pages - and most importantly the research articles they cite: What every MD, immunologist, virologist and epidemiologist should know about vitamin D and the immune system vitamindstopscovid.info/05-mds/ and Vitamin D autocrine signaling - illustrated tutorial https://vitamindstopscovid.info/02-autocrine/ .

Excessive inflammation is largely caused by lack of helminths

Boosting inadequate 25-hydroxyvitamin D levels to at least 50 ng/mL from significantly lower levels will generally enable the immune system to mount strong innate and adaptive responses to bacterial, viral, fungal and yeast pathogens. It will reduce excessive inflammation caused by immune dysregulation such as in Th1 lymphocytes, as described by Chauss et al. 2021 (link and summary aminotheory.com/cv19/icu/#2021-Chauss).

However, the fundamental cause of this excessive inflammation in most humans and in most domestic and agricultural animals is lack of helminths - intestinal worms. Indiscriminate, cell-destroying, inflammatory immune responses are the only ones which work on these multicellular parasites.

This use of vitamin D is something of a hack. The real problem is overly-aggressive, inflammatory immune responses which evolved to counteract the anti-inflammatory compounds exuded by the helminths which infested our ancestors. Some individuals today are genetically predisposed to particularly strong inflammatory responses, and so, without helminths, suffer the self-destructive consequences.

Please see vitamindstopscovid.info/06-adv/ for research into this fascinating field, which very few medical professionals, or even vitamin D researchers, are aware of. This page covers the use of higher than usual vitamin D3 intakes, to attain much higher than 50 ng/mL 25-hydroxyvitamin D levels for the purpose of suppressing many inflammatory autoimmune conditions, including psoriasis, rheumatoid arthritis, multiple sclerosis, cluster headaches and migraine.

A single oral dose of 0.014 mg calcifediol per kg bodyweight for 4 hour repletion of 25-hydroxyvitamin D

If you have read the research articles cited by the above-linked web pages and come to understand the immune system’s need for 25-hydroxyvitamin D the way I do, you will recognise that - except for those who have been properly supplementing vitamin D3 for months at least - most people are trying to live and battle potentially deadly diseases with only a fraction of the 25-hydroxyvitamin D their immune system needs.

Bolus D3 takes, very approximately, 4 days to significantly boost these levels - but even after 7 days, the (typically well over 70kg) patients of Han et al. above who had a 500,000 IU D3 bolus over 5 days only raised their levels to about 55 ng/mL.

Oral (or perhaps intramuscular, sub-cutaneous or intravenous) calcifediol is the only way of boosting 25-hydroxyvitamin D levels substantially in a few hours. The importance of this in the emergencies listed above cannot be underestimated. The only research I know of which reports the pharmacokinetics of ~0.5 mg calcifediol doses is a patent by the Spanish pharmaceutical company Feas Farma, for the very same 0.266mg, oil filled, calcifediol capsules which were used in Castillo et al. (see vitamindstopscovid.info/05-mds/). The patent is Calcifediol Soft Capsules, 2016 patents.google.com/patent/WO2016124724A1/.

This graph, adapted directly from the patent, shows average 25-hydroxyvitamin D levels being raised from ~18 ng/mL to well over 50 ng/mL in 4 hours after healthy volunteers ingested two 0.266mg calcifediol capsules - a total of 0.532mg.

Castillo et al. 2020 used the exact same two capsule dose of calcifediol in an RCT with hospitalised COVID-19 patients, in Cordoba, Spain. The spectacular nature of their results was partly explained by randomisation placing patients with more comorbidities in the control group. However, the authors argue that the great majority of the health benefits they observed was due to the calcifediol. This is supported by the statistical analysis of Jungreis and Kellis 2020.

Their results - largely attributed to the rapid 25-hydroxyvitamin D boost from the initial calcifediol dose, but which are also partly due to 0.266 mg being given on days 3, 7, 14 etc, as well - were:

ICU admissions dropped from 50% to 2%.
Deaths dropped from 8% to zero.

Sunil Wimalawansa MD is a Professor of Medicine (now retired, ex University of Texas Medical Branch at Galveston and Robert Wood Johnson Medical School, now Rutgers University, CV, Google Scholar) who has been researching and raising awareness of vitamin D since the late 1990s. The most common response he gets from doctors is: “How can it be true? Its too simple.”.

He recommends a single oral dose of 0.014 mg per kilogram bodyweight, which is 1 mg for 70 kg, about twice what Castillo et al. used:

www.linkedin.com/feed/update/urn:li:activity:6803351558714204160/
www.linkedin.com/posts/sunilwimalawansa_multisystem-inflammatory-syndrome-mis-activity-6815294839769436160-99qJ/

Since lives hang in the balance, since this is a one-off attempt to save the person from harm or death, and since the Castillo et al. dosage was far below what might lead to toxicity, it makes sense to use more, to ensure the best outcome even if there is poor absorption, or difficulties raising 25-hydroxyvitamin D due to obesity.

One microgram of calcifediol is about as effective at raising 25-hydroxyvitamin D levels, over weeks and months, as 4 micrograms of vitamin D3. On this basis, 1 milligram of calcifediol is roughly equivalent to 4 mg vitamin D = 160,000 IU. This would be a small bolus dose of vitamin D3 - and still far below whatever intake might lead some people to toxicity.

The initially boosted 25-hydroxyvitamin D levels should be maintained with daily vitamin D3 with quantities such as those specified below in green, as IUs per kg bodyweight. For 70 kg people not suffering from obesity, this is 5000 to 7000 IU a day.

This is from the recently revised Front Line COVID-19 Critical Care Consortium I-MASK+ early treatment and I-RECOVER long COVID protocols: covid19criticalcare.com/covid-19-protocols/. (I know of no research which supports this table’s lower ratios for underweight people.)

Prescription and non-prescription sources of calcifediol

For more detailed information on calcifediol availability, see: vitamindstopscovid.info/04-calcifediol/ Below, “c/#xxx” indicates a link to a section of this page.

The least expensive, easiest to use, form of calcifediol is Feas Farma’s Hidroferol 0.266 mg capsules, as used in the patent trial and by Castillo et al. c/#04-faes Unfortunately, these prescription-only capsules seem to be available only in Spain, some nearby countries, and from an Italian company as Neodidro.

The price seems to be about €10 for 10 capsules, which is around USD$5 per milligram.

These would be perfectly easy to take: Four capsules for 70 kg, or one capsule for every 19 kilograms bodyweight. The actual quantity is not critical.

The most expensive form is the prescription-only Rayaldee capsules, in the USA, which costs USD1,341 per milligram: c/#03-ray.

More expensive and less convenient than Hidroferol/Neodidro, but much easier to obtain, are two similar tablet products from Dutch nutritional supplement (mainly for agriculture) giant DSM www.dsm.com . Originally “Dutch State Mines”, this highly successful company now concentrates on nutrients and other products and services, is no longer involved in mining, and has repurposed its name as an acronym for Do Something Meaningful. DSM have their own yeast-based calcifediol plant and purchase all the production from the largest calcifediol plant in the world, in China, which makes it more efficiently from woolfat. The majority of DSM’s calcifediol is used for agricultural feed, but in 2021 they ventured into retailing calcifediol as an alternative to vitamin D3 cholecalciferol for long-term supplementation.

I think vitamin D3 is fine for long-term repletion, though am sure that the more expensive calcifediol works well too.

My interest in calcifediol tablets or capsules is solely for the purpose of having them on-hand, ready for emergency repletion of 25-hydroxyvitamin D. On this basis, there’s no point in buying calcifediol for use by yourself or by anyone whose good nutrition you can ensure at present. This is because you should use proper vitamin D3 supplementation now- and so never need emergency 25-hydroxyvitamin D repletion.

However, you might want to buy some - as I did - in case you need to provide it for someone else, in an emergency - someone who had not been properly supplementing vitamin D3 for months already.

This section is intended partly for autodidact non medically trained people such as myself, who take full responsibility for their decisions and actions, and mainly for medical professionals who want a stock of calcifediol on hand to help their patients in emergencies.

Since most readers will be unable to obtain the Faes Farma capsules, below I assume the use DSM d.velop or Fortaro tablets. I expect DSM will also market similar tablets in Europe, since they obtained permission to do so in mid-2021.

Firstly, for online ordering in the USA, with delivery to US addresses only, d.velop. Please follow see c/#06-dvelop for notes on ordering this via a package forwarding company for delivery to other countries.

Each packet contains 60 tablets, each with 10ug 0.01mg calcifediol. This is 0.6mg calcifediol for USD$20 including shipping within the USA. So this is USD$33.33 per milligram calcifediol, not counting sales tax, which was added when I had some packets sent to a California-based package forwarding company.

There are now several “d.velop” products. The calcifediol tablets are at: dvelopimmunity.com/products/vitamin-d. Click the “ONE MONTH SUPPLY” option for one-off orders of one or more boxes of 60 tablets.

Secondly, for online ordering in Australia, Fortaro: c/#05-fortaro. These are available at shop.fortaro.com/products/fortaro with any number of small plastic bottles of 60 tablets for shipping to Australian addresses for AUD$24.95 each (about the same price as d.velop) or to addresses outside Australia, for the same price, with a limit of 3 bottle per international order.

The Fortaro tablets are about the same size as the d.velop tablets, but lack their indentation in the bottom. Each tablet contains 0.01mg calcifediol, weighs about 0.15 grams and is 6mm in diameter. These small tablets have no taste and puff up and disintegrate in a few seconds when placed in water.

The tablets would be easy to take, such as 3 to 5 at a time, with drinks of water. More than this at a time would be possible, but the tablets are small and I suggest not putting too many in anyone’s mouth at once.

0.014 mg per kilogram means:

Number of tablets = bodyweight in kilograms x 1.4.

The remainder of this article concerns how to prepare these d.velop and Fortaro tablets as a drinkable suspension, if taking them as tablets is not desired. Reasons for this might include:

Children - especially those who are ill or distressed - might not like or be safe ingesting small tablets. They might inhale and breath them in.
Both children and adults might find it odd that Doctor or Nurse is giving them so many tablets, even though they are small. Also, some people may mistakenly think, due to frequent statements to this effect, that “vitamin D is a hormone”. So the prospect of 50, 100 or more tablets might evoke fears of “megadosing on hormones”.

Making a drinkable suspension from 0.01mg calcifediol tablets (updated 2022-02-22 and 2022-02-26)

(Mini update 2022-02-25: Xanthan gum is superior to the glucose syrup or glycerol approaches described below. I will write this up properly soon. The suspension looks similar to the one pictured below but has nearly twice the volume, remains softly suspended for much longer, has no taste and has only 0.5 grams of carbohydrates (plus whatever amount might be in the tablets) - so it should be safe for diabetics. Add 0.5 grams of xanthan gum [WP] to 100 d.velop or Fortaro tablets and shake or stir them to distribute the xanthan gum over the surface of the tablets, rather than in the bottom of the container. Add 100 ml water and stir immediately for a 30 seconds as the tablets disintegrate. If you have milligram scales, it couldn’t be easier. Without such scales, the 0.5 grams of xanthan gum, which is not at all critical, could be measured visually with 4 tablets (0.6 grams) as an reference. A heaped teaspoon full is 4 grams, so dividing that by 8 will be good enough. This is easy to drink 0 to 10 minutes after stirring.)

For those who want to prepare the above-mentioned tablets into a drinkable form, here is an account of my experiments so far.

My first attempt at making a drinkable solution was to add just water. It worked, but the suspension settled rapidly. It was drinkable if stirred and consumed within seconds, but I still needed to wash some of it out from the glass with extra water. You can see this attempt at: c/#liquid.

On 2022-02-19 tried 1/3 glycerol (from a pharmacy) and 2/3 water. This causes the very fine suspended particles to remain in suspension, after stirring, for 5 or more minutes without significant settling. It also imparts a sweet taste and makes the preparation somewhat more viscous. See my notes below the photos on the safety of ingesting glycerol.

The photos below are of my glycerol experiment. I think this suspension roughly resembles the widely used cephalexin antibiotic suspension, which needs to be well shaken before drinking. Some cephalexin suspensions include xanthan gum.

I later tried 1/3 glucose syrup and 2/3 water, 12.5 grams total, with 25 tablets (3.75 grams) in a 22mg test tube, which half the diameter of the small glass pictured below. The results were very similar. This was confectioner’s glucose syrup, from a supermarket, which is about 80% carbohydrates, mainly starch. The label states that sugar content was 28%. The Wikipedia page [WP] states that confectioner’s syrup typically contains 19% glucose and 14% maltose.

Both the glycerol + water and the glucose syrup + water suspensions taste to me like what I imagine would be the taste and sensory experience of drinking rather sweet, finely suspended, powdered chalk. There’s no weird taste, as is usually the case with antibiotics.

I think that if some food dye and/or fruit syrup was added, many children would regard it as yet another irky thing Doctor or Nurse has concocted to seem nice, but really isn’t.

If there is not enough calcifediol for 0.014 mg per kg for multiple patients, I suggest dividing it evenly between them all. Half this - 0.5 mg for 70 kg bodyweight, as used by Castillo et al. - would still be highly effective.

Here is a recipe for 100 tablets = 1 milligram of calcifediol, suitable for 70 kg bodyweight.

Unpack 100 tablets. These weigh 15 grams and occupy about 20 millilitres.
Mix 15 grams of glycerol or glucose (confectioner’s) syrup (12 mL) and 35 grams of water (35 mL). I did this separately and added it to tablets already in the glass, but it would be easier to mix the liquids in the glass and then add the tablets.
Wait a minute of two for the tablets to puff up and disintegrate, then stir thoroughly.
If this is left to stand for more than a few minutes, stir it again before giving it to the person to drink.

The result is about 50ml of liquid, weighing 65 grams and containing 1 milligram of calcifediol = 15.4 parts per million calcifediol by mass. The desired concentration of calcifediol AKA 25-hydroxyvitamin D in the bloodstream is 50 ng/mL, which is 0.05 parts per million by mass.

Perhaps this suspension would be useful for topical application, where localised 25-hydroxyvitamin D deficiency may be a problem for some reason, such as burns, infections or auto-immune rashes. As far as I know, there have been no measurements of the concentration of 25-hydroxyvitamin D inside immune cells, after diffusing from a 50 ng/mL level in the bloodstream - where ~85% of it is is tightly bound to the vitamin D binding protein [WP], 15% is less tightly to albumin proteins and only 0.03% is in the free state. If tissue levels of free 25-hydroxyvitamin D match the small, free, proportion of it in the bloodstream, then this is very low at 0.0003 * 50 ng/mL = 0.000015 parts per million. Even brief application of this suspension might significantly boost local tissue levels of 25-hydroxyvitamin D for some hours.

I wouldn’t make any great claims about this suspension as a gastronomic experience, but it has the potential to save people in clinical emergencies from serious harm and death, while tasting better than the average antibiotic liquid concoction.

While glycerol is probably safe, I am inclined to prefer glucose syrup. I can buy 500 grams of it from the cooking section of a supermarket, with illustrations of toffees on the label, so I find it hard to imagine a 70 kg person being harmed by drinking 15 grams of it. Honey would be another alternative.

However, people with diabetes probably should not ingest anything containing these quantities of glycerol or starch-sugar syrup.

Glycerol is a widely used food additive. Athletes frequently ingest large amounts of glycerol per kg bodyweight, such as 1,200 mg / kg, in more dilute solutions, to improve their hydration prior to long periods of exertion. 15 grams of glycerol for 70 kg bodyweight is 214 mg / kg. A 2017 European Food Safety Authority committee report Re-evaluation of glycerol (E 422) as a food additive declined to set an acceptable daily intake. They noted that 125 to 333 mg / kg per hour was sufficient to reduce intra-cranial pressure in the treatment of glaucoma. They report that glycerol has very low toxicity. I think that glucose syrup simpler and safer. (Xanthan gum has no toxicity concerns and works even better.)

Nutrition Matters

Calcifediol to boost 25-hydroxyvitamin D…