Monday 18 January 2021

Covid-19 and Vitamin D : Miracle in Andalucía


Andalucía, Spain

Encouraged by the very positive result of the RCT of vitamin D as Calcifediol in the treatment of Covid-19 pneumonia, and evidence of benefit of vitamin D many reports, the public health authorities in Andalucía decided to take action. 

The Covid-19 hospital admission rates, ICU admission rates, and death rates had risen during the early winter, as expected following the summer suppression effect as seen in other European countries. The rates had appeared to have reached, or were close to, the winter peak and so this was the ideal time to initiate correction of widespread vitamin D deficiency as a preventative measure. This was not to be a clinical trial: the time for such had passed. A randomised trial would have involved much planning and bureaucracy, and most importantly it would have put a large control group of people at risk from being deprived of the expected benefits of vitamin D. Would people allocated not to receive vitamin D obey this restriction? 

The number of deaths each day had increased during October and November and a high number of deaths would be expected through the winter until the spring equinox, after which deaths per day would reduce as in 2020. In biological and solar respects we have just two seasons of the year, summer and winter, separated by the spring and autumn equinoxes. In the summer vitamin D is produced and domestic solar energy is produced, but not significantly in the winter.

Previous Blog posts have described the very successful randomised controlled trial of Calcifediol, the rapidly acting 25(OH)-vitamin D, that took place in Córdoba, in Andalucía, southern Spain. The result was a 96% efficacy in the reduction of need for ICU transfer. In that in the control group, 2 of the 13 transferred to the ICU died, a reduction of the number of transfers from 50% to 2% would inevitably have led to a reduction in the number of deaths by more than 96%. 

This and other aspects of the role of vitamin D deficiency in serious outcome from Covid-19 led in Andalucía to a scientific assessment and report. We have seen superficial and poor quality assessment in the UK by NICE, and a very detailed analysis by a team in the MIT, which indicated the clinical trial in Córdoba to be without significant procedural error and with a less than a million to one probability of the findings being by chance.

The scientific report was viewed by the regional government in Andalucía on November 8th. It was accepted that vitamin D has a major influence on Covid-19 infection and that by enhancing defensive immunity it makes a major contribution to minimising the damaging and fatal effects of Covid-19. The instruction was for doctors treating Covid-19 patients to prescribe vitamin D as calcifediol, and for it to be issued to elderly residents of care homes. Vitamin D would be actively encouraged in others.

During December a miracle occurred in Andalucía. The number of deaths per day dropped dramatically, against the experience of nature. Perhaps it was due to the favourable influence of God. On the other hand it might have been the result of the vitamin D initiative, which in an immunological way would convert the winter into summer.

The reduction of Covid-19 effects can be seen in the following figures, taken from the Andalucía website.

We can see in Figure 1 the rapid increase in hospital admissions at the onset of the pandemic in March 2020 and then the rapid decline in April. There was a very low number of hospital admissions during the summer months, under the influence of the sun and the production of vitamin D. With the end of the summer, the number of hospitals admissions increased again to 300 per day in November.

On November 8th the directive went out for vitamin D to be used for prevention and the remarkable decline in hospital admissions during December is clearly visible.

Figure 1. Andalucía: Hospital admissions each day

The pattern of admissions to intensive care units was of the same pattern, shown in Figure 2.

Figure 2. Andalucía: ICU admissions each day

And in Figure 3 we see the dramatic effect on deaths, falling from 60 per day to 3 per day.

Figure 3. Andalucía: Deaths each day

Figure 4, below, concentrates on the time after November 1st. The effect of the vitamin D initiative is clear.

Figure 4. Andalucía: Deaths each day, November 2020 to January 2021

Meanwhile, in the UK the number of deaths continued to increase to about 1,000 per day.

Figure 5. UK: Deaths each day, November 2020 to January 2021 (note scale)

The message is clear. If we want to bring this pandemic to an end we must optimise defensive immunity. To achieve this we must correct widespread vitamin D deficiency. Vitamin D 4,000 units daily is safe and will be appropriate for prevention in most people. If there is a sense of urgency, if a person is ill with Covid-19 respiratory disease, then it is necessary to follow the protocol used Andalucia and use Calcifediol.


We know that vitamin D is produced by the action of UV on 7-dehydro-cholesterol that is produced in the skin. 

Vitamin D must then be part-activated to 25(OH)vitamin D, otherwise known as calcifediol. This is what we measure in the blood in routine tests. Calcifediol is the form of vitamin D that is the reserve in the blood, to be available for use whenever needed, and this has been essential during the Covid-19 pandemic.

The part-activation of vitamin D to calcifediol takes place in the liver and the process is slow. In nature this is perfectly satisfactory as it is providing a steady-state function. But at present, when the Covid-19 pandemic is exposing the pre-existent pandemic of vitamin D deficiency, it is not adequate to requirements.

The appearance of calcifediol in the blood after vitamin D is taken by mouth is slow.

Figure 5. Increase in blood level of calcifediol after oral vitamin D, various regimens

Using different dose regimes it can be seen in Figure 5 that it can take up to two weeks before a safe blood level >30ng/ml is achieved. This is fine if the vitamin D is given to a person who is well, in prevention of Covid-19, but a very ill person with Covid-19 pneumonia would be likely to require ICU admission or even  die within this time. 

But the group in Córdoba with great understanding of pharmacodynamics used vitamin D as calcifediol and Figure 6 illustrates why, and why it was so successful.

Figure 6. Blood levels of calcifediol after calcifediol by mouth or injection

Whether given by injection (ampoule) or by mouth (capsule) calcifediol achieves good levels within just a few hours rather than weeks. The effect is therefore virtually instantaneous, as the calcifediol will be taken up by the immunity cells, thereby activating defensive immune processes and switching off the damaging cytokine storm.

This was the inspirational logic of the Córdoba study group: patients with Covid-19 pneumonia required treatment that would be active immediately, not in two weeks time. Calcifediol was the way to achieve this, and so it was to be. The clinical trial had the most remarkable result, released on September 3rd,  that it appeared that to the rest of the world it seemed to be too good to be true. ICU admissions reduced from 50% to 2%, with no deaths.

The important thing about calcifediol is that it must be brought into activity immediately by conversion into 1,25(OH), otherwise known as calcitriol. Some conversion takes place in the kidney cells to provide the circulating hormone that controls the level of ionised calcium in the blood. More importantly at present, is the production of 1,25(OH)D that takes place in the immune cells.

Calcifediol and vitamin D equivalence

Calcifediol is measured in mass units, micrograms. In the Córdoba clinical trial, capsules of 266 micrograms were used, but this dose was expressed as 0.266 milligrams. More confusion, but the UK practice is to avoid decimal points as they cause confusion and the decimal pint can be missed. I have noted previously in respect of vitamin D there can be confusion between mcg and mg, and so it is safer to use units. The use of units goes back to the days of biological assay, before vitamin D could be "weighed".

I will try to explain the equivalence of vitamin D and calcifediol, to the best of my inadequate understanding. My reading is that of vitamin D taken by mouth, approximately 20% appears as calcifediol in the blood. I cannot determine what happens to the remaining 80%, but it is only calcifediol (and calcitriol) that are routinely measured in the blood. It might be that the efficiency of the liver is only 20%, but his would be surprisingly low in a biological enzyme system. The alternative is that 80% could be diverted into deposition in the body fat, ad there can be a lot of it. I suspect that either more research needs to be done or I need to do a lot more reading of basic science.

In practice 5mcg of vitamin D seems to be required to create 1mcg of calcifediol. 

5mcg vitamin D = 200 units gives 1mcg calcifediol

To create 250mcg calcifediol requires:

250 x 200 units of vitamin D = 50,000 units vitamin D.

I do not understand why the capsules of calcifediol are 266mcg rather than 250mcg. I will try to find out the answer, and I expect there is one. 
The patients in the Córdoba trial received the equivalent of 100,000 + 50,000 + 50,000 + 50,000 = 250,000 units vitamin D within the first two weeks.

In the Andalucía public health initiative, calcifediol 266 micrograms is given twice in the first month, equivalent to 100,000 units vitamin D, then once each subsequent month, equivalent to 50,000 units each month.

What happens next?

The rest of the world should have followed the Córdoba protocol but it did not do so. The UK NICE stated that the result of the study should not influence the treatment of Covid-19.  A second large trial was demanded, and one was arranged in Spain. By the end of 2020, and by when 45,000 deaths had occurred since the result of the Córdoba study, the result of the second clinical trial had not appeared. Deaths continue, up to 1,000 per day. ICUs are under great pressure.

The study has now been completed but the journal in which the results will be published has an embargo on the release of information. I am given to understand that the result is excellent, perhaps even better than the Córdoba study itself.

A positive result must be anticipated by European and other governments and although vaccines are expected to suppress Covid-19 in the future, vitamin D as calcifediol is required for those sick now, preventing many deaths and taking pressure off the hospitals. 

But where is the calcifediol going to come from? Are world supplies of vitamin D adequate to meet the needs of the population?

Or will denial of vitamin D continue? Will new information be kept away from the public eye?

The virtual end of the pandemic in Andalucía is still virtually unknown outside Andalucía.

Andalucia government

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  1. Thank you for posting this. I have been following cases/ deaths on worldometers every day since the begining of the pandemic. I had noticed recently that the death rates in Spain were low compared to other European countries and wondered if the Calcifediol protocol was being used.
    I have had Calcifediol prescribed as drops daily for vit D deficiency for several years now. I take 3 drops a day and each drop is supposed to be 200iu. On this I maintain very high levels - at one point over 70ng/ml. I have not had a test for a while now but will be getting one in late Feb. On cholecalciferol I could not get up to 30ng/ml on 3000iu a day. I suspect my liver was just not doing it's job properly.

    1. Don't forget, Calcifediol is measured as mass. 200 micrograms probably. which is about 40,000 units vitamin D. This is a high dose for each day and so keep a check on you blood level. 70ng/ml is OK, but keep below 100.

    2. It definitely says on the bottle that 1 drop is 200 iu. I thought that was about 5mcg.

    3. I am sure it says on the bottle that 1 drop is 200iu. I thought 200iu was the equivalent of 5mcg.

    4. Sorry 1st reply did not show up!

    5. This is probably drops for babies

    6. No they are for adults. Each drop is 5mcg. I looked at the information sheet again despite it being difficult to read - small print.

  2. Madge Hirsch, may I ask what is the brand name of the calcifediol drops that you take please? Thank you.

  3. Thank you for this information Dr Grimes. It is so frustrating that inadequate advice on D3 is being palmed off on the population.
    I will be 69 this year. For a decade + I have taken 5,000 IUs D3 daily - upping this in the last 2 years to 8,000 IUs daily. My question is; will this give me an effective amount of *calcifediol* if I can't source calcifediol drops in the UK? Are these drops only available on prescription?

  4. MrsPepperpot, if you use cholecalciferol for years now, it won't be necessary to switch to a product as calcifediol, since your 25 (OH) D level should be at least > 60 ng/mL already. The only advantage you have with calciferol is the incredible speed to be bio-available. therefore, it is advisable to recommend a product as calcifediol to friends and family.

    1. The other advantage of Calcifediol as a daily treatment is that it does not need to be hydroxylated by the liver as does cholecalciferol. If you have a degree of liver malfunction ( like in my case mild fatty liver) you might have difficulty maintaining good blood levels. Remember that it is Calcifediol that is tested for in the blood tests.

  5. where can I find the resource of figure 4? The graph has not been updated since December 19th.

    1. Figures 4 and 5 updates with January 18th data for Andalucía, January 20th for UK. Web link for Andalucía in the text, repeated here: I will put further updates in a future post.

  6. David, I have just come across, a remarkable fact. That Scientific paper written by the young doctor Marta Entrenas, has been read 88 million times on the web, which is believed to be by far a record for any scientific paper

  7. Opk makes this drug. There trials are criminally slow. We need to put pressure on governments and the WHO to fast track this. Vaccines are going to be too slow we need solutions now

    1. Governments and WHO are too busy counting the dead.

  8. Looking at the latest data, is Andalucia different from the rest of Spain?

    1. It looks a though a third wave of positive cases is appearing in Andalucía, perhaps the result of a new mutation rather than just more enthusiastic case-finding. The ICU admissions and deaths are remaining low, thanks to the vitamin D initiative.

    2. Thank you Dr. David Grimes.

      I am more curious about the Vitamin D initiative.

      According to the government in andalucía, only the elder in nursing homes receive calcifediol to mitigate the effects of covid-19.

      What about the rest of south spains population for the prevention of covid-19 and are hospitals already using calcifediol according to the protocol of Castillo et al.? to treat covid-19? That would be great!

      If so, it would make sense to me that in the last 7 days around 200 people died due to covid in andalucía, whereas in Catalonia die 200 each day.

    3. David, they let their guard down over Christmas and relaxed their restrictions. Whether it is the Kentish strain has not been said but it was commented by the Andalucian minister for health that this outbreak was very fierce, but was showing signs of slowing. Nevertheless, they are now re allocating surgical facilities to Covid pacients.

  9. Dear David
    Thank you for the mostly good news regarding the "new Cordoba study".I hope that your source of information is reliable and that the results are really that good. It is almost impossible to do better than in the first study (96% regarding ICU).Do you know more about the embargo of the journal?
    I wanted to ask you about the German translation of your book. You wanted to discuss this with your colleague David Anderson. What is his opinion on this?
    Best regards from Switzerland!
    Stefan Volken

  10. Volken,

    I have not seen anything issued, but the technical lead on the Cordoba paper, Jose Manuel Quesada has on two occasions late last November publicly stated in interviews that the results are good.

    More pertinent is the announcement by Reuters on the 15th of Jan that the supplier of the drug Faes Farma is expanding its overall capacity by 200%. No mention was made however whether it was for calcifediol or other products

  11. 27 Nov 2020

    José Manuel Quesada Gómez, investigador del Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), habló del calcifediol en la mitigación de la gravedad del Covid-19. Hay un consenso general de que un buen estado de 25 de vitamina D es bueno para los huesos y para órganos como los pulmones, modulando la respuesta. Los datos preliminares de cinco hospitales de Andalucía arrojan una reducción de muertes del 50%. En estos momentos, "podemos proponer que el tratamiento de calcifediol, con las dosis que hemos diseñado, podemos proponerlo para diminución de muerte y de problemas pulmonares de manera eficaz y segura", pronunció. Asimismo, es un tratamiento económico. Aseveró que es un tratamiento interesante para abordar las complicaciones de Covid-19.

    Faes Farma expansion

    sorry both in Spanish, but google translate is very good

  12. Dear David
    Could you please write about Ivermerctin? Also which countries are using Calcifediol for treatment apart from Andalucia? I have been trying to push this to BME' leaders but they now seem more interested in campaigning for priority for vaccines.

  13. Why is vitamin D the only vitamin measured in i.u. units? Have you ever wandered?
    The reason is quite sinister. It was found by big pharma about 80 ago years that vit D could address 72 health issues which is a threat to their profits and they came up with a cunning and evil plan so that people would be frightened of taking the correct amounts and would take the bare minimum.

    Many millions of people have died due to issues related to this deficiency.

    First they bribed the committee member to 'accidentally' misplace the decimal point so 4000 daily recommended amount became 400 i.u. Doctors to this day still recommend 400 i.u.

    The second sinister thing they did was to devise a new unit with lots of zeroes which would make it scary in the correct amount required by the body which is around 4000 to 20000 i.u. depending on body mass and obesity level, etc.

    People are frightened of the zeros as was the deliberate and malicious intention by big pharma when they imposed vitamin D to be measured in i.u units.

    It is the only vitamin to be measured in i.u. Look at at any multi vitamin bottle. Everything is measured in mg except vitamin D .

    Why? Do you ever wander?

    Because it a threat to the Medical Mafia.

    What is i.u. ? 25 MICROGRAMS = 1000 I.U. 40 I.U =1 MICROGRAM

    1 MICROGRAM=0.000001 Gram. (A millionth of a gram).

    I suggest we measure paracetamol in i.u. so that a standard 500mg tablet comes out at 20 000 000 i.u. !!! So people will be very scared to take 20 million i.u of paracetamol.

    Yeah 20 million i.u.

    Got a headache? Here take 20 million i.u of paracetamol or even better 40 million i.u.

    (A standard paracetamol tablet is 500 milligrams=20000000 I.U)

    Thus people poop their pants when anyone mentions 4000 or 10000 i.u of D so conditioned are people by Big Pharma as soon as you mention 4000 or 10000 people will automatically THINK /SAY kidneys stones, hyperglycemia, kidney problems, muscle and bones... Just like Pavlovs dogs salivating when he rang a bell.

    Now for those 72 illnesses treatable with D plus co-factors.

  14. Suppose you ate only 1/20 of your normal meal. What would happe?n
    The recommended 400 i.u s is set very low to keep you ill so that you remain a cash cow for big pharma.
    Did you know that 500mg of paracetamol = 20 000 000 i.u. =20 MILLION i.u.
    The i.u. is designed with 2 extra zeros to scare you so that to take very low amounts and stay ill and make money for big pharma. The I.O.M members were bribed with lucrative consultancy jobs and persuaded to make a 'mistake' and recommend 400 i.u. daily.
    The fact that you were alarmed at 5000 i.u shows this fear in action.. I doubt you would have bothered asking if it showed 5 i.u on the bottle...

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