Wednesday, 10 November 2021

Covid-19 & Vitamin D: Vaccinations need Vitamin D

It is not vaccines or vitamin D, 

it is vaccines and vitamin D



My most recent Blog post described the numbers of cases and deaths in a number of countries during the Covid-19 pandemic, and the disturbing fact that there have been many more Covid-19 cases and deaths during 2021 than during 2020. What has gone wrong? Why has the extensive vaccination process not reduced the numbers? 

The numbers of cases in most European nations are increasing,  with problems illustrated by newspaper headlines.



The increase of cases is disturbing in Germany, but much worse in Austria.

2021. Covid-19 cases per day in Germany


2021. Covid-19 cases per day in Austria

Why is this happening? 

There was until very recently something called 'full vaccination', but this is a term that is now obsolete. It meant two vaccinations, but now a so-called 'booster' dose is essential. However the second vaccination is proving to be effective for a shorter time than following the first vaccination. The six month gap before the 'booster' is being shortened. It is possible that vaccinations will be given at as little as three or four month intervals.

Such a vaccination policy would be a nuisance for the population and very costly for national public health authorities, but on the other hand extremely remunerative for vaccine manufacturers.

Our authorities assume the effectiveness of serial vaccinations. Safety remains uncertain but is likely to remain untested and unrecorded. But the vaccination policy will continue.

The curious of us will ask, "Why is it that vaccination becomes progressively less effective and of shorter duration? Surely we should expect increasing immunity with each vaccination, not decreasing immunity?"

Official UK evidence


The UK Health Security Agency (UKHSA) published its 'COVID-19 vaccine surveillance report Week 42'. In this report we read:

"N antibody levels appear to be lower in individuals who acquire infection following 2 doses of vaccination". 

'N antibodies' are antibodies to the nucleocapsid of the virus, which do not result from the vaccination, but just from Covid-19 itself. Antibodies are one component of immunity.

This statement or finding might be interpreted as suggesting that the vaccination actively damages the immune system, but this is not necessarily the case. However it is certainly of concern that people who have had two vaccinations can become ill with Covid-19 within a few weeks. Obviously something is going wrong with immunity following vaccinations against Covid-19 if they are not preventing infection. The official answer is "We need more vaccinations", but is this sensible? It would be better to understand what is happening. A general principle is that if a medical intervention does not work, then either double the dose or stop and think.

Vaccinations are given whether or not a person vaccinated has had and recovered from Covid-19. It would be interesting to know if previous infection has a negative effect on antibody response to subsequent vaccinations, but we are not informed. There is much about which we are not informed, and so some guess-work is necessary.

Vaccines are designed to produce an immune response, and the inflammatory component of this response seems to be greater with the new genetic inoculations than with traditional vaccines, hence a much higher incidence of untoward inflammatory events. There is actually a very good reason why this leads to decreasing immunity.

The evolution of the immune response 

It is necessary to understand the immune response that has developed during 500 million years of evolution. 

Evolution is full of mysteries, but a critical stage of evolution was the appearance of an intracellular protein that became the key to immunity. This protein is what we now call VDR, which stands for Vitamin D Receptor. It was the evolution of VDR 500 million years ago that was probably the initiator of the Cambrian explosion of advanced life-forms. The development of immunity meant that very primitive animal life, for example plankton, could evolve into more complex forms without being at the total mercy of pre-existing bacteria and viruses. 

And so it is today. Without immunity we would not survive infancy and we would become extinct. Immunity is vital and we have seen the effects of seriously damaged immunity in the recent AIDS pandemic. We must not forget this. We must respect immunity and the need for its optimisation. We must understand it.

The evolution of VDR was critical, but VDR would have had no function had it not been for Vitamin D which had evolved a billion years earlier. 

Plankton

Plankton at the surface of the oceans were at risk of physical damage by UV from the Sun. They ultimately developed genetically programmed diurnal vertical migration, meaning that they spend the night at the surface and descend deeper in the water during the day. 

But they developed another method of protection from UV, a chemical sunscreen. Starting from the long-chain squalene, otherwise known as shark oil, they became capable of synthesising steroid compounds, a process that is blocked by statin drugs (taken only by humankind in recent years). The important sunscreen steroid became the oil 7-dehydrocholesterol, 7-DHC. This will sound familiar to readers of the Blog. UV converts 7-DHC in the skin into cholecalciferol which we know as vitamin D. Within plankton this physico-chemical process absorbs UV energy and thus protects the plankton from damage. 

Squalene





7-dehydrocholesterol, 7-DHC, indicating the bond broken by UV


Vitamin D, cholecalciferol


For a billion years vitamin D had no function and it was merely a waste product of the sunscreen 7-DHC. But by another accident of evolution it became critical because it was able to activate VDR into the major player in the immune process. The Cambrian explosion was initiated.

Understanding our immunity

We know about T-cells that produce tissue immunity and B-cells that produce humoral antibody immunity, but the important process is the rapid escalation of immunity that is essential in response to infection if an optimal effect and recovery is to be achieved. This will also apply to the pseudo-infection of vaccination. The driving force is to switch on the genes that bring about multiplication of the immune cells and their effects, a genetically controlled amplification that can be 75-fold. 

The genes are activated by an intracellular dimer composed of VDR and RXR, Retinoid X Receptor.  However the VDR component must first be activated by 1,25(OH)D, otherwise known as calcitriol, the fully active form of vitamin D that is produced within immune cells. 

Activation of the genes will switch on or increase the production of defensive proteins including antibodies that act within tissue fluids to control and eliminate infection, the purpose of immunity.


The immune cells are able to  increase greatly the synthesis of VDR, but before the gene-activating VDR-RXR dimer can be formed, VDR must be activated, 'unlocked', by 1,25(OH)D which cannot be synthesised de novo. It can only be formed by hydroxylation (addition of an -OH group) of 25(OH)D, the number indicting the point on the molecule to which the -OH group becomes attached. 25(OH)D is the form of Vitamin D that has already been hydroxylated in the liver and which circulates in the blood.

Consumption of Vitamin D and exhaustion of reserves

Too much 1,25(OH)D produced in response to the escalation of immunity could cause subsequent problems of 'hypervitaminosis D', with an excess of calcium in the blood and in the urine. But evolution has solved this problem: the 1,25(OH)D molecule can be used only once, after which it is inactivated by conversion into 24,25(OH)D. The process of escalation of immunity requires a large number of single-use 1,25(OH)D molecules to activate a multitude of VDR molecules. Therefore a constant supply of 1,25(OH)D is essential and so there must be in the blood a good reserve of its immediate precursor 25(OH)D, the circulating form of vitamin D that is also known as calcidiol or calcifediol. 

A serious infection such as Covid-19 will consume significant amounts of 1,25(OH)D, and so we can expect to see a reduction of the blood level of 25(OH)D as a result of such an infection. As far as I am aware, such research has not been performed during the pandemic, or at least not published, despite how simple it would be. 

The magnitude of the inevitable fall in blood level of Vitamin D, 25(OH)D, following vaccination has not been reported. Perhaps it has not been investigated, but if it has been investigated by the pharmaceutical companies, the results will only be published if there is commercial benefit. Obviously, as with Covid-19, a good level of Vitamin D, 25(OH)D, in the blood (greater than 40ng/ml, 100nmol/L) would have sustained the escalation of immunity. But if before the infection or vaccination the blood level had been critically low (less than 20ng/ml, 50nmol/L), then a reduction would have reduced the level to a point that the escalation of the immune process would be halted, with a high risk of significant illness, perhaps critical or fatal.

Figure. The effect on Vitamin D of Covid-19 and Vaccinations in
two hypothetical patients with different pre-illness 25(OH)D levels.
My blood level is slightly above the green line.
The national average is the blue line



The Figure illustrates what I think is happening in respect of Covid-19 and vaccinations. I am suggesting for the point of illustration that an initial episode of Covid-19 will reduce the blood level of vitamin D by 5ng/ml (12.5nmol/L), and there is some in vitro experimental evidence of this. I suggest that the vaccination has a similar impact, reducing blood levels by the same amount. 

If the pre-Covid-19 blood level is good at 40ng/ml, 100nmol/L, then the person illustrated by the green line will be safe. Even after Covid-19 and two vaccinations the blood level will safe at about 30ng/ml, 75nmol/L. The importance of a reserve of 25(OH)D in the blood is of obvious importance.

However, if the pre-Covid-19 blood level is only 20ng/ml, 50nmol/L, the successive immunological actions will reduce the blood level of the individual illustrated by the blue line to below the very critical level of 10ng/ml, 25nmol/L. Critical or fatal illness is likely to be the result, but susceptibility to illness will extend beyond Covid-19.

The blood levels used are not arbitrary. They are very clear from a recent study from Israel that will be the subject of my text Blog post. About half of the UK population is likely to have blood level of vitmain D less than 20ng/ml, 50nmol/L.

The proposal

My proposal is that the decline of immunity following vaccinations is not because of a 'poisoning' of immunity, but because the reservoir of Vitamin D as 25(OH)D within the blood becomes exhausted by the immune responses to successive vaccinations.

The investigation of this would be very simple. Blood would be taken for Vitamin D measurement immediately before vaccination and one month later. The two samples would be analysed together, following the second blood test. Previous Covid-19 would need to be recorded, and of course the dose of any vitamin D supplement taken. 

This simple study could be undertaken in any public health vaccination centre. Ethical approval would be needed but I can envisage no conflict with ethics and what is in the best interests of individuals and the population. My view is that it has been unethical to withhold Vitamin D during this pandemic, contrasting with the official narrative that Vitamin D is of no value in the management of Covid-19. 

In some respects it is too late for serial readings with more than one vaccination. However it would be very interesting to determine blood levels of vitamin D both before and after a booster vaccination. I would predict very low Vitamin D levels.

A further study would be a randomised trial of the effect of a single large dose of Vitamin D perhaps 100,000 units, which is a months requirement, given two weeks before vaccination, giving time for it to be hydroxylated in the liver to 25(OH)D, calcifediol, the blood form and immediate precursor of 1,25(OH)D. The outcome measures would be symptoms or illness following vaccination, and also the antibody response to the vaccination.

The response

The question is whether there is any official interest in exploring disappointments with the vaccination programme, and the fact that there have been more Covid-19 cases and deaths in 2021 compared to 2020, a feature in most if not all nations. Media reports are interesting. 

The increase of Covid-19 cases and deaths in 2021 suggests that the vaccines are failing, but factual reports of this are immediately dismissed as misinformation.



The problems go beyond Covid-19 in that we are now hearing reports of increasing pressures from hospital admissions in greater numbers than are seasonal, and that most are not Covid-19. If admissions due to other conditions are increasing, it is likely that we are faced with impaired immunity due to exhaustion of body stores of Vitamin D in turn resulting from the vaccination programme. This could be corrected very easily and very rapidly.


We are also hearing official reports of excess deaths from cardiovascular disease in recent weeks. Why should this suddenly occur? Could this serious phenomenon be result of the vaccination programme? Is it the direct result of exhaustion of Vitamin D reserves due to the effects of the vaccination process? Could it be stopped by finding and correcting VItamin D deficiency? The challenge is urgent and the problem must not be witheld from the population.





Vitamin D in its metabolic forms has been very successfully ignored by official bodies during the pandemic of Covid-19. Evidence of benefit has been side-lined for the flimsiest of reasons and without any debate. The reason for this has been to protect the vaccine roll-out. The vaccines in use have still not been licensed and are still being used under Emergency Use Authorisation (EUA). This is dependent on there being no alternative prevention or treatment, resulting in the burial not just of Vitamin D but also ivermectin and hydroxychloroquine. 

At present new antiviral drugs are being tested and roll-out is anticipated in late 2021 0r early 2022. One is molnupiravir, produced by Merck and with anticipated price of  $700 per dose, about 10,000 times the price of a capsule of vitamin D. The other is manufactured by Pfizer. As the medicines must be given early in the corse of the illness, rationing on financial grounds is going be challenging.

If new anti-virals can now be used, why not Vitamin D and others? The EUAs can hardly be withdrawn at this stage as more than four billion people have now been vaccinated against Covid-19. If EUAs have become logistically irrelevant, Vitamin D can be given officially without causing the EUAs to be revoked.

It is time for Vitamin D to be released from its imprisonment.


Sunday, 24 October 2021

Covid-19 & VItamin D. 2020 & 2021 : Nature and anti-nature

 

1768: Edward Jenner and smallpox vaccination


Covid-19 & Vitamin D.  2020 & 2021 : Nature and anti-nature


Has the 2021 vaccination programme been of any benefit?


Covid-19 made an impact in the UK in March 2020. By March 23rd there had been a total of 258 Covid-19 deaths and so "Lockdown" became national policy, with closure of universities, schools, places of worship, places of entertainment and leisure, and also much of the economy. The impact of lockdown on the pandemic was not very obvious, and we can see its non-effect on the time-line. 


Figure 1. UK: Covid-19 deaths per day in early 2020


Covid-19 deaths continued to increase and a peak was reached in mid-April 2020 with almost 1,000 deaths each day. After that there was a daily decline. This was entirely predictable as we know from experience that deaths from respiratory infections decline during the summer months. The reason for this is that starting in mid-April, the Sun rises to more than 45 degrees above the horizon, and thereby it has the intensity to produce Vitamin D from 7-dehydrocholesterol synthesised in the skin.


Many medical scientists were aware of the importance of the Sun and Vitamin D in optimising defensive immunity. The science of this had developed since about 1980 and many valuable research papers were readily available. I, and many medical scientists who were much more knowledgable on the subject than I was, tried to bring this to the attention of the government and its agencies, but our voices fell on deaf ears and the news media were not interested. The science was completely ignored in favour of dubious mathematics.


Covid-19 cases and deaths continued to fall steadily to a minimum in August 2020, when deaths each day were in single figures. At this time vitamin D stores would be maximal. The hospitals that had been struggling with the impact of Covid-19 found themselves almost empty with little work to do. This was of course a good thing, if only temporary.


Figure 2. UK: Covid-19 deaths per day during 2020

It was anticipated that case numbers and deaths would increase after mid-September, when Vitamin D synthesis would come to an end at the UK latitude of about 53 degrees north of the equator, and when Vitamin D stores would diminish. So it did, and the numbers of Covid-19 deaths each day increased to a plateau in late November and December, about 500 each day. This cycle was under the influence of nature, to be precise, the Sun and Vitamin D. 2020 was the year of nature, and the pattern is exactly what would have been predicted on the basis of experience of previous epidemics.


I would have hoped that the favourable impact of Vitamin D production on the pandemic during the summer, would have led intelligent and knowledgeable people to develop a public health policy of adequate dose Vitamin D supplementation for the winter, knowing of the high prevalence of vitamin D deficiency. But it was not to be: vitamin D was ignored and its potential benefits were denied.


The refusal of the government and its agencies to accept Vitamin D as a prevention and treatment of Covid-19 led to the astonishing and very regrettable fact that 26 working doctors in the UK died from Covid-19 during March, April, and early May 2020. 25 of the 26, 96%, were of Black African or South Asian ethnicity. Vitamin D deficiency was the obvious explanation. It is a disgrace that this was not acknowledged by the government and that it was ignored by medical professional bodies. But it was not ignored by my intelligent, knowledgeable, and caring medical friends, Professor Parag Singhal and Professor David Anderson. Their action was to advise by email immediate vitamin D supplement to doctors of Black African or South Asian ethnicity and to provide supplements whenever necessary. The deaths came to an abrupt end but the story was not acknowledged.


2021 the year of anti-nature


In the UK in early 2021, rather than a continuing winter plateau of cases and deaths, January saw a sudden increase from about 500 Covid-19 deaths each day to a rapid peak reaching 1,500 Covid-19 deaths each day. This was followed by a decline during February. This was all unexpected and puzzling, especially as it followed the introduction of the new vaccines in mid-December.


Figure 3. UK: Covid-19 deaths per day in 2020 and early 2021


The number of cases per day fell rapidly from a maximum of 68,053 on January 8th 2021 to 2,235 on May 23rd. At this stage we were tentatively reassured. 


Figure 4. UK: Covid-19 cases per day 2021 

Was the pandemic was going away? But this graph shows 2021 only until mid-May. 


In July, at the height of a good summer, there was a sudden increase in Covid-19 cases. The number of new cases per day increased to an astonishing 54,674 on July 17th, then reducing but stabilising at about 40,000 per day up to the present time. This was completely unexpected, especially as the vaccination programme was going so well, with most of the population double-vaccinated. The policy became third vaccinations for all.


Figure 5. UK: Covid-19 cases per day in late 2020 and in 2021


This dramatic increase in cases in July (marked in the yellow box) was against the pattern of nature, and against our experience of natural vitamin D dependent immunity. The quiet summer of 2020 was not the experience of 2021. What has been happening? Is there a causal relationship between the vaccination programme of 2021 and the peak of Covid-19 cases? Are the PCR tests identifying viruses or just spike proteins from the vaccines?


The Netherlands had the same experience, the onset slightly later than the UK, but the increase far steeper so that the peak was reached in mid-July in both countries. The rate of increase in the Netherlands was quite remarkable for a viral epidemic. A significant number of cases per day continues, with a further increase during October.


Figure 6. Netherlands: Covid-19 new cases per day during 2021


This pattern in a less dramatic form is seen in most other countries in Europe – in France, Switzerland, Germany, Denmark, Spain, Ireland, Italy, Finland, Norway, Austria, Belgium, and others. 


Iceland has experienced the most dramatic peak of all during the summer of 2021. What was happening in this, one of the most vaccinated of countries? 


Figure 7. Iceland: Covid-19 new cases per day during 2021
from: Our World in Data


The steepness of the peak in Iceland during late July and August 2021 is perhaps more suggestive of a chemical attack on the population rather than a microbial epidemic. This extraordinary peak has not received any official comment, perhaps because it is completely out of keeping with the official narrative of the pandemic and the vaccination programme. A sudden peak in mid-summer is not we expect from a microbial epidemic or pandemic.


In late October 2021 we see the start of another peak, perhaps an early warning of a winter effect. The example in Figure 8 is Austria, which also experienced a summer increase. This late October increase is also seen in the UK, the Netherlands, Belgium, France, Poland, Norway, and Finland.


Figure 8. Austria: Covid-19 new cases per day during 2021


Tropical countries experienced nature in 2020, vaccines in 2021


We saw very low levels of Covid-19 in tropical and semi-tropical countries during 2020. We expected  2021 to show a similar low risk, but 2021 turned out to be very different.


Cambodia, for example


The first case in Cambodia was in January 2020, and by the end of the year there had been just 378 cases. By March 31st 2021 there had been 2,440 cases, and by October 17th 116,860 Covid-19 cases had been recorded.


Figure 9. Camdodia: Covid-19 new cases per day during 2020 and 2021
from: Our World in Data

There were no Covid-19 deaths in Cambodia during 2020. The first Covid-19 death was on March 11th 2021. Then there was a rapid increase in deaths, and by October 17th  2,670 Covid-19 deaths had been recorded. Why was 2021 so different from and so very much worse than 2020?


Figure 10. Camdodia: Covid-19 deaths per day during 2020 and 2021
from: Our World in Data

Was it just a coincidence that the vaccination programme in Cambodia started on February 10th 2021, immediately before the first death and the rapid increase in cases and deaths? The pattern was the same in the neighbouring countries of Laos and Vietnam, and also in the larger countries of Malaysia and Indonesia.


2020 and 2021


2020, as we have seen, was the year of nature, with no pre-hospital Covid-19 interventions other than lockdown and population control. The pandemic progressed in an anticipated way, with optimism that through subclinical infection during the summer months, nature would extend natural immunity against Covid-19, and that the pandemic would have a much reduced impact during 2021.


Since the time of Edward Jenner who introduced vaccination against smallpox, vaccines have been based on nature. An attenuated or a dead micro-organism (or part of it) would be injected into the body to produce a mild pseudo-infection so that immunity would be achieved. This natural approach has worked well for many years. 


But in 2021 we have experienced the new so-called vaccines, which are in truth experimental gene therapies, the brilliant products of the biotechnology laboratories. These “vaccines” had not been licensed and were used under Emergency Use Authorisation. But this did not inhibit the evangelism of governments and the enthusiasm of the people.


We expected that the vaccines would add to the immunity provided by nature, and that the pandemic would effectively disappear during 2021. But it has not worked out as planned. We have had more Covid-19 cases and deaths in 2021 than in 2020. In the UK we had approximately 2.5 million Covid-19 cases in 2020, but so far this year we have had more than 5.5 million cases. 


In the UK during the summer of 2021 we have experienced between 30 and 50 times more cases of Covid-19 per day (green line) compared to 2020 (blue line). We expect an increase during the autumn, but we expected fewer rather than more cases in 2021 than in 2020.


Figure 11. UK: Covid-19 new cases per day during 2020 and 2021

Please note that the case numbers in July 2021 were 30 times greater than just two months earlier, in May 2021. This is very mysterious, but as usual, the victims are blamed for their alleged misbehaviour. But is there a biological explanation for this great increase during the summer months?


Figure 12. UK: Covid-19 deaths per day during 2020 (blue) and 2021 (green)

We have seen the high numbers of deaths during the first three months of the pandemic in 2020, deaths mainly of the vulnerable including the very elderly, the very obese, and UK residents of Black African and South Asian ethnicity. But the daily deaths came down to single figures during August 2020.


Figure 12 shows that in the UK Covid-19 deaths decreased substantially during July and August 2020, the year of nature, as shown by the blue line. In 2021, as shown by the green line, the numbers of deaths each day were initially low but then they increased


On September 9th 2020 there were 3 Covid-19 deaths in the UK. On the same day in 2021 there were 185 Covid-19 deaths. Between July 1st and October 10th, there were 2,009 Covid-19 deaths in 2020, but 6,370 in 2021. This is both astonishing and disturbing. What is happening?


Why should 2021 have been so much worse than 2020? We expected that nature would bring about minimal Covid-19 cases and deaths during the summer of 2021, and that the numbers would have been even lower than in 2020 with the additional benefit of the vaccination programme. But we saw a massive increase in the number of cases and an increase in deaths. 


Something has gone seriously wrong.


Although extensive data are available from Worldometer and Our World in Data we do not question what we are doing. There is no open debate in the national press or broadcast media. We hear little from government agencies. We see no debate in medical journals and we hear no debate from medical organisations, for example the Royal College of Physicians of London. Although it has led medical knowledge and progress during the past 500 years, it has unquestioningly followed the government narrative during the pandemic. 


If the major difference between 2020 and 2021 is extensive vaccination. Can we really see any evidence of a favourable impact of the vaccination programme on the course of the pandemic? Is it conceivable that the vaccination programme has been detrimental?


UK Health Security Agency – an important clue


The UKHSA, in its Covid-19 Vaccine Surveillance Report Week 42, drew attention to an unexpected, and as yet unpublicised observation. It reported increases in Covid-19 case reports across all age-groups and regions of the UK. But the important observation was on page 23: 


(ii) waning of the N antibody response over time and 

(iii) recent observations from UK Health Security Agency (UKHSA) surveillance data that N antibody levels appear to be lower in individuals who acquire infection following 2 doses of vaccination. 

"N antibody" is antibody to nucleocapsid.


This official observation indicates that in double vaccinated individuals, the immunity antibody response is impaired. This would explain why the number of cases of Covid-19 has been increasing during the summer of 2021, and why Covid-19 cases and deaths are occuring in the double-vaccinated. The effect of a third vaccination remains to be seen.


What next?


During the week ending October 24th 2021, the UK has experienced 328,287 new cases of Covid-19, and 948 Covid-19 deaths. This is with 80% of the population older than 15 years being "fully" vaccinated. We need something more, and vitamin D is glaringly obvious but still denied. 


The term "fully vaccinated" is becoming obsolete: there is no such thing. With declining immunity following double vaccination, and uncertainty after a third, it looks as though vaccinations will continue perhaps indefinitely, at shorter and shorter intervals.


WHO policy in 2020 and 2021 has been “2 Vs”:  Vaccination and Ventilation, nothing in between. More and more vaccinations are being performed. People who test positive for Covid-19 receive no treatment until they arrive in hospital and on the ICU.


What will 2022 bring? We obviously need something else for prevention and treatment. Will the denial of Vitamin D continue? If so, why?


Pharmaceutical companies are busy producing new treatments for Covid-19, but the very successful clinical trials of Calcifediol and Calcitriol (the activated forms of Vitamin D) remain ignored. Despite effectiveness, safety and cheapness, all forms of Vitamin D remain unused within official public health measures and within our hospitals. We have experienced more than 139,000 Covid-19 deaths in the UK, and the denial of Vitamin D is more than regrettable.


Covid-19 cases and deaths are increasing as we enter our winter, the Vitamin D deficiency season. Are we going to correct widespread VItamin D deficiency?


Should those receiving their third vaccination be given a vitamin D bolus dose in advance to minimise suppression of immune response?












Friday, 17 September 2021

Covid-19 & Vitamin D: Success of Calcitriol in New York study

New York: the successful RCT of Calcitriol, activated Vitamin D



To understand the basis of this important paper (details below), it is necessary to have some understanding of Vitamin D metabolism and activation. A recap:

Vitamin D (cholecalciferol) is produced only by the action of UV from the sun on the oil 7-dehydrocholesterol (7-DHC), which is synthesised in our skin and that of many other mammals. It is also synthesised in plankton in the sea, the food of fish. Vitamin D is thus produced directly in our skin (about 80%) or it is taken in our food (about 20%), mainly oily fish.

Whether produced in our skin or consumed in our food, Vitamin D is taken in the blood-stream to the liver. It is there stored while it is slowly converted into its part-activated form 25(OH)D, otherwise known as Calcifediol. If Vitamin D is taken by mouth by someone deficient, it takes up to two weeks before it achieves blood levels that are appropriate for optimal defensive immunity (greater than 30ng/ml, 75nmol/L). This is too slow for correction of vitamin D deficiency at the time of critical Covid-19 infection, and giving Vitamin D itself to the critically ill has been predictably without benefit.

It would always be sensible to correct Vitamin D deficiency in advance of possible infection so as to optimise defensive immunity. It is much more urgent to optimise defensive immunity in someone already very ill with Covid-19, whether vaccinated or not. An imaginative approach was pioneered in Spain, in C√≥rdoba and Barcelona, by treating patients admitted to hospital on account of serious Covid-19 with the activated form Calcifediol. The results have shown spectacular benefit. 

For reasons explained previously, these results have been ignored and the papers have been rubbished by individuals who should have know better. The UK National Institute for Health and Care Effectiveness (NICE) advised that doctors should not use Calcifediol. This would inevitable have contributed to the 133,000 Covid-19 deaths in the UK, and many more thousands in other countries.

A huge amount of Calcifediol is produced each year, mainly in China, but a problem has been that the great majority is destined for cattle. We accept without question the common occurence vitamin D deficiency in human beings, even at times of crisis, but it is not acceptable in cattle. Calcifediol is readily available across the counters of pharmacies in Spain and Italy, but not in other countries. Approval for human use in Covid-19 would have been a simple process but it did not happen.

Calcifediol circulates in the blood as a reservoir, ready for instant use when required. Natural vitamin D has one -OH group. The part-activation to Calcifediol requires a second -OH groups, hence -diol. When Calcifediol is required, is is taken up into target cells (including cells of immunity) and a third -OH group is added, and thereby it is converted into the fully-active form Calcitriol. When Calcitriol, 1,25(OH)D, has been used, and it can only be used once, it is inactivated by the addition of another -OH group to form 24,25(OH)D.

Most Calcitriol is created and used within cells, but there is a biological need for a tiny amount of Calcirtriol to circulate in the blood. This is created in cells of the kidneys and its purpose is calcium homeostasis, to maintain a steady blood level of ionised calcium. Clinical problems arise in advanced kidney disease, when there are insufficient specialised kidney cells to produce adequate Calcitriol, and this has been recognised for more than forty years. Calcitriol as a pharmaceutical product is now readily available for human use, and there is considerable experience of its use.

Because vitamin D is activated too slowly for use in those very ill with Covid-19, and because the proven Calcifediol is not available for human use in most countries (Spain, Italy and I think now Australia excepted), it has been suggested that the readily-available and immediately-active Calcitriol be of clinical value. 

It has now been tested as a pharmaceutical agent in severe Covid-19 infection and the result is available.

The RCT of Calcitriol

https://pubmed.ncbi.nlm.nih.gov/34508882/


Bone  2021 Sep 8;116175. doi: 10.1016/j.bone.2021.116175. Online ahead of print.

Elamir YM et al.


Mount Sinai Beth Israel, Mount Sinai Morningside, Mount Sinai West Hospitals, New York.


The clinical trial has been undertaken in New York and it was published on-line September 8th 2021 as a pre-print.

It is a study of 50 patients admitted to three hospitals on account of Covid-19 pneumonia. 25 of the 50 were randomly allocated (electronically) to receive Calcitriol in a dose of 0.5 micrograms daily for 14 days, or until discharge from hospital if earlier.

Please note that 0.5 microgram is a very tiny amount and it must not be confused with milligrams, and so it is better to avoid abbreviations. 0.5 microgram is 500 nanograms.

The success of randomisation is given in the text of the paper, comparing baseline characteristics in the two groups. Randomisation was not absolutely perfect, and for example the average age of the control group was 64 years compared to 69 in the Calcitriol group. On the other hand 19 of the control group were over the age of 65 compared to 14 in the Calcitriol group.  There are no differences between the treatments and control groups that would be expected to have a significant influence on the outcome of the trial should there be major outcome differences, and that was the case.

The outcome measures are as follows:

Increase of oxygen concentration in the blood:

The unit of measurement is ratio of peripheral arterial oxygen saturation to the inspired fraction of oxygen (SpO2/FIO2), the greater the better.

Control group      31.2                  Calcitriol group    94.0

Discharged with no need for supplementary oxygen:

Control group      21 / 25               Calcitriol group    24 / 25

Length of stay (mean of 25 patients):

Control group      9.24 days           Calcitriol group    5.5 days

Transfer to ICU:

Control group      8 / 25                 Calcitriol group   5 / 25 

Need for invasive ventilation:

Control group      2 / 8                  Calcitriol group   0 / 5

Deaths:

Control group      3 / 25                 Calcitriol group    0 / 25

Readmission within 30 days:

Control group      4                        Calcitriol group    2

There were no ill-effects from Calcitriol and no examples of elevation of blood levels of calcium (hypercalcaemia) in the two groups. 


Conclusion

In all measures of outcome, there was a clear advantage among the patients randomised to Calcitriol. 

The most important are:

Out of 8 control patients requiring transfer to ICU, there was a reduction by 3 in the Calcitriol group. This is a 37.5% reduction and it would be great importance in reducing the pressures on ICUs.

3 control patients died, but no patients treated with Calcitriol died. 3 out of 25 deaths were eliminated, which is 12% death rate becoming zero.

Do not consider this clinical trial in isolation

This Calcitriol trial must not be considered on its own, and no clinical trial must be considered in isolation. The Criteria of Sir Austin Bradford Hill must always be in our minds, the several dimensions of proof. Is there evidence of vitamin D deficiency leading to critical or fatal Covid-19? Yes. Have there been previous studies of association and temporality? Yes. Is there consistency in the studies? Yes. Is there evidence from basic science that Vitamin D and its activated forms Calcifediol and Calcitriol would help in defensive immunity? Yes. Is it plausible that Calcitriol would be of benefit in someone critically ill with Covid-19? Yes. Are there other clinical experiments that indicate benefit from Vitamin D in its activated forms? Yes. Add this evidence to the New York clinical trial and we can see justification for using Calcitriol in the treatment of people admitted to hospital on account of serious Covid-19.

The important "significance" is clinical significance, and this involves the totality of supporting evidence as outlined. The study taken in isolation might be put aside as lacking statistical significance as indicated by high p-values, a statistical concept that is a huge oversimplification and is a short-cut taken by people who do not bother to read the results of the study in detail. A high p-value means that the result might be a chance finding, but this chance is diminished by taking into account the totality of information, as we learn from Sir Austin Bradford Hill. 

In respect of clinical significance, if we are dealing with a pandemic causing 136,000 UK deaths, if the proposed treatment is safe (the most over-riding issue), and if there is very strong supporting information, is a possibility of a chance result a reason not to give the treatment? Further surveillance will give greater information without waiting for more people to die. This is acceptance of clinical significance.

If deaths go down from 3/25 in the control group to 0/25 in the Calcitriol group, is the pragmatism of clinical medicine to use the Calcitriol overridden by the statistical purism that the difference might be a chance finding, and that the result is meaningless? The decision to use must include other evidence concerning Vitamin D and Calcifediol.

Remember that vaccines were authorised despite no evidence of an effect on hospital admissions or deaths, and without completed safety studies. Emergency Use Aurthorisation is also a pragmatic response to s serious pandemic.

What next?

There is clearly an international directive that any benefits of Vitamin D (or its active metabolites) must be denied, so as to enable Emergency Use Authorisation (EUA) for the unlicensed vaccines.

What can be done by official bodies to silence this study of Calcitriol? Some criticism will be found.

Can Calcitriol come into clinical use for patients with Covid-19 pneumonia? Yes, quite easily. It is in the power of any clinical doctor to prescribe Calcitriol in the protocol used in this trial. Will such doctors be over-ruled by hospital managers? If so what would be the logic? It would be a major interference with legitimate clinical responsibility.

Calcitriol is licensed for clinical use, but this obviously does not yet extend to serious Covid-19 infection. However off-label prescribing is acceptable. As stated by the UK General Medical Council (GMC):

"The physician must be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate safety ad efficacy. Prescribing may be necessary when no suitably licensed medicine is available to meet the patient's need (or when prescribing is part of approved research)."

The respect paid to Hill's Criteria is obviously of great importance.

The New York RCT stated at the end, rather modestly, that further larger scale trials should follow. To state this is not the reponsibility of the researchers. Benefit has clearly been demonstrated and to this we must add the powerful scientific basis, and the results of positive trials of Calcifediol. 

It is perhaps logical that a second trial might be undertaken, but there are ethical constraints as we are dealing with life and death.

If a further clinical trial of Calcitriol were to take place, it must be with informed consent of the subjects. Would such informed subjects agree to be controls and deny themselves treatment demonstarted to eliminate a 12% death rate and other disadvantages?

Would any informed person refuse treatment with Calcitriol if admitted to hospital with Covid-19 pneumonia?

It will be interesting to watch the sequence of events to silence this RCT and prevent the use of Calcitriol.

What about Calcifediol

The use of Calcifediol is more physiological, optimising circulating blood levels and provide a source of the precursor of Calcitriol to be produced within the immune cells. Normally we would not expect Calcitriol from the circulation to become active within immune cells where so much of it can be produced.

In practical terms it would seem to be the best plan for clinical doctors to prescribe Calcitriol 0.5 micrograms daily for 14 days in the treatment of patients with Covid-19 pneumonia, until our national leaders approve of Calcifediol to be used in appropriate dose (already worked out) in the treatment of human beings, in addition to cattle.

The pandemic continues. Covid-19 deaths continue. WHO states "population controls and vaccines", but we clearly need something in addition. The New York study provides the immediate answer.










Saturday, 11 September 2021

Covid-19 & Vitamin D : "How do we get out of this mess?"

 "How do we get out of this mess?"


Scene: 10 Downing Street, Prime Minister’s office.


PM – UK Prime Minister, Boris Johnson


Well, er, thanks you for coming in to se me today


PV – Sir Patrick Vallance, Chief Scientist


It is always a great pleasure to see you Prime Minister..


CW – Professor Chris Whitty, Chief Medical Officer


Yes, and also a great honour.


Prime Minister

Well, thank you. But today we have a very serious problem. It looks as though we are in a bit of a mess.


Patrick Vallance

Really, PM. I thought the vaccination programme had gone really well with most adults being vaccinated.


Prime Minister

Well, yes. But it does not seem to be working.


Chris Whitty

What, Prime Minister? The vaccines are not working?


Prime Minister

That is the view of many Members of Pariament who have been contacting me, and also some newspaper editors.


Patrick Vallance

They can’t really mean it. If this news were to be broadcast they would be no end of disruption. There would be a riot.


Prime Minister

They have spoken me very confidentially and no news of this sort has been issued. But they point out to me that despite all the work of our mathematician advisors, the numbers are not going down as they should and are in fact going up!


Chris Whitty

What do you mean Prime Minister?


Prime Minister

To put it simply, they tell me that there have been more Covid-19 cases and deaths in 2021 than in 2020. They expected that the vaccination programme would have made the pandemic better, not worse. Patrick, please tell me precisely what is happening out there.


Patrick Vallance

It is all very difficult, Prime Minister.


Prime Minister

I want you to explain it to me in clear and simple terms.


Patrick Vallance

Well yes, there have been more Covid-19 cases and deaths in 2021 than in 2020. The Worldometer data informs everyone that we have just passed 7 million cases. In 2020 there we had about 2.5 million cases, but this year we have had 4.5 million cases –


Prime Minister

This is terrible, and it is only early September! Is it going to go away or is it going to get even worse?


Patrick Vallance

We hope that the pandemic will come to an end, but the mathematicians think that there might be another peak.


Prime Minister 

They always say that there is going to be another peak but I suspect that they have no real idea. They have got it so wrong previously, predicting major epidemics that did not happen. We might as well appoint a government Chief Astrologer as ask the mathematicians what will happen in the future.


Chris Whitty

I agree, Prime Minister.  The leaders of the medical professional organisations have no confidence in the mathematical projections and are fed up with covering up for what is going wrong.


Prime Minister

We must give a  positive impression to the public, no matter how negative the news. At a time like this we could do with Dom. He would be able to spin the bad news to make it look good, with a quick catch-phrase.


Patrick Vallance

We must continue the policy of vaccinating the entire population, with comprehensive vaccination of all young people in secondary schools, and as soon  possible those in primary schools.


Prime Minister

Well said. This will be a positive step which might keep bad news out of the headlines.


Chris Whitty

There is a problem with vaccinating children in that doctors are very unhappy about it, especially paediatricians. They are very concerned about the known side-effect of myocraditis, heart damage, and even more about unknown side-effects in the future.


Prime Minister

But the paediatricians do not see the big picture, and that is our responsibility. We must stop Covid-19 now. The future is less important than the present, and the future will be somebody else’s problem, not our's. Did the clinical trials not show that the vaccines are very effective and very safe?


Patrick Vallance

Yes, but there has been a re-analysis of the data. The vaccines did show a reduction of Covid-19 cases, but when all illness were put together, the subjects vaccinated were at a slight disadvantage. It is possible that in young people disadvantages outweigh benefits to the individual.


Prime Minister

We must keep that quiet. I have not heard of it in the newspapers. We must emphasise benefits to the population at large rather than to an individual. It is the duty of people to be vaccinated. But my MPs are telling me that there are reports that most of the Covid-19 cases and deaths are in people who have been vaccinated.


Chris Whitty

That is true, but only in very recent studies. If we look at the first six months of this year, we find that most cases and deaths are in the non-vaccinated. This is obvious because so few people had been vaccinated early in the year. Using the old data in the USA has enabled there to be continuing reports of a pandemic of the unvaccinated.


Patrick Vallance

Yes, that is a clever spin, as during the early part of the year not many people had been vaccinated and so they inevitably made up the majority of cases and deaths. 


Prime Minister

This is the line that we must take. 


Patrick Vallance

Yes, and it is going well. The press have been very helpful. I noted a headline in the Guardian on September 14th that  informs its readers that only 1.2% of those dying from Covid-19 had been fully vaccinated. It was in smaller print that it was revealed that the data were from January to July when initially very few if any people had been double vaccinated, in fact virtually no-one before the end of March.


Chris Whitty

The other point is that there was a very large number of deaths from Covid-19 in January and February, about 1,000 each day, and at that time vaccination rates were very low, with large numbers of non-vaccinated people dying. In the early summer death numbers were very few, just single figures each day in May and June, with very little influence on the six month total. 


Prime Minister

I hope we will be able to suppress the very recent data. I am told that August data will show a very different and much higher proportion of double vaccinated people dying from Covid-19.


Chris Whitty

I doubt if we will be able to keep the recent data hidden from the public for long, Prime Minister. The data are on the Worldometer and Our World in Data every day, and these websites are closely followed.


Prime Minister

Yes, there are too many amateur epidemiologists.


Chris Whitty

Many people follow me on Twitter. On August 20th I tweeted: “Four weeks working on a Covid ward makes stark the reality that the majority of our hospitalised Covid patients are unvaccinated and regret delaying. Some are very sick including young adults. Please don’t delay your vaccine”.


Prime Minister

Very good Chris. That is excellent. I hope many people have re-tweeted it. But I hear that the majority of Covid cases and deaths are now in people double vaccinated. Perhaps your information is out of date.


Patrick Vallance

Recent data is that most of those with Covid-19 are fully double-vaccinated. The numbers published by Public Health England are that up to August 15th, of Covid-19 hospital admissions in those over the age of 50, 31% were unvaccinated, 10% single vaccination, 58% double vaccinated.

When it comes to deaths there is a very similar picture. Just 30% unvaccinated, 9% single vaccination, 61% double vaccination.


Prime Minister

Gosh, that is terrible news. Are the vaccines really helping? What about those below the age of 50?


Patrick Vallance

Better news. With hospital admissions 74% unvaccinated, 15% single vaccination, 9% double vaccination. With deaths, 64% unvaccinated, 10% single and 24% double vaccinated.


Prime Minister

That is much better. Well we must concentrate on these numbers for the younger age groups so as to encourage more vaccinations. However, we must be aware of what I am being told about the pandemic getting completely out of hand, mainly in the far East.


Chris Whitty

People are becoming aware about what is happening in Israel. Although it is about the first and the most vaccinated nation in the world, there is now an increasing peak of cases and deaths almost entirely among the double vaccinated. People are very alarmed. In fact during the past week the number of vaccinations per day has gone down my more than a half. 


Prime Minister

Perhaps people in Israel are starting to suspect that vaccinations are more of a problem than a help.


Patrick Vallance

But the goverment of Israel is proposing booster vaccinations as soon as possible. Also there is a major peak in Japan, even more dramatic than in Israel.


Prime Minister

I had also heard about Israel, and that the proposal is for extensive third vaccinations. I suppose the peak in Japan could be due to the Olympic Games.


Patrick Vallance

Third vaccines for all would certainly be good news for the vaccine manufacturers. Even more so if vaccines had to be given every few months in the forseeable future.


Chris Whitty

But there is concern expressed that the vaccines might doing more harm than good,  and that natural immunity is better than immunity provided by vaccines.  Vaccines seem to be losing their benefit much earlier than expected, and the risk of the Delta variant is much higher among those vaccinated. The evidence is that people vaccinated are several times more likely to be infected than those who have natural immunity from previous infection.


Prime Minister

That makes me feel good having had Covid-19. What exactly is the Delta Variant?


Patrick Vallance

It emerged in India, immediately after the vaccination programme took off. It is sometimes called the Vaccine Variant, but only behind closed doors.


Prime Minister

I am told that in the Observer on August 29th there was a report that Covid-19 cases in the UK are 26 times higher than a year ago. Is this true?


Patrick Vallance

I am afraid it is. We expected that with the vaccination programme cases and deaths would be even lower in 2021 than in 2020, but it is not working out that way.


Chris Whitty

I also read the Observer article. In addition it stated that hospital admissions and deaths are a fraction of what they were in August 2020.


Prime Minister

Is this true?


Chris Whitty

I suspect not. According to Worldometer Covid-19 deaths suddenly started to increase in mid-August and now exceed 2020 figures. For example on September 7th 2020 there were just 3 Covid-19 deaths, but on the same day this year there were 209. This is the general pattern at present.


Prime Minister

Cripes! This is terrible. What can we do?


Patrick Vallance

We can hope that it improves, but otherwise we must divert attention. We must continue to make vaccination for the young our main priority, and blame the unvaccinated young for the deteriorating situation.


Prime Minister

But what if there is a backlash against vaccinations?


Patrick Vallance

Well Prime Minister, the main impact will be on the share prices of the pharmaceutical companies. Many of us have a lot to lose.


Chris Whitty

We must continue to emphasise the importance of vaccinations.


Prime Minister

What about the other things, vitamin D, ivermectin, hydoxychloroquine and so on?


Chris Whitty

We have followed your instructions and kept these out of the news and out of clinical use. I must say that the doctors have been very unhappy about this. They are aware that we have had 133,000 Covid-19 deaths and they think that most of these could have been avoided had we used vitamin D in particular from the very beginning.


Prime Minister

Well, that is just speculation.


Chris Whitty

The doctors have been concerned that they have been unable to offer any treatment to Covid-19 patients until they arrive on the intensive care units. If Pfizermectin materialises, that will be a help.


Prime Minister

As I have said I appreciate your success in keeping vitamin D in particular hidden from view, but I am very pleased to have received it myself when I was so very ill with Covid-19. We have had to follow WHO and FDA instructions that there must be no alternative to vaccines, otherwise the Emergency Use Authorisations would not have been granted.


Patrick Vallance

Whatever the benefits Prime Minister, if we bring Vitamin D and its activated form Calcifediol into use now, there will be public outcry from the relatives of the dead as to why we did not do so at the beginning.


Prime Minister

It is all very difficult. We really are in a mess but at present beneath the surface. We simply must continue with vaccinations, otherwise the public will lose confidence in us.


Patrick Vallance

And if cases and deaths increase we must blame it on new variants.


Prime Minister

And people who have not been vaccinated.


Chris Whitty

Prime Minister, I am still concerned that the public might become aware of what is happening around the world. The public have been expecting that the vaccinations would make things better. What will happen if the pandemic continues to get worse?


Patrick Vallance

It is inevitable that the pandemic will settle in time, and the official line is that when it does, it will be the result of the highly successful vaccination programmes.


Prime Minister

While we are here, what is the situation with deaths and ill-effects from the vaccines?


Chris Whitty

The Yellow Card system is functioning but there seems to be little notice taken and certainly no actions. We rely on the fact that in individual cases, proof is not possible and we emphasise that co-incidences do happen.


Patrick Vallance

I read that the coroner concluded that the death of Lisa Shaw, the BBC presenter, was the direct result of the very recent vaccination. 


Prime Minister

I am told that the BBC will keep quiet about this unfortunate case. Let’s hope so. The last thing we want is a succession of claims of vaccine damage,


Patrick Vallance

Especially as the government has accepted financial liability.  


Prime Minister

I certainly never expected the Covid-19 pandemic to turn out to be anything like as bad and complicated as it has turned out to be. And it seems to be far from over. The end of September is likely to see the mess even worse, unless the pandemic goes away. I am sure we will be meeting again very soon. 


Exit Patrick Vallance and CW.