Monday 22 February 2021

Covid-19 & Vitamin D : more human sacrifice demanded

Covid-19 and vitamin D: still "not enough evidence" unless more people die

So many deaths. How many could have been avoided?
 How long must we wait for vitamin D to be approved officially?

My previous post continued the collection of more evidence in support of an important role of vitamin D during the present pandemic, with details of the new study from Barcelona

But what is really going on? Why are so many deaths allowed to continue when we are ignoring the evidence supporting vitamin D?

The proposal is that:

 “Vitamin D deficiency is common, especially in the elderly, the obese, in UK citizens with an ethnic melanin-rich skin, and in the winter; 

vitamin D deficiency creates a serious biological disadvantage, at present in respect of Covid-19 infection;

vitamin D is essential for the escalation of defensive immunity at the time of serious infection;

correction of vitamin D deficiency is a medical duty; 

correction of vitamin D deficiency by an oral supplement  corrects the biological disadvantage.” 

This would seem to be a non-controversial  proposal in that it is based on many observations and much knowledge.

During the past eleven months there have many substantiated claims of benefit from vitamin D, but also many denials. The reason why vitamin D has turned out to be so controversial is very difficult to understand, but the reality is that correction of vitamin D deficiency has been neglected by our supposedly scientifically-directed government and by public health policy, at very great human cost. It has been suggested by the research group in Heidelberg that the UK might have experienced 90,000 fewer deaths from Covid-19 if the public health bodies had corrected widespread vitamin D deficiency, especially in the  population groups know to be at risk of both serious vitamin D deficiency and death from Covid-19. 

Desperate times demand desperate measures

However, correction of vitamin D deficiency appears to be a step too far. Why the hesitation? Widespread vitamin D deficiency is well-known in medial science, if not by the general public. Vitamin D supplementation, ideally preceded by checking blood level, should be a natural almost knee-jerk response to what can only be described as an overwhelming pandemic of a novel virus that has caused more that 4 million cases and more than 120,000 deaths in the UK alone. Optimisation of defensive immunity (knowing of the importance of vitamin D in this process) would be a sensible and obvious action.  

What on earth has gone wrong? I have been overwhelmed by evidence supporting the above proposal and yet NICE (the UK National Institute for Clinical and Care Excellence with considerable international influence) repeatedly claims in a parrot-like fashion that there is not enough of it. How much is “enough”? Is evidence to be measured by weight of paper, or in the current era by accumulated word-count? The knee-jerk reaction of NICE is vitamin D denial.

Pascal’s wager

The practical objective is to activate a decision. Are we as a nation going to correct vitamin D deficiency or are we not? It is an application of Pascal’s wager.


If vitamin D deficiency is an important and effective factor in serious and fatal Covid-19:

What can be gained by promoting vitamin D? 

Answer: many deaths prevented. 

What is to be lost if it turns out that vitamin D deficiency is

not important and vitamin D is not effective? 

Answer: just wasted effort, as vitamin D is cheap and safe. 

If vitamin D deficiency is an important factor in serious and fatal Covid-19:

What would be gained if we refuse to correct wide-spread vitamin D deficiency, as NICE proposes

Answer: nothing.

What is to be lost  

Answer: many avoidable deaths.

If vitamin D is not of value, there is no loss from either promoting or not promoting it.  

It is glaringly obvious that the choice with the greatest utility,  potential benefit, is to promote vitamin D, with the possibility of the prevention of many deaths (perhaps many thousands) and with no disadvantage.

The choice with the greatest loss is to refuse to promote vitamin D (which turns out to be effective as all evidence indicates) with the result of many avoidable deaths, and with no gain. This is the position of NICE. There is much evidence, but allegedly "not enough". Utility is not a consideration of NICE.

Why is NICE involved in decision-making? 

NICE is an advisory body. It has no executive function and it does not make decisions. Unlike clinical doctors it has no direct clinical responsibility to individual named people. NICE has a main function of evaluating pharmaceutical agents and clinical procedures, and advising government and hospital trusts on best practice. 

We are dealing with widespread vitamin D deficiency, which is responsible for many deaths from Covid-19. This is beyond doubt but it is carefully avoided by NICE. It would seem to be a straightforward clinical responsibility to detect and correct vitamin D deficiency, like hypothyroidism (underactive thyroid) or diabetes (especially Type 1). 

It is very strange that NICE has become involved in this artificial evaluation of the need to correct deficiency of vitamin D, which is converted into a hormone within the body. What can be controversial about correcting a vitamin or hormone deficiency? If NICE did not exist would there even have been a controversy? It is interesting to note that NICE has been completely bypassed by the government in the vaccine roll-out programme, even though vaccines are pharmaceutical products and not natural substances.

NICE avoids any mention of vitamin D deficiency and treats vitamin D as a pharmaceutical product. That is its modus operandi. NICE has stated that there is no proof that Vitamin D is of  value in Covid-19, but introduces the word “proof” without defining it. Proof is the fulfilment of predetermined criteria, but like so many others, NICE has not stated its criteria of proof. It demanded a randomised controlled trial (RCT), but when one appeared (from Córdoba) it demanded another. Now that it has appeared (from the University of Barcelona) we await with interest the official response of NICE. So far, just silence.

I learned about "proof" in Euclidian geometry when I was at school. It was followed by quod erat demonstrandum (QED), "what was to be shown", or it has been demonstrated, perhaps quite easily done! "Demonstration" is an important concept: I can demonstrate gravity but I cannot prove it. The extent of vitamin D deficiency can be demonstrated. The disadvantages of vitamin D deficiency, including with Covid-19, can be demonstrated. The benefit of vitamin D supplementation can be demonstrated. How does demonstration differ from proof?

RCT from Barcelona

Since the appearance a week ago of the results of the Barcelona RCT we have had no official response from NICE. However we have had a response from Professor Adrian Martineau, one of its members. Professor Martineau, together with Professor Sattar from Glasgow, set the scene in a dismissal of the Barcelona study, critical of aspects of the methodology. Guess what? They demand more RCTs, but they must be “robust” (good management-speak). 

One criticism was an apparent "absence of registration" of the trial before it commenced. This is an administrative issue that would have no bearing on outcome. The study had permission from the hospital ethics committee. Without this there would have been a valid criticism, but lack of prior registration can surely not invalidate the findings of the study.

Another criticism is a lack of clarity of the process of randomisation. The 930 patients were randomly allocated to one of eight dedicated Covid-19 wards. On three of them the patients received high quality standard care. On the other five wards, the patients received in addition calcifediol, a natural substance, part-activated vitamin D with a very rapid action. 


The purpose of randomisation is to produce two groups as near identical as possible, except for the the treatment under investigation, in this case calcifediol. Randomisation could be made in a number of ways: the spin of a coin, the random selection of an envelope containing an allocation code, a random number generated by a computer, year of birth odd or even number, etc. The Córdoba study involved electronic randomisation. The Barcelona study just tells us that the patients were "randomized" to the wards, with no indication of the method. At a time of very busy hospital activity, randomisation could simply have been the on the basis of the next available bed on any of the eight wards, as there would be very few empty beds to choose from. The absence of method of randomisation in the paper could be corrected easily, but would it have any impact on the result?

The success of randomisation can be determined by comparing characteristics of the two groups of patients. Ideally they should show no significant differences, but the variations of humankind mean that randomisation is seldom perfect, even with a sample size of 930 as in the Barcelona study. Experiments in physics, chemistry, or plant and animal studies can be controlled rigorously, but not so with humankind and civil liberties. Pragmatic randomisation must be used, with as large numbers as possible to minimise the effect of natural variation.

The randomisation profile of the Barcelona study is shown in the table.

There are inevitable differences between the two columns, but the majority are of no significance. We can see that randomisation was generally successful. 

Baseline vitamin D (calcifediol) testing

The median average blood level of the 752 of the 930 patients tested at baseline was 14ng/ml, very low at less than 20ng/ml. This indicates a high risk of serious or fatal Covid-19, above 30mg/ml being safe. 

Of 495 patients with blood vitamin D less than 20ng/ml, 332 (67% of 495, 44% of 752) were found to be calcifediol treated patients, a higher proportion than 163 (33% of 495, 22% of 752) in the controls. This would give a disadvantage to the calcifediol treated group but it was not brought out in paper.

The study reported the only significant difference of randomisation to be the baseline measurements of vitamin D, blood levels of 25(OH)D which is calcifediol. The median average is 12ng/ml in the controls and 15ng/ml in the group randomised to receive calcifediol. 

The difference between 12 and 15 does to appear to be very great but the report states that it is statistically significant. The sample sizes are good, but we are not given the standard deviations and so we are not able to calculate the standard errors, from which, with the sample sizes, we would be able to calculate for ourselves the statistical significance of the differences.  

There is a conflict between the two methods of assessing differences of baseline blood calcifediol levels between the two groups. We cannot be clear whether or not the calcifediol treated group had an initial advantage as suggested in the randomisation table. Does this invalidate the trial? No. We must accept the result but ask clarification from the authors.

The primary endpoint

The most serious criticism by Professor Martineau is a departure from the protocol during the Barcelona RCT. This was for a reason that I regard as for strongly valid ethical reasons. 

Conducting a trial of 930 critical ill patients is not easy. We are not dealing with laboratory animals, and the over-riding objective of the attending physicians in their clinical practice must have been to minimise possible deaths of their patients. 

The primary endpoint was reached, with 21.1% of the control patients requiring admission to the ICU compared to 5.4% of the calcifediol-treated patients, a highly significant result, 74% efficacy (21.1-5.4=15.7; 15.7x100÷21.1=74%). This is a large difference in outcome that cannot be ignored, and it appears that it was not ignored during the trail.

The second endpoint: is human sacrifice essential?

The next endpoint was to be death following transfer to ICU. Calcifediol was of demonstrated great benefit in the first stage. The trial could have been stopped at this point, with great help if the protocol were to be used in other hospitals. 

For the second phase in the ICU something had to be sacrificed. Was it to be rigour of the protocol or was it to be human life? – a conflict between experimental purity and the welfare of the very ill patients. The latter option was chosen as the way forward, the welfare of the sick. 

It had to be decided whether the control patients who had been randomised not to receive calcifediol were to continue without it when on the ICU. The pragmatic decision was made to allow the clinical judgement of the attending physicians. Of the 80 control patients admitted to the ICU, 50 were started on calcifediol. Human sacrifice was thereby minimised, to the displeasure of Professor Martineau as implied in his criticism of departure from the protocol.


The paper from Barcelona first presented analysis of deaths on the basis of "intention to treat". The result was 56% efficacy. But this method is not really justified as the majority of the control patients received calcifediol when on the ICU.

The analysis was repeated for the sum of the 551 randomised calcifediol patients and the 50 control patients given calcifediol when on the ICU, a total of 601. Of these 49 (8.15%) died. Of the 329 patients who did not receive calcifediol, 44 (13.4%) died. This is a 39% efficacy of the reduction of deaths by calcifediol (13.4-8.15=5.25; 5.25% is the gain from taking calcifediol; 5.25x100÷13.4=39% efficacy).

Had calcifediol been withheld from all control patients on the ICU, we would anticipate more deaths among the control patients, thereby increasing statistical efficacy, but this cannot be proved without further human sacrifice.

1,25(OH) vitamin D is consumed

A further "criticism" was the usual comment by Professor Sattar that a low blood level of vitamin D as calcifediol is the result of the disease. There is some truth in this statement in that it is well-known that a molecule of intracellular 1,25(OH)D can only be used once, and after use it is inactivated to 24,25(OH)D. This means that at a time of escalation of defensive immunity it is essential for the body to have a good supply of vitamin D as calcifediol circulating in the blood. Without this there is a high chance of critical disease and death.

Professor Sattar dismisses the RCT from Barcelona as ….not a useful study….”, and follows “We must await robust randomised trials to form appropriate conclusions”.

How do we define "conclusions"?

Professor Martineau does not discuss the ethical issues of the trial. He states: “Overall, more methodological detail is needed before the claims of treatment benefit can be substantiated.” Professors Sattar and Martineau do not define what they mean by "substantiation" and “conclusions”. 

If we await a conclusion we will wait indefinitely while counting the dead. In science a conclusion is never reached, just a revolving wheel of research, often changing direction. There is no absolute truth. The paradigm, the clinical action, the acceptance of Pascal’s Wager, is pragmatic proof based on the best evidence we have at present, warts and all. 

The meaning of Proof

The RCT is only just a part of proof, and a part that is not essential. This was understood by Sir Austin Bradford Hill, whose wisdom should be central to the current so-called controversy concerning the correction of vitamin D deficiency at the time of the Covid-19 pandemic and the 120,000 associated deaths in the UK.

Using Bradford Hill’s criteria, the evidence to support the use of vitamin D in the prevention and treatment of Covid-19 is far stronger than the evidence that cigarette smoking causes lung cancer, or that driving a car under the influence of alcohol, or without a seat-belt, increases risk of death. The governments of the day took action, with good results, and without RCTs. 

The government of today should take action and advise the use of vitamin D in a dose to correct deficiency so as to optimise immunity rather than simply to avoid rickets. This should not be controversial to those with understanding of the issues. Had it been done, there might have been 90,000 fewer Covid-19 deaths.

The disappearance of the Barcelona study

The power of Professor Martineau and NICE must not be underestimated. 

The result from Barcelona was published on a pre-publication website under the control of The Lancet. This is useful as publication can be a slow process. The Barcelona study was undertaken in March, April and May 2020. The result has taken a long time to come  to attention, at a time when we have required "desperate measures" to reduce the pressure on ICU beds and the number of Covid-19 deaths. 

Five days after its appearance and after a further two days following the comments by Professors Martineau and Sattar, the paper was taken down from its web-site. It can no longer be viewed, but no doubt many people (such as me) will now have a PDF. This is censorship, the burial of important information. Perhaps it will reappear with clarification of the process of randomisation. Time will tell.

The RCT from Córdoba was rubbished in a few sentences by Professor Neil Gittoes, who was acting on behalf of NICE. As a result of his cursory comments, NICE stated:

"The clinical management of patients with COVID-19 should not be changed based on the results of this study."

A team from the Massachusetts Institute of Technology undertook a very thorough review of the Córdoba study and came to the opposite conclusion from Professor Gittoes, reporting that process was acceptable and that the probability of a chance finding was less than one in a million. NICE has not commented on the MIT analysis.

And so we have three individuals, Professors Gittoes, Sattar, and Martineau who have been allowed to use extreme power to prevent the nation-wide treatment of patients with Covid-19 pneumonia using vitamin D as calcifediol, despite great evidence of the dangers of vitamin D deficiency and the benefit of correction. Their analyses have been very superficial. There views have not been challenged in the medical or national press.


The Córdoba RCT result became available on September 3rd 2020. Since then there have been more than 56,000 Covid-19 deaths in the UK. Had treatment with calcifediol (price €10 per patient, no side-effects) been instituted, several thousand of these patients would not have died. Are these deaths of no importance?

Who is to be held accountable?

This Blog post contains a lot of numbers as I felt that my comments should be justified. If any reader spots a fault in the calculations. please inform me immediately.

Monday 15 February 2021

Covid-19 and Vitamin D – Success of Calcifediol in Barcelona

The Barcelona study of the use of Calcifediol in the treatment of Covid-19 pneumonia:

74% efficacy in the need for transfer to ICU

39% efficacy in reduction of deaths

Will this study influence NICE and the Vitamin D deniers?

September 3rd 2020 saw the release of the results of a randomised controlled clinical trial (RCT) of calcifediol, from Córdoba, Spain. Of 75 patients admitted to hospital with Covid-19 pneumonia, 25 received standard care. Of these 13 (50% needed transfer to the ICU, and 2 (8%) died. 50 were randomised to receive calcifediol (part-activated vitamin D) in addition to standard care. Of these just one (2%) required transfer to the ICU and he survived.

This dramatic benefit was effective, cheap, safe, and readily available. It was just what was needed when deaths from Covid-19 were expected to increase with the end of the summer having been reached. But the benefit was ignored and calcifediol was not accepted as a treatment by doctors who were treating the seriously ill. Desperate times need desperate measures, but this did not include proven and safe calcifediol for reasons that to me were incomprehensible. Vitamin D denial is not rational as it ignores vast evidence of the extent of vitamin D deficiency, its great disadvantage during the pandemic, and the demonstrated benefit of correction of the deficiency.

The UK National Institute for Clinical and Care Excellence (NICE) stated that clinical practice should not be influenced by the result of the Córdoba study, despite its obvious great advantage. This was a centralisation of clinical decision-making previously unknown. In the early summer NICE had deferred a decision concerning the clinical use of vitamin D in the Covid-19 pandemic until it had seen evidence from an RCT. This was absurd as a widespread vitamin / hormone deficiency was clear, and correction of deficiency should have been obvious good clinical practice without the necessity of approval by NICE.

When the result of the Córdoba RCT appeared, NICE still stated that there was not enough evidence to recommend vitamin D for use in Covid-19, and it deferred approval once again, until the publication of another RCT

It is now available. 

The RCT from Barcelona.

As in the Córdoba RCT, vitamin D was given in the form of calcifediol. To recap, when vitamin D is formed in the skin or taken by mouth, it enters the blood and is transported to the liver. In the liver it enters a slow process of hydroxylation, forming 25(OH)D, otherwise known as calcifediol. This is the form in which vitamin D is found in the circulation and it is what we measure in blood testing.  

If we give vitamin D by mouth or injection to someone who is deficient, it will take up to two weeks before it reaches a good blood level (>30ng/ml, 75nmol/L). This is too slow for the maximum effect required in someone who is critically ill with for example Covid-19 pneumonia. On the other hand, when calcifediol itself is given by mouth or injection it will reach a good blood level within two hours. This is just what is required for the critically ill patient.

The Barcelona study involved 930 patients with severe Covid-19, some with chronic conditions, co-morbidities. They were admitted to the eight COVID-19 wards in the Hospital del Mar, Barcelona, between March 1st and May 31st 2020.  This shows how long it takes for the results of an RCT to come to fruition. Each patient was randomly allocated to one of the eight wards. On five of these wards the patients were treated with standard high quality care plus calcifediol. The patients admitted to the other three wards acted as controls, receiving high quality standard care but not calcifediol. This is the way in which randomisation was considered by the investigators to be practicable. The main predetermined primary end-point was admission rate to the Intensive Care Unit (ICU).  The second end-point was the incidence of death.

551 patients were randomised to receive calcifediol; 379 patients acted as controls. 


Of the 930 subjects, 752 had blood vitamin D levels measured on admission. The median average level was 14 ng/ml (35 nmol/L), very low. 

Vitamin D deficiency (defined as less that 20ng/ml, 50nmol/L) was found in 495 of the 930 (65%). 332 of the deficient (55.2%) were in the calcifediol group and 163 (49.5%) in the control group.

Patients with a blood vitamin D level of 20ng/ml or greater were at about half risk of ICU admission compared to those vitamin D deficient, relative risk 0.45.

110 of the 930 patients required ICU transfer. 

These included 80 of the 379 (21.1%) of the control patients, and 30 of the 551 (5.4%) of the calcifediol treated patients. We can immediately see a dramatic benefit of calcifediol in respect of the first end-point

The reduction in need for ICU was reduced from 21.1% to 5.4%, highly significant. The absolute risk reduction of 15.7% translates into 74% efficacy in reduction of need for ICU.

Ethical considerations

The clinical trial is in two distinct parts. It could have stopped at the point of proven benefit from calcifediol, knowing that this would be of major impact if adopted by other hospitals. Progression into the second phase of risk of death posed very serious ethical considerations, and these must not be dismissed. No doubt they had been addressed by the ethics committee that approved the trial with respect of international conventions, the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization.

As a major benefit of calcifediol had been demonstrated in reduction of need for ICU, would it be ethically justified to continue to withhold calcifediol from the 80 control patients who had deteriorated to the point of admission to ICU? 

The correct consideration was that human sacrifice should not be part of a controlled clinical trial, whether or not supposedly fully informed patient consent was given. 

At the point of ICU admission the patients were critically ill and were under the care of clinical doctors whose over-riding concern must have been to minimise the deaths of their patients. The ultimate rigour of a clinical experiment should not and did not have priority. A decision whether control patients admitted to the ICU should receive calcifediol at that time was left to the attending physician.


Of 930 patients enrolled into the trial, 93 (10%) died.

Of 379 randomised to be controls, 50 of the 80 requiring ICU support received calcifediol on transfer.

On the basis of intention to treat, out of 551 patients who received calcifediol on admission, 36 (6.5%) died, compared to the original control group 57 out of 379 died (15%). This gives an efficacy of 56% (= 57x100/379).

The 551 patients who received calcifediol on admission to hospital were combined with the 50 (out of 80) who were started on calcifediol only on admission to ICU, giving a total of 601 patients who received calcifediol. Of these 601, 49 (8.15%) died, compared to 44 out of the 329 (13.4%) who never received calcifediol, a 39% efficacy of calcifediol. This is the more realistic efficacy.

There was a 20% mortality rate on the ICU of those who had started on calcifediol on admission to hospital, compared to 26% mortality rate of those started on calcifediol only on transfer to ICU. 

The 93 patients who died had a median vitamin D level of 9.5 ng/ml (24nmol/L), significantly lower than those who survived, 14 ng/ml (35 nmol/L).


65% of patients with Covid-19 pneumonia had vitamin D deficiency, <20ng/ml, <50nmol/L.

Initial average blood level of vitamin D in those who died was 9.5ng/ml compared to 14ng/ml in those who survived.

Prevention of admission to ICU: 74% efficacy,  21.1% of control patients, and  5.4% of calcifediol treated patients.

Reduction of deaths: 39% efficacy, 13.4% of these who did not receive calcifediol, and 8.15% of those who received calcifediol.

Need for ICU was lower in those with higher initial levels of vitamin D, relative risk 0.45.

Limitations of the study

Criticisms of the Barcelona study by Vitamin D-Deniers will be inevitable. However the study must be put into context with so many other studies that have demonstrated the wide extent of vitamin D deficiency, the disadvantages of vitamin D deficiency, and the value of correction of the deficiency with supplements. 

I have mentioned the ethical issues that led to departures from the trial protocol so as to minimise the risk of death in control patents who had deteriorated to require transfer to the ICU. This was correct within the ethical codes and it does not detract from the results of the trial.

The use of randomisation by ward in a busy hospital was a pragmatic decision in a situation where individual randomisation with use of placebo would be problematic. Randomisation was not as simple as for example an RCT of vaccines or other trial medications in fit and healthy volunteers. The important thing is that there were two comparable groups with no possibility of placebo effect in patients so critically ill.

Despite randomisation, subsequent analysis showed that there was a slight difference in median average blood levels between the two groups, slightly higher in the calcfediol treated group. This would give an advantage to the calcifediol group, but only in the view of people who recognise the advantage of vitamin D.

I have previously demonstrated by the application of the criteria of Sir Austin Bradford Hill, the proof that vitamin D deficiency or supplementation is of critical importance in death or survival from Covid-19. Like other studies, the Barcelona trial cannot be regarded as proof in itself but it adds to the criteria of association, reproducibility, temporality, and experimentation.


It is beyond reasonable doubt that vitamin D deficiency is not just common but is particularly common in those seriously ill with Covid-19, and that vitamin D replacement therapy has a vital role to play in minimising deaths during the present pandemic.

It is no longer acceptable for people to die from Covid-19 when deficient in vitamin D.

It is no longer acceptable for vitamin D (ideally in the form of calcifediol) to be withheld from people admitted to hospital severely ill with Covid-19 who are at risk of escalation to ICU and possible death.

Tuesday 9 February 2021

Covid-19 & Vitamin D : The common link. Remember William of Ockham?

Covid-19 & Vitamin D : Anti-science – the disappearance of vitamin D deficiency. Remember William of Ockham?

 "Entia non sunt multiplicanda sine necessitate"

Do not multiply entities without necessity

The simplest explanation is likely to be true

William of Ockham

William of Ockham (c 1287–1347) was a monk philosopher, whose recent claim to fame was his investigation into the strange deaths of monks as featured in the remarkable book "The Name of the Rose", by Umberto Eco. In the subsequent film, Sean Connery played the role of William. The more recent television series was too blood-thirsty for me and in this respect departed from the book. The reason for the deaths was the aged librarian keeping younger monks from viewing the monastery's unique copy of Aristotle's Book of Humour and Laughter. The librarian believed that humour was subversive and might destabilise the monastery or even the Church. However he could not bring himself to destroy such a valuable part of historical literature, but he kept it hidden. Many monks wanted to find it and read it, and this had to be suppressed.

But William of Ockham is more famous for his "Razor". His philosophical point was to "cut down" convoluted explanations of things that were not understood. William's view was that the simplest explanation was likely to be correct, and in trying to explain a number of phenomena, a single explanation might be sought. In more recent years Einstein also expressed the importance of a unifying explanation, but he advised "Keep things simple, but not too simple". 

Nicolas Copernicus was not satisfied with the geostationary Earth, with each of the known planets all having their own bizarre orbits around it. This is an example of Ockham's Razor in action: Copernicus replaced this highly complex explanation of celestial mechanics with a more simple model of a heliocentric planetary system, all planets including the Earth orbiting the Sun. A single concept, simple and true.

This became the philosophy of science in the age of enlightenment., the concept of a common thread, attempting within the restrictions of knowledge to create a unifying explanation. The example of electro-magnetism is a clear example, space-time another.

In medicine we have also been unifying explanations. The initially separate diseases of tabes dorsals, general paralysis of the insane, ascending aortic aneurysm, Argyll-Robertson pupils, tumours called gummas, skin rashes, and an earlier genital sore were noted to be associated, well before sophisticated epidemiology. The association  led to the recognition of a unifying syndrome of syphilis. The identification of the causative micro-organism Treponema pallidum came later. Association is major way to identify causation.

More recently it was noticed that patients (usually young men) were displaying features of unusual infections and tumours, leading to rapid death. The unifying explanation was the recognition that they had impaired immunity, called acquired immunodeficiency syndrome, AIDS. 

Association is very powerful, leading to explanations. Sometimes it is obvious, the association between high blood levels of alcohol and road traffic accidents. Sometimes it can be misleading. The association of policemen at the scene of a robbery does not make them robbers. The association between death and positive testing for Covid-19 is accepted but not always clear. Bradford Hill's criteria are of great importance.

The pandemic of Covid-19 has led to recognition of the association of many characteristics with vitamin D deficiency. It might be expected that the search for a unifying explanation might by now be well-established in health care, but this is not necessarily the case in non-medical health care.

Let us hesitate for a moment and just think of our thoughts should the following happen when we wake up in the morning:

the light does not work;

another light does not work;

the radio does not work;

the television does not work;

the kettle does not work;

the toaster does not work;

the cooker does not work.

"What a coincidence that the have all stopped woking at the same time."

Ockham's Razor: the electricity has gone off. The unifying hypothesis.

How the important unifying immune suppression of vitamin D deficiency was missed

Vitamin D concentrations and COVID-19 infection in UK Biobank.  Diabetes & Metabolic Syndrome: Clinical Research & Reviews. Volume 14, Issue 4, July–August 2020, Pages 561-565

"We found no evidence that (25(OD)D) explains susceptibility to Covid-19 infection, either overall or between ethnic groups." Hastie CE et al.

This is a remarkable paper that has been widely quoted as demonstrating the lack of importance of vitamin D during the present pandemic of Covid-19. It comes to a completely different conclusion from another study that used the same data.

"Severe vitamin D deficiency remains an issue throughout the UK, particularly in lower socioeconomic areas. In some groups, levels of deficiency are alarmingly high with one-half of Asian and one-third of Black African ancestry populations affected across seasons."

The conclusion of the paper by Hastie and colleagues is to be found at the beginning, and so very few people will have read beyond it and looked at the data. The data were taken from the UK BioBank project, but completely misinterpreted.

The UK Biobank project holds data on voluntary participants and complete data on 348,598 were available. Covid-19 tests were perform on 1474 individuals and 449 were positive.

"UK Biobank is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. The database is regularly augmented with additional data and is globally accessible to approved researchers undertaking vital research into the most common and life-threatening diseases. It is a major contributor to the advancement of modern medicine and treatment and has enabled several scientific discoveries that improve human health."

Blood levels of vitamin D had been performed as part of the Biobank database, several years in advance of the Covid-19 pandemic.

Analysis was based on positive or negative Covid-19 testing, and also on ethnicity and a number of bio-medical and socio-economic parameters.

The results of the analysis are as follows.

Average blood level of vitamin D 

It is clear that there is a major difference, with those of Black and South Asian Ethnicity (BAME) having lower levels of vitamin D than ethnic white people, but all were much lower than the ideal range that I would consider to be 100–150 nmol/L, 40–60

Deficiency of vitamin D      

Deficiency of vitamin D is defined in the paper as less than 25nmol/L (10ng/ml), and insufficient was defined as less than 50nmol/L (20ng/ml ).

Vitamin D deficiency was found in the ethnic groups with the following frequencies:

The much higher level of deficiency among BAME groups is clear. 

Experience during the Covid-19 pandemic indicates that the ideal blood level of vitamin D is 100–150 nmol/L (40–60ng/ml).

This ideal blood level would result in a much greater occurrence of vitamin D deficiency in all groups.

Odds Ratio for Covid-19 based on vitamin D 

For those deficient in vitamin D, the overall Odds Ratio for Covid-19 = 1.37, in other words 37% higher than in the average population.

The analysis went through "adjustments" that made this positive Odds Ratio for Covid-19 to be a negative Odds Ratio of 0.92, indicating that rather than vitamin D deficiency making Covid-19 more likely, it made it less likely.

The analysis is starting to look suspicious.

Odds ratio for Covid-19 based on ethnicity 

For reference, white = 0

Ethnicity and poverty are clearly main determinants of Covid-19.
We were not given blood vitamin D levels for characteristics other than ethnicity.

So far it looks to be straightforward. Black and South Asan people have a high risk of Covid-19. They also have a high incidence of vitamin D deficiency. Knowing that vitamin D has a pivotal role in escalating defensive immunity in response to infection, it seems reasonable, even obvious, to assume that the low vitamin D level in BAME people leads to high risk of Covid-19 death.

But this must be explained away.

Characteristics of study population by presence or absence of confirmed COVID-19 infection. 

Percentages are displayed in this table, an extract of that published. Deprivation 1 = least deprived, Deprivation 5 = most deprived.

I have looked at this extract and the original paper itself on many occasions, wondering if I am losing my eyesight or intellect. There appear to be inconsistencies or errors, but perhaps there is something that I am missing.

For example, it appears that 89.63% (Covid-19 negative) or 88.64 (Covid-19 positive) currently smoke cigarettes, and only 10.27% and 11.36% are non-smokers. Surely this is the wrong way round.

68.21% had long-term disability and 31.79% did not have disability. Surely this must be the wrong way round.

94.59% had diabetes and 5.41% did not have diabetes. Surely the wrong way round.For the purpose an analyse I have assumed that they are the wrong ay round, just the minority of people spoke cigarettes and have diabetes and long-term disability. 


the disappearance of vitamin D

The following characteristics show a positive association with Covid-19:

Male, Black, South Asian, social derivation grade 5 (worst), obesity, disability, long-term illness (assume "yes"), diabetes (assume "yes").

In Hastie's paper the importance of vitamin D is eliminated by "adjustment", the method of this being obscure. However we start with what we might consider to be the importance of vitamin D deficiency (as acknowledged in the second paper), but then it disappears. Black people might have a high risk of Covid-19, but it is because they are Black. South Asian people might have a high risk of Covid-19, but it is because they are South Asian. 

The same goes for people who are obese, the risk is because they are obese and vitamin D deficiency is not important. And it is the same with disability, social deprivation, long-term disability, and diabetes. They are all assumed to have their own explanations for Covid-19 susceptibility independent of vitamin D. 

This is like in pre-Copernicus times when each planet had its orbit independent of the sun. In defiance of the razor of William of Ockham, new entities of susceptibility to Covid-19 must be invented for being Black or being South Asian, and well as being poor, disabled, long-term ill, having diabetes or obesity. The common thread has been completely missed.

Let us imagine that the importance of vitamin D deficiency in deaths from Covid-19 is represented by a circle, as in Figure 1. This does not appear to be very clever but now let us watch how vitamin D deficiency virtually disappears.

Black people are deficient in vitamin D and so we can discount vitamin D as the high death rate is explained by skin colour and the social effects of this. The same with South Asian ethnicity. The same also applies to obesity, disability, long-term illness, social deprivation, and diabetes. So if we put these together we finish up with a pie chart (below) in which the importance of vitamin D effectively disappears. Hence the conclusion that "We found no evidence that (25(OD)D) explains susceptibility to Covid-19 infection, either overall or between ethnic groups."

Scientific reasoning would look for a common theme, and knowing of the well-established metabolic importance of vitamin D in defensive immunity, it would be reasonable to test this as a common explanatory thread, the sun around which the planets orbit. The way to look at the relationship of variables is not the pie chart but the Venn diagram. 

First, a simple Venn diagram. It indicates that vitamin D deficiency is common. It indicates that most ethnic Black and South Asian people are vitamin D deficient, and similarly most  people with the worst socio-economic deprivation. Also that most people with serious Covid-19 are vitamin D deficient. Most people with vitamin D deficiency do not have Covid-19. Some people can have all factors. 

But such a simple Venn diagram as this cannot display all the parameters described in this study. It needs to be reconstructed.

In the Venn diagram below I have identified that the common thread is vitamin D deficiency, for the simple reason that all the other characteristics have been shown independently to have a high prevalence of vitamin D deficiency. The model would look like the figure below, the most simple model of the relationships, and I think it is true, although mathematically unsophisticated.

I do not pretend to be a mathematician or statistician, and this Venn diagram is a gross oversimplification. I will leave greater accuracy to experts, and perhaps a reader might help me. It shows however a dynamic relationship between the variables. They overlap, meaning that, as we know, South Asian people have a high incidence of diabetes as well as vitamin D deficiency. Perhaps they also have a high prevalence of social deprivation, but not exclusively. I cannot show all the overlaps on a two dimensional construction.

So here we have it. There is the single entity that William of Ockham might have approved of, the common thread that links all the features together. We need not seek a special explanation for each of the features, but we can fit them together in a form of syndrome. The reason for the high susceptibility of BAME people to serious and fatal Covid-19 can be explained simply on the basis of vitamin D deficiency. The same for the obese, the poor, the long-term ill, and the socially deprived.

The important thing is that the simple factor of vitamin D deficiency can be reversed immediately, "at a stroke". It has not been achieved because of the failure of our medical and political leaders to be aware of William of Ockham and his understanding of scientific thinking. 

If vitamin D deficiency were to be regarded as the cause of all these features, they would all fit inside the vitamin D deficiency circle, but most of the areas of the circles lie outside the vitamin D deficiency circle. Vitamin D deficiency is not a "cause"; it is a common and easily reversed susceptibility factor.

But what about Covid-19? Why is it absent from this Venn diagram? The reality is that is not its own risk indicator, but it is at present all around us, and this is shown in the figure below.

In this Figure I have tried to make the complexity simple, but perhaps too simple. It illustrates the co-morbidities that are a feature of Covid-19 illness. It is perhaps not surprising that the sun as vitamin D is at the centre. The model has a great similarity to the model of the solar system as imagined by Copernicus.

In trying to be clear I have diminished the extent of vitamin D deficiency. In the final figure, below, I illustrate fatal Covid-19, showing that virtually all patients are deficient in vitamin D. We still see the impact of co-morbidities that make the patient more likely to die. 

Each susceptibility factor has its own cause, but in respect of illness and death form Covid-19 they share the common susceptibility factor of vitamin D deficiency. And of course many people have Covid-19 without having any of characteristics of high risk.

It is much easier to correct vitamin D deficiency than all the individual factors. Why it has not been done is a failure of medical-scientific leadership.

Vitamin D deficiency and Covid-19 : its vital importance in a world pandemic

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