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 ng.ml.

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. 


Adjustments: 

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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9 comments:

  1. Trying to understand the figures
    I think all the smking data means is
    both colums add up to 100% - both columns are similar in that 89% smoked and 11% didn't - hence there was no difference in terms of smoking a\nd covid.
    But this leads to the discovery that the sample is heavily dominated by smokers - 90% of the 348,000 people
    As far as I can see, the study presents data quite simply for all factors - but only provides a confusing paragraph for ethnicity and Vit D status. The illustration of VitD data seems absent. The paper does say - Table 1 presents study participants by presence or absence of positive COVID-19 test result. Median 25(OH)D concentration measured at recruitment was lower in patients who subsequently had confirmed COVID-19 infection (28.7 (IQR 10.0–43.8) nmol/L) than other participants (32.7 (IQR 10.0–47.2) nmol/L). It predicted COVID-19 infection univariably (Table 2; OR = 0.99, 95% CI 0.99–0.999, p = 0.013), but not after adjustment for covariates (OR = 1.00; 95% CI = 0.998–1.01; p = 0.208)............So low VitD was associated with Covid-19 infection. And BAME's generally have lower VitD status - however the authors have managed to create some science which states these two factors are not linked, maybe by introducing social factors which amy noot actually be so significant. The authors don't present the VitD status of each ethnic group but create subgroups not linked to ethnic status. SOmething very odd going on here. Dominated by smokers, and little info given as to exact VitD status of the ethnic groups - which would be the main point of the analysis. I am not a scientist - hope this is of interest.

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    1. Hi Andrew – I think that you, like me, gradually realise the absurdity of the paper, that 90% of the participants in the study appear to smoke. Shurly shum mishtake!! Something odd going on. But a fresh look at the data tells us that vitamin D deficiency is of central importance in serious or fatal Covid-19. And it could easily be corrected.

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  2. Thank you for highlighting the inconsistencies. We also raised the issue about the timing of the Vitamin D and the Covid-19 pandemic. Many of these patients may have had treatment since the levels of vitamin D were measured over a decade ago. May be a letter to the editor and the analysis you have done so elegantly needs to be made public.

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    1. Thanks Ed. I wll try to bring this to the attention of the journal publisher. The paper makes a mockery of peer review.

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  3. Very clearly and plausibly explained! Just great, David!! you have to send it to David Davis, then he can explain it to Boris Johnson and the COVID-19 Taskforce! Best regards from Switzerland! Stefan

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    1. Thanks Stefan. Use this this as much as possible in Switzerland. Use the German translation.

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  4. Hastie's study seems almost designed to come to the conclusion that vitamin D is not associated with Covid-19. She writes in a response to criticism that it's important to compensate for "factors known to strongly influence vitamin D": https://link.springer.com/article/10.1007%2Fs00394-020-02430-x
    But confounding factors should be risk factors for Covid-19, not for vitamin D.

    When she compensates for all these factors contributing to vitamin D deficiency, then she needs many Cov-19 cases to reach a stastistic significant result. Bu she has only 447 covid-19-positives in her study.

    Li did a similar study, also on data from UK Biobank, and found significant association after compensating for confounding factors. Li et al writes that they found this relation because they had much more data than Hastie. http://www.aginganddisease.org/EN/10.14336/AD.2020.1108

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  5. Brilliant once again, DG! William of Ockam must be up there cheering

    Edward de Bono said “The need to be right all the time is the biggest bar to new ideas. It is better to have enough ideas for some of them to be wrong than to be always right by having no ideas at all.”

    However it surely requires a special form of planktonic cerebral dysplasia to insist on being wrong all the time*. Of course Billindagated money would help.

    (*A rather sloppy metaphor that, David A; plankton produce vitamin D, as any cod-fearing monkfish out of water would know... Ed)

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