Wednesday, 14 April 2021

Covid-19 & Vitamin D: One year after the onset

We have experienced a year of the Covid-19 pandemic. and now in the UK it is looking very different.

Figure 1. UK: Covid-19 deaths each day, from March 20th 2020


On March 10th 2020 the WHO declared a pandemic of Covid-19. It was on March 20th that the pandemic became real in the UK. Deaths had risen to about 50 per day. On March 23rd there had been a total of 258 deaths, and something had to be done. That something was "lockdown", intended to reduce spread of the respiratory virus. Face masks must be worn in public places, and there was to be social distancing with a minimum of two metres between individuals. People could not visit each other's houses. The residents of homes for the elderly or seriously disabled could not be visited by their families. Public events such as concerts and worship were stopped. Universities were closed and then schools. Holidays were cancelled. Elective admissions to hospital for surgery were cancelled. Many workplaces were closed and air travel virtually came to an end. Public transport was  strongly discouraged and the roads were very quiet.

These were physical methods to try to reduce transmission, but respiratory viruses are notoriously difficult to control. Deaths increased to almost 1,000 per day during the following month. We had no natural immunity and our vitamin D reserves were at the lowest part of the annual cycle. It is much easier to control micro-organisms that are transmitted in contaminated water or food, or contagious diseases that are transmitted by direct contact (touch). Air transmission is not visible and not easily controlled. 

The introduction of lockdown was not based on evidence as it had never been attempted previously, at least not on a large scale. It seemed to be sensible, given the very limited understanding by the government of the nature of the pandemic. We subsequently entered the summer recess of Covid-19 illness and death during the "vitamin D immunity season". Later in the year when we moved into the "vitamin D deficiency season", further lockdown measures were introduced. 

It is easy to say that the deaths would have been even higher without lockdown, but we must remember that the UK had about the highest death rate from Covid-19 at that time. Since then the UK has been overtaken by nine European nations with higher numbers of deaths per million.

Figure 2. Covid-19 deaths per million, in European and American nations

Figure 2 illustrates the 38 nations of the world with more that 1,000 Covid-19 deaths per million. Most are in Europe, with 9 in the Americas. Some of the nations in Europe are very small, Gibraltar, San Marino, and Andorra in particular.

From late April the daily deaths declined in the UK and other northern hemisphere nations, and this coincided with increasing sun energy each day at sea level, and therefore increasing vitamin D production. It can be said that the weather was warmer but humankind is isothermal. We maintain constant body temperature but the average blood level of vitamin D is much greater in the summer than in the winter. The winter–summer pattern of illness is the same in all temperate zone countries, no matter what the ambient temperature. Vitamin D activates defensive immunity and so it is to be expected that the number of deaths from respiratory infections will reduce during the summer, as happens every year. There are in practice two seasons to the year: the vitamin D immunity season, and the vitamin D deficiency season. This is very obvious in Figure 3, which illustrates the effect of the sun and vitamin D production. 

Figure 3. UK: Covid-19 deaths each day, from March 20th 2020



The decline in case and death numbers continued into the summer as vitamin D production increased, and blood levels of 25(OH)D, calcifediol, the reserve supply also increased. And then of course, as reserves fell when we entered the vitamin D deficiency season, deaths form Covid-19 increased again.

It is interesting to note that we were warned early in 2020 that it would become so much worse in the autumn as there would be an additive effect of the influenza virus. This showed a fundamental lack of medical education, a phenomenon that I learned when I was at Manchester University in 1964. Observation (that important scientific process that in 2020 was rejected in respect of vitamin D) demonstrated that simultaneous virus infections generally do not occur. A virus is greedy: it does not want to share the infection with a competitor. Covid-19 had an advantage in 2020 in that the human host had not encountered it previously and therefore humankind had no immunity. Covid-19 rapidly established respiratory infection, and in the usual way it programmed its infected cells to produce Interferon. This prevented infection by other viruses. 

And that is what happened: during the autumn of 2020 the usual  winter viruses failed to appear. There was just Covid-19. 

The increased case and death rate up to the end of 2020 was as expected, but in January there was a sudden peak that has not really been explained. It is shown in Figure 3. Although mutations appear, we were not told of a mutation that would create up to 2,000 deaths per day in January 2021. Many mutations have been described but this is inevitable and there does not seem to have been a rogue mutation. Of course natural immunity optimised by vitamin D would provide defence against all mutations. The reason for the January peak, "the third wave", remains unexplained. 

This phenemenon was seen in some other European countries, but not in all. It was obvious in Ireland and Spain. This peak, or wave, settled rapidly at the end of January in the UK and these other countries. 

Figure 4. Ireland: Covid -19 deaths 2021, showing the January peak (data incomplete).



Figure 5. Spain: Covid -19 deaths 2021, showing the January peak (data incomplete).

Andalucía in Spain is particular interesting. When the second wave of Covid-19 was very active in October and November, the regional government introduced in November a policy of providing vitamin D in the activated form calcifediol, 25(OH)D, to elderly people. This policy was followed by a dramatic reduction of deaths during December, which I referred to as the "Andalucía miracle" whether the result of intervention by vitamin D or by God. At the end of December vaccine provision was added to the vitamin D initiative. 

Figure 6. Andalucía: Covid -19 deaths 2020-21, showing the three peaks.

But as we can seen in Figure 6, in January the decrease in deaths was suddenly reversed. There was a rapid increase in cases, hospital admission, and deaths from Covid-19. A third peak was reached and then a rapid decline, that is very obvious from daily numbers.

After one of the highest Covid-19 death rates in the world, the UK now finds itself in an excellent position.  The UK now appears to be close to the end of the pandemic. 



Figure 7. UK: Covid -19 cases per day March-April 2020 & 2021

The very low number of death each day now, in early April 2021, is very different what was happening this time a year ago. The trajectory is downwards in 2021.

Figure 8. UK: Covid -19 deaths each day March-April, 2020 & 2021


The difference from 2020 to 2021 is the result of a high level of herd immunity within the nation. It is not that the virus has "gone away", as viruses do not go away. The clinical effects of the virus might "go away" but this is because of herd immunity. It has always been the same.

A recent report (March 30th 2021) from the Office of National Statistics (ONS) informs us that more than half the population have antibodies to Covid-19. How many of these had an illness and how many had received the vaccine were not disclosed. About half the population had received a vaccine during the very extensive vaccination programme, and the number taking vitamin D had increased greatly, but without any national counting. It is suggested that vitamin D consumption has increased by a factor of perhaps 13. On the day of the ONS report Morrison's Supermarket had sold out and further supplies were only on order.

There continues with no official mention of vitamin D. There has been the accumulation of a great deal of knowledge concerning the extent of vitamin D deficiency and the great disadvantage of this when ill with Covid-19, with high risk of critical illness or death. But clinical medicine in the UK remains silent. An as yet unpublished study from Tameside, UK, indicates that 70% of individual doctors would take, prescribe, and advise vitamin D, but this was part of a large grass-roots movement, not officially sanctioned and not measured.

There has been a reduction on the number of Covid-19 cases and deaths in many European countries, but none as dramatic as the UK. The UK has a higher rate of vaccinations than other countries. I display in the figures the deaths per day, but the "cases" (less easily defined) show the same patterns but with larger numbers. The nations are not complete but those that have interested me during the past year.


Figure 9. Switzerland: Covid -19 deaths 2021, showing the January peak 
and subsequent decline


Figure 10. Austria: Covid -19 deaths 2021, showing the January peak 
and subsequent but incomplete decline

Figure 11. Germany: Covid -19 deaths 2021, showing the January peak 
and subsequent decline


Figure 12. Netherlands: Covid -19 deaths 2021, showing the January peak 
and subsequent decline


However the decline is not yet apparent in some other European countries. 


Figure 13. France: Covid -19 deaths 2021 (data incomplete)


Figure 14. Belgium: Covid -19 deaths 2021 



Figure 15. Italy: Covid -19 deaths 2021 


Figure 16. Sweden: Covid -19 deaths 2021 (data incomplete, numbers are very low)




Figure 17. Poland: Covid -19 deaths 2021 

These are examples of the experience of several European countries but not all. Some are approaching the end of the pandemic, and it is hoped that the others will follow shortly. 

It can be anticipated that during May 2021, as in May 2020, cases and death numbers will fall thought the vitamin D production season. If there is widespread immunity, the increase in the winter will be minimal.

Deaths have also been falling in North America.

Figure 18, Canada: Covid -19 deaths 2021 

Figure 19. USA: Covid -19 deaths 2021 

What has been happening in tropical countries will be the subject of  future post.




























Friday, 19 March 2021

Covid-19 & Vitamin D : do not sit on the fence when there is blood on the floor

Covid-19 & Vitamin D

No sitting on the fence: there is blood on the floor!

2008. I just managed to get out of the way !

When the pandemic of Covid-19 appeared a year ago there was a great deal of evidence predicting that our known widespread deficiency of vitamin D would cause a serious problem. It would produce a problem of sub-optimal immunity, and thus a high risk of death from critical or fatal infection. And this is what happened. As expected the deaths occurred in excess in communities known to have a high prevalence of vitamin D deficiency: the ethnic Black African and Asian (BAME), the obese, and the elderly in particular. 

The early missed opportunity

There could have been community-based blood testing to detect individuals with vitamin D deficiency, but it did not happen and vitamin D testing was discouraged by public health bodies. Vitamin D could have been given to all, on the basis that in a single dose of 100,000 units it would have corrected deficiency of those deficient and would have done no harm to those not deficient. Blood testing within the following three months would identify the need to continue with a supplement. Alternatively a vitamin D supplement dose of 20,000 units each week or 3,000 units each day would have been appropriate and perfectly safe.

But official correction of vitamin D deficiency did not happen. We had to wait for more than 100,000 deaths before vaccines became available. 

We have had a large number of "scientists" who have dominated the political agenda. There have been mathematicians, statisticians, epidemiologists, virologists, nutritionalists, sociologists, the chief medical officer and the chief scientists, both of who have enjoyed an academic career. Some of them have mentioned vitamin D with a remarkable lack of enthusiasm, in complete contrast to their embrace of vaccines.

The dead hand of NICE

The reason for the denial of use of vitamin D has never been clear. The large amount of evidence from the forty years preceding the pandemic made little difference to official advice. Reference was always made to the reports by NICE, the National Institute for Health and Care Excellence. 

The reason why the correction of a vitamin deficiency had to be referred to NICE is difficult to understand, as it would be an automatic clinical duty to correct a vitamin or hormone deficiency, be it vitamin D, vitamin C, vitamin B12, the prescription of insulin or thyroxine and so on. But NICE has somehow been given the responsibility for the correction of vitamin D deficiency, and a series of its reports failed to approve the use of vitamin D, but always failing to acknowledge deficiency. 

NICE informed the nation of a lack of evidence and demanded randomised controlled clinical trials (RCTs). 

A report from NICE on June 29th told us that:

"There is no evidence to support taking vitamin D supplements to specifically prevent or treat Covid-19" 

This avoided any mention of the fact that research points to the majority of the population being deficient of vitamin D. If NICE is supposed to help doctors in their treatment of ill patients, it failed miserably to do so. The response has been very far from Excellent.

Once again more evidence, randomised controls were demanded. The result of the first RCT, from Córdoba, Spain, appeared on September 3rd. The response of NICE was that the (very positive) result should have no influence on the way in which doctors treat patients (with Covid-19 pneumonia). 

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

On December 18th NICE published a joint report with SACN (Scientific Advisory Group on Nutrition) and PHE (Public Health England) in which Sir Paul Chrisp (director of the centre for guidelines at NICE) stated:


"While there is insufficient evidence to recommend vitamin D for the prevention or treatment of Covid-19 at this time, we encourage people to follow government advice on taking the supplement thought the autumn and winter period."


The reason for this change of direction is that the Health Secretary Matt Hancock had stepped outside NICE advice. He had become aware of the importance of vitamin D in the prevention of Covid-19 and he issued a directive that all elderly people should be issued with a vitamin D supplement. NICE could not disagree with a minister and so it had to use double-speak, taking advantage of the many synonyms in the English language. To "recommend" and to "encourage" are verbs without an obvious difference in meaning.


NICE cannot be regarded as having the best interests of the sick and dying at heart.


NICE denies responsibility


The full NICE report that included the first RCT of vitamin D as 25(OH)D or calcifediol, its natural rapidly-acting form, appeared in December 2020. Although the earlier report carried its "recommendation" that doctors should not have their treatment of patients be influenced by this first RCT, the full report carried an interesting disclaimer:


"The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian."


NICE and other documents carried generally very negative reviews of vitamin D, and denied the role of vitamin D in defensive immunity, ignoring the accumulated evidence. It has been the same in other commentaries, at best balanced, always stating a need for more research, but when is there not a need for more research? Does science ever stand still? Is a balanced view of help to a doctor caring for the sick and dying?

There was undue publicity given to two barely comprehensible papers that were pre-published in January 2021. 



One was from Canada, the other was from Greece.They stated that there was no evidence of benefit from vitamin D. They were of very poor quality and added nothing, but headlines were dramatic.

The very positive result of the second controlled trial, from Barcelona, has received no official comment. It was "rejected" by Professor Adrian Martineau, a member of NICE. Still a demand for more RCTs that would inevitably necessitate more human sacrifice.

No evidence?

The common suggestion of "no evidence" is absurd. Let us assume that there had been a murder and that ten detectives were sent out to investigate. On the following day eight detective returned to HQ and reported that they had all found incriminating evidence that pointed to one man who appeared to be guilty of the crime. On the following day the other two detectives returned and stated that there was no evidence of the accused man being responsible for the crime. Would their finding of "no evidence", or rather their failure to find evidence, invalidate the evidence found by the others? 

Of course there is ample evidence to suggest that vitamin D would be of benefit in Covid-19, but most people seem to be unaware of it.

A view from an ivory tower

A recent editorial in the British Medical Journal on the subject of Covid-19 and vitamin D was written by two nutritionalists and a professor of primary care diabetes, the latter having previously written what I can only describe as a non-medical appraisal of the high Covid-19 death rate of BAME people without once mentioning vitamin D! Even though it was in the British Medical Journal, the editorial was of no practical value to practising doctors. There was no practical advice as to how to reduce the deaths from Covid-19 in any ethnic groups. 

"Existing evidence supports a compelling case for further research." Let's just kick the can down the road while more people die. 

The authors of this editorial, like perhaps all commentators on the subject of Covid-19 and vitamin D, did not have responsibility for patients admitted to hospital with Covid-19 pneumonia. Whether or not they themselves took vitamin D was not declared. They gave no advice as to whether such patients should be treated with calcifediol as in the Córdoba protocol, but they gave ample discouragement. 

Advisors to government but not to doctors

Government advisors on the Covid-19 pandemic live in offices, ivory towers. They do not live in the emergency areas of hospitals. They never see blood on the floor. They do not know what it is like to make life or death decisions. They do not understand the pressure to do the very best to help an individual patient. But they inhibit rather than help those front-line doctors who need support.


A report in December 2020 from an all-party committee of parliament also managed to find no place for vitamin D. The ignorance is wide-spread.


MD in Private Eye is not one to follow central directives, but his first and very brief mention of vitamin D during the pandemic informed us that "The jury is still out". He followed this by a plea to be given vitamin D should he develop Covid-19 (Eye 1452). If the jury is still out it indicates that evidence has been withheld or that the judge has failed to give direction. However MD showed some of the pragmatism that doctors require, but in advice to others he followed the official line: he clearly sat on the fence of indecision.




Clinical decisions

For a clinical doctor to make a decision to prescribe vitamin D / calcifediol for a patient with Covid-19 pneumonia is actually very straightforward and I am sure that non-one would argue with it. Surely a doctor would not regard herself or himself of being at risk of charges of negligence or other disciplinary charge should vitamin D be prescribed. But doctors are frightened of giving vitamin D. 

Decision-making is encapsulated in Pascal's Wager, that I have described previously.

To give vitamin D as calcifediol to a patient admitted to hospital with Covid-19 pneumonia would have a high probability (about 70%, but not certainty) of reducing the need for ICU transfer and death, and it would have a cost of about £10, with no side-effects. 
To deny the patient calcifediol would correspondingly fail to reduce the need for ICU transfer and failed to reduce the number of deaths.

What could be a more simple decision than this? Obviously vitamin D / calcifediol must be given, that is if the objective of the doctor is to minimise illness and reduce the chance of the death of a patient. Can anyone provide a reason why a patient critically ill with Covid-19 pneumonia should not be treated with calcifediol, or why anyone deficient in vitamin D not have the deficiency corrected?

Why is calcifediol not being given to patients with Covid-19 pneumonia in the UK? Because NICE says that it should not be given. Doctors and their managers are frightened of not obeying NICE. Can NICE justify it actions in denying vitamin D to those are dying?

Legal claims

It has just emerged that there is a now a group legal claim against the UK government as to why not more was done to protect the population, so as to keep the number of deaths well below 125,000. 



The legal claim is bound to uncover the fact that vitamin D and its active metabolite calcifediol (25(OH)D) had been withheld, when all the evidence pointed to it being very helpful and life-saving. 83,000 people have died since the result of the Córdoba study became available on September 3rd, and a significant number of these deaths were therefore avoidable. The question in a court of law would be, "Why was vitamin D not given?" The government will point out that it was only following the advice given by NICE. NICE will defend itself by pointing out its disclaimer, which I will repeat as it is vitally important in its defence. The disclaimer must have been written by lawyers.

"The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian."


Who will be held guilty?

This declaration clearly shifts the blame for the deaths of patients to hospital doctors, for following its repeated advice!

This is a disgrace.

The responses of doctors and their professional organisations, and the General Medical Council will be interesting.





 










Monday, 8 March 2021

Covid-19 & Vitamin D – Haredi, BAME, Obese, Elderly at risk



Covid-19 & Vitamin D – medical ignorance continues and we are failing to help the vulnerable

Haredi Jewish community

BAME, Obesity, Haredi Jews, Elderly: 

more excess deaths 

There is much denial of the importance of vitamin D in human health, and especially during the present pandemic of Covid-19. So much has been learned, or at least should have been learned from recent experience, and a pandemic such as this brings a great deal of information to widespread attention. Many features of the health of the population come together to produce a picture that is much more clear than in the past. The life and death occurrences become understandable but only if we base them on the scientific progress that has occurred during the past forty years. However, knowledge of this appears to have been missed by most doctors, and the key points remain unclear to the majority.

I have explained previously that vitamin D first appeared two billion years ago. Early sea life, plankton, was able to produce the oil 7-dehydrocholesterol, which UV from the sun converts into vitamin D. 500 million years ago, the more complex life-forms that had evolved fed on the plankton, and it came to pass that they consumed vitamin D which was able to activate the intracellular protein that we now know as Vitamin D Receptor (VDR). This led to the very complex but brilliantly effective cascade of defensive immunity. How this all happened during evolution is far from clear, but it did happen.

Most people know about rickets, "bendy bones" that cause skeletal deformities, widespread during the late industrial revolution. It seems to have been forgotten that this was the result of atmospheric pollution blocking the penetration of sunlight to ground level. 

Atmospheric pollution in England 1950

Atmospheric pollution in India 2020

Deficiency of what later became identified as vitamin D was the reason for the development of rickets, and following its isolation initially from fish oil, rickets could easily be treated. 



Skeletal deformity typical of rickets


When vitamin D was first isolated, it could not be measured by chemical means, but it was measured by its biological activity. One unit of vitamin D was defined as the daily requirement of a 10g immature mouse. It appears that this is generally not known, but to scale up from this the daily requirement for a 60kg human being would be 6,000 units per day, and for a 120kg obese person 12,000 units per day. In that adult humans of these weights are "mature", it would be sensible to take halves, 3,000 units per day for normal weight and 6,000 units per day for the obese. 

SACN, the UK scientific advisory committee for nutrition, appears to be unaware of the pivotal role of vitamin D in defensive immunity and tells us that all we need is 400 units per day. This is the equivalent to a mouse taking 0.07 units per day, but it appears to be adequate to reverse rickets in a human child. It is the importance of the immune function of vitamin D that, during the pandemic, has become crystal clear to those who are not asleep.

"Sunshine Clinic" 1961

By the middle of the 20th century the use of Cod Liver Oil and also "sunshine clinics" for children led to rickets becoming extremely rare. With the controls of atmosphere pollution the use of fish oils declined and sunshine clinics were closed. During the second half of the 20th century it became possible for vitamin D in the blood to be measured by physical-chemical means, initially as a research tool and then in standard clinical practice.

It became clear that although rickets was rare, vitamin D deficiency as defined by a blood test was common, especially in certain groups of the population. The importance of this has not been clear until recently and it has been necessary to refine the definition of vitamin D deficiency.


Black African and Asian Minority Ethnic people (BAME)

The second half of the 20th century in the UK had seen immigration of many people from the Commonwealth, especially from India, Pakistan, several nations of Africa, and the islands in the Caribbean. During the 1960s and thereafter cases of rickets appeared in the children of these immigrants, and also tuberculosis among the adults. Later, it was noticed that the incidences of coronary heart disease and diabetes were also greater. Underlying this was the development of vitamin D deficiency with movement from the tropics to more than 50 degrees north of the equator.

The extent and severity of vitamin D deficiency can be seen in the bar chart, each vertical black line representing one of the 1754 ethnic South Asian subjects who I investigated about 20 years ago. 



Very few had a blood vitamin D level in the "safe" range above the red line, greater than 30ng/ml (75nmol/L), and only 4 had a blood level in the ideal range (40–60ng/ml (100–150nmol/L). The median average was 9ng/ml (22.5nmol/L). More than half were seriously deficient. In a comparable group of 865 ethnic white people, the median average was 18ng/ml (45nmol/L).

Vitamin D deficiency is very common in ethnic South Asian people and it is still not being appreciated. Public health has much to learn.

The Covid-19 pandemic has seen a particularly high mortality rate among BAME people, those of Black African and Asian ethnicity. This was serious and brought about three "detailed" investigations, but not detailed enough. The three reports concluded that social deprivation and racism were the reason for the excess deaths. The medically well-known and easily reversible deficiency of vitamin D was not considered. Medical leaders remained silent and an important opportunity to minimise deaths was missed.

Comment on the Report by Dame Doreen Lawrence


December 2020 saw the publication of an Interim Report of the UK All Party Parliamentary Group on Coronavirus. In its 90 pages there was not a single mention of vitamin D, but this is perhaps not surprising as parliament is noted for its lack of scientific understanding. The report indicated that compared to the national average, there has been a four times higher Covid-19 mortality of ethnic Black Africans and three times higher for ethnic Asians. No explanation was offered.

Racism and socio-economic disadvantage of BAME people were also the conclusion of a BBC television programme on March 2nd 2021. Vitamin D was mentioned, only to be rapidly dismissed. It was as though fifty years of clinical medicine had been forgotten, and forty years of biomedical research had never happened. In fact it appeared that there had been a complete failure to learn from medical experience during the past year.   

BBC television programme on March 2nd that also missed the opportunity

It was acknowledged that not just the poor BAME experienced excess deaths from Covid-19, but also BAME doctors. The vitally important fact that of 25 working doctors who died form Covid-19, 24 were BAME was not mentioned. The 24 deaths were in vain and lessons were not learned.

"It could not be skin colour that caused excess deaths because Black people in Africa have very low death rates". 

An unbelievably ridiculous deduction, completely ignoring the interaction between genetics and environment (sickle cell disease is another example of this, advantageous in the tropics where there is malaria, but a great disadvantage when living in the UK). 

It also ignores the effect of transmigration, and the evolutionary selection of white-skinned people to live distant from the equator, where sunlight intensity is low. For this to come from a doctor shows staggering ignorance, of which those responsible for medical education should be ashamed. The truth is that BAME people have moved from the tropics to a country that is closer to the North Pole than to the Equator. The diminution of sun exposure and vitamin D production is responsible for the excess deaths, the melanin-rich skin blocking UV and making vitamin D production very inefficient. 

The vitamin D deficiency of BAME people was ignored yet again. It is the most if not the only biologically plausible explanation of the excess deaths, not only from Covid-19 but from several others causes of early death. At a time of crisis with more than 120,000 deaths, it would be sensible to correct vitamin D deficiency immediately rather than waiting to correct low income, low quality housing, inner city living, and racism in all walks of life, none of which could be achieved before the premature deaths of many more people.

It would have been so simple to correct widespread vitamin deficiency in the BAME groups but it did not happen. Was this the result of ignorance by medical scientific advisors, or was it wilful ignoring? Could the ignoring be called racism?


Obesity and vaccine failure

It has been reported from research in Rome that in the obese the vaccines produce only half the antibody response that would be expected. The reasons for this were explored but without any consideration of vitamin D.


This headline is not really surprising. An ideal blood level of vitamin D as 25(OH)D, calcifediol, is essential for the immune response that is necessary for the success of vaccination. It was predictable that the success of vaccination would be diminished in the obese. This is one of the groups with a high risk of death from Covid-19.

It is well-established that the obese have a high incidence of vitamin D deficiency. When vitamin D as cholecalciferol is produced in the skin or taken by mouth, it is taken to the liver, where the slow conversion to 25(OH)D calcifediol takes place. This is much slower in the obese and much vitamin D is deposited in fat cells. Following exposure to UV, the important 25(OH)D appears in the blood only slowly and inadequately in the obese. Strictly speaking, the low blood levels of vitamin D in the obese is an expression of reduced bio-availability rather than absolute deficiency, much of the vitamin D being in the fat cells and unavailable to the blood and for metabolic use.

It has also been observed in the recent past that vaccination against hepatitis B virus has a high failure rate in the presence of vitamin D deficiency.

It would have been sensible to use vitamin D and vaccination together, vitamin D being given perhaps a month before the vaccine.

Center for Disease Control, USA

Reducing obesity is a good thing but experience tells us that it is slow and difficult. The neglect of the immediate correction of vitamin D deficiency in the obese has led to many avoidable deaths.


Headline from March 4th 2021. It should been in 2020.

The obese might be given priority for vaccines, but had they been given priority for vitamin D a year ago, many deaths would have been avoided.


Haredi Jews

This small group of UK citizens has had a particularly high death rate from Covid-19. The group comprises only 260,000 people who live in a small number of close-knit communities with little integration with general society. Although unmistakable from their dress, they are mainly unseen within the nation and so their high Covid-19 death rate has not been noticed. There are ten times more Moslem people in the UK and their high death rate is much more obvious.

Recently headlines have appeared in the UK from the BBC and in the Guardian.





The same has been reported concerning the ultra-orthodox Jews in Israel. 

The Times of Israel, March 4th 2021


Observation of the Haredi Jews in the UK will lead to a suspicion, or perhaps a glaringly obvious certainty that they are vitamin D deficient. They dress with traditional extreme modesty, which together with the extensive facial hair of the men and large-brimmed hats would minimise exposure of the skin to the sun, even in the summer. The women expose only their hands and face. 

And so it is. Investigation in Israel has confirmed the suspicion of vitamin D deficiency among the ultra-orthodox

A report from Israel in 2001 concerned the investigation of Jewish mothers, blood for vitamin D being analysed within three days following child-birth. Some of the women had been taking a vitamin D supplement during pregnancy, but just in the minimal dose of 400 units daily. For the purpose of analysis the mothers were divided into the orthodox and the non-orthodox. 

Israel is a land with plenty of sunlight, but being outside the tropics it has a winter and a summer. However vitamin D deficiency was disturbingly common. We need to remember that experience during the pandemic of Covid-19 has demonstrated that a blood level above 30ng/ml (75nmol/L) is safe with minimal risk of critical or fatal disease, and within the range of 40–60ng/ml (100–150nmol/L) is ideal. But in the Israel study the mothers were classified as "deficient" if the level was less than 5ng/ml, and "insufficient" if less than 10ng/ml. These levels were very low, and less than 5ng/ml could give rise to rickets in the offspring. Less than 10ng/ml (25nmol/L) is generally regarded as serious vitamin D deficiency.

The results of the study are shown in the bar-chart.




We can 
see that one quarter of the non-orthodox mothers had blood vitamin D levels less than 10ng/ml, fewer in those who had received a vitamin D supplement during pregnancy. We were not informed of the blood levels achieved by taking the supplement.

Half of the orthodox Jewish mothers had blood vitamin D levels less than 10ng/ml. This was helped but incompletely by the vitamin D supplement, 400 units daily.


A summer day in Israel

Here we see a photograph of two orthodox Haredi couples in Israel. This was taken at midday in mid-summer, as indicated by the very small shadows. The men's faces are shaded by their hat brims and their hands are in their pockets. It can be appreciated why the blood levels of vitamin D in the orthodox Jews are very low, and that of the mothers did not show any increase in the summer, whereas there was an increase in the non-orthodox.  

With the prevalence and severity of vitamin D in Haredi people in Israel, we can only expect the deficiency to be the same or even worse in those living in the UK. The research that I have demonstrated was in Israel twenty years ago. Why does it appear to be unknown? Why has the susceptibility of the Haredi people in the UK been officially "explained" by socio-economic factors, even when this has been eliminated in comparison with Christian men in London.

                              

Knowing of the importance of vitamin D in defensive immunity and the susceptibility of those deficient to critical and fatal Covid-19, it would have been very simple to investigate  deficiency of vitamin D among the Haredi groups in the UK. But this simple study was not undertaken. Medical scientists (other than those developing vaccines) are asleep and so the expected vitamin D deficiency was never confirmed and of course never corrected.

We can hardly expect the Haredi Jews to change their traditional dress and lifestyle, but to have corrected vitamin D deficiency would have prevented many deaths. Our failure to do so is the result of medical ignorance, that I hope experience during the Covid-19 pandemic will correct.


The elderly

Headline, May 14th 2020

We have watched the large number of Covid-19 deaths among the elderly, whist knowing of the importance of vitamin D in defensive immunity, and also knowing of the inability of the skin of the elderly to produce vitamin D. This was first demonstrated in 1980. 

The skin produces the oil 7-dehydrocholesterol (7-DHC) and  UV from the sun acts on it and converts it into vitamin D. But the thin dry skin of the elderly produces only small amounts of 7-DHC and therefore vitamin D production in the skin is inadequate all the year round. Deficiency is inevitable and all elderly people require a supplement by mouth; the sun will not help.

Vitamin D production in the skin, young and elderly

But what has been done? There has been advice for the elderly to take vitamin D 400 units daily, the requirement to prevent rickets in a child, but not to restore blood levels that will optimise defensive immunity at the time of serious infection. 


Four neglected groups

We have seen that as a nation we have ignored the medical scientific knowledge of the past forty years, and we have neglected the welfare of four important groups of our population, the obese, those with ethnic melanin-rich skin that is inefficient at producing vitamin D when living at 54 degrees north of the equator, the Haredi Jews who have minimal exposure to the sun all the year round, and our elderly who are unable to produce vitamin D.

Vaccines are now being used extensively to provide immunological protection of the population, but there are concerns about the protective value of vaccines against a wide range of mutations of Covid-19. These fears might be unfounded but there is inevitably uncertainty about the future. 

However it should be realised that vaccine success depends on the optimal immune process that is determined by adequate vitamin D. It must also be remembered that optimal immunity is successful against all viruses and all mutations.

It is not a question of vitamin D or vaccines, it is vitamin D and vaccines. But vitamin D should be given first, and that should have been one year ago when the pandemic emerged.

It is important to learn, not just from the past forty years of research into vitamin D and defensive immunity, but especially from the great experience generated during the pandemic of Covid-19. But we must be prepared to learn and not deny new knowledge.  




https://www.ypdbooks.com/2147-vitamin-d-deficiency-and-covid-19-its-central-role-in-a-world-pandemic-YPD02419.html











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. 


Randomisation

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.


Deaths

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.


Accountability

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.

davidgrimes1@mac.com