Vitamin D – evidence neglected during the Covid-19 pandemic

The neglected importance of natural immunity and vitamin D during the pandemic of Covid-19

What is natural immunity?

A good starting point is to remember the HG Wells story “War of the Worlds”, published in 1897.  Technologically advanced life forms from Mars invaded Earth, and after leaving a trail of destruction they suddenly all died. The cause of death was considered to be “the bacillus”, an infection. The “germ theory” of the causation of disease was a new medical-scientific concept at the time. The invaders from Mars died because they had no immunity to protect them against the Earth's bacteria that caused fatal infection.

Humankind has inherited natural immunity, which evolved during the 3,500 million years since life on Earth began. It was present in a simple form in early life-forms, including plankton that emerged 1,500 million years ago. 

It is interesting that plankton were, and still are, able to synthesise the oil 7-dehydrocholesterol (7-DHC), which UV from the Sun converts into cholecalciferol. In the early 20th century this became known as vitamin D.

Figure 1. UV from the sun acts on 7-DHC

The hormone cholecalciferol is a vital component of the escalation of defensive immunity in humankind and other advanced land animals, but it was of no value to the plankton that initially produced it. Their immunity had not evolved to require vitamin D / cholecalciferol. The conversion of 7-DHC into cholcalciferol within plankton absorbed damaging energy of UV radiation close to the surface of the ocean and it thus acted as a "sunscreen" to protect the plankton. 

Much later (420 million years ago), fish needed vitamin D for their boney skeleton and advanced immunity, but being covered in scales or thick skin, and living at depths, meant that they could not poduce it from the Sun. They therefore obtain their vitamin D from consumption of plankton in the aquatic foord chain. When we eat fish, the vitamin D that we take in is derived from plankton.

Advanced defensive immunity appeared as a very sopisticated evolutionary development in the complex life-forms that  appeared "suddenly" in the Cambrian era, about 500 million years ago. 

Bacteria and viruses had been present since early evolution, before the critical  appearance of plankton. However further evolution of complex animal life could not advance until defensive immunity against bacterial and virus infection had developed. Any new life form of a more advanced nature would have died in the way of the Martian invaders in the story by HG Wells. The development of sophisticated defensive immunity must have been among the most critical steps in evolution.

The components of immunity

It is as well to know just a little of the highly complex cascade of immunity. Only 10% of the cells of our body are human. 90% are tiny micro-organisms, and they must be kept under control. When we die, they take over and we decompose, but while we are alive our defensive immunity is of vital importance.

There are two major components of immunity, antibodies in the circulation, and the much more complex but the less easy to measure tissue immunity. Both are activated by signals of invasion of our body tissues by micro-organisms.

The genes of the cells of immunity must themselves be activated so as to escalate defensive cell processes and proteins. The key to this is a complex protein molecule called VDR that is synthesised within the cells, and this was a critically important evolutionary event.

But by an “accident" of evolution, VDR is synthesised in an incomplete form: it lacks a small steroid component. We could call this an ecomomy of evolution because this "small steroid component" of a complex molecule is created elsewhere in the body. We synthesise in our skin the oil 7-dehydrocholesterol (7-DHC) and and as we have seen, by another accident of evolution, UV from the sun converts this into the hormone cholecalciferol, that we also know as vitamin D. 

Vitamin D (in the activated form 1,25(OH)D) is the component required by VDR (Vitamin D Receptor) to make it complete and therefore active. It can then switch on the genes that control the escalation of immunity.

There is no need to expand on the highly complex process of defensive immunity at this stage. It is important to appreciate its activation and its importance.

Figure 2: The activation of defensive immunity

What did we know in January 2020?

Vitamin D had been discovered early in the 20th century. It was recognised that deficiency was common in people who were deprived of sunlight, resulting from indoor life and serious atmospheric pollution. 

The main results of this were childhood rickets (vitamin D deficient bone disease) and tuberculosis (due to vitamin D deficient sub-optimal immunity). It was identified that both could be reversed by exposure to the sun or by consumption of fish oils.

An epidemic of AIDS occurred at the end of the 20th century, and this was characterised by defective tissue immunity due to suppression of T-lymphocytes, that under normal circumstances are activated by vitamin D + VDR. This gave us a great deal of insight into the effects of the suppression of immunity, with consequent increased incidence of tuberculosis, other microbial infections, certain cancers, neurological disease, and heart deaths.

 

From the experience of the early and late 20th century, the importance of natural defensive immunity and the critical role of vitamin D in its escalation were well known before the arrival of the Covid-19 pandemic.

It was also known that vitamin D deficiency is common and that certain groups within the population are especially susceptible.

The elderly

As mentioned, we produce within our skin the oil 7-DHC, in the same way as plankton and many land animals.

UV from the sun converts 7-DHC into cholecalciferol / vitamin D, but the problem in the elderly is that the skin becomes thin and dry. Adequate amounts of 7-DHC are no longer synthesised in the skin, and so adequate amounts of vitamin D cannot be produced. This has been known since 1985.

Figure 3: Production of vitamin D in the skin of the young and the elderly

Elderly people will inevitably be increasingly deficient of vitamin D, no matter how long they sit in the sun. However there will be variation among the elderly and this requires further research with blood levels. 

A supplement of vitamin D in adequate dose is essential in the elderly, so as to prevent deficiency and maintain optimal immunity.

This should have been a public health priority as soon as the onset of the pandemic was anticipated. The neglect of this policy led to large numbers of deaths of the elderly from Covid-19.

A small supplement of vitamin D (400 units each day) was belatedly recommended to elderly people in mid-2020, but with the intention of protecting against the very rare bone disease osteomalacia (not the much more common osteoporosis which is not due to vitamin D deficiency). No mention was made of the need to optimise immunity by correcting vitamin D deficiency, nor any attempt to detect vitamin D deficiency by blood testing.

Black African and South Asian ethnic groups

In the 1920s it was observed informally in Glasgow and other industrial cities that rickets and tuberculosis tend to co-exist within families. A remarkable study conducted in Bombay showed the same thing, but the two conditions occurred in the families of the wealthy, who had an indoor life, whereas these medical conditions were rare in the much more healthy poor families who worked in the fields (Hutchison HS, Shah SJ. QJMed 1922; 15: 167-195). VItamin D deficiency was clearly the problem. 

In the UK since the 1960s it has been known that children of ethnic Black African and South Asian parents have a significantly high incidence of rickets, and that adults have a high incidence of tuberculosis, both resulting from vitamin D deficiency. We have known of the much higher prevalence of severe vitamin D deficiency in people of Black African and South Asian ethnicity in the UK compared to ethnic white. 

It has been known that the pigmentation of dark skin blocks UV penetration, and although of benefit in the intense sunlight of the tropics, it seriously reduces the amount of vitamin D produced in the skin when living in the UK for example, closer to the North Pole than to the Equator. Extensive clothing and vegetarian diet worsen the vitamin D deficiency.

Knowing of their consequent reduced immunity, there should have been a public health imperative to correct the severe vitamin D deficiency in the Black African and South Asian ethnic groups. Failing to do so resulted in the devastating effect of Covid-19 on these groups. 

Figure 4: A view of the Muslim section of
the cemetery of Bradford, UK, in 2020

Three official reports into the high mortality of Black African and South Asian ethnic people from Covid-19 concluded that it was the result of socio-economic disadvantage and racism. In just one of the three was vitamin D mentioned, only to be dismissed immediately. There was no biological consideration.

26 practising doctors died from Covid-19 in early 2020, and of these 25 were of Black African and South Asian ethnicity. No notice was taken of this disturbing fact, even though it negated the sociological conclusion of the reports. The relevant racism was the deliberate ignoring of the special needs of the Black African and South Asian ethnic groups.

Figure 5: Practicing doctors who died
from Covid-19 in the UK in 2020

Ignoring the established high prevalence of serious vitamin D deficiency in people of Black African and South Asian ethnicity was a serious dereliction of duty by those responsible for public health, resulting in high death rates from Covid-19. How did this come about? Who was responsible? Have lessons been learned?

The Obese

It was also known before the Covid-19 pandemic that obese people, as well as having overall poor health, have on average low blood levels of vitamin D. It was again predictable that the obese would be vulnerable to serious and perhaps fatal Covid-19. And so it turned out.

If an obese person receives a given exposure to UV, the blood levels of vitamin D will increase less than, perhaps 50% less than, with a non-obese person. The reason is that vitamin D, being an oil, is taken into the fat calls of the body.

Figure 6: Production of vitamin D in the skin
of the obese and the non-obese

The obese could also have been protected against Covid-19 by correction of low blood levels of vitamin D. This did not happen and so when the Covid-19 pandemic arrived, the obese suffered disproportionately, with a large impact on intensive care units.

This was predictable and action should have been taken in early 2020. Why did this not happen?

What did we learn in 2020?

Suggestions that vitamin D should be given to optimise natural immunity during the pandemic of Covid-19 were met by scepticism and claims that there was "no proof of benefit". The definition of “proof” was never declared. Proof is pragmatic and it means the fulfilment of pre-determined criteria, and these criteria must be clear and testable.

When it was stated repeatedly that there was “not enough evidence”, it was not clear how much evidence would be “enough”. The famous criteria of proof defined by Sir Austin Bradford Hill were not considered, even though they were fulfilled.  When the results of randomised trials  became available, it was stated that they were “too small”, despite clear statistical significance and no untoward effects demonstrated.

Observations that people critically ill with Covid-19 almost always had very low blood levels of vitamin D led to criticisms that this was the result of the illness rather than causative. This had some truth, as the low blood levels of vitamin D were both causative and the result. The details were not clearly understood by the critics. 

In Galilee, Israel, severity of Covid-19 was assessed against blood levels of vitamin D that had been recorded before the pandemic. All of the critically ill patients had pre-illness vitamin D deficiency, and most of them had severe deficiency. 

It was clear that a blood level of vitamin D above 100nmol/L (40ng/ml) provided protection against critical Covid-19, whereas blood level below 50nmol/L (20ng/ml) gave a significant risk of critical Covid-19. 

This is the most important message of 2020 that could, or should, have underpinned policy in the future. The obvious public health objective would be to make certain that blood vitamin D levels are in the safe range.

Why was this study ignored by those "experts" who were in charge of public health? Why were they asleep?

How much vitamin D supplement should be taken?

The answer must be “Sufficient to achieve the target blood level”. This is the same as in the treatment of diabetes with insulin or other treatments of deficiency disorders. To heal rickets in children, just a small quantity of vitamin D is necessary, 400 units each day. However it is clear that a higher dose is necessary to optimise immunity.

Vitamin D and insulin were isolated at about the same time, but it was not possible a century ago to measure their mass. They had to be measured in internationally agreed biological units. One unit of vitamin D was defined as the daily requirement of a ten gram mouse. Scaling up from that, the daily requirement of a 60kg human would be 6,000 units per day.

Strictly speaking we should express a dose as for example, 6,000iu per day. However many people might not understand that "iu" means "international units". As with insulin, I use the term "units" as it is clear, well-known, and it is standardised.

To be cautious it is as well to have a starting dose of 3,000 units per day, adjusting the dose as necessary in future months. Dose adjustments do not need to be made for the elderly or those with a dark skin. However the obese will require a higher dose of vitamin D, and this should be related to body weight.

The vitamin D that we take as a supplement is also the result of solar UV acting on 7-DHC, but in the skin and wool of sheep. Vitamin D is a component of the oil in the fleece of a freshly sheared sheep. It is extracted in an organic solvent and purified to provide supplements for indoor farm animals (80%) and for humans (20%). The vets are ahead of the game, and we seem to care more about farm animals than about humans.

Effect of immune response on vitamin D

Vitamin D circulates in the blood as a reservoir, ready for use whenever necessary. Its circulating reservoir form is as 25(OH)D, a hydroxyl group (–OH) being added during a slow process that takes place in the liver. It is as 25(OH)D, also known as calcidiol or calcifediol, that we measure vitamin D in the blood. 

As with all reservoirs, it desirable for it to be almost full rather than almost empty. Water in our reservoirs is continually used and continually refilled by nature; vitamin D is also continually used and must be continually replenished by nature, by the Sun. 

A molecule of vitamin D in its fully activated form 1,25(OH)D can be used only once to activate VDR, the key complex intracellular molecule that will activate the genes necessary to optimise defensive immunity. 1,25(OH)D is then automatically and irreversibly de-activated, so as to prevent dangerous accumulation. Immune cells can synthesise any number of VDR molecules, but vitamin D must come from the skin (as a hormone) or from the diet (as a vitamin).

So when defensive immunity is active, vitamin D will be consumed and stores circulating in the blood will become depleted. Immunity is active in response to an infection, but also in response to a vaccination, which acts like an infection so as to produce defensive capability for the future.

It follows that during the pandemic of Covid-19 repeated infections and repeated vaccinations will have resulted in vitamin D depletion. This in turn could be the reason for the current problem of excess illness and excess deaths, affecting not just the UK but many other countries of the world. 

The answer to current problems of excess illness and death is quite simple. We must apply our knowledge of the great importance of vitamin D. There is a big opportunity, and meeting this opportunity is imperative.