2023 – a retrospective of vitamin D

My garden today

We are now in the late Spring of 2023. This is my first Blog post of this year, and it had been uncompleted for a few months. I must say that I have been both disappointed and disheartened at the very negative attitude of our medical and political leaders in respect of Vitamin D and natural immunity. But there is a future to think of, and perhaps the importance of Vitamin D will be revealed to the population in the not too distant future.

When the pandemic of Covid-19 arrived in Europe in early 2020, we knew that it would be essential to optimise natural defensive immunity of the population. Although in 1968-69 we had to let the pandemic of "Hong Kong" flu take its course, fifty years later we had accumulated a great deal of research knowledge. In 2020 we knew  how to optimise defensive immunity. We anticipated that as a result of the new knowledge and the correction of widespread Vitamin D deficiency, the deaths from Covid-19 would be very many fewer than during Hong Kong flu pandemic. This has turned out not to be the case: there were thought to have been about 50,000 Hong Kong flu deaths in 1968–69, but as of May 27th 2023 Worldometer reports 225,324 Covid-19 deaths in the UK.

By "we" I mean those people fortunate to have had a background in and knowledge of medical science. I was a young doctor, the  resident medical officer (RMO) of the Manchester Royal Infirmary in 1968-69, and I remember the pandemic very clearly. I subsequently worked as a general internal physician and gastroenterologist in East Lancashire, but I absorbed the new knowledge of the vital importance of Vitamin D in activating defensive immunity. I was also aware of the disturbing extent of Vitamin D deficiency, especially among Black African and South Asian ethnic groups in the UK. 

It turned out to be a naive assumption of mine that in 2020 public health and medical services would want to provide the very best of preventative medicine and treatment of the sick. The knowledge of the importance of Vitamin D was readily available, and it must have been known to public health doctors and the senior medical advisors of government. I was just an ordinary physician in an ordinary hospital in ordinary Lancashire, but as I had been able to absorb the medical-scientific information, surely much more important physicians than I must also have absorbed it. 

Perhaps I seriously underestimated the ignorance of medical scientists who should have known more than I knew. The alternative view is that they deliberately ignored their existing knowledge of the importance of Vitamin D, and deliberately avoided reporting on the new knowledge that appeared during the pandemic.

Pre-pandemic knowledge

Vitamin D had been identified about one hundred years ago, initially through its evolutionary late function of bone maturation. Deficiency of vitamin D was demonstrated to be the cause of rickets in young children, the result of serious atmospheric pollution together with an increasingly indoor life during the industrial revolution. Observation led to the recognition that rickets could be cured by removal of the children from the polluted industrial cities to the alpine villages of Austria, or to the coastal fishing villages of Scotland. The former provided vitamin D production by the action of the sun on the skin, the latter also by the consumption of oily fish, which obtain vitamin D from the oceanic food chain starting in plankton.

It is worth remembering that plankton evolved 1.5 billion years ago, but living at the surface of the oceans they were vulnerable to damage and death from solar UV radiation. They evolved two defensive mechanisms. One was diurnal vertical migration, in which they would sink to a protective depth during the day and rise to the surface during the night, this becoming a genetically controlled process. 

The second protection became the synthesis of the oil molecule 7-dehydrocholesterol, abbreviated as 7-DHC. The important characteristic of 7-DHC is that it absorbs UV energy wavelength 290–315 nm, using the energy to break a specify bond in the molecule rather than it producing heat and radiation damage to the plankton. This sunscreen function is very effective. The by-product of the chemical change is a derivative molecule called cholecalciferol, that we generally know as vitamin D.

Plankton had no use for vitamin D, and it remained a molecule without a function for one billion years. During this important era, evolution was active in producing immunity, essential for further developments of animal life. Ultimately vitamin D gained a function in activating the new immunity cascade, and this was vital to protect against damage from pre-existing bacteria and viruses. The more complex forms of animal life that were to appear during the Cambrian explosion, the "biological big bang", 500 million years ago required this defensive immunity for survival. Fortunately for a fictitious episode of humankind, the invaders in HG Wells’ "War of the Worlds" did not have the benefit of this immune mechanism and they soon succumbed to the micro-organisms with which we share this planet.

To condense a complex process, vitamin D acquired directly from solar UV acting on 7-DHC in our skin, or indirectly by mouth, is not biologically active. It passes in the blood-stream to the liver where a slow process takes place adding a hydroxyl (-OH) group to the molecule. It then returns to the blood as 25(OH)D, also known as calcifediol or calcidiol, and it circulates as a reservoir ready for use when it is needed. At times of microbiological challenge, the cells of immunity, various immunocytes, take up 25(OH)D from the circulation and convert it by the addition of another -OH group into 1,25(OH)D, also known as calcitriol. This is the active form, which unlocks the complex vitamin D receptor (VDR) molecule, and as a result activates  the genes that control the escalation of defensive immunity. An adequate blood level of 25(OH)D is essential for immunity to be maximal and maintained.

The slow process of the conversion of vitamin to into 25(OH)D, calcifediol, in the liver is satisfactory under normal circumstances. It can take up to two weeks for a single dose of vitamin D to reach a peak of 25(OH)D in the blood, but in nature it is a continuous process, at least during the summer months. However, if the part-activated 25(OH)D, calcifediol, is given by mouth, it does not require the liver hydroxylation stage and it reaches  a high (normal) blood level after about two hours. This was first reported by Dr TCB Stamp of University College Hospital London in The Lancet July 20 1974  It was therefore known in advance of the pandemic and we have seen its remarkable importance in clinical studies from Spain, but no clinical use in the UK and other countries.

It had also been established that certain groups within our population, those living closer to the North Pole than to the Equator, are at particular risk of vitamin D deficiency, and thus of sub-optimal immunity. These are in particular citizens whose ethnic origin is in Africa and the Caribbean, or in South Asia, people with a dark skin that is inefficient at producing vitamin D. The pigment melanin in the skin is protective against radiation damage. It absorbs solar UV, which is therefore not available to the substrate 7-DHC. Also vulnerable are the elderly, whose dry skin does not synthesise sufficient 7-DHC to allow production of adequate amounts of vitamin D. Another group vulnerable to serious vitamin D deficiency are people who avoid exposure of the skin to the sun, usually for religious reasons. Finally the obese, in whom the oil vitamin D becomes trapped in the fat cells of the body.

These facts were known, and it was predicted that these groups would be particularly prone to the serious and perhaps fatal effects of the new virus responsible for Covid-19, to which we had no historical or inherited immunity. There was a way of helping people with an ethnic dark skin, the elderly, and the obese, and those who avoided the sun. It would have been possible to contact and provide them with vitamin D supplement, a process that was shown to be feasible in a study by Professor Adrian Martineau. It would however have been much quicker to assume vitamin D deficiency (known to be widespread) and to correct it with a supplement in a dose that would be effective in the deficient but of no danger to those not deficient.

In practice, for reasons that are obscure, this did not happen. It was a callous denial of knowledge by public health bodies and medical organisations. When people developed Covid-19 symptoms and tested to be positive, they were told to go home and then to send for an ambulance only if they had difficulty breathing. How different the outcome might have been if the positive test and been followed by a single dose of vitamin D 100,000 units, a one month supply. Blood test for vitamin D level could also have been performed. The neglect of people with early proven Covid-19 can be viewed as criminal negligence of those responsible for public health.

But despite official disinterest or dismissal, clinical research into vitamin D and Covid-19 was undertaken in many parts of the world.

Clinical Research, 2020 to 2022

Clinical research, like all scientific research, starts with an observation.The next stage is that the observation must be reproduced, and by others. The observation is usually two variable characters that appear to be associated. This association must be consistent, with other of Sir Austin Bradford Hill's criteria of causation. We need to remind ourselves of these, as they are so important,

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1. Strength of association
2. Consistency
3. Specificity
4. Temporality
5. Biological gradient
6. Plausibility
7. Coherence
8. Experiment
9. Analogy
10. Reversibility (not always possible)

I drew attention to Hill's Criteria in November 2020, demonstrating that they were fulfilled in respect of a causative role of vitamin D deficiency in Covid-19. Strictly speaking, vitamin D deficiency is not "the cause" of the disease but it is a factor that increases susceptibility to the disease, by disabling immunity. This important because a disease or an injury is generally a product of cause and susceptibility. Serious or fatal forms of the microbial diseases tuberculosis and Covid-19 are due to a combination of the specific micro-organism, and the susceptibility factor of inadequate blood levels of vitamin D. AIDS also makes those affected susceptible to a variety of infections as a result of suppressed immunity.

In a similar way death from a road traffic accident is directly the result of trauma but also perhaps a susceptibility factor of a high level of alcohol in the blood. If government or public health officials want to reduce the number of deaths from road traffic accidents they must minimise susceptiblity factors. There is an enforced maximum allowed blood level of alcohol in car drivers. Public health officials might similarly be expected to demand a minimum blood level of vitamin D, as a way of reducing susceptibility to microbial diseases. It is not happening, in a way that is as negligent as would be ignoring blood levels of alcohol in car drivers.

We can note at present that lessons have not been learned by our medical officials. For example in the British Medical Journal of May 13 2023 contained an article "What is the future for covid drugs and treatments?" There was no mention of optimising natural immunity by correction of vitamin D deficiency.

However not all of clinicial medicine in the UK has been asleep. Supplementation of the population with vitamin D has improved during the pandemic, especially in ethnic minority groups, thanks to the initiatives of individual general medical practitioners, acting independently of government and WHO guidelines.

During the pandemic, which is now officially at an end, I have reviewed 38 papers concerning the benefits of vitamin D in the prevention and treatment of Covid-19. I will present condensed forms of the reviews, but in subsequent Blog posts. 

A new book is about to be available: