Covid-19, Vitamin D : "I had a dream"

Covid-19, Vitamin D, and the UK Government

"I had a Dream"  by David Grimes

Day 0 (early May 2020)

The scene:

10 Downing Street, London W1

The Press Room

The reporters are waiting, now on-line.

Enter three men, and stand behind their lecterns.

Professor Chris Whitty,      Prime Minister Boris Johnson,  Sir Patrick Vallance

Prime Minister, Boris Johnson (it is he, recovered)

This morning we have, er, some very good news for you all, in fact spectacular news, the very best that we have had for a long time. I will ask Chris Whitty to give more details.

Professor Chris Whitty, Chief Medical Officer

Thank you Prime Minister. The good news today is that we now have a new way to reduce dramatically serious illness and deaths from Covid-19. The way to do this is remarkably simple. We have heard a great deal about the development of vaccines to provide immunity, but it is unlikely that they will be available and tested for safety until the end of the year. In the meantime we have a great opportunity at hand today. It is vitamin D. It will boost our immunity and reduce deaths at a stroke.

Prime Minister

So there we are. I told you that we had really good news today, great news. Really great news. I will turn to Patrick to explain further.

Sir Patrick Vallance, Chief Scientist

Thank you Prime Minister. Vitamin D is not new. In fact it first appeared on the evolutionary scale 1.2 billion years ago, but its importance in immunity has been a feature for only the past 500 million years. The next bit is slightly technical. Vitamin D is created by the action of the sun on 7-dehydro-cholesterol and this is manufactured in our skin. It enters the blood stream and becomes activated in the liver and kidneys. It combines with what are called vitamin D receptors (VDRs) on the surface of target cells, like putting a plug in electrical socket. It then activates several genes, like switching on an electrical appliance once it is plugged in. The activated genes include those that enable the proliferation of the defensive immunity cells, such as T-lymphocytes and macrophages. This is an essential response to infection. 

Prime Minister

I think I can just about understand that. Would you like to add anything Chris?

Chris Whitty

It was realised only recently, early in the 20th century, just before World War One, that vitamin D is actually important for immunity. At that time rickets was common in our industrial cities and this was shown to be due to shortage of vitamin D, the result of air pollution preventing the penetration of full intensity sunlight to ground level. It was noted that rickets and tuberculosis frequently co-existed within families. It is now clear from the experience of the AIDS epidemic in particular that tuberculosis becomes activated when immunity is suppressed. Vitamin D deficiency is another but much milder form of immunodeficiency. 

Prime Minister

Do you mean that air pollution causes suppression of immunity and that is why it is bad for us?

Patrick Vallance

Yes, and we have seen that the pandemic of Covid-19 took hold in northern Italy, which has the greatest air pollution in Europe. I believe that vitamin D levels have been very low in Northern Italy and also in many parts of Spain, but the reason for this is not yet  clear. Air pollution will also explain why the pandemic is causing more deaths in our inner cities than in rural areas.

Prime Minister

I think there is more evidence concerning the value of vitamin D in Covid-19.

Patrick Vallance

Yes. It is possible to measure the amount of vitamin D in the body by a simple blood test that has been available in all NHS hospitals for several years, and it is available in many countries in the world.  It is important for the blood level of vitamin D to be greater than 30ng/ml, or 75nmol/L. Less than 10 is regarded as serious deficiency. An imaginative study has been reported from the Philippines by Professor Mark Alipiort, who unfortunately has been very ill with pneumonia, but I have the good news that he is now recovering. Vitamin D testing was undertaken in 212 patients with proven Covid-19 in three hospitals in south-east Asia. 

Prime Minister

Chris, can you tell us the results?

Chris Whitty

The results are dramatic. Of the 55 patients with ideal blood levels of vitamin D, 47 had just mild disease. In 4 the disease was moderate, in 2 severe, and in 2 critical. But on the other hand, only 2 patients with low blood levels of vitamin D had mild disease, and in the other 155 patients the disease was moderate, severe or critical. 

Prime Minister

Gosh! So there was a clear benefit form having a good blood level of vitamin D. I think there has been another study. Patrick.

Patrick Vallance 

Yes Prime Minister. This was in Indonesia. As the pandemic started in the far East, there have been more opportunities for research. 780 patients with Covid-19 were tested for blood levels of vitamin D, and they were followed up to observe clinical outcome. Chris.

Chris Whitty

Almost half of the patients had low levels of vitamin D, and almost half of the patients died. Of the 380 with good levels of vitamin D, that is above 30, only 16 died.  Of the 400 with low levels of vitamin D, almost all died.

Prime Minister

This is really amazing. Are there any other studies?

Chris Whitty

Yes. I have just received this morning a report from an imaginative Dr Gerry Schwalfenberg in Edmonton, Alberta, in Canada. He realised a little while ago that low blood vitamin D level is a bad thing and it is especially common in elderly people living in care homes. He looks after residents in a nursing home and so he gave them all vitamin D 2,000units each day by mouth and later he tested the blood levels. In 94% of the residents, the levels were above 32ng/ml (80nmol/L). Those whose blood levels remained low were given a higher dose of vitamin D

Prime Minister

Has that been of benefit to them?

Chris Whitty

Yes it has. Not a single resident of this nursing home has been ill with Covid-19, whereas there have been many cases in all the other neighbouring nursing homes

Prime Minister

That is even more really good news. Are there any more examples, Chris?

Chris Whitty

Yes. With exception of San Marino, Belgium has in Europe the highest number of Covid-19 deaths relative to population size. We have just this morning read a report from Belgium that vitamin D levels were much lower in the patients who died from Covid-19

Prime Minister

So we have a great opportunity to protect the wonderful and proud people of our great country, and defeat the most dangerous enemy that we have faced since the second world war. Patrick, what is the next step?

Patrick Vallance

We have these clinical studies and we have the basic science of the vital role of vitamin D in the process of immunity. We need to protect people by issuing them with vitamin D. There are two dosage regimes. The first is to use capsules or tablets of vitamin D. A dose of 2,000 units a day is usually adequate, but at this time of national emergency I would recommend 4,000 units a day. An alternative is to give a single dose of 100,000 units, in an oil which can be given by injection or by mouth. Its effect will last for about two months.

Prime Minister

Will this be expensive? Do we need to ask the permission of the Chancellor of the Exchequer?

Patrick Vallance 

It is cheap. The single dose will cost about £1, and the 4,000 unit capsules will cost about £10 for a year’s supply. We obviously must multiply these numbers by the number of the UK population.

Prime Minister

That is even more good news. I am sure that our Chancellor of the Exchequer Rishi Sunak will be very pleased. Chris, do you have any comments?

Chris Whitty

It will take a little time for the public health departments in the UK to organise the distribution of vitamin D.

Prime Minister

But surely this is very urgent. People are still dying of Covid-19, about 500 each day.

Chris Whitty

Yes, but we need to prioritise distribution of vitamin D to those most at risk. This will obviously be health service workers, and then care workers, and then the residents of care homes.

Prime Minister

I think that I might have heard a suggestion that people of black African and Asian ethnicity might be at risk from Covid-19. Patrick, do you know if this might be true?

Patrick Vallance

I might have also have heard the suggestion that people of black African and Asian ethnicity might be at special risk. There is a view that they must all be rehoused as a matter of urgency, but that is a challenge that we cannot meet today. I am also given to understand from the newspapers, but I have not seen any official figures, that 26 doctors in the UK have died from Covid-19, and that 25 of them were of black African and Asian ethnicity. That is quite a coincidence. However it has been known for a long time that such people are almost all deficient in vitamin D as the result of dark skin and sun-avoiding behaviour.

Prime Minister

And so must they also have a priority for receiving vitamin D?

Sir Patrick Vallance

Yes, Prime Minister. But the more people who have priority, the more difficult the task of distribution.

Prime Minister

But if vitamin D is so urgent and so cheap might people want to buy their own supplies?

Chris Whitty

Yes Prime Minister, that is what I have done.

Sir Patrick Vallance

And so have I.

Prime Minister

I think I was given a vitamin D injection when I was in hospital.

Chris Whitty

That is probably why you recovered so well and so quickly when you were so close to death.

Prime Minister

Yes, and once again I would like to thank all the brave staff for the wonderful treatment and care that I was given. So, the vitamin D story seems to be straightforward. Are there any dissenting voices?

Patrick Vallance

There are a few. Notably the Oxford group, who are busy developing and testing a vaccine. They feel that vitamin D is an untested diversion from what they are doing. 

Chris Whitty

And there are many who feel that social justice for the ethnic and socio-economically disadvantaged should have priority over vitamin D supplements.

Prime Minister

That is tricky. So I think we must go ahead with vitamin D immediately. Today at the latest. Are there any questions? Laura.

Laura Keuensberg (BBC)

Thank you all for this welcome news.

Laura Keuensberg

Could I please ask where vitamin D supplements come from and is there an adequate supply?

Prime Minister

Patrick, this is one for you.

Patrick Vallance

Thank you Laura. Most of the vitamin D supplements come from sheep’s wool, and some from fish oil. The oil from sheep’s wool must be processed to isolate 7-dehydro-cholesterol, and then this must be irradiated with UV light to convert it into vitamin D. A possible problem is that the great majority of this production takes place in China. The world annual production is 97 metric tons. Most of it goes into animal feed, very important now that so many animals are kept indoors. 15.3 metric tons become available for pharmaceutical use and 4.5 tons for food additive. The UK might require about 1 million tons or more, but I am told that Donald Trump has bought it all.

Prime Minister

Thank you Laura. Beth, you have a question.

Beth Rigby (Sky News)

You have mentioned the Oxford group who are inventing a

Beth Rigby

vaccine at this moment. I am told that  they demand a randomised control trial to see if there is any truth in the idea that vitamin D might be helpful in Covid-19. Is such a trial underway in the UK?

Prime Minister

Patrick should be able to answer this one.

Patrick Vallance

I do not have a full picture of any research that is going on at present. Perhaps Chris would know more.

Chris Whitty

I do not know of any, but research that individual hospitals undertake is up to themselves. The information about vitamin D that I have is that common sense tells us how good it is, and that is why I take it. If we have a controlled trial, half the subjects will take vitamin D and half will take a placebo, a dummy tablet. I would not be happy for me or any of my family or friends (with an occasional exception) to take the placebo as it might put me or others at a high risk of death. Unless we keep the subjects in the dark (perhaps literally) I do not see any controlled trial taking place. In other words at this stage, to conduct a placebo controlled trial of vitamin D would not be ethical, and with informed consent it would not be possible. The weight of evidence indicating that vitamin D is helpful in preventing serious illness and death from Covid-19 is well beyond reasonable doubt, to use a legal expression.  We know that vitamin D is safe, but we do not yet have this information about the Oxford Vaccine, which is not yet available.

Prime Minister

Thanks you Chris. That is very clear. Heather, you have a question.

Heather Stewart (Guardian)

We hear great deal about testing. How many people in the UK have had their blood vitamin D levels tested?

Heather Stewart

Prime Minister

Chris, can you answer this?

Chris Whitty

The short answer is that I have no idea. Hospitals do not inform the centre about the blood tests that they do.

Prime Minister

Thank you Heather. I think you have another question

Heather Stewart

Yes Prime Minister. Thank you. At the Guardian I am told that during the past month we have had a lot of letters about the value of vitamin D in the pandemic, mainly written by doctors. We published just one letter but we thought that the others must be from food-fad enthusiasts. Do you mean to say that they were all right in what they had written to us?

Prime Minister

Patrick, you might answer this.

Patrick Vallance

Well, Heather, it looks as though they were right.

Prime Minister

Tim, you have question.

Tim Shipman (Times & Sunday Times)

Tim Shipman

It sounds as though there might be a long and widespread knowledge of the value of vitamin D in immunity and defence against infection. We have just heard about it for the first time this morning, and so may I ask when you first heard about it?

Prime Minister

Speaking for myself, it was just after breakfast this morning. What about you Patrick?

Patrick Vallance

I heard about it yesterday evening. I was alerted by a member of my staff who had just seen some interesting Blog posts and Tweets.

Prime Minister

And you Chris ? When did you first hear about it?

Chris Whitty

When Patrick phoned me yesterday evening.

Tim Shipman

Why did you as Chief Medical Officer not know about the value of vitamin D in defensive immunity?

Chris Whitty

Well, I can’t be expected to know everything. I thought vitamin D was all about bones and children with rickets.

Prime Minister

Let’s move on. Bob, you have a question.

Robert Peston (ITV News)

Robert Peston

Prime Minister, what can people do if supplies of vitamin D are not sufficient for our needs?

Prime Minister

That is difficult one Bob. Over to you Patrick.

Patrick Vallance

We can eat oily fish, such as mackerel in particular. Do you remember the days when as children we were given disgusting Cod Liver Oil? It turns out that our mothers were right. We can also obtain vitamin D from the sun, and in fact we usually obtain most of our vitamin D from the sun. We need to expose our skin, not quite all of it, to the sun, at this time of the year in the UK for up to one hour between 10:00am and 4:00pm. We can do this in our gardens, in the parks, and on the beach, or anywhere that is isn’t too cold, and of course when it is not raining.

Prime Minister

That might be bit tricky with social distancing, but we must act very quickly. I suppose we might do what I believe is happening in supermarkets and other places. People would apply for and be given a ticket to lie semi-naked in a park (not in a supermarket) or on a beach. We do not want too many people in one place at one time, and so the ticket would be valid for one hour only. And we would need to have police on patrol. We should be able to create a web-site for this later today and have it up and running by tomorrow morning. Are there any more questions?

Goes on for another half hour with the usual questions and the usual evasive answers.

Day 1.

The daily Covid-19 briefing becomes chaotic as Matt Hancock (Secretary of State for Health), Angel McLean (Deputy Chief Scientific Advisor), and Jenny Harries (Deputy Chief Medical Officer) are inundated with questions about vitamin D that they are unable to answer. 

The briefing is brought to a rapid close.

Newspaper headlines:

All hospital patients with Covid-19 given vitamin D

Crowds outside pharmacies

Vitamin D is in short supply

Demand for permits is overwhelming

Web-site for permits to sunbathe in public places crashes. 

Public parks crowded with semi-naked people

Queues of cars at approaches to beaches

Asian groups complain that sunbathing advice is against their religious practices

Day 2

Newspaper headlines:

Government suspends daily Covid-19 announcements

Vitamin D supplies to the public are exhausted

Black market develops for vitamin D

People fighting for entry into parks

Sunbathers refuse to leave after one hour

Police cannot control crowds

Day 3

Newspaper headlines:

Public Health agencies are struggling to prioritise the vitamin D supplies that they have been able to obtain.

China refuses to release more vitamin D

It is not yet warm enough to shear sheep

Fish shops noting a big demand for mackerel

Day 4

Newspaper headlines:

Vitamin D : Civil disobedience.

Family doctors are struggling with demand for 

vitamin D blood tests

Crowds outside hospitals demanding vitamin D

Heavy rain diminishes crowds in parks

Day 5

Newspaper headlines:

Why was vitamin D not stockpiled?

If vitamin D has been known for a long time to help immunity, 

why was it not recommended two months ago?

Large protests in Trafalgar Square

Chief Medical Officer and Chief Scientist resign

Calls on Prime Minister to resign 

Day 6

Newspaper headlines:

Rapid decrease of deaths from Covid-19

Lockdown ended to enable people resume normal lives

Day 7

Newspaper headlines:

In anticipation of future epidemics, Government sets up 

Scientific Advisory Committee for Immune Defence

..........................................

And then I woke up, listened to the radio news and I realised that it had all been a dream, but a pleasant dream. It would have been nice to remain asleep but now I was awake I had to continue with the daily nightmare of Covid-19 with no action taken to stop deaths.

How many more will die today? Will there be any more deaths of black African and Asian doctors? Or more nurses and care workers? When will someone listen to what many doctors are saying and writing about the potential value of vitamin D? When will "vitamin D" appear in the newspapers, on the radio, on the television, or at the government daily Covid-19 briefing? When will we have a televised debate on the value of vitamin D, with full display of the large evidence? 

I often hear and read vitamin D sceptics saying: "Vitamin D in Covid-19 is unproven". If commentators knew the meaning of "proof" they would not make such a ridiculous statement. Absolute proof rarely exists in the real world, and so, as in law, we must look at all the evidence, and then we must make a judgement on the basis of "Beyond reasonable doubt".

My Blog posts during the past six week have had more than 20,000 readers. Although the message does not appear to be reaching those in political power, it seems to be contributing to a  much larger "grass-roots" movement. There has been an increasing demand for vitamin D, and supplies from some sources have been exhausted.

But perhaps the dream of government endorsement of the proven importance of vitamin D in maximising immunity will become a reality. Hopefully very soon.

Covid-19, Vitamin D, Ethnicity – and official inaction

Covid-19, Vitamin D, Ethnicity and official inaction

Garden during lockdown

During the UK lockdown and the delightful weather that accompanied it, I have spent much time in the garden, and  I remembered research that I undertook in 1990. It was part of investigation into determining the reasons why socio-economic disadvantage and Asian ethnicity might be associated with illness and reduced life-expectancy, especially in the north-west of England. The investigation concluded that the key to this problem (and it still exists) is reduced exposure to the sun and thereby low vitamin D levels in the body. A small part of the investigation was a short study of whether the ownership of a garden would influence blood levels of vitamin D.

Figure 1. Vitamin D levels determined by housing type and season

There is a difference as can be seen in Figure 1. People living in a house with a garden have on average a higher blood vitamin D level than those without a garden, in summer and in winter. Note that the averages were all below the ideal level of 30ng/ml. People whose houses do not have gardens are likely to be relatively socio-economically disadvantaged, and as we can see deficient in vitamin D. This should be officially recognised.

The study shows something else. Blood levels of vitamin D are higher in the summer than in the winter, as has been demonstrated on many occasions. This explains "winter flu", more deaths in the winter than in the summer, and perhaps why at present Covid-19 is worse in the northern hemisphere where we have been emerging from our winter than in the southern hemisphere, where the summer is just at an end. When we experience winter flu, it is not that the virus by some unnatural miracle "wakes up", it is that our immunity "goes to sleep" because of less vitamin D.

We now have the experience of Covid-19 in hospitals in south-east Asia, and their research that has demonstrated clearly the important protective action of vitamin D.

Indonesia

A new study has recorded blood levels of vitamin D in 780 hospital patients with Covid-19. Almost half of them died, and although Indonesia is very close to the equator, more than half of the 780 were deficient in vitamin D (blood levels less than 30ng/ml).

Figure 2. Outcome of Covid-19 related to vitamin D status

We can see in Figure 2 that of the 388 patients with blood levels of vitamin D greater than 30ng, only 16 died, but of the 179 with lowest levels of vitamin D, less than 20ng/ml, 177 died. Blood level of vitamin D was an extremely powerful predictor of either survival or death. 

I wonder how many Covid-19 patients in the UK have had blood levels of vitamin D tested.

Philippines

Figure 3. Severity of Covid-19 related to vitamin D status

I have described this study in a previous post. I have displayed in Figure 3 numbers rather than percentages. 55 out of 212 patients had blood vitamin D levels greater than the ideal minimum of 30ng/ml. Of these 55, 47 had mild disease, and the disease was moderate in 4, serious in 2, and critical in 2. Only 2 patients with low blood levels of vitamin D had mild disease and 155 had moderate, severe, or critical disease. Patients who had died were not included in this study.  

The message

Look at results: based on three categories of blood levels of vitamin D, which category would you choose to be in? I would choose greater 30ng/ml. It is very clear that if you want a Covid-19 illness to be only mild, make certain that you have plenty of vitamin D in your body.

I would certainly not want my blood level to be less than 30, as if I catch Covid-19 I would want the illness to be mild, rather than moderate, serious, critical or fatal.

There has been some controversy in the past as to what the ideal blood level of vitamin D should be. It should be based on its relationship to disease, and it is quite clear from these two studies using Covid-19 as a model that the ideal blood level of vitamin D is greater than 30ng/ml (=75nmol/L).

I am pleased to report that last time my blood level of vitamin was measured, about two years ago, it was about 38ng/ml. It is unusual to have such a level unless eating fish for every meal, having a great deal of sun or UV exposure, and of course taking a supplement of vitamin D3. If taking a supplement it needs to be in a dose of about 2,000 units (= 50mcg) each day, or perhaps twice this during the present pandemic. Recommended doses of 400 units (10mcg) will not achieve a target blood level of 30, unless accompanied by a lot of fish or UV light.

The importance of vitamin D in immunity

Vitamin D is essential for maximum immunity as well as muscle-skeletal health, as I have pointed out in previous posts. The “immunity” of an individual cannot be measured directly, although critical illness or death from Covid-19 will give a good indication of low immunity. To assess immunity when not desperately ill, the best test would be the blood level of vitamin D.

The medical and scientific advisors to the government cannot be ignorant of the immune-enhancing effects of vitamin D and the need to keep the blood level above 30ng/ml to achieve maximum immunity. The information has been published in a variety of medical journals, mainly since 1983.

They should know that vitamin D is created by a non-enzymatic photochemical reaction, the direct effect of the sun on the steroid precursor 7-dehydro-cholesterol (7-DHC). This first occurred 1.2 billion years ago in plankton in the oceans. It was an important accident because the synthesis of vitamin D absorbs UV energy from the sun, thereby reducing tissue damage from UV energy. This is important in humankind today, and for example we find that melanoma is less severe in people who have generated a good blood level of vitamin D.

Evolution since 500 million years ago led to the double activation of vitamin D in the liver and kidneys, and it then became a hormone with biological functions. This function is the activation of an enzyme in the cell wall, the vitamin D receptor (VDR), which also had to evolve. Vitamin D in its activated form 1,25-(OH)D (calcitriol) combines with VDR, forming a hetero-dimer, what is called a ligand. This acts within target cells (including immune cells) and in turn activates specific genes. This process will switch on the amplification of the defensive immune process in response to infection. 

Ethnic variations

Previous posts have indicated the undue burden of the black African and Asian communities of the UK during the pandemic of Covid-19. This must be known to the network of scientific advisors, but why do they keep quiet? The government, or the public health bodies of the nations of the UK, are not releasing information concerning those who have died from Covid-19, unlike the health service of Italy which released good quality useful information. The UK government does not officially accept that black African and Asian ethnicity is a strong risk factor for the need of ventilatory support and death from Covid-19. 

In parliament last week the acting prime minister did not know the number of health service staff who had died from Covid-19. There has been no government comment on the fact that so far 23 out of 24 doctors who have died from Covid-19, were of black African or Asian ethnicity. The usual explanation of the excess deaths in ethnic minorities is socio-economic disadvantage, but the paradox of the doctors’ deaths  invalidates this. The explanation is not sociological: it is biological, vitamin D deficiency resulting from skin pigmentation and sun-avoiding behaviour.

The medical and scientific advisors to the government must be aware of this. But why silence? Why the refusal even to discuss it? We might expect that news reporters or politicians are not aware of the science of vitamin D, but some of the network of scientific advisors must know the published details.

Why no action?

During the present pandemic of Covid-19 the UK government is being advised by its Scientific Advisory Group for Emergencies (SAGE), but generally the government receives its nutritional advice from the Scientific Advisory Committee for Nutrition (SACN). Vitamin D is considered to be part of nutrition, and so SACN has, or had, a Vitamin D Working Group. It produced its 289 page report in 2016 and it was subsequently disbanded. 

The report provides a major review of the metabolism and function of vitamin D (it uses units of nmol/L and mcg doses, but I will show both). It emphasises the importance of vitamin D in musculoskeletal health.  It states that the blood level of vitamin D should not be below 10ng/ml (=25nmol/L). It states that when a vitamin D supplement is necessary, usually in pregnancy, a dose of 10mcg (400units) is safe and adequate. However it also states that it is only adequate to achieve this minimal blood level of 10ng/ml (=25nmol/L). It can be seen from the Philippine and Indonesian studies that this minimal blood level would condemn many Covid-19 patients to intensive care and possible death.

The report (now engraved in stone with no review planned) identifies a role of vitamin D in immunity but comes to no conclusion as to its usefulness. When sitting in a committee there is no necessity for speculation, and demands for "proof" can be very rigorous. Most people do not realise that proof is pragmatic, and it can change with time and circumstances. As I indicated in previous post, Sir Austin Bradford Hill in his "criteria", regards careful observation as the basis of proof when experimentation is not always possible. The acceptance that cigarette smoking causes lung cancer was based on observation (of doctors) rather than experimentation. 

And so it is with vitamin D. The studies from Indonesia and the Philippines are observational, but the observations are powerful. It is up to individuals to make their own decisions. We might decide not to smoke cigarettes, and in this we are encouraged by the government. On the basis of similar observations (and with a strong scientific basis) we might decide to take a vitamin D supplement, but at this time of national emergency the government is providing no encouragement.

The government will not go beyond the SACN report, and its advisors always refer to it. Knowledge is officially “complete”, but in reality it is incomplete. The government, and therefore the nation at this time of more than 26,000 deaths from Covid-19, is stuck with a poor quality approach to vitamin D, which holds so much potential.

The pandemic also provides a unique opportunity for clinical research into vitamin D. However if I were asked to be recruited into a clinical trial of vitamin D I would say "Yes, as long as I receive vitamin D and not the placebo". In practice I would not be accepted for such a trial as I already take a vitamin D supplement. If a vitamin D trial is conducted with the participants giving  true informed consent, I cannot foresee the trial taking place. The evidence of life-saving benefit is now so great that to accept a placebo on entry to hospital with Covid-19  could be regarded as attempted suicide, given the one third mortality risk.

In the meantime we each need to make a pragmatic decision, assuming that we have been given the necessary information, and that is only rarely the case. What is to been gained  by taking a vitamin D supplement? The answer is a much reduced risk of needing intensive care or dying. What is to be lost? Perhaps dying or requiring intensive care, but nothing else. Taking vitamin D 100,000 units as just a single dose will do no harm and will cost approximately £1. 

The studies from Indonesia and the Philippines are powerful indicators of the benefits of vitamin D, which does not actually prevent Covid-19 infection, but it prevents serious disease and death. This is new information that should be regarded as a "game changer". We must absorb this new information and incorporate it into action.

The great economist John Maynard Keynes stated: “When the facts change, I change my mind - what do you do, sir?”  The answer from the government at present is “Nothing”.

Covid-19, Vitamin D, and ethnicity - evidence

Covid-19, Vitamin D, and ethnicity

Sunset over the River Mekong, from Vientiane

The Covid-19 epidemic in the UK has highlighted the health disadvantage of those of black African and Asian ethnicity (BAME). For example, in respect of Covid-19, 72% of health and social care staff deaths, 35% of intensive care cases (13% of population), and in the USA 12% of deaths in California (6% of population).

This is usually assumed to be the result of socio-economic disadvantage, but it is now clear that this is not altogether true. The epidemic has seen a number of deaths of doctors in the UK, and the great majority of them have been of black African and Asian ethnicity. Doctors are neither socio-economically disadvantaged nor poor. They would not be living in overcrowded houses. 

All citizens of black African and Asian ethnicity have one thing in common: they have dark skins. Dark skin leads to deficiency of vitamin D. 

Melanin-pigmented skin is less efficient than white non-pigmented skin at synthesising vitamin D. Melanin can absorb or dissipate 99% of UV light  and therefore reduces its chemical effect on 7-DHC: there is less synthesis of vitamin D. 

Vitamin D is produced by the action of the sun on the skin, splitting the precursor molecule 7-dehydrocholesterol (7-DHC). Vitamin D enters a cascade process  that results in activation of genes concerned with the defensive immune process (Figure 1).

Figure 1. The activation of vitamin D and its effects

The other important factor is that people of black African and Asian ethnicity tend to have sun-avoiding behaviour, whereas white-skinned people in northern Europe have obvious active sun-seeking behaviour. They take their clothes off when the sun shines, they wear shorts and minimal tops, they go to the sea-side and lie on the beach in the sun, they go on holiday to sunny resorts. People of black African and Asian ethnicity tend not to behave in such ways.

Medoc peninsula, near to Bordeaux

Vitamin D measurements and units

Before looking at the results of studies, we might look at the measurement of the blood level of vitamin D, which is measured as cholecalciferol, 7-(OH)D. The “normal range “ of vitamin D is not an acceptable measure as it would be based on a range found within the population. It would include many who would be regarded as deficient, perhaps half the population. It is preferable to use the term “ideal range”, based on what experience tells us excludes those with disease states or risks that are associated with very low levels of vitamin D. This itself is controversial.

The most well-established disease state resulting from vitamin D deficiency is bone disease. It is due to the fact that ossification is impaired, that calcium cannot be incorporated into the basic fibrous structure of the bones, which is called matrix, a lattice-work of soft tissue. This bone disease is osteomalacia, softening of the bones. When it occurs in children, whose bones are still growing, it is called rickets. The bones bend as the toddler learns to walk. This is unlikely to occur if  the blood level of vitamin D is above 10ng/ml (25nmol/L). To achieve this a very low dose is necessary, perhaps 400units (10mcg) per day, as advised by the UK government through its Scientific Advisory Committee on Nutrition (SACN).

There is another factor. As I pointed out in a previous post, vitamin D when doubly activated to calcitriol in turn activates vitamin D receptors (VDR). VDR is inherited as part of our genome, but over millennia numerous mutations have occurred. When they become part of population genomics the mutations are called polymorphisms (“different shapes”). Some of these are not efficient and fail to activate adequately the intracellular vitamin D responsive elements (VDRE) so that the appropriate genes in the nucleus are not activated.  As a result of these polymorphisms the effects of vitamin D deficiency (such as osteomalacia) can occur even when the blood level of vitamin D is in the ideal range.

Many, if not all, of the researchers who are investigating the effects of vitamin D are of the opinion that the ideal blood level of vitamin D set at 20ng/ml (50nmol/L) is wrong. Long-term follow up of people according to blood level of vitamin D has shown that there advantages in having a level of 30ng/ml (75nmol/L) or even 40ng/ml (100nmol/L)

We see another problem in that there are two units of vitamin D in both blood levels and doses. There was a time when the only measure of vitamin D was to see how much of it would heal rickets in rats. This is the basis of the use of units, an international standard. In more recent years it has been possible to measure vitamin D chemically, hence shift to use microgrammes (mcg) rather than units. 

In many biochemical tests the use of mass measurement has changed to the use of SI units, the French Système International (d’unités). Most nations use this but some do not. For example the USA still uses mass units (milligrammes) for reporting blood levels of cholesterol whereas most the world uses millimoles (the amount rather than the weight of the substance). 

In respect of dose, 400units is equivalent to 10mcg (minimum dose), 2,000units is 50mcg (the daily one that I would recommend).

Sorry about the potential problems, and they can lead to errors.

Covid-19 in the Philippines

A study has just been undertaken in the Philippines by Dr. Mark Alippio, a clinical professor and medical radiation scientist in the College of Allied Health Sciences, Davao Doctors College. It is very recent and an observational study of 212 patients in three South-east Asian hospitals. The study looks at a possible association of vitamin D with Covid-19 clinical outcomes. He obtained information from the medical records of patients in the hospitals, where vitamin D testing was taking place during the Covid-19 epidemic.

We can see from the bar chart in Figure 2 the blood levels of vitamin D in the 212 patients studied. In 25.9% of the subjects  the level is greater than 30ng/ml, in 37.7% in the range 20 to 30ng/ml, and in 36.3% less than 20ng/ml.

Figure 2. Vitamin D status of 212 study subjects

30ng/ml = 75nmol/L,  20ng/ml = 50nmol/L

The study looks at the relationship between blood level of vitamin D and severity of the Covid-19 disease. All had positive tests for SARS-CoV-2 virus. The patients are divided into four groups for the purpose of analysis:

• Mild disease, with normal chest X-ray.
• Moderate disease, with evidence of pneumonia on the chest X-ray.
• Severe disease, pneumonia with respiratory distress and abnormal blood gases (low oxygen +/- high carbon dioxide).
• Critical, involving intensive care.

Patients who had died were not included in this study, which was a "snapshot" rather than a longitudinal study.

The associated blood levels of vitamin D with clinical status can be seen on the bar-chart on Figure 3.

Figure 3. Vitamin D in respect of severity of Covid-19

We see that a blood level of vitamin D greater 30ng/ml (75nmol/L) is found in 85% of those with mild disease.

A similar level of vitamin D is found in only 7.3% of those with moderate disease and in only 3.6% of those with severe or critical disease. It would be interesting to know if these patients had sub-optimal polymorphisms of VDR, but this is well beyond feasibility in this study.

Lower blood levels of vitamin D, less than 30ng/ml, are found in those with more severe and critical disease.

It is not entirely possible to avoid Covid-19 infection, but it is clear from this study that a high blood level of vitamin D is of enormous advantage in keeping the disease at a mild level. This is what we want to achieve.

This study could be repeated today in any UK NHS hospital, as I read is happening in Grenada, Spain. The only things to prevent it are inertia and ignorance. The result would be available within a few days.

In the meantime deaths continue, especially among those of black African and Asian ethnicity, including from the Philippines.

Vitamin D deficiency and Asian ethnicity

I would like to refer to a study that I undertook a number of years ago. It looked at the blood levels of vitamin D in 1574 people of Asian ethnicity and 818 white British. The averages are presented as the median, the middle of the range as will be seen on the bar charts.

First the results from the Asian ethnic group (Figure 4).

Figure 4. Distribution of blood levels of vitamin D with Asian ethnicity

In Figure 4 each vertical column (1574 of them) represents one individual, the height of the column is determined by the blood level of vitamin D in that individual. The orange arrow indicates the median, the middle of the range. 

We can see that the arrow crosses the distribution with the blood level of 9.8ng/ml (22nmol/L), indicated by the yellow line. This is very low and what is called “serious deficiency”. It indicates that more than half of the group are in a range were there is a risk of osteomalacia and seriously suboptimal immune defence mechanisms. It is the range in which Covid-19 might cause critical care need, or perhaps lead to death.

Only 119 out of the 1574 (7.6%) have blood levels above 30ng/ml (75nmol/L), a level indicted by the red line above which a Covid-19 sufferer might anticipate just mild disease. Many vitamin D investigators regard 40ng/ml (100nmol/L) as being the ideal level. Only 15 (1%) have a blood level greater than 40.

Greater than 80ng/ml (200nmol/L) is potentially harmful, but harm from vitamin D is very rare. It is not possible to have blood levels of vitamin D too high from sun exposure because circulation through the exposed skin de-activates surplus vitamin D.

Now we see the results of the subjects with white British ethnicity (Figure 5).

Figure 5. Distribution of blood levels of vitamin D in white British 

The middle of the range, the median, can be seen to cross the range on the yellow line indicating 17ng/ml (42nmol/L). This means that more than 50% of the subjects are deficient in vitamin D as judged by a cut-off level of 20ng/ml, and 150 (18%) are seriously deficient with blood levels below 10ng/ml.

Only 107 (13%) had a blood level above 30ng/ml and 47 (6.7%) above 40ng/ml (100nmol/L).

Implications

These results are alarming and show the extent of vitamin D deficiency in the UK, especially among ethnic Asian people but also among non-ethnic minority people.

Under normal circumstances there might be concern, but now  we are in a national crisis of a pandemic of Covid-19 with 17,333 deaths during the past six weeks. We know that those of black African and Asian ethnicity are over-represented in numbers of deaths and the need for intensive care support, but this information is given to us by the press and not by the government.

The study from the Philippines indicates that we need a blood level of 30ng/ml (75nmol/L) to be safe from serious disease. We can see that in my study of subjects in Blackburn, UK only 7.6% of the ethnic Asian group do the blood levels achieve this. 

We have seen the distribution of blood levels of vitamin D in the subjects of that study. We must remember that the Philippines lie only a short distance north the equator, Davao del Sur is at the southern tip of the Philippines and at only 6.8 degrees north. The British Isles lie between 50 and 60 degrees north, latitudes where the intensity of the sun and vitamin D synthesis are much less.

We can see from the Philippines study the practical demonstration of the danger of a low blood level of vitamin D in Covid-19 infection.


We can also see the proportion of people with black African and Asian ethnicity who are deficient in vitamin D. We know that vitamin D is necessary for our defence mechanisms to be boosted to maximum efficiency, and this is what we all need now.