Sunday, 28 June 2020

Covid-19 & Vitamin D : more information


The pandemic of Covid-19 is running its course and it is now approaching its end. We might be told by government spokespersons that "we are winning", but that is fantasy. What would have happened if we had lost? 

There will now be many trillions of Covid-19 virus copies and we cannot destroy them all. Similarly they cannot all mutate into a milder form simultaneously. To do so would not be an advantage for Covid-19 as it already has a low population mortality rate. It is a disadvantage for a parasite to kill its host as then it and subsequent generations will die. Talk of eradicating a virus is wrong  as viruses do not "go away". 

Pandemics come to and end because we either die or develop immunity: it is the disease that goes away, not the virus. The incidence of winter respiratory virus diseases declines when in April the intensity of the sun at 50 degrees north of the equator becomes adequate to produce vitamin D on exposed skin.



UK experience
It is interesting to look at what has happened in the UK. We have had a large number of cases and deaths from Covid-19 (309,360 cases, 4583 per million population).  What is meant by a "case" is not always clear. It could be a mild and brief upper respiratory tract infection or it could be life-threatening pneumonia that is survived. International statistics do not differentiate. Death is more definite, but there is still a dilemma. If an elderly person with an advanced chronic disease such as dementia contracts Covid-19 and dies, it is likely that Covid-19 will be recorded as the cause of death, but not always. It could be argued that Covid-19 is only about 10% responsible for death, and advanced dementia the remainder. If a young person is killed in a car crash and tests positive for Covid-19, I hope that road traffic accident would be the registered cause of death.

Cases per million world-wide


San Marino, and to a lesser extent Andorra, have had a bad time during the pandemic. We can see that they have had by far the largest number of cases per million. They are small states, with populations of 33,400 and 77,200 respectively. If we remove these two unusual and rather tragic "outliers", we can appreciate the larger nations.




Vatican City has had 12 cases of Covid-19. With a population of only 801 this works out at 14,981 cases per million. There have been no deaths.

Two months ago Luxembourg had by far the most cases per million, but several others have now caught up and the USA has surged ahead. A large number of cases is not always matched by a large number of deaths. Unfortunately it is in San Marino and Andorra.

Deaths per million world-wide

Add caption

The UK has at present the fourth highest number of Covid-19 deaths per million in Europe, perhaps in the world. San Marino still has the highest, with Belgium second. Andorra has a slightly higher number than the UK. We can also identify the few nations with more than 200 deaths per million population.

It is tempting to compare two countries to try to explain the differences in incidence or deaths. It has been attempted by many experts but they have given up. Comparing two countries cannot result in a meaningful conclusion. There are 215 nation states on the WorldoMeter web site but only one pattern does appear. This is a latitude effect, case severity rates increasing with distance from the equator. This is most notable in the northern hemisphere, and it is Europe that has seen the major impact of Covid-19.

Whatever we have done in the UK to prevent deaths can hardly be described as a great success. But there remains something that could have been of great benefit, but of which the government's medical-scientific advisors have remained ignorant or which they have negligently ignored. It is Vitamin D.

Messages from the Far East
The early observations from the Far East indicated a high death rate of people with very low vitamin D levels. We have seen three of these in previous posts, and now there are others from Singapore, Germany and the UK. once again they are "preliminary reports" that not have been "peer-reviewed". The objective is to provide rapid help for those who trying to deal with the pandemic, not to write a retrospective review.

Singapore
This study assessed the severity of Covid-19 in an individual by whether there was a need for oxygen therapy. On admission 17 patients were given a combination of vitamin D, magnesium, and vitamin B12 (DMB). 26 patients acted as controls. 3 of the 17 given DMB turned out to requires oxygen, compared to 16 out of 26 in the control group. 2 of the DMB group required ITU admission compared to 16 in the control group. 

As a result of this short study, all patients subsequently admitted to hospital with Covid-19 in Singapore have received vitamin D, magnesium, and vitamin B12..

https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v1.full.pdf

Germany
This studyundertaken in Saarland,  was retrospective and was not directly concerned with Covid-19. It had followed up for ten years 9,548 people aged 50–75 and assessed mortality patterns. Vitamin D deficiency was defined as less than 12ng/ml (30nmol/L), which is a level that will not lead to bone disease (rickets or osteomalacia). 

A blood level of 12 to 20ng/ml (30 to 50 nmol/L) was defined as vitamin D insufficiency. The studies from the Philippines and Indonesia used vitamin D 30ng/ml (75nmol/L) as threshold for ideal blood levels. Apart from the use of two measurements, the lack of a consensus of the ideal blood level of vitamin D means that studies are not always comparable.

First, it found that most of the people had inadequate levels of vitamin D. 15% had very low levels of vitamin D, less than 12ng/ml (30nmol/L). 44% had levels 12–20ng/ml (30–50 nmol/L). This in itself is alarming; very few will have had vitamin D levels greater than  30ng/ml (75nmol/L).

The result was a two-fold increase in mortality from respiratory disease in those deficient or insufficient in vitamin D, with blood levels less than 20ng/ml (50nmol/L. It is suggested that this should be relevant in the prevention of deaths from Covid-19, and that correction of widespread vitamin D deficiency / insufficiency should receive attention.

https://pubmed.ncbi.nlm.nih.gov/24682834/

Newcastle upon Tyne, UK
A short observational study compared patients who were managed on a medical ward compared to those who had deteriorated to the extent that they required ITU care. Those requiring ITU care had lower blood levels of vitamin D, indicating that in at least one UK hospital blood levels of vitamin D were actually being measured. The ITU patients were also younger, but this might have been due to an admission policy. 

https://www.medrxiv.org/content/10.1101/2020.06.21.20136903v1

Evidence
The evidence increases in favour of a benefit from vitamin D in the prevention of serious and fatal Covid-19. There have been many observational studies that have all shown a similar benefit from vitamin D, and there have been no studies that have shown the opposite. There is no evidence of undesirable effects. On June 25th 2020, there have been 9,560.837 reported cases of Covid-19 and 485,622 deaths, We have not been made aware of a single case of ill-effect or death from vitamin D.

Judgement
Whether or not to take or advise vitamin D requires judgement, a balance or risks, weighing possible benefit against possible danger. The possible benefit is "not dying". There is no danger. 

Is there a dilemma? No!



Further action and the "second wave"
The obvious way to stop a pandemic (the serious disease not the virus itself) is to optimise the immunity of the population. As explained earlier, this cannot be achieved by a vaccine as the time-scale is much too short, and it is not of course possible to develop the vaccine before the virus has emerged. Immunity is optimised by making certain that the immune system has available a good reservoir of vitamin D to enable escalation at the time of serious infection, for example Covid-19. 

Vitamin D cannot be synthesised
The point is that vitamin D is a vitamin, meaning that it is not possible for the body to synthesise it. The body can synthesise 7-dehydro-cholesterol (7-DHC) and this has been feature of animal life for more than 500 million years. It is an accident of evolution that UV light from the sun converts 7-DHC into vitamin D (Hormone-D if you prefer). This is a physico-chemical processes and not metabolism. The immune cells covert 25(OH)D (the circulating blood reservoir of vitamin D) into 1,25(OH)D, the active form but this can ahead only if there is adequate 25(OH)D in the blood. During a serious infection vitamin D as 1,25(OH)D is "consumed" and so the blood level will fall, but it will remain in the ideal range (>30ng/ml) as long as the blood level was good (about 40ng/ml) initially.

What is the ideal level of vitamin D?
This brings us to consider the controversial point as to  the "normal" blood level of vitamin D. Normal is a statistical concept, meaning what is found in about 90% of the healthy population. It is appropriate in a metabolically controlled substance in the blood, such as sodium (Na), but it is not appropriate in respect of vitamin D, which cannot be synthesised and which is not under metabolic control. 

It is appropriate to use the term "ideal" as the blood level of vitamin D (as 25(OH)D.


The Maasi people of east Africa are found where humankind originated and from where most have emigrated to lands distant from the equator. They live an outdoor life-style close to the equator, and have dark skins that protect them from the high energy UVB light to which the are exposed. The availability of industrial textiles today will improve protection from the intense sunlight.

It is interesting that the great apes have white skin, and this is protected from UV light by thick hair. It was when evolution progressed in East Africa to relatively hairless Homo Sapiens that a dark skin became an evolutionary advantage. The earlier Neanderthal man is thought to have had a pale skin, giving an advantage in emigration to Europe.

The Maasai people have an average blood vitamin D level slightly greater than 40ng/ml (100nmol/L). This is the safe and effective level that evolution and nature determined. We should accept this as the ideal, with observation that it gives a health advantage, for example Philippines, Indonesia, Singapore. 

Vitamin D deficiency 
Emigration, "civilisation", and religion have diminished exposure to the sun, but evolution has given an advantage to those with white skins when living far distant from the equator, especially in extreme north-west Europe. This was millennia ago, but during the 19th and 20th centuries there was a large migration from South Asia and Africa to Northern Europe and North America. It is clear that this transmigration has resulted in a poor health profile. Although initially there is inevitably social-economic disadvantage, vitamin D deficiency will also become inevitable. This is the main and the most easily reversed reason for the poor health profile of BAME people, clearly demonstrated in the Covid-19 pandemic

It is negligent that BAME people in the UK and other countries are generally not informed of their inevitable vitamin D deficiency. For reasons that are also negligent, blood testing for vitamin D are discouraged. However I tested blood vitamin D levels in 1,500 South Asian people and the results are in a previous post. Pregnant BAME women are often but always given vitamin D supplement.

Some ethnic Asian friends tell me that now knowing about the dangers of vitamin D deficiency and their susceptibility to it, they spend more time outdoors in the sun. This is commendable, but there remains the fact that melanin, the skin pigment, absorbs UV light and is an excellent sun-screen. It diminishes production of vitamin D.

To ensure a good supply of vitamin D as 25(OH)D in the blood,] (40nm/ml, 100nmol/L) it is usually necessary to take a supplement by mouth, about 3,000 units per day.

Coming very soon:

















6 comments:

  1. Dear David
    Thank you for informative article. I do not know why you have not included India in your graphs where the infection is rising exponentially

    ReplyDelete
  2. I feel significant information.

    ReplyDelete
  3. It is frustrating that the Talking Heads on TV lament the severity of Covid but are afraid to say "Take Your 4000 IU Vitamin D Daily!" In the UK, 94% of doctors dying are BAME (non-white). Only 44% of physians are BAME. These are people who have money and access to healthcare. And they died! Take Your D! It will not stop Covid, will not stop the spread (masks do!), but it may make sure you survive!

    ReplyDelete
  4. NICE report on Covid-19 and Vitamin D has just been published. The key message is "There is no evidence to support taking vitamin D supplements to specifically prevent or treat COVID‑19. However, all people should continue to follow UK Government advice on daily vitamin D supplementation to maintain bone and muscle health during the COVID‑19 pandemic." Also states "It has also been hypothesised that vitamin D may have a role in the body's immune response to respiratory viruses." This is unbelievable, as it ignores much recent evidence and it still goes on about taking 400 IU/day. I wonder who has influenced the panel of reviewers.

    Dr Roy Fisher
    Retired Consultant Clinical Biochemist

    ReplyDelete
  5. Im sure the graph of covid19 deaths/million has the wrong figure for italy. I believe it would be above 550 for italy so larger than shown on your graph

    ReplyDelete