Thursday, 23 April 2020

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.








14 comments:

  1. I wish the government would read this. I wish Public Health England would read this - instead of recommending just supplementing with 10mcg of vitamin D3 per day.

    ReplyDelete
  2. So what are you doing to get this information out there to the people that need to know?

    ReplyDelete
    Replies
    1. Ask a question at the coronavirus press conference

      www.gov.uk/ask

      I have posted material to Keir Starmer (my MP) and emailed Chaand Nagpaul the BMA BAME boss (he said it is one of many factors and has not mentioned it since) and some journalists.

      Delete
  3. come read many more fascinating articles/posts about Vitamin D3 and Covid-19 at this facebook group>>>

    Coronavirus COVID-19 Censored Information By the Other CV -PANIC groups

    https://jefftbowles.com/vitamin-d3-deficiency-is-killing-blacks-with-covid-19-at-5x-the-rate-of-whites-with-covid-19/

    https://www.grassrootshealth.net/blog/first-data-published-covid-19-severity-vitamin-d-levels/
    In several posts over recent months, we have discussed the many ways that optimal vitamin D levels are necessary to initiate and maintain a healthy immune response, especially within the respiratory system. Our paper, Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-1...

    GRASSROOTSHEALTH.NET
    First Data to be Published on COVID-19 Severity and Vitamin D Levels - GrassrootsHealth
    In several posts over recent months, we have discussed the many ways that optimal vitamin D levels are necessary to initiate and maintain a healthy immune response, especially within the respiratory system. Our paper, Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-1...

    ReplyDelete
  4. This is a letter I have just sent to the Guardian...I am a retired British endocrinologist and I live in Italy. This epidemic is really about nationwide Vitamin D deficiency, a newly modified virus, and the folly of relying on ‘expert’ committees rather than science and good sense. Throughout evolution, we have always been confronted by new viruses that exploit weaknesses in our bodies and brains. We have evolved a front-line defense system that depends on Vitamin D3, a unique chemical produced when UV light from the sun breaks 7-dehydrocholesterol deep in our skin. Antibodies come later, and will only save those who also have this first line of defense. That is why dark-skinned people in the UK, including health care workers, are dying in disproportionate numbers, with our paltry sunlight and their natural sunblock. It would cost £50 million to make the whole of Britain instantly Vitamin D-replete for three months, by each of us taking a mere 2,5 mg (100,000IU) of cholecalciferol (AKA Vitamin D3) NOW. But ‘NICE’ NHS experts have set amounts we can legally buy far too low, and, appealing to their own puffed-up authority, forbid us to buy decent levels off our own bat in any pharmacy, as we can do legally in Italy. Last week one such committee in Manchester actually turned down my offer to send 1200 such doses for front-line NHS staff at Manchester’s new Nightingale Hospital. Such mindlessness may help Big Politics, Big Pharma and Bill Gates, but it unnaturally selects against the rest of us, and especially our BAME colleagues.

    Professor David C Anderson MD MSc FRCP FRCPath

    ReplyDelete
    Replies
    1. please write to the FT, NY Times and the Times. The WSJ already carried an OpEd piece on Vit D and COVID

      Delete
  5. Interesting.
    But, how does this relate to the terrible effect of CV-19 in Italy and Spain? I live in Andalucia, and the coast along by Marbella and Fuengirola - where there's a large N European population - has been the worst affected in the region. Plenty of leather-skinned erstwhile pasty Brits and Germans and Swedes, etc, over there, clearly getting lots of sun. I live in a mountain village of mainly Spanish people, where there's been one case of CV-19, and locals religiously keep out of the sun all year round. Vitamin D deficiency is a growing problem around the world, it has been suggested this is to do with low Magnesium levels due to soil depletion - even home grown, organic veg are reputed to provide less Mg than 50 years ago. where I live, all the produce is from the campos around us, there's no large scale agribusiness, and methods are same as they were centuries ago. If you don't eat the fruit and veg pretty much within a couple of days, it collapses and goes rotten overnight. Of course, behaviours are implicated in your theory, and I am especially concerned with some groups of UK based children being covered all day (I used to live in east London) but, we surely need to ask more questions about why Vit D deficiency is becoming such a problem?
    Thanks for a stimulating piece of work!

    ReplyDelete
    Replies
    1. I think you're right about the magnesium...

      Delete
    2. Pollution in Italy - Dr Grimes addresses that in a blog post twice back: http://www.drdavidgrimes.com/2020/04/vitamin-d-and-immunity-important.html

      Delete
  6. There are bound to be multiple variables, viz... In the virus itself; in skin colour; in latitude and weather; in behaviour vis a vis the sun; in social class; and in VDR polymorphisma. Maybe there are more. But all of this means that, since there is no downside to having a high 25(OH)D3 level until you get way above 70 ng/ml, but a big downside at the lower limit of normal, we need a high intake to provide optimal cover for all possible subgroups. IMHO, 2.5 mg of Cholecalciferol as a single dose every 2 months is about optimal. Taken 6 times a year, you have good compliance and it is economical, and easily tracked. The dose can then be fine-tuned for such variables as BMI and gender.

    ReplyDelete
  7. As I understand it, vitamin K2 is also needed to 'direct' calcium to bones and teeth instead of accumulating in soft tissues and creating havoc. Vitamin K1 is found in dark green leafy veg but apparently it isn't always converted to the helpful form K2 in the body very well, which may be a problem for vegetarians and vegans who avoid animal products. K2 is found in things like Gouda cheese, butter, egg yolks, dark chicken meat etc.

    ReplyDelete
  8. It looks like US prisoners may all have been infected with COVID-19 but 96% are asymptomatic. Many are black or latino (groups with high COVID-19 mortality in the general US population). This could reflect the amount of exercise taken outside and their above average vit D status:
    uk.reuters.com/article/uk-health-coronavirus-prisons-testing-in/in-4-u-s-state-prisons-nearly-3300-inmates-test-positive-for-coronavirus-96-without-symptoms-idUKKCN2270RY

    'The Vitamin D Status of Prison Inmates'
    With respect to sun exposure, inmates at the minimum security level were allowed an average daily sun exposure of about 5–10 hours/day during which time they may engage in exercise, working outside the facilities as road crews, park maintenance crew, or in farms. Inmates at the medium security level spent an average of 1–5 hours/day in recreational activities under supervision. Inmates at the maximum security level spent only one hour in recreational activities per day under a heavy guard.
    'The Vitamin D Status of Prison Inmates'
    www.ncbi.nlm.nih.gov/pmc/articles/PMC3944727

    This study shows that black prisoners have lower incidence of vit D deficiency than in the African American population as a whole and that vit D levels increase with time spent in prison. It is in Massachusetts prisons and I imagine the effect would be more pronounced in southern states with higher UVB intensity.

    ReplyDelete
  9. please also see King, E. (2020, June 17). The Role of Vitamin D deficiency in COVID-19 related deaths in BAME, Obese and Other High-risk Categories. https://doi.org/10.31232/osf.io/73whx

    ReplyDelete
  10. Lypharbio provide both powder and oil form for vitamin K2 mk4 and mk7 supplements with different specifications. We use pharmaceutical grade excipients, which is suitable for various health-enhancing products. The excipients also can be customized according to customer requirements. Lypharbio supply both natural and synthetic for vitamin mk7 powder. vitamin k2 powder suppliers

    ReplyDelete