COVID-19





The role of vitamin D and COVID-19

29 June 2020 - Eshani Kings's article was published on the Cytoplan website...

'This in-depth and detailed article is provided by Eshani King, a researcher in immunology and health.

It is now widely known that a disproportionate number of COVID-19 related mortalities in the UK have been in non-white, BAME populations [2]. The obese, diabetics, hypertensives and the elderly have also been disproportionately affected. BAME doctors account for 94% of total deaths of doctors but comprise 44% of doctors [1]. The suggestion that these deaths result from deprivation does not fit with the high numbers of deaths of doctors and others in higher socio-economic classes; there must be a different and perhaps more comprehensive explanation.

This review examines the compelling body of evidence strongly implicating varying levels of serum vitamin D levels in the significantly disparate outcomes between different groups of people and between different countries. It explores the extent of vitamin D deficiency, highlighting countries and categories of people most likely to be deficient.'


Vitamin D

Can it help with COVID-19?

Why it is essential and how to ensure you get enough.

Eshani King, Researcher in Evidence Based Immunology and Health

2 May 2020, updated 5 June 2020

(The graphs mentioned have not been capable of being reproduced.)

1. Introduction to Vitamin D

Vitamin D is a fat-soluble vitamin. Other fat-soluble vitamins are A, E and K, but vitamin D is quite unique and very unlike other vitamins for two significant reasons:

  • Firstly, it is not really a vitamin but acts as a hormone throughout the body. Like all sex hormones, for example, oestrogen and testosterone and all steroid hormones, for example cortisol and adrenaline, vitamin D is synthesised from a starting point of cholesterol.

  • Secondly, it is the only “vitamin” that we have evolved to derive mainly from sun exposure rather than from food sources.

Vitamin D (the same form as that found in D3 supplements), is made by the action of UVB sunlight on 7- dehydrocholesterol in the skin. It is then converted in the liver to an intermediary form, 25 (OH)D or 25-hydroxyvitamin D. This is converted in the kidneys or other cells by the action of 1 α-hydroxylase to the active form 1,25 (OH)2 D or 1,25- dihydroxy vitamin D, also known as calcitriol.

  • Calcitriol functions as a hormone in every cell of the body, all of which have vitamin D receptors (VDR) for binding it.

  • VDRs are nuclear transcription factors, epigenetically controlling the expression of up to 2,000 different genes. They are found in abundance in the cells of the immune system and various other tissues including the prostate gland, breast, and the brain. Its role in the brain remains to be explored.

  • In addition to its long-known role in bone health, vitamin D also plays an important and central role in immune-enhancement and immune-modulation. The cells involved in immunity also have the enzyme 1 α-hydroxylase found in the kidney which converts inactive vitamin D to active calcitriol. This means that these cells have access to additional active vitamin D. Having sufficient Vitamin D can optimise the immune system’s response to infections such as SARS-CoV-2.

  • It is less well known that optimum vitamin D status can also help prevent the many health conditions and cancers listed further below.

  • Very little, or approximately 10%, of our vitamin D needs can be met by food; humans were originally dark skinned and evolved near the equator to derive the vast majority of their vitamin D needs directly from sun exposure.

The pigment melanin in darker skins that protects skin from burning and damage from UVA light also prevents some UVB light reaching the layers where the vitamin is made, but this is a good compromise where sunshine is strong. As humans moved gradually northwards, they adapted to the lack of sunlight by losing the melanin pigmentation and becoming light-skinned enabling continue to make enough Vitamin D. The further north people migrated, the lighter skinned they became. The bones of these people also became smaller in order to compensate for the lack of availability of vitamin D which is necessary for bone health and for absorption of calcium. This is the most likely rationale for these two adaptations in Caucasian populations. Today, people of African origin retain their genetically superior bone size and bone density and are therefore more resistant to osteoporosis in later life, but they are vulnerable to becoming vitamin D deficient when they no longer live in places with sufficiently strong UVB light.

In 1920, the importance of sunlight for immunity was understood even though vitamin D, a fat soluble vitamin, had not yet been identified; TB patients were put out in the sunlight in what was then known as “solariums” and fed cream and egg yolk. Children were given cod liver oil daily, one of the very few good food sources of vitamin D and people consumed far more animal fats, and oily fish. Fast forward one hundred years to 2020, and we seem to have forgotten many of the basic factors required for an optimally functioning and powerful immune system. What little vitamin D we do get from our diet is far less than it was two generations ago because of modern avoidance of dietary animal fats and the increasing number of vegetarians and vegans. The type of vitamin D, D2 or ergocalciferol, found in vegetarian sources is slightly different in chemical composition to D3 and has been shown in studies to be poor at converting into the active form of vitamin D in the body.

However, the single major factor contributing to low vitamin D status today is undoubtably far less exposure to UVB from sunlight due to a combination of various factors; greater periods of time spent indoors on computers etc., the increased use of UV blocking sun creams and the general belief that sun exposure is harmful. This has unfortunately led to a massive deficiency of this critically important hormone in the UK population.


2. How Widespread is Vitamin D Deficiency?

2.1 Vitamin D Deficiency in BAME Populations v White Caucasians

It is generally known that BAME populations living in the UK and the US are deficient in vitamin D. Let us look at how deficient they might be. To do that we need to be familiar with what serum levels of 25(OH)D relate to deficiency, sufficiency, and optimal status

  • a serum level of 20ng/ml is generally accepted as being enough to prevent deficiency and resultant conditions such as rickets, osteoporosis and osteomalacia,

  • 30 ng/ml is “sufficient” but not optimal.

  • it is thought by at least 48 experts in this field that a far higher level of 40-60ng/ml is required to achieve optimum immune system and cancer fighting capability.

  • 40-60ng/ml is also the level required to achieve normalised parathyroid function and the level maintained by indigenous peoples such as the Maasai, despite their very dark skin.

Interestingly, studies have found that men generally have lower vitamin D levels than women.

The following is a table produced by Grassroots Health, USA showing rates of deficiency and sufficiency in different ethnic groups in the US. The differences between BAME categories and the white population are very striking.

  • Only 6% of black ethnic groups have optimal vitamin D levels of 40ng/ml but surprisingly,

  • only between 15-20% of white skinned individuals attain this level.

  • The most dramatic difference is that whilst only around 15% of the white population is deficient, meaning they have levels below 20ng/ml,

  • between 55-60% of the black ethnic population is deficient, a very high percentage.

  • The vitamin D status of Asians, Hispanics and others lie in between these extremes.

This demonstrates that although vitamin D deficiency is a significant problem in the BAME community, it is a far more widespread issue, with many who are white skinned also suffering from vitamin D insufficiency and less than 20% of them achieving optimal serum levels of at least 40ng/ml in the US.

The level of deficiency in the UK is far worse. According to a published study, the UK has the highest levels of deficiency in Europe with average blood levels of only 19 ng/ml, under half the minimum optimal level. The level of vitamin D deficiency in the UK and N Ireland is quite startling.

  • 56.4% and 66.2% of the population have levels below 20ng/ml; similar to that seen in the American black population in the table above.

  • The UK is followed closely by Belgium with 19.7ng/ml.

  • No other country comes close to the UK for severe deficiency; however, the percentage of the population with levels below 10 ng/ml is over 15%, with Belgium again in second place with 7.3%.

Given these are the averages for the whole population, the vitamin D levels for BAME populations in Britain are therefore likely to be far worse. This has significant implications for the entire BAME community, and most of the white skinned population too, many of whom may well be suffering ill health from conditions which could have been avoided had they had adequate levels of vitamin D.

In addition to the disproportionate number of COVID-19 related deaths in the BAME communities in the UK, it is of note that the Somali population of Sweden has also suffered disproportionately: despite comprising less than 1% of the population, press reports on 11 May state that they accounted for 18% of COVID-19 related deaths countrywide and 40% of Stockholm’s COVID-19 related deaths.

Generally, however, vitamin D status in Scandinavian countries is, given their latitude, surprisingly better than southern European countries with average serum levels of 26-29 ng/ml. This is thought to be the result of widespread awareness of the issue, food fortification having been in place for many years, and a far higher consumption of vitamin D containing oily fish and fats. It is interesting that as a result of a review by the independent Swedish Council on Health Technology Assessments of 16,000 studies through May 2013, the Swedish were advised to consume plentiful quantities of animal fats and cream and to eliminate/reduce sugar and carbohydrates as a strategy to prevent diabetes, cardiovascular disease, and obesity. Meanwhile, in contrast, nutritional advice in the UK has been strongly geared towards a low animal fat diet.


2.2 What Other Categories of People Might be Vitamin D Deficient?

What is perhaps not generally known is that the obese, another high-risk group for COVID-19, are also highly likely to be vitamin D deficient as they require 2-5 times (or even more) vitamin D than others, dependent on the level of obesity. Unless they are taking exceptionally high levels of supplements they are highly likely to be even more deficient than BAME categories. The fat-soluble vitamin is thought to become trapped in fat cells although the exact biochemistry of this is uncertain. The elderly is another category highly likely to be vitamin D deficient unless they supplement as older skin gradually loses the ability to make vitamin D by up to 75%.

It is also of note that virtually all of the other remaining categories that have an increased risk from COVID-19 are also likely to have a high level of vitamin D deficiency. Other health conditions well documented in a vast body of medical literature, including interventional studies, shown to be caused by (and not merely associated with) lack of optimal vitamin D include:

- asthma, allergic rhinitis, and other respiratory diseases - Crohn’s disease

- high blood pressure - dermatological conditions

- heart disease - bone loss

- fatigue (often misdiagnosed as fibromyalgia) - hair loss

- bone and back pain - muscle pain

- depression - infertility

- obstructive sleep apnoea -acute respiratory infection

- nasal polyps - Otis media

- diabetes - chronic rhinosinusitis

- cancer (including breast, melanoma, ovarian, prostrate, head and neck, Hodgkin’s, and non-Hodgkin’s lymphoma) -Alzheimer’s

- osteoporosis -osteoarthritis

- autoimmune diseases e.g. lupus, rheumatoid arthritis -asthma

Although there may also be other factors involved in the above conditions, such as various nutrient deficiencies and the metabolism of excessive quantities of carbohydrates/glucose, vitamin D deficiency is thought to be a major contributory factor in the genesis of these conditions. Although high serum vitamin D levels could have prevented their onset, subsequent supplementation may or may not be effective in alleviating a condition once it has become established, depending on the nature of the particular conditions.

Despite this, there is still every expectation that increasing the serum levels of vitamin D for people with these conditions, all of whom are highly likely to be vitamin D deficient, can help combat viral infection as this involves different biological mechanisms.

It is of interest that some pharmaceutical drugs including some antihypertensives, antibiotics, antiepileptics and anti-inflammatory agents used to treat some of these conditions can reduce serum vitamin D, exacerbating existing vitamin D deficiency.

All-cause mortality has also been shown in a number of robust studies to be inversely related to serum vitamin D levels; the lower your vitamin D levels, the more likely you are to die of any cause. Many conditions associated with vitamin D deficiency have already been mentioned but that list is by no means exhaustive. As the requirements for vitamin D rise in pregnancy, vitamin D deficiency is all too common in pregnancy and is implicated in the potentially dangerous condition of pre-eclampsia. Vitamin D deficiency in pregnancy not only has implications for the mother’s own health but will also cause the unborn child to be epigenetically “imprinted” to be susceptible to chronic disease in later life. It is therefore very important that expectant and breast-feeding mothers continue to receive adequate daily dose of vitamin D.


3. Connection Between Vitamin D Deficiency and Respiratory Tract Infections

Multiple cross-sectional studies and interventional studies (where giving vitamin D supplements improved outcomes) have associated lower vitamin D levels with a statistically significant increase in rates of infection with respiratory viruses including influenza .

A recently published paper, William B. Grant et al “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths” April 2020: https://www.grassrootshealth.net/wp-content/uploads/2020/04/Grant-GRH-Covid-paper-2020.pdf discusses the sizeable body of compelling literature evidencing the role of vitamin D in preventing respiratory illnesses, and also suggests possible reasons why no association was found in other research. Note that these include inappropriate supplement dosing (e.g. too little, or huge monthly doses rather than daily) or not ensuring that test subjects had adequate nutrients, deficiencies of which could prevent a vitamin D intervention from being effective, particularly magnesium and vitamins A and K2.

In addition, Dr Rachel Neal who is currently leading the world’s second largest trial of high dose vitamin D supplementation, reported that a study of 78,000 patients last year found that patients with low levels of vitamin D were twice as likely to develop acute respiratory infections and be sicker for longer that patients with high vitamin D levels .

In another study described by Dr Holick, it was demonstrated that supplementing one group of postmenopausal women with 2,000 IU of vitamin D resulted in a 90% reduction in upper respiratory tract infections compared with a group receiving only 400 IU. Note that 400 IU is the level currently recommended by Public Health England. In another study, vitamin D blood levels of at least 38ng/ml were associated with a two-fold reduction in the risk of developing acute respiratory tract infections. In contrast, as already noted, the average serum level for the UK is only 19ng/ml.

Although the 1918 Spanish flu is not examined further here it may be of interest that the sunnier US states such as Texas were observed to have had lower death rates than the Northeast.

The seasonality of flu very probably has little to do with the premise that viruses degrade in the heat (which needs far higher temperatures than our UK summers) but more to do with the fact that we rely on sunlight for a high proportion of our vitamin D requirements. Any reserves of vitamin D made in the summer months, meagre as they are, are depleted from September onwards so that by December/January, serum levels become perilously deficient in many people.


4. The biological role of Vitamin D in the immune response to infection

This is a very simplified account of what is a highly complex interacting system of responses by the human immune systems. All cells involved in the immune function are richly endowed with vitamin D receptors. Vitamin D status can determine whether or not a virus can be dealt with by the body’s first line of defence, the innate immune system, which responds within a matter of minutes and hours. The response includes vitamin D dependent stimulation of natural killer cells and various types of T cells and leukocytes; production of the powerful human antivirals, cathelicidin and defensins; glutathione; interferons; and an array of other inflammatory and anti-inflammatory cytokines and chemokines. Vitamin D plays a central role in balancing cytokines to prevent inflammation which can result if the level of pro-inflammatory cytokines escalate in an uncontrolled manner in what is often referred to as a cytokine storm, sometimes seen in COVID-19 critical cases.

A strong and balanced response by the innate immune system is often able to fight off infection within a few hours or days resulting in asymptomatic or mild cases. If not, the infection will progress and, antibodies will start to be produced by the adaptive immune system in 5-7 days. Vitamin D again acts as an immunomodulator in the adaptive response, preventing over stimulation of the antibody producing system and B cells which can otherwise result in autoimmunity, a condition in which antibodies start attacking a person’s own body.

Vitamin D is also an anti-coagulant, known to reduce blood clotting which can lead to hypoxia, or lack of oxygen, another serious consequence of some COVID-19 infections.

Asymptomatic cases: Mild or no symptoms can also be the result of a previous encounter with the same virus or a virus which had similar antigens. For instance, recent research has shown that 50% of people have existing memory in the form of T-cells from previous encounters with one of the 4 cold causing coronaviruses that can also recognise and cross react with antigens, including the S spike protein, from SARS-CoV-2. This is good news as it could mean half of us probably have some degree of pre-existing immunity. If this is proved to be the case then only a further 20% or so need to contract the virus before herd immunity is achieved.

Gender differences: Major genes coding for innate immunity are located on the X-chromosome. Women therefore have two copies and men, one. The interaction of these genes together with their generally higher vitamin D status as well as hormonal factors are thought to result in women being less adversely affected by COVID-19 and by all infections generally than men.

Children have less developed and less specialised adaptive immunity which produces broad spectrum, less specific antibodies and are thus more dependent on the first line defences of their innate immune response. The maturing immune system is also primed towards an anti-inflammatory state. In addition, children tend to have greater sun exposure and therefore higher vitamin D levels. They also have greater exposure to dirt and a higher level of interaction with micro-organisms in the general environment, all of which re-enforce and strengthens the innate immune response. It also plays a critical role in maturation of the developing adaptive immune system. The stronger innate and anti-inflammatory responses might be reasons why children are far less affected and are mostly asymptomatic.

Common misconceptions about the importance of antibodies: Whist antibodies are very important; the absence of specific antibodies does not necessarily mean that a person cannot fight off an infection nor that they will not develop immunity. Antibody production is only part of a whole arsenal of defensive responses and it is not the sole or indeed necessarily the main way in which immune memory is established. T cells can also “remember” a previous infection. There have been recent COVID-19 cases of two adults who have agammaglobulinemia, a genetic mutation rendering them incapable of producing the B cells that produce antibodies. They nevertheless overcame a COVID-19 infection, and although they became quite ill with pneumonia, neither needed a ventilator or intensive care. This is reminiscent of several similar cases reported in the late 60’s where children with agammaglobulinemia overcame measles in the normal fashion with similar symptoms to a child without the condition and developed immune memory despite having no antibodies.

Conversely, a high level of antibodies does not necessarily mean a high level of protection. In fact, the prevalence of a high titre of a certain type of antibody called a binding antibody actually results in a subsequent encounter with the same virus triggering a full blown hyper-inflammatory reaction and possibly even death. This has been seen in previous vaccines to Dengue, RSV and other coronaviruses. Our immune systems are far more complex than we are led to believe by certain sections of the media. Vitamin D plays an important role in producing balanced responses and reducing inflammation or inappropriate immune responses.


5. New Evidence linking COVID-19 Related Deaths to Vitamin D Deficiency

5.1 Connections and Correlation Studies

A recent study of 20 European countries by Queen Elizabeth Hospital Foundation Trust found a correlation between level of vitamin D deficiency and COVID-19 related deaths and cases. https://link.springer.com/article/10.1007/s40520-020-01570-8

It is of note that the UK and Belgium, the very two countries that have the highest levels of vitamin D deficiency in Europe are also those with very high numbers of COVID-19 related deaths per million of population.

A recently published pre-print of research by Northwestern University analysing data from 10 countries found a strong correlation between low vitamin D levels and cytokine storms in COVID-19 patients as well as a correlation between vitamin D deficiency and mortality: https://www.medrxiv.org/content/10.1101/2020.04.08.20058578v4, with commentary by the researchers at: https://www.sciencedaily.com/releases/2020/05/200507121353.htm

Recent Irish research published by Trinity College, Dublin, the TILDA study, https://tilda.tcd.ie/publications/reports/pdf/Report_Covid19VitaminD.pdf

also supports the premise that vitamin D deficiency is widespread and is likely to be a major factor in poor outcomes from COVID-19.

Another point of interest is that UVB light required to make vitamin D is blocked very effectively by air pollution. Northern Italy and Wuhan where COVID-19 related death rates were much higher than elsewhere are both known to suffer from particularly poor air quality. Whilst air pollution was thought to be a factor in the very high death rates in these two areas, lack of vitamin D may have compounded this effect.


5.2 Direct Evidence for Vitamin D Deficiency in COVID-19 Related Deaths

We now have direct evidence linking deaths and critical outcomes to COVID-19 related deaths from studies yet to be peer reviewed. This following graph from Grassroots Health summarise the results of a small study from the Philippines. It illustrates that only 4% of those who had vitamin D blood levels above 30ng/ml became critically or severely ill, whilst 96% of those whose levels were below 30ng/ml became critically or severely ill. 96% of mild cases were found to have sufficient, >30ng/ml, blood levels of vitamin D. The researchers did not look at optimal levels above 40ng/ml.

Indonesian research published more recently and updated on 6 May using data from 780 patients who had tested positive for COVID-19 [71] have confirmed these findings. While only 4% of patients with sufficient levels of vitamin D (>30ng/ml (OH)D) died, the mortality rate was 87.8% and 98.9% in the insufficient (20-30ng/ml) and deficient (<20ng/ml) groups, respectively. After adjusting for confounding factors such as age, co-morbidities and sex, the researchers still found that death was 7.63 times as likely in the insufficient group and 10.12 times as likely in the deficient group.

When taken together with the large body of interventional studies on respiratory infections, the strong biological plausibility, the correlations between countries, and the knowledge that high risk groups are almost certain to be vitamin D deficient to begin with, the results of these latest studies point strongly to the conclusion that there is a compelling case implicating vitamin D deficiency in COVID-19 outcomes and deaths.


6. Should I supplement?

Public Health England advise 400 IU or 10 mcg per day. However:

  • Even 2,000 IU daily has been shown to only achieve serum levels of 30ng/ml. Increase above this level does not lead to a proportional rise in serum vitamin D as the effect on serum levels gradually reduces.

  • Studies show that almost 6,000-10,000 IU per day from a combination of food, light, and supplements is required to maintain optimal blood levels of 40ng/ml levels.

  • Food can typically provide no more than 10% of your vitamin D requirements

  • Requirements depend on body mass; the obese may require double or triple the average amounts.

  • Daily dosing rather than weekly or monthly is very important as the half life of unconverted vitamin D is only 24 hours; the unconverted form is of great importance in immunity, cancer prevention and other actions of vitamin D that are not related to bone health. For bone health, however, weekly, or monthly doses may be perfectly good.

It is preferable to obtain as much vitamin D as possible from sensible sun exposure than supplements as the half-life of 25(OH)D in the body is 2-3 weeks when it derives from supplements but double that when it is produced from vitamin D formed in the skin. Adequate intake of levels of other vitamins and minerals is necessary, particularly vitamin A, Vitamin K2, and magnesium, in order to optimise vitamin D utilisation and prevent imbalances which could have detrimental effects. Calcium, however, should not be taken alongside vitamin D, unless there is little in the diet as vitamin D increase calcium uptake. Too much calcium can lead to kidney stones, calcification, and other issues.

That said, in the UK it is very difficult to get enough vitamin D from sunlight for the following reasons:

  • In summer, white skinned individuals following the recommended sunlight exposure of 15 minutes 3 times a week and wearing shorts and t-shirt were found to achieve blood levels of vitamin D, 25 (OH) D of less than 20 ng/ml, leaving them deficient.

  • Someone with white skin in a bathing suit can make 20,000 IU in 20-25 minutes of sun exposure in high summer. Synthesis is self-limiting: continued sun exposure does not result in continued synthesis beyond around 25,000 IU. The amount of UVB required to achieve this, 54mJ/cm2 , is termed 1 minimal erythemal dose or MED. However, it is not possible for darker skins to make enough vitamin D at UK latitudes even in summer. As an illustration, a fair white-skinned person exposed to 1 MED can achieve a 50-fold increase in serum vitamin D, but a very dark-skinned person of the same age shows no significant increase after the same exposure. In contrast they would need 5-10 times 1 MED merely to make 60% of the same level.

  • even white skins cannot make vitamin D in the winter months between October and April when the UVB light is much weaker as a UVB index of at least 3 is required.

  • Even in summer the UVB rays are not strong enough to make much vitamin D before around 10 am or after around 3pm.

  • air pollution can drastically reduce UVB penetration and UVB cannot travel through glass; driving with the windows up or sitting in a glass enclosed conservatory will cause exposure only to more harmful UVA light.

A free app called Dminder, developed by Dr Holick can be used to gauge how long it is safe to stay in the sun. From your location, skin type, clothing, and other relevant factors it calculates how much vitamin D you have made. According to Dr Holick’s guidelines, the skin should be exposed for roughly quarter to half the time it takes for the area to turn pink 24 hours later, before applying sun-cream as sun-cream very effectively blocks virtually 100% of UVB light required to make vitamin D, (while not completely blocking harmful UVA light). This exposure time can vary from a few minutes to an hour depending on the time of day, month and type of skin but can make the equivalent of:

With whole body exposed (in a bathing costume) - 10,000-25,000 IU

With only arms and legs exposed - 2,000-4,000 IU

A tan can provide some protection against the UVA rays that sun-creams still allow through but even with a tan, it is not advisable to have excessive sun exposure. Staying in the sun too long without a tan with only sun cream protection, however, is even more likely to result in too much exposure to harmful UVA light. Burning is not advisable and should always be avoided.

In practical terms, difficulty in getting sufficient vitamin D from the sun means supplementing in winter for white skinned populations, and throughout the year for darker skinned and elderly populations. In summer, the darker the skin, the higher the amounts needed from supplementation with even white skinned individuals requiring some degree of supplementation. Anyone who is deficient, with a serum level below 20ng/ml, should consider doubling or even tripling their daily dose for 3-6 weeks to raise their levels more quickly before reducing to normal levels thereafter. Otherwise it could take several months to raise levels sufficiently.


Can too much vitamin D be toxic?

  • Given the body’s capacity to make the equivalent of up to 25,000 IU per day, suggestions that levels above 2,000-4,000 IU may be toxic are unfounded.

  • Daily doses of 10,000 IU and even 30,000 IU have been demonstrated by research to be perfectly safe.

  • Toxicity is extremely rare and a review of 15 studies show that toxicity is not seen until blood levels reach above 200ng/ml.

  • To put that into context, lifeguards are known to maintain blood levels of above 100ng/ml without ill effects.

  • The European Food Safety Panel’s Statement of Scientific Opinion acknowledges that no adverse effects have been observed at 10,000 IU or 250 mcg per day.

  • People with impaired kidney function, however, should be closely monitored and remain under the guidance of a medical professional.

  • Calcium should not be supplemented at the same time unless the diet is lacking calcium. This is because vitamin D increase the absorption of calcium from the intestines and too much calcium may cause health issues.


If I get more sun exposure, will I increase my risk of skin cancer?

Concerns about cancer dangers from sun exposure have been misconstrued, largely as a result of the huge success of sun cream sales and marketing efforts. Although there is an association between excessive sun exposure and non-melanoma skin cancers, and excessive sun exposure or burning is definitely inadvisable, there is no credible scientific evidence that moderate sun exposure can cause melanoma, by far the more dangerous skin cancer.

  • Whilst non-melanoma skin cancer is relatively common, it is treatable and has a very low (<1%) death rate.

  • Almost 90% of skin cancer deaths are caused by melanoma.

  • Having an indoor occupation is associated with twice the risk of melanoma as having an outdoor occupation.

  • Outdoor workers, while receiving 3-9 times the sun exposure of indoor workers and having a higher incidence of sunburn have had no increase in melanoma since before 1940 . In contrast, melanoma in indoor workers has increased exponentially

  • 75% of melanomas are found in areas which are seldom exposed to the sun.

  • While sun exposure has profoundly decreased by around 90% since 1935, there has been an exponential increase in melanoma incidence by 3,000%

  • Sunscreen use has not decreased the incidence of melanoma. Melanoma increased as sunscreen use increased

  • Increases in melanoma is correlated to decrease in personal annual sun exposure

  • Use of some sun creams can block virtually all vitamin D producing UVB light while allowing through, harmful UVB.

Clearly there are other risk factors for melanoma Some of these are being sunburnt when young, being obese, having high levels of PCB’s in the blood , and high alcohol consumption. Sun exposure in the present which is no more than moderate is not a risk factor. In contrast, sun exposure has been found to result in the following positive outcomes:

  • A large Swedish study with a 20 year follow up period found that women who sunbathe regularly have half the risk of death during a 20-year period than those who remain indoors.

  • Women who avoid the sun have 10 times the risk of breast cancer as those who get plenty of sun exposure.

  • Sun exposure dramatically improves mood through production of serotonin and endorphins.

  • People who spend a lot of time outdoors have 1/50th the risk of developing Parkinson’s disease.

  • Sun exposure helps set our internal body clocks which helps with sleep.

  • Sun exposure increases levels of brain derived neurotrophic factor (BDNF), important for neuronal plasticity, neuronal growth, memory, and learning. Decreases in BDNF are associated with Alzheimer’s, Multiple Sclerosis (MS) and Parkinson’s disease

  • sun exposure reduces diabetes, heart disease and asthma.

  • It is possible that sun exposure may have other unknown positive effects on the human body besides these.


A few more sun related findings to conclude with:

  • avoidance of sun exposure has been found to be a risk factor for death of similar magnitude to smoking!!

  • For each death caused by diseases associated with sun exposure, there are 328 deaths caused by diseases associated with sun deprivation

Ironically, 83% of Australian dermatologists were found to be vitamin D deficient.

The dangers and extensive ill effects on health of a lack of moderate sun exposure and consequential lack of vitamin D and other benefits, appears to, by far, outweigh any potential health benefit from avoiding it.


2 May 2020, updated 5 June 2020

Eshani King BSc(Hons) Biochemistry, FCA, CTA, BFP

Researcher in Evidence Based Immunology and Health

Email: Eshani.king@ajkcc.co.uk

APPENDIX

Vitamin D3, (Cholecalciferol)

In 1920, the importance of vitamin D was understood even though it had not yet been identified; TB patients were put out in the sunlight in what was then known as “solariums”. Children were given cod liver oil daily, one of the very few good food sources of vitamin D. Fast forward one hundred years to 2020, and we find that in the mad rush to treat every possible ailment with palliative drugs (which only treat the symptoms, rather than the cause), we seem to have forgotten many of the basic factors required for an optimally functioning and powerful immune system.


5 Tips to Boost Your Immunity

1) Vitamin D (also C, B12, A and K, magnesium and Zinc.) - Sunbathing comes into its own at last!

2) Sleep

3) Hot baths - Saunas are ideal when you have access to one, but hot baths instead can be beneficial.

4) Plenty of moving - Strava is a great app to encourage this.

5) Avoiding watching The News as it can add to stress and fear - these things weaken immunity. You can still stay informed by reading up from what you feel are trusted sources. CBD oil can be good for calming, headaches, sleep and menopause symptoms.

You may be onto this connection already but if we encourage friends and family to top up their Vitamin D to boost their immunity - we can be part of the prevention. The fact that many of us have been getting a lot more rest and sleep will be great for immunity too. I know there's a lot of info around but I've used some of my time recently reading up and studying it from what I believe to be trusted sources and have been following it all since January / Wuhan so I felt sure it was coming, a long time before they took any measures or took it seriously over here. I don't watch it on the news at all because of the way it is reported.

Covid-19 - Do many people have pre-existing immunity?

T-cells really are the superstars in fighting COVID-19 - but why are some of us so poor at making them?

Thank you to Dr Doshi for raising the profile of T-cells. Incidentally, German researchers found that a staggering 81% of individuals had pre-existing T-cells that cross-react with SARS-CoV-2 epitopes [1]. This fits with modelling in May by Imperial College’s Professor Friston, a world authority in mathematical modelling of complex dynamic biological systems, indicating that around 80% and 50% of the German and UK populations, respectively, are resistant to COVID-19: https://unherd.com/2020/06/karl-friston-up-to-80-not-even-susceptible-to...

Antibodies can only latch onto and help destroy pathogens outside cells and may also occasionally, paradoxically, enhance a pathogen’s ability to infect cell instead by antibody dependent ”enhancement” or ADE. It is only the T-cell that can cleverly sense and destroy pathogens inside infected cells using “sensors” which detect foreign protein fragments.

In the late 60s the Lancet described a case of a child with agammaglobulinemia, a condition in which absence of B cells prevent them from producing antibodies, who overcame a measles infection quite normally and did not become re-infected thereafter. We now know that, although this condition can compromise immunity, in that particular case the rest of the immune functions, including T-cells, must have been perfectly up to the job of clearing infection and establishing immune memory without help from antibodies. The importance of T-cells in fighting SARS-CoV-1 and establishing immune memory has also been well documented and discussed in a number of pre-COVID papers from 2017 and earlier [2].

Then, early in April, it was reported that two patients with agammaglobulinemia overcame COVID-19 infections without requiring ventilation [3], prompting the Italian authors to write: “This observation suggests that T‐cell response is probably important for immune protection against the virus, while B‐cell response might be unessential”.

All this should have shifted the focus of efforts towards T-cells at an early stage - the real question is why mainstream media and others continued to focus efforts and narrative on antibodies. Is it because vaccines are good at provoking antibody responses but not so great at generating T-cells? Some of the vaccines presently under trial do elicit some T-cells but it seems that neither the quantity nor variety are hugely impressive.

Does this matter? Apparently so: Research establishments including Yale found that in mild or asymptomatic cases, many T-cells are produced. These were highly varied, responding not just to parts of the Spike, S protein or Receptor Binding Domain but to many other parts of the virus [1, 4-6]. Notably, in these mild cases there were few or no detectable antibodies. Conversely, the severely ill produced few T-cells with less variety but had plenty of antibodies. What is also of interest is that men produced fewer T-cells than women, and unlike women, their T-cell response reduced with age [7].

So why are some people unable to mount a good protective T-cell response? The key to this question might be a 10-year-old Danish study led by Carsten Geisler, head of the Department of International Health, Immunology and Microbiology at the University of Copenhagen [8]. Geisler noted that "When a T cell is exposed to a foreign pathogen, it extends a signalling device or 'antenna' known as a vitamin D receptor, with which it searches for vitamin D,", and if there is an inadequate vitamin D level, "they won't even begin to mobilize." In other words, adequate vitamin D is critically important for the activation of T-cells from their inactive naïve state. The question of whether T-cells might also need a continuing supply of vitamin D to prevent the T-cell exhaustion and apoptosis observed in some serious COVID-19 cases [9] deserves further research.

High levels of vitamin D are also critical for first line immune defences including physical mucosal defences, human antiviral production, modulating cytokines, reducing blood clotting and a whole host of other important immune system functions [10]. The obese, diabetics and people of BAME origin are far more deficient in vitamin D and men have lower levels than women [10].

Another intriguing clue is that Japan has the highest proportion of elderly on the planet but despite lack of lockdowns, little mask wearing and high population densities in cities, it escaped with few COVID deaths. Could this, at least in part, be because of extraordinarily high vitamin D levels of over 30 ng/ml in 95% of the active elderly [11]? By comparison, UK average levels are below 20ng/ml [10]. Vitamin D is made in the skin from the action of UV sunlight, food usually being a poor source, but the Japanese diet includes unusually high levels. Sunny countries near the equator (e.g. Nigeria, Singapore, Sri Lanka) also have very low COVID related deaths.

The results of the first vitamin D intervention double blind RCT for COVID was published on 29 August by researchers in Córdoba, Spain. This very well conducted study produced spectacular outcomes for the vitamin D group (n=50), virtually eliminating the need for ICU (reducing it by 96%) and eliminating deaths (8% in the n=26 control group). Although this was a small trial, the ICU results are so dramatic that they are statistically highly significant [12].

Substantially more vitamin D is required for optimal immune function than for bone health. It seems Dr Fauci is not ignorant of this, having apparently confirmed on TV and by email that he takes 6,000 IU daily! (see Dr John Campbell on YouTube Vitamin D and pandemic science, 16 September 2020). Meanwhile the US’s health body continues to recommend only 600-800 IU and the UK’s, only 400 IU.

It is high time for joined up solid scientific rationale to overthrow mainstream narratives based on an alternative 'science' controlled by industry interests/politics. Beda M Stadler, the former Director of the Institute for Immunology at the University of Bern, a biologist and Professor Emeritus, certainly appears to think so (see Ivor Cummins Ep91 Emeritus Professor of Immunology... Reveals Crucial Viral Immunity Reality on YouTube, 28 July 2020).

In the same way that prior infections protect us against future infections by means of cross-reacting T-cells, overcoming COVID-19 naturally offers potential for greater protection against future coronaviruses. Vaccines have their place but so do our amazingly complex, sophisticated, highly effective immune systems which have evolved over millennia to protect us from a world teeming with trillions of pathogens.

References

1. Annika Nelde, Tatjana Bilich, Jonas S. Heitmann et al. SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition, 16 June 2020, Research Square https://www.researchsquare.com/article/rs-35331/v1%20

2. William J.Liuabc et al. T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV.Antiviral Research. Volume 137, January 2017, Pages 82-92 https://doi.org/10.1016/j.antiviral.2016.11.006

3. Soresina, A, Moratto, D, Chiarini, M, et al. Two X‐linked agammaglobulinemia patients develop pneumonia as COVID‐19 manifestation but recover. Pediatr Allergy Immunol. 2020; 31: 565– 569. https://doi.org/10.1111/pai.13263

4. Avraham Unterman, et al. Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19. medRxiv 2020.07.16.20153437; doi: https://doi.org/10.1101/2020.07.16.20153437

5. Leticia Kuri-Cervantes, et al. Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection. bioRxiv 2020.05.18.101717; doi: https://doi.org/10.1101/2020.05.18.101717

6. Floriane Gallais, Aurelie Velay, Marie-Josee Wendling, Charlotte Nazon, Marialuisa Partisani, Jean Sibilia, Sophie Candon, Samira Fafi-Kremer. Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion. medRxiv 2020.06.21.20132449; doi: https://doi.org/10.1101/2020.06.21.20132449

7. Takahashi T, Wong P, Ellingson M, et al. Sex differences in immune responses to SARS-CoV-2 that underlie disease outcomes. Preprint. medRxiv. 2020;2020.06.06.20123414. Published 2020 Jun 9. doi:10.1101/2020.06.06.20123414

8. Von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol. 2010;11(4):344-349. doi:10.1038/ni.1851

9. Diao B, Wang C, Tan Y, et al. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020;11:827. Published 2020 May 1. doi:10.3389/fimmu.2020.00827

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

11. Nakamura K. Vitamin D insufficiency in Japanese populations: from the viewpoint of the prevention of osteoporosis. J Bone Miner Metab. 2006;24(1):1-6. doi:10.1007/s00774-005-0637-0

12. Marta Entrenas Castillo et al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. The Journal of Steroid Biochemistry and Molecular Biology. Volume 203, October 2020, 105751. https://doi.org/10.1016/j.jsbmb.2020.105751

Competing interests: No competing interests

Link for article HERE.