Monday 28 November 2022

Covid-19 & VItamin D: So much evidence of benefit, now from the USA

When the pandemic of Covid-19 emerged two years ago, those medical scientists with a knowledge of the importance of defensive immunity realised that the most immediate and important action must be the correction of Vitamin D deficiency, which is found in the majority of the population. 

Research during the previous forty years had worked out the details of the escalation of defensive immunity in response to infection, information that was not available in the previuos major pandemics of infuenza. The new information involved the vital role of Vitamin D, in its activated form 1,25(OH)D. It was also known that Vitamin D deficiency is very common in the UK and other European countries. It had been established that Vitamin D deficiency is particularly common and severe in certain groups such as the elderly, the obese, people with diabetes or malignancy, and people of South Asian and Black African ethnicity living in Europe. All such groups had a high mortality rate from Covid-19.

Despite advice from independent scientists, those not employed directly by governments, Vitamin D was ignored. The government policies in the US and UK (and elsewhere) were for vaccines to be developed to control Covid-19 infections and for no natural preventative or known pharmaceutical interventions to be considered. 

Deaths from Covid-19

It was not long before Covid-19 caused large numbers of deaths, but those who had died had been offered no immunological protection. Medical scientists who knew of the importance of vitamin D deficiency at this time of pandemic brought this to national attention, but they were ignored. Our political, medical, and public health leaders denied the importance of Vitamin D in the process of immunity. We were perpetually told that there was no evidence that Vitamin D would help in the treatment of Covid-19. Of course there was no specific evidence for the simple reason that the virus was new. We could say the same about vaccines.

But there was good evidence that optimisation of immunity would be an advantage in face of a pandemic, and that Vitamin D is vital for that optimisation. I have pointed out Pascal's Wager, that in the absence of conclusive information (eg the existence of God, or the benfit of Vitamin D in Covid-19) it is important to take the line of least damage and maximum potential benefit. The potential benefit of Vitamin D is far greater than any significant disadvantage, as judged by experience gained during many decades of use. After all, the idea would be to correct deficiency of a natural vitamin/hormone, not to introduce a new and barely-tested medicine.

The denial of VItamin D

Has it been ignorance or ignoring?

Our national officials continued to deny the potential benefits of Vitamin D. They continued to advise witholding VItamin D for immunity optimisation until "proof" of benefit had been demonstrated in a randomised controlled trial (RCT). They seemed to be unaware of the meaning of "proof", and unaware of the serious limitations of an RCT (cost, ethics, logistics). It was obvious that there would be many Covid-19 cases, hospital admissions, and deaths while an RCT would be planned, undertaken, analysed, published, and debated. The realisation of emergency was demonstrated by the introduction of injected mRNA (aka vaccination) given after only rudimentary clinical testing, but natural Vitamin D cheap, safe, and readily available was not allowed.

From May onwards in 2020 nature provided a predictable respite from Covid-19 as the result of the natural summer-time production of Vitamin D, but even this was not officially recognised. Was it ignorance or deliberate ignoring of Vitamin D? Our medical-scientific leaders should not have been ignorant of Vitamin D and its importance in immunity, but supression of that information was essential for the emergency use authorisation (EUA) that would allow the release of new and barely tested "vaccines".

As the pandemic progressed we received a great deal of information concerning the importance of low blood levels of vitamin D in the devlopment of critical and fatal Covid-19, protection by good blood levels (40–50 ng/ml, 100-125nmol/L). The evidence in favour of an important and readily available role for vitamin D in safely minimising the impact of the pandemic has been consistently ignored or suppressed.

Information concerning the importance of vitamin D has continied to accumulate, recently from Belgium and Mexico, and most recently from the USA.

Evidence for the USA

Important evidence became available on November 12th 2022. The study came from the Department of Veterans Affairs (VA) health network in the USA. It was a retrospective cohort study, with the title "Association between vitamin D supplementation and COVID-19 infection and mortality". The authors were from a variety of important medical and university institutions in the USA.

The study identified the records of veterans of the US armed forces, who had blood tests and/or prescriptions for vitamin D between January 1st 2019 and December 31st 2020, which is  before vaccines were introduced. 

34,710 had received a prescription for vitamin D2 (of fungal origin) and 220,265 had received a prescription for vitamin D3 (of animal origin, usually from the oils of sheep's wool). 407,860 controls were identified (no vitamin D supplement taken).

The study objectives were to calculate the time to Covid-19 infection, and the mortality within 30 days of infection.

For the purpose of the study 33,216 subjects treated with vitamin D2 (average age 58) were carefully matched with 33,216 controls (average age 58). 220,265 subjects treated with vitamin D3 (average age 64) were matched with 407,860 controls (average age 63). The details of the matches are shown in the paper.

In the vitamin D3 group, there were 359,091 men and 39,915 women, 71,071 Black and 283, 248 White subjects.

VItamin D results

For the vitamin D3 group, the Vitamin D blood level results before the pandemic are as follows:

Figure1. Blood levels of Vitamin D in the subjects of the USA VA study.
ng/ml and nmol/L

Experience in other observational studies indicates that the risk of critical or fatal Covid-19 is extremely low when the blood level of vitamin D is at or greater than 40 ng/ml, 100 nmol/L. Other studies have show that only about 15 – 25% of people fall into this range. In this present VA study only 25% of the 399,006 subjects had a "good" level of vitamin D, 75% being deficient, and 17% being very deficient with high Covid-19 mortality risk.

Men were found to have on average lower blood levels of vitamin D compared to women.

Black subjects tended to have lower blood levels of Vitamin D and higher rates of Covid-19 infection.

The group taking vitamin D2 was too small for detailed analysis.

The dose of Vitamin D taken had a very wide range, from 20 units per tp 15,000 units.

Outome assessment

There were clear advantages in those taking Vitamin D supplements compared to untreated controls, as shown in Figure 2. The results are displayed as hazard ratios (HR), the control risk being standardised as 1.0 and the Vitamin D treated groups a lower number indicating benefit (lower infection or death rates).

Figure 2. Hazard ratios for Covid-19 infection
based on blood levels of Vitamin D (lower HR greater risk)

For Vitamin D3 treated subjects, the HR for Covid-19 infection is 0.797. For Vitamin D2 treated subjects, the HR for Covid-19 infection is 0.720. The benefit is shown clearly in the bar chart of Figure 3. The outcome for those taking D2 was slightly better than those taking D3, but there was a risk reduction of 25 – 30% for both groups. A clear benefit.

Figure 3. Hazard ratios for Covid-19 infection 
for Vitamin D3 and D2

In Figure 4 we can see that for Vitamin D3 treated subjects, the HR for death within 30 days of Covid-19 infection was 0.667. For Vitamin D2 treated subjects the HR for death within 30 days of Covid-19 infection was 0.765. The outcome for those taking Vitamin D3 (the great majority) was significantly better than for those taking Vitamin D2. 

Figure 4. Hazard ratios for death within 30 days of Covid-19
for Vitamin D3 and D2

For the subjects taking Vitamin D3, the risk reduction for death within 30 days of Covid-19 infection is 33% compared to controls. This a major benefit.

Further information is given in the paper.

The analysis was based on medical records. No toxic effects of Vitamin D were recorded.

The greatest benefit was seen in the subjects with the most severe Vitamin D deficiency, less than 20ng/ml, 50nmol/L. Vitamin D supplement of 50,000 units per day brought about an infection HR of 0.51, which is a 49% reduction of Covid-19 infection risk. This is a great short-term benefit but the dose is very high for long-term use.

The risk reduction for Covid-19 infection in men and women was similar, HR 0.8 in men and HR 0.77 in women, corressponding to 20% and 23% risk reduction respectively.

Figure 5. Hazard ratios for Covid-19 infection
men and women

Risk reduction was greater in Black subjects compared to White.

Figure 6. Hazard ratios for Covid-19 infection
Black and White subjects

The respective HRs indicate a 30% risk reduction for Black subjects receiving a Vitamin D supplement comared to a 20% risk reduction in matched White subjects. This probably represents initially lower blood levels of Vitamin D in the Black subjects.  

Vitamin D: blood levels and supplements.

The USA VA study was retrospective controlled. The variables of initial blood levels of Vitamin D and the dose of Vitamin D supplement were recorded. They were only linked when the analysis was undertaken. The supplements, with a wide range of doses, were not necessarily based on blood levels at the time of prescription. 

It might be expected that those with good blood levels of Vitamin D would not need or be given a supplement, but in practice many were. The results of the study indictate that those with initial very low blood levels of Vitamin D benefited more than those with good blood levels. However those with good blood levels (40ng/ml, 100nmol/L or greater) also benefited. Risk reductions are shown in Figure 7.

Figure 7. Risk reduction from Vitamin D
based on initial blood level of Vitamin D

Thus is very interesting. The subjects with the lowest blood levels of Vitamin D experienced overall a 30% risk reduction for Covid-19 infection. This is good. Those with the next lowest blood levels experienced a 19% risk reduction.

However, the subjects that would not be considered to be Vitamin D deficient experienced a 14% risk reduction when given Vitamin D supplements. This suggests that in advance of a pandemic, giving a Vitamin D supplement to all people would be of considerable advantage, without needing to test for blood levels until later.


This is yet another study that has shown the disadvantage of low blood levels of Vitamin D, and the great medical/biological advantage of correction with a Vitamin D supplement.

How long can our major media, medical scientific, public health, and political leaders continue to ignore and deny the great importance of and benefits from Vitamin D?

From February 2020 onwards many cases of and deaths from Covid-19 could have been prevented if the pre-existing knowledge of the importance and safety of Vitamin D had been been put into action. Of course there was no pre-pandemic experience of Vitamin D supplement in respect of Covid-19, but action could have been taken, the application of Pascal's wager. There was too much demand for "proof" and "more evidence" from people who could not understand the nature of proof. 

The authors state: "When we extrapolate our results for Vitamin D3 supplementation to the entire US population in 2020, there would have been approximately 4 million fewer Covid-19 cases and 116,000 deaths avoided".

If only.....

But for the next pandemic there is official prediction only for more mRNA vaccines, but no mention of Vitamin D, despite all the evidence of effectiveness and safety.

Tuesday 27 September 2022

Covid-19 & Vitamin D: RCT benefit in Belgium & Mexico


In this Blog post we are going to look at two placebo controlled Randomised Controlled Trials (RCT) that have demonstrated the effectiveness of Vitamin D in reducing the impact of Covid-19. They were performed in Belgium and Mexico. Before this we will recap the UK RCT that I analysed in detail in my previous Blog post.

RCT in the UK

The clinical trial initially undertaken in the UK was intended to evaluate the efficacy of Vitamin D in the prevention of serious Covid-19. It was to be a true Randomised Controlled Trial, but it failed. It was not controlled in that subjects in the control group, being informed that they were not to receive Vitamin D, took Vitamin D on their own initiiative. 

The trial was therefore unable to compare outcome measures of the subjects receiving Vitamin D with true controls. It was also under-powered to answer the question "Should we be promoting Vitamin D to the people of the UK (and elsewhere) to protect them against damaging effects of Covid-19 ?" There were too few serious outcome end-points among the study sample of 6,000 normal healthy volunteers to produce a meaningful result.

The main researcher of the study was Professor Adrian Martineau, more recently commented: 

"The challenges of the Vitamin D RCT – too many are already taking it." 

This means that, as in his study, true controls are unlikely to be available.  

Covid-19 pandemic

The UK study was undertaken during 2020, the first year of the Covid-19 pandemic, when there was clearly a need to give maximum protection to the population. The policy was lockdown and mask-wearing, damaging and probably without benefit. Real protection would come from optimising defensive personal immunity. The national policies were to encourage the devlopment of vaccines for this purpose, but in advance there was the opportunity to use Vitamin D. However natural immunity was never seriously considered officially, despite its success in previous pandemics of respiratory viruses. Vitamin D had the advantages of being available immediately, being very cheap, known to be very safe, and having a strong research foundation of optimising natural defensive immunity.

The ignoring of Vitamin D

Many studies had shown that low blood levels of Vitamin D were associated with and predicted serious or fatal Covid-19, whereas high levels gave a biological advantage. Early clinical trials of Vitamin D (in its rapidly acting part-activated form 25(OH)D Calcifediol) demonstrated clear advantage when given at the time of admission to hospital, but these studies were rubbished in the UK by just three people who were very influential but should have known better. Doctors were advised, directly or indirectly, not to use Vitamin D. We were told that we must wait for the result of the RCT to be conducted by a London team led by Professor Adrian Martineau.

And so we waited patiently. Vaccinations arrived and were given in two phases in 2021 with a booster in early 2022, but nevertheless there were 200,000 Covid-19 deaths in the UK. How many of these deaths might have prevented if Vitamin D been given? Especially if patients admitted to hospital with Covid-19 had been given Vitamin D in its part-activated form Calcifediol, which had been been shown to be very effective in RCTs in Córdoba and Barcelona.

Waiting for the result of the UK RCT turned out to be an exercise in futility: when the result became available in March 2022 it was found to be of no value in assessing the efficacy of Vitamin D (details in previous Blog post). What a wasted opportunity to help the population during the pandemic. 

Meanwhile other studies were in progress.

Liège, Belgium

An RCT study from Belgium was conducted at the University Hospital of Liège. It recruited adult patients admitted to hospital on account of Covid-19 and with blood vitamin D levels of only 20ng/ml (50nmol/L) or less. They were all expected to survive at least 4 days, by which time a significant proportion of the Vitamin D given would be converted into 25(OH)D, calcifediol. Patients taking vitamin D in any form on admission to hospital were excluded.

The patients were therefore all selected as being Vitamin D deficient. They all received high quality clinical care in hospital. They were randomised to receive in addition either Vitamin D 25,000 units as an oil daily for four days to correct deficiency and then 25,000 units weekly for maintenance, or (the controls) to receive an identical liquid oil placebo. 

22 patients were randomised to receive placebo and 21 to receive Vitamin D. The average mean blood level of vitamin D was similar in the two groups. The mean of the placebo group was 16.87 ng/ml, 42.2 mol/L, and of the Vitamin D group 17.87 ng/ml, 44.7 mol/L

Figure 1. Data from the Belgium RCT. (nmol/L = 2.5x ng/ml)

The outcome measures are all in favour of correction of Vitamin D deficiency, even though correction occurred fairly late in the course of Covid-19, but before a clinically critical level was reached. In a small RCT in Brazil, Vitamin D itself given on admission to ICU conferred no benefit, but this was too late and the Vitamin D would take several days to become part-activated to 25(OH)D, Calcifediol. 

We can see in Figure 1 that the length of stay in hospital was reduced by 50% in the Vitamin D group compared to controls (4 versus 8 days).

On day 7 following admission to hospital, 12 out of 22 (55%) control patients were still in hospital, compared to 4 out of 21(19%) of the Vitamin D treated patients.

ICU admission rates were 5 out of 22 (23%) in the control group compared to 2 out of 21 (10%) in the Vitamin D treated group.

Other favourable outcome measurements can be seen in Figure 1, and we can also see that there were 3 Covid-19 deaths in the controls and just one in the Vitamin D treated group.

It is quite clear that this is another RCT that shows that correction of Vitamin D deficiency in defence of patients against Covid-19 is very important. 

Unfortunately during the pandemic doctors have not been allowed to give Vitamin D to hospital patients. How many people have died unnecessarily because of false government dogma?

Mexico City

Mexico City

One of the problems of the UK inconsequential trial was that low risk normal people were recruited. This meant that we could expect only small numbers of important end-points, and there were just three ICU admissions (one in each group) with no deaths. Conclusions could not be drawn, and higher risk subjects would need to be recruited to achieve a meaningful result from a realistic sample size.

The result of an RCT of Vitamin D has been reported from Mexico, and this recruited 321 health-care workers from four hospitals in Mexico City. The study was between July 15th and December 30th 2020, The subjects were considered to be at high risk of serious Covid-19. 94 of the subjects analysed at the end of the study had received Vitamin D 4,000 units daily (a "good" dose), and 98 had received a placebo of identical appearance. Randomisation was successful with no significant differences between the two groups at baseline. More than half the subjects failed to complete the study, mainly the result of too much high pressure work.

Mexico City is only 19 degrees north of the equator (compared to London at 53 degrees) and it is important to note that only 10% of the 321 initially recruited had a blood level of Vitamin D 30ng/ml, 75nmol/L, or more, that is in what other studies have shown to be the safe range. 

Therefore 90% can be judged to be Vitamin D deficient with sub-optimal blood levels.This observation shows that serious Vitamin D deficiency can be common at all latitudes world-wide, the result of indoor working and sun avoidance. 

Further details of baseline Vitamin D status are shown in Figure 2.

Figure 2. Data from Mexico RCT. (nmol/L = 2.5x ng/ml)

The outcome results are also shown in Figure 2. The numbers of subjects are reduced because of the large drop-out rate, explained by the subjects to be the result of very heavy workloads.

During follow-up 24 (24.5%) of the subjects taking placebo tested positive for SARS CoV-2, compared to 6 (6.4%) of the subjects taking Vitamin D. There were no deaths in either group, but one taking placebo required admission to hospital. The blood level of Vitamin D as 25(OH)D, calcifediol, increased significantly in those taking Vitamin D but not in the placebo group.

This was a another positive result of an RCT of Vitamin D in appropriate dose reducing the incidence Covid-19.


Vitamin D deficiency is the major risk factor for serious Covid-19, and correction of Vitamin D deficiency has been shown again to give a biological advantage. But once again it has not resulted in a policy of vitamin D encouragement and I have not seen these two studies mentioned in the major media or in the medical press.

Are our medical-scientific leaders detached from current medical research, or are they choosing to deliberately ignore it? There is a single-minded policy of multiple vaccinations, and also what appears to be a deliberate policy of avoiding any debate concerning ineffectiveness and possible resulting damage.

Friday 26 August 2022

Covid-19 & Vitamin D: UK unhelpful clinical trial

London – Greenwich and Canary Wharf

It has been established very well during the Covid-19 pandemic that a low blood levels of Vitamin D recorded in advance of illness (Santander, Heidelberg, Israel ) is the most significant but potentially reversible risk indicator of critical disease and death. Vitamin D deficiency is also the common factor within the major at-risk groups, the obese, the elderly, and those of South Asian and Black African ethnicity who li
ve in the UK and other northern European countries. 

It has been established that Vitamin D in its "raw" form when given to the critically ill in Intensive Care Units (ICU) is not effective (Brazil), the simple reason being that as we know, it takes up to two weeks for the Vitamin D to be converted in the liver into its hydroxylated pre-active form, 25(OH)D, also known as Calcifediol. When Calcifediol is given by mouth it takes just two hours to achieve good blood levels. It is Calcifediol, 25(OH)D that we measure in the blood as Vitamin D.

Randomised controlled trials (Cordoba and Barcelona) have shown that when Calcifediol is given to patients admitted to hospital on account of severe Covid-19, it is remarkably successful in reducing the risk of escalation to ventilatory care and death. Why it has not been used widely in the UK and elsewhere is a mystery.

Correction of vitamin D deficiency

It would be a sensible public health initiative to correct Vitamin D deficiency within the population, especially in those at particular risk. A "safe" level of Vitamin D in the blood should be achieved, ideally before admission to hospital. Vitamin D is cheap, readily available, and safe when given in physiological doses checked by blood levels. 

It is clear that a low blood level of vitamin D (=Vitamin D deficiency) can be a serious disadvantage, and restoration to an ideal blood level of 40ng/ml (100nmol/L) would be sensible. But how to achieve this is the challenge. 

The physiological way to obtain Vitamin D is by exposure of the skin to the sun, at times when at close to sea level the sun is more than 45 degrees above the horizon, judged by the length of the shadow being less that the height. This could be recommended but an excessive single exposure leading to burn is to be avoided.

It has been demonstrated that not only people with ideal blood levels of Vitamin D have a reduced risk of critical or fatal Covid-19, but also people who are taking vitamin D supplements at the time of hospital admission on account of Covid-19 (Tameside, UK). 

The biology of the pivotal role of Vitamin D, in its fully activated form 1,25(OH)D, in the escalation of natural defensive immunity has been established during the past forty years.

With the onset of a serious pandemic due to a new respiratory virus, it would seem to be sensible to act on a knowledge of medical science supported by early reports of the dangers of low blood levels of Vitamin D. Correcting Vitamin D deficiency would have been of great potential benefit, with no danger. I have drawn attention to the report of just a single case of vitamin D toxicity occurring during the pandemic.

Randomised controlled trial – RCT – from UK

Official advice concerning the use of Vitamin D during the pandemic was very negative, ridiculously so given the circumstances and 200,000 Covid-19 deaths in the UK. The pandemic emergency resulted in vaccines being issued on the basis of Emergency Use Authorisation (EUA), meaning that only short term and rudimentary RCTs in healthy people had been completed. 

When it came to vaccinations in pregnancy there were no RCTs, which can be regarded as negligent. Safety was to be judged on the basis of "post–marketing surveillance". And this is the important thing: the main purpose of RCTs is to establish safety, following the thalidomide tragedy of the 1960s. When taking medicines, effectiveness is less importance than safety. A medicine might not do good, but it must not do harm – primum non nocere.

Whereas the "vaccines" against Covid-19 are a new RNA technology with safety being far from clear, Vitamin D is a natural substance that has been in use for a century. The standard dose range is known, with appropriate blood levels. The exceptionally rare side-effect of Vitamin D intoxication (hypervitaminosis D) is always the result of major dose error and is both easily recognised and completely reversible. The need for RCTs of Vitamin D was much less pressing than for vaccines.

The challenge of prospective randomised trials of vitamin D, or anything else, is that if low-risk individuals are to be studied, very large numbers must be recruited if the endpoint of critical illness or death is to be reached in significant numbers. Administration costs are inevitably very high, and follow-up times will be long. It imight be sensible to concentrate on a smaller number of individuals who are at high risk of serious or fatal Covid-19. Hence the success of the RCTs from Spain, small numbers showing a big effect with statistical significance.

I have also shown in previous Blog posts the wisdom of Sir Austin Bradford Hill, whose criteria of pragmatic "proof" (it is never absolute) identifies an RCT as being only one component. For ethical and operational reasons an RCT might not be possible, or be of only limited value. There is also the wisdom of Blaise Pascal, who realised that decision-making is also pragmatic, a trade-off between likely benefit and possible adverse outcome.

United Kingdom - the COVIDENCE UK study

Early in the pandemic in the UK, a large community-based clinical trial of Vitamin D in the prevention of Covid-19 was proposed by Professor Adrian Martineau. Funding of the study became an immediate problem as a large administrative staff would be essential and there would be no pharmaceutical company support. However the study was undertaken and the result became available in early 2022.

6200 adults were incorporated into the trial, with a number of exclusion criteria including current Vitamin D supplementation. 2958 of these were randomised to receive Vitamin D.

2690 (86.8%) of those to receive VItamin D had blood Vitamin D levels less than 30ng/ml, 75nmol/ml. This shows the extent of clinically significant Vitamin D deficiency. They had suboptimal blood levels as identified in the observational studies described in Heidelberg, Israel, and other places. 

1334 were given a lower dose of vitamin D supplement, 800 units per day, and 1356 were given a higher dose, 3200 units per day.

The controls did not have blood testing and they were informed that they were not to receive a Vitamin D supplement. This is important as, with the Heidelberg and Israel studies, the identification of Vitamin D deficiency before the study would have created the ethical dilemma if they were not to have the deficiency corrected.

There was no placebo given to the control group. This weakened the trial and in the knowledge that they were not to receive Vitamin D that was being tested, the controls would be likely to take a Vitamin D suplement not given to them. In fact 49.9% of them did so on at least one occasion.

The trial commenced in December 2020, with six month follow-up of individuals. The vaccination process was under way at that time and 89.1% of the subjects received one or more doses of a Covid-19 vaccination during the study period. This would obviously complicate the interpretation of the results.

The baseline Vitamin D levels can be seen in Figure 1. Both units in current use are shown, nmol/L and ng/ml. We can see no significance difference between the two treatment groups at the baseline. We see again the high prevalence of low sub-optimal blood levels of Vitamin D.

Figure 1. Baseline blood levels of Vitamin D

In Figure 2 we can see the blood levels of Vitamin D at the end of the study. The ideal blood levels can be judged to be greater than 75nmol/L, 30ng/ml, and preferable to be 100nmol/L, 40ng/ml. We can see that the former level is achieved by taking 800units per day, and the higher level by taking 3,200units per day.

In previous posts I have generally advised a supplement of 3,000units per day (the dose that I take, but as 20,000units once each week) but I have also emphasised the importance of checking blood levels so as to monitor the appropriate dose of the supplement. I have drawn parallels with monitoring the treatment of other hormone deficiencies, namely thyroxine and TSH levels in hypothyroidism, and glucose in diabetes.

Figure 2. End of study blood levels of Vitamin D

It is interesting to note that mean blood level of Vitamin D in the "No offer" group at the end of the study was 66.6nmol/L, 26.6ng/ml. As mentioned above the baseline blood Vitamin D levels in the "No offer" group, the intended controls, were not measured. There is no reason why they should not have been the same as in the treatment groups, which is about 41nmol/L, 16.5ng/ml. The fact that at the end of the study the mean blood level was 66.6nmol/L, 26.6ng/ml, indicates that many of those in the "No offer" were taking Vitamin D supplement of their own initiative, as some admitted. The increase would be 66.5%.

Clinical outcome was of course reported in the results of the study. We can see in Figure 3 that there were no significant differences in the cases of Covid-19 in the three groups, 2.97% in the high dose group, 3.63% in the low dose group, and 2.64% in the "No offer" group. There was similarly no significant difference in hospital admission rate. Ventilation was necessary in only one in each group, and there were no deaths.

Figure 3. Covid-19 infections related to Vitamin D supplement

Figure 4 shows us that there were very few acute respiratory infections, with no significant differences between the groups. The infection rate was highest in the Vitamin D high dose group.

Figure 4. Acute respiratory infection related to Vitamin D supplement


The main conclusion of the study as mentioned in the paper is that a public health policy of Test and Treat Vitamin D Deficiency is a practical proposition. To quote from the paper:

"Ultimately, however, this trial was designed to investigate the effectiveness of a pragmatic 'test–and–treat' approach to boosting population vitamin D status, rather than  biological efficacy of vitamin D to prevent ARIs [acute respiratory infections], and our findings should be interpreted accordingly."

It is not possible to form a conclusion concerning the effectiveness or otherwise of Vitamin D supplementation, but it appears that in prevention among asymptomatic people, a dose of 3,200units is perhaps of no advantage over a lower dose of 800units each day. However the absence of Covid-19 and respiratory deaths in all groups indicates that the study was underpowered (too small) to assess effect on deaths. To do so it would have been necessary recruit at least ten times the number of subjects.

This was a field study and the supplement dose was not adjusted to meet the needs of individual people. It was "one size fits all", but there might be an advantage of personalised approach with intermediate blood testing.

Of greatest importance in assessing Vitamin D efficacy is that the study was compromised by the "control" group being uncontrolled. It would have been scientifically more robust if they had been given a placebo, but that was not the case. This might have been for ethical rather than operational reasons, and similarly no base-line Vitamin D testing for the "control" group. However for a "test-and-treat" evaluation, the management of controls was not important and indeed the presence of controls was not really necessary.

In practice, those randomised to be controls were informed that they were not to receive a Vitamin D supplement, termed "no offer". It would appear that they did not want to miss out on what would be a very safe and potentially great advantage in the face of the pandemic, and many accepted Pascal's Wager, that is they took Vitamin D in unknown amounts, but sufficient to increase the mean blood level of Vitamin D by 66.5%. 

The other confounding factor was the distribution of vaccines at the same time of the study. This was among all groups but it could confuse and diminish any assessment of clinical outcome.

Of 6,000 people taking Vitamin D supplement (including a significant but unknown number of "controls"), only three required ventilatory care for Covid-19 and there were no deaths. This in itself tells us the value of taking a Vitamin D supplement to correct deficiency.

Tracing for and testing of vitamin D deficiency was achieved in this study. 

Assessment of correction of Vitamin D deficiency was inconclusive.

There are of course several other studies, and a study from Mexico will be the subject of the next Blog post.

Monday 11 July 2022

Covid-19 & Vitamin D: A Single Case of Vitamin D "intoxication" but much misunderstanding

During the past two years much has been made of the possible but exceptionally rare dangers of Vitamin D, assertions by those who have succeeded in suppressing an official use of Vitamin D which would optimise natural defensive immunity against Covid-19. This is the opposite of media silence concerning documented dangers from the new Covid-19 vaccines (which I believe might be prevented by correcting Vitamin D deficiency).

There have been in the past occasional case reports of "hypervitaminosis D", which is an excessive blood level of Vitamin D with undesirable but easily reversible metabolic consequences. A single case of hypervitaminosis D has been documented in the UK during early July 2022. It was treated both simply and effectively. The BMJ Case Report was followed by widespread reporting in the press, far more than the incident demanded. Unintentionally the press spread disinformation due to misunderstanding, as we will see below. The initial report was in the British Medical Journal, warning doctors about possibly more cases in the future.


British Medical Journal, July 2022

The report was cascaded by several UK newspapers to alert the public. Since i published this Blog post yesterday (July 11th) I have been informed that it has also been reported in Germany and Australia. 

All the newspaper reports over-simplified the medical paper and missed the most important points.

Sky News

The Times

Daily Mirror

Evening Standard


Hypervitaminosis D

An excess of Vitamin D can lead to an increase of the blood level of calcium, which is mobilised from the bones. In turn, the high blood level of calcium (hypercalcaemia) has metabolic effects on the kidneys that increase the volume of urine production (polyuria), leading to dehydration. This is exacerbated by the other effect of vomiting. Correction of the problem is simple, by intravenous saline. 

Hypervitaminosis D is extremely rare and it has not been reported in various recent Vitamin D trials. The point is that hypervitaminosis D is always the result of errors of dose, and there is a ready explanation for this. When it occurs Vitamin D has usually been given together with calcium supplements.

Identification of VItamin D

When Vitamin D was first identified and isolated in the early 20th century, the amount of it for metabolic use was so small that it could not be "weighed". Measurement was by biological assay, and expressed as International Units (iu), an agreed international standard. One unit of Vitamin D was defined as the daily requirement of an immature ten gram (10g) mouse, the amount required to ensure its bone development without rickets.

Everyone was happy with this and Vitamin D for human use was expressed in units (strictly "iu"). 400 iu was considered to be the daily amount to prevent rickets in children, and recent consideration has been for about ten times this for optimising immunity in the human adult. The daily need can be scaled up from one unit for the 10g mouse to 6,000iu for the 60kg human, but half this would be satisfactory.

1922 – the identification of Insulin

Insulin was identified and isolated in 1922, at about the same time as Vitamin D. Similarly insulin was present in such tiny amounts that could not be weighed and so the daily need and dose were expressed as international units of biological action. The use of biological units continues to this day without any clumsy attempts to change to mass units, weights, even though the mass of insulin can be measured.

It is now known that one unit of insulin weighs 0.0347 mg, which equals 34.7 micrograms. One unit of Vitamin D weighs 0.000025 mg or  0.025 micrograms (see below). Insulin has a much greater mass than VItamin D beacuse it is a large very complex protein molecule, whereas Vitamin D is a simple oil.

It was identified that the body produces on average during each day about one unit of Insulin per hour. 24 units of Insulin per day was the initial stating dose, divided into two or three injections (8+8+8 or 16+8 units) to coincide with major meals. Insulin resistance means that increasing doses are necessary to achieve normal blood glucose levels in some people.

Imagine the confusion if people with diabetes were to be told to take 0.2776 milligrams or 277.6 micrograms of Insulin (8 units) three times a day! Chaos would be inevitable, especially as the dose must be modified to suit the individual. Diabetes specialists are sensible and keep to the units that everyone understands

Measurement of Vitamin D

One unit of Vitamin D can now be measured as 25 billionths of a gram, 0.000000025 grams, or 0.025 micrograms. This is obviously infinitessimally small, too small to see. Vitamin D can now be measured in mass units rather than biological assay units, but this has created its own problems.

As with Insulin, everyone has been happy with internationally agreed biological units, iu, of Vitamin D. The arrival of mass units (based on weight) has caused confusion and it is this that can lead to the problem of hypervitaminosis D.

The move to mass units

Whereas most doctors and the general population think of Vitamin D in terms of units, the important UK Standing Advisory Committee on Nutrition (SACN) uses mass units. Hence confusion. The same would have happened in other countries.

400 units of Vitamin D is accepted as being the minimum daily dose of Vitamin D to prevent rickets in a child. 400 units is 10 micrograms, also expressed as mcg or μg. 

Metric units

People are accustomed to using the metric unit gramme, or gram, and are aware that a milligram (mg) is a small proportion of this, but few are aware that milligram is actually one thousandth of a gram.

The microgram does not appear in the lives of most people. It is a unit of measurement effectively confined to scientific disciplines, and the scientific knowledge of the great majority of the population is abysmally low. Few people can even guess that a microgram is one thousandth of a milligram, a millionth of a gram. Such a tiny amount is beyond general comprehension. The minimum daily requirement of Vitamin D is 10 millionths of a gram (10 μg)  and the requirement for optimal immunity is 100 millionths of a gram (100 μg). Here lies the opportunity for confusion and danger.

The abbreviations mcg or μg are also unknown to most non-scientific people. Unfortunately mg can be assumed and has been expressed in the press. This immediately leads to a dose excess by a factor of one thousand.

The development of confusion

If a person takes Vitamin D 4,000 units each day, all will be well, simple and easily understood. 4,000 is a large number, but remember the 10 gram mouse.

But if we transcribe this to 100 mcg or μg there is opportunity for confusion and error. It is possible that in error 100mg will be taken, which is 4,000,000 units, a thousand-fold increase.

This is the way in which severe hypervitaminosis D can occur. Fortunately it is easy treated.

The sensible way forward is regard Vitamin D in the way that we sensibly regard Insulin: keep to well-understood international units, and forget what in practice is the pseudo-science of using tiny mass units in public life.

Advice from the Newspapers

Sky News

Sky News misinterpreted the units. Sky News reported that the subject of the case report was taking 50,000mg of vitamin D each day, which was obviously absurd. 50,000mg is 50g, the size and weight of a large egg.  but the reporter had no knowledge of units of measurement

50,000 mg is 50,000,000 micrograms, 50 million! With a Vitamin D conversion factor of 40 it would be 2,000,000,000 units, 2 billion units! How the press can misinform.

The patient, described in the British Medical Journal (BMJ)

Although maintaining anonymity, the BMJ gives information about the circumstances of the Vitamin D excess. 

"The middle-aged male patient had a variety of health issues, including tuberculosis, an inner ear tumour (left vestibular Schwannoma) that had resulted in deafness in that ear, a build-up of fluid in the brain (hydrocephalus), bacterial meningitis, and chronic sinusitis."

The description continues:

"He had been taking high doses of more than 20 over the counter supplements every day containing vitamin D 150,000 iu (daily requirement 10 mcg or 400 iu); vitamin K2 100 mg daily (daily requirement 100–300 μg); vitamin C; vitamin B9 (folate) 1,000 mg (daily requirement 400 μg); vitamin B2 (riboflavin); vitamin B6; omega-3 2,000 mg twice daily (daily requirement 200–500 mg); plus several other vitamin, mineral, nutrient and probiotic supplements."

 What we can see is vast uncontrolled polypharmacy self-administered by someone with no understanding of what he was doing. It is very sad but we are in an era of "healthism" in which taking supplements is almost routine. Those people selling the supplements should exert some control over excess consumption, and this should have been the most important message of the case report. 

In a medical world supplements, replacement therapies, are given on the basis of need. Type 1 diabetes is a condition of insulin deficiency, and insulin replacement therapy is given under controlled conditions, with careful monitoring of blood levels of glucose and HbA1c. 

Clinical and public health medicine should have a firmer grip on Vitamin D, so that supplements are given following blood level testing, with follow-up to ensure appropriate dose. Medicine is negligent in not achieving this, with public health and health service managers even more negligent in discouraging it.

Incidentally, the BMJ Case Report is not perfect. It uses both mcg   and μg as abbreviations for micrograms. My preference is the abbreviation "mcg" as this is simple to type. To type "μg" requires looking up symbols. Using Greek letters without necessity is an example of pseudo-science.

The Case Report uses IU as a cumbersome and not always intelligible abbreviation for international units. Once again we should take the lead from Insulin and use the simple abbrevation "unit" which is what everyone has used during the past hundred years.

It mentions in respect of VItamin D a "daily requirement 10 mcg or 400 iu". This is the dose that is necessary to avoid rickets, but it is increasingly recognised that about ten times that dose is necessary to optimise immunity.

When I read "Hypervitaminosis D, as the condition is formerly known...." I was rather surprised as I did not know of a more recent term. I now realise that this is a typo, and that "formerly" should have been "formally", a similar word with a very different meaning.

Blood levels of Vitamin D

The blood level of VItamin D is not generally measured, and indeed clinical doctors in the UK are discouraged from requesting it. After ingestion or production in the skin, Vitamin D is transported to the liver. It is then hydroxylated to 25(OH)D, which is the circulating reservoir available for immediate use. It is Vitamin D as 25(OH)D that is measured in the blood as a routine. 25(OH)D is also known as Calcidiol or Calcifediol. 

It is not appropriate or possible to use international units in measuring blood levels of Vitamin D. It is only since the measurement by mass units that the blood levels have been able to be expressed.

Blood levels have been initially expressed by the mass unit of nanogram

The same problem again: only people with a scientific background might understand this unit. One nanogram is a thousandth of a microgram, and so one nanogram is a thousandth of a millionth of a gram. Perhaps the general population does not need to be troubled by this.

There is a movement towards using SI units (International System of Units), involving molar measurements. And so 40ng/ml (40 nanograms per millilitre) is equivalent to 100nmol/L (100 nanomols per litre), a conversion factor of 2.5.


It is also possible to measure the blood level of circulating fully-activated Vitamin D, 1,25(OH)D. Most 1,25(OH)D (Calcitriol) is produced in the cells of immunity in response to infection, but a small amount is produced in kidney cells to circulate and act on bone and maintain an accurate blood level of ionised calcium. 1,25(OH)D is present in the blood in only very tiny amounts, measured in picograms per millilitre. A picogram is a thousandth of a nanogram, in other words a million millionths of a gram. In practical terms this need not concern us, but it demonstrates the tiny amounts of hormones that are necessary for bodily health.

Complexity can lead to error

I hope that the numbers displayed have not been overwhleming. The complexity outlined is in the use of varying terms of measurement, not of the need for and benefits from VItamin D.

I would strongly recommend the continuing use of International Units, or just "units" that we have all been accustomed to during the past century. As it works perfectly well and without confusion with Insulin, let Vitamin D be the same.

I would also recommend that doctors in clinical and public health take more responsibility for Vitamin D, identifying deficiency by blood testing, prescribing or advising appropriate dose, and using blood levels to monitor the dose of the supplement.

It is also important that pharmacists and others who are selling Vitamin D directly to the public take responsibility in advising against excessive dose and uncontrolled polypharmacy in general. 

Many strengths of Vitamin D capsules are available. Perhaps the highest strength should be 20,000 units, with emphasis that it is a convenient and effective dose to be taken only once a week. This is what I take.

On the rear of this packet, the manufacturer clearly states that this is a once per week dose, and that doctors and pharmacists must confirm this.

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