Covid-19 and Vitamin D: a wasted opportunity

Dr David S Grimes MD FRCP, retired consultant physician

When the pandemic of COVID-19 arrived in Europe in early 2020, many realised that the population required protection by the natural process of defensive immunity. The influenza pandemic of 1969 resulted in an estimated 60,000 deaths in the UK but at that time there was no public health policy, and the understanding of defensive immunity was rudimentary. But in the 21st century medical science has advanced with a much greater understanding of immunity and the pivotal role of vitamin D in activating the escalation of immunity at the time of infection.

I expected that a public health initiative in correcting vitamin D deficiency would be cheap, safe, and immediately available. The nation had the opportunity to act in a way that was not possible in the 20th century but my expectations were not met. The resistance to the use of vitamin D was difficult to understand.

Reports from SE Asia early in the pandemic demonstrated that people who were seriously ill or who had died from COVID-19 had much lower blood levels of vitamin D than those with only mild illness. This amplified the importance of correcting vitamin D deficiency. The relationship between low blood levels of vitamin D and unfavourable outcome from Covid-19 was subsequently demonstrated in India, Singapore, Saarland (Germany), Newcastle upon Tyne, Bari (Italy), Chicago, Israel, Iran, Heidelberg, Boston, Tehran, Birmingham (UK), Turkey, Mexico, St Petersburg, Rhône (France), Santander (Spain), and Ireland.

An unfavourable outcome from COVID-19 associated with low blood levels of vitamin D cannot be disputed.  However could the low blood levels might be the result of the serious infection, as it is known that a molecule of 1,25(OH)D can be used only once, and so vitamin D is consumed during escalation of defensive immunity. What was required was knowledge of blood levels of vitamin D before the infection and results of such studies soon became available.

A study from Heidelberg demonstrated this. A low blood level of vitamin D on admission to hospital was associated with an unfavourable and often fatal outcome. Vitamin D deficiency therefore preceded death and was predictive of that death. In a similar study in Israel low blood levels of vitamin D recorded well before the onset of illness predicted critical or fatal COVID-19.

It was noted that Covid-19 death rates were particularly high in certain groups of the population. These included the elderly, obese, and those of south Asian or black African ethnicity. The elderly are inevitably vitamin D deficient as their dry skin does not produce the oil 7-dehydrocholesterol which is the precursor of vitamin D. Vitamin D deficiency is also particularly common in the obese as fat soluble vitamin D is trapped in the adipose tissue.

The high COVID-19 death rate in people of south Asian ethnicity quite rightly attracted attention, and three inquiries were conducted to identify the cause. The conclusions were that south Asian ethnic people were susceptible to COVID-19 death because of poverty, racism, and socio-economic disadvantage. Vitamin D deficiency was not even considered.

My own research identified 26 doctors who were working in the UK and who died between the onset of the pandemic and May 3rd 2020. 25 of them were of south Asian or black African ethnicity. Being doctors they were not socio-economically disadvantaged, but they would all have been severely deficient of vitamin D.

When vitamin D is produced by the action of solar UV radiation on the oil 7-dehydro-cholesterol that is synthesised in the skin, it is taken in the blood to the liver. In a similar way vitamin D taken by mouth or by injection is also taken to the liver. It will rest in the liver while it is slowly part-activated into 25(OH)D, also known as calcidiol or calcifediol. This process will take up to two weeks, but calcifediol given by mouth takes just two hours to achieve good blood levels.

A study was undertaken in Córdoba hospitals and involved patients admitted to hospital on account of COVID-19. They were given randomly either just high quality standard treatment or calcifediol in addition. The results were dramatic. Of the 26 standard care only patients, 13 (50%) required admission to intensive care and 2 died. Of the 50 patients given calcifediol in addition, only 1 (2%) required ICU admission and there were no deaths. The UK National Institute for Health and Care Excellence (NICE) informed doctors that the results of this trial should not influence the way in which they treat patients. This instruction (August 2020)  of staggering arrogance must be held responsible for many deaths, as well as seriously undermining the excellence of clinical medicine in the UK and elsewhere.

A larger study was undertaken in Barcelona, again of patients admitted to hospital with Covid-19. Of the 379 control patients, 80 (21.1%) required admission to ICU, compared to 30 (5.4%) the 551 patients given calcifediol. Deaths were 15% in the control group and 6.5% in the calcifediol group.

Once again this dramatic benefit was not allowed to translate into clinical benefit of dying patients around the world. Although readily available for the public in Spain and Italy, in other countries it was used only in farm animals. A license for human use could readily have been achieved.

The slow part-activation of vitamin D to calcifediol appears to have been unknown to clinical scientists in Brazil, where an RCT used vitamin D in its natural form in patients who already been admitted to ICU and were obviously extremely ill. The vitamin D conferred no advantage, with similar death rates in treated patients and controls. What the RCT in Brazil told us is that when people are sick with COVID-19 vitamin D must be given in its rapidly acting part-activated form calcifediol, as given in Spain.

When people became ill and were tested positive for COVID-19, they were sent home from the testing centre with instructions to isolate and to attend the hospital if they had difficulties with breathing. No initial treatment was given. It would have been sensible for them to have been given vitamin D when they tested positive. If a person with COVID-19 was admitted to hospital as emergency they could have been given calcifediol immediately. This did not happen. In the winter of 2020–2021 number of cases and deaths from COVID-19 increased, despite the introduction of the vaccination program.

How many of deaths could have been prevented safely and at very low cost, and how much pressure could have been taken off the hospitals and their intensive care units? I asked this question to senior medical people but I was told that there was “not enough evidence” to introduce treatment with vitamin D and calcifediol. I was told that we must wait for the results of the UK Martineau study.

Professor Adrian Martineau proposed in 2020 a new RCT to assess the effect of vitamin D in the prevention of COVID-19, with minimisation of serious illness and death. The subjects of the trial were to be normal people within the community who were perfectly fit and healthy. They were allocated to receive either vitamin D 800 units each day or 3,200 units each day, and those in the control group were not offered any vitamin D and were not given a placebo.

In March 2022 the result of the study told us nothing about the effectiveness of vitamin D. There are two serious problems. The first is that the “control” group was not controlled. The subjects were told that they would not be receiving vitamin D, and so many of them obtained their own supplies: the average blood level at the end of the study was almost as high as the treated groups. The other problem is that the study was simply much too small, it lacked power. There were no deaths in the study and just one person in each group required intensive care unit ventilation. Advantages or disadvantages of vitamin D could not be established, and this was stated in the paper.

The conclusions two and half years after the start of the Covid-19 pandemic are that:

  1. there is a need for correction of vitamin D deficiency in advance of serious infection;
  2. people who are deficient of vitamin D are at particular risk of critical or fatal Covid-19;
  3. vitamin D supplements are of benefit in reducing the impact of Covid-19;
  4. voices to deny the benefits of vitamin D have been wrong;
  5. many thousands of people who died form Covid-19 need not have done had vitamin D deficiency been corrected early in the pandemic;
  6. vitamin D supplement could be given to all adults, but ideally when they are demonstrated by blood test to be deficient;
  7. people who test positive for COVID-19 should be given a single supplement dose of vitamin D 20,000 units, and this should be repeated weekly if the blood test shows deficiency;
  8. If someone has COVID-19 sufficiently serious to necessitate admission to hospital, there is obviously an element of urgency and so vitamin D must be given in the form of calcifediol;
  9. one unit of vitamin D is by definition the requirement of a 10 gram mouse. Scale up from this and a 60kg human should need 6,000units each day. Just half of this should be adequate, 3,000units daily or 20,000units once a week;
  10. keep to units, as with insulin, because using the mass unit microgram causes confusion with the danger of excessive dose;
  11. in the case of urgent need for vitamin D to optimise defensive immunity at the time of serious infection, it is necessary to use calcifediol, 532 micrograms as an initial first dose followed by 266 micrograms on days 3, 7 and 14 (it is not appropriate to express calcifediol as units, but the doses equate to 20,000 and 10,000 units of vitamin D).

Further reading






UK, Martineau