Covid-19: Public health agencies review whether vitamin D supplements could reduce risk
BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m2475 (Published 19 June 2020) Cite this as: BMJ 2020;369:m2475
All rapid responses
Dear Editor
The cost of a serum Vitamin D (25-hydroxy) profile is £40 at one London Medical Unit.
Surely many people would regard that as good value for money during the Covid-19 pandemic especially if they are in a high risk category.
Competing interests: No competing interests
Dear Editor
Most of the reported COVID-19 deaths in Sweden are in the elderly - is there a problem with vitamin D deficiency in this age group?
Latest reported deaths in Sweden are 5,526 (pop. 10.23 million), with 1,428 deaths in people over 90. 2,300 deaths are reported for people in the age group 80-90. So that’s 3,728 of the deaths. Then there are reportedly 1,194 deaths in the age group 70-79. That’s 4,922 deaths across the age group 70 to over 90. There are 379 deaths reported across the ages 60-69. And 156 deaths in the age group 50-59. With a total of 69 deaths across the ages of 0-49 years.[1]
So most of the deaths are in the elderly age group 70 to 90, i.e. 4,922 deaths, people who are also likely to have comorbidities.
Some previous studies have identified vitamin D deficiency in Swedish nursing homes, see for example "Vitamin D deficiency was common among nursing home residents and associated with dementia: a cross sectional study of 545 Swedish nursing home residents"[2], and "Vitamin D deficiency in elderly people in Swedish nursing homes is associated with increased mortality"[3].
Considering Sweden as a whole, it seems most of the population remains alive and not adversely affected by SARS-CoV-2 in the prime of their lives. Perhaps Sweden has made the right decision not to grossly disrupt its society and the lives of millions of people with draconian lockdowns?
Internationally, the focus now should be on finding effective treatments and strategies for the sick, i.e. generally elderly people. And recommending long-term practical preventive measures for the population generally, to reduce the prospect of the illnesses which exacerbate the effects of the SARS-CoV-2 virus, and enhance health, e.g. promoting optimum vitamin D levels.
References:
1. As at 10 July 2020 on the Statista webpage: Number of coronavirus (COVID-19) deaths in Sweden in 2020, by age groups: https://www.statista.com/statistics/1107913/number-of-coronavirus-deaths...
2. Arnljots, R., Thorn, J., Elm, M. et al. Vitamin D deficiency was common among nursing home residents and associated with dementia: a cross sectional study of 545 Swedish nursing home residents. BMC Geriatr 17, 229 (2017). https://doi.org/10.1186/s12877-017-0622-1
3. Maria Samefors et al. Vitamin D deficiency in elderly people in Swedish nursing homes is associated with increased mortality. European Journal of Endocrinology. May 2014. 170:5, 667-675.
Competing interests: No competing interests
Dear Editor
According to its website NICE “provides national guidance and advice to improve health and social care”. It does not specify that this must be based on evidence rather than common sense.
Emerging data strongly suggests that a vitamin D3 blood level of at least 75 nmol/L (30 ng/ml) is needed for protection against COVID-19 [ ]. Government recommendations for vitamin D intake – 400 IU/day for the UK and 600 IU/day for the USA (800 IU for >70 years) and the EU – are based primarily on bone health. This is woefully inadequate in the pandemic context. An adult will need to take 4000 IU/day of vitamin D3 for 3 months to reliably achieve a 75 nmol/L level. Persons of colour may need twice as much.
The NICE Evidence Summary adds nothing to this statement and does nothing to refute it. It shows no understanding of dosage requirements for vitamin D. It perpetuates the erroneous assumption that “For most people, 10 micrograms of vitamin D (400 IU) a day will be enough and people should not take more than 100 micrograms a day because it could be harmful.”
This is inaccurate by about an order of magnitude, and is based on a misreading of the data. The UK Scientific Advisory Committee on Nutrition (SACN) report of 2016 which set the recommended Upper Level (UL) intakes of 50mcg/2000iu per day says;
“Excessive vitamin D intakes have, however, been shown to have toxic effects (Vieth, 2006).” However, in 2006 Vieth clearly stated [ ], and documented, that; "Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L." To achieve that blood level requires a sustained intake of over 500mcgs (20,000 IU) per day.
The risk from not acting is therefore much greater than the risk from acting. There is no significant down-side to making vitamin D available to everyone, in appropriate doses (5,000 to 10,000 IU per day for an adult), now. That’s the common sense approach.
1. Downing D. HOW WE CAN FIX THIS PANDEMIC IN A MONTH. Orthomolecular Medicine News Service http://orthomolecular.org/resources/omns/v16n34.shtml
2. Vieth R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr. 2006;136(4):1117-1122. doi:10.1093/jn/136.4.1117
Competing interests: No competing interests
Dear Editor
With all due respect to Dr Chrisp it might be more important for NICE to grasp what Prof Cobbold and Dr Grant are talking about than for them to grasp the reasons behind NICE's narrow parameters for inquiry. If Cobbold and Grant are right - as I suspect - it could relieve untold human misery and get the world back to the normal life we should all require. Moreover, if the government fail to institute measures to bring the nation's Vitamin D up to recommended levels it will surely be much to blame for the consequences.
Paul Chrisp, 'Re: NICE response to Vitamin D correspondence', 9 June 2020, https://www.bmj.com/content/369/bmj.m2475/rr-8
Competing interests: AgeofAutism.com, an on-line daily journal, concerns itself with the potential environmental sources for the proliferation of autism, neurological impairment, immune dysfunction and chronic disease. I receive no payment as UK Editor
Dear Editor
In response to correspondence from Dr Ellen Grant (2 July 2020; https://www.bmj.com/content/369/bmj.m2503/rr-5) and Professor Peter Cobbold (20 June 2020; https://www.bmj.com/content/369/bmj.m2475/rr) on the NICE rapid evidence summary on vitamin D for COVID-19 (29 June 2020), we would like to clarify the following.
First, the authors appear to have misunderstood the role that NICE plays in clinical research. The remit of NICE is not to conduct scientific trials, but to produce guidance and advice for health, public health and social care practitioners based on evidence, and the expert interpretation of that evidence for UK clinical practice.
Second, the authors may have missed the description in the scope that stated the purpose of the NICE evidence summary on vitamin D for COVID-19 (1) was to review the best available evidence on the effectiveness and safety of vitamin D supplementation for the treatment or prevention of COVID-19, or the susceptibility to COVID-19 based on vitamin D status.
The evidence summary did not aim to define a level at which vitamin D status is deficient. Rather, it reiterated current UK Government advice and the findings of the 2016 Scientific Advisory Committee on Nutrition (SACN) report on vitamin D and health (2) that to protect musculoskeletal health, 25(OH)D levels should not fall below 25 nmol/L.
The scope of the NICE evidence summary also did not include studies on vitamin D for acute respiratory tract infections more generally, or the association of vitamin D status with immunity, hypertension or obesity, for example. However, a rapid review on vitamin D and acute respiratory tract infections (3), as well as a rapid scoping exercise on nutrition and immune function in relation to COVID-19 (4) was released by SACN at the same time as the NICE evidence summary was published.
While we coordinated with SACN on the release of the two reviews, they are ultimately separate. Should there be any changes to the UK government advice on vitamin D levels we will update our evidence summary accordingly.
Finally, the research included in this summary was selected following a thorough and precise literature search. Although no published randomised controlled trials on vitamin D and COVID-19 were found, 5 observational studies from peer-reviewed journals met the criteria for inclusion and were selected.
To clarify, NICE evidence summaries do not routinely include preprints (such as the Indonesian study mentioned), because they have not been through a minimum quality standard of peer-review prior to publishing.
However, both preprints and ongoing studies were listed in appendices to the evidence summary to alert readers to the wider, emerging evidence base. Our team is also continuing to monitor ongoing research on the subject should a review and update of the evidence summary become necessary.
1. National Institute for Health and Care Excellence. (2020). COVID-19 rapid evidence summary: vitamin D for COVID-19. Available at: https://www.nice.org.uk/advice/es28/chapter/Key-messages (Accessed: 6 July 2020).
2. The Scientific Advisory Committee on Nutrition. (2016). SACN vitamin D and health report. Available at: https://www.gov.uk/government/publications/sacn-vitamin-d-and-health-report (Accessed: 6 July 2020).
3. The Scientific Advisory Committee on Nutrition. (2020). Rapid review: Vitamin D and acute respiratory tract infections. Available at: https://www.gov.uk/government/groups/scientific-advisory-committee-on-nu... (Accessed: 6 July 2020).
4. The Scientific Advisory Committee on Nutrition. (2020). Rapid scoping exercise: Nutrition and immune function in relation to COVID-19. Available at: https://www.gov.uk/government/groups/scientific-advisory-committee-on-nu... (Accessed: 6 July 2020).
Competing interests: No competing interests
Dear Editor
BAME clinical and support staff are dying in disproportionate numbers, as are those in the general population.
Natural migration patterns may throw light on this issue. It has been suggested that Covid-19 in the Philipines has a low death rate (1), due in part to protection from sun produced vitamin D. However, in the bleak climate of the UK, the mortality of nurses originating from the Philipines has been such as to raise concern with the ambassador. Very real issues of poverty and discrimination have been raised as possibly contributing. But the first 10 doctors who died of covid here were of a BAME background, and were much less likely to be poor than nurses.
Following the finding of high numbers of rickets in Glasgow children of Asian origin, much work has been done in the UK. In particular, the neonate's status depends on its mother's status, so supplements have been recommended in the final months of pregnancy, and not just in veiled Muslim women of Asian heritage (2).
In the US, fibroblasts from skin biopsies were cultured from citizens of european origin, and compared with those with Asian heritage. The enzyme 25(OH)D-24-hydroxylase was more active in the latter, who would therefore be more likely to be vitamin D deficient, and to require higher doses to rectify this deficiency (3). The same authors have found low levels of vitamin D, due to dark skins in US Afro-Americans, who have recently suffered so grieviously from covid.
It is to be hoped that the COVIDENCE UK study will take these sort of factors into account, and give us more evidence on whether or not an adequate vitamin D level for the individual protects against covid infection in the first instance, and more importantly, whether it protects from the later cytokine storm that can be so lethal.
(1).Editorial. low population mortality from COVID‐19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity
https://onlinelibrary.wiley.com/doi/full/10.1111/apt.15777
(2).Vitamin D deficiency in UK Asian families: activating a new concern.
https://adc.bmj.com/content/86/3/147
(3).Vitamin D Metabolism Is Altered in Asian Indians in the Southern United States: A Clinical Research Center Study
https://academic.oup.com/jcem/article/83/1/169/2865135
Competing interests: No competing interests
Dear Editor
May I seek Prof Green’s thoughts?
Times past, faraway land.
As an ancient, I remember a fellow child with cervical gland tuberculosis being treated with Cod Liver Oil.
There was no Streptomycin then. The treatment appeared to have been successful. Nature may have played a part.
I also remember Shark Liver Oil being used as a substitute for Cod Liver Oil (the War, WW 2: that is). Either Cod Live Oil was in short supply, or Sharks were more plentiful.
All livers are rich in vitamin D and also in vitamin A.. I accept that Vitamin D is useful in countering Covid-19. And I take D 3.
Q. Instead of giving vitamin D to patients and possible future patients, should not Vitamin A also be added?
I see no prospect of poor Britain finding the money to determine Vitamin D levels of patients (let alone all residents). Would it not be cheaper to give all adults a tablespoon of Cod liver Oil or Shark Liver Oil every day?
The vegetarians will have to be exempted.
Competing interests: No competing interests
Dear Editor
What is the point of this endless dither when the correct levels for Vitamin D are already well established and would help to raise overall resistance to infectious disease this winter? Just what are we scared of?
Competing interests: AgeofAutism.com, an on-line daily journal, concerns itself with the potential environmental sources for the proliferation of autism, neurological impairment, immune dysfunction and chronic disease. I receive no payment as UK Editor
Dear Editor,
The use of Vitamin D in pandemic infection is not new. In 1848 the physicians of the Brompton Hospital undertook a study of the use of Cod Liver Oil (very high in vitamin D) in 1000 patients with phthisis (Tuberculosis, TB) (1). In 500 patients given usual treatment the mortality was 33%. In 500 similar patients given daily Cod Liver Oil the mortality was 19%, a massive 42% reduction in death rate. The subsequent widespread use of Cod Liver Oil may well have contributed to the reduction in incidence and severity of TB over the following century, well before the advent of antibiotic therapy.
While Covid 19 is very different from TB, the human immune system has probably changed little over 170 years. The need for an adequate level of Vitamin D for fighting severe Covid infection deserves urgent study and probably a positive approach to this simple therapy.
1. Green M, Cod Liver Oil and Tuberculosis, BMJ 2011; 343: 1305-1307 BMJ 2011:343:d7505
Competing interests: No competing interests
COVID-19 and Vitamin-D – NICE; Unthinking discrimination against BAME, Elderly and Obese? Affirmative-action needed to mitigate D deficiency, in high-COVID-risk groups.
Dear Editor
In response to the comments of Dr Paul Crisp, Director of Nice, https://www.bmj.com/content/369/bmj.m2475/rr-8:
Multiple preprints suggest vitamin D deficiency factors in COVID-19 severity and mortality risk in BAME Persons, Elderly and Obese, COVID-19 patients. Vitamin D is a steroid hormone family (cheap, well-researched, natural, with limited side-effects, and a million-year evolutionary efficacy and safety-history), sharing many VDR (vitamin D receptor) pathways[1] with Dexamethasone (a useful pharmaceutical steroid, 60 years old but not part of our evolutionary history, with a long list of potential side effects). Given VDR commonalities with Dexamethasone; immune biology, and wider emerging evidence; it might logically be expected vitamin D, like Dexamethasone, will likely, reduce immediate impact of COVID-10 severity and mortality. Vitamin D may further have longer term beneficial effects – longer term outcomes of Dexamethasone in COVID-19 have yet to be announced.
Thus, did NICE/NHS/PHE, our health guardians, in the fog and darkness of COVID-19, leave their ‘pandemic-act-decisively’ hat in the dexamethasone draw, when considering the needs:
- to test COVID-19 patients for vitamin D deficiency;
- to widen clinical recommendations for clinical testing;
- and or increase provision for automatic higher vitamin D repletion dosing;
thus ensuring better repletion of groups most at risk of Vitamin D deficiency.
This hesitancy ironically manifests, despite Vitamin D deficiency disease being a recognised, NICE defined, clinical condition; with NICE advice on; testing, repletion, and wider parameters. https://cks.nice.org.uk/vitamin-d-deficiency-in-adults-treatment-and-pre...
Within this framework, it is NICE, who delineates the very narrow parameters within which NHS clinical practitioners may test, in the terms;
- “Only test vitamin D status if someone has symptoms of deficiency or is at very high risk”[2];
- recommended supplementation is limited to RNI[2], unless the patient is deficient (which requires a test – hence the catch-22).
Thus, perversely, UK Doctors are discouraged from testing, and or sufficiently supplementing, those at greatest risk of both D-deficiency and COVID-19 mortality, namely; BAME Persons, Elderly, Obese, the Institutionalised, and Hospitalised; with their higher D repletion requirements – confusing / limiting the capacity of Doctors to address vitamin D deficiency in those that are most in need.
NICE unquestionably has authority and capacity to swiftly widen the groups who may be tested for vitamin D levels; and/or facilitate GPs administering, without testing, higher vitamin-D-boluses to all patients at medium-risk of deficiency (BAME, Elderly, Obese, Pregnant et al.).
As below,[3] Australia tests more widely; and New Zealand recommends routine administration of 50,000iu per month; for medium-risk patients.
In contrast to the more visionary pragmatic Antipodean approach, NICE/SACN/PHE have arguably failed to address, with sufficient granularity, the niche-needs of minority groups, BAME, Elderly and Obese Persons, relying instead on generalised-population-based statistics. COVID mortality and infection rates are interestingly lower in the Antipodes, and a recent Australian spike has occurred in a complex with a high minority ethic populous.
NICE, by their failure to decisively address, both; the long-standing-high-risk of vitamin D deficiency; and likely related increased COVID-19 mortality rates, in these groups, arguably sadly open themselves to criticisms of discrimination by; Ethnicity, Age, Fat-mass, Institutionalised and Hospitalised Status, as well as failure to act D-decisively in a pandemic, based on likely benefits v harms.
A recommendation by NICE to vitamin D test COVID-19 Patients in hospitals and care homes, would have both; helped address D deficiencies in COVID-mortality-at-risk-group patients; and also provided valuable population data, including as to D status of the most COVID-mortality vulnerable; namely BAME Persons including those of African Americans origin, Elderly, Obese and Hospitalised– thus further and usefully informing public health policy.
A wider and a final search before NICE publication on 29th June, would have revealed omitted preprints, which together suggest a strong direction of emerging research; reflected in approximately 12 preprints including one in England (134 COVID-19+ patients), and more widely a German paper looked at D and respiratory function.[4] Preprints were relatively easily found; as many were listed in the BMJ Rapid Response Letter dated 25th June 2020.[3] https://www.bmj.com/content/369/bmj.m2475/rr-1
Subsequent known studies include; Cincinnati[5] (689 Covid-19+ patients); Israel[6] (14,832; 7087 COVID-19+ patients), and a military hospital in Brazil[7] (172 COVID-19+ patients). Two of the original seven[8] are no longer available; one of them following the sad death of the lead, Prabowo Raharusun GP, whilst working on the COVID-19 front-line.
A late NICE addendum would have allowed their listing/consideration on 29th June, in final summary conclusions. Adjustment for factors impacted by vitamin D such as hypertension, cardiovascular disease and obesity are complex,[9] with limited value if not suitably nuanced. Hill criteria offer an alternative assessment protocol.[10]
Is it not time for pandemic-urgent recognition of the need for vitamin-D-clinical-sufficiency equality for all, including BAME Persons, the Elderly and Obese.
1. Navarro-Barriuso, J., Mansilla, M.J., Naranjo-Gómez, M. et al. (2018). Comparative transcriptomic profile of tolerogenic dendritic cells differentiated with vitamin D3, dexamethasone and rapamycin. Sci Rep 8, 14985 (2018). https://doi.org/10.1038/s41598-018-33248-7 Available at https://www.nature.com/articles/s41598-018-33248-7 (Accessed: 13 July 2020).
2. NICE. (2017). Vitamin D: supplement use in specific population groups. Public health guideline [PH56] Published date: 26 November 2014 Last updated: 30 August 2017. https://www.nice.org.uk/guidance/ph56/chapter/1-Recommendations#recommen... (Accessed: 10 July 2020).
3. Brown, R. (June 25 2020). Pandemic - ‘Action This Day’ – Measure Vitamin D in COVID-19 Patients – Time is of Essence – BAME, Elderly and Obese are Disproportionately Dying. In response to Covid-19: Public health agencies review whether vitamin D supplements could reduce risk. BMJ 2020;369:m2475
doi: https://doi.org/10.1136/bmj.m2475 (Published 19 June 2020). Available at https://www.bmj.com/content/369/bmj.m2475/rr-1 (Accessed: 10 July 2020).
4. Brenner, B., Holleczek, B., & Schoettker, B. (June 23 2020). Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: potential for limiting the death toll during and beyond the COVID-19 pandemic. medRxiv 2020.06.22.20137299; doi: https://doi.org/10.1101/2020.06.22.20137299 Available at https://www.medrxiv.org/content/10.1101/2020.06.22.20137299v1 (Accessed: 10 July 2020).
5. Mendy, A., Apewokin, S., Wells, A., & Morrow, A. (2020). Factors Associated with Hospitalization and Disease Severity in a Racially and Ethnically Diverse Population of COVID-19 Patients. medRxiv : the preprint server for health sciences, 2020.06.25.20137323. https://doi.org/10.1101/2020.06.25.20137323 Available at https://www.medrxiv.org/content/10.1101/2020.06.25.20137323v2 (Accessed: 10 July 2020).
6. Merzon, E., Tworowski, D., Gorohovski, A., Vinker, S., Cohen, A., Green, I., & Morgenstern, M. (July 3 2020). Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study. medRxiv 2020.07.01.20144329; doi: https://doi.org/10.1101/2020.07.01.20144329. Available at https://www.medrxiv.org/content/10.1101/2020.07.01.20144329v1 (Accessed: 10 July 2020).
7. Tort, A., Mercado, E., Martínez‑Cuazitl, Nieto, A., & Pérez, R. (April 30 2020). La deficiencia de vitamina D es un factor de riesgo de mortalidad en pacientes con COVID-19. (Deficiency of vitamin D is a risk factor of mortality in patients with COVID-19) https://dx.doi.org/10.35366/93773 doi: 10.35366/93773 Available at https://www.medigraphic.com/pdfs/sanmil/sm-2020/sm201_2za.pdf (Accessed: 10 July 2020).
8. Brown, R. (May 19, 2020). ‘Low Vitamin D: high risk COVID-19 mortality? Seven preprints suggest that is case. Does low ‘D’ put BAME and elderly, at particular COVID-19 risk? Testing and Data Required’, BMJ, 369(m1548). DOI: 10.1136/bmj.m1548 Available at: https://www.bmj.com/content/369/bmj.m1548/rr-19 (Accessed:10 July 2020).
9. Fan, X., Wang, J., Song, M., Giovannucci, E., Ma, H., Jin, G,. Hu, Z., Shen, H,. & Hang, D. (July 4 2020). Vitamin D status and risk of all-cause and cause-specific mortality in a large cohort: results from the UK Biobank, The Journal of Clinical Endocrinology & Metabolism, , dgaa432, https://doi.org/10.1210/clinem/dgaa432 Available at https://academic.oup.com/jcem/article-abstract/doi/10.1210/clinem/dgaa43... (Accessed: 10 July 2020).
10. Annweiler, C., Cao, Z., Sabatier J. (June 7 2020). Point of view: Should COVID-19 patients be supplemented with vitamin D? Review article| Volume 140, P24-26, October 01, 2020. DOI:https://doi.org/10.1016/j.maturitas.2020.06.003 Available at https://www.maturitas.org/article/S0378-5122(20)30292-9/abstract (Accessed: 10 July 2020).
Competing interests: No competing interests