December 17, 2020

expert reaction to rapid COVID-19 guidance on vitamin D, published by NICE, PHE and SACN

Leading health bodies, National Institute for Health and Care Excellence (NICE), Public Health England (PHE) and Scientific Advisory Committee on Nutrition (SACN), have published a rapid guidance on vitamin D for COVID-19.

Dr David Armstrong (Consultant Rheumatologist, WHSCT, Clinical Lead for Fracture Liaison & Osteoporosis, Visiting Professor, NICHE, Ulster University), said:

“It is great to see NICE, SACN and PHE interested in vitamin D research, and recognising the urgent need for good quality and relevant data in this area, especially in older, vulnerable or residential care patients.  It is important that people do not interpret the statement in a negative way – that vitamin D is of no health benefit – when we have good evidence of its benefit in many scenarios, including for bone and muscle health.  It is more important than ever that people avoid vitamin D deficiency – but we also look forward to seeing more evidence of its effects in the management of the serious respiratory illness caused by SARS-CoV-2.”

Dr Emeir McSorley, Senior Lecturer in Human Nutrition, Ulster University, said:

“Adhering to vitamin D guidelines is important for optimal musculoskeletal and bone health as well as having an important role in immune function, particularly in the elderly (Laird, 2014).  We welcome the call by this Expert Panel for more robust research with respect to vitamin D and its role in immune response.  In particular, there is a need to determine the exact supplementation dose required to prevent deficiency in older, more vulnerable groups such as those residing in care homes.  Furthermore, effective monitoring of vitamin D status among community-dwelling older adults and care home residents, is needed as part of a strategy to promote better quality of life and health outcomes in the elderly.”

Reference: Laird E, McNulty H, Ward M, Hoey L, McSorley E, Wallace JM, Carson E, Molloy AM, Healy M, Casey MC, Cunningham C, Strain JJ.

Vitamin D deficiency is associated with inflammation in older Irish adults.

J Clin Endocrinol Metab. 2014 May;99(5):1807-15. doi: 10.1210/jc.2013-3507. Epub 2014 Feb 25.

Prof Martin Hewison, Professor of Molecular Endocrinology, University of Birmingham, said:

“The new guidance from NICE, SACN and PHE on vitamin D recommendations for the UK is hugely disappointing, and I am sure that this response will be echoed by many other vitamin D researchers in the UK and worldwide.  SACN, NICE and PHE have indicated that people should follow their original advice given several years ago that everyone in the UK should supplement with vitamin D during winter months but that supplementation with 400 IU/day vitamin D is sufficient to prevent most people from falling below a level of 25 nmol/L serum vitamin D.  These are the lowest vitamin D supplementation recommendations in the world, despite recognition of the prevalence of vitamin D-deficiency in the UK.  Awareness of vitamin D-deficiency in the UK has increased during the COVID-19 pandemic.  This is partly due to lack of sunlight access during lockdown, and partly because several studies have shown that patients with worse COVID-19 outcomes have lower levels of vitamin D.  The increased risk of COVID-19 in ethnic minorities has also been linked to lower vitamin D levels in these populations.  A possible beneficial effect of vitamin D in protecting against COVID-19 infection and disease severity is also supported by basic science data for the immunomodulatory effects of vitamin D¹.  NICE, SACN and PHE insist that more evidence is required.  This includes randomised supplementation trials.  This is very difficult within the timeframe of the pandemic – it may take several months for vitamin D supplementation to elevate serum vitamin D levels.  Moreover, to the best of my knowledge, despite many attempts by various groups to secure support for this type of study during the first few months of lockdown, there has been no UK funding of vitamin D-COVID-19 studies.  NICE, SACN and PHE always state that ‘more studies are needed’ but this is impossible if UK funders will not support these studies.  While this situation persists there is inaction that can readily be avoided with some modest changes to recommendations for vitamin D supplementation which is cheap and safe.

“Several groups, including one that I have participated in, have suggested a higher level of vitamin D supplementation.  Specifically increasing this to 800 IU/day vitamin D.  This is still relatively conservative – groups in the North America are recommending 4,000 IU/day – but is much more likely to improve the vitamin D status of people in the UK.  In rejecting this request to increase recommend vitamin D supplementation NICE, SACN and PHE continue to promote the idea of vitamin D ‘toxicity’, despite no evidence of this in trials where up to 4,000 IU/day vitamin D were used.  This obsession has become a major hurdle to better vitamin D health in the UK.  Many vitamin D researchers have worked tirelessly over the summer to provide a framework in which vitamin D supplementation could be incorporated into the general strategies being used to defeat COVID-19.  NICE, SACN and PHE have rejected this, and their ‘new’ recommendations provide little or no help at all for the UK public.”

1 https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbm4.10405

Dr Zaki Hassan-Smith, Consultant Endocrinologist (University Hospitals Birmingham NHS FT) and Visiting Professor (Health and Life Sciences, Coventry), said:

“I support the conclusions on the rapid guidance on vitamin D for COVID-19 produced by PHE, SACN and NICE.  The general recommendations align with our current evidence base.

“Vitamin D deficiency is common and severe deficiency can be associated with conditions such as rickets and osteomalacia.  Vitamin D supplementation is also used in patients with conditions affecting their bone health such as osteoporosis.

“As background there has been debate over the role of vitamin D in a range of non-skeletal conditions.  There was previous evidence (prior to the emergence of COVID-19) that linked vitamin D status to rates of respiratory infection, and there is also some evidence for a role in Acute Respiratory Distress Syndrome.

“I would support the advice for widespread supplementation in winter months to prevent syndromes of severe vitamin D deficiency in the UK population.  I also support the current position that whilst there is insufficient evidence to support the use of vitamin D specifically to prevent or treat COVID-19, this area should be kept under review with guidance updated as necessary.  Free supplementation for clinically vulnerable groups is a welcome public health intervention.”

Dr Claire Hastie, Lecturer in Public Health, University of Glasgow, and HRD-UK (Health Data Research UK), said:

“The NICE rapid guideline on COVID-19 and vitamin D accurately and succinctly summarises the existing evidence.  Vitamin D is indeed important for bone and muscle health, and the national guidelines on supplementation should be followed.  However, published research including multivariate analysis of largescale observational data provides no evidence to suggest that supplementation will reduce the risk of COVID-19 infection or its severity.  To be sure of whether there is any link robustly conducted randomised controlled trails are required.”

Dr Vimal Karani, Associate Professor in Nutrigenetics and Nutrigenomics, University of Reading, said:

“While 400IU of vitamin D supplementation daily might be required to maintain the bone and muscle health, there is no convincing evidence from RCTs to support whether this daily dose of supplementation will prevent or treat SARS-CoV-2 infection.

“We still do not have convincing evidence from the literature concerning the effects of vitamin D supplementation on preventing or treating SARS-CoV-2 infection given the high level of confounding due to age, gender, BMI, blood group and host genetics, which have not been considered in majority of the studies.  Hence, the guidelines for the daily intake of vitamin D, which have not taken into consideration of the various confounding factors, might work only for some people.

“RCTs have shown that high dose of vitamin D supplementation was required to reduce the symptoms of SARS-CoV-2 infection and achieve SARS-CoV-2 RNA negativity; hence, there is no clear evidence of whether a recommendation of 400IU per day will provide the required immunity to fight the infection.  Furthermore, the epidemiological studies and RCTs have demonstrated inconsistencies with regards to the association between vitamin D supplementation and SARS-CoV-2 infection which could be due to the differences in the sample sizes, age, gender, dose of supplementation, duration of supplementation and ethnic background.  Hence, a study with large number of samples is required to confirm the relationship between vitamin D status and COVID-19.

“It is also possible that host genetic susceptibility could play a role in this association which explains why some individuals respond to high doses of vitamin D supplementation while the rest fail.  This has been shown through studies in BAME communities where the prevalence of SARS-CoV-2 infection was higher compared to Caucasians, given that the genetic map varies across different ethnic groups.”

Some references:

https://clinicaltrials.gov/ct2/show/NCT04344041

https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/s12948-020-00139-0

https://www.sciencedirect.com/science/article/pii/S0960076020302764

https://pmj.bmj.com/content/early/2020/11/12/postgradmedj-2020-139065

https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v1

https://www.mdpi.com/2072-6643/12/4/988

https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15534

https://pubmed.ncbi.nlm.nih.gov/31996793/

Dr David Richardson, Founder and Director of DR NUTRITION (a company that provides specialist consultancy on food science and nutrition), & Visiting Professor of Food Bioscience, University of Reading, said:

“The advice to follow the UK advice to take a vitamin D supplement to maintain bone and muscle health is welcomed but the focus is on the therapeutic use for health care providers, health care staff and health professionals i.e. the cure and prevention of COVID 19, where the evidence is still unfolding.

“What the guideline should include is the need for doctors and health professionals to find out the extent of vitamin D deficiency in the general population and vulnerable groups.  The advice does mention the role of vitamin D in supporting the immune system but there needs to be a much stronger public health message.

“The NICE guideline also states concerns about excess intakes of vitamin D mainly massive doses used by the medical profession, not anywhere near the amounts found in foods or food supplements.

“A key message is to AVOID VITAMIN D DEFICIENCIES in the general population and to remind health professionals to study the most recent National Diet and Nutrition Survey (NDNS) – PHE have just published in the last few days the National Diet and Nutrition Survey (NDNS) Rolling Programme Years 9 to 11 showing a continuing downward trend in intakes of micronutrients and nutritional status of the UK population, including vitamin D intakes and nutritional status.  This report, a few days ago does not seem to be getting the publicity it needs because it highlights the terrible micronutrient status of the population especially Vitamin D.

“PHE are dealing with 3 pandemics in the UK: COVID 19, obesity and vitamin D deficiency.”

Dr Bernard Khoo, Senior Clinical Lecturer in Endocrinology, UCL, said:

“This is welcome guidance from NICE, PHE and SACN on the question of vitamin D supplementation during the COVID-19 pandemic.  This guidance has considered the available evidence so far with regards to the value of vitamin D supplementation in preventing and in treatment of COVID-19.  Although there is some promising evidence that vitamin D may be of value, the data is as yet in early stages and we await definitive large-scale randomised controlled trials before vitamin D can be recommended for COVID-19 either as preventative or treatment.

“Vitamin D is an important nutrient for health, particularly to help maintain bone health.  We definitely should be taking supplements during the winter, when there is not enough UV radiation in the sky to help generate vitamin D in the skin.  This situation has not changed and it is for this good reason that the recommendation is that everyone take a daily supplement of 400 units a day from October to March.  This advice is even stronger for the people mentioned in the press release who are more at risk of vitamin D deficiency.”

Prof Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

“This report, which considers all relevant evidence, is important as it reminds the public that on the basis of available evidence, we absolutely CANNOT say that vitamin D is a ‘magic bullet’ against COVID-19 infection.  Far from it – only ongoing trials will lead us to the truth.  This is because nearly all available vitamin D data linked to COVID-19 is observational and riddled with uncertainty, so it’s impossible to determine cause and effect.

“Indeed, one of the best studies in this area and led by our group, did not show vitamin D levels to be linked to COVID-19 risk once we took account of all factors known to effect vitamin D levels.  We also know that many other chronic conditions linked to low vitamin D levels have not been benefited or lessened in occurrence with Vitamin D supplements in large placebo controlled randomised trials.  As such, people who wish to supplement with vitamin D tablets over the winter period should not think they will become immune to COVID-19 infection.  Rather, they need to continue to maintain all the proven and recommended precautions such as social distancing, as strongly as before, to protect themselves and their loved ones from being infected.”

Prof Adrian Martineau, Clinical Professor of Respiratory Infection and Immunity, Queen Mary University of London, said:

“The tone of this updated NICE guideline on COVID-19 and vitamin D is noticeably more positive than before.  NICE recognises the need for research in this area, and makes specific recommendations about the design of future clinical trials to evaluate a potential role for vitamin D in COVID-19 treatment.  The need for trials of vitamin D to prevent COVID-19 is also acknowledged, but suggestions regarding design of such studies are not made.

“Pending results of these trials, it makes sense for the UK population to follow existing government guidance to take a daily supplement containing 10 micrograms (400 units) of vitamin D during the autumn and winter months.  This safe dose has proven benefits for bone and muscle health.  There is a chance that it might reduce risk and/or severity of COVID-19 into the bargain – clinical trials currently in progress will hopefully shed light on this question.  The recent undertaking by the UK government to provide vitamin D supplements to vulnerable groups free of charge is a welcome first step towards achieving better uptake of this important public health recommendation.”

Prof Keith Neal, Emeritus Professor of the Epidemiology of Infectious Diseases, University of Nottingham, said:

“It has been long standing advice from the NHS and PHE about taking vitamin D during the winter months.  This is more important as during the summer months many vulnerable stayed inside and their levels will have fallen more than usual.  Although there is no reliable evidence on vitamin D and COVID there is good evidence of its benefits generally.”

‘COVID-19 rapid guideline: vitamin D’ by NICE, PHE and SACN was published at 00:01 UK time on Thursday 17 December 2020.

Declared interests

Dr Emeir McSorley: “No conflicts.”

Dr Zaki Hassan-Smith: “No conflicts to declare.”

Dr Claire Hastie: “No conflicts of interest.”

Dr Vimal Karani: “None.”

Dr David Richardson: “I am Scientific Adviser to the Council for Responsible Nutrition UK (CRNUK).”

Dr Bernard Khoo: “No conflicts to declare.”

Prof Naveed Sattar: NS was co-author on papers which did not find and independent link between vitamin D levels and incident COVID-19 infection.

Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, Jani BD, Welsh P, Mair FS, Gray SR, O’Donnell CA, Gill JM, Sattar N, Pell JP. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr. 2020 Jul-Aug;14(4):561-565. doi: 10.1016/j.dsx.2020.04.050. Epub 2020 May 7. Erratum in: Diabetes Metab Syndr. 2020 Sep – Oct;14(5):1315-1316. PMID: 32413819; PMCID: PMC7204679.”

Prof Adrian Martineau: “I am Chief Investigator of the CORONAVIT trial – the UK’s national clinical trial of vitamin D supplementation to reduce risk and/or severity of COVID-19. https://clinicaltrials.gov/ct2/show/NCT04579640

I am the senior author on the meta-analysis by Jolliffe et al ( https://www.medrxiv.org/content/10.1101/2020.07.14.20152728v3 ), which demonstrates a modest protective effect of vitamin D supplements on acute respiratory infections other than COVID-19, and which is referenced in the updated NICE guideline.”

None others received.