Rationale

Why the panel made the recommendations

The panel agreed that there was little evidence for using vitamin D supplements to prevent or treat COVID‑19. However, they agreed that vitamin D use is well established for maintaining bone and muscle health. They expressed concerns that not everyone is aware of, or is following, UK government advice on taking a vitamin D supplement, so wanted to include a recommendation to emphasise the existing guidance. They stressed that everyone should consider taking a supplement containing 10 micrograms (400 units) of vitamin D daily between October and early March, when people in the UK do not make enough vitamin D from sunlight. They also stressed that this was particularly important during the COVID‑19 pandemic, when people may have been indoors more than usual over the spring and summer.

The panel discussed that, for most people, 10 micrograms (400 units) of vitamin D a day will be enough to prevent serum 25(OH)D concentration from falling below 25 nmol/litre. They also noted that taking too high a dose of vitamin D over a long period of time could be harmful because it can cause too much calcium to build up in the body (hypercalcaemia). This can weaken the bones and damage the kidneys and the heart. They were aware that the tolerable upper intake level for adults and young people over 11 years is 100 micrograms (4,000 units) daily, and that this dose should not be exceeded. They discussed monitoring requirements if people have renal impairment or high doses are given, and were aware of cautions for use in people with certain medical conditions, such as sarcoidosis. They agreed that, if people are unsure whether they can take vitamin D, they should discuss this with their healthcare professional. The panel also discussed that vitamin D3 (colecalciferol) supplements can be derived from an animal source. They noted that people's concerns about using animal products because of a religious or ethical belief need to be considered when discussing vitamin D products.

The panel also noted that it is important for some populations to take a supplement containing 10 micrograms (400 units) of vitamin D daily throughout the year. This includes people who are at a higher risk of not getting enough vitamin D because, for example, of lack of exposure to sunlight during the spring and summer months.

The panel discussed access to vitamin D supplements, and were aware of the NICE guideline on vitamin D: supplement use in specific population groups and the NHS service supplying free daily vitamin D supplements for people at high risk (clinically extremely vulnerable) from COVID‑19. This service has been set up because it is particularly important for people who have been indoors more over the spring and summer when shielding to take vitamin D for bone and muscle health.

Preventing COVID-19

The panel were presented with evidence from the NICE evidence review of vitamin D for COVID-19 on using vitamin D supplements to prevent SARS‑CoV‑2 infection (and subsequent COVID‑19), and evidence on vitamin D status and its association with COVID‑19.

No evidence relevant to the protocol was found for the prevention question. The panel discussed the evidence for the association of vitamin D status with COVID‑19. They agreed that low vitamin D status was associated with more severe outcomes from COVID‑19. However, it is not possible to confirm causality because many of the risk factors for severe COVID‑19 outcomes are the same as the risk factors for low vitamin D status. Vitamin D is a negative acute phase reactant, meaning its serum concentration falls during a systemic inflammatory response, which may occur during severe COVID-19 illness. Therefore, it is difficult to know if low vitamin D status causes poorer outcomes or vice versa.

The panel discussed the significant limitations in the retrospective association studies. These included historic and inaccurate vitamin D status measurements, lack of generalisability to UK practice, the likelihood of confounding and general low quality of the evidence.

Because COVID‑19 mainly affects the respiratory tract, the panel also heard indirect evidence from the updated Scientific Advisory Committee on Nutrition (SACN) rapid review on using vitamin D supplements to prevent acute respiratory tract infections. They agreed that a systematic review and meta-analysis by Jolliffe et al. (2020) reported a modest protective effect of vitamin D supplementation compared with placebo. From subgroup analyses, this protection was associated with daily doses of 10 micrograms to 25 micrograms (400 units to 1,000 units) of vitamin D, but not higher doses. Also, from subgroup analysis, the protection was only seen in children and young people aged from 1 year to under 16 years (the panel noted that, for COVID‑19, poorer outcomes are more common in an older adult population). Beneficial effects on acute respiratory tract infection prevention were not seen with higher doses of vitamin D supplementation (over 25 micrograms [1,000 units] daily or more), when supplementation was weekly or monthly, or in adults. The SACN rapid review highlighted limitations with the studies included in the meta-analysis by Joliffe et al. (2020) including:

  • inconsistency between study results

  • differences between studies in vitamin D supplementation doses and regimens, settings, populations, durations and definitions of outcomes (including type of respiratory infection).

The panel were also aware of the updated SACN recommendations that a vitamin D intake of 10 micrograms (400 units) daily, as currently recommended, may provide some additional benefit in reducing the risk of acute respiratory tract infections. However, they noted that this topic is being kept under review and these recommendations may be updated if findings from robust, high-quality randomised controlled trials provide further clarification.

Based on direct evidence from the NICE evidence review and indirect evidence from the SACN rapid review of vitamin D in acute respiratory tract infection (which did not include COVID‑19 as an outcome), the panel agreed that there was not enough evidence to recommend vitamin D supplements solely for preventing COVID‑19.

The panel agreed that people should be encouraged to follow the existing UK government advice on vitamin D supplementation. They also agreed that the recommendations in this guideline on vitamin D supplements and COVID‑19 prevention should be considered for an update as additional evidence becomes available.

The panel agreed that there is a need for research into vitamin D supplementation for preventing COVID‑19. However, they discussed issues around ethics, trial design and comparators, and agreed that it would be more appropriate for the research community to define an appropriate PICO (population, interventions, comparators, outcomes) framework. They were aware that the updated SACN rapid review on using vitamin D supplements to prevent acute respiratory tract infections has a recommendation that research is urgently needed on vitamin D and risk of acute respiratory tract infection in black, Asian and minority ethnic groups, and people living with overweight or obesity. The panel also noted that several randomised controlled trials of vitamin D supplements in preventing COVID‑19 are known to be in progress.

Treating COVID-19

The panel were presented with evidence from the NICE evidence review of vitamin D for COVID-19 on using vitamin D supplements for treating COVID‑19. This comprised 1 small, very low-quality, randomised controlled trial in secondary care from Spain (Castillo et al. 2020) that used oral calcifediol (25[OH]D), which is the circulating metabolite of vitamin D, and not commonly used in the UK. The panel noted the very high dose used. This was estimated to be equivalent to around 5,000 micrograms (200,000 units) of vitamin D in the first week (about 700 micrograms [28,000 units] daily) and 1,300 micrograms in following weeks for the duration of the study (about 200 micrograms [8,000 units] daily). They also noted the lack of generalisability to UK practice. The panel had concerns about:

  • differences in comorbidities between the 2 comparator groups

  • use of 'standard care' including anti-inflammatory medicines that are not considered standard care for COVID‑19 in UK practice

  • the lack of blinding, which could result in biased estimates.

Based on direct evidence from the NICE evidence review, the panel agreed that there was not enough evidence to recommend using vitamin D for treating COVID‑19. They also agreed that the recommendation on vitamin D supplements and treatment should be considered for an update as additional evidence becomes available. Because of the lack of evidence identified, the panel made a research recommendation around the clinical effectiveness of vitamin D supplements for treating COVID‑19. They stressed that future studies should be high-quality randomised controlled trials.

As additional evidence becomes available, this guidance will be updated in line with NICE's interim process and methods for guidelines developed in response to health and social care emergencies.

Full details of the evidence are in the NICE evidence review of vitamin D for COVID-19.

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