Vitamin D and COVID-19

VITAMIN D AND COVID19  18 JUNE 2020 1

18 JUNE 2020

This rapid review of the science of Vitamin D and COVID-19 from the Royal Society

is provided to assist in the understanding of COVID-19.

This paper is a pre-print and has not been subject to formal peer-review.

Summary

Vitamin D deﬁciency is associated with an increased risk of

both respiratory viral infections and inﬂammatory conditions.

Vitamin D has an important regulatory role in the human

immune system, so a deﬁciency of Vitamin D is likely to

cause immune dysregulation, which may reduce the ﬁrst line

of our defence against COVID-19. It is therefore biologically

plausible that Vitamin D deﬁciency may contribute to

susceptibility to COVID-19 infection. However, there is no

direct causal link yet between Vitamin D deﬁciency and

increased susceptibility to COVID-19.

Deﬁciency in Vitamin D is more commonly found in older

individuals, those of black or Asian ethnic origin, and people

who are obese. These are also factors known to increase

risk of more severe COVID-19. However, correlations are not

the same as causality.

The UK has one of the highest levels of Vitamin D deﬁciency in

Europe. There is a direct causal relationship between Vitamin

D deﬁciency and bone, tooth and muscle health. Vitamin D also

has an important regulatory role in the human immune system.

It is clearly prudent to prevent Vitamin D deﬁciency as part of

a healthy lifestyle strategy. NICE recommends that “all adults

living in the UK should be advised to take a daily supplement

containing 400 international units (10 micrograms) of Vitamin

D throughout the year, including in the winter months.” High

doses of Vitamin D supplements are unnecessary in most

individuals and very high doses can be toxic. We recommend

that HMG provides a stronger public message about the

importance of preventing Vitamin D deﬁciency.

More research is required to test the possibility that

Vitamin D deﬁciency predisposes to COVID-19, particularly

in those groups with a high risk of COVID-19 mortality, such

as the institutionalised elderly and people with a black, Asian or

minority ethnic (BAME) background. We also recommend that

hospitals consider assaying serum Vitamin D levels in patients

with SARS-CoV-2 infection.

Introduction

Vitamin D is essential for good health. Ninety percent of the

Vitamin D in the human body is produced in the skin from

exposure to the sun. Only about 10% comes from food. It

is only relatively recently that humans have moved from a

mainly outdoor lifestyle (farming, etc.) to one which is mainly

indoors (oce work, etc.). It is reasonable to suppose that

a deﬁciency of Vitamin D in many humans is therefore a

modern phenomenon, mainly due to a lack of sunlight.

The spectrum of visible light from the sun, from red to violet,

has insucient energy to generate Vitamin D in the skin. It is

the higher energy ultra-violet (UV) light that is needed. The

UVB part of the spectrum (290-315 nm) generates Vitamin

D, as well as causing damage to the DNA in most vertebrate

skin. UVB is almost 100% blocked by standard window glass,

unlike visible light: direct exposure to sunlight is required.

1. Vitamin D deﬁciency

NICE estimates that about one-quarter of the UK population

is deﬁcient in Vitamin D, rising to about one-third in winter

months, owing to reduced sun exposure

. Vitamin D status

is reﬂected by the level of serum 25OHD. There is no

consensus on a precise deﬁnition of Vitamin D deﬁciency,

but the NICE guidelines are that serum 25OHD levels greater

than 50 nmol/L are sucient, and less than 30 nmol/L are

deﬁcient

. Vitamin D deﬁciency has been associated with a

variety of health problems: weak immune system, rickets,

fatigue, bone fractures, headaches and cancers, with varying

degrees of evidence to support the claims. Vitamin D

toxicity, from taking too high a dose of Vitamin D, is rare and

associated with serum levels of at least 300 nmol/L, and

usually above 600 nmol/L

VITAMIN D AND COVID19  18 JUNE 2020 2

Low Vitamin D status is expected to be exacerbated

in many people by staying indoors during lockdown.

It is therefore important that individuals take outside

activity where possible. NICE’s recommended oral

supplement is 10 micrograms/day

, however, in the

USA the recommendation is 15 micrograms/day for

those under 70 years old, and 20 micrograms/day

for the over 70s

1.1 Vitamin D deﬁciency in Europe

The UK has one of the highest levels of Vitamin D

deﬁciency in Europe. Serum 25OHD levels in adults in

17 dierent European countries show that only Finland

and Norway are more deﬁcient than the UK

It is interesting to compare the prevalence of Vitamin D

deﬁciency (serum 25OHD concentrations less than

30 nmol/L) in the UK, Germany and Ireland, countries

of broadly similar latitudes. Averaged over a year,

Germany has 13.8% deﬁcient, Ireland has 12.4% and

the UK has 22.1%. The UK population is 32% Vitamin D

deﬁcient in the winter and 15% deﬁcient in summer

Some northerly countries strongly fortify their food with

Vitamin D to counter their lack of sunlight, for example,

Canada, whose population is only 10% Vitamin D

deﬁcient following their Vitamin D food fortiﬁcation.

2. Vitamin D and acute respiratory infections

Numerous laboratory studies report that Vitamin D

metabolites support innate immune responses to respiratory

viruses other than SARS-CoV-2

7, 8, 9, 10, 11, 12

, the virus that causes

COVID-19. Clinically, Vitamin D deﬁciency has been shown

to associate independently with an increased risk of diverse

acute respiratory infections (ARI)

. A 2017 meta-analysis of

data from 11,321 participants in 25 randomised controlled

trials (RCTs) of Vitamin D supplementation to prevent ARI

revealed a modest protective eect of the intervention

(OR 0.88, 95% CI 0.81 to 0.96) that was stronger in those

with the lowest baseline Vitamin D status (OR 0.58, 95%

CI 0.40 to 0.82)

. It is unknown whether Vitamin D deﬁciency

also predisposes to SARS-CoV-2 infection. Importantly,

Vitamin D also diminishes the production of inﬂammatory

cytokines, which appear to play a central part in the

pathogenesis of severe COVID-19

2.1 Vitamin D and COVID-19

RCTs of Vitamin D supplementation for the prevention

or attenuation of COVID-19 have yet to be published, but

several lines of evidence suggest a possible role of Vitamin

D deﬁciency in its pathogenesis. First, an epidemiological

study

reported that severe outbreaks with high fatality rates

have occurred exclusively above the +30ºN latitude line,

in the winter hemisphere, where deaths per million ranged

from 3% to 37% with (mean = 11%) in latitudes between 30ºN

and 55ºN. By contrast, outbreaks in the tropics and southern

summer hemisphere were very mild with an average of 0.2%

deaths per million. This pattern was not explained by the

trajectory of spread of infection

. COVID-19 mortality has

been concentrated in groups at increased risk of Vitamin D

deﬁciency including people of black, Asian or minority ethnic

(BAME) background; people with higher body mass index;

and the institutionalised elderly. Where Vitamin D status has

been measured, a lower 25OHD level was associated with

higher mortality

. Third, adverse outcomes of COVID-19 are

associated with virus-driven hyper-inﬂammation

: evidence

from an RCT indicated that Vitamin D supplementation

accelerates resolution of systemic inﬂammation in another

pulmonary infection (tuberculosis)

3. Next steps

3.1 Further research

More research is required to test the possibility that

Vitamin D deﬁciency predisposes to COVID-19. We also

recommend that hospitals consider assaying serum

Vitamin D levels in patients with SARS-CoV-2 infection.

It will be important to compare the 25OHD levels between

those with asymptomatic or mild SARS-CoV-2 infection

and those with COVID-19.

3.2 Vitamin D supplementation

In order to prevent Vitamin D deﬁciency, NICE proposes

• All adults living in the UK should be advised to take

a daily supplement containing 400 international units

(10 micrograms) of Vitamin D throughout the year,

including in the winter months.

• Dietary and lifestyle advice should also be given.

We recommend that HMG provides a stronger approach

to Vitamin D intake. The magnitude of the dose should

be updated as more evidence becomes available. It is

important to emphasise that higher doses of Vitamin D

supplements are unnecessary in most individuals and

very high doses can be toxic.

VITAMIN D AND COVID19  18 JUNE 2020 3

References

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3. Op. cit., note 1

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DISCLAIMER

This paper has drawn on the most recent evidence up to 18 June 2020 and has not been subject to formal peer-review. Further evidence on this topic

is constantly published and the Royal Society may return to this topic in the future. This independent overview of the science has been provided in

good faith by subject experts and the Royal Society and paper authors accept no legal liability for decisions made based on this evidence.

THANKS

The Royal Society is grateful to the Leverhulme Trust for its support for the Society’s pandemic response work.

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