Vitamin D – the sunshine vitamin, and potential COVID treatment?

Annabel van Griethuysen looks into vitamin D and considers its importance in the fight against COVID-19.

Vitamin D is unique amongst vitamins. It can be synthesised in the body using UV rays from sunlight, with production in the skin. It will then be further metabolised to form ‘active vitamin D’ or calcitriol. Diet is another source of vitamin D, although it provides a relatively small amount compared to the amount made by exposure to sunlight.

Vitamin D is present in two naturally occurring forms within food. First, vitamin D₂ or ergocalciferol, is made through sunlight exposure to yeast sterol ergosterol. This is the vegan source of vitamin D and is found in products such as sun exposed mushrooms. The other form, vitamin D₃ or cholecalciferol, is found in food sources such as oily fish. The precursor to vitamin D₃, 7-dehydrocholesterol (7-DHC), is the type produced within the skin in humans and is further isomerised to form vitamin D₃.

Vitamin D has a variety of functions in the body, including the absorbtion of calcium and controlling rate of bone growth.

7-DHC is biologically inactive until it undergoes further metabolism in the liver and kidney (Drake V, 2011). In these organs, the biologically inactive vitamin D undergoes hydroxylation (introduction of a hydroxyl (-OH) group). This is done by vitamin D-25 hydroxylase to form 25(OH)D. This first hydroxylation complete, the product then travels to the kidney to undergo a further hydroxylation by a second enzyme 25(OH)D-1α-OHase to form the biologically active form of vitamin D: 1,25(OH)₂D (Holick et al, 2011).

In supplements, vitamin D is manufactured either from the UV irradiation in yeast to form the vegan D₂ supplement, and from lanolin (the wax found on sheep wool) to make vitamin D₃. Both have been seen to raise serum levels of 25(OH)D however vitamin D₂ may be less potent at high, therapeutic doses than vitamin D₃ (Houghton L A & Vieth R, 2006).

Once this biologically active form of vitamin D is produced, henceforth known as vitamin D, it interacts with vitamin D receptors found on a variety of tissues such as the intestine and kidneys (Holick et al, 2011). 

Vitamin D has a variety of functions throughout the body. The most commonly understood is its role in the absorption of calcium. It stimulates the intestinal absorption of both calcium and phosphorous. In the absence of vitamin D, only 10-15% of dietary calcium and 60% of dietary phosphorous is absorbed.

Table 1 - Increase in absorption of minerals in the intestine during vitamin D sufficiency

(Holick et al, 2011)

Vitamin D also has a role to play in the control of rate of bone growth by interacting with osteoblast cells and promoting the maturation of osteoclast cells to mobilise calcium from the skeleton.

Vitamin D food sources

Vitamin D is found in a limited number of foods:

• Cod liver oil
• Swordfish
• Salmon
• Tuna
• Sardines
• Beef liver
• UV exposed mushrooms

Other sources come from fortified foods:

• Orange juice
• Milk
• Yoghurt
• Spreads

Despite vitamin D being present in a number of foods as listed, the majority of the vitamin is actually made within the skin. Even with sunlight exposure, dietary vitamin D and food-based sources, it is very rare for overdoses to occur as the body will only synthesise as much active vitamin D as it requires.

Vitamin D production in the skin

Due to the fact that the majority of vitamin D is manufactured in the skin, the effects of limited sun exposure can lead to deficiency. This is particularly challenging for certain ethnicities, or those living in more northerly locations. Vitamin D synthesis is most effective when the skin is exposed to sunlight of 270-300nm, which occurs when the UV index is above 3. The angle of the sunlight also makes a difference to the production of vitamin D, with higher angles, such as at the equator, producing more vitamin D.

Incidental exposure, sometimes as little as five minutes a day for individuals with fairer complexions, can be sufficient for vitamin D production, if the wavelength of light is adequate. This takes longer for individuals with darker skin, due to the increase in melanin, and can take up to 20 minutes. However, the sunlight available in the UK can only produce negligible vitamin D in winter months and so vitamin D status in individuals in the UK drops during this time. This can be avoided through having adequate exposure to the sun, reported to be about nine minutes with 35% of skin exposed, through the summer months, generally accepted as March-September. This amount of skin exposure can be achieved by wearing a t-shirt and shorts whilst outdoors.

When compared to only having the hands and face exposed, which results in about 10% of skin exposure, this is not effective, even in the peak summer months, to produce enough vitamin D to prevent deficiency. It is important to note however, the exposed skin needs to be unprotected by creams, make up, or sun protecting compounds, as these block the essential UVA-B wavelengths of light needed to create vitamin D (Webb et al, 2018). This has been a source of disagreement in public health messages, due to the potentially damaging effects of UV light on the skin and the links to the development of skin cancer increasing the use of UV protection.

Vitamin D deficiency

Vitamin D deficiency is measured through serum 25(OH)D concentration. Generally a serum level below 75nmol/L is considered deficient, and a level below 25-30nmol/L increases the risk of physical health problems such as osteomalacia. Various groups are more at risk of low vitamin D due to a variety of different factors:

• Babies and young children – especially if not playing outside
• Pregnant women and breastfeeding mothers
• People over 65 years darker skin tones e.g. Asian, African, Afro-Caribbean and Middle Eastern descents
• People who cover up their skin when outside
• Living in the north
• Polluted air
• People who spend most of their time inside

The NDNS survey of UK adults (19-64 years old) has found that vitamin D deficiency is common. In the summer months, where vitamin D production is generally higher as explained above, 8.4% of those surveyed were deficient for vitamin D, rising to 39.4% in the winter. Even more interestingly, a clear pattern of deficiency is noted as you move north in the UK. In the summer months, as you move from the south of England to the north of Scotland, vitamin D deficiency rises from 0% to 8.6% in the summer and then 9.5% to 40.6% in winter months (Webb, 2018).

These high risk groups should be encouraged to take a supplement: 10 micrograms per day for adults and older people, and 7 - 8.5 micrograms for children and infants. Older people are at particular risk of vitamin D deficiency due to reduced subcutaneous synthesis of vitamin D, reduced exposure to sunlight due to a less active lifestyle and other diseases such as renal failure. This leads to increased bone loss and sarcopenia. There are several trials looking into the role of supplementing vitamin D in muscle loss and sarcopenia in particular for older people, although the results are controversial (Remelli et al, 2019).

Vitamin D also has an emerging role in mental health, particularly depression and anxiety. Deficiency of vitamin D worldwide has been linked as an enhanced risk factor for major depressive disorders. The evidence for a causal relationship was previously mixed, with much of the research either being conducted in children and adolescents with autism and/or ADHD, or postmenopausal women and women over 70 years of age. Many of these studies produced conflicting results of the causal link, or the efficacy of vitamin D as a treatment for depression type symptoms.

It has been suggested that the lifestyle factors leading to increased vitamin D production, such as time spent outside, may be partially responsible for the link between elevated serum levels of vitamin D and less severe depression or anxiety symptoms (Libuda et al, 2019). However, other studies looking specifically at older people have found a small but statistically significant improvement in mental health when supplemented with a standard monthly dose of vitamin D supplementation over a 12-month follow-up (Guger et al, 2019). There are also links suggested between lifelong vitamin D status and the risk of development of dementias in later life.

Vitamin D also has links with various physical health outcomes, with a Cochrane review in 2014 reporting a relevant and significant lower all-cause mortality of 7% and cancer specifically at 13% with vitamin D supplementation. There is also a positive effect on lung health due to the anti-inflammatory and immunomodulant properties of vitamin D with community acquired pneumonia (Amrein et al, 2019).

Vitamin D in the prevention and treatment of acute respiratory infections has been of interest since the 1930s.

Vitamin D and Covid-19

Vitamin D in the prevention and treatment of acute respiratory infections has been of interest since as early as the 1930s when cod liver oil was investigated to help cure the common cold. With the emergence and ongoing global burden of COVID-19, it warrants further investigation as a potential treatment.

As COVID-19 is a novel infection, relatively little was initially known about the protective factors for infection, however, in a study in 20 European countries up to May 2020, when looking at serum vitamin D levels, a significant negative correlation was found. There have been reports also indicating possible links between vitamin D and Covid severity and mortality, although these findings appear less robust (Ali N, 2020). It is reported that the potential mechanisms for defence against not only COVID-19 but other influenza type infections, include the ability of vitamin D to act as cathelicidins (a small, antimicrobial peptide) and defensins (host defense peptides). These lower the potential viral replication rate and reduce cytokine production, reducing the host inflammatory response.

It is also noted that those at risk of vitamin D deficiency are also those at highest risk of severe COVID-19 infection, such as older people or those in ethnic minority populations. Although we do not yet have sufficient data to indicate a causal relationship, there is growing strong evidence that supports a potential relationship between COVID-19 severity and death and vitamin D status, one link being that for each degree of latitude north, the mortality from COVID-19 increases by 4% (Rhodes et al, 2020).

It has been suggested that those with COVID-19, or influenza infections, could take a short, intense vitamin D supplementation course of 10,000IU/day initially and then 5000IU/day in the aim to raise serum levels to 100-150nmol/L to help reduce severity of infection (Grant et al, 2020). Also to consider is the potential that the UK population may be experiencing lower post summer serum levels of vitamin D in winter 2020, due to lockdown and the limitations on holidays, being outside, and working and spending more time at home. Therefore, as dietitians, we should continue to promote the NHS message for all adults to take 10µg or 400IU per day to maintain normal serum levels through the winter (NHS, 2020). 

Vitamin D continues to be an exciting area of emerging nutritional science, with an ever expanding understanding of its various roles, functions and therapeutic applications. However, the underlying public health message can continue to be the same: the importance to eat a varied diet as high in vitamin D as possible, but more importantly, the need for sun exposure and supplementation in darker, colder, shorter days.

References

Ali Nurshad (2020) Role of vitamin D in preventing of COVID-19 infections and severity. Journal of Infection and Public Health 13: 1373-1380

Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeegger S, Köstenberger M, Berisha A T, Martucci G, Pilz S & Malle O (2020) Vitamin D deficiency 2.0: an update on the current status worldwide. European Journal of Clinical Nutrition

Drake V (2011) Vitamin D and Skin Health. Micronutrient Information Centre. Accessed 4/11/20. Available at http://lpi.oregonstate. edu/mic/micronutrients-health/skin-health/nutrient-index/vitamin-D#production

Grant W B, Lahore H, McDonnell S L, Baggerly C A, French C B, Aliano J L, Bhattoa H P (2020) Evidence that Vitamin D Supplementation Could Reduce Risk of Influenze and COVID-19 Infections and Deaths. Nutrients 12: 988

Gugger A, Marzel A, Orav E J, Willett W C, Dawson-Hughes B, Theiler R, Freystätter G, Egli A, Bischoff-Ferrari H A (2019) Effects of monthly High-Dose Vitamin D on Mental Health in Older Adults: Secondary Analysis of a RCT. JAGS 67: 1211-1217

Holick M F, Binkley N C, Bischoff-Ferrari H A, Gordon C M, Hanely D A, Heaney R P, Murad M H & Weaver C M (2011) Evaluation, Treatment, and prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 96(7): 1911-1930. 

Houghton L A & Vieth R (2006) The case against ergocalciferol (Vitamin D₂) as a vitamin supplement. Am J Clin Nutr 84(4): 694-697 Libuda L, Laabs B-H, Ludwig C, Bühlmeier J, Antel J, Hinney A, Naaresh R, Fõcker M, Hebebrand J, Kõnig I R & Peters T (2019) Vitamin D and the Risk of Depression: A Causal Relationship? Findings from a Mendelian Randomization Study. Nutrients 11: 1085

NHS (2020) Vitamin D. Accessed 4/11/20. Available at nhs.uk/conditions/vitamins-and-minerals/vitamin-d/

Remelli , Vitali A, Zurlo A & Volpato S (2019) Vitamin D Deficiency and Sarcopenia in Older Persons. Nutrients 11: 2861

Rhodes J M, Subramanian S, Laird E, Griffin G & Kenny R A (2020) Perspective: Vitamin D deficiency and COVID-19 severity- plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis. JIM

Webb A R, Kazantzidis A, Kift R C, Farrar M D, Wlkinson J & Rhodes L E (2018) Meeting Vitamin D Requirements in White Caucasians at UK Latitudes: Providing a Choice. Nutrients 10 (4): 497