During this anxious and difficult time we are trying to keep you up to date with emerging research about useful interventions for protecting health and supporting immunity. Our previous blog has highlighted nutrients that have been considered important for protecting against infections. Research is currently emerging with the nutrients vitamin D and selenium at the forefront. Population groups which are most likely to be severely affected by Covid-19 are also most likely to be deficient in vitamin D and selenium.

Of course this can, on the surface, be attributed to coincidence and other factors, but this blog aims to describe the functions of both nutrients which play an essential role in immune function, reduced risk of infection and supporting lung health.

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Vitamin D

Sources

Vitamin D is produced when the skin is exposed to UVB radiation (from sunlight) a molecule known as 7-dehydrocholesterol (derived from cholesterol) is converted to cholecalciferol, also known as D3. Cholecalciferol can also be obtained from the diet or by supplementation (D3). Cholecalciferol travels to the liver where it is converted to 25-hydroxyvitamin D (25OHD). The kidney then converts 25OHD to 1,25-hydroxyvitamin D (1,25OHD), also known as calcitriol the active form of vitamin D, which possesses hormonal properties and regulates calcium and phosphate balance. It can additionally be obtained from dietary sources (oily fish, eggs and butter) or by supplementation. Note vitamin D3 is the bioactive form and therefore should be supplemented in this form. Vegan dietary sources of vitamin D such as mushrooms provide the D2 form of the vitamin which needs further conversion to D3 by the body.¹

Deficiency

Public Health England now recommend that everyone should supplement 25ug per day of vitamin during winter months (October- May) as much of the population, especially those north of Birmingham, cannot get access to enough UV light to produce adequate levels of vitamin D during the winter months. People from ethnic groups who have darker skin are less efficient at producing vitamin D as their skin naturally protects against UV radiation. Additionally older adults are more likely to be vitamin D deficient particularly if they stay indoors during the winter months and especially those who are institutionalised. The Scientific Advisory Committee on Nutrition’s (SACN) report in 2016 stated that around 30-40% of the population had a plasma 25(OH)D (vitamin D3)  concentration < 25 nmol/L in winter compared to 2-13% in summer (the NHS considers insufficiency to be <50nmol/L). The most at risk population were institutionalised adults who were unable to build up vitamin D reserves during the summer months due to lack of sunlight exposure.^2,3

Population groups most affected by covid-19 are older adults, especially those institutionalised in care homes and those from dark skinned ethnic backgrounds, these are also population groups which are most likely to be vitamin D deficient. Even when age and socioeconomic factors are taken into account black people are over twice as likely to die of Covid-19 as their white counterparts. Pakistani and Bangladeshi people are 1.8 times more likely, whereas the risk for Chinese and mixed race ethnicities are almost the same as white people.⁴

Melanin is the pigment in the skin that protects from UV radiation and also provides pigment. The darker the skin is the more melanin is present and therefore the less efficient the production of vitamin D. The ability to produce vitamin D and therefore vitamin D status may at least in part explain these differences in disease risk.

With elderly, institutionalised and darker skinned populations being particularly affected by Covid-19 and are also most likely to be deficient in vitamin D this paints a picture for a potential association between vitamin D status and severity of infection.

Vitamin D and Immune Function

As the vitamin D receptor is expressed on immune cells (B cells, T cells and antigen presenting cells) and these immunologic cells are all are capable of synthesizing the active vitamin D metabolite, vitamin D has the capability of acting in a milieu of immunological functions. Vitamin D can modulate both the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection.  It is also associated with modulating the inflammatory response by signalling the increased production of ant-inflammatory molecules and decreasing the production of pro-inflammatory molecules. This switch in immune response in theory may have some potential benefit in cases of ‘cytokine storm’ – a massive release of proinflammatory molecules (which has been observed in those infected with COVID) which can cause acute respiratory distress syndrome.⁵

Vitamin D is known to mitigate the scope of acquired immunity and regenerate endothelial lining. This may be beneficial in minimizing the alveolar damage caused in ARDS. Level I evidence showed that there is a 12% overall protective effect of vitamin D supplementation against bacterial and viral acute respiratory tract infection, increasing to 19% in those individuals on the daily or weekly regimen of vitamin D. Furthermore, there is a 70% protective effect when vitamin D deficiency is corrected with supplementation. Research has shown that low vitamin D status was associated with increased risk of infection and increased severity which was  further exacerbated in those with   underlying lung conditions.^6,7

Summary of vitamin D3 in relation to COVID-19^8–12

• Research suggests SARS-Cov-2 virus enters cells via ACE2 Coronavirus viral replication downregulates ACE2 dysregulating the renin-angiotensin system (RAS) and leads to a cytokine storm) in the host, causing Acute Respiratory Distress Syndrome (ARDS).
• Research shows that Vitamin D acts to rebalance RAS and attenuates lung injury
• Research shows that Vitamin D supplementation increases immunity and reduces inflammatory responses and the risk of acute respiratory tract infection
• Vitamin D deficiency is strongly associated with ARDS and poor mortality outcomes, as well as being associated with many comorbidities associated with Covid-19 case fatalities.
• High dose oral Vitamin D has been shown to improve mortality in patients with severe vitamin D deficiency.
• Chronic vitamin D deficiency induces lung fibrosis through activation of the RAS.

A prospective study in Ireland known as TILDA (The Irish Longitudinal Study on Ageing) has been observing and measuring parameters in the over 55 population since 2016 and therefore have a bank of data with regards to vitamin D status of the individuals who are taking part. Initial statistics have identified that during the winter period, 21.3% of adults aged >55 years were vitamin D deficient. The highest rates of deficiency were observed for those aged 80-84 years and those aged >85 years 46.6%. For those aged >70 years, the deficiency rates were 27.1%. Across all ages, deficiency rates were similar for both men and women though with men tending to have slightly higher deficiency rates overall. Deficiencies were reduced in the summer but not by sufficient amount to ameliorate the reductions during the winter. Vitamin D deficiency was also more prevalent in individuals with diabetes and underlying lung conditions.⁶

The authors of the TILDA study are pressing for Governments to increase recommendations for Vit D supplementation to 2,000-3,000 i.u. (50ug-75ug) (Public Health England have only just increased the NRV from 10ug to 25ug).

We know that these population groups are most like to be severely affected by Covid-19. The study concluded that Vitamin D is a potent immune modifying micronutrient and if vitamin D status is sufficient, it could  benefit  vulnerable adults in particular those 70+ years and older who are ‘cocooning’ during the COVID-19 outbreak.

Additionally a correlation has been seen where COVID-19 dominates in the northern hemisphere, which is just coming out of winter when vitamin D levels are known to be reduced. Are also predominant in areas which has latitudes above 20^ON, again associated with reduced vitamin D status. An anomaly to this is Japan, where fatalities are lower, however their diet is rich in sources of vitamin D, especially oily fish.¹¹

• • The most severe outbreak in the north has been Italy where it is noted vitamin D deficiency is one of the highest in Europe.
  • Japan is an outlier in the north, with only a very mild outbreak and has the lowest incidence of Vitamin D deficiency thanks to its high fish-content diet¹⁴. [NB: Other factors no doubt contribute in both countries but culture and behaviour account for speed of spread not case fatality rates].

“..We would like to call attention to the possible association between severe vitamin D deficiency and mortality pertaining to COVID-19. Given its rare side effects and relatively wide safety, prophylactic vitamin D supplementation and/or food fortification might reasonably serve as a very convenient adjuvant therapy for these two worldwide public health problems alike.”¹³

Selenium

Selenium is a trace mineral which plays an essential role in supporting normal immune function. Studies have demonstrated an enhancement of both cell-mediated and humoral immune responses by increasing levels of selenium intake. It has been shown to stimulate antibody formation and the activity of helper T cells along with the cytotoxic T and NK cells. It is also implicated in the stimulation of the phagocytic cell migration and in the phagocytosis all of which are essential processes for prevention of and fighting off infection.

Selenium is also an essential antioxidant that supports (precursor) the production of the master intracellular antioxidant, glutathione. Dietary selenium deficiency that causes oxidative stress in the host can alter a viral genome so that a normally benign or mildly pathogenic virus can become highly virulent in the deficient host under oxidative stress. In the deficient state, the selenium supplementation is helpful for the prevention and treatment of viral infections.¹⁴

• Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses
• In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains.
• This suggests that Se-deficiency affects cell-mediated immunity to a greater extent than humoral immunity for antiinfluenza viral responses in this model.
• The notion that Se “boosts” the immune system has been supported by studies involving ageing immunity or protection against certain pathogens
• Replication of a mild strain of influenza virus in Se-deficient mice results in a novel virulent strain that causes severe lung pathology even when passed into Se-adequate mice
• These studies demonstrated that the Se status of the host can profoundly influence the genome of viral pathogen, leading to a new viral strain. Thus, host nutritional status should be considered when studying the mechanisms underlying the evolution of emerging viruses and may assist in predicting new viral outbreaks and devising new strategies to limit the emergence and spread of these pathogenic forms.

Sources of selenium depend on the selenium content of soil and food but can be found in Brazil nuts, oily fish, eggs and seaweed. It is thought that average intake of selenium is 39ug/day which is below even the RDA of 75ug/day, optimum intake is considered to be at least 185ug/day.

Research – Covid-19

Researchers publishing in the American Journal of Clinical Nutrition studied the relationship between selenium and status and Covid-19 infections in China. It is particularly useful as China is known to have populations that have both the lowest and highest selenium status in the world, due to geographical differences in the soil which affects how much of the trace element gets into the food chain.

Researchers found that areas with high levels of selenium were more likely to recover from the virus. For example, in the city of Enshi in Hubei Province, which has the highest selenium intake in China, the cure rate (percentage of Covid-19 patients declared ‘cured’) was almost three-times higher than the average for all the other cities in Hubei Province.  By contrast, in Heilongjiang Province, where selenium intake is among the lowest in the world, the death rate from Covid-19 was almost five-times as high as the average of all the other provinces outside of Hubei. Most convincingly, the researchers found that the Covid-19 cure rate was significantly associated with selenium status, as measured by the amount of selenium in hair, in 17 cities outside of Hubei.²⁰

Margaret Rayman, one of the authors of this paper has previous highlighted the importance of selenium for many conditions including cardiovascular disease and cancer, as well as highlighting the incidence of selenium deficiency across Europe. This latest pandemic has motivated her to revisit her previous work on selenium function and deficiency. She states “Given the history of viral infections associated with selenium deficiency, we wondered whether the appearance of Covid-19 in China could possibly be linked to the belt of selenium deficiency that runs from the north-east to the south-west of the country.”²¹

Like vitamin D selenium levels are low in older people, making them more susceptible to viral activity. Boosting selenium in the older population is useful for supporting immune function.

It is also prudent to consider selenium intake across the whole population to aid general resilience and potentially improve recovery rates.

Both vitamin D and selenium are nutrients which are often deficient particularly in the UK and play an essential role in supporting the immune system and providing resistance to infection. Therefore it is important to ensure adequate intake and exposure for all individuals.

One of our blog readers has kindly pointed out that research shows insufficient magnesium will prevent vitamin D from being effective. Please read this article for more information.

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