What is vitamin D and how is it made?
Vitamin D is not just a vitamin, but a steroid hormone which regulates a huge proportion of our biological functions. Modulating our immune system is one of the expansive roles of vitamin D which we require to function optimally. Vitamin D is normally synthesized in skin by exposure of our skin to the sun, where UV light generates pre-Vitamin D. This undergoes further reactions to make an active form of vitamin D, cholecalciferol or Vitamin D3.
In northern latitudes such as the UK, Northern American and Norther Europe, there isn’t enough UV radiation of the right wavelength to make Vitamin D in the winter when the sun is low in the sky, particularly in polluted cities. Many of us are vulnerable to suboptimal levels of vitamin D3, even in the summer, as we often spend most of our time inside at work and are covered with clothes. Whilst there are some foods high in vitamin D, mainly oily fish with eggs, liver and butter providing small amounts, with fortified foods being another source. As Vitamin D is fat-soluble, people eating a low-fat diet will also have low absorption of Vitamin D. Public Health England and other organisations suggest that we take a dietary supplement during the winter months, between October and March[i].
Vitamin D deficiency
Lack of vitamin D is associated to an ever-increasing range of diseases[ii] and ill health[iii] including poor musculoskeletal health. One of the main functions of vitamin D is the maintenance of plasma concentration of calcium but it also modulates a huge diversity of physiological functions including insulin secretion, synthesis and secretion of parathyroid and thyroid hormones, and function within the immune system[iv].
Recent research has found that vitamin D can regulate both the innate and adaptive immune system[v], potentially as the B and T cells, and APC cells have vitamin D receptors. Vitamin D is required for the following immune system functions:
Vitamin D deficiency is linked to increased susceptibility to infection[vi] and increased autoimmune disease. In people with autoimmune diseases, the immune system (T cells) mistakenly attacks your body and its own cells. Having optimal levels of vitamin D helps to increase the amount of a molecule CD31 and this regulates the immune system[vii] so that it doesn’t attack the body’s own cells.
In the UK, at least one in 5 people is deficient in Vitamin D with levels lower than 25nmol/ L.[viii] IN the US, The Endocrine Society define deficiency as blood serum levels of 25-hydroxycholecalcifer0l (25 (OH)D3) under 20nmol/L deficient as this is the level that parathyroid levels involved in calcium balance start to rise outside of healthy ranges and there is a physiological instigation of Vitamin D deficiency. In the UK[ix], Vitamin D deficiency are blood serum levels under 25nmol/l and insufficiency are levels under 50nmol/l.
Populations with vitamin D deficiency
Elderly – vitamin D levels are lower as you age as the synthesis of vitamin D in skin declines with age. Older adults 63% more likely to have vitamin D deficiency (NHANES) and 46% have vitamin D insufficiency compared to young adults
Obese – Obese individuals have lower levels of Vitamin D as fat soluble vitamin D has greater difficulty being released into the blood stream. Obese individuals have greater than 50% less bio-availabilty of vitamin D than non-obese individuals. Obese adults in the US had 3 times higher prevalence of vitamin D deficiency and 1.9 times prevalence of vitamin D insufficiency than non-obese adults.
Northern latitudes – anyone living in the UK, Canada, northern US and Europe has lower levels of vitamin D as there is less UVB radiation reaching the atmosphere so there less of it to reach our skin to facilitate the production of vitamin D.
In darker skinned people – Those with darker skin often have lower levels of vitamin D synthesis as it is decreased to compensate for the role of protection by melanin[xii], a natural sun screen which protects us from the damaging effects of UV radiation. Non-Hispanic blacks have 24.6% higher vitamin D deficiency and 3.7 times higher vitamin D insuffiency than non-Hispanic whites (NHANES).
These groups coincide with the groups that have had higher hospitalisations and deaths as result of being infected with SARS-Cov-2 and COVID19. A CDC study in 14 US states 48% of people hospitalised for COVID19 were obese[xiii]. We know that there is a higher risk of COVID19 complications and hospitalisation for those over 65. There are suggestions that African Americans are at higher risk of complications with COVID19 - 33% of people hospitalised for COVID19 were African- American who only constitute 13% of of US population in comparison of 45% of hospitalisations were of white people who makeup 76% of the population in US.
A study in BMJ in March 2020[xiv] found that Somali immigrants living in Stockholm Sweden make up 40% of COVID 19 related deaths at that time whilst Somalis only make up 0.84% of population. Somalis living in Sweden have extreme vitamin D deficiency due to hereditary and cultural factors (wearing the hijab), and the northern latitude decreasing UV radiation required for Vitamin D synthesis. These possible correlation or association of vitamin D deficiency may also partly explain why there is a higher prevalence of COVID19 complications and death in the BAME community although socio-economic factors and higher prevalence of metabolic disease including diabetes, cardiovascular disease and hypertension.
Vitamin D supplementation
I haven’t gone into the potential mechanisms of how vitamin D might support the immune system, and in particular against SARS-Cov-2 (via normalising ACE2 receptor levels which are downregulated when SARS-Cov-2 binds via spike protein[xv] to gain entry to our cells[xvi]), but we know that people with deficiency may have weaker innate immune response. A meta-analysis in the BMJ[xvii] looked at 25 randomised controlled studies that show that Vitamin D is protective of respiratory tract infections. Daily or weekly supplementation reduced the risk of respiratory tract infection by more than 50% in people with low base line Vitamin D levels. People with higher base line vitamin D had 10% reduced risk with supplementation.
As Vitamin D status could impact our resilience to SARS-Cov-2 and associated complications including death[xviii], PHE has revised its advice during the COVID19 pandemic and suggested that we continue to supplement whilst we are in lockdown as we are spending more time inside. We know that 1000iu of Vitamin D increases 25-hydroxy vitamin D (active precursor) by 5 ng/ml so to ensure we are all over the threshold nearer to optimal levels of 50 to 125ng/ml, suggest taking a supplement of 3000 to 4000iu a day[xix]. Genetic factors can affect how much we absorb. In addition, there are small genetic changes in vitamin D metabolism genes called polymorphisms (SNPs)which have an effect on serum concentrations of 25-hydroxyvitamin D.
In order to cope with COVID19 pandemic , preventative measures could include vitamin D administration to high risk populations – darker skinned, older and obese adults with low sun exposure and individuals with respiratory tract infections as this is unlikely to be harmful and may be beneficial. We may also want to look at supplementing those with co-morbidities that affect risks involved with SARS-Cov-2 infection including cancer, diabetes, hypertension and cardiovascular disease. As we learn more about this novel coronavirus and how it affects our physiology, we will be able to learn how we can best protect ourselves.
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