In light of the persuasive circumstantial evidence that vitamin D deficiency may play a major contributory role to Covid-19 infection, progression, severity and mortality, and given the high prevalence of vitamin D deficiency in the UK, in an analogous manner to vitamin C for scurvy, we advocate widespread supplementation with adequate doses of vitamin D. This vitamin is cheap, safe and may prove very significant in the fight against Covid-19.
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Our latest Health Assessments look specifically at Covid-19 and are ideal for;
- Those who have not had Covid-19 but are concerned about the impact any underlying health conditions could have should they contract Covid-19; and
- Those who have had Covid-19 yet are still suffering from symptoms and are concerned whether any underlying health conditions they may have had before they contracted the disease are now impacting on their ability to recover from it.
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The role of vitamin D as both a predictor of risk and also as a preventive and therapeutic strategy with respect of Covid-19 is attracting increasing attention.
Vitamin D is a lipid-soluble compound derived from cholesterol that is classified as both a vitamin and steroid hormone. It exists in 2 forms: ergocalciferol (Vitamin D2), obtained largely from foodstuffs e.g. oily fish and cholecalciferol (vitamin D3), produced in the skin under ultraviolet light exposure. Both of these are then converted in the liver and kidney to more active forms. Vitamin D exerts its effects by binding to the vitamin D receptor (VDR) and it is now recognised that the VDR is widely distributed throughout many tissues in the body and influences the activity of a vast number of genes.
Perhaps the best known actions of vitamin D are on bone and calcium metabolism, with deficiency in children resulting in rickets and in adults osteoporosis (thin bones). However, vitamin D is now known to exert other wide ranging effects including:
- muscle function – deficiency causes weakness especially of thigh and shoulder muscles
- nervous system – improves nerve signalling
- predisposition to many cancers (including breast, colorectal, prostate and lung)
- glucose metabolism and risk of diabetes,
- cardiovascular health and predisposition to atherosclerosis
- immune responses – including regulation of innate and adaptive immune responses. It is these which are of increasing interest with regard to Covid-19.
Sources of vitamin D
In the UK, a healthy, balanced diet provides all the nutrients needed except vitamin D, as few foods naturally contain it. Only oily fish is a significant source, while egg yolks, meat and a few fortified foods provide small amounts. In the UK, unlike many other countries, milk is not routinely fortified with vitamin D and is therefore not a good source. Other foods contain no vitamin D or negligible amounts. Instead, we obtain most of our vitamin D through skin synthesis in response to sun exposure, but this is subject to several factors:
- Light of the critical wavelength for synthesis cannot pass through glass so outdoor exposure is necessary.
- Season – sunlight of the critical wavelength only reaches the UK between April and September. It is absorbed by the atmosphere during winter months.
- Latitude – in the south of the UK there is more sunlight of the critical wavelength than the north.
- Weather – more vitamin D can be synthesised on bright sunny days than on cloudy days.
- Air pollution – reduces the critical UV light waves available for skin synthesis.
- Time of day – more vitamin D is synthesised when sunlight is most intense in the middle of the day compared to early morning and late afternoon.
- Colour of skin – darker skins require up to 6 x more time in the sun to synthesise the same amount of vitamin D as light skins. Those of Black, Asian and Minority Ethnic (BAME) ethnic origin are significantly more likely to have lower vitamin D levels than Caucasians.
- Lifestyle – time spent outside with bare skin exposed facilitates vitamin D synthesis, which is greatly diminished when most skin is covered by clothes, as can be the fashion or in the case in girls and women with certain religious and cultural traditions.
- Sunscreen use – while we are all encouraged to use high factor sunscreen when outside in the sun, it blocks dermal synthesis of vitamin D.
- Other clinical conditions such as intestinal malabsorption, chronic liver and kidney disease will reduce absorption or production of active vitamin D
Prevalence of Vitamin D deficiency
It has only been possible to accurately measure circulating Vitamin D for the last few years. The units by which it is measured are either nmol/L or ng/ml and this requires to be checked when comparing data. In the UK, we generally use nmol/L and deficiency is classified as levels <30 nmol/L with 30-50 being borderline. However, as we gain further knowledge of the powerful roles and effects of vitamin D, it is increasingly accepted that we should aim for levels >100 nmol/L. While low levels occur in around 30-40% of the total UK population, the prevalence levels vary widely according to the factors above and in some groups can be as high as 90%.
Vitamin D and respiratory infections
The link between vitamin D and infectious disease was first recognised, albeit inadvertently, in the historical treatment of patients with tuberculosis (TB) who, until the end of the last century, were treated in sanatoriums in sunny locations and wheeled out for daily sunbathing as a routine part of their treatment. Furthermore, in the 19th century, cod liver oil (one of the most potent sources of vitamin D) was routinely used in the treatment of TB.
Several studies have demonstrated an inverse link between vitamin D levels and risk of acute respiratory infections with lowest levels being associated with up to 2-fold increased risk of infection. In a retrospective study of over 14,000 individuals who caught influenza (another corona virus), low Vitamin D levels were associated with 58% higher risk. Similarly, a review of 25 trials involving over 10,000 individuals reported that supplementing vitamin D resulted in an overall 12% decreased risk of respiratory tract infections but with a stronger benefit in those with very low baseline vitamin D levels. Numerous other studies have shown a similar beneficial effect of vitamin D in reducing risk of respiratory infections. Interestingly, daily or weekly doses were more effective than intermittent bolus doses.
Influence of seasonality
Due to it being produced in response to sun exposure, there is a clear association between seasonality and Vitamin D levels with them being lowest in winter and highest in summer. Rates of influenza infection follow this seasonality being highest in winter months and virtually disappearing in summer. It is not a coincidence that the current 2nd wave of Covid-19 is correlating with shorter days and reduced sunshine and lower vitamin D production.
Vitamin D and Covid-19 infection
Specific to Covid-19 infections, an early small study recorded Vitamin D deficiency in 85% of patients admitted to ITU and across Europe, several studies have demonstrated countries with highest rates of vitamin D deficiency are associated with highest rates of Covid-19 infection and death. This is likely to explain at least in part the unexpected low prevalence of Covid-19 infection and mortality across sub-Saharan Africa. In the USA, there is almost twice the Covid-19 mortality rate in Northern (>400N latitude) vs Southern States. Furthermore, Italy and Spain, two of the most badly affected countries with Covid-19 also have highest rates of low vitamin D, especially in the elderly in whom mortality rates are highest.
The protective role of vitamin D may also explain, at least in part, the disproportionate high infection and mortality rates in BAME (Black, Asian and Minority Ethnic) UK individuals, African Americans and the institutionalised; particularly care-home residents all of whom have a very high rate of vitamin D deficiency.
It is postulated that given the wide influence of vitamin D on body organs, its low levels may play a major role in the link between age, obesity, co-morbidities (e.g. diabetes, hypertension) and increased susceptibility to complications and mortality to Covid-19
Mechanisms by which Vitamin D might exert its beneficial effect
Respiratory epithelial cells which cover the 70m2 of lung tissue express enzymes which synthesise active vitamin D and the latter has been shown to play a role in activating the so called innate immune response. This local synthesis of vitamin D subsequently results in production of powerful antimicrobial and antiviral proteins, which block entry of viruses into cells as well as suppress viral replication and stimulate digestion of infected cell organelles. Such vitamin D induced actions have been demonstrated to reduce infection to a wide range of viruses. as well as being a powerful stimulant to the overall immune response. Importantly, vitamin D has also been shown to decrease production of pro-inflammatory-cytokines and it these which are responsible for the so-called cytokine storm and consequent catastrophic inflammatory response within the lungs and adult respiratory distress syndrome (ARDS). The strength of this response correlates with circulating vitamin D levels.
Vitamin D also plays an important function in activating the so called adaptive immune response whereby the body responds to specific infections by activating so called T and B cells resulting in specific antibody production. The activity of the responsible enzyme is dependent on concentrations of circulating vitamin D levels. Although not specifically demonstrated for Covid-19, this increase in response to other viruses has been shown to enhance viral neutralisation and clearance while modulating subsequent proinflammatory responses.
Vitamin D and cardiovascular system in Covid-19
Covid-19 has been associated with a range of cardiac complications including heart attacks, weakness of the heart muscle, arrythmias and pulmonary emboli (clots) and in some studies these have been shown to still be present many months after the initial infection. The vitamin D receptor is present in the heart and blood vessels and low levels have been shown experimentally to result in increased atherosclerosis, and increased tendency for clotting as well as being linked to risk factors for cardiovascular disease in Covid-19 disease including hypertension, obesity, diabetes and chronic kidney disease.
Clearly, in light of all this circumstantial evidence that vitamin D deficiency may play a major contributory role to susceptibility and progression of Covid-19 infection, it is not surprising that there are an increasing number of clinical trials looking at administering vitamin D on various Covid-19 outcomes. To date, none of these have been completed and published their results.
What is an appropriate dose of Vitamin D and is it safe?
Sun exposure for 15-30 minutes a day with no sunscreen is generally all that is required for adequate production of vitamin D, considering the factors listed above. Reassuringly, vitamin D excess as a result of excessive sunshine exposure does not occur as synthesis is inhibited when sufficient levels are achieved. However, conversely, prolonged unprotected sun exposure is not advisable due to risk of skin cancer.
If modest sun exposure is not possible and certainly during winter months, exogeneous supplementation is usually required and is perhaps the easiest action. The current ‘recommended’ daily dose for supplementation is just 400 IU (25 μg) which most physicians would consider to be far too low. A more practical recommendation for effective supplementation to achieve circulating levels of 100-125 nmol/L is to take 10,000 IU a day for 4 weeks and reduce to 4000 IU daily thereafter. Given vitamin D is stored in fat tissue, in slim people and the elderly, it would seem sensible to reduce these doses by 50%. The mistake many GPs seem to make is to prescribe an appropriate course of high strength tablets for several weeks but to then discontinue it with an inevitable decline in levels again.
As vitamin D is fat soluble and absorbed within the small intestine, there is no difference in absorption between taking it as capsules or nasal spray. It needs be emphasised that vitamin D supplementation is safe, cheap and without side effects unless one takes massive doses for a prolonged period of time when it can lead to increased excretion of calcium in the urine and risk of kidney stones as well as elevated circulating calcium levels.