Vitamin D is essential for the immune defense. Because deficiencies of the nutrient are becoming increasingly common and vaccines only have limited effect, we can expect new waves of COVID-19 during the winter period. Vitamin D counteracts chronic inflammation which is seen in rheumatoid arthritis, diabetes, and other chronic diseases. Multiple studies have shown a link between low blood levels of vitamin D and the occurrence of these diseases. In a new meta-analysis that is published in Molecular and Cellular Biochemistry, scientists look closer at the scientific data for risk factors involved with vitamin D deficiencies and the advantages of taking vitamin D supplements in connection with COVID-19, rheumatoid arthritis, and other inflammatory diseases.
Our primary source of vitamin D is exposure to the sun during the summer period. However, we see increasing deficiency problems globally as a result of being indoors too much and because of sun awareness campaigns that make us avoid the sun. Ageing processes, having dark skin, being overweight, or suffering from diabetes are all factors that contribute to the deficiency problem. An estimated one billion people worldwide lack vitamin so the deficiency problem is considered a pandemic that contributes to virus infections, diabetes, cardiovascular disease, cancer, and other serious ailments. Multiple studies have linked low blood levels of vitamin D to corona infections and rheumatoid arthritis, but there are conflicting results. The scientists behind the new meta-analysis therefore decided to look closer at scientific data collected from various electronic databases such as PubMed, Google Scholar, Connected Papers etc. to find out more. They explain why there has been conflicting data and why some of the scientific data needs to be reevaluated, especially when it comes to vitamin D levels in the blood.
Vitamin D and its role in the immune defense
It is commonly known that vitamin D is important for our calcium metabolism, and it is also a known fact that extreme vitamin D deficiency can cause rickets. Most of the cells in the body have vitamin D receptors, even the white blood cells of the immune defense.
Vitamin D is important for our innate immune defense – including the dendrite cells, macrophages, neutrophiles, and NK cells that serve as storm troops with their ability to attack various types of microorganisms. Vitamin D is also important for the formation of certain antibiotic peptides that suppress bacterial growth and prevent viruses from penetrating the respiratory mucosa. That way, vitamin D has a vital role in our innate immune defense that is designed to fight most germs without us noticing.
Vitamin D is also important for the adaptive immune defense that sets in when the task becomes too challenging for the innate immune defense. The adaptive immune defense consists of T cells and B cells that are able to launch targeted attacks and form immunity. T cells have a vital role when it comes to fighting virus infections, but if there is not enough vitamin D, the T cells are unable to divide explosively to form an army of goal-oriented T cells. In that case, virus and other types of pathogens are able to spread.
Vitamin D is also important for the white blood cells and their ability to communicate, which they do with help from various cytokines. Some cytokines initiate inflammatory processes that are a vital part of the immune system’s attack strategy. Other cytokines inhibit inflammation once a virus or another pathogen has been defeated. It is crucial that the cytokine production is properly balanced and controlled in order to avoid life-threatening cytokine storm and hyperinflammation, which is chronic inflammation that sets the stage for a host of different chronic diseases.
Vitamin D and its role in COVID-19
A COVID-19 infection starts by virus particles infecting cells in the nose. Spike proteins on the virus surface attach to the ACE2 receptors in the cells. If the immune system functions optimally, it is able to fight the virus and form immunity before the virus ran replicate and spread. But if the immune defense does not function optimally, COVID-19 is able to spread to other cells with ACE2 receptors in the lower respiratory tract. This can result in bronchitis and pneumonia combined with fever. Most people develop a mild to moderate infection but in severe cases, an acute respiratory failure called acute respiratory distress syndrome (ARDS) may develop.
A virus can also spread to other tissues that have ACE2 receptors and cause circulatory failure and organ failure, which is the main reason why the weakest patients succumb. Complicated COVID-19 infections are also characterized by cytokine storm and hyperinflammation that can damage healthy tissue.
It is therefore the immune system’s capacity that determines if a person rejects the COVID-19 infection, develops a mild infection, or suffers life-threatening complications.
In their new meta-analysis, the scientists look closer at vitamin D’s role in the immune defense and why COVID-19 originally started spreading in the winter of 2019 in the northern hemisphere, where vitamin D deficiency is more common. We may possibly see the same waves of virus infection this winter because vaccines only have a limited effect.
The researchers also look at how vitamin D counteracts cytokine storm and hyperinflammation and disturbances in the ACE2 receptors, which can lead to pulmonary edema and circulatory failure.
In a larger review, the scientists refer to different studies from Europe, Israel, and China that have linked low levels of vitamin D in the blood to a substantially increased risk of COVID-19 infections and being put in intensive care and dying of the disease.
The meta-analysis even reveals that the few studies that failed to show a relation between vitamin D and COVID-19 were not representative of the general population. The studies were also insufficient because levels of vitamin D were measured before the COVID-19 infection without taking into consideration the fact that vitamin D levels vary a lot from summer to winter.
Vitamin D supplements for preventing and treating COVID-19
Several studies have looked at vitamin D supplements and their potential for preventing COVID-19 infections and related deaths. In a British study (CORONAVIT) from Queen Mary University, over 5,000 participants were given 20 or 80 micrograms of vitamin D daily to see if this could lower their risk of COVID-19 or other respiratory infections and reduce the severity of their symptoms. The study was a so-called open study without a placebo group. In other studies of COVID-19 patients with low vitamin D levels, the scientists start by administering large doses of vitamin D to optimize blood levels of the nutrient. After that, patients are given a lower dose for maintenance. In Spain, researchers have completed a pilot study where COVID-19 patients were given standard therapy or supplements of vitamin D3 (calcifediol), a form of the nutrient that works a lot faster than other types of vitamin D. Only two percent of the patients in the vitamin D group required intensive care compared with 50 percent of patients in the non-supplemented group. There were no deaths in the vitamin D group and all patients were discharged without further complications. The study is published online in The Journal of Steroid Biochemistry and Molecular Biology.
Vitamin D’s role in rheumatoid arthritis and other inflammatory diseases
Rheumatoid arthritis is a chronic autoimmune joint disease with inflammation that can destroy the joint tissue, impair quality of life, and increase mortality. Although the main reason remains unknown, there are several factors that can affect the disease – including genetic, environmental, and dietary ones.
The new meta-analysis reveals a variety of epidemiological data showing that lack of vitamin D is linked to the development of rheumatoid arthritis and the activity of the disease, which is primarily due to the vitamin’s anti-inflammatory properties.
A more recent study of 645 patients with early-detected rheumatoid arthritis showed that lack of vitamin D can predict the development of the disease. Several studies have demonstrated that high-dosed vitamin D supplementation can mitigate the symptoms of rheumatoid arthritis. Other studies have not been able to demonstrate a similar outcome. The scientists therefore say that the vitamin dosage and the duration of the intervention is of vital importance to its effect. It is crucial to take enough vitamin D to optimize blood levels of the nutrient and to continue taking a maintenance dose.
Vitamin D sources and our actual need for the nutrient
The summer sun is our main source of vitamin D because. We only get a limited amount of the nutrient from our diet. Therefore, the Danish Veterinary and Food Administration advises everyone to take a vitamin D supplement during the winter period, while it is recommended for vulnerable groups to take a supplement all year round.
High-dosed (20-80 micrograms) vitamin D supplements are available on the market. Our actual need for the nutrient hinges on a variety of factors such as sun exposure, age, skin type, BMI, and chronic diseases. EU’s Scientific Committee on Food has set 100 micrograms per day as the safe upper intake level for adults (including pregnant and breastfeeding women). Vitamin D is lipid-soluble so we get the best utilization of the nutrient by taking it in some kind of oil in soft gelatin capsules.
Blood levels of vitamin D
Sneha Verma et al. Vitamin D deficiency: concern for rheumatoid arthritis and COVID-19? Molecular and Cellular Biochemistry 2021
José L Hernandez et al. Vitamin D Status in Hospitalized Patients with SARS-CoV2- Infection. The Journal of Clinical Endocrinology & Metabolism. 27 October 2020
Northwestern University. Vitamin D levels appear to play role in COVID-19 mortality rates. Science Daily. May 2020
Ali Daneshkhah et al. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv April 30, 2020
Queen Mary University of London. Clinical trial to investigate whether vitamin D protects against COVID-19. 13 October 2020
Marta Entrenas Castillo et al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. The Journal of Steroid Biochemistry and Molecular Biology. October 2020
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