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Particular type of vitamin D blocks dangerous inflammation

- even in the case of COVID-19

Particular type of vitamin D blocks dangerous inflammationVitamin D is important for a well-functioning immune defense and a number of other functions. A team of scientists from Purdue University and National Institutes of Health in the United States has recently uncovered mechanisms that enable vitamin D to reduce hyperinflammation in severe COVID-19 cases. The scientists refer to a particularly active vitamin D metabolite that is formed in immune cells, in the lungs, and various other places. It is important to have adequate levels of vitamin D at all times, and it is equally vital for the body to be able to activate vitamin D, a process that requires the presence of magnesium.

Vitamin D has multiple roles in the immune system, and having a well-functioning immune defense is essential for being able to fight off infections. Under normal circumstances, a group of white blood cells called Th1 cells initiate a pro-inflammatory phase. Once the intruding microbe has been defeated, the Th1 cells launch an anti-inflammatory phase. The pro-inflammatory phase involves the presence of free radicals which are highly reactive and potentially harmful molecules. Therefore, it is imperative for this powerful phase to be brief, controlled, and effective in order to avoid damage to the surrounding tissue.
Apparently, vitamin D helps the immune defense shift over to its anti-inflammatory phase much faster. The scientists behind the new study therefore assume that vitamin D could be of potential value to patients suffering from severe inflammation.

COVID-19 complications are caused by hyperinflammation

Most cases of COVID-19 are mild and uncomplicated. However, in severe cases, the pro-inflammatory phase launched by the Th1 cells cannot not be controlled and leads to hyperinflammation and acute respiratory distress syndrome – or ARDS. Hyperinflammation may even occur in the epithelial cells of the blood vessels and in other organs, resulting in circulatory failure and, eventually, death.
The capacity of the immune system determines our ability to tackle a COVID-19 infection, and that was why the scientists focused on the ability of a virus to trigger a biochemical pathway in the innate immune defense called the complement system which is also able to trigger inflammation.

Lack of vitamin D and problems with activating the nutrient

The scientists say that the type of uncontrolled hyperinflammation seen in complicated COVID-19 cases are most likely a result of the patients not having sufficiently high blood levels of vitamin D, or not being able to activate the vitamin.
Cholecalciferol, the form of vitamin D that we synthesize in our skin when we expose ourselves to UVB rays from sunlight or that we get from supplements, is not biologically active. In order for this to happen, it must first be converted enzymatically in a two-step process.
The first step takes place in the liver. Here, a form of vitamin D called 25-hydroxyvitamin D3 (calcidiol) is formed. This is the form that serves as a vitamin D deposit and also the form that is measured in the blood. When vitamin D is required by the cells, it has to go through the second step of conversion (in the kidneys). Here, 25-hydroxyvitamin D3 is converted into biologically active vitamin D3, or 1,25-dihydroxyvitamin D3 (calcitriol). This is the active steroid form of vitamin D that binds to vitamin D receptors in most of the body’s cells. Science has primarily focused on the activation process in the kidneys, but studies conducted during the past decade have shown that the activation also takes place in immune cells, in the lungs, the blood vessels, colon, and in other tissues. The cells in all these different sites must therefore be able to activate vitamin D whenever it is need. Magnesium is needed in both of these enzyme processes. If we don’t get enough magnesium, in other words, we are not able to get the full benefit of vitamin D from sunlight, from food, or from supplements.

Autocrine vitamin D regulates T cells and inflammation

The form of vitamin D that is activate outside the kidneys is called autocrine vitamin D. By analyzing blood samples and tissue samples from patients with COVID-19 and from healthy controls, the scientists behind the new study observed that this was the form of vitamin D that caused the Th1 cells to interrupt the inflammatory processes. The researchers stress that their study is not a clinical study and that human studies are needed to determine if vitamin D supplements have a therapeutic potential. The study is published in Nature Immunology.

Vitamin D supplementation of COVID-19 patients lowers mortality and the need for intensive care

Back in 2020, a Spanish study revealed that vitamin D supplementation of critically ill COVID-19 patients had the potential to save lives. At the University Hospital of Córdoba, 76 hospitalized COVID-19 patients were assigned to either standard therapy or a combination of standard therapy and high-dosed vitamin D supplementation. They used calciferol (25-hydroxyvitamin D3) because it is easier and faster for the body to utilize. It turned out that only two percent of the patients in the vitamin D group were admitted to intensive care, whereas 50 percent of patients in the non-supplemented group required intensive care. There were no deaths among the vitamin D-treated patients and they were all discharged without further complications.

Vitamin D sources and individual requirements

As mentioned, vitamin D appears to have potential when it comes to preventing infections and controlling inflammation in complicated COVID-19 cases and other viruses. Still, it requires that we get enough vitamin D and that we are able to activate the nutrient in the body.
The sun during the summer period is our primary source of vitamin D. We only get limited quantities from the food we eat. For that reason, health authorities have started recommending vitamin D supplements for everyone during the winter period, and they even advise vulnerable groups of people to take a supplement all year round.
High-dosed vitamin D supplements are available on the market. Our actual need for the vitamin depends on a variety of factors including such things 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 vitamin D for adults (including pregnant and breastfeeding women). Vitamin D is lipid-soluble so we get the best utilization by taking capsules with vitamin D in oil. Also, we need sufficient amounts of magnesium from food or supplements to activate vitamin. The magnesium in supplements should always be in a form that has good absorption.

  • Blood levels of vitamin D are categorized as actual deficiency (below 30 nmol/L), insufficiency (30-50 nmol/L), and sufficiency (above 50 nmol/L).
  • Leading experts say that the optimal vitamin D status lies in the range of 75-120 nmol/L


Daniel Chauss et al. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells. Nature Immunology. 2021

Purdue University. Researchers study the link between vitamin D and inflammation. ScienceDaily 2021.

J. Wesley Pike and Mark B. Meyer. Fully-activated Vitamin D (calcitriol) is produced inside and outside of the kidneys. J Clin Invest 2020

Qi Dai et al. Magnesium status and supplements influence vitamin D status and metabolism: results from a randomized trial. The American Journal of Clinical Nutrition. 2018

Marta Entrenas Castillo et al. Effect of calciferol 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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