Vitamin D3 and Immune system? Is there a connection?

  • Interview

Interview with the Head of R&D, Kathrin Bühler

Vitamin D3 is well known for its influence on calcium metabolism. However, recently - especially in context of the ongoing pandemic - other functions of vitamin D3 such as immune response, gained widespread attention. We talked with our Head of R&D, Dr. Kathrin Bühler, whether there is a connection between vitamin D3 and the immune system.

There were several articles in newspapers and magazines talking about a link between vitamin D3 status and SARS-CoV-2 infections. What is the background of this topic?

To answer this question, allow me to first give some general information on the history and the metabolism of vitamin D3.

In the early 20th century, a substance found in cod liver oil was discovered to cure rickets. This substance was then named ‘vitamin D3’. In the following years it became evident that vitamin D3 is a key element in the mineral metabolism, especially Ca-metabolism. These effects are now often referred to as the ‘classical effects’ of vitamin D3.

Researchers also found that vitamin D3 needs to undergo two conversion steps to become metabolic active. The first step happens in the liver to form 25-hydroxyvitamin D3 (25OHD3), the circulating form. The second step happens mainly in the kidney but also in other tissues and converts 25OHD3 into 1,25-diyhdroxyvitamin D3 (1,25(OH)2D3).

1,25(OH)2D3, which is the metabolic active form of vitamin D3, was only discovered in the 1970s. To exert its effects in the body, 1,25(OH)2D3 needs to bind to the vitamin D3 receptor (VDR) in the cell.

The VDR is where the link of vitamin D3 to infections comes into play. The VDR is not only present in tissues related to mineral metabolism such as for example the gut and bones, but also in many other tissues, such as the placenta, muscle, immune cells etc. And where there is a VDR, an interaction with 1,25(OH)2D3 is more than likely. These effects, that are not directly related to mineral metabolism, are called ‘non-classical effects’.

During the Covid-19 Pandemic, several studies were published stating a connection between vitamin D3 status, risk of infection and severity of the disease. The discussion has put the spotlight on these non-classical effects of vitamin D3, especially the potential effects on the immune system.


„The active form of vitamin D3 (1,25(OH)2D3) acts as an immunomodulator and is related to inflammatory reactions, where 1,25(OH)2D3 supports the anti-inflamatory response.“

What exactly are the effects of vitamin D3(metabolites) on the immune system?

The effects are manifold. In summary it can be said that 1,25(OH)2D3 acts as an immunomodulator that ensures the immune system is doing a proper job. This means a quick and sharp response when the infection takes place but also a fast return to the normal state once the danger has passed. This second part is related to inflammatory reactions, where 1,25(OH)2D3 supports the anti-inflammatory response. Furthermore, there is evidence that 1,25(OH)2D3 modulates the immune system in a way that makes it more tolerant against ‘perceived threats’ as they can occur in allergies, autoimmune disease or in pregnancy.

Can such a link between vitamin D3 and immune system also be found in livestock?

Most research on the link between immune system and vitamin D3(-metabolites) has been done so far in humans, rats, mice and in the lab using cell cultures. Only since a few years researchers started to look at non-classical effects in other animals. They found for example that wild boar and red deer that received a specific fodder containing vitamin D3 showed less severe tuberculosis lesions than unsupplemented animals. In broilers, the use of 25OH and 1,25(OH)2D3-glycosides from plant origin reduced the inflammatory response. Similarly, calves suffering from pneumonia that were injected with 1,25(OH)2D3 showed an improvement of the clinical symptoms, a stimulation of anti-inflammatory responses and an increase of antimicrobial peptides.

How can the immune system of livestock be supported?

Immunity or resilience to infections of livestock depends on various factors such as

  • Age (e.g. higher susceptibility in older animals)

  • Management (e.g. avoidance of stress)

  • Genetic disposition (e.g. some animals are more resistant to coccidiosis than others)

Another important factor is of course nutrition. On the one hand, it provides the energy and elements necessary for maintaining the immune system. On the other hand, nutrition can directly modulate the immune system as it has been described for vitamin D3 and its metabolites.