Vitamin D

History of vitamin D

Vitamin D was categorized as a vitamin when it was discovered in 1922. It is not a true vitamin because an ongoing nutrient source is not required to sustain normal levels in the body. Vitamin D is properly classified as a secosteroid (derived from steroid) hormone precursor. A hormone is a chemical substance produced by one organ and then transported in the bloodstream to a target organ, where it causes a specific biological action.
Vitamin D has several metabolites (forms). This summary is limited to two metabolites: 25-D and 1,25-D.
25-D (also known as calciferol, 25-hydroxycholecalciferol) increases calcium absorption in the gut and at high levels, acts as an antagonist on the Vitamin D Receptor. 25-D is produced in the liver and synthesized in the cells of the skin in reaction to sunlight. 25-D dietary sources (fish, fish oils, eggs), foods that are supplemented with vitamin D (dairy products, cereals.) and vitamin supplements.
25-D is the major circulating form of vitamin D. It is used in the production of (1,25-D) in the kidneys.
1,25-D (also known as calcitriol or 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin-D3) is a potent secosteroid paracrine mediator and virtually affects all cellular activity.
1,25-D is primarily formed in the kidneys; but may also be formed skin, macrophages and other tissues.
Vitamin D dysregulation

The innate immune system refers to the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner. This means that the cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. The innate immune system provide immediate defense against infection.

Vitamin D is an important immune-modulator.

1,25-D can activate the innate immune system. Elevated levels can be found in patients with chronic conditions.
25-D can suppress the innate immune system.
Normally, production of 1,25-D is tightly controlled by the kidneys in response to a complex system of hormonal regulation. However, when nucleated cells are infected with bacterial pathogens, 1,25-D is generated by the inflammatory response. This causes the level of 1,25-D to exceed the upper limit normally controlled by the kidneys.

It is essential to measure both 25-D and 1,25-D to evaluate vitamin D levels and dysregulation. The level of 25-D doesn’t directly reflect the level of 1,25-D. Patients with Th1/Th17 inflammation often have a low level of 25-D while the level of 1,25-D is high. T helper 17 cells (Th17) are a subset of T helper cells producing interleukin 17 (IL-17) discovered in 2007. They are considered developmentally distinct from Th1 and Th2 cells and excessive amounts of the cell are thought to play a key role in autoimmune disease such as multiple sclerosis, psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn’s disease.