Sarcoidosis

Worldwide, this disease is relatively uncommon ranging from 1 to 80 cases per 100,000 people. The relationship to vitamin D is that in this condition large amounts of Calcitriol are produced bypassing the typical regulation controls.

Sarcoidosis is an inflammatory disease where granulomas (small clusters of immune cells) form in various organs, particularly the lungs and lymph nodes. In sarcoidosis, activated macrophages in these granulomas can convert Calcifediol to its active form, Calcitriol, independent of the body’s D3 regulation. This can lead to hypercalcemia (elevated calcium levels) and hypercalciuria (elevated calcium in urine). Hypercalcemia is an often cited reason for vitamin D toxicity. Clearly, in this case sarcoidosis is too blame and not vitamin D since the disease bypasses the regulatory mechanisms.

Vitamins

Calcitriol

[Vitamin D](vitamin-d), also known as calcitriol in its active form, is produced in the kidneys and helps the body absorb calcium, among other important functions like supporting the immune system. It is made from another form of vitamin D (/vitamins/vitamin-d/calcifediol) and is carefully regulated to keep its levels in check. While calcitriol is the active form, it’s not a good indicator of overall vitamin D storage in the body. Instead, vitamin D levels in storage are better measured by checking calcifediol levels. Some diseases, like sarcoidosis, can cause too much active vitamin D, while others, like chronic kidney disease, can prevent enough from being made.

For more technical details, read on.

The name Calcitriol (aka vitamin D) refers to a hormone that is produced via hydroxylation of Calcifediol in the human liver. Calcitriol is typically bound by the D-binding protein (DBP) but has a lower affinity DBP than Calcifediol but higher than Cholecalciferol. Calcitriol is the active form of the hormone and facilitates calcium uptake among a myriad of other functions, such as immune system-related ones.

Vitamins

Vitamin D

Vitamin D, technically a hormone, is made in the skin when UVB rays convert a cholesterol compound into D3 (Cholecalciferol, or Calciol). Many people don’t make enough due to lack of sun exposure, so we rely on food (like fatty fish) or supplements. Plants provide D2 (Ergocalciferol), but D3 works better in our bodies.

D3 has three key forms:

Calciol: Stored in fat for long-term use; this is the form we produce or ingest.
Calcifediol: Formed in the liver for short-term storage, circulating in blood and commonly tested to check D3 levels.
Calcitriol: The active form, made in the kidneys, with a short lifespan but crucial for biological effects.

We’ll be using the terms Calciol → Calcifediol → Calcitriol throughout future discussions.