Fróđleikur: Calcitriol (INN), also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active metabolite of vitamin D with three hydroxyl groups (abbreviated 1,25-(OH)2D3 or simply 1,25(OH)2D), It was first identified by Michael F. Holick in work published in 1971. Calcitriol increases the level of calcium (Ca2+) in the blood by increasing the uptake of calcium from the gut into the blood, increasing reabsorption of calcium by the kidneys, and possibly increasing the release of calcium into the blood from bone.
Forms of vitamin D Vitamin D has several natural forms (metabolites). For practical purposes, this explanation is limited to three of those forms: vitamin D3, 25(OH)D and 1,25(OH)2D.
Vitamin D3Vitamin D3 is formed in the skin in response to exposure to sunlight. Vitamin D3 may also be obtained from naturally occurring dietary sources (e.g., fish, fish oils, liver, eggs, etc.), processed foods that are supplemented with vitamin D3 (e.g., dairy products, cereals, etc.) and vitamin D3 supplements.
25(OH)DVitamin D3 is transported to the liver where it’s converted to 25(OH)D (also known as calcidiol or calciferol). 25(OH)D is not very active biologically. 25(OH)D is the major circulating form of vitamin D and the form that is usually measured to assess vitamin D status. It’s main purpose is conversion to 1,25(OH)2D, the biologically active form of vitamin D.
25(OH)D has a half life of 2-6 months and is stored as a safeguard for later use during months when sunlight is less available.
1,25(OH)2D1,25(OH)2D (also known as calcitriol) is, primarily, formed in the kidneys but it’s also generated locally by many other body tissues. 1,25(OH)2D is a potent secosteroid paracrine (cell to cell) mediator and it affects almost all cellular activity.
Normally, production of 1,25(OH)2D is tightly controlled by the kidneys in response to a complex system of hormonal regulation. But if nucleated cells are infected with bacterial pathogens, 1,25(OH)2D is generated by the inflammatory response. This causes the level of 1,25(OH)2D to exceed the upper limit normally controlled by the kidneys.
It also results in a depletion of the precursor 25(OH)D which often leads to a misdiagnosis of vitamin D deficiency.
It is essential to measure both 25(OH)D and 1,25(OH)2D to rule out a vitamin D deficiency. The level of 25(OH)D doesn’t directly reflect the level of 1,25(OH)2D. Patients with Th1/Th17 inflammation (who have not been supplementing with vitamin D) often have a low level of 25(OH)D while the level of 1,25(OH)2D is high. Testing only 25(OH)D, as is usually done, may result in a false diagnosis of vitamin D deficiency. The key result is the level of 1,25(OH)2D because it is the active metabolite.
Long-term problems associated with dysregulated vitamin D metabolism include upset calcium homeostasis and bone loss. See Vitamin D Metabolism Dysregulation
Symptoms of elevated 1,25(OH)2D
Mildly elevated 1,25(OH)2D can cause a variety of inflammatory symptoms. Extremely high 1,25(OH)2D is known as hypervitaminosis-D. Hypervitaminosis-D may cause a variety of symptoms such as constipation, anorexia, dehydration, fatigue, irritability, vomiting, headache, weight loss, polyuria, polydipsia and hypercalcemia.