Calcifediol, also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D, is a prehormone that is produced in the liver by hydroxylation of vitamin D3 by the enzymecholecalciferol 25-hydroxylase. Physicians worldwide measure this metabolite to determine a patient's vitamin D status. At a typical daily intake of vitamin D3, its full conversion to calcifediol takes approximately 7 days. Calcifediol is then converted in the kidneys into calcitriol, a secosteroidhormone that is the active form of vitamin D. It can also be converted into 24-hydroxycalcidiol in the kidneys via 24-hydroxylation.
Blood test
In medicine, a 25-hydroxy vitamin D blood test is used to determine how much vitamin D is in the body. The blood concentration of calcifediol is considered the best indicator of vitamin D status. This test can be used to diagnose vitamin D deficiency, and it is indicated in patients with high risk for vitamin D deficiency and when the results of the test would be used as supporting evidence for beginning aggressive therapies. Patients with osteoporosis, chronic kidney disease, malabsorption, obesity, and some other infections may be high risk and thus have greater indication for this test. Although vitamin D deficiency is common in some populations including those living at higher latitudes or with limited sun exposure, the 25D test is not indicated for entire populations. Physicians may advise low risk patients to take over-the-counter vitamin D in place of having screening. It is the most sensitive measure, though experts have called for improved standardization and reproducibility across different laboratories. According to MedlinePlus, the normal range of calcifediol is 30.0 to 74.0 ng/mL. The normal range varies widely depending on several factors, including age and geographic location. A broad reference range of 20–150 nmol/L has also been suggested, while other studies have defined levels below 80 nmol/L as indicative of vitamin D deficiency. US labs generally report 25D levels as ng/mL. Other countries often use nmol/L. Multiply ng/mL by 2.5 to convert to nmol/L.
Clinical significance
Increasing calcifediol levels are associated with increasing fractional absorption of calcium from the gut up to levels of 80 nmol/L. Urinary calcium excretion balances intestinal calcium absorption and does not increase with calcifediol levels up to ~400 nmol/L. A study by Cedric F. Garland and Frank C. Garland of the University of California, San Diego analyzed the blood from 25,000 volunteers from Washington County, Maryland, finding that those with the highest levels of calcifediol had a risk of colon cancer that was one-fifth of typical rates. However, randomized controlled trials failed to find a significant correlation between low-dosage vitamin D supplementation and the risk of colon cancer. A population study in Copenhagen, Denmark, found a correlation between both low and high serum levels and increased mortality, with a level of 50–60 nmol/L being associated with the lowest mortality. The study did not show causation.
Interactive pathway map
History
Research in the laboratory of Hector DeLuca identified 25D in the 1968 and showed that the liver was necessary for its formation. The enzyme responsible for this, cholecalciferol 25-hydroxylase, was isolated by Michael F. Holick in 1972.
