The ABCs of Vitamin D

Vitamin D is produced from 7-dehydrocholesterol in the skin when the skin is UV-irradiated by sunlight. In humans, vitamin D3 or cholecalciferol is specifically produced. Plants produce predominately vitamin D2 or ergocalciferol. While human bodies can utilize vitamin D2, they preferentially use D3 and the rest of this post will be talking about D3.

Vitamin D is actually more of a steroid hormone than a vitamin. Unlike vitamins, Vitamin D is produced in the body, and like hormones, it is produced in skin cells and acts on cells at sites distant from its site of production. The primary functions of vitamin D include actions to increase blood calcium levels. Low blood calcium levels cause a release of parathyroid hormone (PTH), which in turn activates vitamin D. Vitamin D then actively increases calcium absorption from the intestine and helps mobilize calcium from the bone. Vitamin D has been studied and associated with health benefits ranging from decreasing the risks of getting various types of cancer to lowering the risks of heart attacks and type 1 diabetes, causing it’s measurement to become an almost routine part of most physicals and resulting in a large testing volume in the lab.

In the body, Vitamin D exists in multiple forms. The vitamin D produced in the skin is hydroxylated in the liver to give 25-hydroxy-vitamin D (25-OH-D), the main circulating form of Vitamin D. This form is not biologically active. When the correct physiological signals are received however (low calcium and high PTH), another hydroxyl group is added to 25-OH-D in the kidneys, to form the biologically active form, 1,25-dihydroxy-vitamin D (1,25-diOH-D). 1,25-diOH-D is present in very low concentrations.

25-OH-D is the form measured when assessing a person’s overall vitamin D status. It is in the greatest concentration in the body and has a half-life of 2 to 3 weeks. It can be measured by a variety of immunoassays as well as by tandem mass spectrometry. Unfortunately not all assays measure the same forms of 25-OH-D, and thus values can differ significantly depending on the assay used to measure them. This is a major problem because vitamin D has health-based reference intervals, not population based. This means that studies have determined that 25-OH-D concentrations below 30 µg/dL suggest vitamin D deficiency. So all assays use this 30 µg/dL cut-off, even though all assays don’t measure the same amount of vitamin D in samples. Cholesterol is another example of an analyte with health-based reference intervals. We say a person’s cholesterol should not exceed 200 mg/dL, rather than establishing the population-based reference intervals for cholesterol for our population.

1,25-diOH-D is much more difficult to measure because it occurs in much lower concentrations, with a half-life in the body of 4 to 6 hours. It is generally only measured when renal function is impaired, or to check for diseases involving vitamin D metabolism. It is often ordered in error when the healthcare provider actually wants to know the patients overall vitamin D status, the 25-OH-D concentration. Assays for measuring 1,25-diOH-D include radioimmunoassays and extraction followed by liquid chromatography-tandem mass spectrometry. This testing is usually performed in reference labs.

-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.