Vitamin D, 25-Hydroxy

Serum

0.5 mL

0.3 mL (Note: This volume does not allow for repeat testing.)

Red-top tube or gel-barrier tube

Rule out vitamin D deficiency

Values of vitamin D vary with exposure to sunlight. The assay measures other vitamin D metabolites, including dihydroxylated metabolites such as 24,25, 25,26, and 1,25 dihydroxy vitamin D; however, since the physiological concentrations of these metabolites are insignificant compared to those of 25-hydroxy vitamin D, the accuracy in assessing vitamin D levels is not compromised.

Immunochemiluminometric assay (ICMA). This assay is performed on the DiaSorin LIAISON® instrument in multiple laboratories throughout LabCorp. This highly automated test measures both D₂ and D₃ together and reports a total 25-hydroxy vitamin D. Major clinical studies, including (but not limited to) the Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) data base, the Women's Health Initiative (WHI) Studies, and the Harvard-Based Health Professionals Studies, employed DiaSorin reagents.

30−100 ng/mL

The majority of 25-OH vitamin D (25-D) in the circulation is derived from the conversion of 7-dehydrocholesterol in the skin that is irradiated with ultraviolet radiation in the UVB range (wavelength 290 nm to 315 nm).^1-5 The extent of vitamin D formation is not tightly controlled and depends primarily on the duration and intensity of the UV irradiation. Levels produced typically reach a plateau within 30 minutes of exposure. Unfortunately, use of a sunscreen with SPF as low as 15 reduces the rate of vitamin D production by 99.9%. Overproduction of vitamin D in the skin is prevented by the photosensitive conversion of vitamin D to tachysterol or lumisterol. Vitamin D is not very water-soluble, so it must be delivered to and carried in the blood as a complex with vitamin D-binding protein. Once in the circulation, vitamin D is metabolized to 25-hydroxy vitamin D (25-D) by the liver. The 25-D form of the hormone is the principle circulating reservoir in plasma and is generally the best indicator of overall vitamin D status. 25-D is further metabolized by the kidney to produce the biologically active form of vitamin D, 1,25-dihydroxy vitamin D (1,25-D). Renal production of 1,25-D is tightly controlled by parathyroid hormone and is important in the regulation of serum calcium homeostasis.

The hormonally active form of vitamin D,1,25-D plays an integral role in calcium homeostasis and the maintenance of healthy bone.^1-4 1,25-D stimulates the absorption of calcium at the level of the intestine and may also serve to increase calcium and phosphate resorption at the kidney level. Vitamin D deficiency leads to the mobilization of calcium from bone. Individuals with more severe vitamin D deficiency can develop osteomalacia and/or osteoporosis. Osteomalacia in children, also referred to as rickets, results in well-described skeletal malformations, since children's bones are actively growing. Recent clinical and epidemiological studies suggest that vitamin D deficiency may play a role in several conditions unrelated to bone, including prostate cancer, breast cancer, colon cancer, heart disease, hypertension, multiple sclerosis, and type 1 diabetes.

A number of studies have shown that vitamin D deficiency is very common, especially in certain high-risk populations.^1,2 This situation has occurred, in part, because the foods in the typical American diet are very low in vitamin D. Fatty fish, such as mackerel and salmon, and fish liver oils are some of the few natural dietary sources of vitamin D. Most people do not eat enough of these foods to maintain adequate vitamin D levels. In the United States, vitamin D is added to milk in order to prevent the occurrence of rickets in the pediatric population. Unfortunately, too many children do not drink enough milk to raise their vitamin D levels to the optimum range. Also, recent studies have shown that the level of vitamin D in fortified milk is frequently much lower than that recommended by the FDA. Human milk contains very little vitamin D because many mothers are deficient, so children of mothers who choose to breast-feed are at risk of developing rickets if they are not given supplemental vitamin D. The American Academy of Pediatrics recommends that infants who are exclusively breast-feeding should be given a supplement of vitamin D.

Several factors are associated with an increased risk of developing vitamin D deficiency. At risk populations include:^1-5

• Individuals with low dietary vitamin D levels. Infants fed only mother's milk and children who do not drink fortified milk are at risk.

• Individuals with malabsorption syndromes. Patients with pancreatic enzyme deficiency, Crohn's disease, cystic fibrosis, celiac disease, and surgical resection of stomach or intestines are at risk.

• Individuals with severe liver disease. Hepatic disease can reduce the conversion of vitamin D to 25-D and can lead to malabsorption of vitamin D.

• Individuals with kidney disease. Nephrotic syndrome can increase the urinary loss of vitamin D.

• Individuals taking certain drugs. Several medications, including phenytoin, phenobarbital, and rifampin accelerate the breakdown of vitamin D by the liver.

• Individuals who live at higher latitudes. Individuals who live in northern climates are at increased risk of deficiency, especially in winter months due to diminished exposure to UVB radiation.

• Individuals who spend little time outside. Individuals who are homebound or simply choose to remain inside are at increased risk.

• Older adults. The skin becomes less efficient at producing vitamin D as one ages because of diminished levels of vitamin D precursors in the skin.

• Individuals with decreased sun exposure for cultural reasons. Women in some societies are required to cover themselves with heavy clothing, reducing exposure to the sun's rays.

• Races with high melanin levels. Increased skin pigmentation can reduce the efficiency of vitamin D conversion in the skin as much as 50-fold. Individuals with dark complexions living at higher latitudes are at increased risk.

Serum concentrations of 25-D are known to vary with age, sex, race, season, and geographic location. This has led to the establishment of seasonal expected ranges for geographic locations and local populations. This approach provides a “reference interval” but does not adequately determine health status with regard to vitamin D levels if a significant portion of the reference population is, in fact, deficient. A more useful parameter in clinical practice would be a nutritional threshold below which an individual could be characterized as vitamin D-deficient. Vitamin D deficiency has been defined by the Institute of Medicine and an Endocrine Society practice guideline as a level of serum 25-hydroxy vitamin D <20 ng/mL.^1,3 The Endocrine Society went on to define vitamin D insufficiency as levels between 21 and 29 ng/mL.³

Vitamin D plays an integral role in calcium homeostasis and the maintenance of healthy bone. Vitamin D stimulates the absorption of calcium at the level of the intestine and may also serve to increase calcium and phosphate resorption at the kidney level. Deficiency of vitamin D leads to the mobilization of calcium from bone, which can lead to osteoporosis, osteomalacia, and rickets.^1-3 Numerous recent studies have shown a strong association between diminished vitamin D levels and risk for falls⁶ and for both vertebral and nonvertebral fractures.⁷

The World Health Organization's International Agency for Research on Cancer (IARC) has concluded that there is a strong link between an individual's vitamin D levels and the risk of developing colorectal cancer.⁵ Studies have also revealed that low vitamin D levels are associated with an increased incidence of other malignancies, including breast cancer.⁸

Many tissues and cells in the body have vitamin D receptors.^1-3 It has been estimated that the expression of as much as one third of the human genome is influenced by 1,25-(OH)2 vitamin D. Many studies have demonstrated an association of vitamin D deficiency with increased risk for:

• Autoimmune diseases, including both type 1 and type 2 diabetes, rheumatoid arthritis, Crohn's disease, and multiple sclerosis.

• Infectious diseases and asthma

• Cardiovascular disease and hypertension

There are, however, few randomized, controlled trials with a dosing range adequate to provide strong evidence of the benefit of vitamin D in reducing the risk of these chronic diseases.³