Originally published in LabTalk (Volume 4, Issue 2, 2009), the quarterly newsletter of Aculabs.

Vitamin D has been well known for its role in bone metabolism; however, the important role of vitamin D beyond that was the discovery of the 1,25-Dihydroxyvitamin D nuclear receptor in most tissue. Increased interest in vitamin D introduced the recent evidence that vitamin D can regulate the immune system and thereby it is implicated in several immune mediated diseases. In addition, it has been documented that 1,25-Dihydroxyvitamin D may regulate different cellular processes associated with carcinogenesis. Several studies have linked vitamin D levels with different clinical outcomes like incidences of cancer, increased risk of tuberculosis, periodontal disease, reduced muscle tone and lower-extremity function, diabetes, and autoimmune disorders [1,2,3].

According to a new study published May 21, 2009 in the Journal of Neurology, Neurosurgery, and Psychiatry, vitamin D may have an important role in keeping the brain in good working order in later life [4].

Sunlight is the best source of vitamin D production; it helps synthesize vitamin D from its precursor.  Vitamin D is converted to 25-Hydroxy (OH) vitamin D by the liver, which, in turn, is converted to 1,25-Dihydroxyvitamin D by the kidney. 25-OH vitamin D is the major form of the hormone found in the blood and is the inactive precursor to the active hormone, 1,25-Dihydroxyvitamin D. Because of its long half-life, and higher concentration, 25-OH vitamin D is commonly measured to assess and monitor vitamin D status in individuals.

Vitamin D consists of 2 forms: D2, which is obtained from vegetable sources, and D3, which is derived from exogenous (animal-product diets) and endogenous (from cholesterol after exposure to sun) sources. Both D2 and D3 are converted to 25-Hydroxyvitamin D in the liver.

Vitamin D deficiency is more common than it was thought, with an estimated 50% of the elderly and 50% of women at any age having inadequate levels of vitamin D. The recognition of vitamin D deficiency in so many conditions has resulted in an increase in the volume of testing for vitamin D within the past 2 years, at the rate of an 80-90% increase per year.

There are differences among Vitamin D methods, making universal reference ranges difficult to establish. Many tests for 25-Hydroxyvitamin D do not distinguish D2 and D3 forms of the vitamin and report only a total 25-Hydroxyvitamin D. Newer methods, however, may report levels of both 25-Hydroxy D2 and D3, and then add them together for a total 25-Hydroxyvitamin D level which may be confusing to physicians in-training, who might consider a low 25-(OH) D2 or 25-(OH) D3 concentration to indicate vitamin D deficiency, even if the total 25-(OH) D result is within the reference interval, thereby leading to incorrect clinical decisions.

Total 25-Hydroxyvitamin D (D2 + D3) is used to assess vitamin D status; it is the barometer for vitamin D status. Serum 25-Hydroxyvitamin D is not only a predictor of bone health, but is also an independent predictor of risk for cancer and other chronic diseases.  1,25-Dihydroxyvitamin D should be ordered only in rare situations (renal failure, sarcoidosis) and must be interpreted with the help of specialized physicians. There is currently no consensus on the level which indicates deficiency, but 32 ng/mL is accepted as sufficient for bone health.

– Dr. Rita Khoury


  1. The Third National Health and Nutrition Examination Study (NHANES III): Vitamin D status linked to risk of cardiovascular disease (Conchol and Scragg 2007)
  2. The Nurses Health Study (NHS): Vitamin D status linked to colon and breast cancer (Bertone-Johnson et al. 2005; Feskanich et al. 2004)
  3. The Health Professionals Follow-Up Study (HPFS): Vitamin D status linked to risk of myocardial infarction in men (Giovannucci et al. 2008)
  4. The Framingham Heart Study (FHS): Vitamin D status linked to bone health (Bischoff-Ferrari et al. 2004)
  5. Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men. Lee, D. Journal of Neurology, Neurosurgery and Psychiatry, May 20, 2009; advance online edition.


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