Vitamin D status assessment: a clinical perspective

In 2012, more and more health professionals are recognizing the necessity of vitamin D testing and the importance of treating vitamin D deficiency. Vitamin D deficiency is a worldwide phenomenon, occurring not only in high-latitude locations but in such sunny countries as Australia, Italy, Egypt and Mexico. In the last two years alone, more than 16,000 new research papers on vitamin D have been archived in the National Library of Medicine’s PubMed
( Many of these peer-reviewed articles document compelling associations between vitamin D status and medical conditions that affect millions of Americans.1,2 Paralleling this surge in research has been a concomitant surge in vitamin D testing.

The more we test, the more unexpected deficiencies we find. Examples of such unexpected findings here in Minnesota range from adults of all ages to pregnant women on prenatal vitamins to healthcare professionals.

Yet, despite extensive publicity on vitamin D deficiency in both medical journals and the lay press, in 2010, within the Allina Health Care system in Minnesota, more than 30 percent of 10,700 employees were found to have vitamin D levels of less than 20 ng/mL. Six percent had levels below 10 ng/mL. Medical professionals may not recognize either their own risk or their patients’ risk for vitamin D deficiency.

For this reason, both self-care and patient advocacy today mean ensuring normal vitamin D levels via measurement. For those who are already deficient in vitamin D, taking a multivitamin and some milk every day is not sufficient for replenishment. Because of normal human variation in BMI, skin color, age, medication use, absorption, and metabolism—and because geographical location, of course, is another variable—”one size does not fit all.” This means that effective replenishment requires measurement through laboratory testing.

To give some insight into counseling that physicians may provide a patient, I share with you the following account based on a real case study.

Case Study

A previously healthy 42-year-old African American woman consulted with her primary care physician because of two years of worsening fatigue, generalized aches, and subjective weakness. She was surprised by the persistence of these symptoms as she exercised frequently, ate a balanced diet, and swallowed a multivitamin each day. She noted some decreased mood but did not test outside of the normal range for common mood-associated tests such as thyroid, blood sugars, or more serious illnesses.

Clinical Considerations

The range of possibilities to explain these symptoms is, of course, quite broad. Both her physical exam and an extended review of symptoms were normal. This meant that her diagnosis would essentially need to be made based upon laboratory studies. Many lab tests could be ordered for a patient presenting with her symptoms. Because of the new sensitivity to vitamin D deficiency issues, it was one of the tests ordered. The patient’s physician knew that low vitamin D is associated clinically with fatigue, myalgias, weakness, and many other non-specific symptoms.

Results and the patient counseling

The patient’s complete blood count, electrolytes, BUN/creatinine, glucose, and TSH all returned within normal limits. However, her total 25-OH-vitamin D level returned quite low at 12 ng/mL (normal range 30-70 ng/mL). This finding allowed her physician to make the diagnosis of vitamin D deficiency and begin replenishment therapy.

The patient was very surprised by the diagnosis. Her doctor explained that risk factors for low vitamin D include dark skin, larger body sizes (BMI), wearing sun screen, working long hours indoors, and living north of a parallel of latitude corresponding approximately to Atlanta, GA (about 33 degrees north). For many people, taking a multivitamin is not enough to maintain a normal vitamin D level.3,4,5

As part of patient counseling, her doctor explained that our skin, when exposed to the right amount of ultraviolet B (UVB) light from the sun, will make the same vitamin D that is found in most multivitamins and vitamin D supplements. SPF sunblocks will block the body’s capacity to make vitamin D. He also noted, “Multivitamins most often contain 400 IUs. Some prenatal vitamins contain only 200 IUs. For comparison, a summer afternoon at the beach could be as much as 20,000 IUs, which is about the amount of vitamin D found in 50 multivitamins, 100 prenatal vitamins, or 12 gallons of milk.”


At present, there are no national guidelines on vitamin D replacement. Toxicity from supplementation is extremely rare and requires massive doses acutely or very large doses (greater than 10,000 IUs per day) for long periods of time. Replenishment requires extra care in primary hyperparathyroidism (which can coexist with vitamin D deficiency) and secondary hyperparathyroidism (to ensure absence of primary hyperparathyroidism).6,7

Clinically, what really counts is not the vitamin D dose but the serum level achieved. For replenishment, follow-up testing may be required every three months to ascertain the effectiveness of dosing. Replenishment dosing will not equal maintenance dosing. Once the clinician has switched to maintenance dosing, then the testing frequency can be reduced significantly.

The definition of the normal reference range for 25-OH-vitamin D is controversial. The Institute of Medicine of the National Academy of Sciences recently lowered the internationally accepted definition of vitamin D sufficiency from 30 ng/mL to 20 ng/mL. This was based on extrapolations of the best value for clinical outcomes related to bone health.8 In contrast, the Endocrine Society recently recommended a serum level of 40-60 ng/mL for optimal clinical outcomes for overall health.9 These contradictory statements mean that more prospective randomized trials are needed.

For the laboratorian, the implications of the new awareness of the prevalence of vitamin D deficiency are clear: going forward, there will be significantly more testing done in various lab environments. DiaSorin, Inc., provides excellent options for vitamin D assays. In 1996 DiaSorin’s radioimmunoassay (RIA) was the first FDA-cleared device to measure circulating 25(OH)D levels to be used in the assessment of vitamin D sufficiency. In 2004 the company released the LIAISON® 25 OH Vitamin D assay. It was the first fully automated antibody-based chemiluminescent FDA-cleared assay to provide the laboratory with the time-to-first-result of 35 minutes. Three years later, the improved LIAISON 25 OH Vitamin D TOTAL Assay was FDA-cleared, providing laboratories with a more precise assay. This year, DiaSorin will introduce its LIAISON XL, which will offer a higher throughput solution for vitamin D and other specialty assays (180 tests per hour).

Gregory A. Plotnikoff, MD, MTS, FACP, is senior consultant for the Minneapolis-based Allina Center for Health Care Innovation, and is a member of the Vitamin D Scientific Advisory Board for Stillwater, Minnesota-based DiaSorin, Inc.


  1. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86:50-60.
  2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281.
  3. Hall LM, Kimlin MG, Aronov PA, et al. Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations. Nutrition. 2010;140: 542-550.
  4. Johnson MA, Fischer JG, Park S. Vitamin D deficiency and insufficiency in the Georgia Older Americans Nutrition Program. Nutr Elder. 2008;27 29-46.
  5. Holmes VA, Barnes MS, Alexander HD, et al. Vitamin D deficiency and insufficiency in pregnant women: a longitudinal study. Br J Nutr. 2009;102:876-881.
  6. Heaney RP, Vieth R, Hollis BW. Vitamin D efficacy and safety. Arch Intern Med. 2011;171:266.
  7. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr Rev. Oct 2008;66(10 Suppl 2):S178-181.
  8. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. Clin Endocrin Metab. 2011;96:53-58.
  9. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. Clin Endrocrinol Metab. 2011;96:1911-1930.

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