Vitamin D deficiency

JoAnn E. Manson, Patsy M. Brannon, Clifford J. Rosen, Christine L. Taylor.  Vitamin D Deficiency — Is There Really a Pandemic? N Engl J Med 2016; 375:1817-1820.

In recent years, numerous clinical research articles have concluded that large proportions of North American and global populations are “deficient” in vitamin D.  Most of the evidence cited focuses on one of two observations: that many people have serum concentrations of vitamin D (i.e., 25-hydroxyvitamin D [25(OH)D]) below 20 ng per milliliter (50 nmol per liter), which the Institute of Medicine (IOM) estimated in 2011 was the appropriate level4; or that supplementation with 600 to 800 IU per day — the IOM Recommended Dietary Allowance (RDA) for adults — or more fails to achieve serum concentrations above 20 ng per milliliter in some study participants. Such conclusions, however, are based on misinterpretation and misapplication of the IOM reference values for vitamin D. Because such misunderstandings can have adverse implications for patient care, including unnecessary vitamin D screening and supplementation as well as escalating health care costs due to overscreening and overtreatment, it’s important to clarify the meaning of IOM reference values for vitamin D as they relate to both population health and clinical practice.

To understand the concept of nutrient “deficiency” or “inadequacy,” one needs to know how the IOM nutrient reference values are defined and what they reflect. The IOM develops these reference values, referred to as Dietary Reference Intakes (DRIs), for an array of nutrients. Central to the DRI concept is the biologic reality that the need for any nutrient varies from person to person, generally in a normal distribution across the population. These reference values include an Estimated Average Requirement (EAR) for the nutrient, which is the median of the distribution of human requirements. The EAR reflects the most likely requirement for the population, whereas a second DRI reference value, the RDA, reflects the estimated requirement for people at the highest end of the distribution. Practically everyone in the population (at least 97.5%, or within 2 SD of the median) will have a requirement below the RDA.

Because of vitamin D’s established role in bone health (postulated nonskeletal benefits remain under study), the EAR is set at 400 IU per day for persons 1 to 70 years of age and 600 IU per day for persons older than 70 — intakes corresponding to a serum 25(OH)D level of 16 ng per milliliter (40 nmol per liter). The RDAs are 600 IU per day and 800 IU per day, respectively, corresponding to a serum 25(OH)D level of 20 ng per milliliter (50 nmol per liter). Note that the EAR and RDA assume minimal to no sun exposure…

A common misconception is that the RDA functions as a “cut point” and that nearly the entire population must have a serum 25(OH)D level above 20 ng per milliliter to achieve good bone health. The reality is that the majority (about 97.5%) of the population has a requirement of 20 ng per milliliter or less. Moreover, by definition of an average requirement, approximately half the population has a requirement of 16 ng per milliliter (the EAR) or less…

This problem highlights the concern that universal screening based on inappropriate cut points might lead to routine supplementation in generally healthy populations with adequate vitamin D levels. A preferable option would be to encourage patients and the public to choose foods containing, or fortified with, vitamin D — an approach that will be facilitated by new regulations requiring that vitamin D content be listed on nutrition labels.

Although our focus here is providing clarity about the use of nutrient reference values for estimating the prevalence of inadequacy in population groups, these values are also relevant to clinical settings in which patients are counseled individually. The two key clinical questions are whether to screen for vitamin D deficiency and what vitamin D intake to recommend for individual patients. For optimal decision making, the central issue is whether the patient is generally healthy and free of major risk factors for vitamin D deficiency or whether he or she has a skeletal disorder or significant risk factors for vitamin D deficiency (such as osteoporosis, osteomalacia, malabsorption, use of medications [such as anticonvulsants] that can affect vitamin D metabolism, or institutionalization). For healthy patients, routine screening is not recommended by most medical organizations, and the pitfalls would be similar to those described above for population-based studies.