Low vitamin D status: definition, prevalence, consequences, and correction

Abstract

Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D(3) (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D(2) (ergocalciferol) and D(3). An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be approximately 30 to 32 ng/mL or above. Using this definition, it has been estimated that approximately three-quarters of all adults in the United States have low levels. Low vitamin D status classically has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various nonskeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with "high" amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D(3) may be preferable to vitamin D(2).

Figure 1. Spectrum of Vitamin D Status

The spectrum of low vitamin D status is depicted. At very low vitamin D levels, (25[OH]D of approximately 10 ng/ml or below) calcium malabsorption, osteomalacia/rickets and myopathy occur. Less marked vitamin D deficiency (often referred to as inadequacy or insufficiency) has been associated with a variety of adverse health consequences. Consensus regarding an “optimal” 25(OH)D concentration continues to evolve, however there appears to be increasing agreement that values above approximately 30-32 ng/ml are associated with optimal physiologic function.

Figure 2. Distribution of Serum 25(OH)D in Highly Sun-exposed Adults

In these two studies in which the average total body sun exposure was approximately 11 hours per week, a broad, and somewhat Gaussian, distribution of circulating 25(OH)D is apparent. Data adapted from Binkley, et. al., and Barger-Lux, et. al. Note that the Barger-Lux, et. al., study utilized a 25(OH)D assay that measures approximately 10% higher than the HPLC assay used in the Binkley, et. al., report.

Figure 3. Prevalence of Low Vitamin D Status in Various Populations

In these recent cohort studies, low vitamin D status, whether defined as a 25(OH)D below 20 ng/ml or below 30 ng/ml is extremely common. Data adapted from various sources.^{, -}

Figure 4. Variable Response to Daily Vitamin D₃

In these seven Caucasian older adults (age 66-88 years), all of whom started the study with a 25(OH)D level less than 30 ng/ml, the variable response to daily administration of 1,600 IU vitamin D₃ is apparent.