Common Questions
How is vitamin D deficiency determined?
The serum 25-OH vitamin D3 level is the best test for determining a vitamin D deficiency. If there is a high level of clinical concern for vitamin D deficiency and a low-normal 25-OH vitamin D3 level is found, serum parathyroid hormone (PTH) concentration and/or a 24-hour urine calcium should be checked.
The laboratory definition of the lower limit of the optimal range of vitamin D is extremely controversial. Reference ranges, based on population studies, vary considerably among laboratories. For example, in the United Kingdom, where there is relatively less light exposure (higher latitude) and less fortified food than in the United States, the lowest reference range lower limit is 3 ng/mL (8 mM/L). In contrast, the lower limit in some laboratories in the United States is 18 ng/mL (45 mM/L) (1).
The lack of standardization, in addition to different measuring methods, has made it difficult to define the level of deficiency. This variability has led to recommendations to abandon the lower limit of the normal range for serum 25-OH vitamin D3 and use a "target" concentration of 25-OH vitamin D3 instead, the latter derived from PTH measurements. Many experts feel that vitamin D deficiency is the 25(OH) vitamin D level where the mean PTH concentration starts to increase in population studies (2).
This method eliminates geographical and seasonal variations that affect population-based normal ranges. With this "physiologic" approach, the optimal lower limit of 25-OH vitamin D3 has been found to be around 30 to 32ng/mL (70 to 80 mM/L)(3).
These recommendations take into account studies showing that some patients with 25-OH vitamin D3 levels in the low end of the "normal range" have clinical and pathologic evidence of vitamin D insufficiency, as indicated by an elevated PTH reflecting increased bone turnover and mild osteomalacia. However, the more conventional level currently used in laboratories is in the range of 15-20 ng/ml.
Although 1,25-(OH)2 vitamin D3 is the biologically active metabolite of vitamin D, it is not a good measure of vitamin D status. When patients are vitamin D deficient, the parathyroid hormone increases and stimulates renal 1-alpha-hydroxylase, so that 1,25-(OH)2 vitamin D3 levels increase. It is only with severe vitamin D deficiency that a deficiency of 1,25-(OH)2 vitamin D3 occurs. Therefore, earlier stages of vitamin D deficiency can be missed by measuring 1,25-(OH)2 vitamin D3.
- Utiger RD. The need for more vitamin D. N Engl J Med 1998; 338: 828-829.
- Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 2005; 35: 317-22.
- Chapuy MC, Preziosi P, Maamer M, Amaud S, Galan P, Hercberg C, Meunier PJ. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 1997; 7: 439-443.