There is no absolute consensus as to what a normal range for 25(OH)D should be. Part of the difficulty is how a normal range is determined, i.e., typically it is done by obtaining blood from several hundred volunteers and deeming them to be normal and to perform the measurement of the analyte and do a distribution with a mean ± 2SD as the normal range. However, since it is now recognized that 30-50% of both the European and US population are vitamin D insufficient or deficient, the previously reported normal ranges of 10-55 ng/ml are totally inadequate.1, 4, 16, 20-23
Chapuy et al24
reported that a dot plot of serum 25(OH)D levels as a function of PTH levels provided an insight as to what the serum 25(OH)D levels should be to be considered sufficient. They observed that the PTH levels began to plateau at their nadir when 25(OH)D levels were between 30-40 ng/ml. A similar observation was made by Thomas et al and Holick et al.14
FIG. 2 A, Mean (±SE) serum PTH (picograms per milliliter) by serum 25(OH)D subgroups. Subject PTH concentrations (picograms per milliliter) relative to serum 25(OH)D concentrations sorted by subgroups delineated by predefined cutoffs for analyses of (more ...)
Malabanan et al26
did provocative testing by giving healthy adults who had a 25(OH)D of between 11 and 25 ng/ml, 50,000 IU of vitamin D once a week for 8 weeks. At the end of 8 weeks, it was observed that 25(OH)D levels increased on average by more than 100%. An analysis of the change in PTH levels for each of the subjects revealed that on average, the mean decrease on PTH levels declined by 55% in subjects who had 25(OH)D between 11-15 ng/ml and declined by 35% for those with 25(OH)D levels of between 16-19 ng/ml. Those subjects who had 25(OH)D > 20 ng/ml had no significant change in their PTH level. () Thus, based on the provocative testing, it was suggested that vitamin D deficiency should be defined as 25(OH)D above 20 ng/ml. Heaney et al 27
measured the efficiency of intestinal calcium absorption in women who had on average a 25(OH)D of 20 ng/ml and then in the same women who received 25(OH)D3
to raise their blood level on average to 32 ng/ml. They reported a 45-65% increase in the efficiency of intestinal calcium transport when women were able to achieve a 25(OH)D of > 32 ng/ml.
Figure 3 (A) Serum levels of 25(OH)D (-Δ-) and PTH (-o-) before and after therapy with 50,000 IU of vitamin D2 and calcium supplementation once a week for 8 weeks. (B) Serum levels of PTH levels in patients who had serum 25(OH)D levels of between 10 and (more ...)
With all of this information collectively, most experts now agree that vitamin D deficiency should be defined as a 25(OH)D of < 20 ng/ml. Vitamin D insufficiency is now recognized as a 25(OH)D of 21-29 ng/ml. The preferred level for 25(OH)D is now recommended by many experts to be > 30 ng/ml.1, 4, 28
The upper limit of normal has also been questioned.4, 29, 30
The upper limit being 55 ng/ml seemed to be inadequate especially since lifeguards who are exposed to a lot of sunlight typically have reported levels of 100-125 ng/ml.4, 16, 29
There has never been a reported case of vitamin D intoxication from sun exposure, and lifeguards have not been reported to be vitamin D intoxicated. Based on the literature, it appears that vitamin D intoxication does not occur until blood levels are above 150-200 ng/ml.31, 32
Vitamin D intoxication is defined as a 25(OH)D > 150 ng/ml that is associated with hypercalcemia, hypercalciuria and often hyperphosphatemia.
Based on all of this information, many of the reference laboratories are now using a normative range for 25(OH)D to be 20-100ng/ml. However, several reference laboratories are also recognizing the recommendation by some experts that a preferred level of > 30 ng/ml is most desirable.
At least two of the reference laboratories are now using LC-MS routinely to measure 25(OH)D. Since they are able to quantitatively measure 25(OH)D2 and 25(OH)D3, they report them out as individual levels. They also report the total 25(OH)D which is summation of 25(OH)D2 and 25(OH)D3. Physicians only need to be aware of the total 25(OH)D level.