Same 25(OH)D, different risk level
In their poster, Dr. Yazdi and colleagues explain that to assess vitamin D status “one needs to understand regulation of vitamin D metabolism.” 25(OH)D undergoes two alternative fates: 1α-hydroxylation in the kidney, generating 1,25D (the biologically active form) or 24-hydroxylation leading to 24,25D (a biologically inactive metabolite).
For their study, they analyzed pilot data from 11 otherwise healthy individuals who had total baseline plasma 25(OH)D levels < 20 ng/mL, and compared 25(OH)D, 1,25D, 24,25D, and parathyroid hormone before versus after treating them with vitamin D3 supplementation of 50,000 IU per week for 4-6 weeks, aiming for a total 25D level above 30 ng/mL.
They then modeled how the body maintains 1,25D in a normal range and calculated/compared two vitamin D metabolite ratios in vitamin D deficient versus sufficient states: 25(OH)D/1,25D and 1,25D/24,25D. They then evaluated the applicability of these ratios for assessment of vitamin D status.
They explained that suppression of 24-hydroxylase is the first line of defense to maintain 1,25D levels. Secondary hyperparathyroidism is the second line of defense and occurs in severe vitamin D deficiency when the first line is maximally deployed.
Overall, there was poor correlation between 25[OH]D and 1,25D, “consistent with previous evidence that in mild to moderate vitamin D deficiency, 1,25D is maintained in the normal range, and therefore not a useful index for assessing vitamin D status,” the researchers said in their poster.
Hence, they said, the need to add the ratio of 1,25D/24,25D.
They presented a comparison of two study participants: one with a baseline 25[OH]D of 12.3 ng/mL, the other of 11.7 ng/mL. Although both would therefore be classified as deficient according to current guidelines, their 1,25D/24,25D ratios were 20 and 110, respectively.
In the first participant, the parathyroid hormone response to vitamin D supplementation was negligible, at +5%, compared with a dramatic 34% drop in the second participant.
“We think only the one with very high 1,25D/24,25D [ratio of 110] and a significant drop in parathyroid hormone after vitamin D supplementation [-34%] was vitamin D deficient,” the researchers said.
However, Dr. Taylor noted: “The diagnostic cut-offs we describe should be viewed as tentative for the time being. Additional research will be required to fully validate the optimal diagnostic criteria.”
Dr. Yazdi and Dr. Rosen have reported no relevant financial relationships. Dr. Taylor has reported being a consultant for Ionis Pharmaceuticals.
A version of this article originally appeared on Medscape.com.