Some vitamin D tests may give misleading results despite progress made in recent years to improve the quality of these assays, according to the US Centers for Disease Control and Prevention (CDC).
Otoe Sugahara, BS, manager of the CDC Vitamin D Standardization-Certification Program (VDSCP), presented an update of her group's work at ENDO 2024, the Endocrine Society's annual meeting in Boston.
"Though most vitamin D tests in our program have improved, there still remain some sample-specific inaccuracies. The CDC is working with program participants to address these situations," Sugahara said in a statement released by the Endocrine Society.
For example, some assays measure other compounds besides 25-hydroxyvitamin D, which can falsely elevate results of some blood samples, Sugahara reported. Thus, some tests may be misclassified, with results seen as sufficient from samples that should have indicated a vitamin D deficiency.
"While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients," Sugahara and coauthors said in an abstract provided by the Endocrine Society.
Sugahara's report provided a snapshot of the state of longstanding efforts to improve the quality of a widely performed service in US healthcare: testing vitamin D levels.
These include an international collaboration that gave rise in 2010 to a vitamin D standardization program, from which the CDC's VDSCP certification emerged. Among the leaders of these efforts was Christopher Sempos, PhD, then with the Office of Dietary Supplements at the National Institutes of Health.
Many clinicians may not be aware of the concerns about the accuracy of vitamin D tests that led to the drive for standardization, Sempos, now retired, told Medscape Medical News. And, in his view, it's something that busy practitioners should not have to consider.
"They have literally thousands of diseases they have to be able to recognize and diagnose," Sempos said. "They should be able to count on the laboratory system to give them accurate and precise data."
'Nudging' Toward Better Results
The CDC's certification program gives labs and companies detailed information about the analytical accuracy and precision of their vitamin D tests.
This feedback has paid off with improved results, Andy Hoofnagle, MD, PhD, professor of laboratory medicine and pathology at the University of Washington in Seattle, told Medscape. It helps by "nudging manufacturers in the right direction," he said.
"Some manufacturers reformulated, others recalibrated, which is a lot of effort on their part, so that when the patient get a number, it actually means the right thing," said Hoofnagle, who is also chair of the Accuracy-Based Programs Committeeof the College of American Pathologists.
"There are still many immunoassays on the market that aren't giving the correct results, unfortunately, but the standardization certification program has really pushed the field in the right direction," he said.
US scientists use two main types of technologies to measure vitamin D in the blood, Sugahara said. One is mass spectrometry, which separately measures 25-hydroxyvitamin D2 and D3 and sums the values. The other type, immunoassay, measures both compounds at the same time and reports one result for total 25-hydroxyvitamin D.
At the ENDO 2024 meeting, Sugahara reported generally positive trends seen in the VDSCP. For example, the program looks at specific tests' bias, or the deviation of test results from the true value, as determined with the CDC's reference method for vitamin D.
Average calibration bias was less than 1% for all assays in the VDSCP in 2022, Sugahara said. The average calibration bias for immunoassays was 0.86%, and for assays using mass spectrometry, it was 0.55%, Sugahara reported.
These are improved results compared with 2019 data, in which mass spectrometry–based assays had a mean bias of 1.9% and immunoassays had a mean bias of 2.4%, the CDC told Medscape Medical News in an email exchange.
The CDC said the VDSCP supports laboratories and researchers from around the world, including ones based in the US, China, Australia, Japan, and Korea.
Call for Research
Vitamin D tests are widely administered despite questions about their benefit for people who do not appear likely to be deficient of it.
The Endocrine Society's newly released practice guideline recommends against routine testing of blood vitamin D levels in the general population.
Laboratory testing has increased over the years owing to studies reporting associations between blood vitamin D [25(OH)D] levels and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases, wrote Marie B. Demay, MD, of Harvard Medical School in Boston, and coauthors in the new guideline. It was published on June 3 in The Journal of Clinical Endocrinology & Metabolism.
'"Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population," they wrote.
It's uncertain that "any putative benefits of screening would outweigh the increased burden and cost, and whether implementation of universal 25(OH)D screening would be feasible from a societal perspective," Demay and coauthors added.
They noted that the influential US Preventive Services Task Force also has raised doubts about widespread use of vitamin D tests.
The USPSTF has a somewhat different take from the Endocrine Society. The task force in 2021 reiterated its view that there is not enough evidence to recommend for or against widespread vitamin D testing for adults. The task force gave this test an I grade, meaning there is insufficient evidence to weigh the risks and benefits. That's the same grade the task force gave it in 2014.
The USPSTF uses a grade of D to recommend against use of a test or service.
In an interview with Medscape Medical News, John Wong, MD, vice chair of the USPSTF, reiterated his group's call for more research into the potential benefits and harms of vitamin D screening.
One of the challenges in addressing this issue, Wong noted, has been the variability of test results. Therefore, efforts such as the CDC's VDSCP in improving test quality may help in eventually building up the kind of evidence base needed for the task force to offer a more definitive judgment on the tests, he said.
Wong acknowledged it must be frustrating for clinicians and patients to hear that experts don't have the evidence needed to make a broad call about whether routine vitamin D tests are beneficial.
"We really would like to have that evidence because we recognize that it's an important health question to help everybody in this nation stay healthy and live longer," Wong said.
