New guidelines also advise people to limit their vitamin D supplementation to recommended daily doses
Clinical laboratories may eventually receive fewer doctors’ orders for vitamin D testing thanks to new guidelines released by the Endocrine Society. The new Clinical Practice Guideline advises against “unnecessary testing for vitamin D levels.” It also urges healthy people, and those 75-years of age or younger, to avoid taking the vitamin at levels above the daily recommended amounts, according to a news release.
Even though the Endocrine Society does recommend vitamin D supplements for certain groups, it advises individuals to hold off on routine testing. That’s because there appears to be uncertainty among ordering clinicians about what to do for patients based on their vitamin D test results.
“When clinicians measure vitamin D, they’re forced to decide what to do about it. That’s where questions about the levels come in. And that’s a big problem. So, what this panel is saying is ‘Don’t screen,’” Clifford Rosen, MD, Director of Clinical and Translational Research and Senior Scientist, Maine Medical Center Research Institute at the University of Maine, told Medscape Medical News.
“We have no data that there’s anything about screening that allows us to improve quality of life. Screening is probably not worthwhile in any age group,” he added.
“This guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them,” the author of the Endocrine Society guideline, Anastassios G. Pittas, MD (above), Professor of Medicine at Tufts University School of Medicine in Boston, told Medscape Medical News. This new guideline could result in doctors ordering fewer vitamin D tests from clinical laboratories. (Photo copyright: Tufts University.)
Vitamin D Screening Not Recommended for Certain Groups
The Endocrine Society’s new clinical guidelines advise healthy adults under 75 years of age to refrain from taking vitamin D supplements that exceed US Institute of Medicine—now the National Academy of Medicine (NAM)—recommendations.
Additionally, these updated guidelines:
Recommend vitamin D supplements at levels above NAM recommendations to help lower risks faced by children 18 years and younger, adults 75 and older, pregnant women, and people with prediabetes.
Suggest daily, lower-dose vitamin D (instead of non-daily, higher-dose of the vitamin) for people 50 years and older who have “indications for vitamin D supplementation or treatment.”
Advise “against routine testing for 25-hydroxyvitamin D [aka, calcifediol] levels” in all the above groups “since outcome-specific benefits based on these levels have not been identified. This includes 25-hyrdoxyvitamin D screening in people with dark complexion or obesity.”
One exception to the guideline applies to people with already established osteoporosis, according to the guideline’s author endocrinologist Anastassios G. Pittas, MD, Chief of Endocrinology, Diabetes and Metabolism; Co-Director, Tuft’s Diabetes and Lipid Center; and Professor of Medicine at Tufts University School of Medicine in Boston.
Vitamin D’s Link to Disease Studied
During a panel discussion at the Endocrine Society’s annual meeting, members acknowledged that many studies have shown relationships between serum concentrations of 25-hydroxy vitamin D (25(OH)D) and physical disorders including those of musculoskeletal, metabolic, and cardiovascular systems. Still, they questioned the link of vitamin D supplementation and testing with disease prevention.
“There is paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases. … What we really need are large-scale clinical trials and biomarkers so we can predict disease outcome before it happens,” said Panel Chair Marie Demay, MD, Endocrinologist, Massachusetts General Hospital, and Professor of Medicine, Harvard Medical School, Boston, Medscape Medical News reported.
Meanwhile, in their Journal of Clinical Endocrinology and Metabolism paper, the researchers note that use of supplements (1,000 IU or more per day) increased from 0.3% to 18.2%, according to the National Health and Nutrition Examination Survey (NHANES) conducted by the National Center for Health Statistics (NCHS), CDC, for the years 1999-2000 and 2013-2014.
“The use of 25(OH)D testing in clinical practice has also been increasing; however, the cost effectiveness of widespread testing has been questioned, especially given the uncertainty surrounding the optimal level of 25(OH)D required to prevent disease,” the authors wrote.
“Thus, the panel suggests against routine 25(OH)D testing in all populations considered,” the researchers stated at the Endocrine Society annual meeting.
Other Groups Weigh-in on Vitamin D Testing
Pathologists and medical laboratory leaders may recall the explosion in vitamin D testing starting about 20 years ago. Vitamin D testing reimbursed by Medicare Part B “increased 83-fold” during the years 2000 to 2010, according to data cited in an analysis by the American Academy of Family Physicians (AAFP).
Also, the US Preventive Services Task Force (USPSTF) said in a statement that there is not enough information to “recommend for or against” testing for vitamin D deficiency.
“No organization recommends population-based screening for vitamin D deficiency, and the American Society for Clinical Pathology recommends against it,” the USPSTF noted.
Clinical Laboratories Can Get the Word Out
The vitamin D debate has been going on for a while. And the latest guidance from the Endocrine Society may cause physicians and patients to stop ordering vitamin D tests as part of annual physicals or in routine screenings.
Medical laboratories can provide value by ensuring physicians and patients have the latest information about vitamin D test orders, reports, and interpretation.
Scientists believe useful new clinical laboratory assays could be developed by better understanding the huge number of ‘poorly researched’ genes and the proteins they build
Researchers have added a new “-ome” to the long list of -omes. The new -ome is the “unknome.” This is significant for clinical laboratory managers because it is part of an investigative effort to better understand the substantial number of genes, and the proteins they build, that have been understudied and of which little is known about their full function.
The Unknome Database includes “thousands of understudied proteins encoded by genes in the human genome, whose existence is known but whose functions are mostly not,” according to a news release.
The database, which is available to the public and which can be customized by the user, “ranks proteins based on how little is known about them,” the PLOS Biology paper notes.
It should be of interest to pathologists and clinical laboratory scientists. The fruit of this research may identify additional biomarkers useful in diagnosis and for guiding decisions on how to treat patients.
“These uncharacterized genes have not deserved their neglect,” said Sean Munro, PhD (above), MRC Laboratory of Molecular Biology in Cambridge, England, in a press release. “Our database provides a powerful, versatile and efficient platform to identify and select important genes of unknown function for analysis, thereby accelerating the closure of the gap in biological knowledge that the unknome represents.” Clinical laboratory scientists may find the Unknome Database intriguing and useful. (Photo copyright: Royal Society.)
Risk of Ignoring Understudied Proteins
Proteomics (the study of proteins) is a rapidly advancing area of clinical laboratory testing. As genetic scientists learn more about proteins and their functions, diagnostics companies use that information to develop new assays. But did you know that researchers tend to focus on only a small fraction of the total number of protein-coding DNA sequences contained in the human genome?
The study of proteomics is primarily interested in the part of the genome that “contains instructions for building proteins … [which] are essential for development, growth, and reproduction across the entire body,” according to Scientific American. These are all protein-coding genes.
Proteomics estimates that there are more than two million proteins in the human body, which are coded for 20,000 to 25,000 genes, according to All the Science.
To build their database, the MRC researchers ranked the “unknome” proteins by how little is known about their functions in cellular processes. When they tested the database, they found some of these less-researched proteins important to biological functions such as development and stress resistance.
“The role of thousands of human proteins remains unclear and yet research tends to focus on those that are already well understood,” said Sean Munro, PhD, MRC Laboratory of Molecular Biology in Cambridge, England, in the news release. “To help address this we created an Unknome database that ranks proteins based on how little is known about them, and then performed functional screens on a selection of these mystery proteins to demonstrate how ignorance can drive biological discovery.”
In the paper, they acknowledged the human genome encodes about 20,000 proteins, and that the application of transcriptomics and proteomics has “confirmed that most of these new proteins are expressed, and the function of many of them has been identified.
“However,” the authors added, “despite over 20 years of extensive effort, there are also many others that still have no known function.”
They also recognized limited resources for research and that a preference for “relative safety” and “well-established fields” are likely holding back discoveries.
The researchers note “significant” risks to continually ignoring unexplored proteins, which may have roles in cell processes, serve as targets for therapies, and be associated with diseases as well as being “eminently druggable,” Genetic Engineering News reported.
Setting up the Unknome Database
To develop the Unknome Database, the researchers first turned to what has already come to fruition. They gave each protein in the human genome a “knownness” score based on review of existing information about “function, conservation across species, subcellular localization, and other factors,” Interesting Engineering reported.
It turns out, 3,000 groups of proteins (805 with a human protein) scored zero, “showing there’s still much to learn within the human genome,” Science News stated, adding that the Unknome Database catalogues more than 13,000 protein groups and nearly two million proteins.
The researchers then tested the database by using it to determine what could be learned about 260 “mystery” genes in humans that are also present in Drosophila (small fruit flies).
“We used the Unknome Database to select 260 genes that appeared both highly conserved and particularly poorly understood, and then applied functional assays in whole animals that would be impractical at genome-wide scale,” the researchers wrote in PLOS Biology.
“We initially selected all genes that had a knownness score of ≤1.0 and are conserved in both humans and flies, as well as being present in at least 80% of available metazoan genome sequences. … After testing for viability, the nonessential genes were then screened with a panel of quantitative assays designed to reveal potential roles in a wide range of biological functions,” they added.
“Our screen in whole organisms reveals that, despite several decades of extensive genetic screens in Drosophila, there are many genes with essential roles that have eluded characterization,” the researchers conclude.
Clinical Laboratory Testing Using the Unknome Database
Future use of the Unknome Database may involve CRISPR technology to explore functions of unknown genes, according to the PLOS Biology paper.
Munro told Science News the research team may work with other research efforts aimed at understanding “mysterious proteins,” such as the Understudied Proteins Initiative.
The Unknome Database’s ability to be customized by others means researchers can create their own “knownness” scores as it applies to their studies. Thus, the database could be a resource in studies of treatments or medications to fight diseases, Chemistry World noted.
According to a statement prepared for Healthcare Dive by SomaLogic, a Boulder, Colorado-based protein biomarker company, diagnostic tests that measure proteins can be applied to diseases and conditions such as:
“The 27-protein model has potential as a ‘universal’ surrogate end point for cardiovascular risk,” the researchers wrote in Science Translational Medicine.
Proteomics definitely has its place in clinical laboratory testing. The development of MRC-LMB’s Unknome Database will help researchers’ increase their knowledge about the functions of more proteins which should in turn lead to new diagnostic assays for labs.
