Vitamin D Deficiency — Identifying and Managing At-Risk Patients
National data demonstrate a marked decrease in vitamin D levels in the U.S. population over recent decades, prompting the assessment that we are facing a growing epidemic of vitamin D insufficiency.1 With the onset of Fall, and hours of sunlight declining, it’s an appropriate time for physicians to be thinking about vitamin D. Which patients are at risk for vitamin D deficiency? Who should be screened? Who should be receiving a vitamin D supplement?
These are just some of the questions Dr. Vin Tangpricha, Associate Professor of Medicine, Emory University School of Medicine, believes physicians should be asking themselves right now. He discusses the benefits of vitamin D, optimal vitamin D levels and approaches for managing patients at-risk for vitamin D deficiency.
Role of Vitamin D
“There are ‘classic’ and ‘non-classic’ roles for vitamin D,” says Dr. Tangpricha. “The classic role - the one that’s widely recognized - is in maintaining normal calcium homeostasis and proper mineralization of the skeleton. People need optimal vitamin D status to maintain good calcium levels in the blood and to have enough mineral for their bones.”
“The non-classic roles,” he continues, “are the exciting ones, the areas that have been explored over the past ten to twenty years.” The most significant of these is the role vitamin D plays in the immune system to fight infection or to impact different autoimmune diseases. Other areas that have been widely studied are its role in the prevention of cancer, cardiovascular disease and diabetes.
Following the discovery of 1alpha-hydroxylase, an enzyme that activates vitamin D in the tissues of many different organs, vitamin D is now being studied in relation to several hundred diseases, explains Dr. Tangpricha. “Once researchers found this enzyme they went back and looked at large population-based studies and have found an association between low vitamin D and the risk of various chronic diseases.”
Optimal Vitamin D Levels
Dr. Tangpricha notes that there is some debate about the optimum level for vitamin D. “The best marker for vitamin D is 25-hydroxy vitamin D (25(OH)D),” he says. “By itself that’s just one marker of vitamin D status, so we’re trying to identify other associate markers that indicate good health. The research indicates that calcium is best absorbed with a 25(OH)D level greater than 30 nanograms (ng) per ml. People have also looked at maximal suppression of parathyroid hormone and, while there have been a lot of mixed results, there seems to be enough data to indicate that levels above 30 ng/ml result in the best suppression of parathyroid hormone.”
“The strength of the evidence regarding optimal 25(OH)D concentrations does vary from epidemiologic/cross-sectional studies to randomized controlled trials, so there is some controversy as to whether the level should be 20 ng/ml or 30 ng/ml. The Endocrine Society recommends 30 ng/ml because they’ve taken into consideration the entire body of evidence, not just randomized controlled trials, and included many studies suggesting a strong epidemiological association between vitamin D deficiency and risk of disease.2 But if you’re more conservative and want to consider only randomized controlled trials for skeletal benefits, you may believe a 25(OH)D of 20ng/ml is adequate for most healthy populations for skeletal health.”
Vitamin D Deficiency
The lack of consensus on the ‘right’ vitamin D level has led to a debate about when to consider if someone is vitamin D deficient. “Most people won’t question that a level less than 10 ng/ml is severely low and should be treated,” says Dr. Tangpricha. “But where do you draw the line? Do you treat everyone below 20 ng/ml or below 30 ng/ml? That’s where there’s still a debate. The Endocrine Society guidelines recommend everyone should be above 30 ng/ml,2 whereas The Institute of Medicine states that most people should be at least above 20 ng/ml.3 It’s been demonstrated that a large proportion in the U.S. actually are deficient even using the lower cut-off for 25(OH)D1, and furthermore most practicing endocrinologists believe that 30 ng/ml is the healthy level.”
There is a growing body of evidence that vitamin D deficiency can have serious health consequences. “We don’t yet have strong randomized controlled trials but we have a lot of cross-sectional data showing that with vitamin D deficiency there’s an increased risk of heart attack, of cancer, and of developing infection.” The focus for research now is to establish whether an increased level of vitamin D can prevent the disease developing. “My personal opinion is that vitamin D is not a very toxic substance,” says Dr. Tangpricha, “so if your level’s low and there’s some chance of benefit, it’s still prudent to give a vitamin D supplement.”
Declining Vitamin D Levels and Ethnic Differences in the United States
A comparison of serum 25(OH)D levels from the Third National Health and Nutrition Examination Survey (NHANES III), collected during 1988 through 1994, with NHANES data collected from 2001 through 2004 (NHANES 2001-2004) indicated levels in the U.S. are falling. The mean serum 25(OH)D level was 30 ng/mL during NHANES III and decreased to 24 ng/mL during NHANES 2001-2004. At the same time the prevalence of 25(OH)D levels of less than 10 ng/mL increased from 2% to 6%, and 25(OH)D levels of 30 ng/mL or more decreased from 45% to 23%. These trends were consistent across all ages.1
While there may be no clinically significant differences between age groups and genders in prevalence of vitamin D deficiency, there are marked racial/ethnic differences, which may help to explain known racial/ethnic disparities in cardiovascular disease, cancer, and other major health conditions. Nearly all non-Hispanic blacks (97%) and most Mexican-Americans (90%) now have vitamin D insufficiency. The prevalence of 25(OH)D levels of less than 10 ng/mL in non-Hispanic blacks rose from 9% during NHANES III to 29% during NHANES 2001-2004, with a corresponding decrease in the prevalence of levels of 30 ng/mL or more from 12% to 3%.
Increased sunscreen use with a higher sun protection factor, decreased outdoor activity and obesity are all recognized as likely factors contributing to vitamin D insufficiency. It has been suggested that vitamin D supplementation, particularly during the winter months and at higher latitudes, and judicious sun exposure would improve vitamin D status and likely improve the overall health of the US population.1
At Risk Groups
Dr. Tangpricha believes the emphasis for screening of vitamin D levels should be on those groups most at risk for vitamin D deficiency: “First of all people with osteoporosis. These individuals obviously have a need for optimizing their calcium and skeletal mineralization and so should definitely be screened for vitamin D deficiency.”
“Another group who should be screened are those who are chronically ill, don’t go outside very much, and may be at risk of infections or cardiovascular disease. Obese people are at risk of vitamin D deficiency, as are those who are institutionalized, such as in a nursing home.”
“In summary, people who are ill and seeing physicians for different chronic diseases, that may be impacted by vitamin D, should be screened.”
Within the pediatric population Dr. Tangpricha observes there’s been a lot of focus on the breast-fed child. “Those children definitely need some supplementation because breast milk has very little vitamin D. Vitamin D drops are the best way to provide vitamin D to young children, while for more school-aged children a multi-vitamin will usually be sufficient. Children are not often screened for vitamin D deficiency, unless they have some kind of growth disorder or some kind of malabsorptive disorder, but a daily vitamin D supplement, especially during the winter months, is usually a good idea.”
Finally, given the prevalence of vitamin D insufficiency among non-Hispanic blacks and Hispanic-Americans, physicians should consider vitamin D testing for patients in these groups.
Toward Test Standardization
When ordering vitamin D tests physicians should ensure that it is 25-hydroxy vitamin D (25(OH)D) being tested, notes Dr. Tangpricha, as that is what provides a true indication of vitamin D status. “It’s also important to make sure the laboratory performing the testing is complying with good quality control, because there’s a lot of variability in 25(OH)D measurement.” In fact an initiative has been launched by the NIH National Institute of Standards and Technology, in collaboration with the Centers for Disease Control and Prevention (CDC)–to standardize the laboratory measurement of vitamin D status. Participating laboratories will be certified to indicate whether they comply with the established standards of 25(OH)D measurement.4
As the body of evidence grows about the role of vitamin D in disease prevention, this initiative to standardize 25(OH)D testing will be critical to improve the detection, evaluation and treatment of vitamin D deficiency.4
- Ginde A, Liu M, Camargo C Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009 Mar 23;169(6):626-32.
- Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice. Holick et al. J Clin Endocrinol Metab, July 2011, 96(7)
- Dietary Reference Intakes for Calcium and Vitamin D. Institute of Medicine of the National Academies. http://books.nap.edu/openbook.php?record_id=13050&page=8. Accessed Sept 23, 2013
- ODS Vitamin D Initiative.The Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH)
- http://ods.od.nih.gov/Research/VitaminD.aspx. Accessed Sept 23, 2013