Vitamin D, a group of fat-soluble steroid hormones, is considered an essential vitamin for humans, particularly D3 (cholecalciferol), which is obtained from some animal-based products and ultraviolet light, and D2 (ergocalciferol), which is obtained from certain plants. Having adequate stores of vitamin D is necessary for calcium, magnesium, and phosphate absorption. Vitamin D deficiency can lead to a variety of diseases and impact our overall immune system. Vitamin D deficiency is often related to diet and lack of exposure to sunlight. However, there are other reasons why our absorption of vitamin D may be impaired.
Many of our patients in long-term care have an increased risk for vitamin D deficiency. Aging impacts how our skin absorbs sunlight and produces vitamin D3 (J Clin Invest
1985;76:1536–1538). Aging also affects the ability of the kidneys to process vitamin D’s active form (Endocrinol Metab Clin North Am
2013;42:319–332). Home-bound or institution-bound elderly persons also suffer from vitamin D deficiency due to lack of sun exposure (JAMA
1995;274:1683–1686; J Am Med Dir Assoc
2007;8:71–75). Certain medical conditions such as obesity can also affect vitamin D levels. The Centers for Medicare & Medicaid Service’s Local Coverage Determination (LCD) for vitamin D provides a further list of medical conditions that impact vitamin D levels (“Vitamin D; 25 Hydroxy, Includes Fraction(s), If Performed,” LCD ID L33771, rev. Oct. 29, 2020, https://go.cms.gov/3HGDHbI
Vitamin D deficiency impacts calcium, phosphorous, and bone metabolism (J Clin Endocrinol Metab
2011;96:1911–1930). As noted by Bess Dawson-Hughes, MD, of Tufts University School of Medicine’s Bone Metabolism Laboratory, patients who are deficient face an increased risk of osteomalacia (UpToDate
, Sept. 20, 2021; https://bit.ly/3qrI9Fy
). Vitamin D deficiency can thus impact extraskeletal health, which can cause more frequent falls in the elderly.
Vitamin D supplementation can prevent deficiency. Supplementation may also have a positive impact on cognitive and mental health, immune system function, cardiovascular health, and cancer prevention. But evidence supporting beneficial outcomes has been somewhat inconsistent to date.
Clinical Manifestations of Vitamin D Deficiency
The clinical manifestations of vitamin D deficiency vary. Dr. Dawson-Hughes notes in UpToDate that “the majority of patients with moderate to mild vitamin D deficiency ... are asymptomatic,” with normal serum calcium, phosphorus, and alkaline phosphatase levels but perhaps with elevated parathyroid hormones — this combination puts them “at increased risk for having accelerated bone loss.” Patients with severe and long-term deficiency, which can lead to osteomalacia, may have more obvious symptoms such as “bone pain and tenderness, muscle weakness, fractures, and difficulty walking.”
Screening for Vitamin D Deficiency
The serum 25(OH)D concentration is generally used to identify vitamin D deficiency. There is some controversy around appropriate concentrations, but the approximate levels include sufficiency as >20 ng/mL; insufficiency as 12 to 20 ng/mL; deficiency as <12 ng/mL; and toxicity as >100 ng/mL (see CMS LCD ID L33771).
The U.S. Preventive Services Task Force does not recommend routine screening for vitamin D deficiency in the general populace (JAMA 2021;325:1436–1442). However, routine screening for vitamin D levels is currently recommended for at least 30 clinical conditions, a list of which can be found in the CMS LCD (ID L33771). For high-risk individuals, 25 (OH)D levels should be remeasured three and four months down the line.
In vitamin D–deficient patients, Dr. Dawson-Hughes also suggests measuring “serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), electrolytes, blood urea nitrogen (BUN), creatinine, and tissue transglutaminase antibodies (if important to assess for celiac disease),” although routine assessment of bone mineral density is not recommended.
One could certainly make the case for routine screening in long-term care settings, but adhering to the diagnostic list and the limitations on the number of tests (also listed in CMS LCD ID L33771) is advisable. The laboratory assays are not inexpensive, and insurance companies will likely bill the patient for the cost of these tests if the appropriate diagnosis is not listed.
Optimal Vitamin D Intake to Prevent Deficiency
Different dosing regimens have been shown to effectively treat vitamin D deficiency, according to Dr. Dawson-Hughes. Although 50,000 international units (IU) once per week may make sense for some conditions, vitamin D “insufficient” individuals typically need 800 to 1,000 IU per day while those with “sufficient” serum levels may only need 600 to 800 IUs per day.
However, recent studies have found that vitamin D supplementation in vitamin D sufficient individuals may not be necessary. For instance, a 2022 review found that the supplementation of vitamin D in those who have sufficient levels does not “generate benefits for global health or major diseases or medical events such as cancer, cardiovascular events, T2DM, falls or fractures” (Nat Rev Endocrinol 2022; 18:96–110). However, the authors note that there are “probable beneficial effects of combined supplementation of calcium and vitamin D in older adults with poor vitamin D and calcium status on their risks of fracture or falls.” A 2014 umbrella review of systematic reviews and meta-analyses found that there is insufficient evidence for the “effectiveness of vitamin D only supplementation for prevention of osteoporosis or falls” (BMJ 2014;348:g2035).
The current National Institutes of Health recommended dietary allowance by age includes 800 IU for adults older than 70 (Office of Dietary Supplements, “Vitamin D: Fact Sheet for Consumers,” Aug. 17, 2021; https://bit.ly/3fMtQp4
). Because some supplements, such as multivitamins, already contain vitamin D, it is important for care staff to ask what residents are already taking. In addition to vitamin D supplementation, calcium supplementation is also necessary.
The CMS LCD also notes that “patients receiving vitamin D supplementation should also be assessed for vitamin D toxicity and disorders of calcium and phosphorus metabolism.” The symptoms of vitamin D toxicity include “nausea, vomiting, poor appetite, constipation, weakness, and weight loss, as well as elevation in the blood level of calcium which in turn can lead to mental status changes, and heart rhythm abnormalities.”
Vitamin D Levels, Mortality, and the Pandemic
In 2012, a prospective cohort study found that vitamin D deficiency was associated with increased mortality among elderly female nursing home residents in Austria (J Clin Endocrinol Metab 2012;97:E653–E657). The authors found that “the majority of elderly institutionalized women were vitamin D deficient in winter,” with a “significantly increased mortality risk in those patients with the lowest 25(OH)D levels.”
A 2014 meta-analysis of eight cohort studies from Europe and the United States showed that those persons in the lowest quintile of vitamin D concentrations were associated with increased all-cause and cardiovascular mortality (BMJ 2014;348:g3656). The authors also noted that two recent systematic reviews of randomized trials confirmed the link between vitamin D and mortality; however, “the effects were weaker than suggested by observational studies, and vitamin D supplementation seemed to be effective only for the administration of vitamin D3 in subjects with low 25(OH)D levels at baseline.”
In 2020, after researchers began to report a link between vitamin D deficiency and a greater risk of COVID-19 infection (JAMA Netw Open 2020;3:e2019722), a quasi-experimental study on vitamin D and survival in COVID-19 patients came to the conclusion that in frail elderly residents “bolus vitamin D3 supplementation taken during or just before COVID-19 was associated with less severe COVID-19 and better survival rate” (J Steroid Biochem Mol Biol 2020;204:105771). The proposed mechanisms included vitamin D’s modulation of the renin-angiotensin system, thereby reducing pulmonary permeability; the antiviral effects of vitamin D, as documented in many studies; and the stabilizing effect of vitamin D on physical barriers, thereby preventing the virus from reaching tissues as readily. By contrast, corticosteroids, hydroxychloroquine, and dedicated antibiotics showed no predictive difference.
In 2021, a systematic review of eight studies provided “strong evidence that low D3 is a predictor rather than just a side effect of [COVID-19] infection” (Nutrients 2021;13:3596), with the clinical conclusion that “at a threshold level of 30 ng/mL, mortality decreases considerably.” The authors recommended vaccination alongside routine strengthening of the immune system by vitamin D supplementation. Blood levels above 50 ng/mL allow us the best opportunity to get the SARS-CoV2 pandemic under control.
People living in long-term care and assisted living are at increased risk for hypervitaminosis D for many different reasons.
Recommendations to replete vitamin D to a level above 20 ng/mL may be adequate to prevent osteomalacia.
The hormonal and epigenetic effects of vitamin D may make it an important although not yet fully recognized tool in the prevention of viral infections with inflammatory respiratory components, including the SARS-CoV2 virus.
The beneficial effects of vitamin D might require a level above 50 ng/mL, which necessitates checking vitamin D levels.
Guidelines are available that show the indications for and the needed frequency of testing, which is reimbursed by CMS.
There is little empiric evidence that vitamin D supplements improve health and care outcomes in vitamin D sufficient adults.
Dr. Hector is a certified medical director, board certified in family practice, with a CAQ in geriatrics, who currently works in Tucson, AZ, as a clinical associate professor in the Division of Geriatrics, Palliative Care, and General Internal Medicine at the University of Arizona.