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By Traci Pantuso, ND, MS
Adjunct Faculty, Research Investigator, Bastyr University, Seattle
Dr. Pantuso reports no financial relationships relevant to this field of study.
SYNOPSIS: The authors investigated the trends in daily supplemental vitamin D intake of ≥ 1,000 IU and ≥ 4,000 IU and found increasing use of vitamin D supplementation.
SOURCE: Rooney MR, Harnack L, Michos ED, et al. Trends in use of high-dose vitamin D supplements exceeding 1000 or 4000 International Units daily, 1999-2014. JAMA 2017;317:2448-2450.
Vitamin D is a fat-soluble vitamin that either is consumed through dietary sources or synthesized when skin is exposed to ultraviolet light.1 The benefits of adequate vitamin D intake are well demonstrated in the skeletal system, as severe vitamin D deficiency results in rickets in children and osteomalacia in adults.1,2 The role of vitamin D in extraskeletal health is not well understood. Most evidence to support its use is from association and observational studies.1,3,4 Some consider hypovitaminosis D, which is caused by low levels of vitamin D naturally occurring in foods and a lack of sufficient sunlight exposure, to be a pandemic worldwide.5 Individuals with more melanin in their skin and those who use sunblock demonstrate lower rates of vitamin D synthesis resulting from sunlight exposure.4,5 Because of inadequate dietary intake of vitamin D and decreased synthesis from sunlight exposure, many individuals require oral vitamin D supplementation.1-8
To assess the changes in vitamin D intake from 1999 to 2014 and investigate trends of use, Rooney et al used repeat cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), which samples U.S. residents who are not institutionalized. The authors excluded participants who were pregnant, were < 20 years of age, or for whom incomplete information about supplement use was available. Participants self-reported vitamin D supplement use for 30 days. They were asked to bring supplement bottles to aid in reporting. A vitamin D supplementation level of ≥ 1,000 IU and ≥ 4,000 IU was calculated for each NHANES survey period. The researchers used Stata to analyze the data and calculated linear trends. A two-sided P value of < 0.05 was considered statistically significant. The study included 39,243 participants, with a mean age of 46.6 years (standard deviation, 16.8), 51.1% women, and 69.7% self-reported as non-Hispanic white. A significant difference was found in the prevalence of vitamin D use of 1,000 IU per day between 1999 and 2000 and 2013 and 2014. Use of vitamin D ≥ 1,000 IU in the 2013-2014 group was significantly higher at 18.2% (95% confidence interval [CI], 16.0-20.7%) compared to the 1999-2000 group, when use was 0.3% (95% CI, 0.1-0.5%; P for trend < 0.001). The use of ≥ 4,000 IU vitamin D prior to the 2005-2006 period was < 0.1% and was 3.2% (95% CI, 2.5-4.0%) in the 2013-2014 period.
The authors did not differentiate between vitamin D2 and vitamin D3 supplements. The increases in vitamin D supplement intake were found in most age groups, races/ethnicities, and both sexes. The use of ≥ 1,000 IU in the 2013-2014 group was highest in women (25.9%; 95% CI, 22.8-29.3%), non-Hispanic white individuals (21.8%; 95% CI, 19.3-24.6%), and those who were ≥ 70 years of age (38.5%; 95% CI, 31.8-45.7%). The use of ≥ 4,000 IU in the 2013-2014 group was highest in women (4.2%; 95% CI, 3.0-5.7%), non-Hispanic white individuals (3.9%; 95% CI, 3.0-5.1%), and individuals who were ≥ 70 years of age (6.6%; 95% CI, 4.2-10.2%).
Rooney et al found that U.S. adults are supplementing with increasing amounts of vitamin D, and that this increase is highest in non-Hispanic white women > 70 years of age. Three percent of the population studied exceeded the 4,000 IU tolerable upper limit, and 18% exceeded 1,000 IU per day. The recommended dietary allowance (RDA) of vitamin D is 600 IU/day for those between 1 year and 70 years of age and 800 IU/day for adults ≥ 71 years of age.1 The American Academy of Pediatrics recommends 400 IU/day for children < 1 year of age.6
Over the course of the study period, there was a marked increase in the use of vitamin D supplements at the two doses documented. The authors did not discuss potential reasons or theories behind the increase in supplemental vitamin D intake. However, in 2017, the vitamin D industry was estimated to be worth $936 million.9 Currently, serum vitamin D levels are the fifth most commonly ordered lab tests covered by Medicare.9 Serum vitamin D tests increased 80-fold between 2000 and 2010, most likely because of growing knowledge about diseases that could be associated with low vitamin D levels.10
There are many purported uses for vitamin D; it is generally accepted that vitamin D is important physiologically. For example, the National Academy of Medicine (NAM), formerly the Institute of Medicine, concluded that vitamin D was beneficial for bone health. However, evidence is insufficient for extraskeletal health recommendations. Rather than focus on supplementation or dietary recommendations, there is some thought that vitamin D status, as determined by serum levels, is the important variable.
On this note, NAM concluded that taking a serum vitamin D (25(OH)D) level of < 12 ng/mL is indicative of possible risk for vitamin D deficiency. In addition, some people may be at risk for vitamin D deficiency at serum 25(OH)D levels between 12 ng/mL and 20 ng/mL. For most people, a serum 25(OH)D level of 20 ng/mL or higher is recommended. A 25(OH)D serum level > 50 ng/mL is associated with adverse events. Although 25(OH)D serum levels indicate exposure to vitamin D, they do not measure body storage of vitamin D and have not been shown to be a reliable marker for health outcomes.1
Although Rooney et al found an increasing use of supplemental vitamin D in the U.S. population, it also is possible to obtain vitamin D through diet. Few unfortified foods contain adequate amounts of vitamin D naturally. Fatty fish and fatty fish oils contain vitamin D3, and small amounts of vitamin D3 can be found in egg yolks, cheese, and beef liver.7 Mushrooms contain vitamin D2 and may contain more amounts of vitamin D2 if exposed to light.7 Vitamin D needs also can be met through exposure to sunlight. However, cloud cover can reduce ultraviolet energy by 50%, and ultraviolet B radiation, which is required for vitamin D3 synthesis, is unable to penetrate glass.2
There were several strengths in this study, including the large number of participants and the NHANES response rate of 74%. Study limitations included the lack of representation of diverse races and ethnicities, as 69.7% self-reported as non-Hispanic white, and the mean age was 46.6 years. Another major limitation was that many vitamin D supplements have been found to exceed their label claims. According to Labdoor, a company that tests supplements, an analysis of 19 of the best-selling vitamin D supplements in the United States found that all the products tested exceeded their vitamin D label claims by 22%, and six products exceeded their label claims by 40%.11 Multivitamins usually contain label claims of 400 IU/day. Vitamin D intakes > 1,000 IU per day may indicate additional supplemental vitamin D intake. Furthermore, no distinction was made between different formulations of vitamin D (i.e., vitamin D2 vs. vitamin D3). There may be variable physiological effects between these supplements.5
Since some participants’ vitamin D intakes exceeded the RDA, there might be concerns about vitamin D toxicity. Gailor et al reviewed case reports of vitamin D toxicity, which included information about how much vitamin D was taken, the serum vitamin D level at the time of admission, and a complete medical evaluation.10 They found that most cases of vitamin D toxicity are due to intake of vitamin D supplements that exceed their label claims.10 The authors found that serum levels > 150 ng/mL posed toxicity risks and should be avoided.10 Vitamin D intoxication leads to hypercalcemia through higher calcium absorption in the gut and hypercalciuria. Rising calcium levels also may lead to muscle weakness, hypertension, neuropsychiatric symptoms, renal toxicity, and renal calculi.10 Of note, the official upper level is 4,000 IU in adults and children ≥ 9 years of age.
Although reports of vitamin D toxicity appear to be rare, the growth in vitamin D supplement use may increase adverse events. Unfortunately, supplemental vitamin D label claims do not always reflect the actual concentration in the supplement, making it difficult to recommend vitamin D supplements. Certain populations are at risk of vitamin D deficiency, including breastfed infants, people with limited sun exposure, people with dark skin, older adults, people with lower fat absorption, individuals with inflammatory bowel disease, people with obesity, and those who have undergone gastric bypass surgery.1,2,3,6,8 Although serum 25(OH)D levels are the best indicator of vitamin D status, they are not indicative of storage levels of vitamin D in tissue.4,5,7 Patients take vitamin D supplements, so it is important for providers to obtain accurate lists of any other supplements they take. In patients at risk for vitamin D deficiency, obtaining a serum 25(OH)D level may be helpful when recommending adequate amounts of vitamin D through diet, sun exposure, and multivitamin or supplement use. Providers should monitor serum 25(OH)D levels during treatment to ensure that supplementation is not excessive. In all patients, especially those at risk for adverse events due to high intake of vitamin D supplements, education about the inaccuracy of label claims of many vitamin D supplements and risks of toxicity is important.
Financial Disclosure: Internal Medicine Alert’s Physician Editor Stephen Brunton, MD, is a retained consultant for Abbott, Acadia, Allergan, AstraZeneca, Avadel, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Mylan, and Salix; he serves on the speakers bureau of AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, and Novo Nordisk. Peer Reviewer Gerald Roberts, MD; Editor Jonathan Springston; Executive Editor Leslie Coplin; and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.