Vitamin D 1000 IU or more: 1 in 3 of those over age 60 as of 2013– JAMA June 2017

Trends in Use of High-Dose Vitamin D Supplements Exceeding 1000 or 4000 International Units Daily, 1999-2014

JAMA. 2017;317(23):2448-2450. doi:10.1001/jama.2017.4392
Mary R. Rooney, MPH1; Lisa Harnack, DrPH, RD1; Erin D. Michos, MD, MHS2; et al Rachel P. Ogilvie, MPH1; Christopher T. Sempos, PhD3; Pamela L. Lutsey, PhD, MPH1

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1000 IU or more

4000 IU or more

Since 2000, there has been an increase in research on possible health benefits of vitamin D. However, a 2011 Institute of Medicine (IOM; now the National Academy of Medicine) report concluded that vitamin D was beneficial for bone health but evidence was insufficient for extraskeletal health.1 Several large-scale trials are ongoing to evaluate the effect of vitamin D supplementation on extraskeletal outcomes.2 The IOM report noted possible harm (eg, hypercalcemia, soft tissue or vascular calcification) for intakes above the tolerable upper limit, which is the highest level of intake likely to pose no risk of adverse effects for most adults.1

The recommended dietary allowance for vitamin D is 600 IU/d for adults 70 years or younger and 800 IU/d for those older than 70 years. The tolerable upper limit is 4000 IU/d; beyond this level risk of toxic effects increases.1 Multivitamins typically contain about 400 IU/d; consumption of 1000 IU or more daily likely indicates intentionally seeking supplemental vitamin D.

We assessed trends in daily supplemental vitamin D intake of 1000 IU or more and 4000 IU or more from 1999 through 2014.

Methods
Repeat cross-sectional data from the nationally representative National Health and Nutrition Examination Survey (NHANES) were used. NHANES, which includes survey and examination components, samples noninstitutionalized US residents through a complex, stratified, multistage probability sampling design with certain populations overrepresented (overall response, 74%).3 Informed consent was obtained from participants of the NHANES study. This analysis was based on anonymized data freely available to the public and, therefore, was exempt from ethics review.

For this analysis, participants who were younger than 20 years, pregnant, or had inadequate supplement information were excluded. Participants self-reported their daily supplemental vitamin D intake for the past 30 days; they were asked to bring supplement bottles to aid in reporting.3

STATA (StataCorp), version 14.1, was used. Sample weights were applied. The prevalence of daily vitamin D supplementation of 1000 IU or more and 4000 IU or more was calculated for each survey period overall and by sex, age, and race/ethnicity. Linear trends were tested via linear regression, and a 2-sided P value of less than .05 was considered statistically significant.

Results
Of 39 243 participants, the mean age was 46.6 years (SD, 16.8), 51.1% were women, and 69.7% self-reported as non-Hispanic white in weighted analyses. The prevalence of daily supplemental vitamin D use of 1000 IU or more in 2013-2014 was 18.2% (95% CI, 16.0%-20.7%), which was higher than in 1999-2000 (0.3% [95% CI, 0.1%-0.5%]; P for trend <.001) (Table 1).

In 2013-2014, prevalence of daily supplemental intake of 4000 IU or more was 3.2% (95% CI, 2.5%-4.0%) (Table 2). Prior to 2005-2006, prevalence of daily intake of 4000 IU or more was less than 0.1% (P for trend from 2007-2014: <.001).

Trends of increasing supplemental vitamin D use were found for most age groups, race/ethnicities, and both sexes; though there were interactions (Table 1 and Table 2). In 2013-2014, intake of 4000 IU or more daily was highest among women (4.2% [95% CI, 3.0%-5.7%]), non-Hispanic white individuals (3.9% [95% CI, 3.0%-5.1%]), and those 70 years or older (6.6% [95% CI, 4.2%-10.2%]).

Discussion
From 1999 through 2014 the number of US adults taking daily vitamin D supplements of 1000 IU or more and 4000 IU or more increased. Overall, 3% of the population exceeded the tolerable upper limit of 4000 IU daily, and may be at risk of adverse effects as a consequence, and 18% exceeded 1000 IU daily, likely indicating intentionally seeking supplemental vitamin D. These findings extend a prior NHANES report documenting an increase in daily vitamin D supplement intake of 600 IU or more, particularly among women, non-Hispanic white populations, and older persons from 1988 through 2010.4 Concentrations of 25-hydroxyvitamin D (25[OH]D) have also modestly increased over this time frame.4 One limitation of the study is that data were self-reported; however, participants were asked to bring supplement bottles to aid in reporting. Also, the design was serial cross-sectional rather than longitudinal, and clinical outcomes were not available.

Although research has emphasized possible benefits of vitamin D, high dosages pose potential risks.1 A randomized clinical trial with high-dose vitamin D supplementation found increased risk of fractures and falls,5 and an increased risk of kidney stones has been found with vitamin D taken in combination with calcium.6 Some epidemiologic investigations have reported adverse associations of high 25(OH)D levels with prostate cancer, pancreatic cancer, and all-cause mortality.1