European Journal of Clinical Nutrition (2015) 69, 84–89 © 2015 Macmillan Publishers Limited All rights reserved 0954-3007/15 www.nature.com/ejcn

ORIGINAL ARTICLE

Predictors of vitamin D status in subjects that consume a vitamin D supplement MA Levy1,3, T McKinnon1,3, T Barker2, A Dern1, T Helland1, J Robertson1, J Cuomo1, T Wood1 and BM Dixon1 BACKGROUND/OBJECTIVE: Although dietary supplement use has increased significantly among the general population, the interplay between vitamin D supplementation and other factors that influence vitamin D status remains unclear. The objective of this study was to identify predictor variables of vitamin D status in free-living subjects to determine the extent to which vitamin D supplements and other factors influence vitamin D status. SUBJECTS/METHODS: This was a retrospective, cross-sectional study involving 743 volunteers. Serum 25-hydroxy-vitamin D (25(OH)D) level and the variables diet, supplement usage, latitude of residence, ethnicity, age and body mass index (BMI) were used to predict vitamin D status in a summer and winter cohort. RESULTS: Supplemental vitamin D3 consumption was the most significant positive predictor, whereas BMI was the most significant negative predictor, of vitamin D status in each cohort. Other positive predictors were fortified beverage and dairy consumption in the summer and winter cohort, respectively. Negative predictors were: African American, Asian and Hispanic race in the summer; latitude of residence 436 °N, Asian and Hispanic ethnicity in the winter. Mean(± s.d.) 25(OH)D levels were 101.1 ( ±42.1) and 92.6 (±39.0) nmol/l in summer and winter, respectively. Comparing non-supplement vs supplement users, approximately 38 vs 2.5% in the winter and 18 vs 1.4% in the summer had vitamin D levels o 50 nmol/l. CONCLUSIONS: Vitamin D supplementation was the most significant positive predictor of vitamin D status. Collectively, these data point to the practicality of utilizing vitamin D supplements to reduce hypovitaminosis D in adults throughout the United States. European Journal of Clinical Nutrition (2015) 69, 84–89; doi:10.1038/ejcn.2014.133; published online 16 July 2014

INTRODUCTION Numerous factors impact vitamin D status in humans, including dietary intake, skin color, season of the year and geographic latitude.1,2 For most individuals, the latter three factors play a significant role because the primary determinant of vitamin D status is sunlight exposure and the ultraviolet B (UVB)-catalyzed conversion of 7-dehydrocholesterol to cholecalciferol (vitamin D3) in the dermis.3 As such, anything that obstructs UVB transmission to the skin reduces vitamin D synthesis. In fact, one of the unintended consequences of recent recommendations from numerous public health organizations to limit Sun exposure may be that such measures impede the body’s ability to synthesize vitamin D and places individuals at risk for vitamin D deficiency.4 Indeed, several recent surveys have indicated that vitamin D status among American adults and children has declined considerably in the past two decades.5,6 Hence, if current trends to avoid Sun exposure continue, acquisition of vitamin D through non-sunlight sources may become an increasingly important route of meeting physiological needs. Currently, the Institute of Medicine (IOM) recommends a daily intake of 600 IU/d vitamin D from food, supplements and synthesis for men and women less than 70 years of age.7 This level is based on the criteria that it will meet the bone health requirements of 97.5% of the population and maintain circulating levels of 25-hydroxy-vitamin D (25(OH)D) at 450 nmol/l.7 However, optimal levels of vitamin D are in dispute,8–10 and a substantial body of evidence indicates that serum levels

475 nmol/l are conducive to multiple health benefits beyond bone health (for an overview, see Holick11). Indeed, since the release of the IOM report in 2011, the Endocrine Society has released guidelines stating that vitamin D deficiency is defined as serum 25(OH)D levels o 50 nmol/l, vitamin D insufficiency as levels o 75 nmol/l and levels above 75 nmol/l as sufficient.12 Thus, a circulating vitamin D level of 75 nmol/l may be a more appropriate target for most people. Because unfortified vitamin D levels are relatively low in most common foodstuffs, and because so many lifestyle factors influence endogenous vitamin D synthesis, alternative methods of increasing vitamin D intake may provide a means of achieving and maintaining an optimal vitamin D status, particularly during the winter. Primary among these is vitamin D supplementation. However, the influence of vitamin D supplementation on circulating vitamin D levels, particularly in light of the numerous lifestyle factors that influence vitamin D status, remain in question. Therefore, the objective of this study was to identify predictor variables of vitamin D status in free-living subjects to determine the extent to which vitamin D supplements and other factors influence vitamin D status. SUBJECTS AND METHODS Subjects This was a retrospective, cross-sectional study involving healthy volunteers across the United States (including AK and HI). The research protocol was approved by the Western Institutional Review Board

1 USANA Health Sciences, Inc. 3838 West Parkway Blvd; Salt Lake City, UT, USA and 2The Orthopedic Specialty Hospital, 5848 South Fashion Blvd; Murray, KY, USA. Correspondence: Dr BM Dixon, Research & Development, USANA Health Sciences, 3838W. Parkway Blvd., Salt Lake City, 84120, UT, USA. E-mail: [email protected] 3 These authors contributed equally to this work. Received 22 July 2013; revised 24 April 2014; accepted 24 May 2014; published online 16 July 2014

Predictors of vitamin D status MA Levy et al

85 (Olympia, WA, USA). All prospective subjects were employees, or friends or family of employees, of USANA Health Sciences, a manufacturer of nutritional supplements, and were recruited via electronic mail. Initially, subjects were informed of the study purpose and queried as to whether they: i) had consumed daily a supplement containing vitamin D for at least the previous 2 months or ii) had not consumed any supplements containing vitamin D in the previous 2 months. If subjects answered ‘yes’ to either of these queries, they were subsequently screened and not allowed to participate if they had vacationed in a more southern latitude in the previous 2 months, used a tanning bed in the previous 2 months or if they reported taking prescription medications containing vitamin D. A total of 1370 subjects were contacted; 505 did not respond and 122 did not meet the selection criteria. Of the remaining 743 subjects, 401 belonged to the summer cohort and 342 to the winter cohort. For each cohort, the study consisted of two parts: (1) non-fasting blood collection and analysis by a LabCorp facility and (2) an online survey of lifestyle factors associated with vitamin D status. A waiver of documentation of consent was granted and all subjects received an approved subject information sheet. Subjects were recruited and blood collections were performed in late winter (February 1–April 30) and late summer (August 1–October 31) of 2010. Once the blood was analyzed, subjects completed the online survey which requested the following information associated with vitamin D status: gender, ethnicity, height, weight, age, geographic location, duration of daily Sun exposure ( o10 min, 10–30 min or 430 min between 10 am and 3 pm), use of sunscreen (yes/no) and Sun-obscuring clothing, dietary intake of foods known to contain vitamin D and supplement usage. One-week diet history records of selected food items (i.e. milk, oily fish and fortified beverages, which provide 450% of dietary vitamin D in the United States)13 were used to quantify dietary vitamin D intake; 3-month diet history records were used to obtain estimates of supplemental vitamin D intake. Vitamin D levels of food items were calculated using the US Department of Agriculture National Nutrient Database.14 Validity of the diet history records was substantiated by regressing dietary intakes of vitamin D and serum vitamin D levels of subjects reporting o15 min per day Sun exposure and no vitamin D supplement usage. Correlation coefficients of 0.41 and 0.59 were observed for the winter (n = 24, Po 0.05) and summer (n = 25, Po 0.005) cohort, respectively. Latitude of residence and body mass index (BMI) were calculated from the responses. Categorical variables for latitude ( o35 °N, 35–41 °N, 441 °N) were constructed such that sample sizes in summer and winter were approximately equal for each tertile and which divided the continental United States into three approximately equidistant north–south regions. BMI was categorized as underweight (o 18.5), normal (18.5–24.9) and overweight (425) according to the Centers for Disease Control and Prevention (CDC) classifications.15

Vitamin D determination Vitamin D levels were determined at LabCorp facilities employing the Liaison 25(OH)D assay (DiaSorin Corp., Stillwater, MN, USA). LabCorp facilities are accredited and certified for testing serum levels of vitamin D (25(OH)D) (accuracy-based vitamin D) by the College of American Pathology. The Liaison 25(OH)D assay is a chemiluminescent immunoassay used to quantify 25(OH)D and recognizes both 25(OH)D2 and 25(OH)D3 with equal affinity.

Statistical analysis Statistical analyses were performed using Sigmaplot Version 12.0 (Systat Software Inc., San Jose, CA, USA). Spearman correlation was used to examine associations between dietary vitamin D and serum vitamin D status. Baseline characteristics of summer and winter subjects were compared using the Mann–Whitney U test for continuous data or by the chi-square test for categorical data as appropriate. For multivariate regression, serum concentrations of 25(OH)D for both summer and winter were not normally distributed and were log(10) transformed prior to analysis. To facilitate meaningful comparisons of predictor variables, standardized β-coefficient estimates are presented for the regression analysis. For the regression models, independent predictor variables of serum 25(OH)D were first identified using a backward regression from the list of parameters on the survey sheet noted previously. The following continuous predictor variables identified in the backward regression were used in the multiple linear regression models: supplemental vitamin D intake, dietary vitamin D intake from dairy products, oily fish and fortified beverages, and BMI. Dummy variables identified were: latitude of © 2015 Macmillan Publishers Limited

residence and ethnicity. Age, although not statistically associated with 25(OH)D in either of these cohorts, was nevertheless included in the final model because of its known influence on 25(OH)D concentrations.16 Regression models for summer and winter were developed separately because of the influence of season on serum 25(OH)D. Studentized deleted residuals were used to screen for outliers. Observations with studentized residuals 42.5 were removed from the analysis (summer n = 9; winter n = 8).

RESULTS We analyzed serum 25(OH)D levels in 726 healthy subjects aged 20–65 across the United States in the late winter and late summer of 2010. Subject characteristics are presented in Table 1. In each season, male subjects comprised ~ 25% of the study group, while the majority (55–60%) of the subjects were aged 40–59 years. Approximately two-third of the summer and winter cohort consumed ⩽ 200 IU/d vitamin D in their diet. However, nearly 75% of the subjects were taking a vitamin D supplement, resulting Table 1.

Subject baseline characteristics P-value

Summer (n)

Winter(n)

Gender Male Female χ2

97 295

92 242

Age (years) 20–29 30–39 40–49 50–59 60–65 χ2

35 69 86 134 68

22 58 95 112 47

26.4 (6.4)b 9 196 187

26.0 (6.1)b 6 170 158

19 27 316 19 11

9 12 292 15 6

BMI (kg/m2) o18.5 18.5–25 425 χ2 Ethnicity/ancestry African American Asian Caucasian Hispanic Other χ2

b

0.39a

0.23a 0.53c

0.88a

0.11a b

101.1 (42.1)

Dietary vitamin D (IU/d) 0–200 IU/day 4200 IU/day χ2

175.4 (160.8)b 173.1 (126.4)b 0.74c 269 220 121 114 0.37a

Supplemental vitamin D (IU/d) 0 IU/day 0–600 IU/day 4600 IU/day χ2

2282 (2482)b 1967 (2054)b 0.23c 102 89 26 27 264 218 0.72a

Latitude ( °N) o36 36–41 441 χ2

38.2 (5.6)b 137 128 127

92.6 (39.0)

0.008c

Vitamin D status (nmol/l)

38.3 (5.5)b 106 115 113

0.98c

0.66a

Abbreviation: BMI, body mass index. aP-values of chi-square test for ordinally grouped variables. bdata expressed as cohort mean(s.d.). c P-values for Mann–Whitney U test comparing the summer and winter cohort.

European Journal of Clinical Nutrition (2015) 84 – 89

Predictors of vitamin D status MA Levy et al

86 in average supplemental intake of 2282 and 1967 IU/d vitamin D in the summer and winter participants, respectively. Supplemental intake was not different between groups (P40.05). The vast majority of participants self-identified as Caucasian. There was no difference in the mean latitude of residence between the summer and winter subjects. In multivariable linear regression (Table 2), BMI and supplement intake were found to have a significant impact on circulating 25(OH)D levels in both the summer and winter cohorts. In the summer cohort, African American, Asian and Hispanic race or ethnicity was a significant negative determinant of vitamin D status; fortified beverage consumption was a significant positive determinant. In the winter cohort, vitamin D from dairy sources had a significant positive effect on vitamin D levels; residence at a latitude 436 °N and Asian and Hispanic ancestry had a significant negative effect. Figure 1 presents the vitamin D status of study participants in both the summer and winter cohort stratified by level of supplemental vitamin D intake. The most striking finding was that in the winter cohort (Figure 1a), 38% of subjects not taking a vitamin D supplement had circulating levels of 25(OH)D o50 nmol/l. This number was reduced almost fourfold in the same cohort of subjects taking the smallest quantile ( o600 IU/d) of supplements. In this group, 10.3% of subjects had circulating levels of 25(OH)D o50 nmol/l. Notably, none of the subjects in the winter cohort consuming 41200 IU/d of supplemental vitamin D had circulating levels o 50 nmol/l. In the summer

Table 2. Standardized coefficients of predictor variables of serum 25-hydroxy vitamin D levels in the summer and winter cohorta,b Predictor variable

Summer

Winter

Standardized P-value Standardized P-value coefficient coefficient Dietary source of vitamin D Supplemental intake 0.510 Oily fish 0.055 Dairy − 0.017 Fortified beverages 0.117

o 0.001 0.153 0.654 0.003

0.563 0.015 0.119 0.035

o0.001 0.728 0.007 0.443

BMI

− 0.314

o 0.001

− 0.233

o0.001

Latitude o36 °N 441N 36–41N

Reference − 0.050 0.272 − 0.045 0.332

Reference − 0.174 o0.001 − 0.126 0.013

Ethnicity/ancestry Caucasian African American Asian Hispanic Other

Reference − 0.138 o 0.001 − 0.089 0.022 − 0.125 0.001 − 0.006 0.878

Reference − 0.040 − 0.128 − 0.106 0.019

0.355 0.003 0.015 0.647

Age 50–59 20–29 30–39 40–49 60–65

Reference − 0.079 0.062 0.054 0.207 0.013 0.763 0.009 0.834

Reference − 0.047 − 0.015 − 0.010 − 0.020

0.309 0.757 0.839 0.662

Abbreviation: BMI, body mass index. aSummer: n = 392, r2 = 0.475, adjusted r2 = 0.454 Winter: n = 334, r2 = 0.454, adjusted r2 = 0.428. A comparison between the fitted model of summer and winter cohort using the fisher’s z test for correlations revealed that there was no significant difference between the respective r2 values (Z = − 0.37, P40.05). bSummer: August 1–October 31; Winter: February 1–April 30.

European Journal of Clinical Nutrition (2015) 84 – 89

cohort, approximately 18% of the subjects not taking a vitamin D supplement had a circulating level of 25(OH)D o50 nmol/l, a decrease of more than 50% compared with the same group in the winter cohort. Among subjects consuming 41200 IU/d of supplemental vitamin D in the summer cohort, only 2.1% had circulating levels of o50 nmol/l. Table 3 compares the vitamin D intake among subjects who did or did not take a vitamin D supplement in the summer and winter cohort. Among subjects who did not take a vitamin D supplement, there were no significant differences in the proportion (%) of participants consuming the specified quantities of vitamin D between the winter and summer cohorts. Notably, almost 99% of the winter participants, and 100% of the summer participants, did not consume the current recommended dietary allowances (RDA) of 600 IU/d vitamin D through dietary means alone. In fact, approximately 95% of all subjects not taking a supplement failed to consume the estimated average requirement of 400 IU/d. In contrast, among subjects who were taking a vitamin D supplement, approximately 90% of the participants from the winter survey and 95% of the participants from the summer survey consumed the RDA of 600 IU/d. Moreover, approximately 99% of the subjects from the summer and winter survey consumed more than 400 IU/d of vitamin D, the current estimated average requirement. Among participants who consumed a vitamin D supplement, there was no significant difference in the proportion of subjects consuming the specified levels of vitamin D between the summer and winter subjects. DISCUSSION On the basis of the 50 nmol/l cutoff established by the IOM, data from this study indicate that as many as 18% of persons in the summer, and 38% in the winter, exhibit suboptimal vitamin D status in the absence of vitamin D supplement use. However, by the standards of the Endocrine Society, vitamin D insufficiency may be prevalent in as much as 65–70% of participants who do not take a vitamin D supplement, regardless of season. Although vastly different pictures emerge in terms of the proportion of subjects who are considered to be below optimal vitamin D status either by IOM or Endocrine Society standards, it is nevertheless readily apparent from this work that a significant proportion of healthy, free-living people in the United States who do not consume vitamin D supplements are at a significant risk for suboptimal vitamin D status and its attendant morbidities. In this study, supplement intake was found to be the largest determinant of vitamin D status in both summer and winter cohorts. Standardized β-coefficients for supplement intake were 0.51 in the summer and 0.56 in the winter. On the basis of these values, we would predict that if all other variables are held constant, mean serum 25(OH)D levels would increase by 0.51 standard deviations in the summer (i.e. 21.5 nmol/l) and 0.54 standard deviations in the winter (i.e. 21 nmol/l) for an increase in vitamin D supplement intake of 2482 IU/d in the summer and 2054 IU/d in the winter, respectively. It has been estimated that the consumption of vitamin D3 in 40 IU/d increments raises plasma 25(OH)D by about 1.0 nmol/l or 25 nmol/l for every 1000 IU/d.17 Our data predict a two to threefold greater requirement in supplemental vitamin D3 in order to achieve comparable gains in circulating 25(OH)D. This may be attributable to the fact that supplementation levels and vitamin D status in our subjects were, on average, higher than the general population. As has been recently demonstrated, the increase in circulating 25 (OH)D for a given supplemental dose is inversely proportional to the starting concentration.18 BMI was found to be the second largest determinant of vitamin D status with an adjusted β-coefficient of − 0.31 in the summer and − 0.23 in the winter subject populations. These data are consistent with numerous studies demonstrating that obese © 2015 Macmillan Publishers Limited

Predictors of vitamin D status MA Levy et al

87

Figure 1. Proportion of subjects with serum 25(OH)D below 50 nmol/l (■), 50–75 nmol/l (■) and above 75 nmol/l (■) in winter (a) and summer (b). Proportions are significantly different (P o0.05, chi-squared test). Table 3.

Vitamin D intake from diet (non-supplementers) or diet and supplements (supplementers) among subjects in the winter and summer cohort Vitamin D

Non-supplementers Winter

Summer

Supplementers Winter

Summer

Intake (IU/d)

(n)

(%)

(n)

(%)

(n)

(%)

(n)

(%)

0–200 200–400 400–600 600–800 800–1600 1600–2400 42400

64 19 5 1 0 0 0

71.9 21.3 5.6 1.1 0.0 0.0 0.0

72 25 5 0 0 0 0

70.6 24.5 4.9 0.0 0.0 0.0 0.0

1 3 19 6 43 49 124

0.4 1.2 7.8 2.4 17.6 20.0 50.6

0 2 14 11 43 68 152

0.0 0.7 4.8 3.9 14.8 23.4 52.4

individuals have low 25(OH)D concentrations.19 However, an explanation for this correlation is currently under debate. Persons with a high BMI typically have a higher body fat content that may function as a substantial reservoir that not only serves as a storage depot for vitamin D, but also is extremely slow to release vitamin D.20 Indeed, the correlation of circulating vitamin D is higher for adiposity than for body weight or BMI.21 However, the hypothesis that body fat sequesters vitamin D has been challenged, and low circulating 25(OH)D levels in obese individuals may result from a dilution effect of vitamin D within the large body mass.22 Regardless of the mechanism(s), obese patients are at significantly greater risk of vitamin D deficiency. Moreover, the increasing prevalence of overweight and obesity in the US population may exacerbate the prevalence of low vitamin D status.23 Our data, as well as that of others, indicate that it is very difficult to obtain adequate vitamin D through diet alone12 and therefore overweight and obese subjects need to be particularly conscious of the need to acquire adequate levels of vitamin D other than through food sources. Vitamin D can be obtained from a variety of sources. Foremost among these is UVB irradiation, the magnitude of which varies by seasonality and latitude of residence. In our work, latitude was found not to influence vitamin D status in the summer, whereas in the winter, subjects residing at latitudes 436 °N had significantly lower mean serum values (~8–10 nmol/l) than subjects residing at latitudes o36 °N (data not shown). These observations correspond with previous data that show that there is very little difference in the vitamin D-producing capacity of sunshine© 2015 Macmillan Publishers Limited

derived UVB irradiation throughout the continental United States in the summer months, whereas in winter, the level of vitamin D generating UVB radiation may decline to as little as 25% of summertime values at 35 °N, and be nonexistent above 50 °N.12,24 Milk and milk products contribute nearly half of dietary vitamin D intake in Americans and Canadians.13,25 We likewise have found that dairy products contributed 43 and 41% of dietary vitamin D in the winter and summer cohort, respectively. However, our data indicate that dairy consumption was a significant predictor of vitamin D status in the winter, but not in the summer. This observation is difficult to reconcile, particularly because the average vitamin D consumption in each cohort was similar in terms of both dairy intake (73.7 ± 153.1 IU/d summer vs 74.4 ± 98.2 IU/d winter) and total dietary intake (181.2 ± 166.9 I U/d summer vs 172.7 ± 126.7 IU/d winter). It is plausible that in the summer, increased vitamin D synthesis may blunt the influence of dairy consumption on vitamin D status. Alternatively, dairy consumption may attenuate the decline in vitamin D status characteristically observed during the winter months.1 African American, Hispanic and Asian race or ethnicity was a significant negative predictor of vitamin D status in the summer months. Race and ethnicity have been well-documented determinants of cutaneous vitamin D synthesis and status.26–28 Melanin, the principal pigment that gives skin its dark coloration, absorbs UV light and thus reduces vitamin D synthesis. Hence, compared with Caucasians, persons with increased levels of melanin exhibit a lower capacity to synthesize vitamin D during the summer months. Curiously, African American ethnicity did not influence vitamin D status in the winter. This may simply indicate that in the winter months, a myriad of factors such as latitude, daily duration of Sun exposure, and cold weather dress may reduce vitamin D synthesis to such an extent that skin pigmentation is no longer a determining factor of vitamin D status among this specific group. Several limitations of this work should be noted. First, the vast majority of subjects were Caucasian, which may limit the robustness of the data as they pertain to non-Caucasian people. In addition, all of the survey data were self-reported, which may result in inaccuracies.29,30 For example, self-reporting error may be found in measures of height and weight, as our data show that the prevalence of overweight and obesity among these cohorts was approximately 50%, considerably lower than the 69% reported among the US population.31 Alternatively, our data may be accurate but reflect selection bias in our subject recruitment protocol, as supplement use has indeed been correlated with selection of healthier lifestyle choices.32,33 Nonetheless, we attempted to minimize error associated with self-reporting. For example, we utilized a 7-day diet history restricted to selected European Journal of Clinical Nutrition (2015) 84 – 89

Predictors of vitamin D status MA Levy et al

88 food items, measures that improve the accuracy of data collection.34,35 Indeed, our correlation coefficients between dietary sources and serum levels of vitamin D compare favorably with other researchers.36–38 Although initially characterized as an antirachitic factor,39 the physiological function of vitamin D has expanded considerably beyond its role in bone health.40–42 In particular, decreased risks in heart disease,43,44 certain cancers45,46 and all-cause mortality44,47 have been associated with increasing vitamin D status. These and other observations have led some groups to advocate that circulating vitamin D levels from 75 to 100 nmol/l are most advantageous to human health.48–50 However, it is improbable that one could attain these levels, while practicing currently advised Sun-protective behavior, in the absence of vitamin D supplementation.17,51 Estimates of the vitamin D intake required to achieve circulating levels of 75–100 nmol/l, subject to the influences of baseline vitamin D levels, age, lifestyle and genetic factors, range from 600 to as much as 4000 IU/d52,53—values significantly greater than the ~ 200–300 IU/d currently obtained through food alone in Canadians25 and Americans.54 It should be noted, however, that vitamin D status may exhibit a U-shaped phenomenon, such that decreased risks of disease observed at circulating 25(OH)D levels between 75 and 100 nmol/l may increase at concentrations 490–100 nmol/l.55–57 Hence, while vitamin D supplementation is advocated as a means of insuring vitamin D sufficiency (i.e. circulating vitamin D 475 nmol/l),58 uncritical supplementation strategies that could raise circulating levels beyond 100 nmol/l are a matter of concern.55 Indeed, the long-term consequences of high-dose vitamin D supplementation—at levels largely unachievable through dietary intake—remain unknown. As such, the IOM has specified 4000 IU/d as the upper limit of vitamin D in adults, a level of intake that over a long-term period, is deemed not to cause harm in a normal, free-living population.7 Most Americans do not obtain the RDA for vitamin D from foods.7,54 In this study, more than 95% of the subjects did not consume the estimated average requirement, the quantity of vitamin D estimated to meet the needs of 50% of the population, through diet alone.7 Although the vitamin D requirements of most individuals could be met through adequate Sun exposure, concerns regarding the health consequences of increased Sun exposure have led to Sun-protective behaviors that impede endogenous vitamin D synthesis. Hence, consumption of a vitamin D supplement may offer an effective approach to safeguard against vitamin D deficiency. In fact, the conclusions drawn from several studies are that vitamin D supplementation is a cost-effective means to increase vitamin D status and further, that increasing mean serum 25(OH)D levels to 75–110 nmol/l may reduce morbidities associated with vitamin D deficiency.59–62 There is, however, considerable debate surrounding these positions, as evidenced by several recent meta-analyses.63–65 Nevertheless, from the standpoint of an individual, the out-ofpocket expense necessary to meet the current RDA for vitamin D through a vitamin D supplement in the retail market is modest.59,66 In light of the prevalence of low vitamin D status observed in human populations in this and other studies, health guidelines that clearly define the capacity of vitamin D supplements to raise vitamin D status may be warranted. CONFLICT OF INTEREST With the exception of TB, each author is currently (ML, TM, JR, JC, TW & BD) or was formerly (AD, TH) employed by USANA Health Sciences which funded this work. This manuscript was prepared on company time. The remaining authors declare no conflict of interest.

European Journal of Clinical Nutrition (2015) 84 – 89

ACKNOWLEDGEMENTS We would like to thank MM. Gandelman for valuable comments and suggestions on the manuscript

AUTHOR CONTRIBUTIONS All authors critically reviewed and approved of the final manuscript. The authors’ responsibilities were as follows—MAL, BMD and TB: had primary responsibility for the content; MAL performed the statistical analysis; BMD, TB, AD and JR: contributed to the statistical analysis; TM, TH, JC, TW and BMD designed the study; TM and BMD directed the study.

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