Trends in Vitamin A, C, D, E, K Supplement Prescriptions from Military Treatment Facilities: 2007 to 2011

MILITARY MEDICINE, 180, 7:748, 2015

Trends in Vitamin A, C, D, E, K Supplement Prescriptions From Military Treatment Facilities: 2007 to 2011

ENS Travis Y. Morioka, MC USN; 2d Lt Jeremy T. Bolin, USAF MSC; Selasi Attipoe, MA; Donnamaria R. Jones, PharmD; CAPT Mark B. Stephens, MC USN; Patricia A. Deuster, PhD

ABSTRACT Introduction: Although prior studies have examined the prevalence of dietary supplement use among various populations, data on single vitamins prescribed by health care providers are limited. Objective: This study

examined trends in single-vitamin supplement (A, C, D, E, K) prescriptions by providers from military treatment facilities Downloaded from https://academic.oup.com/milmed/article/180/7/748/4160604 by guest on 30 September 2021 from 2007 to 2011. Methods: We examined prescription data from the Department of Defense Pharmacy Data Transac- tion Service to determine trends in the aforementioned single-vitamin supplement prescriptions. Prescription rates per 1,000 active duty personnel were estimated using population data retrieved from the Defense Medical Epidemiology Database (i.e., [number of prescriptions/population size] × 1,000). Results: Across the 5-year period, the number of vitamin D prescriptions per 1,000 active duty personnel increased 454%. In contrast, the number of vitamin A, vitamin E, and vitamin K prescriptions per 1,000 active duty personnel decreased by 32%, 53%, and 29% respectively. Vitamin C prescriptions remained relatively constant. Across all age groups, total single-vitamin supplement prescriptions increased by 180%. Conclusion: Together, prescriptions examined in this study increased steadily from 2007 to 2011, primarily because of the increase in vitamin D prescriptions. The exhibited trend reﬂects the current general-population pattern of dietary supplement use, with large increases in vitamin D and declines in vitamin E.

INTRODUCTION to correct congenital deficiencies in neonates and vitamin D – Most adults in the United States use dietary supplements.1 3 to obese and elderly patients, where levels may be low. However, the medical and scientific communities have vastly Substantial information is available on prevalence of die- divergent opinions on the safety and effectiveness of dietary tary supplement use among the general population through supplements.4–11 Thus, attempts to arrive at a consensus have nationally representative surveys.1,31 To the best of our produced disparate recommendations.12,13 Despite conflicting knowledge, no other studies have examined patterns of what evidence available to consumers, dietary supplement use con- dietary supplements are prescribed by health care providers. tinues to rise.1–3,10 Vitamins, whether taken in combination or Thus, the purpose of this study was to examine prescribing individually, are the most frequently consumed type of dietary patterns of single-vitamin supplements (A, C, D, E, K) by – supplement in military populations.13 15 providers across all military treatment facilities (MTFs) in Single-vitamin supplements may be prescribed in a thera- the Department of Defense from 2007 to 2011. peutic role or for the prevention of chronic disease. Vitamin A may have a role in the treatment of many hyperkeratotic METHODS disorders of the skin,16 but its utility in the prevention of We used data from the Pharmacy Data Transaction Service cardiovascular disease and cancer remains unsubstantiated.17 (PDTS) to capture single-vitamin supplement (A, C, D, E, Although vitamin E may provide benefit in the treatment of and K) prescriptions dispensed by MTF pharmacies between cataracts of macular degeneration,18,19 its role in the preven- 2007 and 2011. The PDTS database is a centralized data tion or treatment of cancers, cardiovascular disease, or repository that pools information from all Military Health dementia remains inconclusive.20,21 Several therapeutic and System (MHS) points of reference; MTFs; TRICARE retail preventive roles have been described for vitamin C, but evi- pharmacy networks, and the Mail Order Pharmacy contrac- dence for prevention of chronic disease remains limited.22 In tor.32 The data included information on total prescriptions addition to improving skeletal health and prevention of per dietary supplement category per year for each MTF and injury from falls and fracture,23–25 vitamin D may have sev- were stratified by gender, age, and branch of service. Patient eral other extraskeletal benefits, including beneficial effects population groups included in the dataset were active duty, on immune and cardiovascular systems.26–30 Some supple- guard, reserve military members and their dependents (i.e., ments may be prescribed more commonly in certain patient spouses and children), and military retirees and their depen- groups than others; examples include prescribing vitamin K dents. However, the data were not stratified by duty or dependent status. Also, the data may include multiple prescriptions for the same patient. Analyses did not include Uniformed Services University, 4301 Jones Bridge Road, Bethesda, preparations that were a multivitamin of two or more vita- MD 20814. This article was presented as a poster presentation at Uniformed mins and/or other active ingredients (e.g., compound with Services University Research Week, Bethesda, MD, May 14–15, 2014. vitamins E and C). Accompanying population data were not doi: 10.7205/MILMED-D-14-00511 available in the data set from PDTS. To examine year by

748 MILITARY MEDICINE, Vol. 180, July 2015 Trends in Vitamin Supplement Prescriptions from MTFs year changes in prescriptions, we calculated prescription rates TABLE I. Percent Change in Number of Prescriptions for Total using data retrieved from the Defense Medical Epidemiology Single-Vitamin Supplement Prescriptions by Age Group From Database (DMED), which includes only active duty personnel. 2007 to 2011 Raw prescription data were divided by total number of active Percent Change of Single-Vitamin duty personnel and multiplied by 1,000 (i.e., [number of pre- (A, C, D, E, K) Prescriptions scriptions from PDTS/population size from DMED] × 1,000) Age Groups (Years) From 2007 to 2011 to reﬂect prescription rates per 1,000 active duty personnel. 0–4 560 5–14 176 15–17 232 RESULTS 18–24 74 25–34 139 MTFs dispensed a total of 842 vitamin A; 190,198 vitamin C; –

35 44 245 Downloaded from https://academic.oup.com/milmed/article/180/7/748/4160604 by guest on 30 September 2021 568,030 vitamin D; 62,493 vitamin E; and 8,967 vitamin K 45–64 222 prescriptions during the 5-year period, for a total of >65 162 830,530. Figure 1 shows the number of single-vitamin supplement prescriptions per 1,000 active duty personnel by year. Vitamin A The most commonly prescribed was vitamin D (68%), followed by vitamin C (23%), vitamin E (8%), vitamin K Vitamin A prescriptions experienced a decrease for both (1%), and vitamin A (<1%). Across the 5-year period, the females and males of 27% and 35%, respectively, from number of vitamin D prescriptions increased 454%. In con- 2007 to 2011. The total number of prescriptions for females trast, the number of vitamin A, vitamin E, and vitamin K outnumbered the number for males by 2 to 1. Vitamin A pre- prescriptions decreased considerably by 32%, 53%, and 29% scriptions decreased 81% for the <18 age group, 15% for the respectively. Vitamin C prescriptions remained relatively 18 to 44 group, and 35% for the >44 age group (Fig. 4). stable and decreased less than 1%. Vitamin C ﬂ Table I re ects the percent change in prescription rates Vitamin C prescriptions over the 5-year period were fairly for all age groups. Age groups were further aggregated constant for both females and males, with an increase of just – (<18, 18 44, >44 years) for analysis. Across all aggregated 9% for the latter. The total number of prescriptions for age groups, total single-vitamin supplement prescriptions females outnumbered those for males by 1.4-fold. Vitamin C increased throughout the 5-year period (Fig. 2). The age prescriptions decreased 3% and 5% for the age categories group with the greatest increase in total single-vitamin sup- <18 years and >44 years, respectively, and increased 4% for plement prescriptions was the <18 group (350%). the18 to 44 year group over the 5-year period (Fig. 5). The average number of all supplement prescriptions over the 5-year period was 587,000 per year for females and Vitamin D 269,000 for males. The prescriptions for females and males Vitamin D prescriptions increased 421% and 626% for increased comparably by 176% and 189%, respectively, for males and females, respectively, over the 5-year period. all supplements combined over the time period of interest Increases of 881%, 1041%, and 389% were observed for the (Fig. 3). age categories <18 years, 18 to 44 years, and >44 years,

FIGURE 1. Total number of prescriptions for each vitamin across the 5-year period (2007–2011).

MILITARY MEDICINE, Vol. 180, July 2015 749 Trends in Vitamin Supplement Prescriptions from MTFs Downloaded from https://academic.oup.com/milmed/article/180/7/748/4160604 by guest on 30 September 2021

FIGURE 2. Total number of supplement prescriptions by age ranges FIGURE 4. Number of vitamin A prescriptions by age group from 2007 from 2007 to 2011. to 2011.

FIGURE 3. Total number of supplement prescriptions (vitamins A, C, D, E, K) by sex from 2007 to 2011. respectively (Fig. 6). Prescriptions for females outnumbered FIGURE 5. Number of vitamin C prescriptions by age group from 2007 those for males by 2.4-fold. to 2011.

Vitamin E Vitamin K Over the 5-year period, vitamin E prescriptions decreased Vitamin K prescriptions decreased for both females and 51% and 53% for females and males, respectively, with the males by 28% and 25%, respectively. The total number of total number of prescriptions for females outnumbering prescriptions for females was nearly equivalent to that for those for males by 2:1. Vitamin E prescriptions for those males. From 2007 to 2011, vitamin K prescriptions <18 years, 18 to 44 years, and >44 years decreased by 22% decreased 23%, 11%, and 36% for the age groups <18 years, 49%, and 55% respectively, from 2007 to 2011 (Fig. 7). 18 to 44 years, and >44 years, respectively (Fig. 8).

750 MILITARY MEDICINE, Vol. 180, July 2015 Trends in Vitamin Supplement Prescriptions from MTFs Downloaded from https://academic.oup.com/milmed/article/180/7/748/4160604 by guest on 30 September 2021

FIGURE 6. Number of vitamin D prescriptions by age group from 2007 to 2011.

FIGURE 8. Number of vitamin K prescriptions by age group from 2007 to 2011.

When comparing supplements prescribed by the age groups, the number of prescriptions for those >44 years outnumbered those in the other age groups for vitamins A, D, E, and K.

DISCUSSION Our study investigated trends in the prescription of five single- vitamin supplements (A, C, D, E, K) by MTF providers from 2007 to 2011. Overall, the total number of single-vitamin supplement prescriptions increased over the 5-year period investigated, which is consistent with national surveys indicating an increase in dietary supplement use among general and military populations.1–3,15 Importantly, this increase was primarily because of the increased rate of vitamin D prescriptions. In our study, the total number of vitamin D prescriptions per 1,000 active duty personnel increased 454% over the 5-year period. This increase in vitamin D prescriptions was observed fl FIGURE 7. among all age groups for the 5-year period and may re ect rap- Number of vitamin E prescriptions by age group from 2007 28,33 to 2011. idly evolving clinical guidelines, as well as burgeoning evidence that low vitamin D levels may play a role in the development of chronic disease.26,29,30,34 Although there is no Summary clear consensus on optimal levels of 25-hydroxyvitamin D MTF supplement prescriptions for vitamins A, C, D, E, and (25(OH)D), a vitamin D deficiency has been defined by most K increased over the 5-year period 2007 to 2011. Vitamin D experts in the field as a 25(OH)D level less than 30 nM.35 was prescribed more than twice as much as all the other In 1997, the U.S. Institute of Medicine (IOM) concluded vitamins combined and was the only one among these five that children and adults up to 50 years of age require only individual vitamins with an overall increase over the 5-year 200 IU of vitamin D per day to maintain skeletal health. period. Vitamin C was relatively constant, and vitamins A, However, recent evidence suggests that 25(OH)D levels of E, and K decreased over the same time period. Prescription 50 nM or higher may be necessary for optimal health.35–37 rates for vitamins C and E were two times higher than for Subclinical vitamin D insufficiency (i.e., at risk for inade- vitamin K and three times higher than vitamin A. quacy, defined as a 25(OH)D of 30–49 nM35) may contribute

MILITARY MEDICINE, Vol. 180, July 2015 751 Trends in Vitamin Supplement Prescriptions from MTFs to the risk of chronic disease, particularly osteomalacia and their beneficiaries; whereas the data from DMED include osteoporosis and possibly cancer, cardiovascular disease, type only active duty personnel. Despite this limitation of this 2diabetes,andautoimmunedisorders.27,28,35,37,38 These study, the patterns tell a story that can be used for education, recent findings led to a new IOM report and new clinical further research, and policy recommendations. Future research practice guidelines from the U.S. Endocrine Society, both of should strive to procure additional patient information such which recommend significantly increasing vitamin D intake as clinical diagnosis, past medical history, nutrition status, over the 1997 recommendations.28,33 However, recent evi- and military-duty status (active vs. beneficiary) as this would dence suggests that 25(OH)D levels greater than 120 nM may provide further insights into results. In addition, it would be be harmful,35,36 so providers who prescribe vitamin D should advantageous to know whether practitioners prescribe these monitor patients’ blood levels to ensure they remain within dietary supplements in accordance with recognized clinical those deemed optimal. recommendations or at the request of the patients. Downloaded from https://academic.oup.com/milmed/article/180/7/748/4160604 by guest on 30 September 2021 Our study revealed decreases in prescriptions for single- In summary, we noted a significant increase in prescrip- vitamin E (32%) and single-vitamin A (53%) supplements tions of vitamin D supplements, a relatively constant trend across the 5-year period. These findings are consistent with in vitamin C prescriptions, and a decrease in prescriptions of others that reported use of vitamin A and vitamin E supple- vitamins A, E, and K over the 5-year period examined. The ments peaked in 1994 or 1998 and then decreased subse- exhibited trends seem to reflect the current pattern of dietary quently for both men and women.39 This change coincides supplement use in the general population, as well as current with published clinical trials and reviews suggesting that clinical issues, particularly with regard to vitamins A, D, vitamins A and E have no effects on the risk of cancer or and E. Future investigation should include the diagnoses for cardiovascular disease.21,40 Nearly all randomized trials of which these supplements are prescribed and whether said vitamin E have shown no benefit for primary or secondary supplements were effective for their intended use. Further prevention of coronary heart disease.41 The Women’s Health work addressing these areas would help close gaps in cur- Study (WHS) revealed vitamin E supplementation had no rent dietary supplement scientific literature. effect on the occurrence of cardiovascular events.21 Similarly, most studies with beta-carotene (to increase vitamin A) have 42–44 ACKNOWLEDGMENT not shown any effect on cancer prevention. It appears that our findings reflect the shifting clinical paradigm with This work was supported by the Center Alliance for Dietary Supplement regard to both vitamin A and vitamin E supplementation. Research, NB91FD. Prescription rates for vitamin C were relatively constant, with a less than 1% change across the 5-year period. Although REFERENCES evidence does not support the use of supplemental vitamin C to prevent chronic disease, there is also no evidence that 1. Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT: Why US adults use dietary supplements. JAMA Internal Med 2013; 173(5): 355–61. supplementing with vitamin C does any harm, as suggested 22,45 2. Briefel RR, Johnson CL: Secular trends in dietary intake in the for other antioxidant vitamins. Based on anecdotal evi- United States. Annu Rev of Nutr 2004; 24: 401–31. dence, vitamin C is often used for the prevention of common 3. Gahche J, Bailey R, Burt V, et al: Dietary supplement use among U.S. colds, but a recent meta-analysis showed that supplementation adults has increased since NHANES III (1988–1994). NCHS Data Brief – with vitamin C was not effective for this purpose.46 2011; (61): 1 8. 4. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C: Mortality The observed decrease in vitamin K prescriptions was in randomized trials of antioxidant supplements for primary and secondary greatest in the age group >44. Observational data suggest prevention: systematic review and meta-analysis. JAMA 2007; 297(8): that low vitamin K consumption or impaired vitamin K status 842–57. may be associated with increased risk of fractures in older 5. Cellini M, Attipoe S, Seales P, et al: Dietary supplements: physician adults.47 However, randomized controlled trials of vitamin K knowledge and adverse event reporting. Med Sci Sports Exerc 2013; 45(1): 23–8. supplementation in predominantly Caucasian populations 6. Fahey JW, Kensler TW: Role of dietary supplements/nutraceuticals in have not shown clinically significant improvements in bone chemoprevention through induction of cytoprotective enzymes. Chem 48–50 mineral density. The observational studies were pub- Res Toxicol 2007; 20(4): 572–6. lished before the period investigated in our study, whereas 7. Huang HY, Caballero B, Chang S, et al: The efficacy and safety of the randomized trials emerged at the onset of the 5-year multivitamin and mineral supplement use to prevent cancer and chronic fi disease in adults: a systematic review for a National Institutes of Health period. It is unclear whether our ndings are a result of state-of-the-science conference. Ann Intern Med 2006; 145(5): 372–85. evolving clinical practice or other confounding variables not 8. Petroczi A, Taylor G, Naughton DP: Mission impossible? Regulatory accounted for in this study. and enforcement issues to ensure safety of dietary supplements. Food One major limitation of our study must be noted: differ- Chem Toxicol 2011; 49(2): 393–402. ent sources were used to obtain population and prescription 9. Rosenberg IH: Challenges and opportunities in the translation of the science of vitamins. Am J Clin Nutr 2007; 85(1): 325S–7S. data. The prescription data were obtained from the PDTS, 10. Sadovsky R, Collins N, Tighe AP, Brunton SA, Safeer R: Patient use whereas the population data came from DMED. Data from of dietary supplements: a clinician’s perspective. Curr Med Res Opin PDTS included active-duty military, veterans, reserves, and 2008; 24(4): 1209–16.

752 MILITARY MEDICINE, Vol. 180, July 2015 Trends in Vitamin Supplement Prescriptions from MTFs

11. Timbo BB, Ross MP, McCarthy PV, Lin CT: Dietary supplements in a 32. The Defense Health Agency Pharmacy Operations Division 2014. national survey: prevalence of use and reports of adverse events. J Am Available at http://pec.ha.osd.mil/pdts/about.php?submenuheader=4; Diet Assoc 2006; 106(12): 1966–74. accessed October 21, 2014. 12. National Institutes of Health State-of-the-Science Panel: National Insti- 33. Rosen CJ, Gallagher JC: The 2011 IOM Report on Vitamin D and Cal- tutes of Health State-of-the-Science Conference Statement: multivitamin/ cium Requirements for North America: clinical implications for providers mineral supplements and chronic disease prevention. Am J Clin Nutr treating patients with low bone mineral density. J Clin Densitom 2011; 2007; 85(1): 257S–64S. 14(2): 79–84. 13. Institute of Medicine (US) Committee on Dietary Supplement Use by 34. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M: Vitamin D Military Personnel: Use of Dietary Supplements by Military Personnel. deficiency in children and its management: review of current knowledge Edited by Greenwood MRC, Oria M. Washington, DC, National Acad- and recommendations. Pediatrics 2008; 122(2): 398–417. emies Press, 2008. 35. Looker AC, Johnson CL, Lacher DA, Pfeiffer CM, Schleicher RL, 14. Lieberman HR, Stavinoha TB, McGraw SM, White A, Hadden LS, Sempos CT: Vitamin D status: United States, 2001-2006. NCHS Data Marriott BP: Use of dietary supplements among active-duty US Army Brief 2011; (59): 1–8. soldiers. Am J Clin Nutr 2010; 92(4): 985–95. 36. Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, et al: Is there a Downloaded from https://academic.oup.com/milmed/article/180/7/748/4160604 by guest on 30 September 2021 15. Knapik J, Steelman R, Hoedebecke S, Farina E, Austin K, Lieberman H: reverse J-shaped association between 25-hydroxyvitamin D and all-cause A systematic review and meta-analysis on the prevalence of dietary mortality? Results from the U.S. nationally representative NHANES. supplement use by military personnel. BMC Complement Altern Med J Clin Endocrinol Metab 2013; 98(7): 3001–9. 2014; 14(1): 143. 37. Yetley EA, Pfeiffer CM, Schleicher RL, et al: NHANES monitoring 16. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current of serum 25-hydroxyvitamin D: a roundtable summary. JNutr 2010; use and future potential role of retinoids in dermatology. Drugs 1997; 140(11): 2030s–45s. 53(3): 358–88. 38. Pramyothin P, Holick MF: Vitamin D supplementation: guidelines and 17. Albanes D, Heinonen OP, Taylor PR, et al: Alpha-tocopherol and beta- evidence for subclinical deficiency. Curr Opin Gastroenterol 2012; 28(2): carotene supplements and lung cancer incidence in the alpha-tocopherol, 139–50. beta-carotene cancer prevention study: effects of base-line characteristics 39. Kim HJ, Giovannucci E, Rosner B, Willett WC, Cho E: Longitudinal and study compliance. J Natl Cancer Inst 1996; 88(21): 1560–70. and secular trends in dietary supplement use: nurses’ health study and 18. Evans JR: Antioxidant vitamin and mineral supplements for slowing health professionals follow-up study, 1986-2006. J Acad Nutr Diet the progression of age-related macular degeneration. Cochrane Database 2014; 114(3): 436–43. Syst Rev 2006; (2): CD000254. 40. Ye Y, Li J, Yuan Z: Effect of antioxidant vitamin supplementation on 19. Age-Related Eye Disease Study Research Group: A randomized, placebo- cardiovascular outcomes: a meta-analysis of randomized controlled trials. controlled, clinical trial of high-dose supplementation with vitamins C PLoS ONE 2013; 8(2): e56803. and E and beta carotene for age-related cataract and vision loss: 41. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ: Use of anti- AREDS report no. 9. ArchOphthalmol 2001; 119(10): 1439–52. oxidant vitamins for the prevention of cardiovascular disease: meta- 20. Grundman M, Petersen RC, Ferris SH, et al: Mild cognitive impairment analysis of randomised trials. Lancet 2003; 361(9374): 2017–23. can be distinguished from Alzheimer disease and normal aging for clinical 42. Omenn GS, Goodman GE, Thornquist MD, et al: Effects of a combina- trials. ArchNeurol 2004; 61(1): 59–66. tion of beta carotene and vitamin A on lung cancer and cardiovascular 21. Lee IM, Cook NR, Gaziano JM, et al: Vitamin E in the primary preven- disease. N Engl J Med 1996; 334(18): 1150–5. tion of cardiovascular disease and cancer: the Women’s Health Study: a 43. Malila N, Virtamo J, Virtanen M, Pietinen P, Albanes D, Teppo L: randomized controlled trial. JAMA 2005; 294(1): 56–65. Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk 22. Gaziano JM, Glynn RJ, Christen WG, et al: Vitamins E and C in the for colorectal cancer in male smokers. Eur J Clin Nutr 2002; 56(7): prevention of prostate and total cancer in men: the Physicians’ Health 615–21. Study II randomized controlled trial. JAMA 2009; 301(1): 52–62. 44. Holick CN, Michaud DS, Stolzenberg-Solomon R, et al: Dietary carot- 23. Jackson C, Gaugris S, Sen SS, Hosking D: The effect of cholecalciferol enoids, serum beta-carotene, and retinol and risk of lung cancer in the (vitamin D3) on the risk of fall and fracture: a meta-analysis. QJM alpha-tocopherol, beta-carotene cohort study. Am J Epidemiol 2002; 2007; 100(4): 185–92. 156(6): 536–47. 24. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al: Fall pre- 45. Lee DH, Folsom AR, Harnack L, Halliwell B, Jacobs DR Jr.: Does sup- vention with supplemental and active forms of vitamin D: a meta-analysis plemental vitamin C increase cardiovascular disease risk in women with of randomised controlled trials. BMJ 2009; 339: b3692. diabetes? Am J Clin Nutr 2004; 80(5): 1194–200. 25. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al: Effect of 46. Hemila H, Chalker E: Vitamin C for preventing and treating the common Vitamin D on falls: a meta-analysis. JAMA 2004; 291(16): 1999–2006. cold. The Cochrane Database Syst Rev 2013; 1: CD000980. 26. Garland CF, Garland FC, Gorham ED, et al: The role of vitamin D in 47. Booth SL, Broe KE, Peterson JW, et al: Associations between vitamin cancer prevention. Am J Public Health 2006; 96(2): 252–61. K biochemical measures and bone mineral density in men and women. 27. Holick MF: Vitamin D deficiency. New Engl J Med 2007; 357(3): 266–81. J Clin Endocrinol Metabol 2004; 89(10): 4904–9. 28. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al: Evaluation, treat- 48. Binkley N, Harke J, Krueger D, et al: Vitamin K treatment reduces ment, and prevention of vitamin D deficiency: an Endocrine Society clin- undercarboxylated osteocalcin but does not alter bone turnover, density, ical practice guideline. J Clin Endocrinol Metab 2011; 96(7): 1911–30. or geometry in healthy postmenopausal North American women. J Bone 29. Lee JH, O'Keefe JH, Bell D, Hensrud DD, Holick MF: Vitamin D defi- Miner Res 2009; 24(6): 983–91. ciency an important, common, and easily treatable cardiovascular risk 49. Bolton-Smith C, McMurdo ME, Paterson CR, et al: Two-year random- factor? Am J Coll Cardiol 2008; 52(24): 1949–56. ized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus 30. Pilz S, Tomaschitz A, Marz W, et al: Vitamin D, cardiovascular disease calcium on the bone health of older women. J Bone Miner Res 2007; and mortality. Clin Endocrinol 2011; 75(5): 575–84. 22(4): 509–19. 31. Radimer KL, Subar AF, Thompson FE: Nonvitamin, nonmineral dietary 50. Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson- supplements: issues and findings from NHANES III. J Am Diet Assoc Hughes B: Effect of vitamin K supplementation on bone loss in elderly 2000; 100(4): 447–54. men and women. J Clin Endocrinol Metabol 2008; 93(4): 1217–23.

MILITARY MEDICINE, Vol. 180, July 2015 753