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

Transcription

1 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 from 2007 Methods: We examined prescription data from the Department of Defense Pharmacy Data Transaction 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 Most adults in the United States use dietary supplements. 1 3 However, the medical and scientific communities have vastly divergent opinions on the safety and effectiveness of dietary supplements Thus, attempts to arrive at a consensus have produced disparate recommendations. 12,13 Despite conflicting evidence available to consumers, dietary supplement use continues to rise. 1 3,10 Vitamins, whether taken in combination or individually, are the most frequently consumed type of dietary supplement in military populations Single-vitamin supplements may be prescribed in a therapeutic role or for the prevention of chronic disease. Vitamin A may have a role in the treatment of many hyperkeratotic disorders of the skin, 16 but its utility in the prevention of cardiovascular disease and cancer remains unsubstantiated. 17 Although vitamin E may provide benefit in the treatment of cataracts of macular degeneration, 18,19 its role in the prevention or treatment of cancers, cardiovascular disease, or dementia remains inconclusive. 20,21 Several therapeutic and preventive roles have been described for vitamin C, but evidence for prevention of chronic disease remains limited. 22 In addition to improving skeletal health and prevention of injury from falls and fracture, vitamin D may have several other extraskeletal benefits, including beneficial effects on immune and cardiovascular systems Some supplements may be prescribed more commonly in certain patient groups than others; examples include prescribing vitamin K Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD This article was presented as a poster presentation at Uniformed Services University Research Week, Bethesda, MD, May 14 15, doi: /MILMED-D to correct congenital deficiencies in neonates and vitamin D to obese and elderly patients, where levels may be low. Substantial information is available on prevalence of dietary supplement use among the general population through nationally representative surveys. 1,31 To the best of our knowledge, no other studies have examined patterns of what dietary supplements are prescribed by health care providers. Thus, the purpose of this study was to examine prescribing patterns of single-vitamin supplements (A, C, D, E, K) by providers across all military treatment facilities (MTFs) in the Department of Defense from 2007 METHODS We used data from the Pharmacy Data Transaction Service (PDTS) to capture single-vitamin supplement (A, C, D, E, and K) prescriptions dispensed by MTF pharmacies between 2007 and The PDTS database is a centralized data repository that pools information from all Military Health System (MHS) points of reference; MTFs; TRICARE retail pharmacy networks, and the Mail Order Pharmacy contractor. 32 The data included information on total prescriptions per dietary supplement category per year for each MTF and were stratified by gender, age, and branch of service. Patient population groups included in the dataset were active duty, guard, reserve military members and their dependents (i.e., spouses and children), and military retirees and their dependents. 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 preparations that were a multivitamin of two or more vitamins and/or other active ingredients (e.g., compound with vitamins E and C). Accompanying population data were not available in the data set from PDTS. To examine year by 748 MILITARY MEDICINE, Vol. 180, July 2015

2 year changes in prescriptions, we calculated prescription rates using data retrieved from the Defense Medical Epidemiology Database (DMED), which includes only active duty personnel. Raw prescription data were divided by total number of active duty personnel and multiplied by 1,000 (i.e., [number of prescriptions from PDTS/population size from DMED] 1,000) to reflect prescription rates per 1,000 active duty personnel. RESULTS MTFs dispensed a total of 842 vitamin A; 190,198 vitamin C; 568,030 vitamin D; 62,493 vitamin E; and 8,967 vitamin K prescriptions during the 5-year period, for a total of 830,530. Figure 1 shows the number of single-vitamin supplement prescriptions per 1,000 active duty personnel by year. The most commonly prescribed was vitamin D (68%), followed by vitamin C (23%), vitamin E (8%), vitamin K (1%), and vitamin A (<1%). Across the 5-year period, the number of vitamin D prescriptions increased 454%. In contrast, the number of vitamin A, vitamin E, and vitamin K prescriptions decreased considerably by 32%, 53%, and 29% respectively. Vitamin C prescriptions remained relatively stable and decreased less than 1%. Table I reflects the percent change in prescription rates for all age groups. Age groups were further aggregated (<18, 18 44, >44 years) for analysis. Across all aggregated age groups, total single-vitamin supplement prescriptions increased throughout the 5-year period (Fig. 2). The age group with the greatest increase in total single-vitamin supplement prescriptions was the <18 group (350%). The average number of all supplement prescriptions over the 5-year period was 587,000 per year for females and 269,000 for males. The prescriptions for females and males increased comparably by 176% and 189%, respectively, for all supplements combined over the time period of interest (Fig. 3). TABLE I. Percent Change in Number of Prescriptions for Total Single-Vitamin Supplement Prescriptions by Age Group From 2007 to 2011 Percent Change of Single-Vitamin (A, C, D, E, K) Prescriptions Age Groups (Years) From 2007 to > Vitamin A Vitamin A prescriptions experienced a decrease for both females and males of 27% and 35%, respectively, from 2007 The total number of prescriptions for females outnumbered the number for males by 2 to 1. Vitamin A prescriptions decreased 81% for the <18 age group, 15% for the 18 to 44 group, and 35% for the >44 age group (Fig. 4). Vitamin C Vitamin C prescriptions over the 5-year period were fairly constant for both females and males, with an increase of just 9% for the latter. The total number of prescriptions for females outnumbered those for males by 1.4-fold. Vitamin C prescriptions decreased 3% and 5% for the age categories <18 years and >44 years, respectively, and increased 4% for the18 to 44 year group over the 5-year period (Fig. 5). Vitamin D Vitamin D prescriptions increased 421% and 626% for males and females, respectively, over the 5-year period. Increases of 881%, 1041%, and 389% were observed for the 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 ( ). MILITARY MEDICINE, Vol. 180, July

3 FIGURE 2. Total number of supplement prescriptions by age ranges from 2007 FIGURE 4. Number of vitamin A prescriptions by age group from 2007 FIGURE 3. Total number of supplement prescriptions (vitamins A, C, D, E, K) by sex from 2007 respectively (Fig. 6). Prescriptions for females outnumbered those for males by 2.4-fold. Vitamin E Over the 5-year period, vitamin E prescriptions decreased 51% and 53% for females and males, respectively, with the total number of prescriptions for females outnumbering those for males by 2:1. Vitamin E prescriptions for those <18 years, 18 to 44 years, and >44 years decreased by 22% 49%, and 55% respectively, from 2007 to 2011 (Fig. 7). FIGURE 5. Number of vitamin C prescriptions by age group from 2007 Vitamin K Vitamin K prescriptions decreased for both females and males by 28% and 25%, respectively. The total number of prescriptions for females was nearly equivalent to that for males. From 2007 to 2011, vitamin K prescriptions decreased 23%, 11%, and 36% for the age groups <18 years, 18 to 44 years, and >44 years, respectively (Fig. 8). 750 MILITARY MEDICINE, Vol. 180, July 2015

4 FIGURE 6. Number of vitamin D prescriptions by age group from 2007 FIGURE 8. Number of vitamin K prescriptions by age group from 2007 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. FIGURE 7. Number of vitamin E prescriptions by age group from 2007 Summary MTF supplement prescriptions for vitamins A, C, D, E, and K increased over the 5-year period 2007 Vitamin D was prescribed more than twice as much as all the other vitamins combined and was the only one among these five individual vitamins with an overall increase over the 5-year period. Vitamin C was relatively constant, and vitamins A, E, and K decreased over the same time period. Prescription rates for vitamins C and E were two times higher than for vitamin K and three times higher than vitamin A. DISCUSSION Our study investigated trends in the prescription of five singlevitamin supplements (A, C, D, E, K) by MTF providers from 2007 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 among all age groups for the 5-year period and may reflect rapidly evolving clinical guidelines, 28,33 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 clear consensus on optimal levels of 25-hydroxyvitamin D (25(OH)D), a vitamin D deficiency has been defined by most experts in the field as a 25(OH)D level less than 30 nm. 35 In 1997, the U.S. Institute of Medicine (IOM) concluded that children and adults up to 50 years of age require only 200 IU of vitamin D per day to maintain skeletal health. However, recent evidence suggests that 25(OH)D levels of 50 nm or higher may be necessary for optimal health Subclinical vitamin D insufficiency (i.e., at risk for inadequacy, defined as a 25(OH)D of nm 35 ) may contribute MILITARY MEDICINE, Vol. 180, July

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

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