CELLINI, MATTHEW; ATTIPOE, SELASI; SEALES, PAUL; GRAY, ROBERT; WARD, ANDREW; STEPHENS, MARK; DEUSTER, PATRICIA A.
Dietary supplement (DS) use among US and British military personnel is widespread (3–6,12,20,27,37). In 2003, Deuster et al. (12) reported that 13% of US Army Rangers were taking creatine and ephedrine products on a regular basis. Likewise, Bovill et al. (6) documented that 87% of elite US soldiers reported using DS. In a survey conducted by Young and Stephens (37), half of the respondents (US Marine Corps recruits) used supplements at some point before boot camp. More recently, Lieberman et al. (20) reported that greater than 50% of soldiers used DS one or more times per week and 22% consumed combinations of three or more different DS each week. To address the use of DS in military populations, the Institute of Medicine (IOM) conducted a landmark review (17). The IOM findings suggested that certain supplements had the potential to negatively affect mission readiness and performance (17) and recommended developing a plan for tracking and monitoring adverse events (AE) from DS and herbal products.
The concern that some DS are unsafe and/or tainted is widely recognized (11,23,26), and the US Food and Drug Administration (FDA) has oversight authority in cases involving problematic products (1,23). Petroczi et al. (23) noted recently that ensuring and enforcing safety are particularly challenging because many DS are sold over the Internet. In addition to the need for better quality control, compliance, and public awareness, a greater emphasis must be placed on reporting of AE, because such reports can help identify signals (17). This directly affects patient safety and public health. In 2008, Gardiner et al. (14) noted that limited coordination exists among national and international surveillance programs for evaluating signals from DS that may indicate potential public health risks. Thus, reporting of potential AE related to the use of DS is sporadic and unpredictable.
Because of the high incidence of DS use and the fact that potentially dangerous supplements are available, this project was designed to assess the overall knowledge and behaviors of health care providers regarding DS and possible AE associated with DS use. Specifically, we sought to determine 1) how providers address the issue of DS with patients, 2) provider and consumer knowledge regarding DS and AE reporting systems, 3) what DS used by patients was viewed as problematic, and 4) what AE was commonly seen and their possible associations with various DS.
Data were received from two prospective, cross-sectional, web-based questionnaires. Both were reviewed and approved by the Uniformed Services University (USU) Institutional Review Board. For the first, an announcement went out to as many Department of Defense (DoD) health care providers and allied health professionals as possible stating they could freely access the Natural Medicines Comprehensive Database (NMCD) to gather evidence-based information on DS and herbal products. Interested health professionals voluntarily entered the database established through the Human Performance Resource Center website (http://hprc-online.org/dietary-supplements/natural-medicines-comprehensive-database) and signed up for a unique identification number and password-protected account. Registered individuals who entered the website were then given an electronic prompt asking them to complete a brief questionnaire (see Supplemental Digital Content 1, http://links.lww.com/MSS/A181, NMCD Questionnaire) designed to assess baseline knowledge about DS use. Participants were then able to search the site for specific information relevant to their clinical practice. After completing their search, site users were prompted to complete a brief postuse questionnaire (see Supplemental Digital Content 1, http://links.lww.com/MSS/A181, NMCD Questionnaire). NMCD automatically stored all responses, and after 12 months, the data were exported as a relational database and returned to the investigators for analysis. All responses were anonymous, and no responses were linked to any form of identification, such as IP address or email domain.
The second questionnaire (see Supplemental Digital Content 2, http://links.lww.com/MSS/A182, USU Alumni Questionnaire) was sent to physicians who had graduated from the USU. The intent of the questionnaire was to learn about physician experiences and behaviors concerning DS, adverse affects their patients might have experienced using DS, and the ability and willingness of physicians to spend time reporting those AE. Participants were sent an email from an alumni database asking them to complete a questionnaire about DS use. The link to the questionnaire was sent out a total of four times to the USU alumni email database. Reminder emails were sent out monthly to nonrespondents. The email contained information about the study and a hyperlink to the questionnaire itself. Clicking on the hyperlink and voluntary completion of the questionnaire served as implied consent to participate. Basic demographic information about the physicians, but no personally identifying information, was collected. The website was open for respondents a total of 4 months, and responses were collected in a central spreadsheet maintained by the Office of Medical Education at USU.
The frequency distributions of the answers were analyzed using Predictive Analytics Software Statistics 18 (SPSS Inc., Chicago, IL). Frequencies of responses were calculated and evaluated.
A total of 1007 health care providers completed the preuse NMCD questionnaire (Appendix A). Of these, 34% of providers completed the postuse questionnaire (Appendix B). Respondents consisted of physicians (251), dietitians/nutritionists (141), physician assistants (71), nurses and nurse practitioners (66), exercise specialists (48), medics/corpsmen (33), basic scientists/researchers (22), clinical psychologists (14), physical therapists (12), medical assistants (3), and other allied health care providers (346). Respondents were primarily men (54%) and ranged in age from 22 to 60 yr; 46% were older than 40 yr. Nearly half (44%) of respondents had more than 10 yr of experience as health care professionals, and most (89%) cared for active duty military personnel.
Nearly four of five (79%) of respondents reported they routinely queried their patients about using DS. Three of four (75%) reported their patients routinely asked about or discussed DS-related issues with them. Only one in five (20%) of providers indicated they had a reliable source of information on DS or herbal products. This same number of respondents (20%) listed the NMCD as one of the reliable sources they used for DS information. Approximately 21% of respondents indicated they spent 31–60 min searching the literature for particular DS product information. Almost all providers (98%) wanted a trustworthy, frequently updated resource with information about DS/herbal product ingredients, their side effects, and common pharmaceutical interactions.
With respect to AE, 35% (n = 352) of respondents reported encountering a patient who had experienced a potential AE associated with supplement use. Only 20% (n = 71/352) subsequently reported the AE. Many respondents (59%) did not know how or where to report the AE. The majority of respondents (86%) wanted access to a simple, electronic online tool to facilitate reporting such events.
Physician responses to NMCD.
To effectively compare results from the NMCD and USU alumni physician questionnaires, we examined frequencies of physician (n = 251) responses. Almost all (96%) reported they cared for active duty military personnel. Of all physician respondents, only 18% indicated they had a dependable source for DS information. The primary DS resources were NMCD®; digital references (e.g., Lexicomp® and Epocrates®); textbooks, guides, reviews, and manuals; and government resources (e.g., National Institute of Health’s Office of Dietary Supplements, the FDA, and PubMed®). Despite not relying on one particular resource for DS information, most physicians (91%) indicated that they routinely asked their patients about DS use. Similarly, most physicians (82%) reported that their patients routinely discussed DS use with them.
Overall, more than half of the physicians (58%, n = 145) reported they had encountered a patient with possible AE from DS; only 16% (n = 23/145) of those reported the event (Fig. 1) and 74% did not know where or how to report such events. Approximately 90% expressed interest in a simple, electronic online tool for reporting AE associated with DS.
USU Alumni Questionnaire (Physicians)
The USU alumni questionnaire was sent to 1940 physicians, and complete data were obtained from 401 (21% response rate). Figure 2 presents the responses regarding how comfortable physicians were with fielding questions about herbal and DS from their patients. Only 5% were extremely comfortable, and likewise, 5% were extremely uncomfortable (5%) handling clinical questions related to DS use. Many respondents were neutral in terms of their having confidence in their ability to answer patient questions about DS. Figure 3 presents the distribution of physicians who believe their patients disclose their use of supplements and who ask them about use of supplements. The majority believed that less than 50% of their patients disclosed use of particular herbal and DS without being specifically prompted. Interestingly, the majority of physician respondents (66%) routinely asked most of their patients about DS use. Importantly, 65% reported they did not have a reliable source of information for herbal and DS. The sources used ranged from mobile applications or online websites like Up-to-Date®, Lexicomp®, MD Consult®, and Epocrates® to governmental sources such as nutrition.gov, PubMed®, Medline Plus®, National Library of Medicine, and the FDA; NMCD was used by only a few. These sources are consistent with the responses from the NMCD questionnaire.
Many USU alumni physicians (61%) responded that they had encountered adverse reactions in patients taking performance enhancing, body building, or weight loss supplements. Table 1 shows the 10 most frequently reported AE; other infrequent AE (less than five) noted in association with supplements included ecchymosis, edema, eosinophilic fasciitis, galactorrhea, hirsutism, neuroleptic malignant syndrome, pancreatitis, priapism, serotonin syndrome, and three deaths. The types of supplements respondents believed commonly associated with these AE included creatine, nitric oxide products, weight loss products, supplement blends, testosterone boosters, ephedra, thermogenic supplements, and energy drinks. One respondent emphasized that no controlled study had yet been conducted while exercising in 130°F environments when wearing full body armor and helmet.
With regard to AE reporting, four of five respondents (80%, n = 197/246) who suspected an AE related to supplement use did not report it. The 20% who did report the AE did so through a variety of venues, including the local hospital pharmacy, administrative medical contacts, FDA MedWatch®, and other hospital or unit reporting systems. Of note, three of four of respondents (approximately 73%) did not know how or where to report DS-associated AE. Most respondents (92%) acknowledged that they would report an AE if the process were linked to the electronic health record. Figure 4 presents the amount of time respondents would be willing to spend reporting AE from DS: 69% would be willing to devote up to 10 min to AE reporting, and some (14%) would commit to more than 10 min to report a suspected AE associated with DS use.
In a 2008 landmark publication, the IOM noted that the DoD had no systematic approach for evaluating the risks and benefits associated with DS use by service members (17). Other recent reports indicate that consumers do not fully understand the potential risks associated with using DS (31), nor do they realize that certain commonly used DS may be questionably marketed (32) or represent an important public health and safety issue (11,23,26). Our overall results support these findings. We found that most military physicians believe they have observed an AE from DS, yet very few have actually reported them. Moreover, most physicians did not know how or where to report an AE potentially associated with DS use. Likewise, the majority of our respondents did not have a trusted source for gathering information on the safety and efficacy of DS and other herbal products.
Concerns about AE from DS and other such products are justified. A sharp increase in the number of emergency department visits involving energy drinks was noted between 2005 and 2009, and more than 67% were classified as AE (25). Interestingly, 4% of persons responding to the 2002 Health and Diet Survey and taking DS believed they had personally experienced an AE from DS use (30). The particular AE related to DS noted by the physicians in our study presented a pattern: exertional rhabdomyolysis, hyperthermia/heat illness, acute renal failure, arrhythmias, and syncopal events. Similar AE appears in the literature as case reports (10,13,19,21,22,24,29,36). Coupled with the AE reports were consistent patterns of specific DS use. The most commonly suspected DS included nitric oxide products, weight loss supplements, testosterone boosters, ephedra, thermogenics, multiingredient products, and energy drinks. Had all of the AE “witnessed” by our respondents been reported to a central location, a trend (or “signal”) might have been detected and resultant actions taken. This is critical because, currently, less than 1% of AE from DS are reported to the FDA (35).
Existing literature suggests that physician knowledge about DS, in terms of AE reporting and regulatory oversight, is limited (2). We assessed the overall knowledge and actions of health care providers relative to DS and possible AE associated with DS use, and our results provide evidence that although 60% of military physicians believe they have observed AE in association with a DS, only 18% have actually reported them. Even when the AE were reported, the processes were inconsistent: ultimately, very few DS AE were sent to the FDA. Having a consistent process for reporting with a centralized database would be helpful for process improvement, signal detection, and improved patient safety. The implications of these findings relative to civilian providers remain to be determined, but a rapid, electronic method for reporting AE while concurrently providing a reliable source for information about DS would help to rectify the knowledge gap.
Our results suggest that one of the primary reasons why physicians report so few AE may likely be due to a deficit in knowledge on how to report AE. Time does not appear to be the primary barrier because more than 97% were willing to spend 1 min or more reporting AE (Fig. 4). Three of four physician respondents (approximately 73%) did not know how or where to report the AE associated with DS. This finding is consistent with a 2007 study of civilians by Ashar et al. (2), which noted physician knowledge of DS regulation and AE reporting was poor. This is unfortunate, however, because most providers are familiar with adverse drug reporting processes for reactions associated with pharmaceutical agents. Similarly, most providers are also familiar with Vaccine Adverse Event Reporting processes. It is unclear why similar interest or process development has not occurred for AE associated with DS use.
Another interesting finding was that although the number of physicians who asked their patients about DS use was high, relatively few providers believed they had an accurate and reliable source of DS information. Glisson and Walker (16) recently reviewed several issues regarding DS and physician counseling: they emphasized caution when advising patients about product safety and efficacy and encouraged all efforts to improve DS manufacturing processes. Health care providers and consumers alike have limited, if any, information regarding the safety and efficacy of DS and often find the labels of DS products difficult to interpret (31). When considered alongside recent reports of questionable marketing practices and potential adulteration or contamination of products (7–9,15,16,18,23,28,32–34), AE associated with DS use represents a significant patient safety and public health issue.
Our study further emphasizes the need for a systematic approach for analyzing risks and benefits of DS as encouraged by the 2008 IOM report (17). Many of our physicians believe they lack sufficient knowledge regarding DS safety and efficacy, and when coupled with consumer assumptions that DS is likely safe and possibly effective (16), the potential for unnecessary exposure to known AE associated with particular DS may go unnoticed. Targeted signal detection and improved provider and patient education can help to close the knowledge gap.
This study does have several important limitations. One is inherent response biases. Individuals responding to the NMCD questionnaire may be more likely to have an interest in DS and accordingly be biased. In addition, the poor response rate among the group of USU alumni might suggest that many military providers do not commonly encounter AE from DS or herbal products, so that only those who had witnessed them responded. In addition, certain military communities prohibit supplement use (aviation), so seeing and therefore reporting a side effect or AE from supplements would be unlikely. Regardless, the data are compelling and point to a gap that can be remedied.
In summary, based on responses from our two independent questionnaires, our study provides evidence that 1) military health care providers generally discuss DS with their patients, 2) the majority of providers encounter AE associated with DS use, and 3) very few providers either report or know how to report DS AE to the FDA. This information is extremely important concerning future policy and educational strategies and underscores the need for centralized processes for AE reporting. This project identified the perceived extent of AE with DS use, information gaps in DS information and AE reporting, and the utility/receptivity of a DoD electronic AE reporting system. Importantly, we determined that a centralized AE reporting system should consolidate AE and serve as a system for identifying signals for removing tainted and harmful DS. Overall, health professionals need to be informed on DS and be taught how to report AE from DS use.
We would like to acknowledge and thank the supporting personnel from the Natural Medicines Comprehensive Database and Dr. Donna Waechter, the Associate Dean for Medical Education at the Uniformed Services University (USU), for their contributions to this project.
This project was funded by USU protocol NA91FD (Center Alliance for Dietary Supplement Research).
The authors declare no conflicts of interest.
The views expressed are those of the authors and do not reflect the official position of the USU, Department of the Army, Department of the Air Force, Department of the Navy, or the US Department of Defense. In addition, the results of the present study do not constitute endorsement by the American College of Sports Medicine.
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