Abstract
Background
“Natural products” (NPs), including dietary supplements, are widely used, yet little is known about NP use for chronic pain and related conditions.
Objective
To develop a new NP survey to better understand reasons for NP use, beliefs, concerns, medication substitution, and provider disclosure.
Methods
Based on similar surveys and input from veteran focus groups and subject matter experts, a new brief NP survey was developed. The survey was piloted among 52 veterans with chronic pain enrolled in Veterans Health Administration (VA) primary care who endorsed NP use at baseline in a pragmatic trial comparing non-drug pain management approaches. Survey data was enriched with sociodemographic and clinical data from a parent trial. Descriptive frequencies and means were calculated.
Results
Of 55 surveys, 52 were completed (response rate, 94.5%). Respondents’ mean age was 57.6 (SD+/−12.5); 42% were women, 21% identified as Black/African American, and 10% Hispanic/Latinx ethnicity. All had chronic pain; 80% experienced disabling pain daily; 67% were prescribed non-opioid pain medication; 15% were prescribed opioids. In the prior 3 months, the mean number of NPs used was 4.6 (SD+/−3.2); 90% reported daily use. Most frequently used NPs were vitamins/minerals (94%), herbals/botanicals (60%); and cannabis (40%); one-third reported substituting NPs for pain medications. The majority endorsed safety concerns about interactions of NPs either with pain medications (55%) or other NPs (52%). Nearly all (98%) believed providers should discuss NP use with their patients, though only 52% had disclosed NP use to their providers.
Conclusions
Among veterans with chronic pain in VA primary care enrolled in a pragmatic trial, a new NP survey revealed prevalent use of multiple NPs concurrently, and in some cases, as substitutes for prescribed medications. Most veterans expressed safety concerns, yet a significant proportion reported not discussing NP use with their providers.
U.S. Veterans experience high rates of chronic pain with upwards of 60% of veterans reporting 1 or more chronic pain conditions.1,2 Moreover, a disproportionate burden of comorbid mental health problems in veterans with chronic pain has been associated with a high prevalence of prescription opioid use and adverse outcomes. 3 Thus, recent data and expert consensus have led healthcare systems, including the Veterans Health Administration (VA), to recommend non-pharmacological therapies (e.g., Cognitive Behavioral Therapy, exercise) and complementary and integrative health (CIH) approaches (e.g., yoga, mindfulness), as first line treatments for chronic pain.4,5 Natural products (NPs) are the most frequently used form of CIH in the U.S., and are often used alone or in combination with medications among those with chronic pain.6,7 Over half of U.S. adults and >70% of U.S. military service members report using NPs.8,9
U.S. retail sales of NPs have increased steadily over the past 2 decades. 10 NPs are non-pharmaceutical substances used to promote health and wellness or for symptom management. 11 NPs include dietary supplements (i.e., multivitamins, fish oil), and foods or liquids (i.e., herbal teas and tinctures). NPs may be applied topically (i.e., creams, gels, oils), or inhaled (i.e., aromatherapy). Some low to moderate quality studies indicate that NPs may reduce various pain-related symptoms either through direct effect or as a placebo.12,13 Although NPs are generally regarded as safe by patients, side-effects and drug-NP or NP-NP interactions exist.14-16 NPs are not subject to the same regulatory oversight as drugs regulated by the U.S. Food and Drug Administration, labeling may be misleading, 17 and some NPs contain toxic adulterants. 18 Thus, patient-provider communication is important in ensuring patient safety.
Moreover, patients may not disclose NP use to clinicians, 19 and clinicians and pharmacists do not typically inquire, 20 despite reports of NP substitution for medication, adverse side-effects in patients with chronic conditions, and potential medication interactions. 21 Overall, little is known about the frequency, duration, type, and patterns of NP use, as well as beliefs, attitudes, concerns, and disclosure to health care providers.
Although publicly available national surveys collect information on NPs among U.S. civilians, (i.e., The National Health and Nutrition Examination and the National Health Interview Surveys), 22 neither is specific to NP use for chronic pain and co-occurring conditions. 23 Moreover, these population-based surveys are lengthy, and require direct input of product labels or selection of items from long lists of products, which may not be feasible for clinical settings or pragmatic trials.
Given that VA-enrolled veterans with chronic pain are increasing encouraged to taper opioids,
24
continued and expanded use of NPs to self-manage pain and related conditions is likely.25-27 However, there are no recent studies that describe the use of NPs for pain management and related symptoms. This study was conducted as a supplement to an ongoing multi-site pragmatic trial, the “
Methods
Natural Products Survey Development
Between November 2020 and June 2021, our team iteratively developed a new survey to inventory and describe NP use in individuals with chronic pain. First, 2 of the study investigators (KS and TF) with prior training and/or clinical experience in NPs created an initial self-administered paper survey based on their working knowledge of the most frequently used and commercially available NPs for pain. Because chronic pain is typically accompanied by sleep disturbance, stress, depression, PTSD, or anxiety,29,30 items assessing NP use for these co-occurring conditions were included.
Next, standing Veteran Engagement Panels (consisting of ≤5 veterans each, not participating in the
Based on this preliminary feedback, aspects of the survey’s appearance, comprehensibility, and content were revised. Next, subject matter experts (SMEs), including 6 researchers and clinicians from across the U.S. with prior experience in NP-related clinical care, survey development, and clinical research were identified. SMEs first individually reviewed the survey and provided written feedback. Next, the study team (KS, TF, and NP) facilitated a group virtual feedback session. SMEs recommended (1) including questions about combination NPs (as opposed to only single vitamins, minerals, or other NPs), (2) narrowing the list of NPs to those primarily used to manage pain, and (3) providing open text response fields for veterans to write in other NPs used. SMEs also provided specific recommendations to clarify terminology, survey instructions, layout, and administration format.
After making revisions based on SME input and obtaining human subjects approval from the University of California, San Francisco, 13 veterans from the SFVAHCS (not participating in the
Natural Products Survey
The finalized paper survey was designed for self-administration and self-report. The survey instructed respondents to gather all NPs used in the prior month and refer to them while completing the survey. The survey contained the following 42 items color coded for readability and to facilitate response entry: Natural product(s) used in the last 30 days including multiple vitamins, mixed B vitamins, single vitamins or minerals, single herbal products (e.g., green tea), non-vitamin NPs (e.g., fish oil/omega-3), cannabis (THC- or CBD-predominant, roughly equal, unknown), other NPs used in the past month, and home remedies. Other NPs and home remedies include NPs with multiple ingredients (other than multivitamins and mixed B vitamins), and respondents were instructed to write in name and brand. For each of these items, participants were asked about frequency, duration, and indications for use [pain or mobility and/or co-occurring conditions, including sleep, posttraumatic stress disorder (PTSD) or anxiety, stress, depression, general health, or other reason], and experience, beliefs, concerns, and disclosure regarding NP use (Supplementary Appendix: Natural Products Survey).
Natural Products Pilot Survey Administration
Study Sample
Between November 2021-May 2022, the finalized NP survey was piloted in a subsample of veterans participating in the
Data Collection and Analyses
Two study staff each entered the survey data (via manual double data entry) and feedback form into a VA-approved REDCap firewall-protected and encrypted database. Each data field was automated to flag outliers, redundancies, and missing data. When surveys were administered over the phone, data was entered electronically, and quality control occurred via automation in REDCap. The NP survey dataset was enriched with baseline demographic and clinical data from the parent trial (
Results
Sociodemographic and Clinical Characteristics of 52 Veterans Completing the Natural Products Survey.
*In addition to VA health care benefit.
Clinically, 88% reported experiencing moderate to severe pain every day with a mean Brief Pain Inventory Severity score of 6.09 (SD +/− 1.16) and Interference score of 6.63 (SD +/−1.70). At baseline, 67% used non-opioid pain medication only; 15% used opioids plus other pain medication; 17% reported no pain medication. Forty-four percent screened positive for PTSD, 63% for moderate depression, and 35% for symptoms of moderate or severe anxiety (Table 1).
The mean number of NPs used (past month) was 4.6 (SD+/− 3.2); 17% used ≥8 or more different NPs; 90% reported daily use; 94% had used NPs for ≥6 months. Veterans reported multiple non-mutually exclusive reasons for NP use (Figure 1). Nearly all (98%) reported use for general health; 63% for pain and/or mobility concerns, 58% for sleep, and 40% for stress. Most (87%) reported use of NPs for ≥ 2 indications. Categories of NPs used were vitamins and/or minerals, which was reported by nearly all respondents (94%), followed by herbals (non-cannabis) (60%); while 40% reported using cannabis (Figure 2). The most frequently used individual NPs were vitamin D (67%), multivitamins (61%), cannabis products (40%), magnesium (36%), green tea (36%), fish oil/omega-3 (33%) and melatonin (33%) (Figure 3). The most frequently reported individual NPs for pain were cannabis products (33%), followed by oral magnesium (13%), multivitamins, turmeric, and capsaicin (12% each), fish oil or omega 3 (10%), and Vitamin D (8%) (Figure 4). Indications for natural product use in the past 30 days. Most frequent categories of natural products used in the past 30 days. Most frequently reported NPs used for any indication (past 30 days). Most frequently reported NPs used for pain in the past 30 days.



Of the 21 (40%) reporting using cannabis products for all indications, most reported using products that had a mix of cannabidiol (CBD, without the psychoactive component) and tetrahydrocannabinol (THC, the psychoactive component in cannabis). Indications for cannabis among those reporting use were pain or mobility (81%), sleep (62%), PTSD or anxiety (43%), stress (43%), and depression (29%).
Veterans’ Attitudes and Practices Related to NP Use.
*Among those responding that they did not speak to their VA healthcare providers(s) about NP use, their reasons follow: 55% assumed providers would not support NPs or discussing NPs “wouldn’t help”; 23% thought it was “unimportant to bring up”; 9% reported that NPs did not come up in their visit; 23% reported another reason.
Veterans’ Beliefs About Natural Products.
Fifty-one of 52 respondents provided feedback on the survey itself. The majority “strongly agreed” or “agreed” with the following: (1) the time required to complete the survey was reasonable; (2) the instructions were useful; (3) questions were in a logical order; (4) questions were of interest; (5) were comfortable answering the questions; (6) information needed to complete the survey was easy to find/gather in their homes, and (7) survey accurately captured their NP use.
Discussion
The development of a new natural products survey was motivated by a lack of information about NP use for chronic pain and related conditions, coupled with the opportunity to capture this information among a diverse group of veterans with chronic pain recruited from VA primary care clinics across the U.S. who were participating in a trial of non-pharmacological pain management approaches and reported NP use at baseline. Moreover, reticence about discussing NP use among patients and clinicians has created a knowledge gap, thus reducing opportunities for informed shared decision-making. The new NP survey not only inventories specific NPs, but also ascertains intensity and indications for use, as well as experiences, beliefs, and practices regarding NPs. Future studies are needed to demonstrate the generalizability and utility of the NP survey in other research and clinical care settings, such as primary care, although, of note, all veterans completing the NP survey were concurrently enrolled in VA primary care and were participating in a pragmatic trial in which the study interventions were delivered by VA clinicians using the VA virtual care platform.
In our sample, nearly a third reported substitution of NPs for medications prescribed for pain and co-occurring conditions. One study found that nearly 1 in 5 U.S. adults used NPs instead of their prescribed medications. 33 As our and other studies have shown, patients may substitute NPs for prescribed pain medications because they feel their pain is inadequately treated, they are concerned about medication side-effects, or they believe NPs to be more effective and/or less harmful. 34 Of concern, the use of NPs in lieu of pain or other medications could result in non-adherence to prescribed medications, which may lead to harm, especially for patients with underlying serious health conditions (i.e., hypertension, diabetes).35,36
Potential harm from NPs could be prevented by providers inquiring about their patients’ use. Nearly all surveyed felt that providers should talk to patients about NP use, and stated they would use NPs for pain or related symptoms if the VA provided them at no cost. Of note, several of the most frequently reported NPs in this study (vitamin D, multivitamins, magnesium) are available on the national VA formulary, such that they may be prescribed at low or no cost. A likely smaller proportion of veterans surveyed reported cannabis use for pain and related conditions, which may represent under-reporting related to the prohibition on cannabis prescribing in the VA as a federal health care system. Some of the expressed barriers and concerns about NPs (e.g., cost, lack of access and information, potential harms, interactions with other NPs and medications) could be mitigated by increased provider involvement, specifically in discussing the risks and benefits of using NPs in the context of underlying health conditions and concomitant medications.6,34,37
Our study revealed, however, that only about half of respondents using NPs had discussed NP use with their providers. Ours and other studies have indicated that since NPs are widely available without prescription and are “natural,” they are generally believed to be “safe.” 38 This may explain prior observations that individuals are comfortable obtaining most information about NPs from the internet, social media, friends, and family, rather than from their health care providers.19,39,40 Also, clinicians and pharmacists generally lack knowledge about NPs, which explains why they may avoid discussions about NPs with their patients.41,42 Online databases (e.g., NatMed Pro, Herbs at a Glance, The Nutrition Source, National Institutes of Health Office of Dietary Supplements, and National Center for Complementary and Integrative Health) readily allow clinicians to access non-commercial, independent information about NP efficacy and safety that is updated semi-regularly.43-47 Broader use of these accessible databases by clinicians would facilitate communication and shared decision-making with patients about NP use, potentially limiting harms and improving the management of chronic pain. 48
A strength of our study was that our purposive sample of veteran respondents was drawn from primary care clinics at 5 geographically diverse VA facilities across the U.S. and was more inclusive and representative than the general VA population with a higher proportion of women, racial/ethnic minority, and younger veterans. In addition, a higher-than-expected response rate (95%) likely reflects not only follow-up by study staff, but also supports findings from our preliminary focus group testing that veterans found the survey of personal interest, non-threatening, and easy to complete, not surprising as survey development occurred in iterative steps with veteran input and feedback. Also, despite most survey respondents not completing college, unemployed and/or low income, and disabled with multiple comorbid mental health conditions, most participants (67%) completed the paper survey on their own without assistance. Nevertheless, roughly a third requested assistance or expressed a preference for a phone survey. Thus, future iterations must attempt to assure an 8th grade reading level to facilitate broader use and self-administration. This may be challenging however, since reading level is partially determined by multiple syllable words, and the specific names of some NPs have multiple syllables and are lengthy.
A limitation of this pilot study is that preliminary survey findings were limited to a relatively small VA primary care-enrolled veteran population (not a general patient population with chronic pain). In addition, these respondents were enrolled in a pragmatic trial comparing non-pharmacological pain management approaches and endorsed NP use at baseline. Therefore, this sample of veterans likely used more NPs the general population, and perhaps started or increased NP use as a function of trial participation (although the comparator interventions were not focused on NP use). Moreover, this sample may have been biased in favor of NP use, yet respondents still expressed concerns about NPs, challenges in accessing NPs, as well as dissatisfaction about their communication with their providers re: NP use. Following this pilot, the NP survey was revised minimally and was incorporated into the
Another limitation is that NP data was collected by self-report only. Respondents were asked to gather all NPs used in the past 30 days and refer to labels while completing the survey. The VA electronic health record (EHR) was not used to validate self-reported NPs because only a minority of veterans have NPs recorded in the EHR and NPs are not systematically updated like other medications because most are not prescribed by VA. The survey was administered during the COVID-19 pandemic and thus home visits were not possible. As video telehealth is more widely used in VA and other healthcare systems, assessments using video/virtual platforms could be leveraged to verify names and brands of NPs. Future studies are needed to further pilot and validate the use of this NP survey in broader veteran and non-veteran populations with chronic pain, and video technology could be used to increase the accuracy/validity of self-report.
In sum, this study on NP use in a small, yet diverse sample of veterans with chronic pain participating in a multi-site pragmatic trial produced an acceptable and feasible survey as well as descriptive information about NPs for pain, an area in which there has been a knowledge gap. Among survey respondents, NP use was intensive and longstanding, and NPs were used for multiple reasons in addition to pain. Respondents also disclosed the substitution of NPs for prescribed medication and lack of disclosure to their providers. While most NPs are generally considered safe, some may be mislabeled, contain adulterants, have side-effects or drug/NP interactions, especially in patients (or veterans) with comorbidities prescribed multiple medications. Although patients strongly endorsed the need to consult their providers about NP use, many clinicians lack knowledge and up-to-date information re: NP use.42,48 Fortunately, clinicians can access several online evidence-informed NP databases that may support communication and informed shared decision-making to improve safety and pain-related outcomes in their patients.
Supplemental Material
Supplemental Material - Natural Product Use for Chronic Pain: A New Survey of Patterns of Use, Beliefs, Concerns, and Disclosure to Providers
Supplemental Material for Natural Product Use for Chronic Pain: A New Survey of Patterns of Use, Beliefs, Concerns, and Disclosure to Providers by Karen H. Seal, MD, MPH, Termeh Feinberg, PhD, Liliana Moore, MA, Nicole A. Woodruff, BS, Natalie Purcell, PhD, MPA, Daniel Bertenthal, MPH, Nicole McCamish, MA, and William R. Becker, MD in Global Advances in Integrative Medicine and Health
Footnotes
Acknowledgments
We acknowledge the contributions of Mr. Allan Chan regarding data collection and management and Tammy Lee, MPH for project oversight. We are also grateful for the contributions of the many veterans who participated in the creation of the Natural Products survey.
Author Contributions
Termeh Feinberg: Conceptualization, Methodology, Writing-Review & Editing; Liliana Moore: Validation, Investigation, Writing-Review & Editing; Nicole A. Woodruff: Validation, Investigation, Writing-Review & Editing; Natalie Purcell: Conceptualization, Methodology, Investigation, Writing-Review & Editing; Daniel Bertenthal: Validation, Formal Analysis, Writing-Review & Editing; McCamish: Conceptualization, Project Administration; William R. Becker: Conceptualization, Conceptualization, Methodology, Funding acquisition.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Salary support was received from cooperative agreement UH3AT009765-03S1 (KHS, LCM, NAW, NP, DB, and NM). At the time of submission, Termeh Feinberg served as a federal contractor to the NIH National Center for Complementary and Integrative Health, and as an advisor to an advocacy group founded prior to this work (The American Herbalists Guild Research Chapter).
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is supported through cooperative agreement UH3AT009765-03S1 from the Office of Dietary Supplements and the National Center for Complementary and Integrative Health, National Institutes of Health.
Disclosure
Supplemental Material
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References
Supplementary Material
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