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Address correspondence to: Emily K. Farina, PhD, RD, Military Nutrition Division, US Army Research Institute of Environmental Medicine, Bldg 42, Kansas St, Natick, MA 01760.
Information on patterns of concomitant dietary supplement (DS) and prescription medication (PM) use among US adults is limited. Thus, the prevalence of concomitant DS and PM use as a function of doctor-informed medical conditions (DIMC) was determined in a cross-sectional, observational study of a nationally representative sample of noninstitutionalized, civilian adults aged ≥20 years in the United States (N=9,950) from the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Data were weighted for the complex, multistage, probability sampling design. Approximately one third (34.3%) of all US adults reported concomitant DS and PM use (approximately one in three adults). The prevalence of use was significantly higher among those with vs without a DIMC (47.3% vs 17.3%). Adults with a DIMC were more than two and a half times more likely to concomitantly use DS and PM than adults without a DIMC, after adjustment for sex, age, education, and household income. Multivitamin plus other ingredient(s), followed by antacids and multivitamin plus botanical ingredient(s), were the most prevalent DS categories used with a PM among those with and without a DIMC. The most prevalent PM categories used with a DS were cardiovascular agents (among those with a DIMC) and hormones (among those without a DIMC). These findings demonstrate that presence of a DIMC may be a risk factor for concomitant DS and PM use among US adults. Multivitamins containing nonvitamin or mineral ingredients are more commonly used than standard multivitamins with PM by US adults. This may be an emerging trend that warrants further consideration.
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More than half of US adults report using at least one dietary supplement (DS) during the previous 30 days.
The incidence of potential interactions between dietary supplements and prescription medications in cancer patients at a Veterans Administration Hospital.
Prevalence of polypharmacy, polyherbacy, nutritional supplement use and potential product interactions among older adults living on the United States-Mexico border: A descriptive, questionnaire-based study.
thereby altering the effectiveness of prescription medications (PM). A review of documented interactions between DS and PM found that DS containing St John's wort, magnesium, calcium, iron, and Gingko biloba had the highest number of potential interactions, whereas DS containing flaxseed, Echinacea, and yohimbe had the highest number of contraindications.
However, information to aid health care and dietetics practitioners in identifying populations at risk for experiencing DS and PM interactions remains limited.
In our study, the prevalence proportion (percent) and point prevalence (total number) of concomitant DS and PM use among all US adults, according to doctor-informed medical conditions (DIMC) were determined by analyzing data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of noninstitutionalized civilian adults and children in the United States. Our analysis included use of the NHANES Dietary Supplement Database (NHANES-DSD), which is the largest publicly available national database of DS use. The DS categories most commonly used with a PM, as well as the PM categories most commonly used with DS, are also reported.
Materials and Methods
Subjects
Data were drawn from NHANES, which is administered and managed by the National Center for Health Statistics (NCHS). Comprehensive sample selection and data collection methods are detailed elsewhere.
Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey. http://www.cdc.gov/nchs/nhanes.htm. Accessed November 29, 2012.
Briefly, sampling is performed with a complex, multistage, probability sampling design to obtain a nationally representative sample of noninstitutionalized civilian adults and children in the United States. This study used data pooled from the 2005-2006 (N=10,348) and 2007-2008 (N=10,149) data collection series. Of the 19,712 subjects with data from both the household interview and mobile examination center, 10,480 subjects aged ≥20 years were eligible for inclusion. Subjects who were pregnant (n=382), and those with missing data for DS use (n=8), PM use (n=5), education (n=8), marital status (n=4), or DIMC (n=123) were excluded. The final sample size was composed of 5,016 men and 4,934 women. NHANES 2005-2006 and 2007-2008 surveys were approved by the NCHS Research Ethics Review Board.
DS Use and Classification
DS use in the past month was assessed by trained interviewers using the computer-assisted personal interviewing (CAPI) system during the household interview. A full description of the DS data collection and CAPI system is provided elsewhere.
Antacids and calcium and/or magnesium-containing antacids taken as a DS were included in DS use variables. To minimize subjective classification, DS were classified into 18 mutually exclusive subgroups by a systematic iterative sorting procedure that used the ingredient count variables (vitamin, mineral, amino acid, botanical, and other) and search terms in the DS name variable and ingredient name variable associated with each DS in the NHANES-DSD. A total of 3,106 distinct DS ID numbers derived from the sample were grouped into relevant categories. Multivitamin categories were defined to be consistent with previous NHANES publications,
such that multivitamins were identified as containing ≥3 vitamins, and may or may not contain minerals. However, standard multivitamins, which were defined as containing no nonvitamin or mineral ingredients, were differentiated from multivitamins containing botanicals and multivitamins containing other nonbotanical ingredients. The detailed classification schematic is provided in Figure 1 (available online at www.andjrnl.org).
PM Use
PM use during the past month was assessed using the CAPI system during the household interview. PM was matched to the PM database Lexicon Plus, a proprietary database of Cerner Multum, Inc, used by NCHS. A full description of the database and PM classification scheme is provided elsewhere.
National Health and Nutrition Examination Survey: 1988-2010 data documentation, codebook, and frequencies, prescription medications - drug information (RXQ_Drug). http://www.cdc.gov/nchs/nhanes/nhanes1999-2000/RXQ_DRUG.htm. Accessed December 2, 2013.
Briefly, PMs were classified according to the PM's first-level drug therapeutic category of the 3-level nested category system. Prescription antacids were included in the PM database, not the DS database. Prescription DS, including calcium (except calcium acetate) and fluoride (except topical gel or cream formulations), were included in the DS database. Over-the-counter niacin, niacinamide, and nicotinic acid were included in the DS database, whereas prescription niacin, potassium, and sodium were included in the PM database.
DIMC and Covariates
Presence of any DIMC and covariates were also assessed using the CAPI system during the household interview. DIMC included asthma, arthritis, congestive heart failure, coronary heart disease, angina, angina pectoris, heart attack, stroke, high blood pressure, high cholesterol, emphysema, chronic bronchitis, any liver condition, thyroid problem, cancer or malignancy, weak/failing kidneys, dialysis during past 12 months, or osteoporosis/brittle bones. Similar conditions were grouped to obtain DIMC categories. Covariates were categorized as follows: sex (male/female), age (20 to 39 years, 40 to 59 years, or ≥60 years), marital status (married or living with a partner or single), education (less than high school graduate or high school graduate or some college or college graduate), and family income (unsure, <$20,000, $20,000 to $44,999, $45,000 to $74,999, or ≥$75,000).
Statistical Analysis
SAS statistical analysis software (version 9.1.2, 2004, SAS Institute Inc) was used to perform analyses. All analyses were adjusted for the complex sampling design of NHANES by specifying the stratum and cluster variable, in addition to the 4-year mobile examination center weight, to ensure sampling errors were estimated by the Taylor series (linearization) method, as suggested in the NHANES analytic guidelines.
The final sample subpopulation and analyses for subgroups were specified using the domain statement, or by including the domain variable in the surveyfreq procedure, such that variance estimates were based on the full-sample size of subjects with data available from the household interview and the mobile examination center. The surveyfreq and surveylogistic procedure in SAS were used to derive descriptive and logistic regression analysis data (after adjustment for sex, age, education, and household income). A conservative 99% CI was calculated for each prevalence estimate and odds ratio. Significant differences were defined as nonconvergent CIs and odds ratios excluding 1.00 in the CI. The point prevalence (total of US adults) was calculated according to the NHANES analytic guidelines for calculating population counts.
Briefly, the total prevalence proportion (percent of all US adults) was multiplied by the population total of US noninstitutionalized civilian adults aged ≥20 years for 2005-2008 reported by the Center for Population Statistics
; that is, ½ (2005-2006 population totals)+½ (2007-2008 population totals)=210,156,452.
Results and Discussion
Several demographic characteristics were significantly associated with concomitant DS and PM use (Table 1). Men were less likely than women to use DS and PM. Subjects aged 20 to 39 years and 40 to 59 years were less likely, respectively, than those aged ≥60 years to use DS and PM. Subjects with education less than that of college graduates were significantly less likely to use DS and PM. Similarly, subjects with a household income <$75,000 per year were significantly less likely to use DS and PM. Multiple DS users and multiple PM users were more likely than single users to concomitantly use DS and PM. After adjustment for age, married subjects, and subjects living with a partner were not significantly more or less likely than single subjects to use DS and PM; thus, marital status was not included as a covariate in subsequent logistic regression models.
Table 1Demographic and concomitant dietary supplement (DS) and prescription medication (PM) use characteristics
Estimates include adjustment for complex sampling design; 4-year mobile examination center exam weight applied.
of a nationally representative sample of 9,950 noninstitutionalized, civilian adults aged ≥20 years in the United States enrolled in the 2005-2008 National Health and Nutrition Examination Survey
Prevalence estimates for DS and PM use are presented in Table 2. Half of US adults reported DS use, and more than half reported PM use. The prevalence of any DS, or any PM use was significantly higher among those with any DIMC than those without any DIMC. The prevalence of DS use was highest among those with osteoporosis, followed by those with thyroid, cancer, arthritis, heart/vascular, kidney, diabetes, respiratory, and liver conditions. The prevalence of PM use was highest among those with a kidney condition, followed by thyroid, osteoporosis, diabetes, cancer, arthritis, respiratory, heart/vascular, and liver conditions.
Estimates include adjustment for complex sampling design; 4-year mobile examination center exam weight applied.
of dietary supplement (DS) and prescription medication (PM) use according to doctor-informed medical condition (DIMC) among a nationally representative sample of 9,950 noninstitutionalized, civilian adults aged ≥20 years in the United States enrolled in the 2005-2008 National Health and Nutrition Examination Survey
Total US adults calculated by multiplying the total prevalence proportion (percent of all US adults) by the population total of US noninstitutionalized civilian adults aged ≥20 years.
Total
51.3 (47.9-54.6)
57.1 (54.7-59.6)
—
—
34.3 (31.9-36.8)
72,083,663
Any DIMC
58.7 (54.7-62.6)
75.2 (72.5-78.0)
47.3 (44.0-50.6)
2.62 (2.13-3.21)
26.8 (24.4-29.3)
56,321,929
No DIMC
41.6 (37.5-45.7)
33.4 (30.5-36.4)
17.3 (14.7-19.9)
—
7.50 (6.18-8.82)
15,761,734
Arthritis
61.9 (58.1-65.7)
82.7 (80.0-85.5)
53.4 (50.2-56.6)
1.79 (1.46-2.20)
13.5 (11.9-15.2)
28,371,121
Heart/vascular
59.9 (55.8-63.9)
76.8 (73.7-79.9)
49.1 (45.4-52.9)
1.86 (1.67-2.07)
16.5 (14.8-18.1)
34,675,815
Respiratory
54.1 (46.9-61.2)
78.4 (72.8-84.0)
45.8 (39.8-51.8)
1.33 (0.98-1.80)
2.90 (2.18-3.61)
6,094,537
Liver
51.1 (41.2-61.1)
70.9 (64.1-77.7)
41.3 (33.1-49.4)
1.31 (0.86-2.00)
1.41 (1.07-1.75)
2,963,206
Thyroid
67.1 (60.8-73.2)
90.8 (87.8-93.8)
62.4 (56.2-68.6)
2.06 (1.58-2.69)
6.15 (5.08-7.23)
12,924,622
Cancer
66.9 (60.3-73.5)
84.9 (80.7-89.1)
59.3 (53.2-65.5)
1.67 (1.32-2.11)
5.15 (4.31-6.00)
10,823,057
Diabetes
57.2 (52.0-62.4)
88.9 (85.4-92.3)
52.4 (46.7-58.1)
1.75 (1.42-2.15)
6.99 (6.03-7.95)
14,689,936
Kidney
58.2 (30.2-86.2)
100.0 (100-100)
58.2 (30.2-86.2)
—
0.09 (0.02-0.15)
189,141
Osteoporosis
76.9 (72.0-1.9)
89.7 (85.5-93.8)
70.5 (65.0-76.1)
2.42 (1.90-3.09)
3.82 (2.93-4.71)
8,027,976
a Estimates include adjustment for complex sampling design; 4-year mobile examination center exam weight applied.
b Adjusted for sex, age, education, and household income.
c Total US adults calculated by multiplying the total prevalence proportion (percent of all US adults) by the population total of US noninstitutionalized civilian adults aged ≥20 years.
Approximately one third of all US adults reported concomitant DS and PM use, representing 72,083,663 adults (approximately one in three adults). The prevalence of concomitant DS and PM use was significantly higher among those with any DIMC than those without, representing approximately one in two adults with a DIMC relative to approximately one in six adults without DIMC. The prevalence of concomitant DS and PM use was highest among those with osteoporosis, followed by thyroid, cancer, kidney, arthritis, diabetes, heart/vascular, respiratory, and liver conditions. The point prevalence (total number of US adults) of concomitant DS and PM use was highest among those with heart/vascular conditions, followed by arthritis, diabetes, thyroid, cancer, osteoporosis, respiratory, liver, and kidney conditions. In regression models, DIMC status was significantly associated with concomitant DS and PM use. Those with any DIMC, as well as each individual DIMC (with the exception of respiratory and liver conditions), were significantly more likely to report concomitant DS and PM use than those without these respective conditions, after adjustment for covariates.
Prevalence of DS categories according to DIMC status are shown in panel A of Figure 2. Multivitamin plus other was the most prevalent DS category used concomitantly with a PM, among both those with and without a DIMC. When DS categories were ranked according to prevalence among those with any DIMC, multivitamin plus other was followed by antacid, multivitamin plus botanical, single vitamin, standard multivitamin, fish oil and n-3 fatty acids, multicomponent botanical, other, joint, and single mineral. The prevalence of use for single botanical, calcium combination, digest, calcium plus vitamin D, coenzyme Q10, vitamin/mineral complex, multibotanical, and single amino acid was <1.0% among those with and without any DIMC.
Figure 2Prevalence (% and 99% CI) of (A) dietary supplement (DS) categories used concomitantly with a prescription medication (PM) and (B) PM categories used concomitantly with a DS, among a nationally representative sample of 9,950 noninstitutionalized, civilian adults aged ≥20 years in the United States enrolled in the 2005-2008 National Health and Nutrition Examination Survey. Stratified according to doctor-informed medical condition (DIMC) status and adjusted for complex sampling design; 4-year sample weights applied. Black bar denotes those with any DIMC; gray bar denotes those with no DIMC. CNS=central nervous system.
Patterns of PM categories differed to some extent according to DIMC status (panel B of Figure 2). Among those with a DIMC, cardiovascular agents (16.2%) were the most prevalent PM category used concomitantly with a DS, followed by central nervous system agents, hormones, metabolic agents, psychotherapeutic agents, anti-infectives, gastrointestinal agents, respiratory agents, miscellaneous agents, coagulation modulators, topical agents, antineoplastics, nutrition-related products, and immunologic agents. Among those without a DIMC, hormones (3.0%) were the most prevalent PM category used concomitantly with a DS, followed by central nervous system agents, cardiovascular agents, anti-infectives, psychotherapeutic agents, respiratory agents, gastrointestinal agents, topical agents, miscellaneous agents, coagulation modulators, metabolic agents, antineoplastics, nutrition-related products, and immunologic agents. Among both those with and without a DIMC, biologic, plasma expanders, and alternative medicine categories had prevalence estimates of 0% (data not shown).
This is the largest population-based study to date of a nationally representative sample of noninstitutionalized, nonpregnant US adults that describes the prevalence and nature of concomitant DS and PM use. The estimates obtained in our analysis are similar to estimates reported previously for DS use
Additional analysis of the data in this study indicate that 69.3% (99% CI 65.0 to 73.6) of PM users aged ≥57 years concomitantly use DS and PM, which is somewhat higher than the 52% estimated by Qato and colleagues
and in addition to age, the findings that female sex, higher education, greater income levels, and presence of a chronic condition were associated with concomitant DS and PM use corroborate reports of others.
DS users report using DS to improve or maintain overall health, as well as for specific reasons, including primarily to promote bone health among women and heart health among men.
Despite popularity of DS, concerns persist regarding purity, toxicity, and mislabeling because regulation of DS under the 1994 Dietary Supplement Health and Education Act is limited relative to that of PM. Several surveys suggest the percent of patients who do not disclose their complementary and alternative medicine use to health care professionals may be >60%.
Thus, the risk for potential interactions between DS and PM to go undetected remains substantial. Information on the types of DS used by individuals with chronic disease may assist health care professionals in determining whether a patient may be at risk for a DS and PM interaction.
The patterns of DS categories used with a PM were similar among those with and without a DIMC. Similar to our findings, multivitamins have been identified as the most common DS used by US adults by other investigators.
However, this analysis documents for the first time that multivitamins containing other or botanical ingredients were more commonly consumed with a PM than standard multivitamins containing only vitamin or mineral ingredients. Multivitamin plus botanical DS were the third most common DS used with a PM—more common than both single botanical DS and multibotanical DS. This is concerning because botanical ingredients, including herbal DS, are known to induce or inhibit cytochrome P450 drug metabolizing enzymes and activity
The term multi, multivitamin, or vitamin was present in 70% of label names in the multivitamin plus other category and in 51% of label names in the multivitamin plus botanical category (data not shown), suggesting a consumer preference for multivitamins that advertise or include these additional nonvitamin or mineral ingredients.
In contrast to the DS categories, the PM categories used with DS differed somewhat between those with and without a DIMC. The finding that cardiovascular agents were the most common PM used with DS among those with a DIMC was also observed by Qato and colleagues
among older adults in the United States. Cardiovascular agents, including antihypertensive and antiarrhythmic agents, appear to be among the most common drug classes to have suspected interactions with DS in clinical trials and case reports.
This is likely due to the high prevalence of heart and vascular conditions in the US population.
This study has some limitations. DIMC status was determined by self-report; thus, some participants may have incorrectly or inadequately reported their conditions. Population estimates of potential DS and PM interactions firmly established in the literature were not ascertained; thus, we cannot conclusively determine the number at risk for known interactions. Nonetheless, using a large DS database with ingredient information permitted identification of nonvitamin or mineral ingredients, including botanicals, contained within multivitamins.
Conclusions
Our analysis identified the presence of a DIMC as a risk factor for concomitant DS and PM use among US adults. Individuals with a DIMC had a higher prevalence of DS use (58.7% vs 41.6%) and PM use (75.2% vs 33.4%), than those without a DIMC. Thus, the increased prevalence of concomitant DS and PM among those with a DIMC is likely due to increased use of DS, in addition to PM, rather than increased use of PM alone. Among those with a DIMC, the prevalence of DS use was >50% for all types of DIMC. Thus, it may not be feasible to identify individuals with a specific condition that merit increased attention relative to others. Rather, these data suggest that a broad spectrum of patients with varied DIMCs may benefit from education and guidance on the risk of DS and PM interactions, particularly the potential of DS to interfere with PM metabolism and increase or inhibit PM potency. In addition to providing patients with education on the limitations of current regulatory practices to ensure safety, reliable sources of DS information, and reading label information, dietetics practitioners may consider encouraging patients to discuss and disclose their supplement use with their physician and team of health care providers.
In addition, the observation that multivitamins containing other or botanical ingredients were more commonly consumed than standard multivitamins warrants further clinical attention. The increasing complexity of combinations of ingredients contained in DS may also require explicit evaluation by health care and dietetics practitioners. Inquiries about patient DS use in an attempt to screen for potential DS and PM interactions may benefit from identifying ingredient information directly from labels. Multivitamin DS, in particular, may need more scrupulous evaluation and should not be assumed to contain only safe ingredients.
Supplementary Materials
Figure 1Classification scheme of dietary supplement (DS) using ingredient count variables in the National Health and Nutrition Examination Survey-Dietary Supplement Database (DSD) 2005-2008. Ingredient count variable names in National Health and Nutrition Examination Survey-Dietary Supplement Database=vitamin count, “dsdcntv”; mineral count, “dsdcntm”; amino acid count, “dsdcnta”; botanical count, “dsdcntb”; and other count, “dsdcnto.”
The count of distinct ID numbers in the “dsdsupid” variable assigned to DS recorded in the National Health and Nutrition Examination Survey-Dietary Supplement Database. Total distinct DS ID numbers in the sample classified into mutually exclusive groups=3,106.
Standard multivitamin: ≥3 vitamins and may include minerals; no amino acid, botanical, or other ingredients
155
Vitamin and/or mineral complex: 2 vitamins, 2 minerals, or 1 vitamin and 1 mineral; no amino acid, botanical, or other ingredients
126
Antacid: identified by search terms antacid or calcium and magnesium
→
32
Calcium+vitamin D: identified by search terms calcium and vitamin D
35
Calcium combination: identified by search terms calcium, cal, or osteo; excludes calcium plus vitamin D and antacids
3
Fish oil and n-3 fatty acid: identified by search terms fish, omega-3, DHA, EPA, salmon, cod, and flax
7
Vitamin and/or mineral complex: remaining vitamin and/or mineral complex DS; excludes calcium plus vitamin D, antacid, calcium combination, and fish oil and n-3
49
Multimineral: ≥3 minerals; no vitamin, amino acid, botanical, or other ingredients
14
Calcium combination: identified by search term calcium, cal, or osteo
→
14
Single vitamin: 1 vitamin; no mineral, amino acid, botanical, or other ingredients
109
Single mineral: 1 mineral; no vitamin, amino acid, botanical, or other ingredients
95
Multicomponent botanical: ≥1 botanical AND ≥1 vitamin OR ≥1 mineral OR ≥1 amino acid OR ≥1 other ingredient
917
Multivitamin plus botanical: ≥3 vitamins and ≥1 botanical, may include minerals and amino acids
→
402
Multicomponent botanical: remaining multicomponent botanical DS; excludes multivitamin plus botanical
515
Multibotanical: >1 botanical; no vitamin, mineral, amino acid, or other ingredients
105
Single botanical: 1 botanical; no vitamin, mineral, amino acid, or other ingredients
250
Single amino acid: 1 amino acid; no vitamin, mineral, botanical, or other ingredients
52
Other: ≥1 other ingredient; no botanicals
1,283
Multivitamin plus other: ≥3 vitamins and ≥1 other ingredient, may include minerals and amino acids, but not botanicals
→
373
Antacid: identified by search term antacid
55
Calcium combination: identified by search terms calcium, cal, or osteo
55
Fish oil and n-3 fatty acids: identified by search terms fish, omega-3, DHA, EPA, salmon, cod, or flax
157
Joint: identified by search term glucosamine, MSM, hyaluronic acid, cosamin, or chondroitin
158
Digestive: identified by search terms fiber, probiotics, acidophilus, dophilus, lactobacillus, lactase, amylase, protease, lipase, trypsin, chymotrypsin, pancreatin, or bromelain
84
Coenzyme Q-10: identified by search term Q-10, Q10, or Q 10
51
Other: remaining miscellaneous DS, such as DS containing electrolytes, melatonin, lipoic acid, yeast, prohormones, protein, creatine, and cider vinegar
268
Other, no information: remaining DS with product information not available
82
a The count of distinct ID numbers in the “dsdsupid” variable assigned to DS recorded in the National Health and Nutrition Examination Survey-Dietary Supplement Database. Total distinct DS ID numbers in the sample classified into mutually exclusive groups=3,106.
The incidence of potential interactions between dietary supplements and prescription medications in cancer patients at a Veterans Administration Hospital.
Prevalence of polypharmacy, polyherbacy, nutritional supplement use and potential product interactions among older adults living on the United States-Mexico border: A descriptive, questionnaire-based study.
Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey. http://www.cdc.gov/nchs/nhanes.htm. Accessed November 29, 2012.
National Health and Nutrition Examination Survey: 1988-2010 data documentation, codebook, and frequencies, prescription medications - drug information (RXQ_Drug). http://www.cdc.gov/nchs/nhanes/nhanes1999-2000/RXQ_DRUG.htm. Accessed December 2, 2013.
E. K. Farina is a fellow, Oak Ridge Institute for Science and Education, Oak Ridge Associated Universities, Belcamp, MD; in support of Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA.
K. G. Austin is a fellow, Oak Ridge Institute for Science and Education, Oak Ridge Associated Universities, Belcamp, MD; in support of Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA.
H. R. Lieberman is a research psychologist, Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA.
STATEMENT OF POTENTIAL CONFLICT OF INTEREST No potential conflict of interest was reported by the authors.
FUNDING/SUPPORT This work was supported by the US Army Medical Research and Material Command (USAMRMC), Department of Defense Center Alliance for Dietary Supplement Research, and an appointment to the Postgraduate Research Participation Program administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and USAMRMC. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Human subjects participated after giving their free and informed voluntary consent. The investigators adhered to the policies for protection of human subjects as prescribed in Army Regulation 70-25, and the research was conducted in adherence with the provisions of 32 CFR Part 219. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations. Approved for public release.
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