Abstract
Aim
This study aimed to examine the trends and determinants of dietary supplement use and to assess the prevalence and predictors of potential drug-supplement interactions among older adults over a 16-year follow-up.
Methods
This repeated cross-sectional study included adults aged ≥ 50 years who participated in the third (2006–2008; n = 3,484), fourth (2009–2011; n = 4,020), fifth (2012–2014; n = 4,342), sixth (2015–2017; n = 4,598), and seventh (2018–2022; n = 4,750) examinations of the Tehran Lipid and Glucose Study (TLGS). Information on dietary supplement use, including individual vitamin supplements and prescription medication use was collected using standardized questionnaires. Trends in supplement use and participant characteristics were evaluated across study phases. Clinically relevant mild-to-moderate potential drug-supplement interactions were defined as the concurrent use of specific dietary supplements and commonly prescribed medications and were classified according to Stockley’s framework. Multivariable logistic regression models were used to identify factors associated with dietary supplement use and potential drug-supplement interactions in the 2018–2022 examination.
Results
Over 16 years, dietary supplement use increased more than 2-fold from 10.4% to 21.1%, mainly from increases in thiamin (2.2% to 13.4%), cobalamin (1.8% to 9.8%), vitamin C (1.3% to 7.9%), vitamin E (1.8% to 8.7%), and zinc (0.2% to 3.3%). Female sex, higher education, and diabetes were associated with higher likelihood of supplement use. In 2018–2022, 4.8% of participants had potential drug-supplement interactions, most commonly vitamin E with aspirin (2.3%) and magnesium or potassium with antihypertensive medications. The likelihood of potential drug-supplement interactions was higher in women (OR = 2.03, 95%CI = 1.61–2.56), participants with primary education (OR = 1.45, 95% CI = 1.09–1.96), smokers (OR = 1.50, 95%CI = 1.07–2.12), and individuals with diabetes (OR = 2.80, 95%CI = 2.13–3.68), hypertension (OR = 2.20, 95%CI = 1.78–2.73), chronic kidney disease (OR = 2.35, 95%CI = 1.88–2.94), or multimorbidity (OR = 2.46, 95%CI = 1.85–3.26).
Conclusion
Over 16 years, supplement use increased among older adults, especially B-complex vitamins, vitamin C, vitamin E, and zinc, with a low but clinically relevant prevalence of drug-supplement interactions.
Supplementary Information
The online version contains supplementary material available at 10.1007/s40520-026-03344-0.
Keywords: Older adults, Elderly, Dietary supplements, Vitamins, Minerals, Drug interactions
Introduction
The global population is aging rapidly, and by 2050, individuals aged over 60 are expected to comprise 22% of the world’s population, almost twice the share recorded in 2015, with the approximately 80% living in low- and middle-income countries [1]. The use of dietary supplements, including vitamins, minerals, herbal products, and nutraceuticals, is highly prevalent among older adults and has increased over recent decades [2]. These products are often consumed alongside prescription and over-the-counter medications [3–5]. While supplements may offer potential benefits, their concurrent use with medications increases the risk of adverse interactions [3–5]. The complexity of supplement use in older adults is further compounded by polypharmacy, age-related changes in pharmacokinetics and pharmacodynamics, and the presence of multiple chronic conditions [6–8].
Patterns of dietary supplement use are shaped by a combination of sociodemographic, clinical, and lifestyle factors [2, 3, 5]. Diet quality, physical activity, and health-seeking practices, may further determine the likelihood of supplement use [2, 3, 5]. Understanding determinants of supplement use is crucial for identifying subpopulations at greater risk of concurrent use with medications and for guiding targeted interventions to optimize safety and effectiveness [8, 9]. Importantly, patterns of dietary supplement use and medication exposure are dynamic and may change over time in response to shifts in health behaviors, disease burden, clinical practice, and public awareness. Therefore, examining long-term trends in dietary supplement use, alongside associated determinants and potential drug-supplement interactions, is essential to capture these temporal changes and to inform up-to-date clinical and public health recommendations.
Despite the widespread use of supplements, longitudinal evidence describing trends and patterns in supplement use and potential drug-supplement interactions in older adults remains limited, especially among Asian populations. Longitudinal population-based cohort studies provide a unique framework to evaluate temporal trends in supplement use, identify predictors of use, and assess the evolving risk of potential drug-supplement interactions in aging populations. Investigating these patterns over extended periods is essential to inform evidence-based public health strategies, clinical guidance, and policy development aimed at minimizing adverse events while promoting safe and effective use of dietary supplements in older adults. In this study, we aimed to examine 16-year trends in dietary supplement use, as well as usage patterns, determinants, and potential interactions with medications, among older adults and the elderly participating in the Tehran Lipid and Glucose Study (TLGS), a population-based cohort of Iranian adults.
Subjects and methods
Study population
This prospective cohort study was conducted within the TLGS framework, a population-based investigation initiated in 1999 to examine NCDs prevalence and prevention in Tehran’s 13th district [10]. The TLGS employed a standardized protocol to assess NCDs risk factors every three years. This study included older adults aged 50 years or older who participated in the third (2006–2008, n = 3484), fourth (2009–2011, n = 4020), fifth (2012–2014, n = 4342), sixth (2015–2017, n = 4598), and seventh (2018–2022, n = 4750) examinations of the TLGS. All participants provided complete data on dietary supplement use, demographics, anthropometrics, clinical, medical, and biochemical measurements. The study protocol was approved by the ethics research council of the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Ethics code: IR.SBMU.ENDOCRINE.REC.1404.087). Written informed consent was obtained from all participants. The study was conducted in accordance with the guidelines outlined in the Declaration of Helsinki.
Assessment of supplement use
Information on use of dietary supplements (i.e., vitamins and minerals) was obtained through structured, interviewer-administered questionnaires combined with direct observation of all medications and supplements. Participants were asked to report all supplements they were using, and to improve accuracy, they were encouraged to bring supplement containers, medication lists, or written records to the interview. Trained interviewers then verified the reported products against these materials whenever possible. This combined approach provided a practical yet reliable method for estimating usual dietary supplement intake [10]. Commonly reported supplements included calcium, vitamin D, iron, zinc, thiamin (B1), folic acid (B9), cobalamin (B12), B-complex, vitamin C, vitamin E, and multivitamin-multimineral products. Supplement users were defined as participants who reported taking any supplements during the interviewer-administered assessment. Participants who reported using multivitamin-multimineral products were also considered users of individual vitamins included in the formulation, including vitamin D, thiamin (B1), folic acid (B9), cobalamin (B12), vitamin C, and E. Participants who did not report using any supplements during the interview were classified as non-users.
In the present study, potential drug-supplement interactions were defined a priori based on established pharmacological and clinical evidence indicating moderate to severe interactions between commonly used vitamin/mineral supplements and prescribed medications in older adults. These interactions were identified when the concomitant use of a specific supplement and a medication was known to (a) increase the risk of clinically relevant adverse effects (e.g., hypercalcemia, hyperkalemia, bleeding, myopathy, or hypoglycemia), (b) alter drug pharmacokinetics or pharmacodynamics (e.g., reduced drug absorption due to chelation or enhanced hypotensive effects), or (c) reduce supplement efficacy or increase nutrient loss (e.g., increased urinary zinc loss with diuretics). Accordingly, participants were classified as having a potential drug-supplement interaction if they reported concurrent use of at least one supplement-drug pair listed in Supplementary Table 1, including interactions involving multivitamin-mineral products. Only interactions with documented moderate to severe clinical relevance were considered in the analysis. The severity and clinical importance of these interactions were classified according to Stockley’s framework [11].
Assessments of covariates
Detailed methodologies for data collection and variable assessment within the TLGS have been previously reported [12]. Trained personnel conducted triennial follow-up visits to obtain and update information on family history of NCDs, tobacco use, medications, physical activity level (PAL), and anthropometric indices [weight, height, waist circumference (WC), and body mass index (BMI)]. Data were collected by trained research staff using standardized and pretested protocols across all study phases. All personnel received uniform training to ensure consistency in questionnaire administration, anthropometric measurements, and biological sample collection, and standard operating procedures were strictly followed. To minimize inter- and intra-observer variability, instruments were regularly calibrated, and periodic supervision and quality control assessments were conducted. Data completeness and accuracy were routinely monitored, and discrepancies were resolved using predefined verification procedures, ensuring methodological uniformity and high data quality despite the involvement of multiple researchers.
Blood pressure (BP) measurements were implemented between 8:00 and 12:00 AM by the trained TLGS staff, manually using an appropriate-sized cuff using Omron M7 sphygmomanometer (HEM-780-E), i.e., calibrated by the Institute of Standards and Industrial Research of Iran [13]. Participants rested seated for 15 min before two BP readings, separated by a 30-second interval. The average of these readings constituted the final BP value.
Detailed biochemical measurements in the TLGS have been described elsewhere [14]. Briefly, fasting blood samples were collected from participants after a 12–14 h fast to determine baseline and follow-up levels of fasting serum glucose (FSG), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). Additionally, a standard oral glucose tolerance test (OGTT) was administered to all consenting adults aged 21 years and older who were not on anti-hyperglycemic medications. The OGTT involved a 75-gram oral glucose load, followed by a two-hour measurement of blood glucose (2 h-SG) levels.
Details of PAL assessment using the validated Iranian version of the Modifiable Activity Questionnaire (MAQ) have been described elsewhere [15]. This instrument captured both leisure time and occupational PAL. Participants were categorized into two PAL groups based on their estimated weekly metabolic equivalent of task (MET) minutes: a low PAL group (< 600 MET-min/week) and a moderate-to-high PAL group (≥ 600 MET-min/week) [16].
T2DM was defined as an FSG ≥ 126 mg/dL, a 2 h-SG ≥ 200 mg/dL, or the use of glucose-lowering medications [17]. Abdominal obesity was defined using Iranian-specific cut-off values, with WC greater than 95 cm in both men and women [18]. General obesity was defined as BMI ≥ 30 kg/m2. Hypertension (HTN) was defined as SBP ≥ 140 or mm Hg DBP ≥ 90 mmHg or self-reported taking BP-lowering medications [19]. To estimate glomerular filtration rate (eGFR), the Chronic Kidney Disease Epidemiology Collaboration equation was used [20]. Chronic kidney disease (CKD) was defined as eGFR < 60 mL/min/1.73 m2 [20]. Multimorbidity was defined as the presence of two or more chronic conditions, including T2DM, HTN, CKD, and general obesity.
Statistical methods
Statistical analyses were conducted using the SPSS for Windows version 20 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were used to summarize characteristics of the study particpants across TLGS examinations, with interval and ratio variables reported as mean ± standard deviation (SD) and nominal or ordinal variables presented as frequencies and percentages. Logistic regression was used to estimate odds (OR) and 95% confidence intervals (CIs) of supplement use in relation to sociodemographic and health-related conditions among the participants in the last TLGS examination (2018–2022).
Result
Table 1 shows demographics, clinical, and biomedical characteristics of the older adults. Across TLGS examinations from 2006 to 2022, older adults showed gradual aging of the cohort, while the proportion of men remained stable at around 44–46%. Smoking prevalence changed little, whereas low PAL increased from 40.7% to 46.8%. Use of cardiometabolic medications increased over time, with glucose-lowering drugs increasing from 13.2% to 22.1%, lipid-lowering agents from 11.2% to 34.9%, and BP-lowering medications from 11.7% to 36.2%. Diuretic use nearly doubled, rising from 5.6% in 2006–2008 to 9.0% in 2018–2022, and aspirin use increased from 23.8% to 35.3%. Educational levels improved, represented by a decline in primary education and an increase in college education from 8.1% to 17.4%, while employment and marital status distributions remained largely stable. Anthropometric indices showed minimal variation, with BMI remaining around 28.5–29.0 kg/m2 and WC around 97–99 cm. Blood pressure decreased slightly over time, and eGFR steadily declined from 67.9 to 63.8 mL/min/1.73 m2. Obesity and abdominal obesity remained highly prevalent with no changes overtime, while the prevalence of T2DM increased from 23.8% to 43.2% and CKD from 25.3% to 36.9%. Multimorbidity remained common across cycles, reaching 56.8% in 2018–2022.
Table 1.
Demographics, clinical, and biomedical characteristics of the older adults acrossTLGS examinations
| 2006-2008 (n=3484) |
2009-2011 (n=4029) |
2012-2014 (n=4342) |
2015-2017 (n=4598) |
2018-2022 (n=4750) |
|
|---|---|---|---|---|---|
| Age, y | 61.6±8.3 | 62.6±9.1 | 63.0±9.5 | 63.4±9.8 | 63.6±9.8 |
| Men, % | 45.5 | 44.7 | 44.6 | 44.4 | 44.1 |
| Current smokers, % | 9.6 | 9.7 | 10.3 | 9.9 | 11.1 |
| Low PAL, % | 40.7 | 40.7 | 40.2 | 42.6 | 46.8 |
| Medications, % | |||||
| Glucose-lowering | 13.2 | 16.0 | 18.4 | 21.0 | 22.1 |
| Lipid-lowering | 11.2 | 18.7 | 33.0 | 35.9 | 34.9 |
| BP-lowering | 11.7 | 28.8 | 25.1 | 31.0 | 36.2 |
| Diuretics | 5.6 | 6.4 | 7.1 | 7.6 | 9.0 |
| Cardiac | 8.5 | 9.0 | 9.4 | 9.2 | 6.9 |
| Steroids | 1.3 | 3.1 | 2.1 | 3.0 | 2.1 |
| Aspirin | 23.8 | 26.7 | 30.1 | 35.0 | 35.3 |
| Thyroids | 3.8 | 4.4 | 5.7 | 7.6 | 10.1 |
| Anticoagulants | 6.7 | 0.9 | 1.6 | 2.1 | 2.6 |
| Job status, % | |||||
| Employed | 33.8 | 33.4 | 34.5 | 36.7 | 36.1 |
| Unemployed | 2.8 | 1.4 | 1.6 | 1.4 | 2.3 |
| House wife/Retired | 63.4 | 65.2 | 63.8 | 61.9 | 61.6 |
| Education, % | |||||
| Primary | 61.2 | 54.0 | 46.2 | 40.2 | 33.1 |
| Intermediate | 30.7 | 63.1 | 42.2 | 46.1 | 51.5 |
| College | 8.1 | 10.0 | 11.6 | 13.6 | 17.4 |
| Marital status, % | |||||
| Single | 0.8 | 1.0 | 1.3 | 1.8 | 2.4 |
| Married | 82.2 | 86.6 | 81.9 | 81.0 | 81.7 |
| Divorced/widowed | 17.0 | 17.4 | 16.8 | 17.3 | 15.9 |
| BMI, kg/m2 | 28.5±4.7 | 29.0±10.3 | 28.9±5.2 | 28.9±4.9 | 28.7±4.7 |
| WC, cm | 96.9±10.8 | 98.9±11.0 | 98.0±11.0 | 98.2±10.9 | 97.6±10.6 |
| SBP, mm Hg | 128±21.0 | 128±79.9 | 127±20.3 | 124±18.9 | 122±17.6 |
| DBP, mm Hg | 76.7±10.9 | 79.9±11.7 | 79.5±10.9 | 77.6±10.5 | 76.6±9.8 |
| FSG, mg/dL | 109±41.5 | 113±41.6 | 111±37.7 | 108±36.9 | 110±36.9 |
| 2h-SG, mg/dL | 128±59.8 | 131±56.9 | 130±50.2 | 135±52.4 | 135±42.5 |
| Serum Cr, mg/dL | 1.10±0.21 | 1.09±0.25 | 1.12±0.27 | 1.14±0.26 | 1.14±0.26 |
| eGFR, mL/min/1.73m2 | 67.9±12.8 | 67.7±12.6 | 66.0±13.2 | 64.1±12.6 | 63.8±12.6 |
| TG-to-HDL ratio | 4.6±3.3 | 3.8±2.8 | 3.6±2.6 | 3.4±2.6 | 3.5±3.2 |
| Obesity, % | 33.7 | 37.0 | 37.4 | 37.3 | 36.4 |
| Abdominal obesity, % | 55.9 | 62.2 | 58.2 | 58.5 | 58.1 |
| T2DM, % | 23.8 | 28.7 | 29.9 | 33.0 | 43.2 |
| HTN, % | 35.9 | 47.9 | 46.6 | 47.7 | 43.9 |
| CKD, % | 25.3 | 24.4 | 30.8 | 34.4 | 36.9 |
| Multimorbidity, % | 92.3 | 90.1 | 51.7 | 52.2 | 56.8 |
Data are mean (SD) or percent. BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FSG, fasting serum glucose; 2h-SG, 2-hour serum glucose; Serum Cr, serum creatinine; eGFR, estimated glomerular filtration rate; TG-to-HDL ratio, triglyceride-to-HDL cholesterol ratio; Obesity, obesity; T2DM, type 2 diabetes mellitus; HTN, hypertension; CKD, chronic kidney disease.
Table 2 shows trends of dietary supplement use among older adults across TLGS examinations. The prevalence of any supplement use more than doubled, increasing from 10.4% in 2006–2008 to 21.1% in 2018–2022. Both single- (from 4.4% to 10.5%) and multiple-supplement use (from 6.0% to 10.5%) increased steadily over time, while non-use declined from nearly 90% to 78.9%. Notable shifts were observed in the pattern of supplement use; vitamin D, B-complex vitamins, thiamin, folic acid, cobalamin, vitamin E, vitamin C, iron, zinc, and multivitamin-multimineral supplements all increased significantly, with the sharpest increases observed for thiamin (2.2% to 13.4%), cobalamin (1.8% to 9.8%), vitamin E (1.8% to 8.7%), vitamin C (1.3% to 7.9%), and zinc (0.2% to 3.3%). In contrast, calcium supplement use declined substantially after 2012–2014, dropping from around 7–8% in earlier examinations to below 1% thereafter.
Table 2.
Trends in dietary supplementsuse in older adults acrossTLGS examinations (2006-2022)
| 2006-2008 (n=3484) |
2009-2011 (n=4029) |
2012-2014 (n=4342) |
2015-2017 (n=4598) |
2018-2022 (n=4750) |
|
|---|---|---|---|---|---|
| Supplement Use | |||||
| No | 89.6 (3122) | 87.1 (3508) | 87.9 (3616) | 84.7 (3794) | 78.9 (3750) |
| Single | 4.4 (152) | 5.5 (220) | 5.0 (216) | 6.9 (319) | 10.5 (499) |
| Multiple† | 6.0 (210) | 7.5 (301) | 7.1 (310) | 8.4 (385) | 10.5 (501) |
| Any supplement use | 10.4 (362) | 12.9 (521) | 12.1 (526) | 15.3 (704) | 21.1 (1000) |
| Type of Supplement | |||||
| Calcium | 7.1 (247) | 8.0 (323) | 7.3 (318) | 0.7 (30) | 1.0 (46) |
| Vitamin D | 5.1 (179) | 6.2 (248) | 5.8 (251) | 5.3 (242) | 6.2 (296) |
| B complex | 1.8 (62) | 2.8 (111) | 2.9 (125) | 6.7 (308) | 7.2 (341) |
| Thiamin | 2.2 (75) | 3.1 (159) | 3.8 (167) | 10.0 (461) | 13.4 (636) |
| Folic acid | 2.8 (96) | 3.9 (158) | 4.4 (192) | 8.8 (406) | 8.3 (392) |
| Cobalamin | 1.8 (64) | 2.9 (115) | 3.1 (134) | 7.2 (330) | 9.8 (467) |
| Vitamin E | 1.8 (64) | 2.9 (115) | 3.2 (141) | 6.4 (296) | 8.7 (412) |
| Vitamin C | 1.3 (47) | 2.4 (95) | 2.6 (115) | 5.2 (237) | 7.9 (374) |
| Iron | 1.1 (38) | 1.3 (52) | 1.6 (68) | 2.4 (110) | 3.3 (159) |
| Zinc | 0.2 (6) | 0.5 (21) | 0.9 (37) | 1.6 (73) | 3.3 (157) |
| Multivitamin-mineral | 1.2 (42) | 2.1 (86) | 2.3 (99) | 4.5 (207) | 5.5 (262) |
Data are % (numbers)
†Excluding multivitamin-mineral
Table 3 shows the sociodemographic, clinical, and lifestyle factors associated with dietary supplement use among older adults in the most recent TLGS examination (2018–2022). Women had significantly higher odds of supplement use than men (OR = 1.83, 95% CI = 1.58–2.12). Higher educational level was also associated with greater supplement use, with both intermediate (OR = 1.38, 95% CI = 1.15–1.67) and college education (OR = 1.45, 95% CI = 1.13–1.85) showing elevated odds compared to primary education. Employment showed a borderline association with higher supplement use (OR = 1.79, 95% CI = 1.00–3.22.00.22, P = 0.052), while being a housewife was not associated with supplement use. Most lifestyle and health conditions, including smoking, PAL, HTN, CKD, and multimorbidity, were not associated with supplement use. Obesity was inversely associated (OR = 0.84, 95% CI = 0.72–0.98), whereas T2DM was positively associated with a 34% higher likelihood of supplement use (OR = 1.34, 95% CI = 1.12–1.60).
Table 3.
Odds ratio (95% Confidence Interval) of supplement use according sociodemographic, clinical and lifestyle characteristics of older adults in the last TLGS examination (2018-2022)
| Odds ratio (95%CI) | P value | |
|---|---|---|
| Gender | ||
| Female | 1.83 (1.58-2.12) | 0.001 |
| Education‡ | ||
| Intermediate | 1.38 (1.15-1.67) | 0.003 |
| College | 1.45 (1.13-1.85) | 0.001 |
| Marital status§ | ||
| Married | 1.09 (0.68-1.72) | 0.726 |
| Divorced/widowed | 1.28 (0.78-2.09) | 0.322 |
| Job status# | ||
| Employed | 1.79 (1.00-3.22) | 0.052 |
| House wife | 0.86 (0.59-1.26) | 0.464 |
| Obesity | 0.84 (0.72-0.98) | 0.033 |
| Smoking | 0.93 (0.72-1.22) | 0.622 |
| Physical activity | 1.04 (0.95-1.13) | 0.400 |
| T2DM | 1.34 (1.12-1.60) | 0.002 |
| HTN | 1.00 (0.86-1.16) | 0.950 |
| CKD | 1.08 (0.92-1.28) | 0.318 |
| Multimorbidity | 1.09 (0.89-1.32) | 0.387 |
Logistic regression was used with adjustment for age and gender.
‡Compared to primary education
§Compared to being single
#Compared to being unemployed
In the last examination, the prevalence of potential drug-supplement interactions was 4.8%, with the highest prevalence observed for vitamin E combined with aspirin (2.3%), followed by magnesium and potassium with antihypertensive medications (1.7 and 1.6%, respectively). As shown in Fig. 1, the likelihood of drug-supplement interactions was higher among women (OR = 2.03, 95% CI = 1.61–2.56, P = 0.001), particpants with primary education (OR = 1.45, 95% CI = 1.09–1.96, P = 0.012), and smokers (1.50, 95% CI = 1.07–2.12, P = 0.020). Patients with T2DM (OR = 2.80, 95% CI = 2.13–3.68, P = 0.001), HTN (OR = 2.20, 95% CI = 1.78–2.73, P = 0.001), CKD (OR = 2.35, 95% CI = 1.88–2.94, P = 0.001), or multimorbidity (OR = 2.46, 95% CI = 1.85–3.26, P = 0.001) also had a higher likelihood of experiencing drug-supplement interactions.
Fig. 1.
Odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with potential drug-supplement interactions among older adults in the TLGS. The figure illustrates higher likelihood of interactions in women, participants with primary education, smokers, and individuals with T2DM, HTN, CKD, or multimorbidity. Drug-supplement interactions were defined as the concurrent use of dietary supplements and medications with documented moderate-to-severe interactions according to Stockley’s framework. T2D, type 2 diabetes; HTN, hypertension; CKD, chronic kidney disease; TLGS, Tehran Lipid and Glucose Study
Discussion
This longitudinal population-based study demonstrated a clear increase in dietary supplement use among older adults, alongside a growing burden of chronic conditions, including T2DM, HTN and CKD. Supplement use more than doubled, with a marked shift toward B-complex vitamins, vitamin C, vitamin E, and zinc, while calcium use declined sharply. Female sex, higher educational attainment, being employed, and T2DM emerged as the strongest predictors of supplement use in the most recent examination. Importantly, the prevalence of potential drug-supplement interactions reached 4.8%, most commonly involving vitamin E with aspirin and magnesium or potassium with antihypertensive medications. The likelihood of these interactions was higher among women, participants with primary education, smokers, and individuals with T2DM, HTN, CKD, or multimorbidity. These findings highlight changing health behaviors in an aging population with increasing multimorbidity and polypharmacy, underscoring the need for careful evaluation of supplement-medication interactions, appropriateness of use, and potential risks in older adults. Understanding these trends can help clinicians and policymakers design targeted, evidence-based strategies to promote safe and effective supplement use in elderly populations with complex health conditions.
Previous longitudinal studies in nationally representative cohorts of older adults have reported similar notable increases in medications and dietary supplement use over time. In a study of community-dwelling adults aged 62–85 years, prescription use increased modestly from 84.1% to 87.7% over five years, and concurrent polypharmacy (use of ≥ 5 prescriptions) increased from 30.6% to 35.8% [5]. While over-the-counter medication use declined, dietary supplement use increased significantly from 51.8% to 63.7%, with substantial rises in the use of statins, antiplatelets, and omega-3 supplements [5]. These changes were accompanied by a higher prevalence of potential major drug-drug interactions, affecting 15% of older adults in 2010–2011 compared with 8.4% in 2005–2006 [5]. Such evidence highlights the growing complexity of medication regimens in older adults and underscores the importance of monitoring concurrent use of medications and supplements to prevent adverse events [5]. Another cross-sectional study on 3,500 older adults and elderly individuals in the United States reported that 81% (95% CI = 79.4%−83.5%) used at least one medication, 42% (95% CI = 39.7%−44.8%) used at least one over-the-counter medication, and 49% (95% CI = 46.2%−52.7%) used dietary supplements regularly [4]. Concurrent use of ≥ 5 medications was reported in 29% (95% CI = 26.6%−30.6%), highest among men (37.1%, 95% CI = 31.7%−42.4%) and women (36.0%, 95% CI = 30.2%−41.9%) aged 75–85 years [4]. Among prescription users, 46% (95% CI = 43.4%−49.1%) also used over-the-counter medications, and 52% (95% CI = 48.8%−55.5%) used dietary supplements [4]. In a recent cross-sectional study of 293 outpatients aged ≥ 60 years, a high prevalence of dietary supplement use was reported, with 83.6% of participants reporting current use and vitamin D being the most commonly consumed supplement (40%) [11]. Female gender was associated with more than double the odds of supplement use (OR = 2.17, 95% CI = 1.16–4.07), and HTN similarly increased the probability (OR = 2.35, 95% CI = 1.24–4.47) [11]. Among those using both supplements and medications, 40.1% had at least one potential drug-supplement interaction and 10.3% had a supplement-supplement interaction, most frequently involving nicotinic acid, vitamin D, and omega-3 fatty acids [11]. The odds of experiencing a potential interaction were significantly higher in individuals with T2DM (OR = 3.67, 95% CI = 2.06–6.54) and HTN (OR = 2.34, 95% CI = 1.34–4.09) [11]. In a descriptive study of 130 adults aged ≥ 60 years recruited from senior centers in the US-Mexico border region, 72.3% reported polypharmacy, with 38.5% taking ≥ 5 medications (major polypharmacy) [3]. Polyherbacy (≥ 2 herbal products) was reported by 16.2%, multiple vitamin/mineral use by 26.2%, and multiple nutraceutical use by 6.9% [3]. Evaluation of potential interactions revealed that 31.5 of participants were at risk for at least one potential drug-supplement interaction [3]. In a cross-sectional survey of 155 older adults (≥ 65 years) in South East England, 33.6% reported using herbal medicinal products (HMPs) or dietary supplements alongside prescription medications, with females more likely than males to be concurrent users (43.4% vs. 22.5%, P = 0.009) [21]. Most concurrent users (78%) combined dietary supplements, commonly cod liver oil, glucosamine, multivitamins, and vitamin D, with medications; 32.6% were at risk of at least one potential drug-supplement interaction [21].
Although the overall prevalence of drug-supplement interactions in our study population was low, the patterns observed, particularly vitamin E with aspirin and magnesium or potassium with antihypertensive agents, remain clinically meaningful considering their potential to amplify bleeding risk, precipitate hypotension, or increase susceptibility to hyperkalemia in older adults. Concurrent use of vitamin E with aspirin can potentiate antiplatelet effects and increase bleeding risk; vitamin E inhibits early platelet activation and augments aspirin-induced suppression of platelet function, and clinical reports and observational data support cautious use of combined therapy in patients at bleeding risk [22]. Mineral supplements commonly used by older adults may alter antihypertensive pharmacodynamics [23]. Oral magnesium has vasodilatory and calcium-channel-blocking actions and meta-analyses of randomized trials report modest but clinically relevant reductions in SBP and DBP when magnesium is added to antihypertensive regimens, implying potential for additive hypotension [23]. Potassium supplementation poses a distinct safety concern in patients receiving renin-angiotensin-aldosterone system inhibitors or potassium-sparing diuretics [24]. These drug classes reduce renal potassium excretion and, particularly in older adults with age-related or CKD-related declines in eGFR, concurrent potassium intake can precipitate clinically significant hyperkaliemia [24]. Although antioxidants and trace elements are often perceived as low-risk, their concurrent use with chronic medications may inadvertently compromise metabolic stability or increase organ stress [25]. High-dose of vitamin C and chromium, may interact with commonly prescribed glucose-lowering, lipid-lowering, or antihypertensive medications which are prevalently used in older individuals, resulting in potentiated or reduced treatment efficacy [25].
The growing use of dietary supplements in our cohort of older adults, occurring alongside a considerable decline in renal function (mean eGFR decreasing from 68.0 to 64.4 mL/min/1.73 m2) and a rising prevalence of CKD (from 25.3% to 36.9%), raises important safety considerations for this population. Reduced kidney function alters the metabolism, utilization, and excretion of many vitamins and minerals, potentially affecting both their therapeutic effectiveness and the risk of toxicity [27]. Fat-soluble vitamins, such as vitamin E, may accumulate and pose safety concerns when used without appropriate monitoring [27], while changes in renal handling of water-soluble vitamins and micronutrients (e.g., vitamin C, B-vitamins) can further modify their expected effects [27]. Even mild reductions in eGFR disrupt key regulators of mineral and bone metabolism, influence bone turnover and reduce responsiveness to vitamin D supplementation [24]. These physiological alterations may heighten the risk of adverse outcomes from vitamin D use, such as disturbed bone mineral metabolism, vascular calcification, or inadequate therapeutic benefit in older adults with declining renal function [26].
Our study has several strengths, including the use of a large, well-characterized, community-based cohort of older adults followed over 16 years, allowing evaluation of long-term trends in supplement use within the context of evolving cardiometabolic health. Repeated assessments of sociodemographic factors, lifestyle behaviors, medications, and biochemical parameters enabled us to capture a comprehensive understanding of supplement use patterns alongside changes in cardiometabolic conditions. Standardized data collection procedures and validated instruments, including interviewer-administered supplement assessments and clinically measured biomarkers, further strengthen the reliability of the findings. Importantly, this study addresses a major evidence gap, as longitudinal data on supplement use and potential drug-supplement interactions among older adults in the Iranian population. Nonetheless, some limitations should be considered. Supplement use was self-reported, which may introduce recall or social desirability bias and does not fully capture dosage, duration, or brand-specific variability; however, combining self-report with interviewer verification likely minimized misclassification [10, 27, 28]. A key limitation is the lack of data on the clinical rationale and administration context for supplement use. We did not capture the specific indications, physician recommendations, or whether supplements were clinician-administered as part of the treatment protocol versus self-administered independently. This precludes analysis of supplement appropriateness, adherence reliability, and the attribution of any observed effects to the procedure versus unsupervised patient behavior. Additionally, residual confounding from unmeasured factors, including socioeconomic inequality, dietary quality, or health literacy, cannot be ruled out.
In conclusion, this 16-year population-based study provides the first comprehensive evidence on long-term trends, determinants, and potential drug-supplement interactions among older adults in Iran. Supplement use increased substantially alongside rising multimorbidity and polypharmacy, emphasizing the need for individualized evaluation of supplement use in clinical practice. Although the overall prevalence of clinically relevant drug-supplement interactions was low, the presence of specific high-risk combinations highlights the importance of monitoring in older adults with chronic cardiometabolic conditions. Future research should prioritize detailed characterization of supplement dosing and duration, assessment of clinical indications and physician guidance, and evaluation of the clinical consequences of drug-supplement interactions. Integrating supplement use into electronic health records, developing national guidelines for safe supplement use in older adults, and exploring targeted educational interventions may help optimize safety and reduce preventable risks in this rapidly growing segment of the population.
Supplementary information
Below is the link to the electronic supplementary material.
Acknowledgements
We thank the Tehran Lipid and Glucose Study participants and the field investigators of the Tehran Lipid and Glucose Study for their cooperation and assistance in physical examinations, biochemical evaluation and database management. This study, was supported by Shahid Beheshti University of Medical Sciences (Grant number: 43016484).
Author contributions
Z.B. and Z.N designed the study and analyzed the data. Z.B. and Z.N wrote the manuscript. F.A. supervised the study design and data analyses. All authors read and approved the final manuscript.
Funding
This work was not supported by any funding agency.
Data availability
Data will be presented upon forwarding the request to the corresponding author and confirming with the director of RIES (azizi@sbmu.ac.ir).
Declarations
Competing interests
The authors declare no competing interests.
Human Ethics and Consent to Participate
The study protocol was approved by the ethics research council of the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Written informed consent was obtained from all participants (Ethics code: IR.SBMU.ENDOCRINE.REC.1404.087). The study was conducted in accordance with the guidelines outlined in the Declaration of Helsinki.
Clinical trial number
Not applicable.
Consent to publish
Not applicable.
Footnotes
Publisher’s Note
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Contributor Information
Zahra Bahadoran, Email: z.bahadoran@sbmu.ac.ir, Email: zahrabahadoran@yahoo.com.
Fereidoun Azizi, Email: azizi@sbmu.ac.ir.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data will be presented upon forwarding the request to the corresponding author and confirming with the director of RIES (azizi@sbmu.ac.ir).