A One Health Perspective on the Clinical, Behavioural, and Environmental Risks of Chronic Proton Pump Inhibitor Use in Older Adults ^†

Abstract

This study explores the clinical, behavioural, and environmental risks of chronic proton pump inhibitor (PPI) use in older adults through a One Health perspective. Among 246 participants, 32.5% were receiving PPI therapy, with 91.3% on long-term treatment, frequently lacking clear clinical justification. Polypharmacy, drug interactions, and risky lifestyle behaviours were common. Environmental review highlighted the potential persistence of PPI transformation products in water systems, raising concerns about ecological impact and antimicrobial resistance. These findings underscore the urgency of implementing deprescribing strategies, enhancing patient education, and adopting sustainable prescribing practices that align human and environmental health.

1. Introduction

The One Health philosophy—emphasising the interconnectedness of human, animal, and environmental health—provides a robust framework for addressing complex, multifactorial health issues. This is especially relevant to vulnerable populations, such as older adults, who face heightened risks due to ageing, multimorbidity, and polypharmacy. Proton pump inhibitors (PPIs), commonly used in this group for acid-related gastrointestinal illness, are effective in the short-term but increasingly controversial when used long-term due to their adverse effects and questionable prescribing practices [1]. Aligned with One Health principles, this study considers not only individual-level clinical and behavioural risks but also the broader environmental implications at the system level of chronic PPI use.

Global data show that 25% of PPI users remain on treatment for over a year, and nearly a third for more than three years—often without clinical justification [2]. In older adults, prolonged PPI use has been linked to nutrient malabsorption, fractures, kidney disease, and cognitive decline [2,3]. These risks are compounded by behavioural and therapeutic inertia [3], the lack of deprescribing guidelines, and the limited uptake of structured interventions. The C-SENIoR trial, a pragmatic study conducted in Portugal, showed the feasibility and value of collaborative, pharmacist-led deprescribing in primary care [4].

From a One Health standpoint, the implications go beyond individual health. Inappropriate prescribing, including PPI, contributes to healthcare overuse, pharmaceutical waste, and environmental contamination via excreted drug residues entering water systems [5]. These can disrupt aquatic ecosystems, underscoring the need for sustainable prescribing practices.

This work adopts a One Health perspective in addressing the clinical, behavioural, and environmental risks of chronic PPI use in older adults. Drawing on cohort data and the current literature, we aim to identify systemic vulnerabilities and propose cross-disciplinary strategies—such as deprescribing, patient education, and policy-level action—to support safer, more sustainable care.

2. Materials and Methods

This repeated cross-sectional study involved two independent cohorts of community-dwelling adults aged 65 and older, assessed in 2023/2024 and 2024/2025 under the ESPIEM (Healthy Ageing—Egas Moniz Interdisciplinary Project). Although the same protocol was used, each cohort comprised a distinct sample. A convenience sample of individuals taking at least two medications was recruited by third-year pharmacy students via personal networks. Participants were eligible for inclusion if they were aged 65 years or older, lived in the community, were taking two or more medications, and were able to provide informed consent. Individuals were excluded if they had cognitive impairment that interfered with consent, were living in institutional care settings, or declined to participate. Data were collected through structured interviews, medication reviews, and lifestyle surveys. Pharmacological risk was assessed using the Medscape Drug Interaction Checker [6]. Lifestyle factors included smoking, alcohol and caffeine consumption, and sunscreen use. Descriptive statistics (frequencies, percentages, means) summarised PPI use and drug interaction risk. Data from both years (n = 246 elderly individuals; 144 in 2023/2024, 102 in 2024/2025) were pooled to describe pharmacotherapy patterns and health behaviours.

As no primary environmental sampling was performed, a focused narrative literature review was conducted to explore the potential environmental risks of chronic pharmaceutical contaminants, with particular emphasis on PPIs and their transformation products in wastewater and surface waters. These findings were qualitatively integrated to inform the ecological implications within a One Health perspective.

3. Results and Discussion

3.1. Participant Profile and PPI Use

Among the 246 participants (mean age: 76.6 years), 80 individuals (32.5%) were receiving PPI therapy. The most commonly prescribed PPI was esomeprazole, followed by pantoprazole and omeprazole (

Table 1. Summary of PPI use, drug interactions, and lifestyle factors among older adults (n = 80).

Category	Number (n)	Percentage (%)
Total PPI users	80	100
Sex distribution (PPI users)
Women	45	56.2
Men	35	43.8
Long-term PPI use (>6 months)	73	91.3
PPI name (dosage)
Esomeprazole (20–40 mg)	26	32.5
Pantoprazole (20–40 mg)	24	30.0
Omeprazole (20 mg)	22	27.5
Lansoprazole (15–30 mg)	7	8.8
Rabeprazole (10 mg)	1	1.3
Drug interactions
Serious 1	25	31.3
Monitor Closely 1	56	70
Lifestyle behaviours
Daily alcohol consumption	43	53.8
Active smoking	5	6.3
Regular coffee intake	47	58.8
Infrequent or no sunscreen use	72	90.0
Healthcare context
Has family doctor	67	83.8
Concomitant medications (mean)	7.5	-
Source of the PPI prescription
Family doctor	47	58.8
Other doctor	32	40.0
Pharmacist	1	1.2

¹ Number of PPI users with ‘Serious’ or ‘Monitor Closely’ drug interactions.

). Of the PPI users, 73 (91.3%) had been on treatment for more than six months.

Polypharmacy was common among PPI users, who were taking an average of 7.5 medications concurrently. A pharmacological review identified 293 ‘Monitor Closely’ drug interactions, affecting 70% of PPI users, and 48 ‘Serious’ interactions (31.3%). One of the ‘Serious’ interactions involved a PPI (omeprazole) and clopidogrel. Additionally, 28.8% of patients on PPIs were also prescribed corticosteroids, non-steroidal anti-inflammatories, or other drugs associated with gastric toxicity, potentially justifying PPI co-prescription but also underscoring the need for regular benefit–risk assessments. In elderly patients, age-related pharmacokinetic changes increase the likelihood of adverse outcomes from prolonged PPI use, including nutrient malabsorption, increased infection risk, and potentially even cognitive decline [1]. Importantly, PPIs are photosensitising drugs that may contribute to UV-induced skin damage [7]. Yet, in our analysis, 90% of users reported rarely or never using sunscreen, revealing a gap in preventive education. Lifestyle analysis revealed further behavioural risk factors: 6.25% of users were current smokers, 58.8% consumed coffee regularly, and 53.8% consumed alcohol—all of which can worsen gastrointestinal symptoms or alter drug metabolism, potentially prolonging or complicating treatment. Despite 83.8% of PPI users having a designated family doctor, the data suggest limited therapeutic reassessment and little emphasis on behavioural counselling, representing missed opportunities for deprescribing and lifestyle optimisation.

These findings reflect a broader trend of long-term PPI overuse globally, often extending beyond the recommended 4–8 week course typically advised for conditions like gastroesophageal reflux disease. In our cohort, 91.3% of PPI users had been on therapy for more than six months, underscoring persistent therapeutic inertia. This aligns with recent findings from a 2025 evaluation of primary care practices in England, where 62% of patients on continuous PPI therapy had no recorded indication, and 99% of those with short-term indications exceeded the recommended duration of use [8].

This highlights the need for greater awareness, regular treatment reassessment, and the implementation of structured deprescribing strategies. A 2024 scoping review emphasised that most interventions targeting inappropriate PPI use rely on education and enablement strategies, with pharmacist-led reviews and algorithm-based tools showing the most consistent effectiveness [9]. Notably, 58.8% of PPIs in our study were prescribed by family doctors, positioning primary care settings as key leverage points for intervention and change. The absence of regular medication reviews, even among patients with routine access to healthcare, reveals systemic shortcomings in care continuity. Addressing both reflective and impulsive behavioural determinants—such as beliefs about medication necessity and habitual prescribing—has been recommended to improve deprescribing outcomes [9]. Integrating pharmacists into geriatric assessments, fostering shared decision-making, and equipping clinicians to discuss lifestyle-related risk factors—such as alcohol use, photoprotection, and dietary triggers—are essential steps to improve outcomes. Given the known photosensitising potential of PPIs, photoprotection counselling should become a routine part of care [7].

3.2. Ecological Considerations

Although our primary data did not include environmental sampling, we conducted a focused review of the environmental science literature to contextualise the ecological implications of chronic PPI use within a One Health framework. From this perspective, the clinical and behavioural challenges discussed above are intrinsically linked to environmental concerns. While PPIs are widely prescribed, their direct detection in surface waters has been limited due to extensive human metabolism and rapid abiotic degradation. However, recent studies have shown that omeprazole, one of the most commonly used PPIs, can undergo photodegradation and hydrolysis in aquatic environments, forming several transformation products (TPs) that may persist for longer than the parent compound [10,11]. Photodegradation experiments in various water types (distilled, river, lake, and seawater) showed that natural constituents such as dissolved organic matter and nitrate ions influence the degradation rate of omeprazole. Seven TPs were identified, some also formed via hydrolysis. These were detected in both influent and effluent samples from wastewater treatment plants, suggesting that conventional treatment processes may not fully remove them. Notably, some TPs appeared more frequently than the parent compound, indicating that environmental monitoring efforts should prioritise these derivatives [11]. Toxicity testing using Vibrio fischeri revealed that while omeprazole itself exhibits high acute toxicity, its photodegradation products are significantly less toxic, suggesting solar photolysis may reduce environmental risk. Nevertheless, the presence of multiple TPs and their potential bioactivity highlight the need for further ecotoxicological evaluation. The persistence of PPIs and their TPs in surface waters may contribute not only to aquatic toxicity but also to the spread of antimicrobial resistance, particularly when residues interact with other pharmaceutical pollutants [5].

This study’s limitations include convenience sampling, recall bias from self-reported data, and the lack of primary environmental sampling, which limits generalisability and prevents direct ecological assessment. Nonetheless, the literature review offers a meaningful basis for future environmental research.

4. Conclusions

This study highlights the complex risks of chronic PPI use in older adults. Clinically, the high prevalence of long-term use, polypharmacy, and serious drug interactions calls for regular medication reviews and appropriate deprescribing. Behavioural factors—such as poor sunscreen use, alcohol and caffeine intake, and continued smoking—reflect missed opportunities for patient education. These issues are compounded by the environmental impact of PPI residues and TPs in wastewater, reinforcing the need for prescribing practices that support both human and ecological health. Recommendations include incorporating environmental considerations into clinical guidelines, promoting photoprotection, and empowering primary care to reduce unnecessary drug exposure. Advancing eco-pharmacovigilance and cross-sector collaboration is key to sustainable prescribing.

A One Health–oriented approach must integrate medication review, lifestyle counselling, and environmental awareness to reduce risk and promote more sustainable, person-centred care. Future research should directly investigate the environmental presence and ecotoxicity of TPs derived from PPIs through primary sampling and experimental models.