A Systematic Review of Long-Term Use of Proton Pump Inhibitors (PPIs) in Older Adults on Polypharmacy: Do PPIs...

Proton pump inhibitors (PPIs) are widely prescribed in older adults, often beyond recommended durations, raising concerns about nutrient depletion. This systematic review examined the impact of long-term PPI use (≥6 months) on micronutrient status in older adults receiving polypharmacy. A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) identified five eligible studies, including 693 participants. Results showed a 12-18% reduction in serum vitamin B12 over 12 months of PPI use. Calcium and parathyroid hormone levels declined significantly in a 12-month cohort, while bone turnover markers increased despite stable bone mineral density. Findings for magnesium were inconsistent, with results ranging from no change after 12 months to pharmacokinetic alterations without systemic depletion. Overall, the evidence consistently supports an association between prolonged PPI therapy and reductions in vitamin B12 and calcium, with conflicting results for magnesium. These deficiencies may contribute to cognitive decline, bone fragility, and increased fall risk in older adults. Routine nutritional monitoring, targeted supplementation, and deprescribing where appropriate should be considered to mitigate these risks, while further large-scale trials are needed in frail geriatric populations.