Association Between Proton Pump Inhibitor Use and Malnutrition Risk in the US General Population Using the GLIM...

Proton pump inhibitors (PPIs) are the global gold standard for acid-related disorders; however, their proliferation into long-term, often non-indicated use raises significant concerns regarding qualitative nutrient depletion.

This study primarily aimed to evaluate the independent association between PPI use and malnutrition risk according to the Global Leadership Initiative on Malnutrition (GLIM) criteria in a nationally representative US population.

We conducted a cross-sectional analysis of 23 363 adults from the NHANES 1999-2020 database. Malnutrition was operationalized via the GLIM approach, integrating phenotypic criteria (weight loss, low BMI, or DXA-derived reduced muscle mass) with etiologic criteria (inflammation or reduced calorie intake). Robust Poisson regression models estimated relative risks (RRs) for general malnutrition, while logistic regression estimated odds ratios (ORs) for severe malnutrition. Models were adjusted for sociodemographics, food security, comorbidities, and appetite-affecting medications.

The prevalence of malnutrition was 18.9% (95% CI: 18.4%-19.4%) and PPI use was associated with a 10% increased risk of malnutrition (RR 1.10; 95% CI: 1.01-1.19; p = 0.031) in the adjusted model. For severe malnutrition, PPI exposure was a robust independent predictor (OR 1.36; 95% CI: 1.13-1.63; p = 0.001). Notably, sex-stratified analysis revealed a RR associated with PPIs was significantly more pronounced in females (RR 1.37; 95% CI: 1.06-1.79; p = 0.018) than in males (RR 1.07; p = 0.11). In the geriatric population (≥ 65 years), chronic PPI use increased the odds of severe malnutrition by 57% (OR 1.57; 95% CI: 1.15-2.14; p = 0.004).

Prolonged iatrogenic hypochlorhydria may represent an important contributor to malnutrition, particularly to its more severe forms and among older adults. These findings support the need for regular medication reviews to identify and discontinue unnecessary long-term PPI therapy. Preserving metabolic and nutritional health may therefore require the implementation of non-pharmacological approaches as first-line management options for acid-related disorders whenever clinically appropriate. Such strategies may help reduce unnecessary long-term PPI exposure and its potential adverse effects on nutritional status.