EFFECT OF PROTON PUMP INHIBITOR USE ON SERUM MAGNESIUM, VITAMIN B12, AND HOMOCYSTEINE LEVELS IN ADULT OUTPATIENTS: A TERTIARY-CARE CROSS-SECTIONAL STUDY

Objectives: Proton pump inhibitors (PPIs) are usually applied in the case of acid-peptic disorders. Long-term use can have an impact on magnesium and Vitamin B12 absorption, and this is capable of increasing the level of homocysteine. It was done to determine the relationship between the use of PPI and serum levels of magnesium, Vitamin B12, and homocysteine in adult outpatients of a tertiary-care hospital. Methods: A cross-sectional study in a hospital was conducted on adult outpatients. According to the medication history, participants were classified into PPI users and PPI non-users. Demographic data, clinical history, and duration of PPI exposure were recorded. Serum magnesium, serum Vitamin B12, and plasma homocysteine were estimated using an automated biochemistry analyser, chemiluminescence immunoassay, and enzymatic immunoassay, respectively. Group comparisons were performed using appropriate statistical tests. Correlation analysis and multivariable regression were used to examine the association between duration of PPI use and biochemical parameters after adjustment for age, sex, diet pattern, and diabetes status. A p<0.05 was considered statistically significant. Results: A total of 240 participants were included (120 PPI users and 120 non-users). The mean age was 44.6±12.8 years in PPI users and 43.1±12.1 years in non-users. Median duration of PPI use was 11 months (IQR: 6–24). Mean serum magnesium was lower in PPI users (1.86±0.24 mg/dL) than non-users (2.02±0.21 mg/dL) (p<0.001). Mean Vitamin B12 was also lower in PPI users (312±128 pg/mL) compared to controls (418±152 pg/mL) (p<0.001). Mean homocysteine levels were higher among PPI users (16.9±6.2 μmol/L) than non-users (12.8±4.9 μmol/L) (p<0.001). Hypomagnesemia (<1.7 mg/dL) was seen in 28.3% of PPI users versus 10.0% of non-users (p=0.001). Vitamin B12 deficiency (<200 pg/mL) was present in 24.2% of PPI users compared with 9.2% of non-users (p=0.002). Hyperhomocysteinemia (>15 μmol/L) was noted in 46.7% of PPI users versus 20.0% of non-users (p<0.001). Longer PPI use showed a negative correlation with magnesium (r=−0.31) and Vitamin B12 (r=−0.34), and a positive correlation with homocysteine (r=+0.38) (all p≤0.001). After adjustment for age, sex, diet pattern, and diabetes, PPI use remained independently associated with lower Vitamin B12 (β=−86 pg/mL) and higher homocysteine (β=+3.4 μmol/L) (both p<0.001), and with lower magnesium (β=−0.12 mg/dL, p<0.001). Conclusion: PPI use was also found to be associated with serum magnesium and Vitamin B12 levels as well as higher levels of homocysteine, with increased time of therapy in this tertiary-care outpatient study. Periodical testing of these parameters could be helpful in patients taking long-term PPI.