Table 2 Quality of evidence and risks of adverse effects associated with long-term proton pump inhibitors (PPIs)

Causality established, idiosyncratic, rare

Acute interstitial nephritis

Observational, case–control

OR 5.16 (2.21–12.05)

Causality proven but of minimal significance

Fundic gland polyps

Observational

OR 2.2 (1.3–3.8) [6]

B12 deficiency

Observational, case–control

OR 1.65 (1.58–1.73) [7]

Weak association, causality probable

Small intestinal bacterial overgrowth

Meta-analysis

OR 2.28 (1.23–4.21) [8]

Spontaneous bacterial peritonitis in cirrhotic patients

Systematic review/meta-analysis

OR 2.17 (1.46–3.23) [9]

Hepatic encephalopathy in cirrhotic patients

Observational, case–control

Dose dependent response, up to OR 3.01 (1.78–5.10) [10]

Clostridium difficile infection

Observational cohort study

OR 2.10 (1.20–3.50)

Iron deficiency

Observational, case control

OR 2.49 (2.35–2.64) [11]

Hypomagnesemia

Observational, population-based cohort

OR 2.00 (1.36–2.93)^a [12]

Weak association, unproven causality

Bone fracture

Observational, case–control

OR 2.65 (1.80–3.90)

Chronic kidney disease

Observational, population-based cohort

HR 1.50 (1.14–1.96) [13]

Dementia

Prospective observational cohort

HR 1.44 (1.36–1.52)

Myocardial infarction

Observational, data mining

HR 1.16 (1.09–1.24)^b

Community-acquired pneumonia

Systematic review/meta-analysis

OR 1.49 (1.16–1.92)^b