Background Gastric acidity is mandatory for pepsin activation, bactericidal effect, secretin and pancreatic enzymes' release. PPIs (proton pump inhibitors) change gastric pH permanently to >3-4.

Purpose The aim of this work is to assess the impact of permanent high gastric pH on absorption and bioavailability (except of CYP450-interactions) and to recommend nutrition support options.

Materials and methods A systematic online literature research was performed on usual platforms. Recommendations rely on a multidisciplinary focus group assessment.

Results Risk factors assigned to long-term inhibition of gastric acidity arise from

· cleavage-resistance of peptide and glycosidic bonds

· mucosal degeneration and leak

· loss of bactericidal action

and comprise

· bacterial overgrowth

· community and hospital-acquired pneumonia

· childhood asthma related to PPI treatments of mothers in pregnancy

· sensitisation to food allergens in the older and in pregnant women (progesterone slows down gastric emptying)

· deterioration of lactose intolerance, celiac disease, atrophic gastritis, rheumatoid arthritis, diabetes mellitus

· modified bioavailability

o malabsorption of micronutrients, for example vit C and B12, folate, Zn, Fe, Mg, Ca

o lower bioavailability, for example ketoconazole, itraconazole, posaconazole, (not: voriconazole), atazanvir, cefpodoxime, cinnarizine, enoxacin, dipyridamole

o higher bioavailability, for example nifedipine, digoxin, penicillins, erythromycin, alendronate.

To prevent these complications, the focus group recommends:

· alternative antacids, step-down, intermittent and on-demand strategies:

o MgCO₃ and H₂-antagonists have a shorter onset and time of pH>3-4 than pantoprazole 40mg (median pH=3.7, pH>4 for 10.8h) or esomeprazole 40mg (median pH=4.7, pH>4 for 16.1h).

· to avoid high allergenic food

o that is crustacean, eggs, fish, milk, peanuts, soybeans, tree nuts or fruits, and wheat

· buffering, pepsin replacement, stimulation of digestion and peristalsis

o Carbonated beverages, quinine water, aperitifs, appetisers, and bitter substances (amara)

o Prokinetic agents (domperidone, bromopride, metoclopramide, quinine, erythromycin)

o Mucosal protectors (curcumin, quercetin, alginates, pectins, glycyrrhizin)

o Melatonin (regulates digestion and has structural similarity to omeprazole)

o Pepsin in HCl preparations

· nutrition and dietary approach combined with physical activity

o High-fibre-, low-fat-, low-carb diet · reassessment of pharmacotherapy

o Weak acids (pK_a<4.5) lose their undissociated state required for diffusion across membranes.

o Absorption is impaired by membrane-bound CYP3A4,5,7 and efflux transporter P-gp.

(a log-conc-diagram, structure formula, tables of relevant drugs and nutrients, as well as references are provided on the poster)

Conclusions PPI safety profiles are troubled by risk factors arising from inappropriate long-term use. Drugs may be more bioavailable as a result of mucosal hyperpermeability, or less bioavailable as a result of altered dissociation. Care should be given to substrates with pK_a<4.5. At least children and pregnant women should prefer alternatives to PPIs.